Sample records for adjacent non-cancerous tissues

  1. Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue.

    PubMed

    Abdel-Gawad, Mahmoud; Elsobky, Emad; Shalaby, Mahmoud M; Abd-Elhameed, Mohamed; Abdel-Rahim, Mona; Ali-El-Dein, Bedeir

    2016-12-01

    The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this

  2. Long non-coding RNA expression profile in cervical cancer tissues

    PubMed Central

    Zhu, Hua; Chen, Xiangjian; Hu, Yan; Shi, Zhengzheng; Zhou, Qing; Zheng, Jingjie; Wang, Yifeng

    2017-01-01

    Cervical cancer (CC), one of the most common types of cancer of the female population, presents an enormous challenge in diagnosis and treatment. Long non-coding (lnc)RNAs, non-coding (nc)RNAs with length >200 nucleotides, have been identified to be associated with multiple types of cancer, including CC. This class of nc transcripts serves an important role in tumor suppression and oncogenic signaling pathways. In the present study, the microarray method was used to obtain the expression profile of lncRNAs and protein-coding mRNAs and to compare the expression of lncRNAs between CC tissues and corresponding adjacent non-cancerous tissues in order to screen potential lncRNAs for associations with CC. Overall, 3356 lncRNAs with significantly different expression pattern in CC tissues compared with adjacent non-cancerous tissues were identified, while 1,857 of them were upregulated. These differentially expressed lncRNAs were additionally classified into 5 subgroups. Reverse transcription quantitative polymerase chain reactions were performed to validate the expression pattern of 5 random selected lncRNAs, and 2lncRNAs were identified to have significantly different expression in CC samples compared with adjacent non-cancerous tissues. This finding suggests that those lncRNAs with different expression may serve important roles in the development of CC, and the expression data may provide information for additional study on the involvement of lncRNAs in CC. PMID:28789353

  3. Increased lipoprotein lipase activity in non-small cell lung cancer tissue predicts shorter patient survival.

    PubMed

    Trost, Zoran; Sok, Miha; Marc, Janja; Cerne, Darko

    2009-07-01

    Cumulative evidence suggests the involvement of lipoprotein lipase (LPL) in tumor progression. We tested the hypothesis that increased LPL activity in resectable non-small cell lung cancer (NSCLC) tissue and the increased LPL gene expression in the surrounding non-cancer lung tissue found in our previous study are predictors of patient survival. Forty two consecutive patients with resected NSCLC were enrolled in the study. Paired samples of lung cancer tissue and adjacent non-cancer lung tissue were collected from resected specimens for baseline LPL activity and gene expression estimation. During a 4-year follow-up, 21 patients died due to tumor progression. One patient died due to a non-cancer reason and was not included in Cox regression analysis. High LPL activity in cancer tissue (relative to the adjacent non-cancer lung tissue) predicted shorter survival, independently of standard prognostic factors (p=0.003). High gene expression in the non-cancer lung tissue surrounding the tumor had no predictive value. Our study further underlines the involvement of cancer tissue LPL activity in tumor progression.

  4. LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.

    PubMed

    Fiano, Valentina; Zugna, Daniela; Grasso, Chiara; Trevisan, Morena; Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna; Merletti, Franco; Richiardi, Lorenzo

    2017-01-02

    Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.

  5. Detection of reactive oxygen metabolites in malignant and adjacent normal tissues of patients with lung cancer.

    PubMed

    Okur, Hacer Kuzu; Yuksel, Meral; Lacin, Tunc; Baysungur, Volkan; Okur, Erdal

    2013-01-17

    Different types of reactive oxygen metabolites (ROMs) are known to be involved in carcinogenesis. Several studies have emphasized the formation of ROMs in ischemic tissues and in cases of inflammation. The increased amounts of ROMs in tumor tissues can either be because of their causative effects or because they are produced by the tumor itself. Our study aimed to investigate and compare the levels of ROMs in tumor tissue and adjacent lung parenchyma obtained from patients with lung cancer. Fifteen patients (all male, mean age 63.6 ± 9 years) with non-small cell lung cancer were enrolled in the study. All patients were smokers. Of the patients with lung cancer, twelve had epidermoid carcinoma and three had adenocarcinoma. During anatomical resection of the lung, tumor tissue and macroscopically adjacent healthy lung parenchyma (control) that was 5 cm away from the tumor were obtained. The tissues were freshly frozen and stored at -20°C. The generation of ROMs was monitored using luminol- and lucigenin-enhanced chemiluminescence (CL) techniques. Both luminol (specific for (.)OH, H(2)O(2), and HOCl(-)) and lucigenin (selective for O(2)(.)(-)) CL measurements were significantly higher in tumor tissues than in control tissues (P <0.001). Luminol and lucigenin CL measurements were 1.93 ± 0.71 and 2.5 ± 0.84 times brighter, respectively, in tumor tissues than in the adjacent parenchyma (P = 0.07). In patients with lung cancer, all ROM levels were increased in tumor tissues when compared with the adjacent lung tissue. Because the increase in lucigenin concentration, which is due to tissue ischemia, is higher than the increase in luminol, which is directly related to the presence and severity of inflammation, ischemia may be more important than inflammation for tumor development in patients with lung cancer.

  6. LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality

    PubMed Central

    Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna

    2017-01-01

    ABSTRACT Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982–1988 and 1993–1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95–2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03–21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression. PMID:27892790

  7. Epigenomic profiling of DNA methylation in paired prostate cancer versus adjacent benign tissue

    PubMed Central

    Geybels, Milan S.; Zhao, Shanshan; Wong, Chao-Jen; Bibikova, Marina; Klotzle, Brandy; Wu, Michael; Ostrander, Elaine A.; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L.

    2016-01-01

    Background Aberrant DNA methylation may promote prostate carcinogenesis. We investigated epigenome-wide DNA methylation profiles in prostate cancer (PCa) compared to adjacent benign tissue to identify differentially methylated CpG sites. Methods The study included paired PCa and adjacent benign tissue samples from 20 radical prostatectomy patients. Epigenetic profiling was done using the Infinium HumanMethylation450 BeadChip. Linear models that accounted for the paired study design and False Discovery Rate Q-values were used to evaluate differential CpG methylation. mRNA expression levels of the genes with the most differentially methylated CpG sites were analyzed. Results In total, 2,040 differentially methylated CpG sites were identified in PCa versus adjacent benign tissue (Q-value <0.001), the majority of which were hypermethylated (n = 1,946; 95%). DNA methylation profiles accurately distinguished between PCa and benign tissue samples. Twenty-seven top-ranked hypermethylated CpGs had a mean methylation difference of at least 40% between tissue types, which included 25 CpGs in 17 genes. Furthermore, for ten genes over 50% of promoter region CpGs were hypermethylated in PCa versus benign tissue. The top-ranked differentially methylated genes included three genes that were associated with both promoter hypermethylation and reduced gene expression: SCGB3A1, HIF3A, and AOX1. Analysis of The Cancer Genome Atlas (TCGA) data provided confirmatory evidence for our findings. Conclusions This study of PCa versus adjacent benign tissue showed many differentially methylated CpGs and regions in and outside gene promoter regions, which may potentially be used for the development of future epigenetic-based diagnostic tests or as therapeutic targets. PMID:26383847

  8. Epigenomic profiling of DNA methylation in paired prostate cancer versus adjacent benign tissue.

    PubMed

    Geybels, Milan S; Zhao, Shanshan; Wong, Chao-Jen; Bibikova, Marina; Klotzle, Brandy; Wu, Michael; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

    2015-12-01

    Aberrant DNA methylation may promote prostate carcinogenesis. We investigated epigenome-wide DNA methylation profiles in prostate cancer (PCa) compared to adjacent benign tissue to identify differentially methylated CpG sites. The study included paired PCa and adjacent benign tissue samples from 20 radical prostatectomy patients. Epigenetic profiling was done using the Infinium HumanMethylation450 BeadChip. Linear models that accounted for the paired study design and False Discovery Rate Q-values were used to evaluate differential CpG methylation. mRNA expression levels of the genes with the most differentially methylated CpG sites were analyzed. In total, 2,040 differentially methylated CpG sites were identified in PCa versus adjacent benign tissue (Q-value < 0.001), the majority of which were hypermethylated (n = 1,946; 95%). DNA methylation profiles accurately distinguished between PCa and benign tissue samples. Twenty-seven top-ranked hypermethylated CpGs had a mean methylation difference of at least 40% between tissue types, which included 25 CpGs in 17 genes. Furthermore, for 10 genes over 50% of promoter region CpGs were hypermethylated in PCa versus benign tissue. The top-ranked differentially methylated genes included three genes that were associated with both promoter hypermethylation and reduced gene expression: SCGB3A1, HIF3A, and AOX1. Analysis of The Cancer Genome Atlas (TCGA) data provided confirmatory evidence for our findings. This study of PCa versus adjacent benign tissue showed many differentially methylated CpGs and regions in and outside gene promoter regions, which may potentially be used for the development of future epigenetic-based diagnostic tests or as therapeutic targets. © 2015 Wiley Periodicals, Inc.

  9. Increased phosphatidylethanolamine N-methyltransferase gene expression in non-small-cell lung cancer tissue predicts shorter patient survival

    PubMed Central

    ZINRAJH, DAVID; HÖRL, GERD; JÜRGENS, GÜNTHER; MARC, JANJA; SOK, MIHA; CERNE, DARKO

    2014-01-01

    Lipid mobilization is of great importance for tumor growth and studies have suggested that cancer cells exhibit abnormal choline phospholipid metabolism. In the present study, we hypothesized that phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is increased in non-small-cell lung cancer (NSCLC) tissues and that increased gene expression acts as a predictor of shorter patient survival. Forty-two consecutive patients with resected NSCLC were enrolled in this study. Paired samples of lung cancer tissues and adjacent non-cancer lung tissues were collected from resected specimens for the estimation of PEMT expression. SYBR Green-based real-time polymerase chain reaction was used for quantification of PEMT mRNA in lung cancer tissues. Lipoprotein lipase (LPL) and fatty acid synthase (FASN) activities had already been measured in the same tissues. During a four-year follow-up, 21 patients succumbed to tumor progression. One patient did not survive due to non-cancer reasons and was not included in the analysis. Cox regression analysis was used to assess the prognostic value of PEMT expression. Our findings show that elevated PEMT expression in the cancer tissue, relative to that in the adjacent non-cancer lung tissue, predicts shorter patient survival independently of standard prognostic factors and also independently of increased LPL or FASN activity, the two other lipid-related predictors of shorter patient survival. These findings suggest that active phosphatidylcholine and/or choline metabolism are essential for tumor growth and progression. PMID:24932311

  10. Increased phosphatidylethanolamine N-methyltransferase gene expression in non-small-cell lung cancer tissue predicts shorter patient survival.

    PubMed

    Zinrajh, David; Hörl, Gerd; Jürgens, Günther; Marc, Janja; Sok, Miha; Cerne, Darko

    2014-06-01

    Lipid mobilization is of great importance for tumor growth and studies have suggested that cancer cells exhibit abnormal choline phospholipid metabolism. In the present study, we hypothesized that phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is increased in non-small-cell lung cancer (NSCLC) tissues and that increased gene expression acts as a predictor of shorter patient survival. Forty-two consecutive patients with resected NSCLC were enrolled in this study. Paired samples of lung cancer tissues and adjacent non-cancer lung tissues were collected from resected specimens for the estimation of PEMT expression. SYBR Green-based real-time polymerase chain reaction was used for quantification of PEMT mRNA in lung cancer tissues. Lipoprotein lipase (LPL) and fatty acid synthase (FASN) activities had already been measured in the same tissues. During a four-year follow-up, 21 patients succumbed to tumor progression. One patient did not survive due to non-cancer reasons and was not included in the analysis. Cox regression analysis was used to assess the prognostic value of PEMT expression. Our findings show that elevated PEMT expression in the cancer tissue, relative to that in the adjacent non-cancer lung tissue, predicts shorter patient survival independently of standard prognostic factors and also independently of increased LPL or FASN activity, the two other lipid-related predictors of shorter patient survival. These findings suggest that active phosphatidylcholine and/or choline metabolism are essential for tumor growth and progression.

  11. PIXE analysis of elements in gastric cancer and adjacent mucosa

    NASA Astrophysics Data System (ADS)

    Liu, Qixin; Zhong, Ming; Zhang, Xiaofeng; Yan, Lingnuo; Xu, Yongling; Ye, Simao

    1990-04-01

    The elemental regional distributions in 20 resected human stomach tissues were obtained using PIXE analysis. The samples were pathologically divided into four types: normal, adjacent mucosa A, adjacent mucosa B and cancer. The targets for PIXE analysis were prepared by wet digestion with a pressure bomb system. P, K, Fe, Cu, Zn and Se were measured and statistically analysed. We found significantly higher concentrations of P, K, Cu, Zn and a higher ratio of Cu compared to Zn in cancer tissue as compared with normal tissue, but statistically no significant difference between adjacent mucosa and cancer tissue was found.

  12. Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

    PubMed

    Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

    2017-09-01

    Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

  13. Prostate tissue metal levels and prostate cancer recurrence in smokers.

    PubMed

    Neslund-Dudas, Christine; Kandegedara, Ashoka; Kryvenko, Oleksandr N; Gupta, Nilesh; Rogers, Craig; Rybicki, Benjamin A; Dou, Q Ping; Mitra, Bharati

    2014-02-01

    Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N = 25) had significantly higher Cd (median ppb, p = 0.03) and lower Zn (p = 0.002) in non-neoplastic tissue than never-smokers (N = 21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p = 0.009, adjacent non-neoplastic tissue Cd/Pb, 6.36 vs. 1.02, p = 0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p = 0.039 and adjacent non-neoplastic, p = 0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process.

  14. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

    PubMed

    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P < 0.05) and higher than in middle and remote paraneoplastic tissue (P < 0.01). There was no statistically significant difference between the expression of these genes in middle and proximal paraneoplastic tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  15. Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue.

    PubMed

    Yang, Qiuyun; Zhao, Jinghe; Cui, Manhua; Gi, Shuting; Wang, Wei; Han, Xiaole

    2015-12-01

    Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. © 2015 Japan Society of Obstetrics and Gynecology.

  16. Transcript levels of ten-eleven translocation type 1–3 in cervical cancer and non-cancerous cervical tissues

    PubMed Central

    Bronowicka-Kłys, Dorota Ewa; Roszak, Andrzej; Pawlik, Piotr; Sajdak, Stefan; Sowińska, Anna; Jagodziński, Paweł Piotr

    2017-01-01

    Decreased expression of ten-eleven translocation (TET1, TET2 and TET3) proteins has been reported in various types of cancer. However, the expression levels of TET proteins in cervical cancer (CC) remain to be elucidated. The present study determined the levels of TET1, TET2 and TET3 transcripts in cancerous (n=80) and non-cancerous cervical tissues (n=41). The results revealed a significant reduction in TET1 transcripts (P=0.0000001) in cervical tissue samples from patients with primary CC compared with samples from control patients. Significantly decreased TET1 transcript levels, as compared to non-cancerous cervical tissues, were also observed in tissue samples with the following characteristics: Stage I (P=0.016), II (P<0.0001), III (P=0.00007) and grade of differentiation G1 (P=0.026), G2 (P=0.00006), G3 (P=0.0007) and Gx (P=0.0004) and squamous histological type (P<0.00001). TET1 transcript levels were significantly lower in patients aged 45–60 years (P=0.0002) and patients age >60 years (P=0.003), as compared with non-cancerous cervical tissues. TET2 transcript levels were lower in cervical cancer tissues classified as stage II (P=0.043) and TET3 transcript levels were lower in stage III samples (P=0.010), tissue samples with a grade of differentiation of G3 (P=0.025) and tissue with squamous type histology (P=0.047), all compared with non-cancerous cervical tissues. The present study demonstrated a significantly reduced level of TET1 transcripts in cancerous cervical tissues, as compared with non-cancerous tissues. Furthermore, decreased TET1-3 transcript levels were identified when patients with CC were stratified by clinicopathological variables, as compared with non-cancerous cervical tissues. PMID:28521490

  17. Comparative trace elemental analysis of cancerous and non-cancerous tissues of rectal cancer patients using PIXE

    NASA Astrophysics Data System (ADS)

    Naga Raju, G. J.; Sarita, P.; Murthy, K. S. R.

    2017-08-01

    Particle Induced X-ray Emission (PIXE), an accelerator based analytical technique has been employed in this work for the analysis of trace elements in the cancerous and non-cancerous tissues of rectal cancer patients. A beam of 3 MeV protons generated from 3 MV Pelletron accelerator at the Ion Beam Laboratory of Institute of Physics, Bhubaneswar, India was used as projectile to excite the atoms present in the tissues samples. PIXE technique, with its capability to detect simultaneously several elements present at very low concentrations, offers an excellent tool for trace element analysis. The characteristic X-rays emitted by the samples were recorded by a high resolution Si (Li) detector. On the basis of the PIXE spectrum obtained for each sample, the elements Cl, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, and Br were identified and their relative concentrations were estimated in the cancerous and non-cancerous tissues of rectum. The levels of Mn, Fe, Co, Cu, Zn, and As were higher (p < 0.005) while the levels of Ca, Cr and Ni were lower (p < 0.005) in the cancer tissues relative to the normal tissues. The alterations in the levels of the trace elements observed in the present work are discussed in this paper with respect to their potential role in the initiation, promotion and inhibition of cancer of the rectum.

  18. Relationship between air pollution and metal levels in cancerous and non-cancerous lung tissues.

    PubMed

    Binkowski, Łukasz J; Rogoziński, Paweł; Błaszczyk, Martyna; Semla, Magdalena; Melia, Patrick M; Stawarz, Robert

    2016-12-05

    We aimed to check the relationships between levels of metals (Ca, Cd, Cu, Fe, Hg and Zn) in cancerous and non-cancerous lung tissues and their link to air pollution, expressed as particulate matter (PM) concentrations. The study also examines the influence on metal concentration in the lung tissue of patients' sex and the distance of their homes from the nearest emitter. We found that the general pattern of ascending concentrations in tumor tissue was as follows: Hg < Cd < Cu < Ca < Zn < Fe. In non-affected lung tissue the order of concentrations of Ca and Fe was reversed. With the exception of Cd and Cu, levels of metals were found in higher accumulations in non-cancerous tissue (e.g., Fe 326.423 and Ca 302.730 μg/g d.w) than in tumorous tissue (Fe 150.735 and Ca 15.025 μg/g d.w). Neither the PM10 (PM of a diameter of 10 μm) concentration nor sex revealed any connection with metal concentrations. The shorter the distance from the emitter, the higher the metal concentrations that tended to be observed for almost all metals, but a statistically significant (but weak) relationship was noted only for Cu in tumor tissue (r s : -0.4869).

  19. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    PubMed

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  20. Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

    DTIC Science & Technology

    2013-10-01

    proposal for the first phase of the project, gene expression and epigenetic alterations are to be analyzed by next generation sequencing. Laser captured... genes and also alternative splicing events which could provide valuable biomarkers for this project. We required RRBS libraries for the methylation...regulated compared to BP in both the benign tissue adjacent to cancer (BPC) and in prostate cancer. Interestingly, both of these genes can also be

  1. Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns.

    PubMed

    Kirby, Marie K; Ramaker, Ryne C; Roberts, Brian S; Lasseigne, Brittany N; Gunther, David S; Burwell, Todd C; Davis, Nicholas S; Gulzar, Zulfiqar G; Absher, Devin M; Cooper, Sara J; Brooks, James D; Myers, Richard M

    2017-04-17

    Current diagnostic tools for prostate cancer lack specificity and sensitivity for detecting very early lesions. DNA methylation is a stable genomic modification that is detectable in peripheral patient fluids such as urine and blood plasma that could serve as a non-invasive diagnostic biomarker for prostate cancer. We measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array. We overlaid the most significantly differentially methylated sites in the genome with transcription factor binding sites measured by the Encyclopedia of DNA Elements consortium. We used logistic regression and receiver operating characteristic curves to assess the performance of candidate diagnostic models. We identified methylation patterns that have a high predictive power for distinguishing malignant prostate tissue from benign-adjacent prostate tissue, and these methylation signatures were validated using data from The Cancer Genome Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene regulatory regions with higher DNA methylation in malignant prostate tissues. DNA methylation patterns are greatly altered in prostate cancer tissue in comparison to benign-adjacent tissue. We have discovered patterns of DNA methylation marks that can distinguish prostate cancers with high specificity and sensitivity in multiple patient tissue cohorts, and we have identified transcription factors binding in these differentially methylated regions that may play important roles in prostate cancer development.

  2. Cancer testis antigen OY-TES-1: analysis of protein expression in ovarian cancer with tissue microarrays.

    PubMed

    Fan, R; Huang, W; Luo, B; Zhang, Q M; Xiao, S W; Xie, X X

    2015-01-01

    Revised manuscript accepted for publication March 5, Objectives: The purpose of this study was to determine the potential of cancer testis antigen OY-TES-1 as a vaccine for ovarian cancer (OC). A tissue microarray (TMA) containing 107 samples from OC tissues and 48 samples from OC adjacent tissues was analyzed by immunohistochemistry with the OY-TES-1 polyclonal antibody. The correlation between OY-TES-1 and clinic pathological traits of OC was statistically analyzed. The expression of OY-TES-1 protein was found in 81% (87/107) of OC tissues and 56% (27/48) of OC adjacent tissues. The immunostaining intensity of OY-TES-1 in OC tissues was significantly higher than that in OC adjacent tissues tested (p = 0.040). OC adjacent tissues only demonstrated lower immunostaining intensity, whereas some of OC tissues presented higher immunostaining intensity and majority showed the heterogeneity of protein distribution. There was no statistically significant correlation found between OY-TES-1 expression and any other clinicopathological traits such as age, FIGO stage, pathological grade, and histological type. OY-TES-1 was expressed in OC tissues with a high proportion, and some of OC tissues presented OY-TES-1 expression in high level vs OC adjacent tissues. OY-TES-1 could be an attractive target for immunotherapy for OC in the future.

  3. Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer

    PubMed Central

    2010-01-01

    Background Polycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women. Methods A total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry. Results Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer. Conclusion Bmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast

  4. Non-Invasive Imaging of In Vivo Breast Cancer Tissue Utilizing Metabolically Incorporated Unnatural Sugars

    DTIC Science & Technology

    2004-08-01

    or misdiagnosed (4). Therefore, much effort is now directed toward developing alternative breast cancer detection technologies that exploit the...AD Award Number: DAMD17-03-1-0548 TITLE: Non-Invasive Imaging of In Vivo Breast Cancer Tissue Utilizing Metabolically Incorporated Unnatrual Sugars...5. FUNDING NUMBERS Non-Invasive Imaging of In Vivo Breast Cancer Tissue DAMD17-03-1-0548 Utilizing Metabolically Incorporated Unnatrual Sugars 6. A

  5. Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

    NASA Astrophysics Data System (ADS)

    Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

    2005-04-01

    Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

  6. Adjacent slice prostate cancer prediction to inform MALDI imaging biomarker analysis

    NASA Astrophysics Data System (ADS)

    Chuang, Shao-Hui; Sun, Xiaoyan; Cazares, Lisa; Nyalwidhe, Julius; Troyer, Dean; Semmes, O. John; Li, Jiang; McKenzie, Frederic D.

    2010-03-01

    Prostate cancer is the second most common type of cancer among men in US [1]. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. Proteomic biomarkers can improve upon these methods. MALDI molecular spectra imaging is used to visualize protein/peptide concentrations across biopsy samples to search for biomarker candidates. Unfortunately, traditional processing methods require histopathological examination on one slice of a biopsy sample while the adjacent slice is subjected to the tissue destroying desorption and ionization processes of MALDI. The highest confidence tumor regions gained from the histopathological analysis are then mapped to the MALDI spectra data to estimate the regions for biomarker identification from the MALDI imaging. This paper describes a process to provide a significantly better estimate of the cancer tumor to be mapped onto the MALDI imaging spectra coordinates using the high confidence region to predict the true area of the tumor on the adjacent MALDI imaged slice.

  7. Endothelin-1 stimulates colon cancer adjacent fibroblasts.

    PubMed

    Knowles, Jonathan P; Shi-Wen, Xu; Haque, Samer-ul; Bhalla, Ashish; Dashwood, Michael R; Yang, Shiyu; Taylor, Irving; Winslet, Marc C; Abraham, David J; Loizidou, Marilena

    2012-03-15

    Endothelin-1 (ET-1) is produced by and stimulates colorectal cancer cells. Fibroblasts produce tumour stroma required for cancer development. We investigated whether ET-1 stimulated processes involved in tumour stroma production by colonic fibroblasts. Primary human fibroblasts, isolated from normal tissues adjacent to colon cancers, were cultured with or without ET-1 and its antagonists. Cellular proliferation, migration and contraction were measured. Expression of enzymes involved in tumour stroma development and alterations in gene transcription were determined by Western blotting and genome microarrays. ET-1 stimulated proliferation, contraction and migration (p < 0.01 v control) and the expression of matrix degrading enzymes TIMP-1 and MMP-2, but not MMP-3. ET-1 upregulated genes for profibrotic growth factors and receptors, signalling molecules, actin modulators and extracellular matrix components. ET-1 stimulated colonic fibroblast cellular processes in vitro that are involved in developing tumour stroma. Upregulated genes were consistent with these processes. By acting as a strong stimulus for tumour stroma creation, ET-1 is proposed as a target for adjuvant cancer therapy. Copyright © 2011 UICC.

  8. Prostate cancer outcome and tissue levels of metal ions

    USGS Publications Warehouse

    Sarafanov, A.G.; Todorov, T.I.; Centeno, J.A.; MacIas, V.; Gao, W.; Liang, W.-M.; Beam, C.; Gray, Marion A.; Kajdacsy-Balla, A.

    2011-01-01

    BACKGROUNDThere are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease outcome.METHODSWe obtained formalin fixed paraffin embedded tissue blocks of prostatectomy samples of 40 patients with PSA recurrence, matched 1:1 (for year of surgery, race, age, Gleason grading, and pathology TNM classification) with tissue blocks from 40 patients without recurrence (n = 80). Case–control pairs were compared for the levels of metals in areas adjacent to tumors. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for quantification of Cd, Fe, Zn, and Se.RESULTSPatients with biochemical (PSA) recurrence of disease had 12% lower median iron (95 µg/g vs. 111 µg/g; P = 0.04) and 21% lower zinc (279 µg/g vs. 346 µg/g; P = 0.04) concentrations in the normal-appearing tissue immediately adjacent to cancer areas. Differences in cadmium (0.489 µg/g vs. 0.439 µg/g; 4% higher) and selenium (1.68 µg/g vs. 1.58 µg/g; 5% higher) levels were not statistically significant in recurrence cases, when compared to non-recurrences (P = 0.40 and 0.21, respectively).CONCLUSIONSThere is an association between low zinc and low iron prostate tissue levels and biochemical recurrence in prostate cancer. Whether these novel findings are a cause or effect of more aggressive tumors, or whether low zinc and iron prostatic levels raise implications for therapy, remains to be investigated. 

  9. Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis.

    PubMed

    Sethi, Manveen K; Thaysen-Andersen, Morten; Kim, Hoguen; Park, Cheol Keun; Baker, Mark S; Packer, Nicolle H; Paik, Young-Ki; Hancock, William S; Fanayan, Susan

    2015-08-03

    Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P<0.05, fold change>1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR(+) CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR(-) tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Changes in NMR relaxation times of adjacent muscle after implantation of malignant and normal tissue.

    PubMed Central

    Ling, C. R.; Foster, M. A.; Mallard, J. R.

    1979-01-01

    In separate experiments, normal foreign tissue and malignant tumour were implanted s.c. into the rat thigh. NMR T1 values of the adjacent normal muscle, resulting from local inflammatory reactions or from malignant invasion, were measured. Elevations in T1 of the underlying muscle occurred within 24 h in both experiments, and it is believed these were caused by rapid inflammatory and immunological reactions to the implants. However the T1 values of muscle samples adjacent to the non-malignant implants decreased during the 11 days after implantation, dropping to values within the normal range. In the second experiment there was progressive malignant invasion into the normal adjacent tissue and the elevated T1 values were maintained throughout the 12-day period. The effects of the implantation on tissue water content are discussed in relation to NMR T1 relaxation times, and the relevance to whole-body NMR imaging of elevated T1 values due to nonmalignant pathological states is considered. PMID:526431

  11. Analysis of the association of the expression of KiSS-1 in colorectal cancer tissues with the pathology and prognosis.

    PubMed

    Huo, Xinkai; Zhang, Lei; Li, Tao

    2018-03-01

    Colorectal cancer is a common malignant tumor of the digestive tract with high morbidity and mortality rates. The aim of the present study was to examine the expression level of KiSS-1 in tumor tissues of patients with colorectal cancer, and to explore the relationship with the clinicopathology and prognosis of patients with colorectal cancer. Frozen tumor tissue and corresponding cancer-adjacent normal tissue specimens were selected from 56 patients with colorectal cancer who were treated in the Department of Surgery of our hospital from May 2009 to December 2011. The expression levels of KiSS-1 messenger ribonucleic acid (mRNA) in tumor tissues and cancer-adjacent normal tissues were detected by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The expression levels of KiSS-1 proteins in colorectal cancer tissues and cancer-adjacent normal tissues were further detected by immunohistochemistry. In addition, the association of the expression level of KiSS-1 proteins in tissues of colorectal cancer patients with pathological parameters and the prognosis of patients with colorectal cancer was analyzed combined with clinical data. The RT-qPCR results showed that the expression of KiSS-1 mRNA in colorectal cancer tissues was significantly lower than that in cancer-adjacent normal tissues (P<0.05). Immunohistochemistry results indicated that the positive expression rate of KiSS-1 proteins in colorectal cancer tissues (26.79%) was significantly lower than that in cancer-adjacent normal tissues (80.36%). The low expression of KiSS-1 in colorectal cancer tissues was associated with the degree of differentiation, invasion and metastasis, as well as clinical staging. The 5-year overall survival rate of patients with colorectal cancer was 55.36% (31/56). The univariate survival analysis showed that patients with lowly expressed KiSS-1 had worse prognosis. The low expression of KiSS-1 is closely associated with the occurrence and development of colorectal

  12. Next-generation sequencing traces human induced pluripotent stem cell lines clonally generated from heterogeneous cancer tissue.

    PubMed

    Ishikawa, Tetsuya

    2017-05-26

    To investigate genotype variation among induced pluripotent stem cell (iPSC) lines that were clonally generated from heterogeneous colon cancer tissues using next-generation sequencing. Human iPSC lines were clonally established by selecting independent single colonies expanded from heterogeneous primary cells of S-shaped colon cancer tissues by retroviral gene transfer ( OCT3/4 , SOX2 , and KLF4 ). The ten iPSC lines, their starting cancer tissues, and the matched adjacent non-cancerous tissues were analyzed using next-generation sequencing and bioinformatics analysis using the human reference genome hg19. Non-synonymous single-nucleotide variants (SNVs) (missense, nonsense, and read-through) were identified within the target region of 612 genes related to cancer and the human kinome. All SNVs were annotated using dbSNP135, CCDS, RefSeq, GENCODE, and 1000 Genomes. The SNVs of the iPSC lines were compared with the genotypes of the cancerous and non-cancerous tissues. The putative genotypes were validated using allelic depth and genotype quality. For final confirmation, mutated genotypes were manually curated using the Integrative Genomics Viewer. In eight of the ten iPSC lines, one or two non-synonymous SNVs in EIF2AK2 , TTN , ULK4 , TSSK1B , FLT4 , STK19 , STK31 , TRRAP , WNK1 , PLK1 or PIK3R5 were identified as novel SNVs and were not identical to the genotypes found in the cancer and non-cancerous tissues. This result suggests that the SNVs were de novo or pre-existing mutations that originated from minor populations, such as multifocal pre-cancer (stem) cells or pre-metastatic cancer cells from multiple, different clonal evolutions, present within the heterogeneous cancer tissue. The genotypes of all ten iPSC lines were different from the mutated ERBB2 and MKNK2 genotypes of the cancer tissues and were identical to those of the non-cancerous tissues and that found in the human reference genome hg19. Furthermore, two of the ten iPSC lines did not have any

  13. Bmi-1 expression modulates non-small cell lung cancer progression

    PubMed Central

    Xiong, Dan; Ye, Yunlin; Fu, Yujie; Wang, Jinglong; Kuang, Bohua; Wang, Hongbo; Wang, Xiumin; Zu, Lidong; Xiao, Gang; Hao, Mingang; Wang, Jianhua

    2015-01-01

    Previous studies indicate that the role of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is responsible for multiple cancer progression. However, Bmi-1 in controlling gene expression in non-small cell lung cancer (NSCLC) development is not well explored. Here we report that the Bmi-1 level is highly increased in primary NSCLC tissues compared to matched adjacent non-cancerous tissues and required for lung tumor growth in xenograft model. Furthermore, we also demonstrate that Bmi-1 level is lower in matched involved lymph node cancerous tissues than the respective primary NSCLC tissues. We find that Bmi-1 does not affect cell cycle and apoptosis in lung cancer cell lines as it does not affect the expression of p16/p19, Pten, AKT and P-AKT. Mechanistic analyses note that reduction of Bmi-1 expression inversely regulates invasion and metastasis of NSCLC cells in vitro and in vivo, followed by induction of epithelial-mesenchymal transition (EMT). Using genome microarray assays, we find that RNAi-mediated silence of Bmi-1 modulates some important molecular genetics or signaling pathways, potentially associated with NSCLC development. Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression. PMID:25880371

  14. Expression of metastasis-associated lung adenocarcinoma transcript 1 long non-coding RNA in vitro and in patients with non-small cell lung cancer.

    PubMed

    Lin, Ling; Li, Haiyan; Zhu, Yefei; He, Susu; Ge, Hongfei

    2018-06-01

    The present study aimed to investigate the association between the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNA (lncRNA) and the recurrence of non-small cell lung cancer (NSCLC) and to elucidate the potential mechanisms of MALAT1 in vitro . Between 1 June 1, 2010 and December 30, 2016, NSCLC tumor tissues and adjacent non-cancerous tissues were obtained from 120 patients with NSCLC, who had undergone surgical resection at Taizhou Hospital of Wenzhou Medical University (Linhai, China). The total RNA of tissues and cells were extracted and the expression of MALAT1 was determined using a wound healing assay and reverse transcription quantitative polymerase chain reaction. In addition, MALAT1 expression in A549 cells was silenced using small interfering RNA. The proliferation, migration and invasion of cells were then assessed using a CellTiter 96 kit and Transwell assays. MALAT1 expression was significantly increased in NSCLC samples compared with expression in adjacent non-cancerous tissues. Furthermore, the expression of MALAT1 in patients with NSCLC that exhibited recurrence was markedly higher than in those that did not. The results of the present study also demonstrated significant associations between high expression of MALAT1 and female sex, Tumor-Node-Metastasis advanced stage, vessel invasion, pathological differentiation and recurrence of patients with NSCLC. The proliferative, migratory and invasive abilities of MALAT1-silenced A549 cells were significantly decreased compared with those of control cells. MALAT1 expression was significantly increased in NSCLC tissues and was revealed to serve a role in the progression of NSCLC.

  15. RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

    PubMed

    Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

    2017-03-28

    The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

  16. RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA

    PubMed Central

    Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S.

    2017-01-01

    The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients. PMID:28206954

  17. Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospray Ionization Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Masterson, Timothy A.; Dill, Allison L.; Eberlin, Livia S.; Mattarozzi, Monica; Cheng, Liang; Beck, Stephen D. W.; Bianchi, Federica; Cooks, R. Graham

    2011-08-01

    Desorption electrospray ionization mass spectrometry (DESI-MS) has been successfully used to discriminate between normal and cancerous human tissue from different anatomical sites. On the basis of this, DESI-MS imaging was used to characterize human seminoma and adjacent normal tissue. Seminoma and adjacent normal paired human tissue sections (40 tissues) from 15 patients undergoing radical orchiectomy were flash frozen in liquid nitrogen and sectioned to 15 μm thickness and thaw mounted to glass slides. The entire sample was two-dimensionally analyzed by the charged solvent spray to form a molecular image of the biological tissue. DESI-MS images were compared with formalin-fixed, hematoxylin and eosin (H&E) stained slides of the same material. Increased signal intensity was detected for two seminolipids [seminolipid (16:0/16:0) and seminolipid (30:0)] in the normal tubule testis tissue; these compounds were undetectable in seminoma tissue, as well as from the surrounding fat, muscle, and blood vessels. A glycerophosphoinositol [PI(18:0/20:4)] was also found at increased intensity in the normal testes tubule tissue when compared with seminoma tissue. Ascorbic acid (i.e., vitamin C) was found at increased amounts in seminoma tissue when compared with normal tissue. DESI-MS analysis was successfully used to visualize the location of several types of molecules across human seminoma and normal tissues. Discrimination between seminoma and adjacent normal testes tubules was achieved on the basis of the spatial distributions and varying intensities of particular lipid species as well as ascorbic acid. The increased presence of ascorbic acid within seminoma compared with normal seminiferous tubules was previously unknown.

  18. Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters.

    PubMed

    Sitter, Beathe; Lundgren, Steinar; Bathen, Tone F; Halgunset, Jostein; Fjosne, Hans E; Gribbestad, Ingrid S

    2006-02-01

    Breast cancer is the most frequent form of cancer in women and improved diagnostic methods are desirable. Malignant cells have altered metabolism and metabolic mapping might become a tool in cancer diagnostics. High-resolution magic angle spinning (HR MAS) MR spectroscopy of tissue biopsies provides detailed information on metabolic composition. The 600 MHz 1H HR MAS spectra were acquired of breast cancer tissue from 85 patients and adjacent non-involved tissue from 18 of these patients. Tissue specimens were investigated by microscopy after MR analysis. The resulting spectra were examined by three different approaches. Relative intensities of glycerophosphocholine (GPC), phosphocholine (PC) and choline were compared for cancerous and non-involved specimens. Eight metabolites, choline, creatine, beta-glucose, GPC, glycine, myo-inositol, PC and taurine, were quantified from the recorded spectra and compared with tumor histological type and size, patient's lymph node status and tissue composition of sample. The spectra were also compared with tumor histological type and size, lymph node status and tissue composition of samples using principal component analysis (PCA). Tumor samples could be distinguished from non-involved samples (82% sensitivity, 100% specificity) based on relative intensities of signals from GPC, PC and choline in 1H HR MAS spectra. Tissue concentrations of metabolites showed few differences between groups of samples, which can be caused by limitations in the quantification procedure. Choline and glycine concentrations were found to be significantly higher in tumors larger than 2 cm compared with smaller tumors. PCA of MAS spectra from patients with invasive ductal carcinomas indicated a possible prediction of spread to axillary lymph nodes. Metabolite estimates and PCA of MAS spectra were influenced by the percentage of tumor cells in the investigated specimens. 2006 John Wiley & Sons, Ltd.

  19. Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer.

    PubMed

    Reddy, Jay P; Atkinson, Rachel L; Larson, Richard; Burks, Jared K; Smith, Daniel; Debeb, Bisrat G; Ruffell, Brian; Creighton, Chad J; Bambhroliya, Arvind; Reuben, James M; Van Laere, Steven J; Krishnamurthy, Savitri; Symmans, William F; Brewster, Abenaa M; Woodward, Wendy A

    2018-06-01

    We hypothesized that breast tissue not involved by tumor in inflammatory breast cancer (IBC) patients contains intrinsic differences, including increased mammary stem cells and macrophage infiltration, which may promote the IBC phenotype. Normal breast parenchyma ≥ 5 cm away from primary tumors was obtained from mastectomy specimens. This included an initial cohort of 8 IBC patients and 60 non-IBC patients followed by a validation cohort of 19 IBC patients and 25 non-IBC patients. Samples were immunostained for either CD44 + CD49f + CD133/2 + mammary stem cell markers or the CD68 macrophage marker and correlated with IBC status. Quantitation of positive cells was determined using inForm software from PerkinElmer. We also examined the association between IBC status and previously published tumorigenic stem cell and IBC tumor signatures in the validation cohort samples. 8 of 8 IBC samples expressed isolated CD44 + CD49f + CD133/2 + stem cell marked cells in the initial cohort as opposed to 0/60 non-IBC samples (p = 0.001). Similarly, the median number of CD44 + CD49f + CD133/2 + cells was significantly higher in the IBC validation cohort as opposed to the non-IBC validation cohort (25.7 vs. 14.2, p = 0.007). 7 of 8 IBC samples expressed CD68 + histologically confirmed macrophages in initial cohort as opposed to 12/48 non-IBC samples (p = 0.001). In the validation cohort, the median number of CD68 + cells in IBC was 3.7 versus 1.0 in the non-IBC cohort (p = 0.06). IBC normal tissue was positively associated with a tumorigenic stem cell signature (p = 0.02) and with a 79-gene IBC signature (p < 0.001). Normal tissue from IBC patients is enriched for both mammary stem cells and macrophages and has higher association with both a tumorigenic stem cell signature and IBC-specific tumor signature. Collectively, these data suggest that IBC normal tissue differs from non-IBC tissue. Whether these changes occur before the tumor develops or

  20. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

    PubMed Central

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

    2011-01-01

    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  1. Pilot clinical study for quantitative spectral diagnosis of non-melanoma skin cancer.

    PubMed

    Rajaram, Narasimhan; Reichenberg, Jason S; Migden, Michael R; Nguyen, Tri H; Tunnell, James W

    2010-12-01

    Several research groups have demonstrated the non-invasive diagnostic potential of diffuse optical spectroscopy (DOS) and laser-induced fluorescence (LIF) techniques for early cancer detection. By combining both modalities, one can simultaneously measure quantitative parameters related to the morphology, function and biochemical composition of tissue and use them to diagnose malignancy. The objective of this study was to use a quantitative reflectance/fluorescence spectroscopic technique to determine the optical properties of normal skin and non-melanoma skin cancers and the ability to accurately classify them. An additional goal was to determine the ability of the technique to differentiate non-melanoma skin cancers from normal skin. The study comprised 48 lesions measured from 40 patients scheduled for a biopsy of suspected non-melanoma skin cancers. White light reflectance and laser-induced fluorescence spectra (wavelength range = 350-700 nm) were collected from each suspected lesion and adjacent clinically normal skin using a custom-built, optical fiber-based clinical instrument. After measurement, the skin sites were biopsied and categorized according to histopathology. Using a quantitative model, we extracted various optical parameters from the measured spectra that could be correlated to the physiological state of tissue. Scattering from cancerous lesions was significantly lower than normal skin for every lesion group, whereas absorption parameters were significantly higher. Using numerical cut-offs for our optical parameters, our clinical instrument could classify basal cell carcinomas with a sensitivity and specificity of 94% and 89%, respectively. Similarly, the instrument classified actinic keratoses and squamous cell carcinomas with a sensitivity of 100% and specificity of 50%. The measured optical properties and fluorophore contributions of normal skin and non-melanoma skin cancers are significantly different from each other and correlate well

  2. Upregulation of long non-coding RNA M26317 correlates with tumor progression and poor prognosis in gastric cancer.

    PubMed

    Li, Li; Wang, Yuan-Yu; Mou, Xiao Zhou; Ye, Zai-Yuan; Zhao, Zhong-Sheng

    2018-04-23

    To investigate the expression and clinical significance of long non-coding RNA (lnc RNA) in gastric cancer, we applied microarray analysis to obtain expression profiles of protein coding genes and lncRNAs in tumor and paired adjacent non-tumor tissues. We found that 41 lncRNAs were upregulated and 31 lncRNAs were downregulated more than 2-fold in gastric cancer versus noncancerous tissues (ratio>2.0, P<.01). We established a co-expression network of the differentially expressed lncRNAs and targeted coding genes that included 17 lncRNAs and 16 coding genes. As the results of microarray analysis showed that lncRNA M26317 was upregulated in gastric cancer tissues we examined the expression level of M26317 in 103 gastric cancer tissues by RT-PCR and 436 gastric cancer tissues by in situ hybridization. Our data confirmed that M26317 was upregulated in gastric cancer tissues. Moreover, expression of M26317 correlated with patient age, size of tumor, Lauren's classification, depth of invasion, lymph node and distant metastasis, TNM stage and poor prognosis (P<.05), but was not associated with gender, location of tumor, and differentiation (P>.05). M26317 may have an important role in malignant transformation and metastasis of gastric cancer. Copyright © 2018. Published by Elsevier Inc.

  3. Expression of Caspase-1 in breast cancer tissues and its effects on cell proliferation, apoptosis and invasion.

    PubMed

    Sun, Yanxia; Guo, Yingzhen

    2018-05-01

    The present study aimed to detect the expression of Caspase-1 in the tumor tissues and tumor-adjacent tissues of patients with breast cancer, and to investigate the effects of Caspase-1 on the proliferation, apoptosis and invasion of breast cancer cells. Reverse transcription-quantitative polymerase chain reaction was used to detect Caspase-1 mRNA expression in breast cancer tissues and tumor-adjacent tissues from patients. Additionally, the human breast cancer MDA-MB-231 cell line was treated with the Caspase-1 small molecule inhibitor Ac-YVAD-CMK, following which the changes to Caspase-1 protein expression were detected via western blotting. The MTT method detected the changes to cell proliferation, flow cytometry detected the rate of apoptosis, and a Transwell assay was employed to assess invasion. Caspase-1 mRNA expression was significantly decreased in the breast cancer tissues of patients, compared with in the tumor-adjacent tissues, a difference that was statistically significant (P<0.05). Treatment with the Ac-YVAD-CMK markedly decreased the protein expression of Caspase-1 in MDA-MB-231 cells, and the difference was statistically significant (P<0.05). Following this treatment of Ac-YVAD-CMK cells, the proliferation and invasion abilities markedly increased, while the apoptotic levels significantly decreased (P<0.05). In conclusion, the expression of Caspase-1 is low in breast cancer tissues, which may promote the proliferation and invasion of breast cancer cells and could be closely associated with the occurrence and development of breast cancer.

  4. Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC).

    PubMed

    Tang, Zhiyuan; Shen, Qin; Xie, Hao; Zhou, Xiaoyu; Li, Jun; Feng, Jian; Liu, Hua; Wang, Wei; Zhang, Shu; Ni, Songshi

    2016-07-19

    Fatty acid binding proteins (FABPs) are intracellular lipid-binding proteins that are involved in a variety of biological cellular processes, including tumorigenesis. In this study, we explored the expression pattern of FABP3 and FABP4 in non-small cell lung cancer (NSCLC) as well as their roles in prognosis. We determined mRNA expression of FABP3 and FABP4 in matched pairs of cancerous and non-cancerous fresh frozen tissues from 30 NSCLC patients. Tissue microarray immunohistochemical analysis (TMA-IHC) was applied to determine the protein expression of FABP3 and FABP4 in 281 cancerous and 121 matched adjacent non-cancerous tissue samples. Our results showed that both mRNA and protein expression of FABP3 and FABP4 were significantly higher in cancerous tissues when compared to non-cancerous tissues. Furthermore, high expression of FABP3 or FABP4 in NSCLC was significantly associated with advanced tumor node metastasis (TNM) stage and had a negative impact on the overall survival of NSCLC patients. Concurrent high expression of FABP3 and FABP4 was significantly related to TNM stage. In conclusion, our research demonstrated that high FABP3 or FABP4 expression had strong prognostic value for overall survival in NSCLC. Detection of FABP3 and FABP4 cooperatively was helpful to predict the prognosis of NSCLC.

  5. Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC)

    PubMed Central

    Tang, Zhiyuan; Shen, Qin; Xie, Hao; Zhou, Xiaoyu; Li, Jun; Feng, Jian; Liu, Hua; Wang, Wei; Zhang, Shu; Ni, Songshi

    2016-01-01

    Fatty acid binding proteins (FABPs) are intracellular lipid-binding proteins that are involved in a variety of biological cellular processes, including tumorigenesis. In this study, we explored the expression pattern of FABP3 and FABP4 in non-small cell lung cancer (NSCLC) as well as their roles in prognosis. We determined mRNA expression of FABP3 and FABP4 in matched pairs of cancerous and non-cancerous fresh frozen tissues from 30 NSCLC patients. Tissue microarray immunohistochemical analysis (TMA-IHC) was applied to determine the protein expression of FABP3 and FABP4 in 281 cancerous and 121 matched adjacent non-cancerous tissue samples. Our results showed that both mRNA and protein expression of FABP3 and FABP4 were significantly higher in cancerous tissues when compared to non-cancerous tissues. Furthermore, high expression of FABP3 or FABP4 in NSCLC was significantly associated with advanced tumor node metastasis (TNM) stage and had a negative impact on the overall survival of NSCLC patients. Concurrent high expression of FABP3 and FABP4 was significantly related to TNM stage. In conclusion, our research demonstrated that high FABP3 or FABP4 expression had strong prognostic value for overall survival in NSCLC. Detection of FABP3 and FABP4 cooperatively was helpful to predict the prognosis of NSCLC. PMID:27323829

  6. Expression of the hMLH1 and hMSH2 proteins in normal tissues: relationship to cancer predisposition in hereditary non-polyposis colon cancer.

    PubMed

    Plevová, Pavlína; Sedláková, Eva; Zapletalová, Jana; Krepelová, Anna; Skýpalová, Petra; Kolár, Zdenek

    2005-02-01

    The majority of tumours in patients with hereditary non-polyposis colon cancer (HNPCC) occur in large intestine and endometrium; also, other tissues are at increased risk. We studied expression of hMLH1 and hMSH2 proteins in 148 normal samples of various tissues from non-HNPCC patients and in 14 normal colon tissues from HNPCC patients. Immunohistochemical technique was used. Intensity of nuclear staining, percentage of stained cells and H-scores were calculated. Tissues were divided into groups. Groups A, B and C included tissues with increased risk of cancer in HNPCC A) stomach, small and large bowel; (B) endometrium; (C) ovary, ureter, urinary bladder, kidney and liver. Group D tissues were without increased risk. Expression of the proteins was significantly higher in groups A, B and C compared with group D (P<0.0001, P=0.0004 for hMSH2 in C versus D). The expression was highest in testis. In colons of HNPCC patients, expression of the mutated gene product was significantly lower than in non-HNPCC patients. In conclusion, hMLH1/hMSH2 protein expression is constitutively higher in certain cell types of certain tissues, including the majority of tissues that are at increased risk of cancer in HNPCC. However, association of strong hMLH1/hMSH2 expression with cancer risk is not strictly valid.

  7. Preliminary observations on differences in the Raman spectra of cancerous and noncancerous cells and connective tissue of human skin

    NASA Astrophysics Data System (ADS)

    Short, Michael A.; Lui, Harvey; McLean, David I.; Zeng, Haishan; Alajlan, Abdulmajeed; Chen, Michael X.

    2005-04-01

    A less invasive method of reliably detecting skin cancers is required. Raman spectroscopy is just one of several spectroscopic methods that look promising, but are not yet sufficiently reliable. More information is needed on how and why the Raman spectra of cancerous skin tissue is different from its normal counterpart. We have used confocal micro-Raman spectroscopy with a spatial resolution of about a micron to obtain spectra of unstained thin sections of human skin. We found that there were clear differences in the Raman spectra between cancerous and non-cancerous tissue both in cells and in the connective tissue. The DNA contribution to the spectra was generally stronger in malignant cells than normal ones. In regions of the dermis far away from the tumor one obtains the usual collagen spectra of normal skin, but adjacent to the tumor the spectra no longer appeared to be those of native collagen.

  8. Expression profile of circular RNAs in human gastric cancer tissues

    PubMed Central

    Huang, You-Sheng; Jie, Na; Zou, Ke-Jian; Weng, Yang

    2017-01-01

    Circular RNAs (circRNAs) represent a newly identified class of non-coding RNA molecules, which interfere with gene transcription by adsorbing microRNAs (miRNAs). CircRNAs serve important roles in disease development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in the occurrence and development of gastric cancer (GC) remains unclear. In the present study, the expression profiles of circRNAs were compared between GC and adjacent normal tissues using a circRNA microarray, following which quantitative polymerase chain reaction (qPCR) was used to confirm the results of the circRNA microarray. Compared with the adjacent, normal mucosal tissues, 16 circRNAs were upregulated and 84 circRNAs were downregulated in GC. A total of 10 circRNAs were selected for validation in three pairs of GC and adjacent noncancerous tissues. The qPCR results were consistent with the findings of the microarray-based expression analysis. Of the circRNAs studied, only circRNA-0026 (hsa_circ_0000026) exhibited significantly different expression in GC (2.8-fold, P=0.001). Furthermore, online Database for Annotation, Visualization and Integrated Discovery annotation was used to predict circRNA-targeted miRNA-gene interactions. The analysis revealed that circRNA-0026 may regulate RNA transcription, RNA metabolism, gene expression, gene silencing and other biological functions in GC. In conclusion, differential expression of circRNAs may be associated with GC tumorigenesis, and circRNA-0026 is a promising biomarker for GC diagnosis and targeted therapy. PMID:28737829

  9. Delayed Acquisition of Non-Adjacent Vocalic Distributional Regularities

    ERIC Educational Resources Information Center

    Gonzalez-Gomez, Nayeli; Nazzi, Thierry

    2016-01-01

    The ability to compute non-adjacent regularities is key in the acquisition of a new language. In the domain of phonology/phonotactics, sensitivity to non-adjacent regularities between consonants has been found to appear between 7 and 10 months. The present study focuses on the emergence of a posterior-anterior (PA) bias, a regularity involving two…

  10. Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

    DTIC Science & Technology

    2016-12-01

    Award Number: W81XWH-11-1-0744 TITLE: Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated...Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non- Neoplastic Prostate Tissue 5b. GRANT NUMBER 10623678 5c...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this project was to develop molecular models to

  11. Overexpression of Pokemon in non-small cell lung cancer and foreshowing tumor biological behavior as well as clinical results.

    PubMed

    Zhao, Zhi-Hong; Wang, Sheng-Fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-Li; Zhang, Jian; Fu, Kai

    2008-10-01

    Transcription factor Pokemon, a central regulation gene of the important tumor suppressor alternative reading frame (ARF), exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in non-small cell lung cancer and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Observe the expression of Pokemon in NSCLC and investigate its mechanism and clinical significance. Determine the expression of Pokemon in human NSCLC cell lines as well as 55 cases of NSCLC tumor tissues, tumor adjacent tissues and surrounding tissues by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and analyze the relationship between Pokemon expression in NSCLC tumor tissues and clinicopathological features. Determine 62 NSCLC tumor tissues (5 years ago) and p14(ARF) expression with immunohistochemical technique, discuss the correlation between them and assess the effect of Pokemon on prognosis of patients with lung cancer. Pokemon mRNA and protein took on high expression in lung cancer cell lines, and the expression difference between cancer tissues, tumor adjacent tissues and surrounding tissues had statistical significance (P<0.05). Pokemon expression and p14(ARF) expression were negatively correlated (r=-0.287). The expression of Pokemon was determined not to be associated with the patient's sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (P<0.05). Furthermore, it was shown that the survival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an

  12. Microfluidic extraction and microarray detection of biomarkers from cancer tissue slides

    NASA Astrophysics Data System (ADS)

    Nguyen, H. T.; Dupont, L. N.; Jean, A. M.; Géhin, T.; Chevolot, Y.; Laurenceau, E.; Gijs, M. A. M.

    2018-03-01

    We report here a new microfluidic method allowing for the quantification of human epidermal growth factor receptor 2 (HER2) expression levels from formalin-fixed breast cancer tissues. After partial extraction of proteins from the tissue slide, the extract is routed to an antibody (Ab) microarray for HER2 titration by fluorescence. Then the HER2-expressing cell area is evaluated by immunofluorescence (IF) staining of the tissue slide and used to normalize the fluorescent HER2 signal measured from the Ab microarray. The number of HER2 gene copies measured by fluorescence in situ hybridization (FISH) on an adjacent tissue slide is concordant with the normalized HER2 expression signal. This work is the first study implementing biomarker extraction and detection from cancer tissue slides using microfluidics in combination with a microarray system, paving the way for further developments towards multiplex and precise quantification of cancer biomarkers.

  13. Expression of transcription factor Pokemon in non-small cell lung cancer and its clinical significance.

    PubMed

    Zhao, Zhi-hong; Wang, Sheng-fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-li; Fu, Kai; Zhang, Jian

    2008-03-05

    Transcription factor Pokemon, a central regulation gene of the important tumor suppressor ARF gene, exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in NSCLC and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Fifty-five cases of NSCLC were involved in this study. The expression of Pokemon in the tumor tissue, the corresponding tumor adjacent tissue and the surrounding tissue was detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, with the aim of investigating the correlation between the expression of Pokemon in tumor tissue of NSCLC and its clinical pathological characteristics. Moreover, a prognostic analysis was carried out based upon the immunohistochemical (IHC) detection of the expression of Pokemon gene in archival tumor specimens (5 years ago) of 62 cases of NSCLC. Statistical significance of the expression of Pokemon mRNA and protein was determined in the tumor tissue, the tumor adjacent tissue and the surrounding tissue (P<0.05). The expression of Pokemon was determined not to be associated with the patients' sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (P<0.05). Furthermore, it was shown that the survival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034). Pokemon was over-expressed in NSCLC tissue and the expression of Pokemon might be of clinical significance in non-small cell lung cancer prognostic evaluation.

  14. Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer.

    PubMed

    Xiong, Hui; Zhang, Jiangnan

    2017-12-01

    The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated modulator of apoptosis (PUMA) genes in patients with colorectal cancer were investigated, to explore the correlation between the expression of ATM and PUMA and tumor development, to evaluate the clinical significance of ATM and PUMA in the treatment of colorectal cancer. Quantitative real-time PCR was used to detect the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67 patients with colorectal cancer and in normal colorectal tissue of 33 patients with colorectal polyps at mRNA level. The expression level of ATM mRNA in colorectal cancer tissues was significantly higher than that in normal mucosa tissues and adjacent non-cancerous tissue (P≤0.05), while no significant differences in expression level of ATM mRNA were found between normal mucosa tissues and adjacent noncancerous tissue (P=0.07). There was a negative correlation between the expression of ATM mRNA and the degree of differentiation of colorectal cancer (r= -0.312, P=0.013), while expression level of ATM mRNA was not significantly correlated with the age, sex, tumor invasion, lymph node metastasis or clinical stage (P>0.05). Expression levels of PUMA mRNA in colorectal cancer tissues, adjacent noncancerous tissue and normal tissues were 0.68±0.07, 0.88±0.04 and 1.76±0.06, respectively. Expression level of PUMA mRNA in colorectal cancer tissues and adjacent noncancerous tissue was significantly lower than that in normal colorectal tissues (P<0.05). The results showed that ATM mRNA is expressed abnormally in colorectal cancer tissues. Expression of PUMA gene in colorectal carcinoma is downregulated, and is negatively correlated with the occurrence of cancer.

  15. Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhu, Hongxue; Department of Urology, Hospital of Xinjiang Production and Construction Corps, Urumqi 830002; Li, Xuechao

    Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cellmore » apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway. - Highlights: • We first report the role of ANRIL in bladder cancer. • ANRIL is obviously up-regulated in bladder cancer tissues. • ANRIL regulates bladder cancer cell proliferation and cell apoptosis through the intrinsic pathway.« less

  16. Coiled-coil domain-containing protein 8 inhibits the invasiveness and migration of non-small cell lung cancer cells.

    PubMed

    Jiang, Gui-Yang; Zhang, Xiu-Peng; Zhang, Yong; Xu, Hong-Tao; Wang, Liang; Li, Qing-Chang; Wang, En-Hua

    2016-10-01

    Lung cancer has always been the leading cause of death among patients with malignant tumors, and the majority of these patients die because of cancer cell invasion and metastasis. Previous studies have implicated coiled-coil domain-containing protein 8 (CCDC8) as a tumor suppressor in several types of cancer, such as breast and prostate cancers. However, the expression levels or functions of CCDC8 in lung cancer have not been elucidated. Here, we used immunohistochemical staining to measure CCDC8 expression in 147 samples from tumors and 30 samples from the adjacent normal lung tissues of patients with non-small cell lung cancer. CCDC8 was shown to be located predominantly in the cytoplasm and partially on the cell membrane, and its expression level was significantly lower in lung cancer samples than that in the adjacent normal lung tissues (P=.001). CCDC8 expression was closely related to tumor differentiation (P=.039), tumor-node-metastasis stage (P=.009), lymph node metastasis (P=.038), and prognosis (P=.043) of lung cancer. Transfection of A549 cells with CCDC8 significantly reduced cell invasion and migration (P<.05), whereas the invasiveness and migration capacity in CCDC8-knockdown A549 cells were significantly increased in comparison with the control cells (P<.05). Furthermore, we demonstrated that CCDC8 can downregulate the expression of Snail and upregulate the expression of E-cadherin by inhibiting p-P38 and p-IκBα. Collectively, CCDC8 may suppress the invasion and metastasis of lung cancer cells, and it may represent a promising therapeutic target for non-small cell lung cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer

    PubMed Central

    2014-01-01

    Background A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient’s gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. Methods A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Results Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue. Conclusions The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patients. PMID:24597571

  18. Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments.

    PubMed

    Akkiprik, Mustafa; Peker, İrem; Özmen, Tolga; Amuran, Gökçe Güllü; Güllüoğlu, Bahadır M; Kaya, Handan; Özer, Ayşe

    2015-11-10

    IGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer.

  19. Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6

    PubMed Central

    Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

    2017-01-01

    AIM To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. METHODS Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. RESULTS After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age (P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P < 0.05). CONCLUSION Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation. PMID:28293090

  20. Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6.

    PubMed

    Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

    2017-02-28

    To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ , as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend ( P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age ( P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues ( P < 0.05). Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation.

  1. The ESR1 and GPX1 gene expression level in human malignant and non-malignant breast tissues.

    PubMed

    Król, Magdalena B; Galicki, Michał; Grešner, Peter; Wieczorek, Edyta; Jabłońska, Ewa; Reszka, Edyta; Morawiec, Zbigniew; Wąsowicz, Wojciech; Gromadzińska, Jolanta

    2018-01-01

    The aim of this study was to establish whether the gene expression of estrogen receptor alpha (encoded by ESR1) correlates with the expression of glutathione peroxidase 1 (encoded by GPX1) in the tumor and adjacent tumor-free breast tissue, and whether this correlation is affected by breast cancer. Such relationships may give further insights into breast cancer pathology with respect to the status of estrogen receptor. We used the quantitative real-time PCR technique to analyze differences in the expression levels of the ESR1 and GPX1 genes in paired malignant and non-malignant tissues from breast cancer patients. ESR1 and GPX1 expression levels were found to be significantly down-regulated by 14.7% and 7.4% (respectively) in the tumorous breast tissue when compared to the non-malignant one. Down-regulation of these genes was independent of the tumor histopathology classification and clinicopathological factors, while the ESR1 mRNA level was reduced with increasing tumor grade (G1: 103% vs. G2: 85.8% vs. G3: 84.5%; p<0.05). In the non-malignant and malignant breast tissues, the expression levels of ESR1 and GPX1 were significantly correlated with each other (Rs=0.450 and Rs=0.360; respectively). Our data suggest that down-regulation of ESR1 and GPX1 was independent of clinicopathological factors. Down-regulation of ESR1 gene expression was enhanced by the development of the disease. Moreover, GPX1 and ESR1 gene expression was interdependent in the malignant breast tissue and further work is needed to determine the mechanism underlying this relationship.

  2. Towards automated early cancer detection: Non-invasive, fluorescence-based approaches for quantitative assessment of cells and tissue to identify pre-cancers

    NASA Astrophysics Data System (ADS)

    Levitt, Jonathan Michael

    Cancer is the second leading cause of death globally, second only to heart disease. As in many diseases, patient survival is directly related to how early lesions are detected. Using conventional screening methods, the early changes associated with cancer, which occur on the microscopic scale, can easily go overlooked. Due to the inherent drawbacks of conventional techniques we present non-invasive, optically based methods to acquire high resolution images from live samples and assess cellular function associated with the onset of disease. Specifically, we acquired fluorescence images from NADH and FAD to quantify morphology and metabolic activity. We first conducted studies to monitor monolayers of keratinocytes in response to apoptosis which has been shown to be disrupted during cancer progression. We found that as keratinocytes undergo apoptosis there are populations of mitochondria that exhibit a higher metabolic activity that become progressively confined to a gradually smaller perinuclear region. To further assess the changes associated with early cancer growth we developed automated methods to rapidly quantify fluorescence images and extract morphological and metabolic information from life tissue. In this study, we simultaneously quantified mitochondrial organization, metabolic activity, nuclear size distribution, and the localization of the structural protein keratin, to differentiate between normal and pre-cancerous engineered tissues. We found the degree mitochondrial organization, as determined from the fractal derived Hurst parameter, was well correlated to level of cellular differentiation. We also found that the metabolic activity in the pre-cancerous cells was greater and more consistent throughout tissue depths in comparison to normal tissue. Keratin localization, also quantified from the fluorescence images, we found it to be confined to the uppermost layers of normal tissue while it was more evenly distributed in the precancerous tissues. To

  3. Learning Non-Adjacent Regularities at Age 0 ; 7

    ERIC Educational Resources Information Center

    Gervain, Judit; Werker, Janet F.

    2013-01-01

    One important mechanism suggested to underlie the acquisition of grammar is rule learning. Indeed, infants aged 0 ; 7 are able to learn rules based on simple identity relations (adjacent repetitions, ABB: "wo fe fe" and non-adjacent repetitions, ABA: "wo fe wo", respectively; Marcus et al., 1999). One unexplored issue is…

  4. Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance.

    PubMed

    Tian, Mengqian; Chen, Ruoyu; Li, Tianwen; Xiao, Bingxiu

    2018-03-01

    Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about circRNAs' diagnostic values for gastric cancer, one of the worldwide most common diseases of mortality. The hsa_circ_0003159 levels in 108 paired gastric cancer tissues and adjacent non-tumorous tissues from surgical patients with gastric cancer were first detected by real-time quantitative reverse transcription-polymerase chain reaction. Then, the relationships between hsa_circ_0003159 expression levels in gastric cancer tissues and the clinicopathological factors of patients with gastric cancer were analyzed. Finally, its diagnostic value was evaluated through the receiver operating characteristic curve. Compared with paired adjacent non-tumorous tissues, hsa_circ_0003159 expression was significantly down-regulated in gastric cancer tissues. What is more, we found that hsa_circ_0003159 expression levels were significantly negatively associated with gender, distal metastasis, and tumor-node-metastasis stage. All of the results suggest that hsa_circ_0003159 may be a potential cancer marker of patients with gastric cancer. © 2017 Wiley Periodicals, Inc.

  5. Dynamics of cancerous tissue correlates with invasiveness

    NASA Astrophysics Data System (ADS)

    West, Ann-Katrine Vransø; Wullkopf, Lena; Christensen, Amalie; Leijnse, Natascha; Tarp, Jens Magelund; Mathiesen, Joachim; Erler, Janine Terra; Oddershede, Lene Broeng

    2017-03-01

    Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.

  6. Long non-coding RNA PVT1 as a novel potential biomarker for predicting the prognosis of colorectal cancer.

    PubMed

    Fan, Heng; Zhu, Jian-Hua; Yao, Xue-Qing

    2018-05-01

    Long non-coding RNA (lncRNA) plays a very important role in the occurrence and development of various tumors, and is a potential biomarker for cancer diagnosis and prognosis. The purpose of this study was to investigate the relationship between the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and the prognostic significance in patients with colorectal cancer. The expression of PVT1 was measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in cancerous and adjacent tissues of 210 colorectal cancer patients. The disease-free survival and overall survival of colorectal cancer patients were evaluated by Kaplan-Meier analysis, and univariate and multivariate analysis were performed by Cox proportional-hazards model. Our results revealed that PVT1 expression in cancer tissues of colorectal cancer was significantly higher than that of adjacent tissues ( P<0.001). High PVT1 expression was increased by 51.4% (108/210), which was significantly correlated with the tumor differentiation, the depth of invasion, the stage of tumor, node, metastasis (TNM), and lymphatic metastasis. The Kaplan-Meier analysis showed that high PVT1 expression resulted in a shorter disease-free survival (Log-rank test P<0.001) and overall survival (Log-rank test P<0.001) compared with the low PVT1 expression group in colorectal cancer patients, whether at TNM I/II stage or at TNM III/IV stage. A multivariate Cox regression analysis demonstrated that high PVT1 expression was an independent predictor of poor prognosis in colorectal cancer patients. Our results suggest that high PVT1 expression might be a potential biomarker for assessing tumor recurrence and prognosis in colorectal cancer patients.

  7. Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

    DTIC Science & Technology

    2015-10-01

    with Cancer in Non-Neoplastic Prostate Tissue PRINCIPAL INVESTIGATOR: Farhad Kosari, Ph.D. CONTRACTING ORGANIZATION: Mayo Clinic Rochester, MN...E-Mail: kosari.farhad@mayo.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Mayo Clinic Rochester, MN 55905-0002 8...with the Tissue Request Acquisition Group (TRAG) at the Mayo Clinic , a process was implemented for the collection of resected prostates from

  8. Investigation of metabolite changes in the transition from pre-invasive to invasive cervical cancer measured using (1)H and (31)P magic angle spinning MRS of intact tissue.

    PubMed

    De Silva, Sonali S; Payne, Geoffrey S; Thomas, Valerie; Carter, Paul G; Ind, Thomas E J; deSouza, Nandita M

    2009-02-01

    The aim of this study was to determine the metabolic changes in the transition from pre-invasive to invasive cervical cancer using high-resolution magic angle spinning (HR-MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n = 5), cervical intraepithelial neoplasia (CIN; mild, n = 5; moderate/severe, n = 40), and invasive cancer (n = 23). (1)H HR-MAS MRS data were acquired using a Bruker Avance 11.74 T spectrometer (Carr-Purcell-Meiboom-Gill sequence; TR = 4.8 s; TE = 135 ms; 512 scans; 41 min acquisition). (31)P HR-MAS spectra were obtained from the normal subjects and cancer patients only (as acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a (1)H-decoupled pulse-acquire sequence (TR = 2.82 s; 2048 scans; 96 min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of choline (P = 0.0001) and phosphocholine (P = 0.002) in tissue from patients with cancer than from patients with high-grade dyskaryosis, but no differences between non-cancer groups. Division by histology of the sample also showed increases in choline (P = 0.002) and phosphocholine (P = 0.002) in cancer compared with high-grade CIN tissue. Phosphoethanolamine was increased in cancer compared with normal tissue (P = 0.0001). Estimated concentrations of alanine (P = 0.01) and creatine (P = 0.008) were significantly reduced in normal tissue from cancer patients compared with normal tissue from non-cancer patients. The estimated concentration of choline was significantly increased in CIN tissue from cancer patients compared with CIN tissue from non-cancer patients (P = 0.0001). Estimated

  9. Visualizing the Histotripsy Process: Bubble Cloud-Cancer Cell Interactions in a Tissue-Mimicking Environment.

    PubMed

    Vlaisavljevich, Eli; Maxwell, Adam; Mancia, Lauren; Johnsen, Eric; Cain, Charles; Xu, Zhen

    2016-10-01

    Histotripsy is a non-invasive ultrasonic ablation method that uses cavitation to mechanically fractionate tissue into acellular debris. With a sufficient number of pulses, histotripsy can completely fractionate tissue into a liquid-appearing homogenate with no cellular structures. The location, shape and size of lesion formation closely match those of the cavitation cloud. Previous work has led to the hypothesis that the rapid expansion and collapse of histotripsy bubbles fractionate tissue by inducing large stress and strain on the tissue structures immediately adjacent to the bubbles. In the work described here, the histotripsy bulk tissue fractionation process is visualized at the cellular level for the first time using a custom-built 2-MHz transducer incorporated into a microscope stage. A layer of breast cancer cells were cultured within an optically transparent fibrin-based gel phantom to mimic cells inside a 3-D extracellular matrix. To test the hypothesis, the cellular response to single and multiple histotripsy pulses was investigated using high-speed optical imaging. Bubbles were always generated in the extracellular space, and significant cell displacement/deformation was observed for cells directly adjacent to the bubble during both bubble expansion and collapse. The largest displacements were observed during collapse for cells immediately adjacent to the bubble, with cells moving more than 150-300 μm in less than 100 μs. Cells often underwent multiple large deformations (>150% strain) over multiple pulses, resulting in the bisection of cells multiple times before complete removal. To provide theoretical support to the experimental observations, a numerical simulation was conducted using a single-bubble model, which indicated that histotripsy exerts the largest strains and cell displacements in the regions immediately adjacent to the bubble. The experimental and simulation results support our hypothesis, which helps to explain the formation of the

  10. The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop) mononucleotide sequence variations, is associated with bladder cancer.

    PubMed

    Shakhssalim, Nasser; Houshmand, Massoud; Kamalidehghan, Behnam; Faraji, Abolfazl; Sarhangnejad, Reza; Dadgar, Sepideh; Mobaraki, Maryam; Rosli, Rozita; Sanati, Mohammad Hossein

    2013-12-05

    Bladder cancer is a relatively common and potentially life-threatening neoplasm that ranks ninth in terms of worldwide cancer incidence. The aim of this study was to determine deletions and sequence variations in the mitochondrial displacement loop (D-loop) region from the blood specimens and tumoral tissues of patients with bladder cancer, compared to adjacent non-tumoral tissues. The DNA from blood, tumoral tissues and adjacent non-tumoral tissues of twenty-six patients with bladder cancer and DNA from blood of 504 healthy controls from different ethnicities were investigated to determine sequence variation in the mitochondrial D-loop region using multiplex polymerase chain reaction (PCR), DNA sequencing and southern blotting analysis. From a total of 110 variations, 48 were reported as new mutations. No deletions were detected in tumoral tissues, adjacent non-tumoral tissues and blood samples from patients. Although the polymorphisms at loci 16189, 16261 and 16311 were not significantly correlated with bladder cancer, the C16069T variation was significantly present in patient samples compared to control samples (p < 0.05). Interestingly, there was no significant difference (p > 0.05) of C variations, including C7TC6, C8TC6, C9TC6 and C10TC6, in D310 mitochondrial DNA between patients and control samples. Our study suggests that 16069 mitochondrial DNA D-Loop mutations may play a significant role in the etiology of bladder cancer and facilitate the definition of carcinogenesis-related mutations in human cancer.

  11. Immunohistochemical quantification of the cobalamin transport protein, cell surface receptor and Ki-67 in naturally occurring canine and feline malignant tumors and in adjacent normal tissues

    PubMed Central

    Sysel, Annette M.; Valli, Victor E.; Bauer, Joseph A.

    2015-01-01

    Cancer cells have an obligate need for cobalamin (vitamin B12) to enable DNA synthesis necessary for cellular replication. This study quantified the immunohistochemical expression of the cobalamin transport protein (transcobalamin II; TCII), cell surface receptor (transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in naturally occurring canine and feline malignant tumors, and compared these results to expression in corresponding adjacent normal tissues. All malignant tumor tissues stained positively for TCII, TCII-R and Ki-67 proteins; expression varied both within and between tumor types. Expression of TCII, TCII-R and Ki-67 was significantly higher in malignant tumor tissues than in corresponding adjacent normal tissues in both species. There was a strong correlation between TCII and TCII-R expression, and a modest correlation between TCII-R and Ki-67 expression in both species; a modest association between TCII and Ki-67 expression was present in canine tissues only. These results demonstrate a quantifiable, synchronous up-regulation of TCII and TCII-R expression by proliferating canine and feline malignant tumors. The potential to utilize these proteins as biomarkers to identify neoplastic tissues, streamline therapeutic options, evaluate response to anti-tumor therapy and monitor for recurrent disease has important implications in the advancement of cancer management for both human and companion animal patients. PMID:25633912

  12. Guanine nucleotide binding protein-like 3 is a potential prognosis indicator of gastric cancer.

    PubMed

    Chen, Jing; Dong, Shuang; Hu, Jiangfeng; Duan, Bensong; Yao, Jian; Zhang, Ruiyun; Zhou, Hongmei; Sheng, Haihui; Gao, Hengjun; Li, Shunlong; Zhang, Xianwen

    2015-01-01

    Guanine nucleotide binding protein-like 3 (GNL3) is a GIP-binding nuclear protein that has been reported to be involved in various biological processes, including cell proliferation, cellular senescence and tumorigenesis. This study aimed to investigate the expression level of GNL3 in gastric cancer and to evaluate the relationship between its expression and clinical variables and overall survival of gastric cancer patients. The expression level of GNL3 was examined in 89 human gastric cancer samples using immunohistochemistry (IHC) staining. GNL3 in gastric cancer tissues was significantly upregulated compared with paracancerous tissues. GNL3 expression in adjacent non-cancerous tissues was associated with sex and tumor size. Survival analyses showed that GNL3 expression in both gastric cancer and adjacent non-cancerous tissues were not related to overall survival. However, in the subgroup of patients with larger tumor size (≥ 6 cm), a close association was found between GNL3 expression in gastric cancer tissues and overall survival. GNL3-positive patients had a shorter survival than GNL3-negative patients. Our study suggests that GNL3 might play an important role in the progression of gastric cancer and serve as a biomarker for poor prognosis in gastric cancer patients.

  13. Non-invasive pH determination adjacent to degradable biomaterials in vivo.

    PubMed

    Bartsch, Ivonne; Willbold, Elmar; Rosenhahn, Bodo; Witte, Frank

    2014-01-01

    An appropriate pH level is an important prerequisite for the physiologal functioning of cells and tissues. Changes in the extracellular pH often lead to specific cellular reactions and an altered metabolism of cells and tissues influences the extracellular pH range. Thus a method to monitor the extracellular pH is a valuable tool to track specific tissue reactions. In this article we describe a method for the determination of the pH range adjacent to degradable biomaterials using wireless in vivo imaging. Using hairless but immunocompetent mice the fluorophor 5-(6)-carboxy SNARF-1 and the in vivo fluorescence and multispectral acquisition and analysis system Maestro it is possible to track shifts in pH in small living animals over a longer period of time. This method is especially suitable for studies which focus on the interaction of degrading biomaterials with their adjacent tissues. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Long non-coding RNA RUNXOR accelerates MDSC-mediated immunosuppression in lung cancer.

    PubMed

    Tian, Xinyu; Ma, Jie; Wang, Ting; Tian, Jie; Zheng, Yu; Peng, Rongrong; Wang, Yungang; Zhang, Yue; Mao, Lingxiang; Xu, Huaxi; Wang, Shengjun

    2018-06-18

    RUNX1 overlapping RNA (RUNXOR) is a long non-coding RNA that has been indicated as a key regulator in the development of myeloid cells by targeting runt-related transcription factor 1 (RUNX1). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells consisting of immature granulocytes and monocytes with immunosuppression. However, the impact of lncRNA RUNXOR on the development of MDSCs remains unknown. Both the expressions of RUNXOR and RUNX1 in the peripheral blood were measured by qRT-PCR. Human MDSCs used in this study were isolated from tumor tissue of patients with lung cancer by FCM or induced from PBMCs of healthy donors with IL-1β + GM-CSF. Specific siRNA was used to knockdown the expression of RUNXOR in MDSCs. In this study, we found that the lncRNA RUNXOR was upregulated in the peripheral blood of lung cancer patients. In addition, as a target gene of RUNXOR, the expression of RUNX1 was downregulated in lung cancer patients. Finally, the expression of RUNXOR was higher in MDSCs isolated from the tumor tissues of lung cancer patients compared with cells from adjacent tissue. In addition, RUNXOR knockdown decreased Arg1 expression in MDSCs. Based on our findings, it is illustrated that RUNXOR is significantly associated with the immunosuppression induced by MDSCs in lung cancer patients and may be a target of anti-tumor therapy.

  15. The regulatory role of SLP-2 and mechanism on CCBE1 gene expression in rectal carcinoma and adjacent lymphatic tube tissues.

    PubMed

    Guo, R-L; Wang, X-R; Wang, Q-G; Li, Z; Lu, X; Miao, R-Z; Chang, H

    2018-01-01

      The incidence of rectal carcinoma (RC) has been increasing recently, and becomes the second most common digestive tumors besides gastric cancer, with a rise in the incidence of RC in younger populations. The early diagnosis and treatment are thus critical for the improvement of survival rate and life quality of patients. Stomatin-like protein 2 (SLP-2) is a type of membrane factor, which is generally found highly expressed in various tumors. Collagen and calcium-binding EGF domain (CCBE1) belongs to lymphatic tube genesis factor. The regulatory role of SLP-2 gene on CCBE1 expression in RC tumor and adjacent lymphatic tube tissues, however, has not been studied. 52 RC patients were recruited, and tumor and adjacent lymphatic tube tissues were collected. Real-time PCR, western blotting and immunohistochemistry (IHC) staining were used to analyze SLP-2 and CCBE1 expressions. Human lymphatic endothelial cells (LECs) were cultured in vitro and were assigned to control, scramble, and SLP-2 siRNA group. MTT assay was used to detect cell proliferation, while caspase 3 activity was detected. SLP-2 and CCBE1 levels were significantly elevated in tumor lymphatic tissues, compared to that in adjacent tissues. Statistically positive correlation between SLP-1 and CCBE2 was found (p<0.05). The downregulation of SLP-2 by siRNA inhibited cell proliferation, elevated caspase3 activity, and decreased CCBE1 expression (p<0.05 compared to control group). SLP-2 is up-regulated in RC lymphatic tissues, and is positively correlated with the level of CCBE1, which provides the academic the basis for the development of medicine targeting SLP-2 in the anti-rectal carcinoma therapy.

  16. Processing multiple non-adjacent dependencies: evidence from sequence learning

    PubMed Central

    de Vries, Meinou H.; Petersson, Karl Magnus; Geukes, Sebastian; Zwitserlood, Pienie; Christiansen, Morten H.

    2012-01-01

    Processing non-adjacent dependencies is considered to be one of the hallmarks of human language. Assuming that sequence-learning tasks provide a useful way to tap natural-language-processing mechanisms, we cross-modally combined serial reaction time and artificial-grammar learning paradigms to investigate the processing of multiple nested (A1A2A3B3B2B1) and crossed dependencies (A1A2A3B1B2B3), containing either three or two dependencies. Both reaction times and prediction errors highlighted problems with processing the middle dependency in nested structures (A1A2A3B3_B1), reminiscent of the ‘missing-verb effect’ observed in English and French, but not with crossed structures (A1A2A3B1_B3). Prior linguistic experience did not play a major role: native speakers of German and Dutch—which permit nested and crossed dependencies, respectively—showed a similar pattern of results for sequences with three dependencies. As for sequences with two dependencies, reaction times and prediction errors were similar for both nested and crossed dependencies. The results suggest that constraints on the processing of multiple non-adjacent dependencies are determined by the specific ordering of the non-adjacent dependencies (i.e. nested or crossed), as well as the number of non-adjacent dependencies to be resolved (i.e. two or three). Furthermore, these constraints may not be specific to language but instead derive from limitations on structured sequence learning. PMID:22688641

  17. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    NASA Technical Reports Server (NTRS)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

  18. Comparison of non-Gaussian and Gaussian diffusion models of diffusion weighted imaging of rectal cancer at 3.0 T MRI.

    PubMed

    Zhang, Guangwen; Wang, Shuangshuang; Wen, Didi; Zhang, Jing; Wei, Xiaocheng; Ma, Wanling; Zhao, Weiwei; Wang, Mian; Wu, Guosheng; Zhang, Jinsong

    2016-12-09

    Water molecular diffusion in vivo tissue is much more complicated. We aimed to compare non-Gaussian diffusion models of diffusion-weighted imaging (DWI) including intra-voxel incoherent motion (IVIM), stretched-exponential model (SEM) and Gaussian diffusion model at 3.0 T MRI in patients with rectal cancer, and to determine the optimal model for investigating the water diffusion properties and characterization of rectal carcinoma. Fifty-nine consecutive patients with pathologically confirmed rectal adenocarcinoma underwent DWI with 16 b-values at a 3.0 T MRI system. DWI signals were fitted to the mono-exponential and non-Gaussian diffusion models (IVIM-mono, IVIM-bi and SEM) on primary tumor and adjacent normal rectal tissue. Parameters of standard apparent diffusion coefficient (ADC), slow- and fast-ADC, fraction of fast ADC (f), α value and distributed diffusion coefficient (DDC) were generated and compared between the tumor and normal tissues. The SEM exhibited the best fitting results of actual DWI signal in rectal cancer and the normal rectal wall (R 2  = 0.998, 0.999 respectively). The DDC achieved relatively high area under the curve (AUC = 0.980) in differentiating tumor from normal rectal wall. Non-Gaussian diffusion models could assess tissue properties more accurately than the ADC derived Gaussian diffusion model. SEM may be used as a potential optimal model for characterization of rectal cancer.

  19. miRNA-148a serves as a prognostic factor and suppresses migration and invasion through Wnt1 in non-small cell lung cancer.

    PubMed

    Chen, Yong; Min, Lingfeng; Ren, Chuanli; Xu, Xingxiang; Yang, Jianqi; Sun, Xinchen; Wang, Tao; Wang, Fang; Sun, Changjiang; Zhang, Xizhi

    2017-01-01

    Lung cancer is the leading cause of cancer death in the world, and aberrant expression of miRNA is a common feature during the cancer initiation and development. Our previous study showed that levels of miRNA-148a assessed by quantitative real-time polymerase chain reaction (qRT-PCR) were a good prognosis factor for non-small cell lung cancer (NSCLC) patients. In this study, we used high-throughput formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays and in situ hybridization (ISH) to determine the clinical significances of miRNA-148a and aimed to find novel target of miRNA-148a in lung cancer. Our results showed that there were 86 of 159 patients with low miRNA-148a expression and miRNA-148a was significantly down-regulated in primary cancer tissues when compared with their adjacent normal lung tissues. Low expression of miRNA-148a was strongly associated with high tumor grade, lymph node (LN) metastasis and a higher risk of tumor-related death in NSCLC. Lentivirus mediated overexpression of miRNA-148a inhibited migration and invasion of A549 and H1299 lung cancer cells. Furthermore, we validated Wnt1 as a direct target of miRNA-148a. Our data showed that the Wnt1 expression was negatively correlated with the expression of miRNA-148a in both primary cancer tissues and their corresponding adjacent normal lung tissues. In addition, overexpression of miRNA-148a inhibited Wnt1 protein expression in cancer cells. And knocking down of Wnt-1 by siRNA had the similar effect of miRNA-148a overexpression on cell migration and invasion in lung cancer cells. In conclusion, our results suggest that miRNA-148a inhibited cell migration and invasion through targeting Wnt1 and this might provide a new insight into the molecular mechanisms of lung cancer metastasis.

  20. Cancer testis antigen OY-TES-1 expression and serum immunogenicity in colorectal cancer: its relationship to clinicopathological parameters.

    PubMed

    Luo, Bin; Yun, Xiang; Fan, Rong; Lin, Yong-Da; He, Shu-Jia; Zhang, Qing-Mei; Mo, Fa-Rong; Chen, Fang; Xiao, Shao-Wen; Xie, Xiao-Xun

    2013-01-01

    Cancer testis (CT) antigens are attractive targets for cancer immunotherapy because their expression is restricted in normal germ line tissues but frequently detected in variety of tumors. OY-TES-1 is identified as a member of CT antigens. Current knowledge about OY-TES-1 expression in colorectal cancer (CRC) is solely based on mRNA analysis. None of previous researches has studied OY-TES-1 at protein level. In this study, OY-TES-1 polyclonal antibody was generated. The expression of OY-TES-1 mRNA and protein was detected by RT-PCR and immunohistochemistry in 60 CRC and paired adjacent non-tumor tissues, 24 colorectal adenoma and 3 normal colon tissues, respectively. Sera from 73 CRC patients were also tested for OY-TES-1 antibody by ELISA. Our results showed that the frequency of OY-TES-1 mRNA expression was statistically higher in CRC (73.3%, 44/60) than that in adjacent non-tumor tissue (55.0%, 33/60) and colorectal adenoma (45.8%, 11/24). For the first time, OY-TES-1 protein expression was found in (43.3%, 26/60) of CRC tissues, but absent in any of adjacent non-tumor and colorectal adenoma tissues. No OY-TES-1 expression was found in normal colon by either RT-PCR or immunohistochemistry. Furthermore, OY-TES-1 protein expression was correlated with tumor invasion stage (P=0.004) and histological grade (P=0.040). Anti-OY-TES-1 antibody was detected in (9.6%, 7/73) of CRC patients' sera but not in 76 healthy donors. This finding demonstrates that OY-TES-1 is frequently expressed in CRC and is able to induce humoral immune response spontaneously in CRC patients, suggesting that it might be a promising immunotherapy target for CRC.

  1. Cancer testis antigen OY-TES-1 expression and serum immunogenicity in colorectal cancer: its relationship to clinicopathological parameters

    PubMed Central

    Luo, Bin; Yun, Xiang; Fan, Rong; Lin, Yong-Da; He, Shu-Jia; Zhang, Qing-Mei; Mo, Fa-Rong; Chen, Fang; Xiao, Shao-Wen; Xie, Xiao-Xun

    2013-01-01

    Cancer testis (CT) antigens are attractive targets for cancer immunotherapy because their expression is restricted in normal germ line tissues but frequently detected in variety of tumors. OY-TES-1 is identified as a member of CT antigens. Current knowledge about OY-TES-1 expression in colorectal cancer (CRC) is solely based on mRNA analysis. None of previous researches has studied OY-TES-1 at protein level. In this study, OY-TES-1 polyclonal antibody was generated. The expression of OY-TES-1 mRNA and protein was detected by RT-PCR and immunohistochemistry in 60 CRC and paired adjacent non-tumor tissues, 24 colorectal adenoma and 3 normal colon tissues, respectively. Sera from 73 CRC patients were also tested for OY-TES-1 antibody by ELISA. Our results showed that the frequency of OY-TES-1 mRNA expression was statistically higher in CRC (73.3%, 44/60) than that in adjacent non-tumor tissue (55.0%, 33/60) and colorectal adenoma (45.8%, 11/24). For the first time, OY-TES-1 protein expression was found in (43.3%, 26/60) of CRC tissues, but absent in any of adjacent non-tumor and colorectal adenoma tissues. No OY-TES-1 expression was found in normal colon by either RT-PCR or immunohistochemistry. Furthermore, OY-TES-1 protein expression was correlated with tumor invasion stage (P=0.004) and histological grade (P=0.040). Anti-OY-TES-1 antibody was detected in (9.6%, 7/73) of CRC patients’ sera but not in 76 healthy donors. This finding demonstrates that OY-TES-1 is frequently expressed in CRC and is able to induce humoral immune response spontaneously in CRC patients, suggesting that it might be a promising immunotherapy target for CRC. PMID:24294369

  2. Epstein–Barr Virus Infection and Gastric Cancer

    PubMed Central

    Chen, Xin-Zu; Chen, Hongda; Castro, Felipe A.; Hu, Jian-Kun; Brenner, Hermann

    2015-01-01

    Abstract Epstein–Barr virus (EBV) infection is found in a subset of gastric cancers. Previous reviews have exclusively focused on EBV-encoded small RNA (EBER) positivity in gastric cancer tissues, but a comprehensive evaluation of other type of studies is lacking. We searched the PubMed database up to September, 2014, and performed a systematic review. We considered studies comparing EBV nucleic acids positivity in gastric cancer tissue with positivity in either adjacent non-tumor tissue of cancer patients or non-tumor mucosa from healthy individuals, patients with benign gastric diseases, or deceased individuals. We also considered studies comparing EBV antibodies in serum from cancer patients and healthy controls. Selection of potentially eligible studies and data extraction were performed by 2 independent reviewers. Due to the heterogeneity of studies, we did not perform formal meta-analysis. Forty-seven studies (8069 cases and 1840 controls) were identified. EBER positivity determined by in situ hybridization (ISH) was significantly higher in cancer tissues (range 5.0%–17.9%) than in adjacent mucosa from the same patients or biopsies from all control groups (almost 0%). High EBV nuclear antigen-1 (EBNA-1) positivity by PCR was found in gastric cancer tissues, but most were not validated by ISH or adjusted for inflammatory severity and lymphocyte infiltration. Only 4 studies tested for EBV antibodies, with large variation in the seropositivities of different antibodies in both cases and controls, and did not find an association between EBV seropositivity and gastric cancer. In summary, tissue-based ISH methods strongly suggest an association between EBV infection and gastric cancer, but PCR method alone is invalid to confirm such association. Very limited evidence from serological studies and the lack of novel antibodies warrant further investigations to identify potential risk factors of EBV for gastric cancer. PMID:25997049

  3. Peri-Implant Tissue Findings in Bone Grafted Oral Cancer Patients Compared to non Bone Grafted Patients without Oral Cancer

    PubMed Central

    Agata, Hideki; Sándor, George K.; Haimi, Suvi

    2011-01-01

    ABSTRACT Objectives The aim of this study was to compare microbiological, histological, and mechanical findings from tissues around osseointergrated dental implants in patients who had undergone tumour resection and subsequent bone grafting with non bone grafted patients without a history of oral cancer and to develop an effective tool for the monitoring of the peri-implant tissues. A third aim was to assess and compare the masticatory function of the two patient groups after reconstruction with dental implants. Material and Methods A total of 20 patients were divided into 2 groups. The first group was edentulous and treated with dental implants without the need for bone grafting. The second edentulous group, with a history of oral cancer involving the mandible, received onlay bone grafts with concurrent placement of dental implants. Microbiological, histological, mechanical and biochemical assessment methods, crevicular fluid flow rate, hygiene-index, implant mobility, and the masticatory function were analysed and compared in both patient groups. Results The microbiological examinations showed no evidence of the three most common pathogenic bacteria: Porphyromonas gingivalis, Prevotella intermedius, Actinobacillus actinomycetencomitans. A causal relationship between specific microbes and peri-implant inflammation could not be found. All biopsies in both patient groups revealed early signs of soft tissue peri-implant inflammation. Conclusions The crevicular fluid volume and grade of gingival inflammation around the dental implants were related. Peri-implant tissue findings were similar in the two patient groups despite the history of oral cancer and the need for bone grafting at the time of dental implant placement. PMID:24421999

  4. The dynamics of spiral tip adjacent to inhomogeneity in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Zhang, Juan; Tang, Jun; Ma, Jun; Luo, Jin Ming; Yang, Xian Qing

    2018-02-01

    Rotating spiral waves in cardiac tissue are implicated in life threatening cardiac arrhythmias. Experimental and theoretical evidences suggest the inhomogeneities in cardiac tissue play a significant role in the dynamics of spiral waves. Based on a modified 2D cardiac tissue model, the interaction of inhomogeneity on the nearby rigidly rotating spiral wave is numerically studied. The adjacent area of the inhomogeneity is divided to two areas, when the initial rotating center of the spiral tip is located in the two areas, the spiral tip will be attracted and anchor on the inhomogeneity finally, or be repulsed away. The width of the area is significantly dependent on the intensity and size of the inhomogeneity. Our numerical study sheds some light on the mechanism of the interaction of inhomogeneity on the spiral wave in cardiac tissue.

  5. [Association of Inorganics Accumulation with the Activation of NF-κB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients].

    PubMed

    Yang, Jiapeng; Li, Guangjian; Huang, Yunchao; Ye, Lianhua; Zhou, Yongchun; Zhao, Guangqiang; Lei, Yujie; Chen, Xiaobo; Wang, Kun; Chen, Ying; Dai, Chun; Zhang, Yanjun

    2016-01-01

    Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB)-inducible nitric oxide synthase (iNOS) signaling pathway of lung tissue in Xuanwei lung cancer patients. From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM) to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured. A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si) content was found in inorganic elemental analysis. The serum interleukin (IL)-1β levels (31.50 ± 19.16) pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33 ± 6.94) pg/mL (P<0.01), with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-κB-p65, and iNOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung-cancer tissues and urine 8-OHdG level (40.124 ± 8

  6. Sucrose-Metabolizing Enzymes in Transport Tissues and Adjacent Sink Structures in Developing Citrus Fruit 1

    PubMed Central

    Lowell, Cadance A.; Tomlinson, Patricia T.; Koch, Karen E.

    1989-01-01

    Juice tissues of citrus lack phloem; therefore, photosynthates enroute to juice sacs exit the vascular system on the surface of each segment. Areas of extensive phloem unloading and transport (vascular bundles + segment epidermis) can thus be separated from those of assimilate storage (juice sacs) and adjacent tissues where both processes occur (peel). Sugar composition, dry weight accumulation, and activities of four sucrose-metabolizing enzymes (soluble and cell-wall-bound acid invertase, alkaline invertase, sucrose synthase, and sucrose phosphate synthase) were measured in these transport and sink tissues of grapefruit (Citrus paradisi Macf.) to determine more clearly whether a given enzyme appeared to be more directly associated with assimilate transport versus deposition or utilization. Results were compared at three developmental stages. Activity of sucrose (per gram fresh weight and per milligram protein) extracted from zones of extensive phloem unloading and transport was significantly greater than from adjacent sink tissues during the stages (II and III) when juice sacs grow most rapidly. In stage II fruit, activity of sucrose synthase also significantly surpassed that of all other sucrose-metabolizing enzymes in extracts from the transport tissues (vascular bundles + segment epidermis). In contrast, sucrose phosphate synthase and alkaline invertase at this stage of growth were the most active enzymes from adjacent, rapidly growing, phloem-free sink tissues (juice sacs). Activity of these two enzymes in extracts from juice sacs was significantly greater than that form the transport tissues (vascular bundles + segment epidermis). Soluble acid invertase was the most active enzyme in extracts from all tissues of very young fruit (stage I), including nonvascular regions, but nearly disappeared prior to the onset of juice sac sugar accumulation. The physiological function of high sucrose synthase activity in the transport tissues during rapid sucrose import

  7. High expression of nucleobindin 2 is associated with poor prognosis in gastric cancer.

    PubMed

    Altan, Bolag; Kaira, Kyoichi; Okada, Shuichi; Saito, Tsugumichi; Yamada, Eijiro; Bao, Halin; Bao, Pinjie; Takahashi, Kengo; Yokobori, Takehiko; Tetsunari, Oyama; Nishiyama, Masahiko; Yamada, Masanobu

    2017-07-01

    Nucleobindin 2 has been reported that its high expression is associated with poor outcome and promotes cell migration and lymph node metastasis in breast cancer, colon cancer, and prostate cancer. However, we aimed to investigate the nucleobindin 2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemical analysis. In our study, nucleobindin 2 level in gastric cancer tissues was higher than in non-tumor tissues. A high expression of nucleobindin 2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and clinical stage. Furthermore, the expression level of nucleobindin 2 protein was independent predictor of progression-free survival. In summary, nucleobindin 2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.

  8. Cryopreserved embryo transfer: adjacent or non-adjacent to failed fresh long GnRH-agonist protocol IVF cycle.

    PubMed

    Volodarsky-Perel, Alexander; Eldar-Geva, Talia; Holzer, Hananel E G; Schonberger, Oshrat; Reichman, Orna; Gal, Michael

    2017-03-01

    The optimal time to perform cryopreserved embryo transfer (CET) after a failed oocyte retrieval-embryo transfer (OR-ET) cycle is unknown. Similar clinical pregnancy rates were recently reported in immediate and delayed CET, performed after failed fresh OR-ET, in cycles with the gonadotrophin-releasing hormone (GnRH) antagonist protocol. This study compared outcomes of CET performed adjacently (<50 days, n = 67) and non-adjacently (≥50 to 120 days, n = 62) to the last OR-day of cycles with the GnRH agonist down-regulation protocol. Additional inclusion criteria were patients' age 20-38 years, the transfer of only 1-2 cryopreserved embryos, one treatment cycle per patient and artificial preparation for CET. Significantly higher implantation, clinical pregnancy and live birth rates were found in the non-adjacent group than in the adjacent group: 30.5% versus 11.3% (P = 0.001), 41.9% versus 17.9% (P = 0.003) and 32.3% versus 13.4% (P = 0.01), respectively. These results support the postponement of CET after a failed OR-ET for at least one menstrual cycle, when a preceding long GnRH-agonist protocol is used. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  9. Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry.

    PubMed

    Gu, Junxia; Liang, Yuting; Qiao, Longwei; Li, Xiaoyun; Li, Xingang; Lu, Yaojuan; Zheng, Qiping

    2013-01-01

    Multiple studies have recently demonstrated the oncogenic property of URI (or RMP, a member of the prefoldin family of molecular chaperones) during progression of hepatocellular carcinoma, ovarian cancer, and possibly prostate cancer. Most recently, we have shown that URI/RMP is up-regulated in cervical cancer, another reproductive system tumor beside ovarian and prostate cancers. To investigate if URI/RMP also plays a role in other reproductive system tumors, especially in endometrioid adenocarcinoma, we analyzed URI/RMP expression in a TMA (tissue microarray) containing tissues from 30 cases of endometrioid adenocarcinoma (which covers tumor tissues from Grade I through Grade III) and adjacent endometrium by immunohistochemistry (IHC) and densitometry analysis using image-pro plus 6.0 software. Our results showed that the mean density of URI/RMP expression in cancerous tissue is slightly higher than that of the adjacent endometrial tissue, though not statistically significant (p>0.05). There is no significant difference either between the mean density of Grade III cancerous tissue and that of Grade I and II cancers. Notably, we detected significantly higher signal intensity in cancerous tissue of all 7 Grade III cases than that of their adjacent endometrial tissue (p<0.05), suggesting a correlation of URI/RMP expression with the differentiation and pathological classification of endometrioid adenocarcinoma. Together, our results demonstrate the heterogeneous expression of URI/RMP in endometrioid adenocarcinoma. The higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma.

  10. Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry

    PubMed Central

    Gu, Junxia; Liang, Yuting; Qiao, Longwei; Li, Xiaoyun; Li, Xingang; Lu, Yaojuan; Zheng, Qiping

    2013-01-01

    Multiple studies have recently demonstrated the oncogenic property of URI (or RMP, a member of the prefoldin family of molecular chaperones) during progression of hepatocellular carcinoma, ovarian cancer, and possibly prostate cancer. Most recently, we have shown that URI/RMP is up-regulated in cervical cancer, another reproductive system tumor beside ovarian and prostate cancers. To investigate if URI/RMP also plays a role in other reproductive system tumors, especially in endometrioid adenocarcinoma, we analyzed URI/RMP expression in a TMA (tissue microarray) containing tissues from 30 cases of endometrioid adenocarcinoma (which covers tumor tissues from Grade I through Grade III) and adjacent endometrium by immunohistochemistry (IHC) and densitometry analysis using image-pro plus 6.0 software. Our results showed that the mean density of URI/RMP expression in cancerous tissue is slightly higher than that of the adjacent endometrial tissue, though not statistically significant (p>0.05). There is no significant difference either between the mean density of Grade III cancerous tissue and that of Grade I and II cancers. Notably, we detected significantly higher signal intensity in cancerous tissue of all 7 Grade III cases than that of their adjacent endometrial tissue (p<0.05), suggesting a correlation of URI/RMP expression with the differentiation and pathological classification of endometrioid adenocarcinoma. Together, our results demonstrate the heterogeneous expression of URI/RMP in endometrioid adenocarcinoma. The higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma. PMID:24228101

  11. Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to human colorectal cancer.

    PubMed

    Kigasawa, Hideaki; Fujiwara, Masachika; Ishii, Jun; Chiba, Tomohiro; Terado, Yuichi; Shimoyamada, Hiroaki; Mochizuki, Makoto; Kitamura, Osamu; Kamma, Hiroshi; Ohkura, Yasuo

    2017-07-01

    The multi-step progression of colorectal cancer through precancerous lesions (adenoma and dysplasia) is associated with cumulative molecular alterations, a number of which have also been demonstrated to be present in morphologically normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal protein cytokeratin 7 (CK7) and the receptor tyrosine kinase, KIT proto-oncogene receptor tyrosine kinase (CD117), encoded by the proto-oncogene c-Kit, are lacking in normal colorectal crypt epithelium and are aberrantly expressed in a subset of colorectal cancer. The aim of the present study was to evaluate the expression of CK7 and CD117 in morphologically normal transitional mucosa adjacent to colorectal cancer. Immunohistochemical staining for CK7 and CD117 was performed in the mucosa adjacent to five groups of surgically resected colorectal tumors [low-grade adenoma, high-grade adenoma, mucosal adenocarcinoma, small-sized invasive adenocarcinoma (≤2 cm) and large-sized invasive adenocarcinoma (>2 cm)]. CK7 was expressed in the mucosa adjacent to a subset of colorectal tumors, and the positivity ratio increased according to tumor grade from low-grade adenoma up to small-sized invasive adenocarcinoma (61.2%). However, the positivity ratio of CK7 in the mucosa adjacent to the large-sized invasive adenocarcinoma (25.0%) was significantly lower compared with that of the next lower grade. CD117 was also expressed in the mucosa adjacent to a subset of colorectal tumors. In contrast to CK7, the positivity ratio of CD117 increased according to tumor grade from low-grade adenoma all the way through to the large-sized invasive adenocarcinoma (45.0%). Based on these results, the mechanism of CK7 and CD117 expression in the transitional mucosa adjacent to colorectal cancer may be different, and analysis of their individual expression may provide novel insights into the development and progression of colorectal cancer.

  12. Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to human colorectal cancer

    PubMed Central

    Kigasawa, Hideaki; Fujiwara, Masachika; Ishii, Jun; Chiba, Tomohiro; Terado, Yuichi; Shimoyamada, Hiroaki; Mochizuki, Makoto; Kitamura, Osamu; Kamma, Hiroshi; Ohkura, Yasuo

    2017-01-01

    The multi-step progression of colorectal cancer through precancerous lesions (adenoma and dysplasia) is associated with cumulative molecular alterations, a number of which have also been demonstrated to be present in morphologically normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal protein cytokeratin 7 (CK7) and the receptor tyrosine kinase, KIT proto-oncogene receptor tyrosine kinase (CD117), encoded by the proto-oncogene c-Kit, are lacking in normal colorectal crypt epithelium and are aberrantly expressed in a subset of colorectal cancer. The aim of the present study was to evaluate the expression of CK7 and CD117 in morphologically normal transitional mucosa adjacent to colorectal cancer. Immunohistochemical staining for CK7 and CD117 was performed in the mucosa adjacent to five groups of surgically resected colorectal tumors [low-grade adenoma, high-grade adenoma, mucosal adenocarcinoma, small-sized invasive adenocarcinoma (≤2 cm) and large-sized invasive adenocarcinoma (>2 cm)]. CK7 was expressed in the mucosa adjacent to a subset of colorectal tumors, and the positivity ratio increased according to tumor grade from low-grade adenoma up to small-sized invasive adenocarcinoma (61.2%). However, the positivity ratio of CK7 in the mucosa adjacent to the large-sized invasive adenocarcinoma (25.0%) was significantly lower compared with that of the next lower grade. CD117 was also expressed in the mucosa adjacent to a subset of colorectal tumors. In contrast to CK7, the positivity ratio of CD117 increased according to tumor grade from low-grade adenoma all the way through to the large-sized invasive adenocarcinoma (45.0%). Based on these results, the mechanism of CK7 and CD117 expression in the transitional mucosa adjacent to colorectal cancer may be different, and analysis of their individual expression may provide novel insights into the development and progression of colorectal cancer. PMID:28693143

  13. Long non-coding RNA LSINCT5 predicts negative prognosis and exhibits oncogenic activity in gastric cancer.

    PubMed

    Xu, Mi-Die; Qi, Peng; Weng, Wei-Wei; Shen, Xiao-Han; Ni, Shu-Juan; Dong, Lei; Huang, Dan; Tan, Cong; Sheng, Wei-Qi; Zhou, Xiao-Yan; Du, Xiang

    2014-12-01

    Long non-coding RNAs (lncRNAs) are recently discovered RNA transcripts that are aberrantly expressed in many tumor types. Numerous studies have suggested that lncRNAs can be utilized for cancer diagnosis and prognosis. LSINCT5 (long stress-induced non-coding transcript 5) is dramatically upregulated in breast and ovarian cancer and affects cellular proliferation. However, the expression pattern of LSINCT5 in gastrointestinal cancer and the association between aberrant expression of LSINCT5 in gastrointestinal cancer and malignancy, metastasis, or prognosis remain unknown. LSINCT5 expression was detected in gastrointestinal cancer and paired adjacent normal tissue samples or cell lines using reverse transcription quantitative PCR (RT-qPCR). We also investigated the potential relationship between tumor LSINCT5 levels and clinicopathological features of gastrointestinal cancer. Finally, we assessed whether LSINCT5 influences in vitro cell proliferation. The expression of LSINCT5 is significantly upregulated in gastrointestinal cancer tissues and cell lines relative to their normal counterparts. In addition, increased LSINCT5 expression was correlated with a larger tumor size, deeper tumor depth, and advanced clinical stage. Kaplan-Meier analysis indicated that gastric cancer (GC) and colorectal cancer (CRC) patients with higher LSINCT5 expression levels have worse disease-free survival (DFS) and disease-specific survival (DSS) rates. Moreover, multivariate analysis revealed that increased expression of LSINCT5 is an independent predictor of DFS and DSS rates in GC patients. The ectopic expression of LSINCT5 in gastrointestinal cancer cell lines resulted in an increase in cellular proliferation; conversely, knock down of LSINCT5 significantly inhibited proliferation. These results suggest that LSINCT5 may represent a novel prognostic indicator and a target for gene therapy in gastrointestinal cancer.

  14. Biogeochemistry of hydrothermally and adjacent non-altered soils

    USDA-ARS?s Scientific Manuscript database

    As a field/lab project, students in the Soil Biogeochemistry class of the University of Nevada, Reno described and characterized seven pedons, developed in hydrothermally and adjacent non-hydrothermally altered andesitic parent material near Reno, NV. Hydrothermally altered soils had considerably lo...

  15. Differentiating cancerous from normal breast tissue by redox imaging

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2015-02-01

    Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (p<0.05) and the redox ratio Fp/(NADH+Fp) was about 27% higher in the cancerous tissues than in the normal ones (p<0.05). Our findings suggest that the redox state could differentiate between cancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

  16. Predictive Genes in Adjacent Normal Tissue Are Preferentially Altered by sCNV during Tumorigenesis in Liver Cancer and May Rate Limiting

    PubMed Central

    Lamb, John R.; Zhang, Chunsheng; Xie, Tao; Wang, Kai; Zhang, Bin; Hao, Ke; Chudin, Eugene; Fraser, Hunter B.; Millstein, Joshua; Ferguson, Mark; Suver, Christine; Ivanovska, Irena; Scott, Martin; Philippar, Ulrike; Bansal, Dimple; Zhang, Zhan; Burchard, Julja; Smith, Ryan; Greenawalt, Danielle; Cleary, Michele; Derry, Jonathan; Loboda, Andrey; Watters, James; Poon, Ronnie T. P.; Fan, Sheung T.; Yeung, Chun; Lee, Nikki P. Y.; Guinney, Justin; Molony, Cliona; Emilsson, Valur; Buser-Doepner, Carolyn; Zhu, Jun; Friend, Stephen; Mao, Mao; Shaw, Peter M.; Dai, Hongyue; Luk, John M.; Schadt, Eric E.

    2011-01-01

    Background In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ∼250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. PMID:21750698

  17. Systematic bias in genomic classification due to contaminating non-neoplastic tissue in breast tumor samples.

    PubMed

    Elloumi, Fathi; Hu, Zhiyuan; Li, Yan; Parker, Joel S; Gulley, Margaret L; Amos, Keith D; Troester, Melissa A

    2011-06-30

    Genomic tests are available to predict breast cancer recurrence and to guide clinical decision making. These predictors provide recurrence risk scores along with a measure of uncertainty, usually a confidence interval. The confidence interval conveys random error and not systematic bias. Standard tumor sampling methods make this problematic, as it is common to have a substantial proportion (typically 30-50%) of a tumor sample comprised of histologically benign tissue. This "normal" tissue could represent a source of non-random error or systematic bias in genomic classification. To assess the performance characteristics of genomic classification to systematic error from normal contamination, we collected 55 tumor samples and paired tumor-adjacent normal tissue. Using genomic signatures from the tumor and paired normal, we evaluated how increasing normal contamination altered recurrence risk scores for various genomic predictors. Simulations of normal tissue contamination caused misclassification of tumors in all predictors evaluated, but different breast cancer predictors showed different types of vulnerability to normal tissue bias. While two predictors had unpredictable direction of bias (either higher or lower risk of relapse resulted from normal contamination), one signature showed predictable direction of normal tissue effects. Due to this predictable direction of effect, this signature (the PAM50) was adjusted for normal tissue contamination and these corrections improved sensitivity and negative predictive value. For all three assays quality control standards and/or appropriate bias adjustment strategies can be used to improve assay reliability. Normal tissue sampled concurrently with tumor is an important source of bias in breast genomic predictors. All genomic predictors show some sensitivity to normal tissue contamination and ideal strategies for mitigating this bias vary depending upon the particular genes and computational methods used in the predictor.

  18. Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors

    PubMed Central

    Pizzamiglio, Sara; De Bortoli, Maida; Taverna, Elena; Signore, Michele; Veneroni, Silvia; Chi-shing Cho, William; Orlandi, Rosaria; Verderio, Paolo; Bongarzone, Italia

    2017-01-01

    We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA) or reverse-phase protein array (RPPA), were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012). The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5), signal transducer and activator of transcription 3 (STAT3), bone morphogenetic protein 6 (BMP6), cluster of differentiation 74 (CD74), transferrin receptor (TFRC), inhibin alpha (INHA), and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88), CD74, iron exporter ferroportin (FPN), high mobility group box 1 (HMGB1), STAT3_pS727, TFRC, ferritin heavy chain (FTH), and ferritin light chain (FTL). Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer. PMID:28216608

  19. Circular RNA 0000096 affects cell growth and migration in gastric cancer.

    PubMed

    Li, Peifei; Chen, Huilin; Chen, Shengcan; Mo, Xiaoyan; Li, Tianwen; Xiao, Bingxiu; Yu, Rui; Guo, Junming

    2017-02-28

    Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. Their role in cancers, especially in gastric cancer, is poorly understood. Circular RNA 0000096 (hsa_circ_0000096) levels in 101 paired gastric cancer tissues and adjacent non-tumorous tissues from patients with gastric cancer were detected by real-time quantitative reverse transcription-polymerase chain reaction. A receiver operating characteristic curve was generated to evaluate the diagnostic value of hsa_circ_0000096. RNA interference was used to manipulate the expression of hsa_circ_0000096. Its biological effects were evaluated by flow cytometry, real-time cell analysis, a wound scratch assay, western blot analysis and xenograft models. Hsa_circ_0000096 was found to be significantly downregulated in gastric cancer tissues and gastric cancer cell lines compared with paired adjacent non-tumorous tissues and normal gastric epithelial cells (P<0.001). Moreover, knockdown of hsa_circ_0000096 significantly inhibited cell proliferation and migration in vitro and in vivo. The results of both immunohistochemical and western blot analyses showed that the protein levels of cyclin D1, cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-2 and MMP-9 were significantly reduced in vitro and in vivo. A gastric cancer xenograft nude mouse model indicated that Ki67 and VEGF were reduced in a dose-dependent manner following knockdown of hsa_circ_0000096. However, the expression of E-cadherin increased. Hsa_circ_0000096 may be used as a potential novel biomarker for gastric cancer. It affects gastric cancer cell growth and migration by regulating cyclin D1, CDK6, MMP-2 and MMP-9.

  20. Biomarkers to Distinguish Aggressive Cancers from Non-aggressive or Non-progressing Cancer — EDRN Public Portal

    Cancer.gov

    Distinguishing aggressive cancers from non-aggressive or non-progressing cancers is an issue of both clinical and public health importance particularly for those cancers with an available screening test. With respect to breast cancer, mammographic screening has been shown in randomized trials to reduce breast cancer mortality, but given the limitations of its sensitivity and specificity some breast cancers are missed by screening. These so called interval detected breast cancers diagnosed between regular screenings are known to have a more aggressive clinical profile. In addition, of those cancers detected by mammography some are indolent while others are more likely to recur despite treatment. The pilot study proposed herein is highly responsive to the EDRN supplement titled “Biomarkers to Distinguish Aggressive Cancers from Nonaggressive or Non-progressing Cancers” in that it addresses both of the research objectives related to these issues outlined in the notice for this supplement: Aim 1: To identify biomarkers in tumor tissue related to risk of interval detected vs. mammography screen detected breast cancer focusing on early stage invasive disease. We will compare gene expression profiles using the whole genome-cDNA-mediated Annealing, Selection, extension and Ligation (DASL) assay of 50 screen detected cancers to those of 50 interval detected cancers. Through this approach we will advance our understanding of the molecular characteristics of interval vs. screen detected breast cancers and discover novel biomarkers that distinguish between them. Aim 2: To identify biomarkers in tumor tissue related to risk of cancer recurrence among patients with screen detected early stage invasive breast cancer. Using the DASL assay we will compare gene expression profiles from screen detected early stage breast cancer that either recurred within five years or never recurred within five years. These two groups of patients will be matched on multiple factors including

  1. Analysis of laser surgery in non-melanoma skin cancer for optimal tissue removal

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, Félix; Salas-García, Irene; Arce-Diego, José Luis

    2015-02-01

    Laser surgery is a commonly used technique for tissue ablation or the resection of malignant tumors. It presents advantages over conventional non-optical ablation techniques, like a scalpel or electrosurgery, such as the increased precision of the resected volume, minimization of scars and shorter recovery periods. Laser surgery is employed in medical branches such as ophthalmology or dermatology. The application of laser surgery requires the optimal adjustment of laser beam parameters, taking into account the particular patient and lesion. In this work we present a predictive tool for tissue resection in biological tissue after laser surgery, which allows an a priori knowledge of the tissue ablation volume, area and depth. The model employs a Monte Carlo 3D approach for optical propagation and a rate equation for plasma-induced ablation. The tool takes into account characteristics of the specific lesion to be ablated, mainly the geometric, optical and ablation properties. It also considers the parameters of the laser beam, such as the radius, spatial profile, pulse width, total delivered energy or wavelength. The predictive tool is applied to dermatology tumor resection, particularly to different types of non-melanoma skin cancer tumors: basocellular carcinoma, squamous cell carcinoma and infiltrative carcinoma. The ablation volume, area and depth are calculated for healthy skin and for each type of tumor as a function of the laser beam parameters. The tool could be used for laser surgery planning before the clinical application. The laser parameters could be adjusted for optimal resection volume, by personalizing the process to the particular patient and lesion.

  2. Lipid Profiles of Canine Invasive Transitional Cell Carcinoma of the Urinary Bladder and Adjacent Normal Tissue by Desorption Electrospray Ionization Imaging Mass Spectrometry

    PubMed Central

    Dill, Allison L.; Ifa, Demian R.; Manicke, Nicholas E.; Costa, Anthony B.; Ramos-Vara, José A.; Knapp, Deborah W.; Cooks, R. Graham

    2009-01-01

    Desorption electrospray ionization (DESI) mass spectrometry (MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of canine spontaneous invasive transitional cell carcinoma (TCC) of the urinary bladder (a model of human invasive bladder cancer) as well as adjacent normal tissue from four different dogs. The glycerophospholipids and sphingolipids that appear as intense signals in both the negative ion and positive ion modes were identified by tandem mass spectrometry (MS/MS) product ion scans using collision-induced dissociation. Differences in the relative distributions of the lipid species were present between the tumor and adjacent normal tissue in both the negative and positive ion modes. DESI-MS images showing the spatial distributions of particular glycerophospholipids, sphinoglipids and free fatty acids in both the negative and positive ion modes were compared to serial tissue sections that were stained with hematoxylin and eosin (H&E). Increased absolute and relative intensities for at least five different glycerophospholipids and three free fatty acids in the negative ion mode and at least four different lipid species in the positive ion mode were seen in the tumor region of the samples in all four dogs. In addition, one sphingolipid species exhibited increased signal intensity in the positive ion mode in normal tissue relative to the diseased tissue. Principal component analysis (PCA) was also used to generate unsupervised statistical images from the negative ion mode data and these images are in excellent agreement with the DESI images obtained from the selected ions and also the H&E stained tissue PMID:19810710

  3. Identification of Novel Long Non-coding and Circular RNAs in Human Papillomavirus-Mediated Cervical Cancer

    PubMed Central

    Wang, Hongbo; Zhao, Yingchao; Chen, Mingyue; Cui, Jie

    2017-01-01

    Cervical cancer is the third most common cancer worldwide and the fourth leading cause of cancer-associated mortality in women. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) may play key roles in the carcinogenesis of different cancers; however, little is known about the mechanisms of lncRNAs and circRNAs in the progression and metastasis of cervical cancer. In this study, we explored the expression profiles of lncRNAs, circRNAs, miRNAs, and mRNAs in HPV16 (human papillomavirus genotype 16) mediated cervical squamous cell carcinoma and matched adjacent non-tumor (ATN) tissues from three patients with high-throughput RNA sequencing (RNA-seq). In total, we identified 19 lncRNAs, 99 circRNAs, 28 miRNAs, and 304 mRNAs that were commonly differentially expressed (DE) in different patients. Among the non-coding RNAs, 3 lncRNAs and 44 circRNAs are novel to our knowledge. Functional enrichment analysis showed that DE lncRNAs, miRNAs, and mRNAs were enriched in pathways crucial to cancer as well as other gene ontology (GO) terms. Furthermore, the co-expression network and function prediction suggested that all 19 DE lncRNAs could play different roles in the carcinogenesis and development of cervical cancer. The competing endogenous RNA (ceRNA) network based on DE coding and non-coding RNAs showed that each miRNA targeted a number of lncRNAs and circRNAs. The link between part of the miRNAs in the network and cervical cancer has been validated in previous studies, and these miRNAs targeted the majority of the novel non-coding RNAs, thus suggesting that these novel non-coding RNAs may be involved in cervical cancer. Taken together, our study shows that DE non-coding RNAs could be further developed as diagnostic and therapeutic biomarkers of cervical cancer. The complex ceRNA network also lays the foundation for future research of the roles of coding and non-coding RNAs in cervical cancer. PMID:28970820

  4. Expression between African American and Caucasian Prostate Cancer Tissue Reveals that Stroma is the Site of Aggressive Changes

    PubMed Central

    Kinseth, Matthew A.; Jia, Zhenyu; Rahmatpanah, Farahnaz; Sawyers, Anne; Sutton, Manuel; Wang-Rodriguez, Jessica; Mercola, Dan; McGuire, Kathleen L.

    2013-01-01

    In prostate cancer, race/ethnicity is the highest risk factor after adjusting for age. African Americans have more aggressive tumors at every clinical stage of the disease, resulting in poorer prognosis and increased mortality. A major barrier to identifying crucial gene activity differences is heterogeneity, including tissue composition variation intrinsic to the histology of prostate cancer. We hypothesized differences in gene expression in specific tissue types would reveal mechanisms involved in the racial disparities of prostate cancer. We examined seventeen pairs of arrays for African Americans and Caucasians that were formed by closely matching the samples based on the known tissue type composition of the tumors. Using pair wise T-test we found significantly altered gene expression between African Americans and Caucasians. Independently, we performed multiple linear regression analyses to associate gene expression with race considering variation in percent tumor and stroma tissue. The majority of differentially expressed genes were associated with tumor-adjacent stroma rather than tumor tissue. Extracellular matrix, Integrin family and signaling mediators of the epithelial-to-mesenchymal transition pathways were all down regulated in stroma of African Americans. Using MetaCore (GeneGo Inc.) analysis, we observed that 35% of significant (p < 10-3) pathways identified EMT and 25% identified immune response pathways especially for Interleukins -2, -4, -5, -6, -7, -10, -13, -15 and -22 as the major changes. Our studies reveal that altered immune and EMT processes in tumor-adjacent stroma may be responsible for the aggressive nature of prostate cancer in African Americans. PMID:23754304

  5. BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression.

    PubMed

    Ren, Wei; Sun, Xiaoxiao; Wang, Ke; Feng, Honglei; Liu, Yuehong; Fei, Chang; Wan, Shaoheng; Wang, Wei; Luo, Jinyong; Shi, Qiong; Tang, Min; Zuo, Guowei; Weng, Yaguang; He, Tongchuan; Zhang, Yan

    2014-03-01

    Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration, and apoptosis. BMP9, the latest BMP to be discovered, is reportedly expressed in a variety of human carcinoma cell lines, but the role of BMP9 in breast cancer has not been fully clarified. In a previous study, BMP9 was found to inhibit the growth, migration, and invasiveness of MDA-MB-231 breast cancer cells. In the current study, the effect of BMP9 on the bone metastasis of breast cancer cells was investigated. After absent or low expression of BMP9 was detected in the MDA-MB-231 breast cancer cells and breast non-tumor adjacent tissues using Western blot and immunohistochemistry, In our previous study, BMP9 could inhibit the proliferation and invasiveness of breast cancer cells MDA-MB-231 in vitro and in vivo. This paper shows that BMP9 inhibit the bone metastasis of breast cancer cells by activating the BMP/Smad signaling pathway and downregulating connective tissue growth factor (CTGF); however, when CTGF expression was maintained, the inhibitory effect of BMP9 on the MDA-MB-231 cells was abolished. Together, these observations indicate that BMP9 is an important mediator of breast cancer bone metastasis and a potential therapeutic target for treating this deadly disease.

  6. Distinctive profiles of tumor-infiltrating immune cells and association with intensity of infiltration in colorectal cancer.

    PubMed

    Wu, Yugang; Yuan, Lei; Lu, Qicheng; Xu, Haiyan; He, Xiaozhou

    2018-03-01

    Tumor-infiltrating immune cells are heterogeneous and consist of characteristic compartments, including T helper (Th)1 and regulatory T (Treg) cells that exhibit distinctive biological functions. The present study investigated the profile of infiltrating immune cells from surgically removed tumor tissues from patients with colorectal cancer. The characteristic transcription factors of Th1 and Th2 cells, Treg cells, Th17 cells and T follicular helper (Tfh) cells were analyzed. The results demonstrated that a marked increased number of Treg cells presented in tumor infiltrates when compared with non-tumor adjacent tissues. An increased number of Th1 and Tfh cells existed in tumor infiltrates compared with non-tumorous adjacent tissues, while the infiltration of Th17 and Th2 cells was similar between tumor and non-tumor adjacent tissues. Furthermore, there were an increased number of Treg cells in tumors with low infiltration compared with those with high infiltration. The expression of CXC motif chemokine (CXC) receptor 3, CXC ligand (CXCL)L9 and CXCL10 was significantly increased on infiltrating T cells in tumors with high infiltration as compared with those with low infiltration. Macrophages exhibited a dominant M2 phenotype in tumor infiltrates of colorectal cancer, whereas a balanced M1 and M2 phenotype presented in macrophages from the peripheral blood. In vitro stimulation of macrophages isolated from tumor tissue of colorectal cancer with granulocyte macrophage colony-stimulating factor and lipopolysaccharide did not drive to an inflammatory phenotype. The results provide insights into the pattern of immune cell infiltration in Chinese patients with colorectal cancer. It may be beneficial that patients with colorectal cancer are screened for the defined profile along with the expression of CXCL9 and CXCL10 in order to achieve better efficacy in clinical applications of immune-based therapy, including anti-programmed cell death protein 1 therapy.

  7. Non-viral gene delivery strategies for cancer therapy, tissue engineering and regenerative medicine

    NASA Astrophysics Data System (ADS)

    Bhise, Nupura S.

    Gene therapy involves the delivery of deoxyribonucleic acid (DNA) into cells to override or replace a malfunctioning gene for treating debilitating genetic diseases, including cancer and neurodegenerative diseases. In addition to its use as a therapeutic, it can also serve as a technology to enable regenerative medicine strategies. The central challenge of the gene therapy research arena is developing a safe and effective delivery agent. Since viral vectors have critical immunogenic and tumorogenic safety issues that limit their clinical use, recent efforts have focused on developing non-viral biomaterial based delivery vectors. Cationic polymers are an attractive class of gene delivery vectors due to their structural versatility, ease of synthesis, biodegradability, ability to self-complex into nanoparticles with negatively charged DNA, capacity to carry large cargo, cellular uptake and endosomal escape capacity. In this thesis, we hypothesized that developing a biomaterial library of poly(betaamino esters) (PBAE), a newer class of cationic polymers consisting of biodegradable ester groups, would allow investigating vector design parameters and formulating effective non-viral gene delivery strategies for cancer drug delivery, tissue engineering and stem cell engineering. Consequently, a high-throughput transfection assay was developed to screen the PBAE-based nanoparticles in hard to transfect fibroblast cell lines. To gain mechanistic insights into the nanoparticle formulation process, biophysical properties of the vectors were characterized in terms of molecular weight (MW), nanoparticle size, zeta potential and plasmid per particle count. We report a novel assay developed for quantifying the plasmid per nanoparticle count and studying its implications for co-delivery of multiple genes. The MW of the polymers ranged from 10 kDa to 100 kDa, nanoparticle size was about 150 run, zeta potential was about 30 mV in sodium acetate buffer (25 mM, pH 5) and 30 to 100

  8. Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer

    PubMed Central

    2011-01-01

    Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT) and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs), whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs). Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these observations, the repression of Bmi

  9. A novel plasma circular RNA circFARSA is a potential biomarker for non-small cell lung cancer.

    PubMed

    Hang, Dong; Zhou, Jing; Qin, Na; Zhou, Wen; Ma, Hongxia; Jin, Guangfu; Hu, Zhibin; Dai, Juncheng; Shen, Hongbing

    2018-06-01

    Emerging evidence indicates that circular RNAs (circRNAs) are implicated in cancer development. This study aimed to evaluate whether circulating circRNAs may serve as novel biomarkers for non-small cell lung cancer (NSCLC). We used RNA sequencing (RNA-seq) and quantitative real-time PCR to explore cancer-related circRNAs. Bioinformatics and functional analyses were performed to reveal biological effects of circRNAs on lung cancer cells. A total of 5471 distinct circRNAs were identified by total RNA-seq, in which 185 were differentially expressed between cancerous and adjacent normal tissues. A circRNA derived from exon 5-7 of the FARSA gene, termed circFARSA, was observed to increase in cancerous tissues (P = 0.016), and was more abundant in patients' plasma than controls (P < 0.001). Overexpression of circFARSA in A549 cell line significantly promoted cell migration and invasion. In silico analysis suggested that circFARSA might sponge miR-330-5p and miR-326, thereby relieving their inhibitory effects on oncogene fatty acid synthase. Summarily, this study revealed circRNA profile of NSCLC for the first time and provided the evidence of plasma circFARSA as a potential noninvasive biomarker for this malignancy. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  10. Adipose-Derived Stromal Vascular Fraction Differentially Expands Breast Progenitors in Tissue Adjacent to Tumors Compared to Healthy Breast Tissue

    PubMed Central

    Chatterjee, Sumanta; Laliberte, Mike; Blelloch, Sarah; Ratanshi, Imran; Safneck, Janice; Buchel, Ed

    2015-01-01

    Background: Autologous fat grafts supplemented with adipose-derived stromal vascular fraction are used in reconstructive and cosmetic breast procedures. Stromal vascular fraction contains adipose-derived stem cells that are thought to encourage wound healing, tissue regeneration, and graft retention. Although use of stromal vascular fraction has provided exciting perspectives for aesthetic procedures, no studies have yet been conducted to determine whether its cells contribute to breast tissue regeneration. The authors examined the effect of these cells on the expansion of human breast epithelial progenitors. Methods: From patients undergoing reconstructive breast surgery following mastectomies, abdominal fat, matching tissue adjacent to breast tumors, and the contralateral non–tumor-containing breast tissue were obtained. Ex vivo co-cultures using breast epithelial cells and the stromal vascular fraction cells were used to study the expansion potential of breast progenitors. Breast reduction samples were collected as a source of healthy breast cells. Results: The authors observed that progenitors present in healthy breast tissue or contralateral non–tumor-containing breast tissue showed significant and robust expansion in the presence of stromal vascular fraction (5.2- and 4.8-fold, respectively). Whereas the healthy progenitors expanded up to 3-fold without the stromal vascular fraction cells, the expansion of tissue adjacent to breast tumor progenitors required the presence of stromal vascular fraction cells, leading to a 7-fold expansion, which was significantly higher than the expansion of healthy progenitors with stromal vascular fraction. Conclusions: The use of stromal vascular fraction might be more beneficial to reconstructive operations following mastectomies compared with cosmetic corrections of the healthy breast. Future studies are required to examine the potential risk factors associated with its use. CLINICAL QUESTION/LEVEL OF EVIDENCE

  11. DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants.

    PubMed

    Gao, Yang; Widschwendter, Martin; Teschendorff, Andrew E

    2018-05-04

    Normal tissue at risk of neoplastic transformation is characterized by somatic mutations, copy-number variation and DNA methylation changes. It is unclear however, which type of alteration may be more informative of cancer risk. We analyzed genome-wide DNA methylation and copy-number calls from the same DNA assay in a cohort of healthy breast samples and age-matched normal samples collected adjacent to breast cancer. Using statistical methods to adjust for cell type heterogeneity, we show that DNA methylation changes can discriminate normal-adjacent from normal samples better than somatic copy-number variants. We validate this important finding in an independent dataset. These results suggest that DNA methylation alterations in the normal cell of origin may offer better cancer risk prediction and early detection markers than copy-number changes. Copyright © 2018. Published by Elsevier B.V.

  12. Integrated analysis of long non-coding RNAs in human gastric cancer: An in silico study.

    PubMed

    Han, Weiwei; Zhang, Zhenyu; He, Bangshun; Xu, Yijun; Zhang, Jun; Cao, Weijun

    2017-01-01

    Accumulating evidence highlights the important role of long non-coding RNAs (lncRNAs) in a large number of biological processes. However, the knowledge of genome scale expression of lncRNAs and their potential biological function in gastric cancer is still lacking. Using RNA-seq data from 420 gastric cancer patients in The Cancer Genome Atlas (TCGA), we identified 1,294 lncRNAs differentially expressed in gastric cancer compared with adjacent normal tissues. We also found 247 lncRNAs differentially expressed between intestinal subtype and diffuse subtype. Survival analysis revealed 33 lncRNAs independently associated with patient overall survival, of which 6 lncRNAs were validated in the internal validation set. There were 181 differentially expressed lncRNAs located in the recurrent somatic copy number alterations (SCNAs) regions and their correlations between copy number and RNA expression level were also analyzed. In addition, we inferred the function of lncRNAs by construction of a co-expression network for mRNAs and lncRNAs. Together, this study presented an integrative analysis of lncRNAs in gastric cancer and provided a valuable resource for further functional research of lncRNAs in gastric cancer.

  13. Characterization of cancer and normal tissue fluorescence through wavelet transform and singular value decomposition

    NASA Astrophysics Data System (ADS)

    Gharekhan, Anita H.; Biswal, Nrusingh C.; Gupta, Sharad; Pradhan, Asima; Sureshkumar, M. B.; Panigrahi, Prasanta K.

    2008-02-01

    The statistical and characteristic features of the polarized fluorescence spectra from cancer, normal and benign human breast tissues are studied through wavelet transform and singular value decomposition. The discrete wavelets enabled one to isolate high and low frequency spectral fluctuations, which revealed substantial randomization in the cancerous tissues, not present in the normal cases. In particular, the fluctuations fitted well with a Gaussian distribution for the cancerous tissues in the perpendicular component. One finds non-Gaussian behavior for normal and benign tissues' spectral variations. The study of the difference of intensities in parallel and perpendicular channels, which is free from the diffusive component, revealed weak fluorescence activity in the 630nm domain, for the cancerous tissues. This may be ascribable to porphyrin emission. The role of both scatterers and fluorophores in the observed minor intensity peak for the cancer case is experimentally confirmed through tissue-phantom experiments. Continuous Morlet wavelet also highlighted this domain for the cancerous tissue fluorescence spectra. Correlation in the spectral fluctuation is further studied in different tissue types through singular value decomposition. Apart from identifying different domains of spectral activity for diseased and non-diseased tissues, we found random matrix support for the spectral fluctuations. The small eigenvalues of the perpendicular polarized fluorescence spectra of cancerous tissues fitted remarkably well with random matrix prediction for Gaussian random variables, confirming our observations about spectral fluctuations in the wavelet domain.

  14. Human tissue models in cancer research: looking beyond the mouse.

    PubMed

    Jackson, Samuel J; Thomas, Gareth J

    2017-08-01

    Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

  15. Silencing of ATF2 inhibits growth of pancreatic cancer cells and enhances sensitivity to chemotherapy.

    PubMed

    Li, Mu; Wu, Xingda; Liu, Ning; Li, Xiaoying; Meng, Fanbin; Song, Shaowei

    2017-06-01

    Pancreatic cancer is one of the leading causes of cancer-related death worldwide. Activating transcription factor 2 (ATF2) is a multifunctional transcription factor, and is implicated in tumor progress, yet its role in pancreatic cancer remains unclear. In the present study, the level of ATF2 in pancreatic cancer tissues and the adjacent non-tumorous tissues was detected by quantitative real-time PCR and Western blot. The roles of ATF2 in the proliferation, cell cycle, and apoptosis of pancreatic cancer cells were investigated through ATF2 silencing, and the effect of ATF2 shRNA on the sensitivity of pancreatic cancer cells to gemcitabine, an anti-tumor drug, was explored. The results of our study showed that the ATF2 level in the pancreatic cancer tissues was higher than that in the adjacent non-tumorous tissues. Silencing of ATF2 was found to inhibit proliferation, arrest cell cycle at G1 phase and induce apoptosis in pancreatic cancer cells. Moreover, ATF2 silencing enhanced gemcitabine-induced growth-inhibition and apoptosis-induction effects in pancreatic cancer cells. In summary, silencing of ATF2 inhibited the growth of pancreatic cancer cells and enhanced the anti-tumor effects of gemcitabine, suggesting that ATF2 plays a pro-survival role in pancreatic cancer. Our results also propose that a high level of ATF2 may serve as a potential biomarker of pancreatic cancer, and that ATF2 may become a potential target for anti-tumor therapy. © 2017 International Federation for Cell Biology.

  16. Grb7 is over-expressed in cervical cancer and facilitate invasion and inhibit apoptosis in cervical cancer cells.

    PubMed

    Zhao, Hong-Bing; Zhang, Xi-Feng; Jia, Xue-Lin; Wang, Hao-Bin

    2017-09-01

    Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling. The objective of this study was to investigate the expression of Grb7 and its clinicopathological significance in cervical cancer. Utilising immunohistochemical staining, we examined the expression of Grb7 in 120 cases of human cervical cancer tissue and 10 cases of adjacent non-cancerous cervical tissue. The positive rate of Grb7 protein expression was 34.2%, which was significantly higher than that in adjacent non-cancerous cervical tissue (0%, p<0.05). The expression of Grb7 was found to be correlated with age, tumor size, serosal invasion, differentiated degree, tumor stage, early or advanced stage and lymph node metastasis. Kaplan-Meier survival analysis showed that patients with positive Grb7 protein expression had a lower overall survival rate than patients without Grb7 expression. In addition, Grb7 plays an important role in promoting tumor progression, including invasion and anti-apoptosis, in cervical cancer cell line. Down-regulation of Grb7 repressed the expression of MMP-9 and Bcl-2, and increased the expression of Bax in Grb7 knockdown Hela cells. Cell invasion assay showed decreased number of Grb7 knockdown Hela cells (18.7±2.1) compared to Hela cells (65.3±2.5, P<0.05). Our results indicated that Grb7 over-expression may facilitate invasion and inhibit apoptosis in cervical cancer and Grb7 is a potentially molecular target of cervical cancer chemotherapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

  17. Creation of an optically tunable, solid tissue phantom for use in cancer detection

    NASA Astrophysics Data System (ADS)

    Tucker, Matthew B.; Wallace, Catherine; Mantena, Sreekar; Cornwell, Neil; Ross, Weston; Odion, Ren; Vo-Dinh, Tuan; Codd, Patrick

    2018-02-01

    An optically tunable, solid tissue phantom was developed in order to aid in the verification and validation of non-destructive cancer detection technologies based on fluorescence spectroscopy. The solid tissue phantom contained agarose, hemoglobin, Intralipid, NADH, and FAD. The redox ratio of the solid phantoms were shown to be tunable; thus, indicating that these phantoms could be used to tailor specific optical conditions that mimic cancerous and healthy tissues. Therefore, this solid tissue phantom can serve as a suitable test bed to evaluate fluorescence spectroscopy based cancer detection devices.

  18. [Expression and Significance of PI-PLCε1 in Colon Cancer].

    PubMed

    Li, Xiao-Ran; Yang, Kun; Huang, Xiao-Li

    2017-11-01

    To study the expression and clinical significance of phosphoinositide-specific phospholipase Cε1 (PI-PLCε1) in the pathogenesis of colon cancer. qRT-PCR and immunohistochemistry were used to detect the expression of PI-PLCε1 in the 42 cases of colon cancer tissues and their corresponding adjacent tissues. And the effects of tumor differentiation and tumor site on the expression PI-PLCε1 of colon cancer tissues were compared. The results of qRT-PCR showed that the expression of PI-PLCε1 in colon cancer tissue significantly lower than that in the adjacent tissue ( P <0.05). The expression of PI-PLCε1 gene of colon cancer tissue was not effected by tumor differentiation and tumor site ( P >0.05). The results of immuno-histochemistry showed that the positive expression rate of PI-PLCε1 protein in colon cancer tissue was significantly lower than that in the adjacent tissue ( P <0.05). The positive expression rate of PI-PLCε1 protein was not effected by tumor differentiation ( P >0.05),but the expression was different in tumor site ( P <0.05). Expression of PI-PLCε1 was reduced in colon tissue and barely to tumor differentiation.

  19. MicroRNA-300 targets hypoxia inducible factor-3 alpha to inhibit tumorigenesis of human non-small cell lung cancer.

    PubMed

    Zhang, Y; Guo, Y; Yang, C; Zhang, S; Zhu, X; Cao, L; Nie, W; Yu, H

    2017-01-01

    Non-small cell lung cancer (NSCLC) is one of the most deadly human cancers. MicroRNA-300 acts as both tumor promoter and suppressor in different types of cancer. Here, we try to identify the function of microRNA-300 in human NSCLC. We compared MicroRNA-300 levels between tumor tissues versus paired adjacent non-tumor lung tissues from NSCLC patients, and in NSCLC versus normal lung cell lines. Effects of microRNA-300 on cell proliferation, invasion and migration were examined in vitro, and on tumor growth in vivo using a xenograft mouse model. Potential mRNA targets of microRNA-300 were predicted and underlying mechanism was explored. MicroRNA-300 expression was lower in both NSCLC tissues and cell lines. Overexpression of microRNA-300 inhibited proliferation, invasion and migration of NSCLC cells in vitro, and tumor growth in vivo. MicroRNA-300 could directly bind to the 3'-UTR of hypoxia inducible factor-3 alpha (HIF3α) mRNA, and inhibit both its mRNA and protein expressions. Restoring HIF3α expression could rescue the inhibitory effects of microRNA-300 on tumorigenesis of NSCLC both in vitro and in vivo. MicroRNA-300 is a tumor suppressor microRNA in NSCLC by downregulating HIF3α expression. Both microRNA-300 and HIF3α may serve as potential therapeutic targets in NSCLC treatment.

  20. Time-dependent diffusion MRI in cancer: tissue modeling and applications

    NASA Astrophysics Data System (ADS)

    Reynaud, Olivier

    2017-11-01

    In diffusion weighted imaging (DWI), the apparent diffusion coefficient has been recognized as a useful and sensitive surrogate for cell density, paving the way for non-invasive tumor staging, and characterization of treatment efficacy in cancer. However, microstructural parameters, such as cell size, density and/or compartmental diffusivities affect diffusion in various fashions, making of conventional DWI a sensitive but non-specific probe into changes happening at cellular level. Alternatively, tissue complexity can be probed and quantified using the time dependence of diffusion metrics, sometimes also referred to as temporal diffusion spectroscopy when only using oscillating diffusion gradients. Time-dependent diffusion (TDD) is emerging as a strong candidate for specific and non-invasive tumor characterization. Despite the lack of a general analytical solution for all diffusion times / frequencies, TDD can be probed in various regimes where systems simplify in order to extract relevant information about tissue microstructure. The fundamentals of TDD are first reviewed (a) in the short time regime, disentangling structural and diffusive tissue properties, and (b) near the tortuosity limit, assuming weakly heterogeneous media near infinitely long diffusion times. Focusing on cell bodies (as opposed to neuronal tracts), a simple but realistic model for intracellular diffusion can offer precious insight on diffusion inside biological systems, at all times. Based on this approach, the main three geometrical models implemented so far (IMPULSED, POMACE, VERDICT) are reviewed. Their suitability to quantify cell size, intra- and extracellular spaces (ICS and ECS) and diffusivities are assessed. The proper modeling of tissue membrane permeability – hardly a newcomer in the field, but lacking applications - and its impact on microstructural estimates are also considered. After discussing general issues with tissue modeling and microstructural parameter estimation (i

  1. Defining Genomic Changes in Triple Negative Breast Cancer in Women of African Descent

    DTIC Science & Technology

    2013-07-01

    Triple negative breast cancer , Ethnic disparities, Breast cancer amongst African - Americans and Africans , Gene expression... Americans . Adjacent Normal AA Native African TN BC Tissue Figure 1. Gene Expression Pattern of Native African Triple Negative Breast Cancer ...and African - American Adjacent Normal Breast Tissue Genes PI: Pegram & Baumbach

  2. Best Merge Region Growing Segmentation with Integrated Non-Adjacent Region Object Aggregation

    NASA Technical Reports Server (NTRS)

    Tilton, James C.; Tarabalka, Yuliya; Montesano, Paul M.; Gofman, Emanuel

    2012-01-01

    Best merge region growing normally produces segmentations with closed connected region objects. Recognizing that spectrally similar objects often appear in spatially separate locations, we present an approach for tightly integrating best merge region growing with non-adjacent region object aggregation, which we call Hierarchical Segmentation or HSeg. However, the original implementation of non-adjacent region object aggregation in HSeg required excessive computing time even for moderately sized images because of the required intercomparison of each region with all other regions. This problem was previously addressed by a recursive approximation of HSeg, called RHSeg. In this paper we introduce a refined implementation of non-adjacent region object aggregation in HSeg that reduces the computational requirements of HSeg without resorting to the recursive approximation. In this refinement, HSeg s region inter-comparisons among non-adjacent regions are limited to regions of a dynamically determined minimum size. We show that this refined version of HSeg can process moderately sized images in about the same amount of time as RHSeg incorporating the original HSeg. Nonetheless, RHSeg is still required for processing very large images due to its lower computer memory requirements and amenability to parallel processing. We then note a limitation of RHSeg with the original HSeg for high spatial resolution images, and show how incorporating the refined HSeg into RHSeg overcomes this limitation. The quality of the image segmentations produced by the refined HSeg is then compared with other available best merge segmentation approaches. Finally, we comment on the unique nature of the hierarchical segmentations produced by HSeg.

  3. Downregulated long non-coding RNA MEG3 in breast cancer regulates proliferation, migration and invasion by depending on p53’s transcriptional activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sun, Lin; Li, Yu; Yang, Bangxiang, E-mail: b19933009@qq.coom

    Long non-coding RNAs (lncRNAs) was found to play critical roles in tumorigenesis, hence, screen of tumor-related lncRNAs, identification of their biological roles is important for understanding the processes of tumorigenesis. In this study, we identified the expressing difference of several tumor-related lncRNAs in breast cancer samples and found that, MEG3, which is downregulated in non-small cell lung cancer (NSCLC) tumor tissues, is also downregulated in breast cancer samples compared with adjacent tissues. For figuring out the effect of MEG3 in breast cancer cells MCF7 and MB231, we overexpressed MEG3 in these cells, and found that it resulted the inhibition ofmore » proliferation, colony formation, migration and invasion capacities by enhancing p53’s transcriptional activity on its target genes, including p21, Maspin and KAI1. MEG3 presented similar effects in MB157, which is a p53-null breast cancer cell line, when functional p53 but not p53R273H mutant, which lacks transcriptional activity, was introduced. Surprisingly, overexpression of MEG3 activates p53’s transcriptional activity by decreasing MDM2’s transcription level, and thus stabilizes and accumulates P53. Taken together, our findings indicate that MEG3 is downregulated in breast cancer tissues and affects breast cancer cells’ malignant behaviors, which indicate MEG3 a potential therapeutic target for breast cancer. - Highlights: • MEG3 RNA is widely downregulated in breast tumor tissue. • MEG3 regulates P53 indirectly through transcriptional regulation of MDM2. • Under unstressed condition, MEG3-related P53 accumulation transcriptionally activates p53’s target genes. • MEG3 expression level tightly regulates proliferation, colony formation, migration and invasion in breast tumor cells.« less

  4. Effects of long non-coding RNA HOST2 on cell migration and invasion by regulating MicroRNA let-7b in breast cancer.

    PubMed

    Lu, Peng-Wei; Li, Lin; Wang, Fang; Gu, Yuan-Ting

    2018-06-01

    The study intends to investigate the effects of long non-coding RNA HOST2 (lncRNA HOST2) on cell migration and invasion by regulating microRNA let-7b (let-7b) in breast cancer. Breast cancer and adjacent normal tissues were collected from 98 patients with breast cancer. Breast cancer MCF-7 cells were divided into the blank, negative control (NC), pcDNA3-Mock, siHOST2, let-7b inhibitor, pcDNA3-HOST2, let-7b mimic, pcDNA3-HOST2 + let-7b mimic, and siHOST2 + let-7b inhibitor groups. RT-qPCR was used to detect the mRNA expressions of HOST2, let-7b, and c-Myc. Western blotting was conducted to measure the c-Myc expression. Scratch test and Transwell assay were applied to detect the cell motility, migration, and invasion. Xenograft tumor in nude mice was performed to evaluate the effect of different transfection on the tumor growth. Compared with adjacent normal tissues, HOST2 expression was higher but let-7b expression lower in breast cancer tissues. HOST2 expression in breast cancer cells was remarkably increased compared with that in the normal breast epithelial MCF-10A cells. In MCF-7 cells, in comparison with the blank and NC groups, expressions of HOST2 and c-Myc were reduced, but let-7b expression was remarkably elevated in the siHOST2 and let-7b mimic groups; the let-7b inhibitor group exhibited higher expressions of HOST2 and c-Myc but lower let-7b expression. Overexpression of HOST2 could promote cell motility, migration and invasion, thus enhancing the growth of breast cancer tumor. By inhibiting HOST2, opposite trends were found. LncRNA HOST2 promotes cell migration and invasion by inhibiting let-7b in breast cancer patients. © 2017 Wiley Periodicals, Inc.

  5. Application of tissue mesodissection to molecular cancer diagnostics.

    PubMed

    Krizman, David; Adey, Nils; Parry, Robert

    2015-02-01

    To demonstrate clinical application of a mesodissection platform that was developed to combine advantages of laser-based instrumentation with the speed/ease of manual dissection for automated dissection of tissue off standard glass slides. Genomic analysis for KRAS gene mutation was performed on formalin fixed paraffin embedded (FFPE) cancer patient tissue that was dissected using the mesodissection platform. Selected reaction monitoring proteomic analysis for quantitative Her2 protein expression was performed on FFPE patient tumour tissue dissected by a laser-based instrument and the MilliSect instrument. Genomic analysis demonstrates highly confident detection of KRAS mutation specifically in lung cancer cells and not the surrounding benign, non-tumour tissue. Proteomic analysis demonstrates Her2 quantitative protein expression in breast cancer cells dissected manually, by laser-based instrumentation and by MilliSect instrumentation (mesodissection). Slide-mounted tissue dissection is commonly performed using laser-based instruments or manually scraping tissue by scalpel. Here we demonstrate that the mesodissection platform as performed by the MilliSect instrument for tissue dissection is cost-effective; it functions comparably to laser-based dissection and which can be adopted into a clinical diagnostic workflow. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Hypermethylation of MDFI promoter with NSCLC is specific for females, non-smokers and people younger than 65.

    PubMed

    Ma, Hongying; Chen, Xiaoying; Hu, Haochang; Li, Bin; Ying, Xiuru; Zhou, Cong; Zhong, Jie; Zhao, Guofang; Duan, Shiwei

    2018-06-01

    Non-small cell lung carcinoma (NSCLC) is a major subtype of lung cancer. Aberrant DNA methylation has been frequently observed in NSCLC. The aim of the present study was to investigate the role of MyoD family inhibitor ( MDFI ) methylation in NSCLC. Formalin-fixed paraffin-embedded tumor tissues and adjacent non-cancerous tissues were collected from a total of 111 patients with NSCLC. A methylation assay was performed using the quantitative methylation-specific polymerase chain reaction method. The percentage of methylated reference was used to represent the methylation level of the MDFI promoter. Data mining of a dataset from The Cancer Genome Atlas (TCGA) demonstrated that MDFI promoter methylation levels were significantly increased in 830 tumor tissues compared with 75 non-tumor tissues (P=0.012). However, the results on tissues obtained in the present study indicated that the MDFI promoter methylation levels in tumor tissues were not significantly different compared with those in the adjacent non-tumor tissues (P=0.159). Subsequent breakdown analysis identified that higher MDFI promoter methylation levels were significantly associated with NSCLC in females (P=0.031), but not in males (P=0.832). Age-based subgroup analysis demonstrated that higher MDFI promoter methylation levels were significantly associated with NSCLC in younger patients (≤65 years; P=0.003), but not in older patients (P=0.327). In addition, the association of MDFI methylation with NSCLC was significant in non-smokers (P=0.014), but not in smokers (P=0.832). Similar results also have been determined from subgroup analysis of the TCGA datasets. The Gene Expression Omnibus database indicated MDFI expression restoration in partial lung cancer cell lines (H1299 and Hotz) following demethylation treatment. However, it was identified that MDFI promoter hypermethylation was not significantly associated with prognosis of NSCLC (P>0.05). In conclusion, the present study indicated that the

  7. Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer

    PubMed Central

    Danforth, David N.

    2016-01-01

    Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women. PMID:27559297

  8. Biological significance of long non-coding RNA FTX expression in human colorectal cancer

    PubMed Central

    Guo, Xiao-Bo; Hua, Zhu; Li, Chen; Peng, Li-Pan; Wang, Jing-Shen; Wang, Bo; Zhi, Qiao-Ming

    2015-01-01

    The purpose of this study was to determine the expression of long non-coding RNA (lncRNA) FTX and analyze its prognostic and biological significance in colorectal cancer (CRC). A quantitative reverse transcription PCR was performed to detect the expression of long non-coding RNA FTX in 35 pairs of colorectal cancer and corresponding noncancerous tissues. The expression of long non-coding RNA FTX was detected in 187 colorectal cancer tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of Long Non-coding RNA FTX expression. The effects of long non-coding RNA FTX expression on malignant phenotypes of colorectal cancer cells and its possible biological significances were further determined. Long non-coding RNA FTX was significantly upregulated in colorectal cancer tissues, and low long non-coding RNA FTX expression was significantly correlated with differentiation grade, lymph vascular invasion, and clinical stage. Patients with high long non-coding RNA FTX showed poorer overall survival than those with low long non-coding RNA FTX. Multivariate analyses indicated that status of long non-coding RNA FTX was an independent prognostic factor for patients. Functional analyses showed that upregulation of long non-coding RNA FTX significantly promoted growth, migration, invasion, and increased colony formation in colorectal cancer cells. Therefore, long non-coding RNA FTX may be a potential biomarker for predicting the survival of colorectal cancer patients and might be a molecular target for treatment of human colorectal cancer. PMID:26629053

  9. Biological significance of long non-coding RNA FTX expression in human colorectal cancer.

    PubMed

    Guo, Xiao-Bo; Hua, Zhu; Li, Chen; Peng, Li-Pan; Wang, Jing-Shen; Wang, Bo; Zhi, Qiao-Ming

    2015-01-01

    The purpose of this study was to determine the expression of long non-coding RNA (lncRNA) FTX and analyze its prognostic and biological significance in colorectal cancer (CRC). A quantitative reverse transcription PCR was performed to detect the expression of long non-coding RNA FTX in 35 pairs of colorectal cancer and corresponding noncancerous tissues. The expression of long non-coding RNA FTX was detected in 187 colorectal cancer tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of Long Non-coding RNA FTX expression. The effects of long non-coding RNA FTX expression on malignant phenotypes of colorectal cancer cells and its possible biological significances were further determined. Long non-coding RNA FTX was significantly upregulated in colorectal cancer tissues, and low long non-coding RNA FTX expression was significantly correlated with differentiation grade, lymph vascular invasion, and clinical stage. Patients with high long non-coding RNA FTX showed poorer overall survival than those with low long non-coding RNA FTX. Multivariate analyses indicated that status of long non-coding RNA FTX was an independent prognostic factor for patients. Functional analyses showed that upregulation of long non-coding RNA FTX significantly promoted growth, migration, invasion, and increased colony formation in colorectal cancer cells. Therefore, long non-coding RNA FTX may be a potential biomarker for predicting the survival of colorectal cancer patients and might be a molecular target for treatment of human colorectal cancer.

  10. Testing wetland axioms at a watershed scale: Case studies of the aggregate hydrologic effects of non-adjacent wetlands

    EPA Science Inventory

    Wetlands not adjacent to streams (i.e. “non-adjacent wetlands”) are hypothesized to affect downgradient hydrology in a number of ways. Non-adjacent wetlands may, for example, attenuate peak flows, serve as focal points for groundwater recharge, and decrease streamflow...

  11. Non-invasive Optical Molecular Imaging for Cancer Detection

    NASA Astrophysics Data System (ADS)

    Luo, Zhen

    Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide

  12. Fluorescence spectroscopy using excitation and emission matrix for quantification of tissue native fluorophores and cancer diagnosis

    NASA Astrophysics Data System (ADS)

    Wu, Binlin; Gayen, S. K.; Xu, M.

    2014-03-01

    Native fluorescence spectrum of normal and cancerous human prostate tissues is studied to distinguish between normal and cancerous tissues, and cancerous tissues at different cancer grade. The tissue samples were obtained from Cooperative Human Tissue Network (CHTN) and National Disease Research Interchange(NDRI). An excitation and emission matrix (EEM) was generated for each tissue sample by acquiring native fluorescence spectrum of the sample using multiple excitation wavelengths. The non-negative matrix factorization algorithm was used to generate fluorescence EEMs that correspond to the fluorophores in biological tissues, including tryptophan, collagen, elastin, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD) and the background paraffin. We hypothesize that, as a consequence of metabolic changes associated with the development of cancer, the concentrations of NADH and FAD are different in normal and cancerous tissues, and also different for different cancer grades. We used the ratio of the abundances of FAD and NADH to distinguish between normal and cancerous tissues, and the tissue cancer grade. The FAD-to-NADH ratio was found to be the highest for normal tissue and decreased as the cancer grade increased.

  13. Long non-coding RNA FEZF1-AS1 is up-regulated and associated with poor prognosis in patients with cervical cancer.

    PubMed

    Zhang, H-H; Li, A-H

    2018-06-01

    Long noncoding RNA FEZF1-AS1 (FEZF1-AS1) has been showed to involve in a variety of cancers. However, its function and clinical significance in cervical cancer (CC) have not been investigated. The aim of this study was to explore the prognostic value of FEZF1-AS1 in CC patients. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression level of FEZF1-AS1 in CC specimens and adjacent normal cervical tissues. Association between FEZF1-AS1 expression and clinicopathological characteristics was analyzed x2-test. The Kaplan-Meier method was used to estimate survival curves, and the log-rank statistic was used to test the role of FEZF1-AS1 expression. The possibility of FEZF1-AS1 as a prognostic biomarker for CC was examined by Cox proportional hazard regression model. We found that FEZF1-AS1 expression levels were significantly higher in CC tissues compared with adjacent non-cancerous tissues (p < 0.01). High expressions of FEZF1-AS1 were significantly association with poorer histological grade (p = 0.004), positive distant metastasis (p = 0.002) and advanced FIGO stage (p = 0.001). Furthermore, patients with low FEZF1-AS1 expression lived shorter than those with high FEZF1-AS1 expression (Log-rank test, p < 0.0034). Cox regression analysis demonstrated that FEZF1-AS1 expression level was an independent prognostic factor for CC overall survival rates (p = 0.008). We firstly provided clinical evidence that FEZF1-AS1 may be a possible biomarker of poor prognosis in CC.

  14. Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

    PubMed

    Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

    2003-10-01

    Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

  15. Identification and prognostic value of anterior gradient protein 2 expression in breast cancer based on tissue microarray.

    PubMed

    Guo, Jilong; Gong, Guohua; Zhang, Bin

    2017-07-01

    Breast cancer has attracted substantial attention as one of the major cancers causing death in women. It is crucial to find potential biomarkers of prognostic value in breast cancer. In this study, the expression pattern of anterior gradient protein 2 in breast cancer was identified based on the main molecular subgroups. Through analysis of 69 samples from the Gene Expression Omnibus database, we found that anterior gradient protein 2 expression was significantly higher in non-triple-negative breast cancer tissues compared with normal tissues and triple-negative breast cancer tissues (p < 0.05). The data from a total of 622 patients from The Cancer Genome Atlas were analysed. The data from The Cancer Genome Atlas and results from quantitative reverse transcription polymerase chain reaction also verified the anterior gradient protein 2 expression pattern. Furthermore, we performed immunohistochemical analysis. The quantification results revealed that anterior gradient protein 2 is highly expressed in non-triple-negative breast cancer (grade 3 excluded) and grade 1 + 2 (triple-negative breast cancer excluded) tumours compared with normal tissues. Anterior gradient protein 2 was significantly highly expressed in non-triple-negative breast cancer (grade 3 excluded) and non-triple-negative breast cancer tissues compared with triple-negative breast cancer tissues (p < 0.01). In addition, anterior gradient protein 2 was significantly highly expressed in grade 1 + 2 (triple-negative breast cancer excluded) and grade 1 + 2 tissues compared with grade 3 tissues (p < 0.05). Analysis by Fisher's exact test revealed that anterior gradient protein 2 expression was significantly associated with histologic type, histological grade, oestrogen status and progesterone status. Univariate analysis of clinicopathological variables showed that anterior gradient protein 2 expression, tumour size and lymph node status were significantly correlated with overall

  16. The cellular environment of cancerous human tissue. Interfacial and dangling water as a "hydration fingerprint".

    PubMed

    Abramczyk, Halina; Brozek-Pluska, Beata; Krzesniak, Marta; Kopec, Monika; Morawiec-Sztandera, Alina

    2014-08-14

    Despite a large number of publications, the role of water in the cellular environment of biological tissue has not been clarified. Characterizing the biological interface is a key challenge in understanding the interactions of water in the tissue. Although we often assume that the properties of the bulk water can be translated to the crowded biological environment, this approach must be considerably revised when considering the biological interface. To our knowledge, few studies have directly monitored the interactions and accumulation of water in the restricted environments of the biological tissue upon realistic crowding conditions. The present study focuses on a molecular picture of water molecules at the biological interface, or specifically, water molecules adjacent to the hydrophobic and hydrophilic surfaces of normal and cancerous tissues. We recorded and analyzed the IR and Raman spectra of the νs(OH) stretching modes of water at the biological interfaces of the human breast and neck tissues. The results revealed dramatic changes in the water content in the tissue and are potentially relevant to both the fundamental problems of interfacial water modeling and the molecular diagnostics of cancer as a 'hydration fingerprint'. Herein, we will discuss the origin of the vibrational substructures observed for the νs(OH) stretching modes of water, showing that the interfacial water interacting via H-bond with other water molecules and biomolecules at the biological surface and free OH vibration of the dangling water are sensitive indicators of the pathology between the normal (noncancerous) and cancerous tissue and cancer types. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Aberrant microRNA-137 promoter methylation is associated with lymph node metastasis and poor clinical outcomes in non-small cell lung cancer

    PubMed Central

    Min, Lingfeng; Wang, Fang; Hu, Suwei; Chen, Yong; Yang, Junjun; Liang, Sudong; Xu, Xingxiang

    2018-01-01

    MicroRNA-137 (miR-137) functions as a tumor suppressor and is silenced by aberrant promoter methylation. Previous studies have demonstrated that miR-137 is downregulated in lung cancer. The purpose of the present study was to investigate miR-137 promoter methylation and to assess its prognostic value in non-small cell lung cancer (NSCLC). The expression of miR-137 was analyzed inhuman lung cancer A549 and H1299 cells and normal bronchial epithelial BEAS-2B cells, 10 paired formalin-fixed paraffin-embedded lung cancer and normal tissue samples, and 56 archived paraffin-embedded lung cancer tissues. Quantitative methylation-specific polymerase chain reaction analysis was used to assess the miR-137 methylation status. The associations between miR-137 promoter methylation and the clinicopathological features and prognosis of patients with NSCLC (n=56) were analyzed using analysis of variance. miR-137 was markedly downregulated in lung cancer cells and lung cancer tissue specimens compared with expression in BEAS-2B cells and matched adjacent normal lung tissues. A significant negative correlation between miR-137 expression and miR-137 promoter methylation was observed in human lung cancer tissues (r=−0.343; P=0.01). Smoking, lymph node metastasis and advanced clinical stage were associated with significantly lower expression of miR-137 in variance analysis. High levels of miR-137 promoter methylation were associated with a significantly poorer disease-free survival rate (P=0.034), but were not associated with overall survival, in Kaplan-Meier analysis and univariate analysis. In conclusion, the results of the present study indicated that miR-137 is downregulated and that its promoter is aberrantly methylated in lung cancer, and that high levels of miR-137 promoter methylation may have prognostic value for poor disease-free survival. PMID:29740491

  18. CIP2A down regulation enhances the sensitivity of pancreatic cancer cells to gemcitabine.

    PubMed

    Xu, Peng; Yao, Jie; He, Jin; Zhao, Long; Wang, Xiaodong; Li, Zhennan; Qian, Jianjun

    2016-03-22

    Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which participates in inhibiting tumor apoptosis in pancreatic cancer cells. Using immunohistochemical staining, we investigated the expression of CIP2A protein in 72 cases of human pancreatic ductal adenocarcinoma (PDAC) tissue and 27 cases of adjacent normal pancreatic tissue. The positive rate of CIP2A protein expression in pancreatic cancer tissue was70.83 %, which was significantly higher than that in adjacent non- cancerous pancreatic tissue (11.11%). The expression of CIP2A was found to be correlated with TNM stage, but not correlated with age, gender, tumor location, smoking status, alcohol consumption, diabetes, high blood pressure, BMI, tumor size, lymph node metastasis or distant metastases. Kaplan- Meier survival analysis showed that patients with positive CIP2A protein expression had a lower overall survival rate than patients without CIP2A expression. COX regression analysis indicated that expression of CIP2A was an independent prognostic factor for pancreatic ductal adenocarcinoma. In addition, down-regulation of CIP2A inhibited cell proliferation and increased sensitivity to gemcitabine in pancreatic cancer cells by decreasing AKT signaling pathway. Our results indicated that down-regulation of CIP2A could be a novel therapeutic strategy for pancreatic cancer.

  19. A rare eicosanoid precursor analogue, sciadonic acid (5Z,11Z,14Z-20:3), detected in vivo in hormone positive breast cancer tissue.

    PubMed

    Park, H G; Zhang, J Y; Foster, C; Sudilovsky, D; Schwed, D A; Mecenas, J; Devapatla, S; Lawrence, P; Kothapalli, K S D; Brenna, J T

    2018-07-01

    Numerous genetic alterations of HSA 11q13 are found frequently in several cancer types, including breast cancer (BC). The 11q13 locus harbors FADS2 encoding Δ6 desaturation which is not functional in several cancer cell lines, including hormone positive MCF7 BC cells. In vitro, the non-functional FADS2 activity unmasks 18:2n-6 elongation to 20:2n-6 and Δ5 desaturation by FADS1 to yield 5Z,11Z,14Z-20:3 (sciadonic acid) rather than 5Z,8Z,11Z,14Z-20:4 (arachidonic acid). In this pilot study we aimed to determine whether 5,11,14-20:3 appears in vivo in hormone positive human BC tissue. Fatty acids were profiled in surgically removed human breast tumor and adjacent normal tissue (n = 9). Sciadonic acid was detected in three of nine breast tumor samples and was below detect limits in normal breast tissue. The internal Δ8 double bond of arachidonic acid is required for normal eicosanoid synthesis but is missing in sciadonic acid. This pilot study demonstrates for the first time in vivo sciadonic acid in hormone positive BC tissue, warranting a larger survey study to further evaluate its appearance and the functional implications. Copyright © 2018. Published by Elsevier Ltd.

  20. RUNX3 methylation in normal surrounding urothelium of patients with non-muscle-invasive bladder cancer: potential role in the prediction of tumor progression.

    PubMed

    Jeong, P; Min, B D; Ha, Y S; Song, P H; Kim, I Y; Ryu, K H; Kim, J H; Yun, S J; Kim, W J

    2012-11-01

    Previously, we reported a causal relationship between RUNX3 methylation and bladder tumor development. Thus, in order to clarify its role in tumorigenesis, this study aims to identify the function of RUNX3 methylation in normal adjacent urothelium of patients with non-muscle invasive bladder cancer (NMIBC). Tumor tissue and donor-matched normal adjacent tissue from 55 patients who underwent transurethral resection (TUR) were selected for the study, and RUNX3 promoter methylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). RUNX3 promoter methylation occurred more frequently in tumor samples than in histologically normal urothelium in patients with NMIBC (P = 0.02). The methylation rates for the RUNX3 promoter in normal adjacent urothelium and tumor tissue were 47% and 69%, respectively. Interestingly, RUNX3 methylation in normal adjacent urothelium was associated with tumor number (P = 0.022) and progression (P = 0.035). Kaplan-Meier estimates revealed that RUNX3 methylation in normal urothelium showed a significant association with time to progression (P = 0.017) in NMIBC patients. Stratifying the patients into 'both methylation', 'one methylation' and 'no methylation' groups for tumors and normal urothelium revealed that no progression occurred in the 'no methylation' group during follow-up. Multivariate Cox regression analysis demonstrated that RUNX3 methylation in normal urothelium [hazards ratio (HR): 5.692, P = 0.042] was an independent predictor of progression. RUNX3 methylation was associated with transition from normal urothelium to bladder tumor. More importantly, RUNX3 methylation in normal adjacent urothelium may predict progression in NMIBC patients who have undergone TUR. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Prostate cancer region prediction using MALDI mass spectra

    NASA Astrophysics Data System (ADS)

    Vadlamudi, Ayyappa; Chuang, Shao-Hui; Sun, Xiaoyan; Cazares, Lisa; Nyalwidhe, Julius; Troyer, Dean; Semmes, O. John; Li, Jiang; McKenzie, Frederic D.

    2010-03-01

    For the early detection of prostate cancer, the analysis of the Prostate-specific antigen (PSA) in serum is currently the most popular approach. However, previous studies show that 15% of men have prostate cancer even their PSA concentrations are low. MALDI Mass Spectrometry (MS) proves to be a better technology to discover molecular tools for early cancer detection. The molecular tools or peptides are termed as biomarkers. Using MALDI MS data from prostate tissue samples, prostate cancer biomarkers can be identified by searching for molecular or molecular combination that can differentiate cancer tissue regions from normal ones. Cancer tissue regions are usually identified by pathologists after examining H&E stained histological microscopy images. Unfortunately, histopathological examination is currently done on an adjacent slice because the H&E staining process will change tissue's protein structure and it will derogate MALDI analysis if the same tissue is used, while the MALDI imaging process will destroy the tissue slice so that it is no longer available for histopathological exam. For this reason, only the most confident cancer region resulting from the histopathological examination on an adjacent slice will be used to guide the biomarker identification. It is obvious that a better cancer boundary delimitation on the MALDI imaging slice would be beneficial. In this paper, we proposed methods to predict the true cancer boundary, using the MALDI MS data, from the most confident cancer region given by pathologists on an adjacent slice.

  2. Immuno-proteomic discovery of tumor tissue autoantigens identifies olfactomedin 4, CD11b, and integrin alpha-2 as markers of colorectal cancer with liver metastases.

    PubMed

    Yang, Qian; Bavi, Prashant; Wang, Julia Y; Roehrl, Michael H

    2017-09-25

    Late-stage colorectal cancer with liver metastasis is common and affords poor prognosis, yet there is a dearth of reliable biomarkers. Cancer is often characterized by an increase in serologic autoantibodies. Hence, we embarked on an immuno-proteomic strategy by using autoantibodies to discover antigens in tumor tissue as potential cancer markers. Matched sets of tissues from primary colon cancer, liver metastases, and adjacent benign tissues were obtained from colon cancer patients. Tissue proteins were extracted, and autoantigens were uncovered by immunoblotting with autoantibodies and sequenced by mass spectrometry. Informatics analyses identified 48 proteins that were found in tumor only but were absent in normal tissue. Five of these were reproducibly found in two independent experiments, including olfactomedin 4 (OLFM4), CD11b, integrin α2 (ITGA2), periostin, and thrombospondin-2. Further confirmation with tissue from 43 patients by Western blotting, immunohistochemistry, and tissue microarray deemed OLFM4, CD11b, and ITGA2 to be significantly overexpressed in both primary colon tumors and liver metastases. These tumor tissue autoantigens may serve as promising markers for developing differential diagnostics and immunotherapies for colorectal cancers, in particular, those with tendency to progress to liver metastases. Late-stage colorectal cancer with liver metastasis is common and affords poor prognosis, yet there is a dearth of reliable biomarkers. Cancer is often characterized by an increase in serologic autoantibodies. Cancer tissue immunogens - antigens capable of inducing specific antibody production in patients - are promising targets for development of precision diagnostics and immunotherapies. In our manuscript, we describe on an immuno-proteomic strategy by using autoantibodies to discover antigens in tumor tissue as potential cancer markers. Matched sets of tissues from primary colon cancer, liver metastases, and adjacent benign tissues were

  3. Tim-3 Up-regulation in Patients with Gastric Cancer and Peptic Ulcer Disease

    PubMed Central

    Naghavi-Alhosseini, Mahdieh; Tehrani, Mohsen; Ajami, Abolghasem; Rafiei, Alireza; Taghvaei, Tarang; Vahedi-Larijani, Laleh; Hossein-Nataj, Hadi; Asgarian-Omran, Hossein

    2017-01-01

    Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an inhibitory immunoregulatory receptor, has been recently implicated in tumor biology and tumor-associated immune suppression. In the present study, expression of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at both mRNA and protein levels. Methods: A total of 133 gastric tissue biopsies, comprising 43 from GC cases, 48 from PUD and 42 from non-ulcer dyspepsia (NUD) serving as controls were collected. Additionally, non-neoplastic adjacent tissue biopsies were also obtained from 6 patients with GC. Infection with Helicobacter pylori was determined by the rapid urease test for all participants and H&E staining was conducted for GC and PUD patients. Tim-3 relative mRNA expression was determined by SYBR Green based Real-Time PCR using β-actin as a reference gene. Tim-3 protein expression was also studied by immunohistochemistry in 7 GC, 7 PUD and 10 NUD tissue samples. Results: Tim-3 was expressed at higher levels in GC (p=0.030) and PUD (p=0.022) cases compared to he NUD group. Among paired samples obtained from gastric cancer patients, tumor tissues showed elevated Tim-3 expression (p=0.019) in comparison with adjacent non-neoplastic biopsies. Tim-3 mRNA findings were supported by detection of more Tim-3 protein in cancerous (p=0.002) and ulcerative (p=0.01) tissues than in controls. Tim-3 was similarly expressed in H. pylori positive and negative cases. Conclusion: Higher Tim-3 expression in patients with gastric cancer and peptic ulcer implies that it might be involved in immune regulation and establishment of these gastrointestinal diseases. Targeted immunotherapy by blocking of inhibitory receptors like Tim-3 could be a promising approach for gastric cancer treatment. PMID:28441784

  4. Exploiting passive nanomedicine accumulation at sites of enhanced vascular permeability for non-cancerous applications.

    PubMed

    Durymanov, Mikhail; Kamaletdinova, Tatiana; Lehmann, Sarah E; Reineke, Joshua

    2017-09-10

    Over the past few decades, enhanced permeability of tumor vasculature was actively exploited for targeted delivery of anticancer nanomedicines resulting in numerous pharmaceutical products. Formation of new immature and leaky vessels along with inflammatory remodeling of existing vessels accompany development of numerous diseases beyond cancer and present an opportunity for passive accumulation of intravenously administered nanomedicines in many pathological tissues. To date, applications of non-cancerous enhanced permeation have been relatively unexploited as target tissues and may create new therapy and prevention technologies for many disorders. Herein, we summarize the current knowledge on the nature of enhanced vascular permeability in multiple non-cancerous pathological tissues. We also discuss the clinical status of nanotherapeutics with selectivity based on passive accumulation in non-cancerous target tissues, their challenges, and prospects. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

    PubMed

    Johnson, Kevin C; Houseman, E Andres; King, Jessica E; Christensen, Brock C

    2017-07-10

    The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and family history of disease, with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 cytosine-guanine dinucleotide (CpG) sites that demonstrated significant associations (Q value <0.01) with subject age. Notably, DNA methylation was not strongly associated with the other evaluated breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations, using normal breast tissue samples (n = 18) and samples of normal tissue adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and invasive breast tumors (n = 731, P = 1.1E-13). DNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer, suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.

  6. The MiAge Calculator: a DNA methylation-based mitotic age calculator of human tissue types.

    PubMed

    Youn, Ahrim; Wang, Shuang

    2018-01-01

    Cell division is important in human aging and cancer. The estimation of the number of cell divisions (mitotic age) of a given tissue type in individuals is of great interest as it allows not only the study of biological aging (using a new molecular aging target) but also the stratification of prospective cancer risk. Here, we introduce the MiAge Calculator, a mitotic age calculator based on a novel statistical framework, the MiAge model. MiAge is designed to quantitatively estimate mitotic age (total number of lifetime cell divisions) of a tissue using the stochastic replication errors accumulated in the epigenetic inheritance process during cell divisions. With the MiAge model, the MiAge Calculator was built using the training data of DNA methylation measures of 4,020 tumor and adjacent normal tissue samples from eight TCGA cancer types and was tested using the testing data of DNA methylation measures of 2,221 tumor and adjacent normal tissue samples of five other TCGA cancer types. We showed that within each of the thirteen cancer types studied, the estimated mitotic age is universally accelerated in tumor tissues compared to adjacent normal tissues. Across the thirteen cancer types, we showed that worse cancer survivals are associated with more accelerated mitotic age in tumor tissues. Importantly, we demonstrated the utility of mitotic age by showing that the integration of mitotic age and clinical information leads to improved survival prediction in six out of the thirteen cancer types studied. The MiAge Calculator is available at http://www.columbia.edu/∼sw2206/softwares.htm .

  7. Tissue Refractive Index Fluctuations Report on Cancer Development

    NASA Astrophysics Data System (ADS)

    Popescu, Gabriel

    2012-02-01

    The gold standard in histopathology relies on manual investigation of stained tissue biopsies. A sensitive and quantitative method for in situ tissue specimen inspection is highly desirable, as it will allow early disease diagnosis and automatic screening. Here we demonstrate that quantitative phase imaging of entire unstained biopsies has the potential to fulfill this requirement. Our data indicates that the refractive index distribution of histopathology slides, which contains information about the molecular scale organization of tissue, reveals prostate tumors. These optical maps report on subtle, nanoscale morphological properties of tissues and cells that cannot be recovered by common stains, including hematoxylin and eosin (H&E). We found that cancer progression significantly alters the tissue organization, as exhibited in our refractive index maps. Furthermore, using the quantitative phase information, we obtained the spatially resolved scattering mean free path and anisotropy factor g for entire biopsies and demonstrated their direct correlation with tumor presence. We found that these scattering parameters are able to distinguish between two adjacent grades, which is a difficult task and relevant for determining patient treatment. In essence, our results show that the tissue refractive index reports on the nanoscale tissue architecture and, in principle, can be used as an intrinsic marker for cancer diagnosis. [4pt] [1] Z. Wang, K. Tangella, A. Balla and G. Popescu, Tissue refractive index as marker of disease, Journal of Biomedical Optics, in press).[0pt] [2] Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette and G. Popescu, Spatial light interference microscopy (SLIM), Optics Express, 19, 1016 (2011).[0pt] [3] Z. Wang, D. L. Marks, P. S. Carney, L. J. Millet, M. U. Gillette, A. Mihi, P. V. Braun, Z. Shen, S. G. Prasanth and G. Popescu, Spatial light interference tomography (SLIT), Optics Express, 19, 19907-19918 (2011

  8. Long Non-Coding RNAs Differentially Expressed between Normal versus Primary Breast Tumor Tissues Disclose Converse Changes to Breast Cancer-Related Protein-Coding Genes

    PubMed Central

    Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U.; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N.; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O.

    2014-01-01

    Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the

  9. Long non-coding RNAs differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes.

    PubMed

    Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Lüders, Torben; Due, Eldri U; Naume, Bjørn; Riis, Margit; Kristensen, Vessela N; Horn, Friedemann; Børresen-Dale, Anne-Lise; Hackermüller, Jörg; Baumbusch, Lars O

    2014-01-01

    Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the

  10. Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer.

    PubMed

    Li, Xiaolei; Zhang, Qianhui; Fan, Kai; Li, Baiyan; Li, Huifeng; Qi, Hanping; Guo, Jing; Cao, Yonggang; Sun, Hongli

    2016-03-24

    (1) BACKGROUND: Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP channels family of Ca(2+)-permeant channels. The proteins of some TRP channels are highly expressed in cancer cells. This study aimed to assess the clinical significance and biological functions of TRPV3 in non-small cell lung cancer (NSCLC); (2) METHODS: Immunohistochemistry was used to detect the expression of TRPV3 in NSCLC tissues and adjacent noncancerous lung tissues. Western blot was used to detect the protein expressions of TRPV3, CaMKII, p-CaMKII, CyclinA, CyclinD, CyclinE1, CDK2, CDK4, and P27. Small interfering RNA was used to deplete TRPV3 expression. A laser scanning confocal microscope was used to measure intracellular calcium concentration ([Ca(2+)]i). Flow cytometry was used to analyze cell cycle; (3) RESULTS: TRPV3 was overexpressed in 65 of 96 (67.7%) human lung cancer cases and correlated with differentiation (p = 0.001) and TNM stage (p = 0.004). Importantly, TRPV3 expression was associated with short overall survival. In addition, blocking or knockdown of TRPV3 could inhibit lung cancer cell proliferation. Moreover, TRPV3 inhibition could decrease [Ca(2+)]i of lung cancer cells and arrest cell cycle at the G1/S boundary. Further results revealed that TRPV3 inhibition decreased expressions of p-CaMKII, CyclinA, CyclinD1, CyclinE, and increased P27 level; (4) CONCLUSIONS: Our findings demonstrate that TRPV3 was overexpressed in NSCLC and correlated with lung cancer progression. TRPV3 activation could promote proliferation of lung cancer cells. TRPV3 might serve as a potential companion drug target in NSCLC.

  11. Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer

    PubMed Central

    Li, Xiaolei; Zhang, Qianhui; Fan, Kai; Li, Baiyan; Li, Huifeng; Qi, Hanping; Guo, Jing; Cao, Yonggang; Sun, Hongli

    2016-01-01

    (1) Background: Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP channels family of Ca2+-permeant channels. The proteins of some TRP channels are highly expressed in cancer cells. This study aimed to assess the clinical significance and biological functions of TRPV3 in non-small cell lung cancer (NSCLC); (2) Methods: Immunohistochemistry was used to detect the expression of TRPV3 in NSCLC tissues and adjacent noncancerous lung tissues. Western blot was used to detect the protein expressions of TRPV3, CaMKII, p-CaMKII, CyclinA, CyclinD, CyclinE1, CDK2, CDK4, and P27. Small interfering RNA was used to deplete TRPV3 expression. A laser scanning confocal microscope was used to measure intracellular calcium concentration ([Ca2+]i). Flow cytometry was used to analyze cell cycle; (3) Results: TRPV3 was overexpressed in 65 of 96 (67.7%) human lung cancer cases and correlated with differentiation (p = 0.001) and TNM stage (p = 0.004). Importantly, TRPV3 expression was associated with short overall survival. In addition, blocking or knockdown of TRPV3 could inhibit lung cancer cell proliferation. Moreover, TRPV3 inhibition could decrease [Ca2+]i of lung cancer cells and arrest cell cycle at the G1/S boundary. Further results revealed that TRPV3 inhibition decreased expressions of p-CaMKII, CyclinA, CyclinD1, CyclinE, and increased P27 level; (4) Conclusions: Our findings demonstrate that TRPV3 was overexpressed in NSCLC and correlated with lung cancer progression. TRPV3 activation could promote proliferation of lung cancer cells. TRPV3 might serve as a potential companion drug target in NSCLC. PMID:27023518

  12. An Integrated Analysis of miRNA and mRNA Expressions in Non-Small Cell Lung Cancers

    PubMed Central

    Ma, Lina; Huang, Yanyan; Zhu, Wangyu; Zhou, Shiquan; Zhou, Jihang; Zeng, Fang; Liu, Xiaoguang; Zhang, Yongkui; Yu, Jun

    2011-01-01

    Using DNA microarrays, we generated both mRNA and miRNA expression data from 6 non-small cell lung cancer (NSCLC) tissues and their matching normal control from adjacent tissues to identify potential miRNA markers for diagnostics. We demonstrated that hsa-miR-96 is significantly and consistently up-regulated in all 6 NSCLCs. We validated this result in an independent set of 35 paired tumors and their adjacent normal tissues, as well as their sera that are collected before surgical resection or chemotherapy, and the results suggested that hsa-miR-96 may play an important role in NSCLC development and has great potential to be used as a noninvasive marker for diagnosing NSCLC. We predicted potential miRNA target mRNAs based on different methods (TargetScan and miRanda). Further classification of miRNA regulated genes based on their relationship with miRNAs revealed that hsa-miR-96 and certain other miRNAs tend to down-regulate their target mRNAs in NSCLC development, which have expression levels permissive to direct interaction between miRNAs and their target mRNAs. In addition, we identified a significant correlation of miRNA regulation with genes coincide with high density of CpG islands, which suggests that miRNA may represent a primary regulatory mechanism governing basic cellular functions and cell differentiations, and such mechanism may be complementary to DNA methylation in repressing or activating gene expression. PMID:22046296

  13. 2-O-Methylmagnolol upregulates the long non-coding RNA, GAS5, and enhances apoptosis in skin cancer cells.

    PubMed

    Wang, Tong-Hong; Chan, Chieh-Wen; Fang, Jia-You; Shih, Ya-Min; Liu, Yi-Wen; Wang, Tzu-Chien V; Chen, Chi-Yuan

    2017-03-02

    Magnolol, a hydroxylated biphenol compound isolated from the bark of Magnolia officinalis, has been shown to exhibit anti-proliferative effect in various cancer cells, including skin cancer cells. Methoxylation of magnolol appears to improve its anti-inflammatory activity, yet the effect of this modification on the agent's antitumor activity remains unknown. In this work, we report that 2-O-methylmagnolol (MM1) displays improved antitumor activity against skin cancer cells compared to magnolol both in vitro and in vivo. The increased antitumor activity of MM1 appears to correlate with its increased ability to induce apoptosis. DNA microarray and network pathway analyses suggest that MM1 affects certain key factors involved in regulating apoptosis and programmed cell death. Interestingly, the level of the long non-coding (lnc) RNA of growth arrest-specific 5 (GAS5) was increased in MM1-treated cells, and inhibition of lncRNA GAS5 inhibited MM1-induced apoptosis. Conversely, overexpression of lncRNA GAS5 inhibited cell proliferation and promoted cell apoptosis in skin cancer cells. The expression of lncRNA GAS5 in the skin cancer tissues was found to be lower than that in the adjacent normal tissues in a majority of patients. Taken together, our findings suggest that MM1 has improved antitumor activity in skin cancer cells, and that this is due, at least in part, to the upregulation of lncRNA GAS5 and the enhancement of apoptosis.

  14. Long non-coding RNA lnc-MX1-1 is associated with poor clinical features and promotes cellular proliferation and invasiveness in prostate cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jiang, Chen-Yi; Gao, Yuan; Wang, Xing-Jie

    Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined bymore » real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer. - Highlights: • LncRNA lnc-MX1-1 is up-regulated in prostate cancer. • Overexpression of lnc-MX1-1 is correlated with poor prostate cancer clinical features. • Knockdown of lnc-MX1-1 reduces proliferation and invasiveness of prostate cancer cells.« less

  15. Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway.

    PubMed

    Wang, Yuanyuan; Lin, Xiangde; Fu, Xinghao; Yan, Wei; Lin, Fusheng; Kuang, Penghao; Luo, Yezhe; Lin, Ende; Hong, Xiaoquan; Wu, Guoyang

    2018-06-18

    Thyroid cancer is one of the most common malignant tumors of the endocrine system. Among all thyroid cancers, papillary thyroid carcinoma (PTC) is the most common type. The BRAF-activated non-coding RNA (BANCR) is a 693-bp nucleotide transcript which was first identified in melanoma. However, the role of BANCR in the development of thyroid cancer remains unclear. Therefore, the present study investigated the potential involvement of BANCR in the development of thyroid cancer in vitro using patient tissue samples and a panel of thyroid cancer cell lines, and in vivo using a xenograft mouse model. We observed that BANCR was expressed at a higher level in human thyroid tumor tissues than that noted in the adjacent normal tissues. The expression level of BANCR differed between cultured thyroid cancer cell lines; BANCR expression was lower in the BCPAP cell line than that observed in the CAL-62, WRO and FTC-133 cell lines. Western blot analysis and flow cytometry revealed that overexpression of BANCR in the BCPAP cell line resulted in increased expression of the cancer stem cell markers, LGR5 and EpCAM. Single-clone formation experiments showed that upregulated expression of BANCR in the BCPAP cell line promoted an increase in the number of clones formed. Similarly, in microsphere formation experiments, overexpression of BANCR resulted in increased number and size of microspheres compared with the control cell line. Western blotting experiments showed that BANCR overexpression in BCPAP upregulated the expression of phosphorylated c-Raf, MEK1/2 and ERK1/2. Inhibition of c-Raf via U0126 decreased the expression of LGR5 and EpCAM, as well as phosphorylated levels of c-Raf, MEK1/2 and ERK1/2 in the BCPAP cells, compared to levels in the DMSO controls. In the xenograft mouse model, BANCR overexpression in the thyroid cancer cells significantly increased tumor growth. Taken together, these results suggest that BANCR plays a role in PTC development by regulating the

  16. Characterization of human breast cancer tissues by infrared imaging.

    PubMed

    Verdonck, M; Denayer, A; Delvaux, B; Garaud, S; De Wind, R; Desmedt, C; Sotiriou, C; Willard-Gallo, K; Goormaghtigh, E

    2016-01-21

    Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins.

  17. Association of proteasomal activity with metastasis in luminal breast cancer

    NASA Astrophysics Data System (ADS)

    Shashova, E. E.; Fesik, E. A.; Doroshenko, A. V.

    2017-09-01

    Chimotrypsin-like (ChTL) and caspase-like (CL) proteasomal activities were investigated in different variants of the tumor progression of luminal breast cancer. Patients with primary luminal breast cancer (n = 123) in stage T1-3N0-2M0 who had not received neoadjuvant treatment were included in this study. Proteasome ChTL and CL activities were determined in the samples of tumor and adjacent tissues. The coefficients of chymotrypsin-like (kChTL) and caspase-like (kCL) proteasome activity were also calculated as the ratio of the corresponding activity in the tumor tissue to activity in the adjacent tissue. ChTL, CL, kChTL and kCL in the tissues of luminal A and B breast cancer with lymphogenic metastasis were compared, and their association with hematogenous metastasis was evaluated. On the one hand, CL activity of proteasomes increased in luminal A breast cancer with extensive lymphogenic metastasis (N2), on the other hand it decreased in the luminal B subtype of cancer. The ratio of proteasomal activity in the tumor and adjacent tissues plays a significant role in the hematogenic pathway of breast cancer progression and is associated with poor metastatic-free survival.

  18. Non-invasive characterization of normal and pathological tissues through dynamic infrared imaging in the hamster cheek pouch oral cancer model

    NASA Astrophysics Data System (ADS)

    Herrera, María. S.; Monti Hughes, Andrea; Salva, Natalia; Padra, Claudio; Schwint, Amanda; Santa Cruz, Gustavo A.

    2017-05-01

    Biomedical infrared thermography, a non-invasive and functional imaging method, provides information on the normal and abnormal status and response of tissues in terms of spatial and temporal variations in body infrared radiance. It is especially attractive in cancer research due to the hypervascular and hypermetabolic activity of solid tumors. Moreover, healthy tissues like skin or mucosa exposed to radiation can be examined since inflammation, changes in water content, exudation, desquamation, erosion and necrosis, between others, are factors that modify their thermal properties. In this work we performed Dynamic Infrared Imaging (DIRI) to contribute to the understanding and evaluation of normal tissue, tumor and precancerous tissue response and radiotoxicity in an in vivo model, the hamster cheek pouch, exposed to Boron Neutron Capture Therapy. In this study, we particularly focused on the observation of temperature changes under forced transient conditions associated with mass moisture transfer in the tissue-air interface, in each tissue with or without treatment. We proposed a simple mathematical procedure that considerers the heat transfer from tissue to ambient through convection and evaporation to model the transient (exponential decay o recover) thermal study. The data was fitted to determined the characteristic decay and recovery time constants of the temperature as a function of time. Also this model allowed to explore the mass flux of moisture, as a degree of evaporation occurring on the tissue surface. Tissue thermal responses under provocation tests could be used as a non-invasive method to characterize tissue physiology.

  19. Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer

    PubMed Central

    Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Yuan, Yuan

    2017-01-01

    Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival. PMID:28350854

  20. Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer.

    PubMed

    Lu, Youzhu; Jing, Jingjing; Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Sun, Mingjun; Yuan, Yuan

    2017-01-01

    Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival.

  1. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  2. Mass counts: ERP correlates of non-adjacent dependency learning under different exposure conditions.

    PubMed

    Citron, Francesca M M; Oberecker, Regine; Friederici, Angela D; Mueller, Jutta L

    2011-01-10

    Miniature language learning can serve to model real language learning as high proficiency can be reached after very little exposure. In a previous study by Mueller et al. [18] German participants acquired non-adjacent syntactic dependencies by mere exposure to correct Italian sentences, but their ERP pattern differed from the one shown by native speakers. The present study follows up on that experiment using a similar design and material and is focused on two important issues: the influence of acoustic cues in the material and the impact of the learning procedure. With respect to the latter we compared alternating learning and test phases to a continuous learning and test phase. In addition, a splicing procedure eliminated prosodic cues in order to ensure that non-adjacent dependencies were learned instead of adjacent ones. Results for the continuous phase design showed a native-like biphasic ERP pattern, an N400 followed by a left-focused positivity. In the alternating design behavioural accuracy was lower and only an N400 was found. The results suggest an advantage of continuous learning phases for adult learners, possibly due to the absence of ungrammatical items present in the test phases in the alternating learning procedure. Furthermore, the replication of the earlier study with prosodically controlled material adds evidence to the general finding that syntactic non-adjacent dependencies can be learned from mere exposure to correct examples. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. The expression and prognostic value of protein tyrosine kinase 6 in early-stage cervical squamous cell cancer.

    PubMed

    Wang, Xiao-Jing; Xiong, Ying; Ma, Ze-Biao; Xia, Jian-Chuan; Li, Yan-Fang

    2016-06-16

    Protein tyrosine kinase 6 (PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis. However, PTK6 expression status and its role in cervical squamous cell cancer are unknown. This study aimed to investigate the expression level and clinical significance of PTK6 in early-stage cervical squamous cell cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen, early-stage cervical squamous cell cancer specimens and adjacent non-tumorous cervical tissues. The expression of PTK6 was detected using immunohistochemical staining in 150 formalin-fixed, paraffin-embedded, early-stage cervical squamous cell cancer sections and 10 normal cervical tissue sections. The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non-tumorous cervical tissues. Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells. The level of PTK6 expression was significantly associated with tumor grade (P = 0.020). The 5-year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression (81.3% vs. 96.2%, P = 0.008). Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival (hazard ratio = 5.999, 95% confidence interval 1.622-22.191, P < 0.05). PTK6 is overexpressed in cervical squamous cell cancer. Increased PTK6 expression is associated with reduced 5-year overall survival. PTK6 expression is an independent prognostic predictor for cervical cancer.

  4. Raman Spectroscopy Study of Prostatic Adenocarcinoma Bulk Tissues

    NASA Astrophysics Data System (ADS)

    Devpura, S.; Dai, H.; Thakur, J. S.; Naik, R.; Cao, A.; Pandya, A.; Auner, G. W.; Sarkar, F.; Sakr, W.; Naik, V.

    2009-03-01

    Prostate cancer is one of the most common types of cancer among men. The mortality rate for this disease can be dramatically reduced if it can be diagnosed in its early stages. Raman spectroscopy is one of the optical techniques which can provide fingerprints of a disease in terms of its molecular composition which changes due to the onset of disease. The aim of this project is to investigate the differences in the Raman spectra to identify benign epithelium (BE), prostatic intraepithelial neoplasia (PIN) and adenocarcinoma of various Gleason grades in archived bulk tissues embedded in paraffin wax. For each tissue, two adjacent tissue sections were cut and dewaxed, where one of the sections was stained using haematoxylin and eosin for histological examination and the other unstained adjacent section was used for Raman spectroscopic studies. We have collected Raman spectra from 10 prostatic adenocarcinoma dewaxed tissue sections using Raman microscope (785 nm excitation laser). The data were analyzed using statistical methods of principal component analysis and discriminant function analysis to classify the tissue regions. The results indicate that Raman Spectroscopy can differentiate between BE, PIN and Cancer regions.

  5. Non-target adjacent stimuli classification improves performance of classical ERP-based brain computer interface

    NASA Astrophysics Data System (ADS)

    Ceballos, G. A.; Hernández, L. F.

    2015-04-01

    Objective. The classical ERP-based speller, or P300 Speller, is one of the most commonly used paradigms in the field of Brain Computer Interfaces (BCI). Several alterations to the visual stimuli presentation system have been developed to avoid unfavorable effects elicited by adjacent stimuli. However, there has been little, if any, regard to useful information contained in responses to adjacent stimuli about spatial location of target symbols. This paper aims to demonstrate that combining the classification of non-target adjacent stimuli with standard classification (target versus non-target) significantly improves classical ERP-based speller efficiency. Approach. Four SWLDA classifiers were trained and combined with the standard classifier: the lower row, upper row, right column and left column classifiers. This new feature extraction procedure and the classification method were carried out on three open databases: the UAM P300 database (Universidad Autonoma Metropolitana, Mexico), BCI competition II (dataset IIb) and BCI competition III (dataset II). Main results. The inclusion of the classification of non-target adjacent stimuli improves target classification in the classical row/column paradigm. A gain in mean single trial classification of 9.6% and an overall improvement of 25% in simulated spelling speed was achieved. Significance. We have provided further evidence that the ERPs produced by adjacent stimuli present discriminable features, which could provide additional information about the spatial location of intended symbols. This work promotes the searching of information on the peripheral stimulation responses to improve the performance of emerging visual ERP-based spellers.

  6. Association between promoter hypermethylation of the DACT2 gene and tumor stages in breast cancer.

    PubMed

    Marusa Borgonio-Cuadra, Veronica; Miranda-Duarte, Antonio; Rojas-Toledo, Xochitl; Garcia-Hernandez, Normand; Alfredo Sierra-Ramirez, Jose; Cardenas-Garcia, Maura; Elena Hernandez-Caballero, Marta

    2018-01-01

    Aberrant methylation of CpG islands in the promoter is a hallmark of cancer, leading to transcriptional silencing of tumor suppressor genes. The aim of this work was to evaluate the promoter methylation status of the DACT2 gene in breast cancer (BC) tissue and to analyze its possible effect on tumor type or grade. CpG island from the DACT2 promoter in region -240 to -14 from transcriptional start site (TSS) were obtained. Through the use of sodium bisulfite DNA conversion analysis, followed by detection with MSP (methylation specific PCR), we analyzed 79 BC and 15 adjacent healthy samples. T he c ases a nalyzed w ere i n s tage I ( 2.5%), I I (38%), or III (59.5%). The most frequent tumor type was invasive ductal carcinoma (71.4%). Methylation analysis comparing tumor tissues with adjacent non-cancerous tissues showed statistical significance. Methylation was observed in 32.9% (26/79) of the samples; no methylation was found in adjacent healthy tissue. DACT2 methylation was associated with tumor stage I-II (p=0.03) and stage III (p=0.004). An association was found of DACT2 promoter methylation with advanced tumor stages. This gene has been suggested as a potential biomarker, however, more investigation is required to validate this function.

  7. Autofluorescence polarization spectroscopy of cancerous and normal colorectal tissues

    NASA Astrophysics Data System (ADS)

    Genova, Ts.; Borisova, E.; Penkov, N.; Vladimirov, B.; Terziev, I.; Zhelyazkova, Al.; Avramov, L.

    2016-01-01

    The wide spread of colorectal cancer and high mortality rate among the patients, brings it to a level of high public health concern. Implementation of standard endoscopic surveillance proves to be effective for reduction of colorectal cancer patients' mortality, since its early diagnosis allows eradication of the disease prior to invasive cancer development, but its application in common clinical practice is still limited. Therefore the development of complimentary diagnostic techniques of the standard white-light endoscopy is on high demand. The non-invasive and highly informative nature of the fluorescence spectroscopy allow to use it as the most realistic prospect of an add-on "red flag" technique for early endoscopy detection of colorectal cancer. Synchronous fluorescence spectroscopy (SFS) is a steady-state approach that is used for evaluation of specific fluorescence characteristics of cancerous colorectal tissues in our studies. The feasibility of polarization fluorescence technique to enhance the contrast between normal and cancerous tissues was investigated as well. Additional linear polarizing optics was used on the way of the excitation and emission fluorescence light beams. The polarizing effects were investigated in parallel and perpendicular linear polarization modes respectively. The excitation applied was in the region of 280 - 440 nm, with 10 nm scanning step, and the fluorescence emission was detected in the region of 300 - 800 nm. Our previous experience with SFS technique showed its great potential for accurate, highly sensitive and specific discrimination between cancerous and normal colorectal tissue. Since one of the major sources of endogenous fluorescence with diagnostic meaning is the structural protein - collagen, which is characterized with high anisotropy, we've expected and observed an enhancement of the spectral differences between cancerous and normal colorectal tissue, which could be beneficial for the colorectal tumour' diagnostics

  8. Promoter methylation assay of SASH1 gene in breast cancer.

    PubMed

    Sheyu, Lin; Hui, Liu; Junyu, Zhang; Jiawei, Xu; Honglian, Wang; Qing, Sang; Hengwei, Zhang; Xuhui, Guo; Qinghe, Xing; Lin, He

    2013-01-01

    To analyze the relationship between the expression of SASH1 and its methylation level of SASH1 gene promoter in human breast cancer. Expression levels of SASH1 were examined in breast cancer tissues and adjacent normal tissues with immunohistochemistry and with real time PCR (RT-PCR) methylation analysis was performed with MassArray. Immunohistochemistry showed that SASH1 expression was strongly reduced in breast cancer compared with adjacent normal tissues. Quantitative methylation analysis by MassArray revealed that CpG sites in SASH1 promoter shared similar methylation pattern in tumor tissue and adjacent normal tissue. The CpG sites with significant difference in methylation level were CpG_26.27 and CpG_54.55. Moreover, 5-aza-2'-deoxycytidine (5-Aza-dc) treatment of tumor cell line MDA-MB-231 caused significant elevation of SASH1 mRNA. Based on these data, we propose that increase of DNA methylation level in the promoter region of gene SASH1, particularly CpG_26.27 or CpG_54.55 sites, possibly repressed SASH1 expression in breast cancer.

  9. CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA.

    PubMed

    Kang, Shuli; Li, Qingjiao; Chen, Quan; Zhou, Yonggang; Park, Stacy; Lee, Gina; Grimes, Brandon; Krysan, Kostyantyn; Yu, Min; Wang, Wei; Alber, Frank; Sun, Fengzhu; Dubinett, Steven M; Li, Wenyuan; Zhou, Xianghong Jasmine

    2017-03-24

    We propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only the presence but also the location of tumors. CancerLocator simultaneously infers the proportions and the tissue-of-origin of tumor-derived cell-free DNA in a blood sample using genome-wide DNA methylation data. CancerLocator outperforms two established multi-class classification methods on simulations and real data, even with the low proportion of tumor-derived DNA in the cell-free DNA scenarios. CancerLocator also achieves promising results on patient plasma samples with low DNA methylation sequencing coverage.

  10. Widespread Non-Hematopoietic Tissue Distribution by Transplanted Human Progenitor Cells with High Aldehyde Dehydrogenase Activity

    PubMed Central

    Hess, David A.; Craft, Timothy P.; Wirthlin, Louisa; Hohm, Sarah; Zhou, Ping; Eades, William C.; Creer, Michael H.; Sands, Mark S.; Nolta, Jan A.

    2011-01-01

    Transplanted adult progenitor cells distribute to peripheral organs and can promote endogenous cellular repair in damaged tissues. However, development of cell-based regenerative therapies has been hindered by the lack of pre-clinical models to efficiently assess multiple organ distribution and difficulty defining human cells with regenerative function. After transplantation into beta-glucuronidase (GUSB)-deficient NOD/SCID/MPSVII mice, we characterized the distribution of lineage depleted human umbilical cord blood-derived cells purified by selection using high aldehyde dehydrogenase activity (ALDH) with CD133 co-expression. ALDHhi or ALDHhiCD133+ cells produced robust hematopoietic reconstitution, and variable levels of tissue distribution in multiple organs. GUSB+ donor cells that co-expressed human (HLA-A,B,C) and hematopoietic (CD45+) cell surface markers were the primary cell phenotype found adjacent to the vascular beds of several tissues, including islet and ductal regions of mouse pancreata. In contrast, variable phenotypes were detected in the chimeric liver, with HLA+/CD45+ cells demonstrating robust GUSB expression adjacent to blood vessels, and CD45−/HLA− cells with diluted GUSB expression predominant in the liver parenchyma. However, true non-hematopoietic human (HLA+/CD45−) cells were rarely detected in other peripheral tissues, suggesting that these GUSB+/HLA−/CD45− cells in the liver were a result of downregulated human surface marker expression in vivo, not widespread seeding of non-hematopoietic cells. However, relying solely on continued expression of cell surface markers, as employed in traditional xenotransplantation models, may underestimate true tissue distribution. ALDH-expressing progenitor cells demonstrated widespread and tissue-specific distribution of variable cellular phenotypes, indicating that these adult progenitor cells should be explored in transplantation models of tissue damage. PMID:18055447

  11. [Expressions of heat shock protein (HSP) family HSP 60, 70 and 90alpha in colorectal cancer tissues and their correlations to pathohistological characteristics].

    PubMed

    Zhang, Wen-Li; Gao, Xue-Qin; Han, Jin-Xiang; Wang, Guo-Qiang; Yue, Long-Tao

    2009-06-01

    Colorectal cancer is the third common malignant tumor in the world. Heat shock protein (HSP) family has been reported to play an important role in carcinogenesis of various cancers. However, little is known about expressions of HSP60,HSP70 and HSP90alpha in colorectal cancer. This study was to investigate expressions of HSP 60, 70 and 90alpha, and analyzed their correlations to pathohistologic characteristics in colorectal cancer. Colorectal cancer tissues and adjacent normal tissues 2 cm away from the tumor focus were collected from 49 patients. Expressions of HSP60, HSP70 and HSP90alpha mRNA were detected by RT-PCR. The protein expressions of HSP60, HSP70 and HSP90alpha were determined by immunohistochemistry and western blot. The mRNA and protein levels of HSP60, HSP70 and HSP90alpha, as well as their positive rates were significantly increased in tumor tissues compared with those in para-cancerous tissues. The overexpression rates of HSP60, HSP70 and HSP90alpha were also significantly higher in the colorectal cancer tissues than those in the corresponding para-cancerous tissues. The positive and overexpression rates of HSP60, HSP70 and HSP90alpha in well, moderately and poorly differentiated colorectal cancer were not significantly different. HSP60, HSP70 and HSP90alpha may play important roles in the pathogenesis of colorectal cancer, although they are not correlated with the pathological grading.

  12. Transcriptional expression analysis of survivin splice variants reveals differential expression of survivin-3α in breast cancer.

    PubMed

    Moniri Javadhesari, Solmaz; Gharechahi, Javad; Hosseinpour Feizi, Mohammad Ali; Montazeri, Vahid; Halimi, Monireh

    2013-04-01

    Survivin, which is a novel member of the inhibitor of apoptosis family proteins, is known to play an important role in the regulation of cell cycle and apoptosis. Differential expression of survivin in tumor tissues introduces it as a new candidate molecular marker for cancer. Here we investigated the expression of survivin and its splice variants in breast tumors, as well as normal adjacent tissues obtained from the same patients. Thirty five tumors and 17 normal adjacent tissues from women diagnosed with breast cancer were explored in this study. Differential expression of different survivin splice variants was detected and semiquantitatively analyzed using reverse transcription-polymerase chain reaction. Results showed that survivin and its splice variants were differentially expressed in tumor specimens compared with normal adjacent tissues. The expression of survivin-3B and survivin-3α was specifically detected in tumor tissues compared with normal adjacent ones (53% in tumor tissues compared to 5% in normal adjacent for survivin-3B and 65% in tumor tissues and 0.0% in normal adjacent tissues for survivin-3α). Statistical analysis showed that survivin and survivin-ΔEx3 were upregulated in benign (90%, p<0.034) and malignant (76%, p<0.042) tumors, respectively. On the other hand, our results showed that survivin-2α (100% of the cases) was the dominant expressed variant of survivin in breast cancer. The data presented here showed that survivin splice variants were differentially expressed in benign and malignant breast cancer tissues, suggesting their potential role in breast cancer development. Differential expression of survivin-2α and survivin-3α splice variants highlights their usefulness as new candidate markers for breast cancer diagnosis and prognosis.

  13. DNA methylation markers for diagnosis and prognosis of common cancers

    PubMed Central

    Hao, Xiaoke; Luo, Huiyan; Krawczyk, Michal; Wei, Wei; Wang, Wenqiu; Wang, Juan; Flagg, Ken; Hou, Jiayi; Zhang, Heng; Yi, Shaohua; Jafari, Maryam; Lin, Danni; Chung, Christopher; Caughey, Bennett A.; Li, Gen; Dhar, Debanjan; Shi, William; Zheng, Lianghong; Hou, Rui; Zhu, Jie; Zhao, Liang; Fu, Xin; Zhang, Edward; Zhang, Charlotte; Zhu, Jian-Kang; Karin, Michael; Xu, Rui-Hua; Zhang, Kang

    2017-01-01

    The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples. We replicated our findings in a separate TCGA cohort of 791 tumor samples and 93 matched adjacent normal tissue samples, as well as an independent Chinese cohort of 394 tumor samples and 324 matched adjacent normal tissue samples. The DNA methylation analysis could predict cancer versus normal tissue with more than 95% accuracy in these three cohorts, demonstrating accuracy comparable to typical diagnostic methods. This analysis also correctly identified 29 of 30 colorectal cancer metastases to the liver and 32 of 34 colorectal cancer metastases to the lung. We also found that methylation patterns can predict prognosis and survival. We correlated differential methylation of CpG sites predictive of cancer with expression of associated genes known to be important in cancer biology, showing decreased expression with increased methylation, as expected. We verified gene expression profiles in a mouse model of hepatocellular carcinoma. Taken together, these findings demonstrate the utility of methylation biomarkers for the molecular characterization of cancer, with implications for diagnosis and prognosis. PMID:28652331

  14. Non-Adjacent Dependency Learning in Infants at Familial Risk of Dyslexia

    ERIC Educational Resources Information Center

    Kerkhoff, Annemarie; de Bree, Elise; de Klerk, Maartje; Wijnen, Frank

    2013-01-01

    This study tests the hypothesis that developmental dyslexia is (partly) caused by a deficit in implicit sequential learning, by investigating whether infants at familial risk of dyslexia can track non-adjacent dependencies in an artificial language. An implicit learning deficit would hinder detection of such dependencies, which mark grammatical…

  15. Insulin receptor isoforms A and B as well as insulin receptor substrates-1 and -2 are differentially expressed in prostate cancer.

    PubMed

    Heni, Martin; Hennenlotter, Jörg; Scharpf, Marcus; Lutz, Stefan Z; Schwentner, Christian; Todenhöfer, Tilman; Schilling, David; Kühs, Ursula; Gerber, Valentina; Machicao, Fausto; Staiger, Harald; Häring, Hans-Ulrich; Stenzl, Arnulf

    2012-01-01

    In different cancers types, insulin receptor isoform composition or insulin receptor substrate (IRS) isoforms are different to healthy tissue. This may be a molecular link to increased cancer risk in diabetes and obesity. Since this is yet unclear for prostate cancer, we investigated IR isoform composition and IRS balance in prostate cancer compared to benign and tumor adjacent benign prostate tissue and brought this into relation to cell proliferation. We studied 23 benign prostate samples from radical cystectomy or benign prostatic hyperplasia surgery, 30 samples from benign tissue directly adjacent to prostate cancer foci and 35 cancer samples from different patients. RNA expression levels for insulin receptor isoforms A and B, IRS-1, IRS-2, and IGF-1 receptor were assessed by quantitative real-time RT-PCR. In addition, RNA- and protein expression of the cell cycle regulator p27(Kip1) was quantified by real-time RT-PCR and immunohistochemistry. Insulin receptor isoform A to B ratio was significantly higher in cancer as well as in tumor adjacent benign prostate tissue compared to purely benign prostates (p<0.05). IRS-1 to IRS-2 ratios were lower in malignant than in benign prostatic tissue (p<0.05). These altered ratios both in cancer and adjacent tissue were significantly associated with reduced p27(Kip1) content (p<0.02). Interestingly, IGF-1 receptor levels were significantly lower in patients with type 2 diabetes (p = 0.0019). We found significant differences in the insulin signaling cascade between benign prostate tissue and prostate cancer. Histological benign tissue adjacent to cancer showed expression patterns similar to the malignancies. Our findings suggest a role of the insulin signaling pathway in prostate cancer and surrounding tissue and can hence be relevant for both novel diagnostic and therapeutic approaches in this malignancy.

  16. Tumor-adjacent tissue co-expression profile analysis reveals pro-oncogenic ribosomal gene signature for prognosis of resectable hepatocellular carcinoma.

    PubMed

    Grinchuk, Oleg V; Yenamandra, Surya P; Iyer, Ramakrishnan; Singh, Malay; Lee, Hwee Kuan; Lim, Kiat Hon; Chow, Pierce Kah-Hoe; Kuznetsov, Vladamir A

    2018-01-01

    Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT) and adjacent non-malignant tissues (AT) typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods. We developed a 24-ribosomal gene-based HCC classifier (RGC), which is prognostically significant in both PT and AT. The RGC gene overexpression in PT was associated with a poor prognosis in the training (hazard ratio = 8.2, P = 9.4 × 10 -6 ) and cross-cohort validation (hazard ratio = 2.63, P = 0.004) datasets. The multivariate survival analysis demonstrated the significant and independent prognostic value of the RGC. The RGC displayed a significant prognostic value in AT of the training (hazard ratio = 5.0, P = 0.03) and cross-validation (hazard ratio = 1.9, P = 0.03) HCC groups, confirming the accuracy and robustness of the RGC. Our experimental and bioinformatics analyses suggested a key role for c-MYC in the pro-oncogenic pattern of ribosomal biogenesis co-regulation in PT and AT. Microarray, quantitative RT-PCR and quantitative immunohistochemical studies of the PT showed that DKK1 in PT is the perspective biomarker for poor HCC outcomes. The common co-transcriptional pattern of ribosome biogenesis genes in PT and AT from HCC patients suggests a new scalable prognostic system, as supported by the model of tumor-like metabolic redirection/assimilation in non-malignant AT. The RGC, comprising 24 ribosomal genes, is introduced as a robust and reproducible prognostic model for

  17. Highly expressed long non-coding RNA NNT-AS1 promotes cell proliferation and invasion through Wnt/β-catenin signaling pathway in cervical cancer.

    PubMed

    Hua, Fangfang; Liu, Shanshan; Zhu, Lihong; Ma, Ning; Jiang, Shan; Yang, Jun

    2017-08-01

    Cervical cancer is the most common gynecological malignancies in women worldwide. The previous study showed that lncRNA NNT-AS1 could play an important role in tumor development and metastasis of colorectal cancer. However, little is known about the function of NNT-AS1 in cervical cancer. The aim of this study was to investigate the expression profile of NNT-AS1 in cervical cancer and assess its possible molecular mechanism. Relative expression levels of NNT-AS1 in cervical cancer tissues were determined by qRT-PCR. The biologic functions of NNT-AS1 in cervical cancer were explored by MTT assay, transwell assay and flow cytometric analysis in vitro. The influence of NNT-AS1 on tumorigenesis was measured by mice xenograft model. In addition, we evaluated the activation of Wnt/β-catenin signaling pathway by luciferase assay and western blot. Our results showed that NNT-AS1 expression in cervical cancer tissues compared with adjacent non-tumor tissues the overexpression of NNT-AS1 was positively associated with advanced FIGO stage, lymph node metastasis, depth of cervical invasion and poorer overall survival. Function assays showed that NNT-AS1 inhibition could suppress cervical cancer cells proliferation and invasion ability in vitro as well as the activation of Wnt/β-catenin signaling pathway. In vivo mice xenograft model revealed that silencing NNT-AS1 could reduce tumor growth in nude mice. The results of the current study suggested that NNT-AS1 might play an important role in cervical carcinogenesis and might serve as a potentially therapeutic target and prognostic marker in the treatment of cervical cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression.

    PubMed

    Lopes-Coelho, Filipa; Gouveia-Fernandes, Sofia; Serpa, Jacinta

    2018-02-01

    The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

  19. Examining incentives for adjacent non-industrial private forest landowners to cooperate

    Treesearch

    Melinda Vokoun; Gregory S Amacher; Jay Sullivan; Dave Wear

    2010-01-01

    Individual landowners may capture non-timber benefits from both their own forested parcels and adjacent parcels owned by different landowners. These benefits may affect incentives for landowners to cooperate in their forest management decisions. Landowner survey data is used to examine incentives to cooperate concerning joint forest management and coordination of...

  20. Differential expression and localisation of gasdermin-like (GSDML), a novel member of the cancer-associated GSDMDC protein family, in neoplastic and non-neoplastic gastric, hepatic, and colon tissues.

    PubMed

    Carl-McGrath, Stacy; Schneider-Stock, Regine; Ebert, Matthias; Röcken, Christoph

    2008-01-01

    Gasdermin-like (GSDML) is a novel member of the cancer associated gasdermin-domain containing (GSDMDC) protein family. The GSDMDC family has been linked to cancer development and progression, and this is the first study analysing the expression and intracellular localisation of GSDML. GSDML gene transcription was analysed using quantitative real-time RT-PCR. Anti-peptide antibodies against GSDML were developed in rabbits, and an in vitro transcription-translation reaction was used to verify specificity. The Protein-G affinity purified antibodies were used in immunohistochemistry and immunoblotting on hepatocellular, gastric, and colorectal carcinomas and non-lesional tissues. The GSDML gene was transcribed in human gastric, liver and colon cell lines, carcinomas and non-lesional tissues. The GSDML protein was localised to the cytoplasm of cells in both tumour and non-lesional tissues. The GSDML protein splicing variants range in molecular weight from 35 to 50 kDa, and the expression profile varies between tumour and non-tumour. A distinctive vesicular staining pattern was exhibited by GSDML in the apical region of gastric chief cells and colonic surface mucous cells, and the basal region of neuroendocrine cells. GSDML may be a secretory or metabolic product involved in a secretory pathway, and changes in the regulation of GSDML splicing variant transcription and translation may be seen in the development and/or progression of gastrointestinal and hepatic cancers.

  1. Coordinated tissue-specific regulation of adjacent alternative 3′ splice sites in C. elegans

    PubMed Central

    Ragle, James Matthew; Katzman, Sol; Akers, Taylor F.; Barberan-Soler, Sergio; Zahler, Alan M.

    2015-01-01

    Adjacent alternative 3′ splice sites, those separated by ≤18 nucleotides, provide a unique problem in the study of alternative splicing regulation; there is overlap of the cis-elements that define the adjacent sites. Identification of the intron's 3′ end depends upon sequence elements that define the branchpoint, polypyrimidine tract, and terminal AG dinucleotide. Starting with RNA-seq data from germline-enriched and somatic cell-enriched Caenorhabditis elegans samples, we identify hundreds of introns with adjacent alternative 3′ splice sites. We identify 203 events that undergo tissue-specific alternative splicing. For these, the regulation is monodirectional, with somatic cells preferring to splice at the distal 3′ splice site (furthest from the 5′ end of the intron) and germline cells showing a distinct shift toward usage of the adjacent proximal 3′ splice site (closer to the 5′ end of the intron). Splicing patterns in somatic cells follow C. elegans consensus rules of 3′ splice site definition; a short stretch of pyrimidines preceding an AG dinucleotide. Splicing in germline cells occurs at proximal 3′ splice sites that lack a preceding polypyrimidine tract, and in three instances the germline-specific site lacks the AG dinucleotide. We provide evidence that use of germline-specific proximal 3′ splice sites is conserved across Caenorhabditis species. We propose that there are differences between germline and somatic cells in the way that the basal splicing machinery functions to determine the intron terminus. PMID:25922281

  2. ¹H NMR-based metabolic profiling of human rectal cancer tissue

    PubMed Central

    2013-01-01

    Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Methods Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Results Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would

  3. The mechanisms for lung cancer risk of PM2.5 : Induction of epithelial-mesenchymal transition and cancer stem cell properties in human non-small cell lung cancer cells.

    PubMed

    Wei, Hongying; Liang, Fan; Cheng, Wei; Zhou, Ren; Wu, Xiaomeng; Feng, Yan; Wang, Yan

    2017-11-01

    Fine particulate matter (PM 2.5 ) is a major component of air pollutions that are closely associated with increased risk of lung cancer. However, the role of PM 2.5 in the etiology of lung cancer is largely unknown. In this study, we performed acute (24 hours) and chronic (five passages) exposure models to investigate the carcinogenetic mechanisms of PM 2.5 by targeting the induction of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties in human non-small cell lung cancer cell line A549. We found that both acute and chronic PM 2.5 exposure enhanced cell migration and invasion, decreased mRNA expression of epithelial markers and increased mRNA expression of mesenchymal markers. Chronic PM 2.5 exposure further induced notable EMT morphology and CSC properties, indicating the developing process of cell malignant behaviors from acute to chronic PM 2.5 exposure. CSC properties induced by chronic PM 2.5 exposure characterized with increased cell-surface markers (CD44, ABCG2), self-renewal genes (SOX2 and OCT4), side population cells and neoplastic capacity. Furthermore, the levels of three stemness-associated microRNAs, Let-7a, miR-16 and miR-34a, were found to be significantly downregulated by chronic PM 2.5 exposure, with microarray data analysis from TCGA database showing their lower expression in human lung adenocarcinoma tissues than that in the adjacent normal lung tissues. These data revealed that the induction of EMT and CSC properties were involved in the lung cancer risk of PM 2.5 , and implicated CSC properties and related microRNAs as possible biomarkers for carcinogenicity prediction of PM 2.5 . © 2017 Wiley Periodicals, Inc.

  4. Microarray profiles reveal that circular RNA hsa_circ_0007385 functions as an oncogene in non-small cell lung cancer tumorigenesis.

    PubMed

    Jiang, Ming-Ming; Mai, Zhi-Tao; Wan, Shan-Zhi; Chi, Yu-Min; Zhang, Xin; Sun, Bao-Hua; Di, Qing-Guo

    2018-04-01

    Circular RNAs (circRNAs) are a novel class of non-protein-coding RNA. Emerging evidence indicates that circRNAs participate in the regulation of many pathophysiological processes. This study aims to explore the expression profiles and pathological effects of circRNAs in non-small cell lung cancer (NSCLC). Human circRNAs microarray analysis was performed to screen the expression profile of circRNAs in NSCLC tissue. Expressions of circRNA and miRNA in NSCLC tissues and cells were quantified by qRTPCR. Functional experiments were performed to investigate the biological functions of circRNA, including CCK-8 assay, colony formation assay, transwell assay and xenograft in vivo assay. Human circRNAs microarray revealed a total 957 abnormally expressed circRNAs (> twofold, P < 0.05) in NSCLC tissue compared with adjacent normal tissue. In further studies, hsa_circ_0007385 was significantly up regulated in NSCLC tissue and cells. In vitro experiments with hsa_circ_0007385 knockdown resulted in significant suppression of the proliferation, migration and invasion of NSCLC cells. In vivo xenograft assay using hsa_circ_0007385 knockdown, significantly reduced tumor growth. Bioinformatics analysis and luciferase reporter assay verified the potential target miR-181, suggesting a possible regulatory pathway for hsa_circ_0007385. In summary, results suggest hsa_circ_0007385 plays a role in NSCLC tumorigenesis, providing a potential therapeutic target for NSCLC.

  5. Gene Expression Profiling of Liver Cancer Stem Cells by RNA-Sequencing

    PubMed Central

    Lam, Chi Tat; Ng, Michael N. P.; Yu, Wan Ching; Lau, Joyce; Wan, Timothy; Wang, Xiaoqi; Yan, Zhixiang; Liu, Hang; Fan, Sheung Tat

    2012-01-01

    Background Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90+ liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90+ cells sorted from tumor (CD90+CSCs) with parallel non-tumorous liver tissues (CD90+NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis. Methodology/Principal Findings CD90+ cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90+ cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90+CSCs and CD90+NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90+CSCs and CD90+NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90+CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90+CSCs compared to CD90+NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90+CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90+CSCs in liver tumor tissues. Conclusions/Significance The identified genes

  6. 1H-NMR based metabonomic profiling of human esophageal cancer tissue

    PubMed Central

    2013-01-01

    Background The biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival. Specially, those that involves in progression of disease would be helpful to mechanism research. Methods In the present study, we investigated the distinguishing metabolites in human esophageal cancer tissues (n = 89) and normal esophageal mucosae (n = 26) using a 1H nuclear magnetic resonance (1H-NMR) based assay, which is a highly sensitive and non-destructive method for biomarker identification in biological systems. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least-squares-discriminant anlaysis (OPLS-DA) were applied to analyse 1H-NMR profiling data to identify potential biomarkers. Results The constructed OPLS-DA model achieved an excellent separation of the esophageal cancer tissues and normal mucosae. Excellent separation was obtained between the different stages of esophageal cancer tissues (stage II = 28; stage III = 45 and stage IV = 16) and normal mucosae. A total of 45 metabolites were identified, and 12 of them were closely correlated with the stage of esophageal cancer. The downregulation of glucose, AMP and NAD, upregulation of formate indicated the large energy requirement due to accelerated cell proliferation in esophageal cancer. The increases in acetate, short-chain fatty acid and GABA in esophageal cancer tissue revealed the activation of fatty acids metabolism, which could satisfy the need for cellular membrane formation. Other modified metabolites were involved in choline metabolic pathway, including creatinine, creatine, DMG, DMA and TMA. These 12 metabolites, which are involved in energy, fatty acids and choline metabolism, may be associated with the progression of human esophageal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different

  7. L1-CAM in cancerous tissues.

    PubMed

    Gavert, Nancy; Ben-Shmuel, Amir; Raveh, Shani; Ben-Ze'ev, Avri

    2008-11-01

    L1-cell adhesion molecule (L1-CAM) is a cell adhesion receptor of the immunoglobulin superfamily, known for its roles in nerve cell function. While originally believed to be present only in brain cells, in recent years L1-CAM has been detected in other tissues, and in a variety of cancer cells, including some common types of human cancer. We review the prevalence of L1-CAM in human cancer, the possible mechanisms involved in L1-CAM-mediated tumorigenesis, and cancer therapies based upon L1-CAM antibody treatment. In colon cancer cells, the L1-CAM gene was identified as a target of the Wnt/beta-catenin-TCF signaling pathway, and L1-CAM was exclusively detected at the invasive front of colon and ovarian cancer tissue. The expression of L1-CAM in normal and cancer cells enhanced tumorigenesis and conferred metastasis in colon cancer cells. Antibodies against the L1-CAM ectodomain severely inhibited the proliferation of a variety of cancer cells in culture and reduced tumor burden when injected into mice harboring cancer cells expressing L1-CAM. These results, in addition to the presence of L1-CAM on the cell surface and its restricted distribution in normal tissues, make it an ideal target for tumor therapy.

  8. [Abnormal expression of genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer].

    PubMed

    Kuznetsova, E S; Zinovieva, O L; Oparina, N Yu; Prokofjeva, M M; Spirin, P V; Favorskaya, I A; Zborovskaya, I B; Lisitsyn, N A; Prassolov, V S; Mashkova, T D

    2016-01-01

    Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors. Dramatic changes in the levels of these mRNAs can impair the synthesis of all-trans retinoic acid, a key natural regulatory retinoid. Apart from that, it was found that mRNA levels of nuclear retinoid receptor genes RXRγ, RARα, RXRα, and gene RDH11 were significantly decreased in 80, 67, 57, and 66% of tumor specimens, respectively. Thus, neoplastic transformation of lung tissue cells is accompanied with deregulated expression of key genes of retinoid metabolism and function.

  9. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

    PubMed

    Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

    2017-11-01

    Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

  10. Characterization of cDNA encoding molt-inhibiting hormone of the crab, Cancer pagurus; expression of MIH in non-X-organ tissues.

    PubMed

    Lu, W; Wainwright, G; Olohan, L A; Webster, S G; Rees, H H; Turner, P C

    2001-10-31

    Synthesis of ecdysteroids (molting hormones) by crustacean Y-organs is regulated by a neuropeptide, molt-inhibiting hormone (MIH), produced in eyestalk neural ganglia. We report here the molecular cloning of a cDNA encoding MIH of the edible crab, Cancer pagurus. Full-length MIH cDNA was obtained by using reverse transcription-polymerase chain reaction (RT-PCR) with degenerate oligonucleotides based upon the amino acid sequence of MIH, in conjunction with 5'- and 3'-RACE. Full-length clones of MIH cDNA were obtained that encoded a 35 amino acid putative signal peptide and the mature 78 amino acid peptide. Of various tissues examined by Northern blot analysis, the X-organ was the sole major site of expression of the MIH gene. However, a nested-PCR approach using non-degenerate MIH-specific primers indicated the presence of MIH transcripts in other tissues. Southern blot analysis indicated a simple gene arrangement with at least two copies of the MIH gene in the genome of C. pagurus. Additional Southern blotting experiments detected MIH-hybridizing bands in another Cancer species, Cancer antennarius and another crab species, Carcinus maenas.

  11. Towards non-invasive characterization of breast cancer and cancer metabolism with diffuse optics

    PubMed Central

    Busch, David R.; Choe, Regine; Durduran, Turgut; Yodh, Arjun G.

    2013-01-01

    We review recent developments in diffuse optical imaging and monitoring of breast cancer, i.e. optical mammography. Optical mammography permits non-invasive, safe and frequent measurement of tissue hemodynamics oxygen metabolism and components (lipids, water, etc.), the development of new compound indices indicative of the risk and malignancy, and holds potential for frequent non-invasive longitudinal monitoring of therapy progression. PMID:24244206

  12. Overexpression of COX-2 in Rat Oral Cancers and Prevention of Oral Carcinogenesis in Rats by Selective and Non-Selective COX Inhibitors

    PubMed Central

    McCormick, David L.; Phillips, Jonathan M.; Horn, Thomas L.; Johnson, William D.; Steele, Vernon E.; Lubet, Ronald A.

    2009-01-01

    Oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide (NQO) demonstrate substantial overexpression of cyclooxygenase-2 (COX-2) when compared to adjacent phenotypically normal oral tissues. By contrast, neither 5-lipoxygenase (5-LOX) nor 12-lipoxygenase (12-LOX) is overexpressed in rat oral cancers. Two chemoprevention studies were performed to test the resulting hypothesis that COX-2 is a useful target for oral cancer chemoprevention in the rat. In both studies, male F344 rats received drinking water exposure to NQO (20 ppm) for 10 weeks, followed by administration of chemopreventive agents from week 10 until study termination at week 26. In the first study, groups of rats were fed basal diet (control), or basal diet supplemented with the selective COX-2 inhibitor, celecoxib (500 or 1500 mg/kg diet); the non-selective COX inhibitor, piroxicam (50 or 150 mg/kg diet); or the 5-LOX inhibitor, zileuton (2000 mg/kg diet). In the second study, rats were fed basal diet (control) or basal diet supplemented with NO-Naproxen (180 or 90 mg/kg diet), a non-selective COX inhibitor that demonstrates reduced gastrointestinal toxicity. When compared to dietary controls, celecoxib decreased oral cancer incidence, cancer invasion score, and cancer-related mortality. Piroxicam decreased cancer-related mortality and cancer invasion score, while NO-naproxen decreased oral cancer incidence and cancer invasion score. By contrast, zileuton demonstrated no chemopreventive activity by any parameter assessed. These data demonstrate that both selective and non-selective inhibitors of COX-2 can prevent NQO-induced oral carcinogenesis in rats. The chemopreventive activity of COX inhibitors may be linked to overexpression of their enzymatic target in incipient oral neoplasms. PMID:20051374

  13. Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer

    PubMed Central

    Kandel, Pujan; Wallace, Michael B.

    2018-01-01

    Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer. With advancements in needle technologies, tumor specimens can be obtained at the time of tissue diagnosis. Tumor tissue can be used for development of personalized cancer treatment, such as performing whole exome sequencing and global genomic profiling of pancreas cancer, development of tissue biomarkers, and targeted mutational assays for precise chemotherapy treatment. In this review, we discuss the recent advances in tissue acquisition of pancreas cancer. PMID:29463004

  14. Evaluation of thyroid tissue by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Teixeira, C. S. B.; Bitar, R. A.; Santos, A. B. O.; Kulcsar, M. A. V.; Friguglietti, C. U. M.; Martinho, H. S.; da Costa, R. B.; Martin, A. A.

    2010-02-01

    Thyroid gland is a small gland in the neck consisting of two lobes connected by an isthmus. Thyroid's main function is to produce the hormones thyroxine (T4), triiodothyronine (T3) and calcitonin. Thyroid disorders can disturb the production of these hormones, which will affect numerous processes within the body such as: regulating metabolism and increasing utilization of cholesterol, fats, proteins, and carbohydrates. The gland itself can also be injured; for example, neoplasias, which have been considered the most important, causing damage of to the gland and are difficult to diagnose. There are several types of thyroid cancer: Papillary, Follicular, Medullary, and Anaplastic. The occurrence rate, in general is between 4 and 7%; which is on the increase (30%), probably due to new technology that is able to find small thyroid cancers that may not have been found previously. The most common method used for thyroid diagnoses are: anamnesis, ultrasonography, and laboratory exams (Fine Needle Aspiration Biopsy- FNAB). However, the sensitivity of those test are rather poor, with a high rate of false-negative results, therefore there is an urgent need to develop new diagnostic techniques. Raman spectroscopy has been presented as a valuable tool for cancer diagnosis in many different tissues. In this work, 27 fragments of the thyroid were collected from 18 patients, comprising the following histologic groups: goitre adjacent tissue, goitre nodular tissue, follicular adenoma, follicular carcinoma, and papillary carcinoma. Spectral collection was done with a commercial FTRaman Spectrometer (Bruker RFS100/S) using a 1064 nm laser excitation and Ge detector. Principal Component Analysis, Cluster Analysis, and Linear Discriminant Analysis with cross-validation were applied as spectral classification algorithm. Comparing the goitre adjacent tissue with the goitre nodular region, an index of 58.3% of correct classification was obtained. Between goitre (nodular region and

  15. Long telomere length predicts poor clinical outcome in esophageal cancer patients.

    PubMed

    Lv, Yanyan; Zhang, Yong; Li, Xinru; Ren, Xiaojuan; Wang, Meichen; Tian, Sijia; Hou, Peng; Shi, Bingyin; Yang, Qi

    2017-02-01

    Abnormal telomere length is widely reported in various human cancers, and it is considered to be an important hallmark of cancer. However, there is remarkably little consensus on the value of telomere length in the prognostic evaluation of esophageal cancers. Here, we attempted to determine the association of variable telomere length with clinical outcome of esophageal cancer patients. Using real-time quantitative PCR, we examined relative telomere lengths (RTL) in a cohort of esophageal cancer and normal esophageal tissues, and statistically investigated the association between RTL and clinical outcomes of esophageal cancer patients. The majority of esophageal cancers in this study had longer RTLs as compared to adjacent non-tumor tissues. Enhanced tumor RTL was associated with smoking habit, poor differentiation, advanced tumor stage, lymph node metastasis and cancer related death. In particular, a close relationship between longer RTL and poor survival was fully demonstrated by using cox regression and Kaplan-Maier survival curves. We found frequent telomere elongation in esophageal cancer tissues, and demonstrated longer RTL may be an independent poor prognostic factor for esophageal cancer patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

  16. [Arf6, RalA and BIRC5 protein expression in non small cell lung cancer].

    PubMed

    Knizhnik, A V; Kovaleva, O B; Laktionov, K K; Mochal'nikova, V V; Komel'kov, A V; Chevkina, E M; Zborovskaia, I B

    2011-01-01

    Evaluation of tumor markers expression pattern which determines individual progression parameters is one of the major topics in molecular oncopathology research. This work presents research on expression analysis of several Ras-Ral associated signal transduction pathway proteins (Arf6, RalA and BIRC5) in accordance with clinical criteria in non small cell lung cancer patients. Using Western-blot analysis and RT-PCR Arf6, RalA and BIRC5 expression has been analyzed in parallel in 53 non small cell lung cancer samples of different origin. Arf6 protein expression was elevated in 55% non small cell lung cancer tumor samples in comparison with normal tissue. In the group of squamous cell lung cancer Arf6 expression elevation was observed more often. RalA protein expression was decreased in comparison to normal tissue samples in 64% of non small cell lung cancer regardless to morphological structure. Correlation between RalA protein expression decrease and absence of regional metastases was revealed for squamous cell lung cancer. BIRC5 protein expression in tumor samples versus corresponding normal tissue was 1.3 times more often elevated in the squamous cell lung cancer group (in 76% tumor samples). At the same time elevation of BIRC5 expression was fixed only in 63% of adenocarcinoma tumor samples. A statistically significant decrease (p = 0.0158) of RalA protein expression and increase (p = 0.0498) of Arf6 protein expression in comparison with normal tissue was found for T1-2N0M0 and T1-2N1-2M0 groups of squamous cell lung cancer correspondingly.

  17. Nonmuscle Tissues Contribution to Cancer Cachexia

    PubMed Central

    Stemmler, Britta

    2015-01-01

    Cachexia is a syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting, and inflammation, being often associated with anorexia. In spite of the fact that muscle tissue represents more than 40% of body weight and seems to be the main tissue involved in the wasting that occurs during cachexia, recent developments suggest that tissues/organs such as adipose (both brown and white), brain, liver, gut, and heart are directly involved in the cachectic process and may be responsible for muscle wasting. This suggests that cachexia is indeed a multiorgan syndrome. Bearing all this in mind, the aim of the present review is to examine the impact of nonmuscle tissues in cancer cachexia. PMID:26523094

  18. Stokes polarimetry imaging of dog prostate tissue

    NASA Astrophysics Data System (ADS)

    Kim, Jihoon; Johnston, William K., III; Walsh, Joseph T., Jr.

    2010-02-01

    Prostate cancer is the second leading cause of death in the United States in 2009. Radical prostatectomy (complete removal of the prostate) is the most common treatment for prostate cancer, however, differentiating prostate tissue from adjacent bladder, nerves, and muscle is difficult. Improved visualization could improve oncologic outcomes and decrease damage to adjacent nerves and muscle important for preservation of potency and continence. A novel Stokes polarimetry imaging (SPI) system was developed and evaluated using a dog prostate specimen in order to examine the feasibility of the system to differentiate prostate from bladder. The degree of linear polarization (DOLP) image maps from linearly polarized light illumination at different visible wavelengths (475, 510, and 650 nm) were constructed. The SPI system used the polarization property of the prostate tissue. The DOLP images allowed advanced differentiation by distinguishing glandular tissue of prostate from the muscular-stromal tissue in the bladder. The DOLP image at 650 nm effectively differentiated prostate and bladder by strong DOLP in bladder. SPI system has the potential to improve surgical outcomes in open or robotic-assisted laparoscopic removal of the prostate. Further in vivo testing is warranted.

  19. TUSC3 induces autophagy in human non-small cell lung cancer cells through Wnt/β-catenin signaling

    PubMed Central

    Peng, Yun; Cao, Jun; Yao, Xiao-Yi; Wang, Jian-Xin; Zhong, Mei-Zuo; Gan, Ping-Ping; Li, Jian-Huang

    2017-01-01

    We investigated the effects of tumor suppressor candidate 3 (TUSC3) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells. We also performed TOP/FOP-Flash reporter assays, MTT assays, Annexin V-FITC/propidium iodide staining, and acridine orange staining to evaluate Wnt/β-catenin signaling, cell proliferation, apoptosis, and autophagy, respectively. Expression of Wnt/β-catenin pathway components and autophagy-related proteins was analyzed using qRT-PCR and Western blotting. We found that TUSC3 inhibited cell proliferation and promoted both apoptosis and autophagy in A549 cells. In addition, TUSC3 increased expression of autophagy-related proteins. It also increased expression of Wnt/β-catenin signaling pathway components and promoted nuclear transfer of β-catenin, resulting in activation of Wnt/β-catenin signaling. TUSC3 thus induces autophagy in human NSCLC cells through activation of the Wnt/β-catenin signaling pathway. PMID:28881786

  20. TUSC3 induces autophagy in human non-small cell lung cancer cells through Wnt/β-catenin signaling.

    PubMed

    Peng, Yun; Cao, Jun; Yao, Xiao-Yi; Wang, Jian-Xin; Zhong, Mei-Zuo; Gan, Ping-Ping; Li, Jian-Huang

    2017-08-08

    We investigated the effects of tumor suppressor candidate 3 ( TUSC3 ) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells. We also performed TOP/FOP-Flash reporter assays, MTT assays, Annexin V-FITC/propidium iodide staining, and acridine orange staining to evaluate Wnt/β-catenin signaling, cell proliferation, apoptosis, and autophagy, respectively. Expression of Wnt/β-catenin pathway components and autophagy-related proteins was analyzed using qRT-PCR and Western blotting. We found that TUSC3 inhibited cell proliferation and promoted both apoptosis and autophagy in A549 cells. In addition, TUSC3 increased expression of autophagy-related proteins. It also increased expression of Wnt/β-catenin signaling pathway components and promoted nuclear transfer of β-catenin, resulting in activation of Wnt/β-catenin signaling. TUSC3 thus induces autophagy in human NSCLC cells through activation of the Wnt/β-catenin signaling pathway.

  1. miR-7 Increases Cisplatin Sensitivity of Gastric Cancer Cells Through Suppressing mTOR

    PubMed Central

    Lian, Yan-Jun; Dai, Xiang; Wang, Yuan-Jie

    2017-01-01

    MicroRNAs have been reported to play an important role in diverse biological processes and cancer progression. MicroRNA-7 has been observed to be downregulated in human gastric cancer tissues, but the function of microRNA-7 in gastric cancer has not been well investigated. In this study, we demonstrate that the expression of microRNA-7 was significantly downregulated in 30 pairs of human gastric cancer tissues compared to adjacent normal tissues. Enforced expression of microRNA-7 inhibited cell proliferation and migration abilities of gastric cancer cells, BGC823 and SGC7901. Furthermore, microRNA-7 targeted mTOR in gastric cancer cells. In human clinical specimens, mTOR was higher expressed in gastric cancer tissues compared with adjacent normal tissues. More interestingly, microRNA-7 also sensitizes gastric cancer cells to cisplatin (CDDP) by targeting mTOR. Collectively, our results demonstrate that microRNA-7 is a tumor suppressor microRNA and indicate its potential application for the treatment of human gastric cancer in future. PMID:28693382

  2. Downregulation of external death receptor genes FAS and DR5 in colorectal cancer samples positive for human papillomavirus infection.

    PubMed

    Karbasi, Ashraf; Borhani, Nasim; Daliri, Karim; Kazemi, Bahram; Manoochehri, Mehdi

    2015-06-01

    Human papillomaviruses (HPV) have frequently been detected in colorectal cancer tumor samples, and may play a role in the pathogenesis of colorectal cancer. This study was designed to investigate the presence of DNA and RNA for the high-risk HPV genotypes 16 and 18 in samples of colorectal cancer tumors and adjacent normal tissues. We also investigated the expression of proapoptotic genes in HPV-positive colorectal tumors compared to normal tissue samples. Samples of tumoral and adjacent normal tissues were fresh-frozen, and HPV DNA was identified by nested and semiquantitative PCR. Real time PCR was used to quantitatively compare the expression of HPV-18 E6 and nine proapoptotic genes in HPV-positive tumors and samples of adjacent normal tissue. HPV-16 DNA was found in 10.5% of the tumor samples, and HPV-18 DNA was found in 23.6% of the samples. Real time PCR results showed lower expression of the E6 gene in HPV-positive tumors than in adjacent normal tissue. The expression of two proapoptotic genes, FAS and DR5, was significantly lower in tumor samples than in adjacent normal tissues. HPV infection, especially HPV-18, may play a role in colorectal cancer tumorigenesis by downregulating death receptor genes and interfering with the extrinsic pathway of apoptosis. Copyright © 2015 Elsevier GmbH. All rights reserved.

  3. A subset of high Gleason grade prostate carcinomas contain a large burden of prostate cancer syndecan-1 positive stromal cells.

    PubMed

    Sharpe, Benjamin; Alghezi, Dhafer A; Cattermole, Claire; Beresford, Mark; Bowen, Rebecca; Mitchard, John; Chalmers, Andrew D

    2017-05-01

    There is a pressing need to identify prognostic and predictive biomarkers for prostate cancer to aid treatment decisions in both early and advanced disease settings. Syndecan-1, a heparan sulfate proteoglycan, has been previously identified as a potential prognostic biomarker by multiple studies at the tissue and serum level. However, other studies have questioned its utility. Anti-Syndecan-1 immunohistochemistry was carried out on 157 prostate tissue samples (including cancerous, adjacent normal tissue, and non-diseased prostate) from three independent cohorts of patients. A population of Syndecan-1 positive stromal cells was identified and the number and morphological parameters of these cells quantified. The identity of the Syndecan-1-positive stromal cells was assessed by multiplex immunofluorescence using a range of common cell lineage markers. Finally, the burden of Syndecan-1 positive stromal cells was tested for association with clinical parameters. We identified a previously unreported cell type which is marked by Syndecan-1 expression and is found in the stroma of prostate tumors and adjacent normal tissue but not in non-diseased prostate. We call these cells Prostate Cancer Syndecan-1 Positive (PCSP) cells. Immunofluorescence analysis revealed that the PCSP cell population did not co-stain with markers of common prostate epithelial, stromal, or immune cell populations. However, morphological analysis revealed that PCSP cells are often elongated and displayed prominent lamellipodia, suggesting they are an unidentified migratory cell population. Analysis of clinical parameters showed that PCSP cells were found with a frequency of 20-35% of all tumors evaluated, but were not present in non-diseased normal tissue. Interestingly, a subset of primary Gleason 5 prostate tumors had a high burden of PCSP cells. The current study identifies PCSP cells as a novel, potentially migratory cell type, which is marked by Syndecan-1 expression and is found in the stroma

  4. [Cancer cachexia and white adipose tissue browning].

    PubMed

    Zhang, S T; Yang, H M

    2016-08-01

    Cancer cachexia occurs in a majority of advanced cancer patients. These patients with impaired physical function are unable to tolerance cancer treatment well and have a significantly reduced survival rate. Currently, there is no effective clinical treatment available for cancer cachexia, therefore, it is necessary to clarify the molecular mechanisms of cancer cachexia, moreover, new therapeutic targets for cancer cachexia treatment are urgently needed. Very recent studies suggest that, during cancer cachexia, white adipose tissue undergo a 'browning' process, resulting in increased lipid mobilization and energy expenditure, which may be necessary for the occurrence of cancer cachexia. In this article, we summarize the definition and characteristics of cancer cachexia and adipose tissue 'browning', then, we discuss the new study directions presented in latest research.

  5. Correlated non-nuclear COX2 and low HER2 expression confers a good prognosis in colorectal cancer.

    PubMed

    Zhou, Fei-Fei; Huang, Rong; Jiang, Jun; Zeng, Xiao-Hong; Zou, Shu-Qian

    2018-06-05

    COX2 and HER2 are shown to be critical in the regulation of cancer progression. However, the prognostic value of nuclear COX2 in colorectal cancer (CRC) and its relationship with HER2 still remains unknown. In this study, the expression and biological significance of COX2 and HER2 were evaluated in CRC at mRNA and protein levels. RNA-Seq data of CRC were downloaded from TCGA, and 229 CRC and 50 non-cancerous subjects were enrolled in this study. Bioinformatics and immunohistochemistry analysis was performed based on the obtained data. Survival analysis was conducted to identify factors associated with overall survival of CRC patients. We showed that mRNA and protein levels of COX2 and HER2 were upregulated in CRC compared with the adjacent tissues. COX2 protein levels and nuclear COX2 expression were correlated with a poor prognosis of CRC patients. In addition, we also revealed that nuclear COX2 expression was positively associated with HER2 expression. Non-nuclear COX2 combined with low HER2 expression, was negatively correlated with Duke's stage and lymph node metastasis, predicting the best outcomes for CRC patients. In addition, our data indicated that non-nuclear COX2 combined with low HER2 expression is an independent prognostic factor for CRC after surgical resection. The study suggests that nuclear COX2 in combination with HER2 can serve as potential biomarkers for the clinical diagnosis and prognosis of CRC, and targeted inhibition of COX2 and HER2 might be an alternative strategy for the management of CRC.

  6. A probable risk factor of female breast cancer: study on benign and malignant breast tissue samples.

    PubMed

    Rehman, Sohaila; Husnain, Syed M

    2014-01-01

    The study reports enhanced Fe, Cu, and Zn contents in breast tissues, a probable risk factor of breast cancer in females. Forty-one formalin-fixed breast tissues were analyzed using atomic absorption spectrophotometry. Twenty malignant, six adjacent to malignant and 15 benign tissues samples were investigated. The malignant tissues samples were of grade 11 and type invasive ductal carcinoma. The quantitative comparison between the elemental levels measured in the two types of specimen (benign and malignant) tissues (removed after surgery) suggests significant elevation of these metals (Fe, Cu, and Zn) in the malignant tissue. The specimens were collected just after mastectomy of women aged 19 to 59 years from the hospitals of Islamabad and Rawalpindi, Pakistan. Most of the patients belong to urban areas of Pakistan. Findings of study depict that these elements have a promising role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu, and Zn was observed. The results showed the excessive accumulation of Fe (229 ± 121 mg/L) in malignant breast tissue samples of patients (p < 0.05) to that in benign tissues samples (49.1 ± 11.4 mg/L). Findings indicated that excess accumulation of iron in malignant tissues can be a risk factor of breast cancer. In order to validate our method of analysis, certified reference material muscle tissue lyophilized (IAEA) MA-M-2/TM was analyzed for metal studied. Determined concentrations were quite in good agreement with certified levels. Asymmetric concentration distribution for Fe, Cu, and Zn was observed in both malignant and benign tissue samples.

  7. Long non-coding RNA gastric carcinoma highly expressed transcript 1 promotes cell proliferation and invasion in human head and neck cancer.

    PubMed

    Liu, Hui; Wu, Yu

    2018-05-01

    Recent evidence indicates that the long non-coding RNA gastric carcinoma highly expressed transcript 1 (GHET1) is involved in the development and carcinogenesis of several tumor types; however, the exact roles of GHET1 and its underlying mechanisms in head and neck cancer (HNC) remain largely unknown. In the present study, the expression patterns of GHET1 in HNC were determined and its clinical significance was assessed. The expression level of GHET1 was significantly increased in HNC tissues, compared with paired adjacent normal tissues. High GHET1 expression was significantly associated with advanced Tumor-Node-Metastasis stages and poor prognosis. Furthermore, inhibition of GHET1 suppressed cell proliferation, induced cell apoptosis and caused cell cycle arrest in vitro . In addition, GHET1 silencing inhibited cell migration and invasion. Taken together, the results of the present study indicated that GHET1 acts as an oncogene in HNC and may represent a novel therapeutic target.

  8. Structural and quantitative expression analyses of HERV gene family in human tissues.

    PubMed

    Ahn, Kung; Kim, Heui-Soo

    2009-08-31

    Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of several human diseases as multi-copy members in the human genome. Their gene expression profiling could provide us with important insights into the pathogenic relationship between HERVs and cancer. In this study, we have evaluated the genomic structure and quantitatively determined the expression patterns in the env gene of a variety of HERV family members located on six specific loci by the RetroTector 10 program, as well as real-time RT-PCR amplification. The env gene transcripts evidenced significant differences in the human tumor/normal adjacent tissues (colon, liver, uterus, lung and testis). As compared to the adjacent normal tissues, high levels of expression were noted in testis tumor tissues for HERV-K, in liver and lung tumor tissues for HERV-R, in liver, lung, and testis tumor tissues for HERV-H, and in colon and liver tumor tissues for HERV-P. These data warrant further studies with larger groups of patients to develop biomarkers for specific human cancers.

  9. Diagnosis of breast cancer by tissue analysis

    PubMed Central

    Bhattacharyya, Debnath; Bandyopadhyay, Samir Kumar

    2013-01-01

    In this paper, we propose a technique to locate abnormal growth of cells in breast tissue and suggest further pathological test, when require. We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps. Normal ductal epithelial cells and ductal/lobular invasive carcinogenic cells also consider for comparison here in this paper. In fact, features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue. We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some extent. PMID:23372340

  10. Decreased expression of connective tissue growth factor in non-small cell lung cancer is associated with clinicopathological variables and can be restored by epigenetic modifiers.

    PubMed

    Drzewiecka, Hanna; Gałęcki, Bartłomiej; Jarmołowska-Jurczyszyn, Donata; Kluk, Andrzej; Dyszkiewicz, Wojciech; Jagodziński, Paweł P

    2016-09-01

    Recent studies indicated undisputed contribution of connective tissue growth factor (CTGF) in the development of many cancers, including non-small cell lung cancer (NSCLC). However, the functional role and regulation of CTGF expression during tumorigenesis remain elusive. Our goal was to determine CTGF transcript and protein levels in tumoral and matched control tissues from 98 NSCLC patients, to correlate the results with clinicopathological features and to investigate whether the CTGF expression can be epigenetically regulated in NSCLC. We used quantitative PCR, Western blotting and immunohistochemistry to evaluate CTGF expression in lung cancerous and histopathologically unchanged tissues. We tested the impact of 5-Aza-2'-deoxycytidine (5-dAzaC) and trichostatin A (TSA) on CTGF transcript and protein levels in NSCLC cells (A549, Calu-1). DNA methylation status of the CTGF regulatory region was evaluated by bisulfite sequencing. The influence of 5-dAzaC and TSA on NSCLC cells viability and proliferation was monitored by the trypan blue assay. We found significantly decreased levels of CTGF mRNA and protein (both p < 0.0000001) in cancerous tissues of NSCLC patients. Down-regulation of CTGF occurred regardless of gender in all histological subtypes of NSCLC. Moreover, we showed that 5-dAzaC and TSA were able to restore CTGF mRNA and protein contents in NSCLC cells. However, no methylation within CTGF regulatory region was detected. Both compounds significantly reduced NSCLC cells proliferation. Decreased expression of CTGF is a common feature in NSCLC; however, it can be restored by the chromatin-modifying agents such as 5-dAzaC or TSA and consequently restrain cancer development.

  11. N-glycosylation of Colorectal Cancer Tissues

    PubMed Central

    Balog, Crina I. A.; Stavenhagen, Kathrin; Fung, Wesley L. J.; Koeleman, Carolien A.; McDonnell, Liam A.; Verhoeven, Aswin; Mesker, Wilma E.; Tollenaar, Rob A. E. M.; Deelder, André M.; Wuhrer, Manfred

    2012-01-01

    Colorectal cancer is the third most common cancer worldwide with an annual incidence of ∼1 million cases and an annual mortality rate of ∼655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers. PMID:22573871

  12. Signaling pathways effecting crosstalk between cartilage and adjacent tissues: Seminars in cell and developmental biology: The biology and pathology of cartilage.

    PubMed

    Maes, Christa

    2017-02-01

    Endochondral ossification, the mechanism responsible for the development of the long bones, is dependent on an extremely stringent coordination between the processes of chondrocyte maturation in the growth plate, vascular expansion in the surrounding tissues, and osteoblast differentiation and osteogenesis in the perichondrium and the developing bone center. The synchronization of these processes occurring in adjacent tissues is regulated through vigorous crosstalk between chondrocytes, endothelial cells and osteoblast lineage cells. Our knowledge about the molecular constituents of these bidirectional communications is undoubtedly incomplete, but certainly some signaling pathways effective in cartilage have been recognized to play key roles in steering vascularization and osteogenesis in the perichondrial tissues. These include hypoxia-driven signaling pathways, governed by the hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF), which are absolutely essential for the survival and functioning of chondrocytes in the avascular growth plate, at least in part by regulating the oxygenation of developing cartilage through the stimulation of angiogenesis in the surrounding tissues. A second coordinating signal emanating from cartilage and regulating developmental processes in the adjacent perichondrium is Indian Hedgehog (IHH). IHH, produced by pre-hypertrophic and early hypertrophic chondrocytes in the growth plate, induces the differentiation of adjacent perichondrial progenitor cells into osteoblasts, thereby harmonizing the site and time of bone formation with the developmental progression of chondrogenesis. Both signaling pathways represent vital mediators of the tightly organized conversion of avascular cartilage into vascularized and mineralized bone during endochondral ossification. Copyright © 2016. Published by Elsevier Ltd.

  13. Association and regulation of protein factors of field effect in prostate tissues

    PubMed Central

    Gabriel, Kristin N.; Jones, Anna C.; Nguyen, Julie P.T.; Antillon, Kresta S.; Janos, Sara N.; Overton, Heidi N.; Jenkins, Shannon M.; Frisch, Emily H.; Trujillo, Kristina A.; Bisoffi, Marco

    2016-01-01

    Field effect or field cancerization denotes the presence of molecular aberrations in structurally intact cells residing in histologically normal tissues adjacent to solid tumors. Currently, the etiology of prostate field-effect formation is unknown and there is a prominent lack of knowledge of the underlying cellular and molecular pathways. We have previously identified an upregulated expression of several protein factors representative of prostate field effect, i.e., early growth response-1 (EGR-1), platelet-derived growth factor-A (PDGF-A), macrophage inhibitory cytokine-1 (MIC-1), and fatty acid synthase (FASN) in tissues at a distance of 1 cm from the visible margin of intracapsule prostate adenocarcinomas. We have hypothesized that the transcription factor EGR-1 could be a key regulator of prostate field-effect formation by controlling the expression of PDGF-A, MIC-1, and FASN. Taking advantage of our extensive quantitative immunofluorescence data specific for EGR-1, PDGF-A, MIC-1, and FASN generated in disease-free, tumor-adjacent, and cancerous human prostate tissues, we chose comprehensive correlation as our major approach to test this hypothesis. Despite the static nature and sample heterogeneity of association studies, we show here that sophisticated data generation, such as by spectral image acquisition, linear unmixing, and digital quantitative imaging, can provide meaningful indications of molecular regulations in a physiologically relevant in situ environment. Our data suggest that EGR-1 acts as a key regulator of prostate field effect through induction of pro-proliferative (PDGF-A and FASN), and suppression of pro-apoptotic (MIC-1) factors. These findings were corroborated by computational promoter analyses and cell transfection experiments in non-cancerous prostate epithelial cells with ectopically induced and suppressed EGR-1 expression. Among several clinical applications, a detailed knowledge of pathways of field effect may lead to the

  14. Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia

    PubMed Central

    NGUYEN, TRI-HUNG; WEBER, WILLIAM; HAVARI, EVIS; CONNORS, TIMOTHY; BAGLEY, REBECCA G.; McLAREN, RAJASHREE; NAMBIAR, PRASHANT R.; MADDEN, STEPHEN L.; TEICHER, BEVERLY A.; ROBERTS, BRUCE; KAPLAN, JOHANNE; SHANKARA, SRINIVAS

    2012-01-01

    Overexpression of TMPRSS4, a cell surface-associated transmembrane serine protease, has been reported in pancreatic, colorectal and thyroid cancers, and has been implicated in tumor cell migration and metastasis. Few reports have investigated both TMPRSS4 gene expression levels and the protein products. In this study, quantitative RT-PCR and protein staining were used to assess TMPRSS4 expression in primary non-small cell lung carcinoma (NSCLC) tissues and in lung tumor cell lines. At the transcriptional level, TMPRSS4 message was significantly elevated in the majority of human squamous cell and adenocarcinomas compared with normal lung tissues. Staining of over 100 NSCLC primary tumor and normal specimens with rabbit polyclonal anti-TMPRSS4 antibodies confirmed expression at the protein level in both squamous cell and adenocarcinomas with little or no staining in normal lung tissues. Human lung tumor cell lines expressed varying levels of TMPRSS4 mRNA in vitro. Interestingly, tumor cell lines with high levels of TMPRSS4 mRNA failed to show detectable TMPRSS4 protein by either immunoblotting or flow cytometry. However, protein levels were increased under hypoxic culture conditions suggesting that hypoxia within the tumor microenvironment may upregulate TMPRSS4 protein expression in vivo. This was supported by the observation of TMPRSS4 protein in xenograft tumors derived from the cell lines. In addition, staining of human squamous cell carcinoma samples for carbonic anhydrase IX (CAIX), a hypoxia marker, showed TMPRSS4 positive cells adjacent to CAIX positive cells. Overall, these results indicate that the cancer-associated TMPRSS4 protein is overexpressed in NSCLC and may represent a potential therapeutic target. PMID:22692880

  15. MicroRNA-490-5p inhibits proliferation of bladder cancer by targeting c-Fos

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Shiqi; Xu, Xianglai; Xu, Xin

    2013-11-29

    Highlights: •We examined the level of miR-490-5p in bladder cancer tissues and three cancer cell lines. •We are the first to show the function of miR-490-5p in bladder cancer. •We demonstrate c-Fos may be a target of miR-490-5p. -- Abstract: MicroRNAs (miRNAs) are non-protein-coding sequences that play a crucial role in tumorigenesis by negatively regulating gene expression. Here, we found that miR-490-5p is down-regulated in human bladder cancer tissue and cell lines compared to normal adjacent tissue and a non-malignant cell line. To better characterize the function of miR-490-5p in bladder cancer, we over-expressed miR-490-5p in bladder cancer cell linesmore » with chemically synthesized mimics. Enforced expression of miR-490-5p in bladder cancer cells significantly inhibited the cell proliferation via G1-phase arrest. Further studies found the decreased c-Fos expression at both mRNA and protein levels and Luciferase reporter assays demonstrated that c-Fos is a direct target of miR-490-5p in bladder cancer. These findings indicate miR-490-5p to be a novel tumor suppressor of bladder cancer cell proliferation through targeting c-Fos.« less

  16. Dlx proteins position the neural plate border and determine adjacent cell fates.

    PubMed

    Woda, Juliana M; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

    2003-01-01

    The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates.

  17. Dlx proteins position the neural plate border and determine adjacent cell fates

    PubMed Central

    Woda, Juliana M.; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

    2014-01-01

    Summary The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates. PMID:12466200

  18. The Perspectives of Haematological Cancer Patients on Tissue Banking.

    PubMed

    Turon, Heidi; Waller, Amy; Clinton-McHarg, Tara; Boyes, Allison; Fleming, Jennifer; Marlton, Paula; Harrison, Simon J; Sanson-Fisher, Rob

    2016-01-01

    A high level of support for tissue banking has been identified amongst both the general public and patients. However, much debate remains about the regulatory framework of tissue banks. This study explored the views of haematological cancer patients regarding tissue banking and how tissue banks should operate. Haematological cancer patients from three outpatient clinics in Australia completed a questionnaire examining their preferences for tissue banking as well as items about their sociodemographic characteristics, disease and treatment history. The majority of participants (95%) reported being willing to allow their leftover tissue to be used for medical research. Three quarters (76%) supported the idea of their medical record being linked to their tissue sample, and 77% preferred a blanket (one-off) consent model for future research use of their tissue sample. Only 57 (27%) participants had been asked to give a tissue sample for research, 98% of whom gave permission. The majority of haematological cancer patients are willing to donate their leftover tissue to a tissue bank and have their medical records linked to tissue samples and prefer a one-off consent process. These novel data from potential donors inform the debate about how tissue banks might operate. Strategic Research Partnership Grant from the Cancer Council NSW to the Newcastle Cancer Control Collaborative (New-3C) and infrastructure funding from the Hunter Medical Research Institute (HMRI). A.W. is supported by an Australian Research Council DECRA fellowship (DE150101262). T.C.M. was supported by a Leukaemia Foundation of Queensland Post-Doctoral Fellowship. A.B. is supported by National Health and Medical Research Council (APP1073317) and Cancer Institute NSW (13/ECF/1-37) Early Career Fellowships.

  19. Bilayered, non-cross-linked collagen matrix for regeneration of facial defects after skin cancer removal: a new perspective for biomaterial-based tissue reconstruction.

    PubMed

    Ghanaati, Shahram; Kovács, Adorján; Barbeck, Mike; Lorenz, Jonas; Teiler, Anna; Sadeghi, Nader; Kirkpatrick, Charles James; Sader, Robert

    2016-03-01

    Classically skin defects are covered by split thickness skin grafts or by means of local or regional skin flaps. In the presented case series for the first time a bilayered, non-crossed-linked collagen matrix has been used in an off-label fashion in order to reconstruct facial skin defects following different types of skin cancer resection. The material is of porcine origin and consists of a spongy and a compact layer. The ratio of the two layers is 1:3 in favour of the spongy layer. The aim of the study was to investigate the potential of this matrix for skin regeneration as an alternative to the standard techniques of skin grafts or flaps. Six patients between 39 and 83 years old were included in the study based on a therapeutic trial. The collagen matrix was used in seven defects involving the nose, eyelid, forehead- and posterior scalp regions, and ranging from 1,2 to 6 cm in diameter. Two different head and neck surgeons at two different institutions performed the operations. Each used a different technique in covering the wound following surgery, i.e. with and without a latex-based sheet under the pressure dressing. In three cases cylindrical biopsies were taken after 14 days. In all cases the biomaterial application was performed without any complication and no adverse effects were observed. Clinically, the collagen matrix contributed to a tension-free skin regeneration, independent of the wound dressing used. The newly regenerated skin showed strong similarity to the adjacent normal tissue both in quality and colour. Histological analysis indicated that the spongy layer replaced the defective connective tissue, by providing stepwise integration into the surrounding implantation bed, while the compact layer was infiltrated by mononuclear cells and contributed to its epithelialization by means of a "conductive"process from the surrounding epithelial cells. The clinical and histological data demonstrate that the collagen bilayered matrix used in this series

  20. A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone

    PubMed Central

    Thibaudeau, Laure; Taubenberger, Anna V.; Holzapfel, Boris M.; Quent, Verena M.; Fuehrmann, Tobias; Hesami, Parisa; Brown, Toby D.; Dalton, Paul D.; Power, Carl A.; Hollier, Brett G.; Hutmacher, Dietmar W.

    2014-01-01

    ABSTRACT The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact ‘organ’ bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo. PMID:24713276

  1. Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baardwijk, Angela van; Bosmans, Geert; Boersma, Liesbeth

    2008-08-01

    Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissuemore » dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An {sup 18}F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 {+-} 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.« less

  2. A model for cancer tissue heterogeneity.

    PubMed

    Mohanty, Anwoy Kumar; Datta, Aniruddha; Venkatraj, Vijayanagaram

    2014-03-01

    An important problem in the study of cancer is the understanding of the heterogeneous nature of the cell population. The clonal evolution of the tumor cells results in the tumors being composed of multiple subpopulations. Each subpopulation reacts differently to any given therapy. This calls for the development of novel (regulatory network) models, which can accommodate heterogeneity in cancerous tissues. In this paper, we present a new approach to model heterogeneity in cancer. We model heterogeneity as an ensemble of deterministic Boolean networks based on prior pathway knowledge. We develop the model considering the use of qPCR data. By observing gene expressions when the tissue is subjected to various stimuli, the compositional breakup of the tissue under study can be determined. We demonstrate the viability of this approach by using our model on synthetic data, and real-world data collected from fibroblasts.

  3. Comparison of plasma and tissue samples in epidermal growth factor receptor mutation by ARMS in advanced non-small cell lung cancer.

    PubMed

    Ma, MeiLi; Shi, ChunLei; Qian, JiaLin; Teng, JiaJun; Zhong, Hua; Han, BaoHui

    2016-10-10

    The aim of this study was to assess the effectiveness and accuracy of blood-based circulating-free tumor DNA on testing epidermal growth factor receptor (EGFR) gene mutations. In total, 219 non-small cell lung cancer patients in stages III-IV were enrolled into this study. All patients had tissue samples and matched plasma DNA samples. EGFR gene mutations were detected by the Amplification Refractory Mutation System (ARMS). We compared the mutations in tumor tissue samples with matched plasma samples and determined the correlation between EGFR mutation status and clinical pathologic characteristics. The overall concordance rate of EGFR mutation status between the 219 matched plasma and tissue samples was 82% (179/219). The sensitivity and specificity for the ARMS EGFR mutation test in the plasma compared with tumor tissue were 60% (54/90) and 97% (125/129), respectively. The positive predictive value was 93% (54/58) and the negative predictive value was 78% (125/161). The median overall survival was longer for those with EGFR mutations than for those without EGFR mutations both in tissue samples (23.98 vs. 12.16months; P<0.001) and in plasma (19.96 vs. 13.63months; P=0.009). For the 68 patients treated with EGFR- tyrosine kinase inhibitors (TKIs), the median progression-free survival (PFS) was significantly prolonged in the EGFR mutant group compared to the non-mutation group in tumor tissue samples (12.26months vs. 2.40months, P<0.001). In plasma samples, the PFS of the mutant group was longer than that of the non-mutant group. However, there was no significant difference between the two groups (10.88months vs. 9.89months, P=0.411). The detection of EGFR mutations in plasma using ARMS is relatively sensitive and highly specific. However, EGFR mutation status tested by ARMS in plasma cannot replace a tumor tissue biopsy. Positive EGFR mutation results detected in plasma are fairly reliable, but negative results are hampered by a high rate of false negatives

  4. The role of lipid droplets and adipocytes in cancer. Raman imaging of cell cultures: MCF10A, MCF7, and MDA-MB-231 compared to adipocytes in cancerous human breast tissue.

    PubMed

    Abramczyk, Halina; Surmacki, Jakub; Kopeć, Monika; Olejnik, Alicja Klaudia; Lubecka-Pietruszewska, Katarzyna; Fabianowska-Majewska, Krystyna

    2015-04-07

    We have studied live non-malignant (MCF10A), mildly malignant (MCF7) and malignant (MDA-MB-231) breast cancer cells and human breast cancer tissue. We demonstrate the first application of Raman imaging and spectroscopy in diagnosing the role of lipid droplets in cell line cultures that closely mimic an in vivo environment of various stages in human breast cancer tissue. We have analyzed the composition of the lipid droplets in non-malignant and malignant human breast epithelial cell lines and discussed the potential of lipid droplets as a prognostic marker in breast cancer. To identify any difference in the lipid droplet-associated biochemistry and to correlate it with different stages of breast cancer, the PCA method was employed. The chemical composition of lipids and proteins, both in the cell line models and in human breast tissue has been analyzed. The paper shows the alterations in lipid metabolism that have been reported in cancer, at both the cellular and tissue levels, and discusses how they contribute to the different aspects of tumourigenesis.

  5. Thermal non-equilibrium in porous medium adjacent to vertical plate: ANN approach

    NASA Astrophysics Data System (ADS)

    Ahmed, N. J. Salman; Ahamed, K. S. Nazim; Al-Rashed, Abdullah A. A. A.; Kamangar, Sarfaraz; Athani, Abdulgaphur

    2018-05-01

    Thermal non-equilibrium in porous medium is a condition that refers to temperature discrepancy in solid matrix and fluid of porous medium. This type of flow is complex flow requiring complex set of partial differential equations that govern the flow behavior. The current work is undertaken to predict the thermal non-equilibrium behavior of porous medium adjacent to vertical plate using artificial neural network. A set of neurons in 3 layers are trained to predict the heat transfer characteristics. It is found that the thermal non-equilibrium heat transfer behavior in terms of Nusselt number of fluid as well as solid phase can be predicted accurately by using well-trained neural network.

  6. Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer

    PubMed Central

    Ren, Zhipeng; Zhang, Guoliang

    2017-01-01

    Esophageal cancer is one of the most common gastrointestinal malignant diseases and there is still no effective treatment. The incidence of esophageal cancer in the world is relatively high and on the increase year by year. Thus, the elaboration on the carcinogenesis of esophageal cancer and the identification of new biomarkers and therapeutic targets is quite beneficial to optimizing the current therapeutic regimen for treating such deadly disease. More and more evidence has shown that non-coding RNAs play an important role in the development and progression of multiple human cancers, including esophageal cancer. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two functional kinds of non-coding RNAs that have been well investigated. They exert tumor suppressive or promoting effect by specifically regulating the expression of certain downstream target genes, which is tumor specific. It is also proved that miRNAs and lncRNAs level in tissue and plasma from esophageal cancer patients are closely correlated with the survival and disease progression, which could be used as a prognostic factor and therapeutic target for esophageal cancer. PMID:28388588

  7. Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer.

    PubMed

    Hou, Xiaobin; Wen, Jiaxin; Ren, Zhipeng; Zhang, Guoliang

    2017-06-27

    Esophageal cancer is one of the most common gastrointestinal malignant diseases and there is still no effective treatment. The incidence of esophageal cancer in the world is relatively high and on the increase year by year. Thus, the elaboration on the carcinogenesis of esophageal cancer and the identification of new biomarkers and therapeutic targets is quite beneficial to optimizing the current therapeutic regimen for treating such deadly disease. More and more evidence has shown that non-coding RNAs play an important role in the development and progression of multiple human cancers, including esophageal cancer. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two functional kinds of non-coding RNAs that have been well investigated. They exert tumor suppressive or promoting effect by specifically regulating the expression of certain downstream target genes, which is tumor specific. It is also proved that miRNAs and lncRNAs level in tissue and plasma from esophageal cancer patients are closely correlated with the survival and disease progression, which could be used as a prognostic factor and therapeutic target for esophageal cancer.

  8. Evaluation of Cancer and Non-cancer Effects of Cumene ...

    EPA Pesticide Factsheets

    Cumene, also known as isopropyl benzene, is a volatile liquid. Cumene, readily absorbed via inhalation is distributed in several tissues, metabolized extensively by cytochrome P-450 isozymes within hepatic and extra-hepatic tissues and excreted through urine. No epidemiological cancer studies for humans are available, however, chronic inhalation exposure studies in rat and mouse have shown increased nasal lesions including atrophy, basal cell hyperplasia, atypical hyperplasia and hyperplasia of the olfactory epithelium glands. In addition, increased incidences of renal tubular adenoma or carcinoma that are related to a2u-globin-induced nephropathy were observed in male rats. Alveolar/bronchiolar adenomas and carcinomas of the lung are observed in male and female mice exposed to cumene. Although no multi-generational reproductive toxicity is available for cumene, cumene-exposed rats appeared to stay in estrus cycle longer than the controls. Short-term acute exposures of animals at high concentrations seem to induce transient reversible neurotoxic effects. Overall, inhalation exposure to cumene induced dose-related increased in the occurances of tumors at various sites. These cancer and non-cancer data in rats and mice as well as genotoxicity data provides consistence evidence for carcinogenic effects of cumene. This poster will be presented at the Society of Toxicology Meeting in San Diego California. The goal of this presentation is systematic evaluation of bot

  9. Overexpression of NEK3 is associated with poor prognosis in patients with gastric cancer.

    PubMed

    Cao, Yongfeng; Song, Jiaye; Chen, Jia; Xiao, Jinzhang; Ni, Jingyi; Wu, Changping

    2018-01-01

    The NIMA-related kinase 3 (NEK3) plays an important role in cell migration, cell proliferation, and cell viability. Recently, NEK3 was reported to enhance the malignancy of breast cancer. However, its role in gastric cancer has not been completely characterized. In this study, we explored the prognostic significance of NEK3 in human gastric cancer. Reverse transcription-polymerase chain reaction and western blot were performed to detect the NEK3 mRNA and protein expression in 6 paired fresh human gastric cancer tissues and surrounding normal tissues. NEK3 levels in gastric cancer and its adjacent normal samples of 168 cases were detected by immunohistochemistry, and the relationships between the NEK3 level and various clinicopathological features were analyzed. NEK3 mRNA and protein were significantly overexpressed in gastric cancer tissues, compared with adjacent normal tissues. Immunohistochemistry staining assay showed the percentage of high NEK3 expression in gastric cancer samples was higher than that in adjacent normal samples. NEK3 overexpression was significantly correlated with pT stage, pathologic TNM stage, lymph node metastasis, and poor prognosis of gastric cancer. Cox multivariate regression analyses suggested that NEK3 was an independent prognostic factor for survival of patients with gastric cancer. The data demonstrate that NEK3 is overexpressed in gastric cancer, which promotes the malignancy of gastric cancer. NEK3 may be as a prognostic biomarker and a potential therapeutic target for gastric cancer. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  10. CPTAC Releases Cancer Proteome Confirmatory Breast Study Data | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    An estimated 252,710 new cases of female breast cancer, accounting for 15% of all new cancer cases, occurred in 2017. To better understand proteogenomic abnormalities in breast cancer, the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) announces the release of the cancer proteome confirmatory breast study data. The goal of the study was to comprehensively characterize the proteome and phosphoproteome on approximately 100 prospectively collected breast tumor and adjacent normal tissues.

  11. Analysis of human tissue optical scattering spectra for the purpose of breast cancer diagnostics using multi-layer perceptron

    NASA Astrophysics Data System (ADS)

    Nuzhny, Anton S.; Shumsky, Sergey A.; Korzhov, Alexey G.; Lyubynskaya, Tatiana E.

    2008-02-01

    Optical scattering spectra obtained in the clinical trials of breast cancer diagnostic system were analyzed for the purpose to detect in the dataflow the segments corresponding to malignant tissues. Minimal invasive probe with optical fibers inside delivers white light from the source and collects the scattering light while being moved through the tissue. The sampling rate is 100 Hz and each record contains the results of measurements of scattered light intensity at 184 fixed wavelength points. Large amount of information acquired in each procedure, fuzziness in criteria of 'cancer' family membership and data noisiness make neural networks to be an attractive tool for analysis of these data. To define the dividing rule between 'cancer' and 'non-cancer' spectral families a three-layer perceptron was applied. In the process of perceptron learning back propagation method was used to minimize the learning error. Regularization was done using the Bayesian approach. The learning sample was formed by the experts. End-to-end probability calculation throughout the procedure dataset showed reliable detection of the 'cancer' segments. Much attention was paid on the spectra of the tissues with high blood content. Often the reason is vessel injury caused by the penetrating optical probe. But also it can be a dense vessel net surrounding the malignant tumor. To make the division into 'cancer' and 'non-cancer' families for the tissues with high blood content a special perceptron was learnt exceptionally on such spectra.

  12. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

    PubMed

    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Whole-Lesion Apparent Diffusion Coefficient-Based Entropy-Related Parameters for Characterizing Cervical Cancers: Initial Findings.

    PubMed

    Guan, Yue; Li, Weifeng; Jiang, Zhuoran; Chen, Ying; Liu, Song; He, Jian; Zhou, Zhengyang; Ge, Yun

    2016-12-01

    This study aimed to develop whole-lesion apparent diffusion coefficient (ADC)-based entropy-related parameters of cervical cancer to preliminarily assess intratumoral heterogeneity of this lesion in comparison to adjacent normal cervical tissues. A total of 51 women (mean age, 49 years) with cervical cancers confirmed by biopsy underwent 3-T pelvic diffusion-weighted magnetic resonance imaging with b values of 0 and 800 s/mm 2 prospectively. ADC-based entropy-related parameters including first-order entropy and second-order entropies were derived from the whole tumor volume as well as adjacent normal cervical tissues. Intraclass correlation coefficient, Wilcoxon test with Bonferroni correction, Kruskal-Wallis test, and receiver operating characteristic curve were used for statistical analysis. All the parameters showed excellent interobserver agreement (all intraclass correlation coefficients  > 0.900). Entropy, entropy(H) 0 , entropy(H) 45 , entropy(H) 90 , entropy(H) 135 , and entropy(H) mean were significantly higher, whereas entropy(H) range and entropy(H) std were significantly lower in cervical cancers compared to adjacent normal cervical tissues (all P <.0001). Kruskal-Wallis test showed that there were no significant differences among the values of various second-order entropies including entropy(H) 0, entropy(H) 45 , entropy(H) 90 , entropy(H) 135 , and entropy(H) mean. All second-order entropies had larger area under the receiver operating characteristic curve than first-order entropy in differentiating cervical cancers from adjacent normal cervical tissues. Further, entropy(H) 45 , entropy(H) 90 , entropy(H) 135 , and entropy(H) mean had the same largest area under the receiver operating characteristic curve of 0.867. Whole-lesion ADC-based entropy-related parameters of cervical cancers were developed successfully, which showed initial potential in characterizing intratumoral heterogeneity in comparison to adjacent normal cervical tissues

  14. Prognostic value of decreased expression of RBM4 in human gastric cancer.

    PubMed

    Yong, Hongmei; Zhu, Huijun; Zhang, Shu; Zhao, Wei; Wang, Wei; Chen, Chen; Ding, Guipeng; Zhu, Lun; Zhu, Ziyuan; Liu, Huaidong; Zhang, Yongjie; Wen, Jinbo; Kang, Xing; Zhu, Jin; Feng, Zhenqing; Liu, Baorui

    2016-06-21

    RNA-binding motif 4 (RBM4) is a multifunctional protein that participates in regulating alternative splicing and mRNA translation. Its reduced expression has been associated with poor overall survival in lung cancer, breast cancer and ovarian cancer. We assessed RBM4 protein expression levels with immunohistochemistry in tissue microarrays containing malignant gastric cancer tissues and benign tissues from 813 patients. We also examined the expression levels of RBM4 mRNA in twenty-five paired gastric cancer samples and adjacent noncancerous tissues. Both RBM4 protein and mRNA expression levels were significantly lower in gastric cancer tissues compared with the adjacent noncancerous tissues. There was a significant association between reduced RBM4 protein expression and differentiation (P < 0.001), lymph node metastasis (P = 0.026), TNM state (P = 0.014) and distant metastasis (P = 0.036). Patients with reduced RBM4 expression (P < 0.001, CI = 0.315-0.710) and TNM stage III and IV (P < 0.001, CI = 4.757-11.166) had a poor overall survival. These findings suggest that RBM4 is a new biomarker in gastric cancer, as the reduced expression of this protein is correlated with poor differentiation, lymph node status and distant metastasis. Further, lower RBM4 expression is an independent prognostic marker for gastric cancer.

  15. Targeting solid tumors with non-pathogenic obligate anaerobic bacteria.

    PubMed

    Taniguchi, Shun'ichiro; Fujimori, Minoru; Sasaki, Takayuki; Tsutsui, Hiroko; Shimatani, Yuko; Seki, Keiichi; Amano, Jun

    2010-09-01

    Molecular-targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non-pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment. © 2010 Japanese Cancer Association.

  16. Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer

    PubMed Central

    2012-01-01

    Background G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E2), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer. Methods The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed. Results Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue. Conclusion The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression. PMID:23273253

  17. Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer.

    PubMed

    Jala, Venkatakrishna Rao; Radde, Brandie N; Haribabu, Bodduluri; Klinge, Carolyn M

    2012-12-28

    G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E2), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer. The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed. Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue. The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression.

  18. Testes-specific protease 50 as an independent risk factor for poor prognosis in patients with non-small cell lung cancer.

    PubMed

    Qiao, Wen-Liang; Shi, Bo-Wen; Han, Yu-Dong; Tang, Hua-Mei; Lin, Jun; Hu, Hai-Yang; Lin, Qiang

    2018-06-01

    Testes-specific protease 50 (TSP50) is normally expressed in the testes and is overexpressed in various types of human cancers, including breast cancer, colorectal carcinoma and laryngocarcinoma. However, little has been reported on the association between TSP50 and non-small cell lung cancer (NSCLC). The present study aimed to detect TSP50 expression in 198 strict follow-up cases of paired NSCLC and 15 cases of normal lung parenchymal specimens using immunohistochemical staining. The expression levels of TSP50 were then correlated with the clinicopathological factors of NSCLC to assess its potential diagnostic and prognostic value. The relationship between TSP50 expression and the clinicopathological parameters of NSCLC was evaluated using χ 2 and Fisher's exact tests. Survival rates for the overall population (n=198) were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox's proportional hazards regression model. P<0.05 was considered to indicate a statistically significant difference. The expression of TSP50 was significantly increased in NSCLC tissue compared with in adjacent non-tumor or normal lung parenchymal tissue (P<0.001). A significant association was revealed between high expression levels of TSP50 and clinicopathological characteristics including tumor differentiation (P=0.012), late tumor status (P=0.004) and late tumor node metastasis stage (P=0.026), as well as a reduced disease free survival (P=0.009) and overall survival rate (P=0.002) in all patients with NSCLC. Multivariate analyses demonstrated that high TSP50 expression in tumor tissues was significantly associated with a shorter disease-free survival rate [hazard ratio (HR) =1.590, 95% confidence interval (CI): 1.035-2.441], and with a shorter overall survival rate (HR=1.814; 95% CI: 1.156-2.846). In conclusion, the present data demonstrated that increased TSP50 protein expression may be a potential predictor of early recurrence

  19. Predictive value of Sox2 expression in transurethral resection specimens in patients with T1 bladder cancer.

    PubMed

    Ruan, Jun; Wei, Bingbing; Xu, Zhuoqun; Yang, Shudong; Zhou, You; Yu, Minhong; Liang, Jiabei; Jin, Ke; Huang, Xing; Lu, Peng; Cheng, Huan

    2013-03-01

    Sox2 is thought to be an important regulator of self-renewal in embryonic stem cell. According to the cancer stem cell (CSC) theory, the overexpression of Sox2 is potentially involved in carcinogenesis and could affect tumor recurrence and metastasis. Previous study proved Sox2 might be prognostic marker for multiple human malignancies. The purpose of this study was to investigate the clinicopathological significance of Sox2 expression in human non-muscle-invasive bladder cancer. We examined Sox2 expression in 32 paired non-muscle-invasive bladder cancer tissues and adjacent non-cancerous tissues by quantitative real-time RT-PCR (qrtRT-PCR). In addition, we analyzed Sox2 and Ki-67 expression in 126 non-muscle-invasive bladder cancer samples and bladder cancer cell line T24 by immunohistochemistry and immunofluorescence assays. The recurrence-free survival was determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for univariate and multivariate analyses of prognostic factors. The expression of Sox2 was significantly increased in non-muscle-invasive bladder cancer tissues. Sox2 expression was significantly correlated with that of Ki-67 (P < 0.001). The expression of Sox2 was significantly associated with tumor size (P = 0.006), tumor number (P = 0.037), and tumor grade (P < 0.001). Patients with high Sox2 expression had significantly poorer recurrence-free survival (P = 0.0002) when compared with patients with the low expression of Sox2. On multivariate analysis, Sox2 expression and tumor grade were found to be independent prognostic factors for recurrence-free survival (P < 0.05). Our data suggested for the first time that the high expression of Sox2 may contribute to the development of non-muscle-invasive bladder cancer and serve as a novel prognostic marker in patients with T1 bladder cancer.

  20. Using circular RNA hsa_circ_0000190 as a new biomarker in the diagnosis of gastric cancer.

    PubMed

    Chen, Shijun; Li, Tianwen; Zhao, Qianfu; Xiao, Bingxiu; Guo, Junming

    2017-03-01

    Circular RNAs (circRNA) are an abundant class of non-coding RNAs in mammalian cells. However, their value in the diagnosis of cancers remains unknown. In this study, we focused on hsa_circ_0000190, which was found to be down-regulated in gastric cancer tissues in our previous microarray screening. The hsa_circ_0000190 levels in 104 paired gastric cancer tissues and adjacent non-tumor tissues, 104 plasma samples from patients with gastric cancer and 104 plasma samples from health controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, the association between the expression level of hsa_circ_0000190 and the clinicopathological features of patients with gastric cancer was further analyzed. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic value. Hsa_circ_0000190 was first found to be down-regulated in gastric cancer tissues (P<0.001) and plasma samples from patients with gastric cancer (P<0.001). Its expression levels were significantly correlated with tumor diameter (P=0.034), lymphatic metastasis (P=0.026), distal metastasis (P=0.001), TNM stage (P=0.001), and CA19-9 levels (P=0.019). The areas under the ROC curve (AUC) of hsa_circ_0000190 in tissues and plasma were up to 0.75 and 0.60, respectively. The sensitivity and specificity of the combination were 0.712 and 0.750; the AUC was increased to 0.775. These results indicated that hsa_circ_0000190 may be a novel non-invasive biomarker for the diagnosis of gastric cancer. Its AUC, sensitivity and specificity are better than commonly used biomarkers such as CEA and CA19-9. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. [Analysis of EML4-ALK gene fusion mutation in patients 
with non-small cell lung cancer].

    PubMed

    Wang, Xuzhou; Chen, Weisheng; Yu, Yinghao

    2015-02-01

    Non-small cell lung cancer (NSCLC) is the main type of lung cancer, and the related locus mutation detection research has become a hot direction of molecular targeted therapy, studying on gene mutation status of echinodem microtubule associated protein like 4-Anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR), detecting the sensitivity of EML4-ALK gene fusion and gene mutation of EGFR. EML4-ALK gene fusion in 85 cases of paraffin embedded tumor tissue and adjacent lung tissue was detected with the application of immunohistochemistry (IHC), Scorpions amplification refractory mutation system (Scorpions ARMS) fluorescence quantitative PCR and fluorescence in situ hybridization (FISH) technology, and EGFR gene in 18, 19, 20 and 21 exon mutation status was detected with the application of ARMS method. In 115 cases of NSCLC, IHC showed 32 cases with ALK (D5F3) expression, the expression rate was 27.8%; ARMS showed 27 cases with EML4-ALK fusion gene mutation, the mutation detection rate was 23.5%; 53 cases were detected with EGFR mutation, the mutation rate was 46%. While FISH showed 23 cases with EML4-ALK fusion gene mutation, the detection rate was 20%, slightly lower than the ARMS detection results, suggesting that ARMS more sensitive. The application of IHC, ARMS fluorescence quantitative PCR and FISH technology can make a rapid and accurate evaluation of EML4-ALK gene fusion.

  2. Prevalence of somatic mitochondrial mutations and spatial distribution of mitochondria in non-small cell lung cancer.

    PubMed

    Kazdal, Daniel; Harms, Alexander; Endris, Volker; Penzel, Roland; Kriegsmann, Mark; Eichhorn, Florian; Muley, Thomas; Stenzinger, Albrecht; Pfarr, Nicole; Weichert, Wilko; Warth, Arne

    2017-07-11

    Mitochondria are considered relevant players in many tumour entities and first data indicate beneficial effects of mitochondria-targeted antioxidants in both cancer prevention and anticancer therapies. To further dissect the potential roles of mitochondria in NSCLC we comprehensively analysed somatic mitochondrial mutations, determined the spatial distribution of mitochondrial DNA within complete tumour sections and investigated the mitochondrial load in a large-scale approach. Whole mitochondrial genome sequencing of 26 matched tumour and non-neoplastic tissue samples extended by reviewing published data of 326 cases. Systematical stepwise real-time PCR quantification of mitochondrial DNA covering 16 whole surgical tumour sections. Immunohistochemical determination of the mitochondrial load in 171 adenocarcinoma and 145 squamous cell carcinoma. Our results demonstrate very low recurrences (max. 1.7%) and a broad distribution of 456 different somatic mitochondrial mutations. Large inter- and intra-tumour heterogeneity were seen for mitochondrial DNA copy numbers in conjunction with a correlation to the predominant histological growth pattern. Furthermore, tumour cells had significantly higher mitochondrial level compared to adjacent stroma, whereas differences between tumour entities were negligible. Non-evident somatic mitochondrial mutations and highly varying mitochondrial DNA level delineate challenges for the approach of mitochondria-targeted anticancer therapies in NSCLC.

  3. Emerging Non-Cancer Applications of Therapeutic Ultrasound

    PubMed Central

    O’Reilly, Meaghan A.; Hynynen, Kullervo

    2015-01-01

    Ultrasound therapy has been investigated for over half a century. Ultrasound can act on tissue through a variety of mechanisms, including thermal, shockwave and cavitation mechanisms, and through these can elicit different responses. Ultrasound therapy can provide a non-invasive or minimally invasive treatment option, and ultrasound technology has advanced to the point where devices can be developed to investigate a wide range of applications. This review focuses on non-cancer, clinical applications of therapeutic ultrasound, with an emphasis on treatments that have recently reached clinical investigations, and preclinical research programs that have great potential to impact patient care. PMID:25792225

  4. Gene mutation analysis in non-small cell lung cancer patients using bronchoalveolar lavage fluid and tumor tissue as diagnostic markers.

    PubMed

    Li, Jian; Hu, Yi-Ming; Wang, Yi; Tang, Xing-Ping; Shi, Wei-Lin; Du, Yong-Jie

    2014-12-09

    Non-small cell lung cancer (NSCLC) is one of the main causes of cancer death in the world. Early detection of NSCLC can improve its outcome. The aim of this study was to identify the mutations of the KRAS and p53 genes in bronchoalveoar lavage (BAL) fluid for the early detection of peripheral NSCLC. We examined the DNA obtained from the tumor, nearby normal lung tissue, and matched BAL fluid for mutations in the KRAS and p53 genes; the material was obtained from 48 patients with peripheral NSCLC, and was analyzed by PCR-single strand conformation polymorphism and DNA sequencing. BAL fluids from 26 patients with benign lung disease were used as controls. Positive rates of KRAS and p53 mutations were distributed as follows: in NSCLC tissue, 52% and 58%; in BAL fluid of NSCLC patients, 38% and 44%; in normal lung tissue, 6% and 4%; and in BAL fluid of patients with benign lung disease, 8% and 4%. The combined detection of both KRAS and p53 mutations yielded a sensitivity of 66% for the diagnosis of peripheral NSCLC, which is markedly higher than that of cytology plus histology by first bronchoscopy (38%, p=0.008). In each patient with the 2 gene mutations in BAL fluid, mutation type and location were the same as those of the primary tumor. Our study indicates that the detection of the KRAS and p53 mutations in BAL fluids could be a helpful addition to cytology and histology examination for the diagnosis of peripheral NSCLC.

  5. Differential Expression of Cytochrome P450 Enzymes in Normal and Tumor Tissues from Childhood Rhabdomyosarcoma

    PubMed Central

    Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

    2014-01-01

    Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs. PMID:24699256

  6. Theoretical and Experimental Estimations of Volumetric Inductive Phase Shift in Breast Cancer Tissue

    NASA Astrophysics Data System (ADS)

    González, C. A.; Lozano, L. M.; Uscanga, M. C.; Silva, J. G.; Polo, S. M.

    2013-04-01

    Impedance measurements based on magnetic induction for breast cancer detection has been proposed in some studies. This study evaluates theoretical and experimentally the use of a non-invasive technique based on magnetic induction for detection of patho-physiological conditions in breast cancer tissue associated to its volumetric electrical conductivity changes through inductive phase shift measurements. An induction coils-breast 3D pixel model was designed and tested. The model involves two circular coils coaxially centered and a human breast volume centrally placed with respect to the coils. A time-harmonic numerical simulation study addressed the effects of frequency-dependent electrical properties of tumoral tissue on the volumetric inductive phase shift of the breast model measured with the circular coils as inductor and sensor elements. Experimentally; five female volunteer patients with infiltrating ductal carcinoma previously diagnosed by the radiology and oncology departments of the Specialty Clinic for Women of the Mexican Army were measured by an experimental inductive spectrometer and the use of an ergonomic inductor-sensor coil designed to estimate the volumetric inductive phase shift in human breast tissue. Theoretical and experimental inductive phase shift estimations were developed at four frequencies: 0.01, 0.1, 1 and 10 MHz. The theoretical estimations were qualitatively in agreement with the experimental findings. Important increments in volumetric inductive phase shift measurements were evident at 0.01MHz in theoretical and experimental observations. The results suggest that the tested technique has the potential to detect pathological conditions in breast tissue associated to cancer by non-invasive monitoring. Further complementary studies are warranted to confirm the observations.

  7. Contribution of Adipose Tissue to Development of Cancer

    PubMed Central

    Cozzo, Alyssa J.; Fuller, Ashley M.; Makowski, Liza

    2018-01-01

    Solid tumor growth and metastasis require the interaction of tumor cells with the surrounding tissue, leading to a view of tumors as tissue-level phenomena rather than exclusively cell-intrinsic anomalies. Due to the ubiquitous nature of adipose tissue, many types of solid tumors grow in proximate or direct contact with adipocytes and adipose-associated stromal and vascular components, such as fibroblasts and other connective tissue cells, stem and progenitor cells, endothelial cells, innate and adaptive immune cells, and extracellular signaling and matrix components. Excess adiposity in obesity both increases risk of cancer development and negatively influences prognosis in several cancer types, in part due to interaction with adipose tissue cell populations. Herein, we review the cellular and noncellular constituents of the adipose “organ,” and discuss the mechanisms by which these varied microenvironmental components contribute to tumor development, with special emphasis on obesity. Due to the prevalence of breast and prostate cancers in the United States, their close anatomical proximity to adipose tissue depots, and their complex epidemiologic associations with obesity, we particularly highlight research addressing the contribution of adipose tissue to the initiation and progression of these cancer types. Obesity dramatically modifies the adipose tissue microenvironment in numerous ways, including induction of fibrosis and angiogenesis, increased stem cell abundance, and expansion of proinflammatory immune cells. As many of these changes also resemble shifts observed within the tumor microenvironment, proximity to adipose tissue may present a hospitable environment to developing tumors, providing a critical link between adiposity and tumorigenesis. PMID:29357128

  8. Optical redox imaging indices discriminate human breast cancer from normal tissues

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2016-11-01

    Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (p<0.05). The redox ratio Fp/(NADH + Fp) was ˜27% higher in the cancerous tissues (p<0.05). Additionally, Fp, or NADH, or the redox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients.

  9. Optical redox imaging indices discriminate human breast cancer from normal tissues

    PubMed Central

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2016-01-01

    Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (p<0.05). The redox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (p<0.05). Additionally, Fp, or NADH, or the redox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

  10. Comparison of oral microbiota in tumor and non-tumor tissues of patients with oral squamous cell carcinoma

    PubMed Central

    2012-01-01

    Background Bacterial infections have been linked to malignancies due to their ability to induce chronic inflammation. We investigated the association of oral bacteria in oral squamous cell carcinoma (OSCC/tumor) tissues and compared with adjacent non-tumor mucosa sampled 5 cm distant from the same patient (n = 10). By using culture-independent 16S rRNA approaches, denaturing gradient gel electrophoresis (DGGE) and cloning and sequencing, we assessed the total bacterial diversity in these clinical samples. Results DGGE fingerprints showed variations in the band intensity profiles within non-tumor and tumor tissues of the same patient and among the two groups. The clonal analysis indicated that from a total of 1200 sequences characterized, 80 bacterial species/phylotypes were detected representing six phyla, Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Actinobacteria and uncultivated TM7 in non-tumor and tumor libraries. In combined library, 12 classes, 16 order, 26 families and 40 genera were observed. Bacterial species, Streptococcus sp. oral taxon 058, Peptostreptococcus stomatis, Streptococcus salivarius, Streptococcus gordonii, Gemella haemolysans, Gemella morbillorum, Johnsonella ignava and Streptococcus parasanguinis I were highly associated with tumor site where as Granulicatella adiacens was prevalent at non-tumor site. Streptococcus intermedius was present in 70% of both non-tumor and tumor sites. Conclusions The underlying changes in the bacterial diversity in the oral mucosal tissues from non-tumor and tumor sites of OSCC subjects indicated a shift in bacterial colonization. These most prevalent or unique bacterial species/phylotypes present in tumor tissues may be associated with OSCC and needs to be further investigated with a larger sample size. PMID:22817758

  11. Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung

    DOE PAGES

    Robinson, Lary A.; Jaing, Crystal J.; Campbell, Christine Pierce; ...

    2016-07-14

    Although ~20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung. Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFRmore » expression. Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non-neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours. Lastly, most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis.« less

  12. Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Robinson, Lary A.; Jaing, Crystal J.; Campbell, Christine Pierce

    Although ~20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung. Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFRmore » expression. Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non-neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours. Lastly, most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis.« less

  13. Gleaning Structure from Sound: The Role of Prosodic Contrast in Learning Non-Adjacent Dependencies

    ERIC Educational Resources Information Center

    Grama, Ileana C.; Kerkhoff, Annemarie; Wijnen, Frank

    2016-01-01

    The ability to detect non-adjacent dependencies (i.e. between "a" and "b" in "aXb") in spoken input may support the acquisition of morpho-syntactic dependencies (e.g. "The princess 'is' kiss'ing' the frog"). Functional morphemes in morpho-syntactic dependencies are often marked by perceptual cues that render…

  14. Discrimination of premalignant lesions and cancer tissues from normal gastric tissues using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Luo, Shuwen; Chen, Changshui; Mao, Hua; Jin, Shaoqin

    2013-06-01

    The feasibility of early detection of gastric cancer using near-infrared (NIR) Raman spectroscopy (RS) by distinguishing premalignant lesions (adenomatous polyp, n=27) and cancer tissues (adenocarcinoma, n=33) from normal gastric tissues (n=45) is evaluated. Significant differences in Raman spectra are observed among the normal, adenomatous polyp, and adenocarcinoma gastric tissues at 936, 1003, 1032, 1174, 1208, 1323, 1335, 1450, and 1655 cm-1. Diverse statistical methods are employed to develop effective diagnostic algorithms for classifying the Raman spectra of different types of ex vivo gastric tissues, including principal component analysis (PCA), linear discriminant analysis (LDA), and naive Bayesian classifier (NBC) techniques. Compared with PCA-LDA algorithms, PCA-NBC techniques together with leave-one-out, cross-validation method provide better discriminative results of normal, adenomatous polyp, and adenocarcinoma gastric tissues, resulting in superior sensitivities of 96.3%, 96.9%, and 96.9%, and specificities of 93%, 100%, and 95.2%, respectively. Therefore, NIR RS associated with multivariate statistical algorithms has the potential for early diagnosis of gastric premalignant lesions and cancer tissues in molecular level.

  15. [Stomach cancer in patients with systemic non-differentiated connective tissue dysplasia].

    PubMed

    Zil'ber, V S

    2014-01-01

    The study was designed as a comparative analysis of clinical and anamnestic data and results of morphological studies of surgically obtained tissues from 61 patients with stomach cancer (SC) aged 29-78 yr with (group 1) and without (group 2) signs of connective tissue dysplasia (CTD). The groups had an identical structure of SC hystological types, but in group 1 the tumours were localized mainly in the stomach body (60.6%, p < 0.05) and in group 2 in the cardia (32.1%, p < 0.05). In group 1, SC was more frequently associated with chronic (sometimes multiple) ulcers outside the tumor (18.2 compared with 7.1% in group 2). Comparative analysis revealed the following features of SC in patients with CTD: predominance of stigmatization signs in the urogenital system (57.6%) and gastrointestinal tract (42.4%), cyst formation in different organs (75.8%) especially in kidneys (48.5%), high frequency of gastric problems in medical history (chronic gastritis, ulcer disease) (72.7 and 35.7% in groups 1 and 2 respectively, p < 0.05) and concomitant pathology of urogenital system (42.4%, p < 0.05). These peculiarities may be used as the marker for the inclusion of patients in the risk group for SC. Taking into account plastic, morphogenetic, and protective functions of connective tissue under physiological conditions, the above epithelial-stromal relationships and peculiarities of reparative processes in gastric mucosa one can not exclude effect of CTD on gastric cancerogenesis. This implies the necessity of further studies.

  16. Non invasive radiofrequency diagnostics of cancer. The Bioscanner — Trimprob technology and clinical applications

    NASA Astrophysics Data System (ADS)

    Vedruccio, Clarbruno; Ricci Vedruccio, Carla

    2011-12-01

    A new paper by Pokorny, Vedruccio, Cifra, Kucera, titled Cancer physics: Diagnostics based on damped cellular elasto-electrical vibrations in microtubules, recently available on Eur. Biophys. J., discloses the mechanism of active grown cancer tissues interaction with a Non- Linear Resonance Interaction (NLRI) Bioscanner Trimprob diagnostic device that is certified and ready to be used to investigate suspected cases of disease and cancer. This technology spreads early capabilities of cancer detection by means of low level radiofrequency oscillations in UHF band. The system is based on an unique and extremely innovative non- linear radiofrequency oscillator working on 462-465 MHz plus the harmonics. The diseased tissues suspected of cancer, are irradiated by means of a handy probe near field emission, while a spectrum analyzer placed in the far field detects by means of a small antenna, the oscillator interaction within the tissues. The Bioscanner is characterized by a high dynamic range, in the order of 30 or more decibel, and is useful for detection of small cancer agglomerates, if used by a well trained operator. At the resonance, the free running oscillator locks-in on the specific interaction frequency, in a sharp frequency window centered on 462 MHz; the resulting effect is evidenced by a deep decrease of the 462 MHz spectral line propagation in the far field around the oscillator probe. The NLRI provides a selective characterization, like a sort of a electronic biopsy response of biologic tissues in support of modern imaging diagnostics. Further to existing literature describing methods for cancer detections by means of electromagnetic fields this paper shows this innovative in vivo medical diagnostic equipment and some clinical applications.

  17. Framework of collagen type I - vasoactive vessels structuring invariant geometric attractor in cancer tissues: insight into biological magnetic field.

    PubMed

    Díaz, Jairo A; Murillo, Mauricio F; Jaramillo, Natalia A

    2009-01-01

    In a previous research, we have described and documented self-assembly of geometric triangular chiral hexagon crystal-like complex organizations (GTCHC) in human pathological tissues. This article documents and gathers insights into the magnetic field in cancer tissues and also how it generates an invariant functional geometric attractor constituted for collider partners in their entangled environment. The need to identify this hierarquic attractor was born out of the concern to understand how the vascular net of these complexes are organized, and to determine if the spiral vascular subpatterns observed adjacent to GTCHC complexes and their assembly are interrelational. The study focuses on cancer tissues and all the macroscopic and microscopic material in which GTCHC complexes are identified, which have been overlooked so far, and are rigorously revised. This revision follows the same parameters that were established in the initial phase of the investigation, but with a new item: the visualization and documentation of external dorsal serous vascular bed areas in spatial correlation with the localization of GTCHC complexes inside the tumors. Following the standard of the electro-optical collision model, we were able to reproduce and replicate collider patterns, that is, pairs of left and right hand spin-spiraled subpatterns, associated with the orientation of the spinning process that can be an expansion or contraction disposition of light particles. Agreement between this model and tumor data is surprisingly close; electromagnetic spiral patterns generated were identical at the spiral vascular arrangement in connection with GTCHC complexes in malignant tumors. These findings suggest that the framework of collagen type 1 - vasoactive vessels that structure geometric attractors in cancer tissues with invariant morphology sets generate collider partners in their magnetic domain with opposite biological behavior. If these principles are incorporated into nanomaterial

  18. The anti-cancer peptide, PNC-27, induces tumor cell necrosis of a poorly differentiated non-solid tissue human leukemia cell line that depends on expression of HDM-2 in the plasma membrane of these cells.

    PubMed

    Davitt, Katlin; Babcock, Blake D; Fenelus, Maly; Poon, Chi Kong; Sarkar, Abhishek; Trivigno, Vincent; Zolkind, Paul A; Matthew, Sheena M; Grin'kina, Natalia; Orynbayeva, Zulfiya; Shaikh, Mohammad F; Adler, Victor; Michl, Josef; Sarafraz-Yazdi, Ehsan; Pincus, Matthew R; Bowne, Wilbur B

    2014-01-01

    We have developed the anti-cancer peptide, PNC-27, which is a membrane-active peptide that binds to the HDM-2 protein expressed in the cancer cell membranes of solid tissue tumor cells and induces transmembrane pore formation in cancer, but not in normal cells, resulting in tumor cell necrosis that is independent of p53 activity in these cells. We now extend our study to non-solid tissue tumor cells, in this case, a primitive, possible stem cell human leukemia cell line (K562) that is also p53-homozygously deleted. Our purpose was twofold: to investigate if these cells likewise express HDM-2 in their plasma membranes and to determine if our anti-cancer peptide induces tumor cell necrosis in these non-solid tissue tumor cells in a manner that depends on the interaction between the peptide and membrane-bound HDM-2. The anti-cancer activity and mechanism of PNC-27, which carries a p53 aa12-26-leader sequence connected on its carboxyl terminal end to a trans-membrane-penetrating sequence or membrane residency peptide (MRP), was studied against p53-null K562 leukemia cells. Murine leukocytes were used as a non-cancer cell control. Necrosis was determined by measuring the lactate dehydrogenase (LDH) release and apoptosis was determined by the detection of Caspases 3 and 7. Membrane colocalization of PNC-27 with HDM-2 was analyzed microscopically using fluorescently labeled antibodies against HDM-2 and PNC-27 peptides. We found that K562 cells strongly express HDM-2 protein in their membranes and that PNC-27 co-localizes with this protein in the membranes of these cells. PNC-27, but not the negative control peptide PNC-29, is selectively cytotoxic to K562 cells, inducing nearly 100 percent cell killing with LDH release. In contrast, this peptide had no effect on the lymphocyte control cells. The results suggest that HDM-2 is expressed in the membranes of non-solid tissue tumor cells in addition to the membranes of solid tissue tumor cells. Since K-562 cells appear to be

  19. Overexpression of paxillin induced by miR-137 suppression promotes tumor progression and metastasis in colorectal cancer

    PubMed Central

    Xu, Rui-Hua

    2013-01-01

    The deregulation of paxillin (PXN) has been involved in the progression and metastasis of different malignancies including colorectal cancer (CRC). miR-137 is frequently suppressed in CRC. PXN is predicted to be a direct target of miR-137 in CRC cells. On this basis, we hypothesized that overexpression of PXN induced by suppression of miR-137 may promote tumor progression and metastasis and predicts poor prognosis. We detected the expression of PXN and miR-137 in clinical tumor tissues by immunohistochemical analysis and real-time PCR, positive PXN staining was observed in 198 of the 247 (80.1%) cases, whereas no or weak PXN staining was observed in the adjacent non-cancerous area. Higher level of PXN messenger RNA (mRNA) and lower level of miR-137 was observed in cancer tissues than adjacent non-cancerous tissues. High expression of PXN and low expression of miR-137 was associated with aggressive tumor phenotype and adverse prognosis. Moreover, the expression of PXN was negatively correlated with miR-137 expression. A dual-luciferase reporter gene assay validated that PXN was a direct target of miR-137. The use of miR-137 mimics or inhibitor could decrease or increase PXN mRNA and protein levels in CRC cell lines. Knockdown of PXN or ectopic expression of miR-137 could markedly inhibit cell proliferation, migration and invasion in vitro and repress tumor growth and metastasis in vivo. Taken together, these results demonstrated that overexpression of PXN induced by suppression of miR-137 promotes tumor progression and metastasis and could serve as an independent prognostic indicator in CRC patients. PMID:23275153

  20. Recurrent triple-negative breast cancer (TNBC) tissues contain a higher amount of phosphatidylcholine (32:1) than non-recurrent TNBC tissues

    PubMed Central

    Masaki, Noritaka; Takei, Shiro; Horikawa, Makoto; Matsushita, Shoko; Sugiyama, Eiji; Ogura, Hiroyuki; Shiiya, Norihiko; Setou, Mitsutoshi

    2017-01-01

    Triple-negative breast cancer (TNBC) is one of the breast cancer subtype that displays a high risk of early recurrence and short overall survival. Improvement of the prognosis of patients with TNBC requires identifying a predictive factor of recurrence, which would make it possible to provide beneficial personalized treatment. However, no clinically reliable predictive factor is currently known. In this study, we investigated the predictive factor of recurrence in TNBC using matrix-assisted laser desorption/ionization-imaging mass spectrometry for lipid profiling of breast cancer specimens obtained from three and six patients with recurrent and non-recurrent TNBC, respectively. The signal for phosphatidylcholine (PC) (32:1) at m/z 732.5 was significantly higher in the recurrence group compared to the non-recurrence group (P = 0.024). PC (32:1) was more abundant in the cancer epithelial area than it was in the surrounding stroma, suggesting that abnormal lipid metabolism was associated with malignant transformation. Our results indicate PC (32:1) as a candidate predictive factor of TNBC recurrence. A future prospective study investigating whether personalized therapy based on PC (32:1) intensity improves the prognosis of patients with TNBC is recommended. PMID:28832678

  1. NON-NAVIGABLE STREAMS AND ADJACENT WETLANDS: ADDRESSING SCIENCE NEEDS FOLLOWING THE SUPREME COURT'S RAPANOS DECISION

    EPA Science Inventory

    In June of 2006, the US Supreme Court ruled in two cases concerning jurisdiction under the Clean Water Act (CWA). The decisions suggest that hydrological permanence of non-navigable streams and adjacent wetlands (NNSAWs) and their effects on the chemical, physical, and biological...

  2. [Tripartite-motif protein 25 and pyruvate kinase M2 protein expression in non-small cell lung cancer].

    PubMed

    Jing, Huai-Zhi; Qiu, Feng; Chen, Shi-Zhi; Su, Lin; Qu, Can

    2015-03-01

    To investigate the expression of tripartite-motif protein 25 (TRIM25) and pyruvate kinase M2 (PKM2) protein in non-small cell lung cancer (NSCLC) and explore their role in the occurrence and progression of NSCLC. The expressions of TRIM25 and PKM2 protein were detected in 60 NSCLC specimens and 20 adjacent normal lung tissue (>5 cm from the lesions) with immunofluorescence histochemical method and in 10 fresh specimens of NSCLC with Western blotting. The results were analyzed in relation with the clinicopathological features of the patients. The positivity rates of TRIM25 expression was 45% in the 60 lung carcinoma specimens, significantly higher than that in the 20 normal lung tissues (10%, P=0.005). TRIM25 protein was expressed in 28.6% of lung adenocarcinoma tissues and in 59.4% of squamous carcinoma tissues (P=0.017). TRIM25 protein expression was positively correlated with the TNM stages and lymph node metastasis of NSCLC (P<0.05). The expressions of PKM2 protein in 60 cases of lung carcinoma was 73.3%,while in 20 cases of normal lung tissues the expressions was 30%(P=0.001). The positivity rates of PKM2 expression differed significantly between lung adenocarcinoma and squamous carcinoma (57.1% vs 87.5%, P=0.008). An inverse correlation was noted between TRIM25 and PKM2 expressions (P=0.026). TRIM25 and PKM2 protein may participate in the occurrence and progression of NSCLC, and their expressions are inversely correlated.

  3. Defining Genomic Changes in Triple-Negative Breast Cancer in Women of African Descent

    DTIC Science & Technology

    2012-06-01

    African and African - American breast cancer cases. Gene Expression Array Studies The 31 triple negative Kijabe samples were... American Adjacent Normal Breast Tissue PI: Pegram & Baumbach Defining Genomic Changes in Triple Negative Breast Cancer in Women of African ...Tissues from African - American and East African Patients with Triple Negative Breast

  4. Association between EML4-ALK fusion gene and thymidylate synthase mRNA expression in non-small cell lung cancer tissues

    PubMed Central

    XU, CHUN-WEI; WANG, GANG; WANG, WU-LONG; GAO, WEN-BIN; HAN, CHUAN-JUN; GAO, JING-SHAN; ZHANG, LI-YING; LI, YANG; WANG, LIN; ZHANG, YU-PING; TIAN, YU-WANG; QI, DONG-DONG

    2015-01-01

    This study aimed to investigate the association of the mRNA expression of the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene with that of thymidylate synthase (TYMS) in non-small cell lung cancer (NSCLC) tissues. Quantitative polymerase chain reaction was used to detect the expression of EML4-ALK fusion gene and TYMS mRNA in 257 cases of NSCLC. The positive rate of EML4-ALK fusion gene was 4.28% in the NSCLC tissues (11/257), and was higher in nonsmokers than in smokers (P<0.05); TYMS mRNA expression was detected in 63.42% (163/257) of cases. An association of the EML4-ALK fusion gene with TYMS expression was detected; a low expression level of TYMS mRNA was observed more frequently when the EML4-ALK fusion gene was present than when it was not detected (P<0.05). In conclusion, patients positive for the EML4-ALK fusion gene in NSCLC tissues are likely to have a low expression level of TYMS, and may benefit from the first-line chemotherapy drug pemetrexed. PMID:26136951

  5. Association between EML4-ALK fusion gene and thymidylate synthase mRNA expression in non-small cell lung cancer tissues.

    PubMed

    Xu, Chun-Wei; Wang, Gang; Wang, Wu-Long; Gao, Wen-Bin; Han, Chuan-Jun; Gao, Jing-Shan; Zhang, Li-Ying; Li, Yang; Wang, Lin; Zhang, Yu-Ping; Tian, Yu-Wang; Qi, Dong-Dong

    2015-06-01

    This study aimed to investigate the association of the mRNA expression of the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene with that of thymidylate synthase (TYMS) in non-small cell lung cancer (NSCLC) tissues. Quantitative polymerase chain reaction was used to detect the expression of EML4-ALK fusion gene and TYMS mRNA in 257 cases of NSCLC. The positive rate of EML4-ALK fusion gene was 4.28% in the NSCLC tissues (11/257), and was higher in nonsmokers than in smokers (P<0.05); TYMS mRNA expression was detected in 63.42% (163/257) of cases. An association of the EML4-ALK fusion gene with TYMS expression was detected; a low expression level of TYMS mRNA was observed more frequently when the EML4-ALK fusion gene was present than when it was not detected (P<0.05). In conclusion, patients positive for the EML4-ALK fusion gene in NSCLC tissues are likely to have a low expression level of TYMS, and may benefit from the first-line chemotherapy drug pemetrexed.

  6. Correlation of circular RNA abundance with proliferation--exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues.

    PubMed

    Bachmayr-Heyda, Anna; Reiner, Agnes T; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Bachleitner-Hofmann, Thomas; Mesteri, Ildiko; Grunt, Thomas W; Zeillinger, Robert; Pils, Dietmar

    2015-01-27

    Circular RNAs are a recently (re-)discovered abundant RNA species with presumed function as miRNA sponges, thus part of the competing endogenous RNA network. We analysed the expression of circular and linear RNAs and proliferation in matched normal colon mucosa and tumour tissues. We predicted >1,800 circular RNAs and proved the existence of five randomly chosen examples using RT-qPCR. Interestingly, the ratio of circular to linear RNA isoforms was always lower in tumour compared to normal colon samples and even lower in colorectal cancer cell lines. Furthermore, this ratio correlated negatively with the proliferation index. The correlation of global circular RNA abundance (the circRNA index) and proliferation was validated in a non-cancerous proliferative disease, idiopathic pulmonary fibrosis, ovarian cancer cells compared to cultured normal ovarian epithelial cells, and 13 normal human tissues. We are the first to report a global reduction of circular RNA abundance in colorectal cancer cell lines and cancer compared to normal tissues and discovered a negative correlation of global circular RNA abundance and proliferation. This negative correlation seems to be a general principle in human tissues as validated with three different settings. Finally, we present a simple model how circular RNAs could accumulate in non-proliferating cells.

  7. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    PubMed Central

    Hellwinkel, Olaf J. C.; Sellier, Christina; Sylvester, Yu-Mi Jessica; Brase, Jan C.; Isbarn, Hendrik; Erbersdobler, Andreas; Steuber, Thomas; Sültmann, Holger; Schlomm, Thorsten; Wagner, Christina

    2013-01-01

    We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ. PMID:23459235

  8. Non-Adjacent Consonant Sequence Patterns in English Target Words during the First-Word Period

    ERIC Educational Resources Information Center

    Aoyama, Katsura; Davis, Barbara L.

    2017-01-01

    The goal of this study was to investigate non-adjacent consonant sequence patterns in target words during the first-word period in infants learning American English. In the spontaneous speech of eighteen participants, target words with a Consonant-Vowel-Consonant (C[subscript 1]VC[subscript 2]) shape were analyzed. Target words were grouped into…

  9. Identification of differentially expressed circular RNAs in human colorectal cancer.

    PubMed

    Zhang, Peili; Zuo, Zhigui; Shang, Wenjing; Wu, Aihua; Bi, Ruichun; Wu, Jianbo; Li, Shaotang; Sun, Xuecheng; Jiang, Lei

    2017-03-01

    Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p < 0.0001) and hsa_circRNA_104700 ( p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p < 0.0001) and 0.616 ( p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.

  10. Increased thyroid cancer incidence in a basaltic volcanic area is associated with non-anthropogenic pollution and biocontamination.

    PubMed

    Malandrino, Pasqualino; Russo, Marco; Ronchi, Anna; Minoia, Claudio; Cataldo, Daniela; Regalbuto, Concetto; Giordano, Carla; Attard, Marco; Squatrito, Sebastiano; Trimarchi, Francesco; Vigneri, Riccardo

    2016-08-01

    The increased thyroid cancer incidence in volcanic areas suggests an environmental effect of volcanic-originated carcinogens. To address this problem, we evaluated environmental pollution and biocontamination in a volcanic area of Sicily with increased thyroid cancer incidence. Thyroid cancer epidemiology was obtained from the Sicilian Regional Registry for Thyroid Cancer. Twenty-seven trace elements were measured by quadrupole mass spectrometry in the drinking water and lichens (to characterize environmental pollution) and in the urine of residents (to identify biocontamination) in the Mt. Etna volcanic area and in adjacent control areas. Thyroid cancer incidence was 18.5 and 9.6/10(5) inhabitants in the volcanic and the control areas, respectively. The increase was exclusively due to the papillary histotype. Compared with control areas, in the volcanic area many trace elements were increased in both drinking water and lichens, indicating both water and atmospheric pollution. Differences were greater for water. Additionally, in the urine of the residents of the volcanic area, the average levels of many trace elements were significantly increased, with values higher two-fold or more than in residents of the control area: cadmium (×2.1), mercury (×2.6), manganese (×3.0), palladium (×9.0), thallium (×2.0), uranium (×2.0), vanadium (×8.0), and tungsten (×2.4). Urine concentrations were significantly correlated with values in water but not in lichens. Our findings reveal a complex non-anthropogenic biocontamination with many trace elements in residents of an active volcanic area where thyroid cancer incidence is increased. The possible carcinogenic effect of these chemicals on the thyroid and other tissues cannot be excluded and should be investigated.

  11. Long non-coding RNA taurine-upregulated gene 1 predicts unfavorable prognosis, promotes cells proliferation, and inhibits cells apoptosis in epithelial ovarian cancer.

    PubMed

    Li, Tong-Huai; Zhang, Jing-Jing; Liu, Shao-Xiao; Chen, Yan

    2018-05-01

    The aim of this study was to evaluate the correlation of long non-coding RNAs (lncRNAs) taurine-upregulated gene 1 (TUG1) with clinicopathological characteristics as well as overall survival (OS) in epithelial ovarian cancer (EOC) patients, and investigate its function in EOC cells proliferation and apoptosis in vitro.LncRNA TUG1 expressions were detected in tumor tissues and paired adjacent tissues obtained from 96 EOC patients. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor plasmids were transfected into SKOV3 cells. CKK-8, annexin V-FITC-propidium iodide, qPCR and western blot assays were performed to detect cells proliferation, cells apoptosis, RNA expression, and protein expression, respectively.LncRNA TUG1 expression was higher in tumor tissue compared to paired adjacent tissue (P < .001), and it was positively correlated with pathological grade (P = .022), tumor size (P = .011) and FIGO stage (P < .001). Kaplan-Meier curve showed that lncRNA TUG1 high expression was associated with worse OS (P = .003). Multivariate Cox analysis indicated that lncRNA TUG1 high expression (vs. low expression) (P = .035) was independently predictive factor for shorter OS. In vitro, cells proliferation was promoted after treatment with lncRNA TUG1 mimic and was suppressed after treatment with lncRNA TUG1 inhibitor. In addition, cells apoptosis rate was decreased in lncRNA TUG1 mimic group compared to NC1 mimic, and increased in lncRNA TUG1 inhibitor group compared to NC2 inhibitor.In conclusion, lncRNA TUG1 is positively correlated with advanced disease and poor prognosis, and it promotes cells proliferation and inhibits cells apoptosis in EOC cells.

  12. Genetic Contribution to Non-Squamous, Non-Small Cell Lung Cancer in Non-Smokers.

    PubMed

    Carr, Shamus R; Akerley, Wallace; Cannon-Albright, Lisa

    2018-04-04

    Lung carcinogenesis is strongly influenced by environmental and heritable factors. The genetic contribution to the different histologies is unknown. A population-based computerized genealogy resource linked to a statewide cancer registry of lung cancer cases (n=5408) was analyzed to evaluate the heritable contribution to lung cancer histology in smoking (n=1751) and non-smoking cases (n=818). Statistical methods were used to test for significant excess relatedness of lung cancer cases. Significant excess distant relatedness was observed for all lung cancer histology subgroups analyzed except the small cell lung cancer subset (p=0.213). When smoking and non-smoking histologic subsets of lung cancer were considered, excess relatedness was observed only in non-smoking NSCLC (n=653; p=0.026) and, particularly, in those non-smokers with non-squamous histology (n=561; p=0.036). Sixty one pedigrees were identified which demonstrated a significant excess risk of non-smoking, non-squamous lung cancer cases; and an excess of female cases was observed among the cases in these high-risk pedigrees. This analysis supports a genetic predisposition to lung cancer carcinogenesis in non-smoking, non-squamous NSCLC cases. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  13. Real time cancer prediction based on objective tissue compliance measurement in endoscopic surgery.

    PubMed

    Fakhry, Morkos; Bello, Fernando; Hanna, George B

    2014-02-01

    To investigate the feasibility of real time cancer tissue diagnosis intraoperatively based on in vivo tissue compliance measurements obtained by a recently developed laparoscopic smart device. Cancer tissue is stiffer than its normal counterpart. Modern forms of remote surgery such as laparoscopic and robotic surgical techniques diminish direct assessment of this important tissue property. In vivo human tissue compliance of the normal and cancer gastrointestinal tissue is unknown. A Clinical Real Time Tissue Compliance Mapping System (CRTCMS) with a predictive power comparable to the human hand and useable in routine surgical practice has been recently developed. The CRTCMS is employed in the operating theater to collect data from 50 patients undergoing intra-abdominal surgical interventions [40 men, 10 women, aged between 32 and 89 (mean = 66.4, range = 57)]. This includes 10 esophageal and 27 gastric cancer patients. A total of 1212 compliance measurements of normal and cancerous in vivo gastrointestinal tissues were taken. The data were used to calibrate the CRTCMS to predict cancerous tissue in a further 12 patients (3 cancer esophagus and 9 cancer stomach) involving 175 measurements. The system demonstrated a high prediction power to diagnose cancer tissue in real time during routine surgical procedures (sensitivity = 98.7%, specificity = 99%). An in vivo human tissue compliance data bank of the gastrointestinal tract was produced. Real time cancer diagnosis based on in vivo tissue compliance measurements is feasible. The reported data open new avenues in cancer diagnostics, surgical robotics, and development of more realistic surgical simulators.

  14. Noninvasive detection of skin cancers by measuring optical properties of tissues

    NASA Astrophysics Data System (ADS)

    Wang, Lihong V.; Jacques, Steven L.

    1995-05-01

    Skin cancer is the most frequently occurring cancer of all cancers. Each yea rover 500,000 new cases of skin cancer will be detected. A high percentage of skin cancers are diseases in which fatalities can be all but eliminated and morbidity reduced if detected early and treated properly. These skin lesions are distinguished generally by subjective visual inspection and their definitive diagnosis requires time-consuming expensive histopathological evaluation of excisional or incisional biopsies. In vivo experimental evidence published in the literature has shown that cancerous skin lesions have different total diffuse reflectance spectra than non- cancerous lesions or normal skin. Therefore, cancerous skin lesions may be differentiated from non-cancerous skin lesions by comparing the optical properties of the skin lesions with those of the surrounding normal skin sites, where the optical properties of the normal skin sites are used to account for different types of skin or different areas of skin. We have demonstrated that the effect of melanin concentration on the diffuse reflectance may be removed by extrapolating the reflectance at different wavelengths to an apparent pivot point. Because the concentration of melanin does not indicate malignancy, the removal of its effect is important to avoid false detection. The total diffuse reflectance depends on the albedo and anisotropy of tissues. Therefore, the total diffuse reflectance will remain the same as long as the anisotropy and the ratio between the absorption coefficient and the reduced scattering coefficient remain the same. Separating the absorption and scattering effects should enhance the detection sensitivity of skin cancers.

  15. Green Tea Polyphenols and Metabolites in Prostatectomy Tissue: Implications for Cancer Prevention

    PubMed Central

    Wang, Piwen; Aronson, William J.; Huang, Min; Zhang, Yanjun; Lee, Ru-Po; Heber, David; Henning, Susanne M.

    2011-01-01

    Epidemiologic, preclinical, and clinical trials suggest that green tea (GT) consumption may prevent prostate cancer via the action of green tea polyphenols including (-)-epigallocatechin-3-gallate (EGCG). In order to study the metabolism and bioactivity of green tea polyphenols in human prostate tissue, men with clinically localized prostate cancer consumed 6 cups of GT (n=8) daily or water (n=9) for 3-6 weeks prior to undergoing radical prostatectomy. Using high performance liquid chromatography 4″-O-methyl EGCG (4″-MeEGCG) and EGCG were identified in comparable amounts, and (-)-epicatechin-3-gallate (ECG) in lower amounts in prostatectomy tissue from men consuming GT (38.9 ± 19.5, 42.1 ± 32.4, and 17.8 ± 10.1 pmol/g tissue, respectively). The majority of EGCG and other green tea polyphenols were not conjugated. Green tea polyphenols were not detected in prostate tissue or urine from men consuming water preoperatively. In the urine of men consuming GT, 50-60% of both (-)-epigallocatechin (EGC) and (-)-epicatechin were present in methylated form with 4′-O-MeEGC being the major methylated form of EGC. When incubated with EGCG LNCaP prostate cancer cells were able to methylate EGCG to 4″-MeEGCG. The capacity of 4″-MeEGCG to inhibit proliferation and NF-κB activation and induce apoptosis in LNCaP cells was decreased significantly compared to EGCG. In summary, methylated and non-methylated forms of EGCG are detectable in prostate tissue following a short-term GT intervention and the methylation status of EGCG may potentially modulate its preventive impact on prostate cancer, possibly based on genetic polymorphisms of catechol O-methyltransferase. PMID:20628004

  16. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

    PubMed

    Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

    2015-12-01

    Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. MiR-137 and its target TGFA modulate cell growth and tumorigenesis of non-small cell lung cancer.

    PubMed

    Liu, X; Chen, L; Tian, X-D; Zhang, T

    2017-02-01

    MiR-137 has been reported to serve as a tumor suppressor in non-small cell lung cancer (NSCLC). However, the potential mechanism remains largely unclear. The present study aimed to explore the potential molecular mechanisms by which miR-137 regulated NSCLC. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to quantify the expression levels of miR-137 in NSCLC tissues and cell lines. Dual-luciferase reporter assay was employed to confirm the specificity of miR-137 target genes. An MTT assay and flow cytometry were used to determine the rates of cell proliferation and cell cycle distribution. Furthermore, the effect of miR-137 up-regulation on TGFA expression was examined by western blot. miR-137 expression levels in NSCLC cell lines or tissue were significantly lower than in a normal human lung cell line or adjacent normal tissues. We further found that upregulation of miR-137 inhibited the proliferation of NSCLC cells, whereas silencing of miR-137 promoted the proliferation of NSCLC. Moreover, we identified TGFA as a direct target gene of miR-137 in NSCLC cell. Finally, Similarly, knockdown of TGFA led to the suppression of NSCLC cell proliferation. Overall, our findings indicated that miR-137 served as a tumor suppressor in NSCLC and its suppressive effect is mediated by repressing TGFA expression.

  18. Development of a multiplex methylation specific PCR suitable for (early) detection of non-small cell lung cancer

    PubMed Central

    Nawaz, Imran; Qiu, Xiaoming; Wu, Heng; Li, Yang; Fan, Yaguang; Hu, Li-Fu; Zhou, Qinghua; Ernberg, Ingemar

    2014-01-01

    Lung cancer is a worldwide health problem and a leading cause of cancer-related deaths. Silencing of potential tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event in the initiation and development of cancer. Thus, methylated cancer type-specific TSGs in DNA can serve as useful biomarkers for early cancer detection. We have now developed a “Multiplex Methylation Specific PCR” (MMSP) assay for analysis of the methylation status of multiple potential TSGs by a single PCR reaction. This method will be useful for early diagnosis and treatment outcome studies of non-small cell lung cancer (NSCLC). Genome-wide CpG methylation and expression microarrays were performed on lung cancer tissues and matched distant non-cancerous tissues from three NSCLC patients from China. Thirty-eight potential TSGs were selected and analyzed by methylation PCR on bisulfite treated DNA. On the basis of sensitivity and specificity, six marker genes, HOXA9, TBX5, PITX2, CALCA, RASSF1A, and DLEC1, were selected to establish the MMSP assay. This assay was then used to analyze lung cancer tissues and matched distant non-cancerous tissues from 70 patients with NSCLC, as well as 24 patients with benign pulmonary lesion as controls. The sensitivity of the assay was 99% (69/70). HOXA9 and TBX5 were the 2 most sensitive marker genes: 87% (61/70) and 84% (59/70), respectively. RASSF1A and DLEC1 showed the highest specificity at 99% (69/70). Using the criterion of identifying at least any two methylated marker genes, 61/70 cancer samples were positive, corresponding to a sensitivity of 87% and a specificity of 94%. Early stage I or II NSCLC could even be detected with a 100% specificity and 86% sensitivity. In conclusion, MMSP has the potential to be developed into a population-based screening tool and can be useful for early diagnosis of NSCLC. It might also be suitable for monitoring treatment outcome and recurrence. PMID:24937636

  19. Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer

    PubMed Central

    Boneberg, E-M; Legler, D F; Hoefer, M M; Öhlschlegel, C; Steininger, H; Füzesi, L; Beer, G M; Dupont-Lampert, V; Otto, F; Senn, H-J; Fürstenberger, G

    2009-01-01

    Background: Angiogenesis and lymphangiogenesis are considered to play key roles in tumour growth, progression and metastasis. However, targeting tumour angiogenesis in clinical trials showed only modest efficacy. We therefore scrutinised the concept of tumour angiogenesis and lymphangiogenesis by analysing the expression of crucial markers involved in these processes in primary breast cancer. Methods: We analysed the expression of angiogenic, lymphangiogenic or antiangiogenic factors, their respective receptors and specific markers for endothelial and lymphendothelial cells by quantitative real-time RT-PCR in primary breast cancer and compared the expression profiles to non-cancerous, tumour-adjacent tissues and breast tissues from healthy women. Results: We found decreased mRNA amounts of major angiogenic and lymphangiogenic factors in tumour compared to healthy tissues, whereas antiangiogenic factors were upregulated. Concomitantly, angiogenic and lymphangiogenic receptors were downregulated in breast tumours. This antiangiogenic, antilymphangiogenic microenvironment was even more pronounced in aggressive tumours and accompanied by reduced amounts of endothelial and lymphatic endothelial cell markers. Conclusion: Primary breast tumours are not a site of highly active angiogenesis and lymphangiogenesis. Selection for tumour cells that survive with minimal vascular supply may account for this observation in clinical apparent tumours. PMID:19672262

  20. Sucrose Non-Fermenting Related Kinase Expression in Ovarian Cancer and Correlation with Clinical Features.

    PubMed

    Hopp, Elizabeth E; Cossette, Stephanie M; Kumar, Suresh N; Eastwood, Daniel; Ramchandran, Ramani; Bishop, Erin

    2017-08-09

    Sucrose non-fermenting related kinase (SNRK) is a serine/threonine kinase known to regulate cellular metabolism and adipocyte inflammation. Since alterations in adipocyte metabolism play a role in ovarian cancer metastasis, we investigated the expression of SNRK in benign and malignant human ovarian tissue using immunohistochemistry and qPCR. The number of SNRK positive (+) nuclei is increased in malignant tissue compared to benign tissue (21.03% versus 14.90%, p < .0431). The most strongly stained malignant SNRK+ nuclei were stage 1 compared to stage 2-4 disease. Differential expression of SNRK in early versus late stage disease suggests specific roles for SNRK in ovarian cancer metastasis.

  1. SHCBP1 is over-expressed in breast cancer and is important in the proliferation and apoptosis of the human malignant breast cancer cell line.

    PubMed

    Feng, Wen; Li, Hong-Chang; Xu, Ke; Chen, Ya-Feng; Pan, Li-Yun; Mei, Yi; Cai, Han; Jiang, Yi-Ming; Chen, Teng; Feng, Dian-Xu

    2016-08-01

    SHC SH2-binding protein 1, a member of Src homolog and collagen homolog (Shc) family, has been recently identified in different contexts in unbiased screening assays. It has been reported to be over-expressed in several malignant cancers. Immunohistochemistry of SHCBP1 on 128 breast cancer tissues and adjacent normal tissues were used to evaluate the prognostic significance of SHCBP1. Survival analyses were performed by Kaplan-Meier method. CRISPR/CAS9 method was used to knockout SHCBP1 expression. CRISPR/CAS9 technology was used to knockout SHCBP1 in 2 breast cancer cell lines. MTT assay, BrdU assay, colony formation assay, cell cycle assay and apoptosis analysis in MCF-7 and MDA-MB-231 cell lines were carried out to evaluate the effects of SHCBP1 on breast cancer in vitro. Immunohistochemical analysis revealed SHCBP1 was significantly up-regulated in breast cancer tissues compared with adjacent normal tissues (82 of 128, 64%). Over-expressed SHCBP1 was correlated with advanced clinical stage and poorer survival. Ablation of SHCBP1 inhibited the proliferation in vitro. SHCBP1 knockout increased cyclin-dependent kinase inhibitor p21, and decreased the Cyclin B1 and CDK1. Our study suggests SHCBP1 is dysregulated expressed in breast cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of breast cancer. Copyright © 2016. Published by Elsevier B.V.

  2. SSX2-4 expression in early-stage non-small cell lung cancer.

    PubMed

    Greve, K B V; Pøhl, M; Olsen, K E; Nielsen, O; Ditzel, H J; Gjerstorff, M F

    2014-05-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies and performed immunohistochemical staining of 25 different normal tissues and 143 NSCLCs. The antibodies differed in binding to two distinctive splice variants of SSX2 that exhibited different subcellular staining patterns, suggesting that the two splice variants display different functions. SSX2-4 expression was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Correlation of circular RNA abundance with proliferation – exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues

    PubMed Central

    Bachmayr-Heyda, Anna; Reiner, Agnes T.; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Bachleitner-Hofmann, Thomas; Mesteri, Ildiko; Grunt, Thomas W.; Zeillinger, Robert; Pils, Dietmar

    2015-01-01

    Circular RNAs are a recently (re-)discovered abundant RNA species with presumed function as miRNA sponges, thus part of the competing endogenous RNA network. We analysed the expression of circular and linear RNAs and proliferation in matched normal colon mucosa and tumour tissues. We predicted >1,800 circular RNAs and proved the existence of five randomly chosen examples using RT-qPCR. Interestingly, the ratio of circular to linear RNA isoforms was always lower in tumour compared to normal colon samples and even lower in colorectal cancer cell lines. Furthermore, this ratio correlated negatively with the proliferation index. The correlation of global circular RNA abundance (the circRNA index) and proliferation was validated in a non-cancerous proliferative disease, idiopathic pulmonary fibrosis, ovarian cancer cells compared to cultured normal ovarian epithelial cells, and 13 normal human tissues. We are the first to report a global reduction of circular RNA abundance in colorectal cancer cell lines and cancer compared to normal tissues and discovered a negative correlation of global circular RNA abundance and proliferation. This negative correlation seems to be a general principle in human tissues as validated with three different settings. Finally, we present a simple model how circular RNAs could accumulate in non-proliferating cells. PMID:25624062

  4. Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene

    PubMed Central

    2013-01-01

    Background To understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes. Methods Two cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression. Results Two libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P < 0.05). The ERGIC3 protein was also over-expressed in lung cancer tissues and cultured cells, and expression of ERGIC3 was correlated with the differentiated degree and histological type of lung cancer. The up-regulation of ERGIC3 could promote cellular migration

  5. Comparison of multivariate analysis methods for extracting the paraffin component from the paraffin-embedded cancer tissue spectra for Raman imaging

    NASA Astrophysics Data System (ADS)

    Meksiarun, Phiranuphon; Ishigaki, Mika; Huck-Pezzei, Verena A. C.; Huck, Christian W.; Wongravee, Kanet; Sato, Hidetoshi; Ozaki, Yukihiro

    2017-03-01

    This study aimed to extract the paraffin component from paraffin-embedded oral cancer tissue spectra using three multivariate analysis (MVA) methods; Independent Component Analysis (ICA), Partial Least Squares (PLS) and Independent Component - Partial Least Square (IC-PLS). The estimated paraffin components were used for removing the contribution of paraffin from the tissue spectra. These three methods were compared in terms of the efficiency of paraffin removal and the ability to retain the tissue information. It was found that ICA, PLS and IC-PLS could remove the paraffin component from the spectra at almost the same level while Principal Component Analysis (PCA) was incapable. In terms of retaining cancer tissue spectral integrity, effects of PLS and IC-PLS on the non-paraffin region were significantly less than that of ICA where cancer tissue spectral areas were deteriorated. The paraffin-removed spectra were used for constructing Raman images of oral cancer tissue and compared with Hematoxylin and Eosin (H&E) stained tissues for verification. This study has demonstrated the capability of Raman spectroscopy together with multivariate analysis methods as a diagnostic tool for the paraffin-embedded tissue section.

  6. Tissue temperature distribution measurement by MRI and laser immunology for cancer treatment

    NASA Astrophysics Data System (ADS)

    Chen, Yichao; Gnyawali, Surya C.; Wu, Feng; Liu, Hong; Tesiram, Yasvir A.; Abbott, Andrew; Towner, Rheal A.; Chen, Wei R.

    2007-02-01

    In cancer treatment and immune response enhancement research, Magnetic Resonance Imaging (MRI) is an ideal method for non-invasive, three-dimensional temperature measurement. We used a 7.1-Tesla magnetic resonance imager for ex vivo tissues and small animal to determine temperature distribution of target tissue during laser irradiation. The feasibility of imaging is approved with high spatial resolution and high signal-noise- ratio. Tissue-simulating gel phantom gel, biological tissues, and tumor-bearing animals were used in the experiments for laser treatment and MR imaging. Thermal couple measurement of temperature in target samples was used for system calibration. An 805-nm laser was used to irradiate the samples with a laser power in the range of 1 to 2.5 watts. Using the MRI system and a specially developed processing algorithm, a clear temperature distribution matrix in the target tissue and surrounding tissue was obtained. The temperature profiles show that the selective laser photothermal effect could result in tissue temperature elevation in a range of 10 to 45 °C. The temperature resolution of the measurement was about 0.37°C including the total system error. The spatial resolution was 0.4 mm (128x128 pixels with field of view of 5.5x5.5 cm). The temperature distribution provided in vivo thermal information and future reference for optimizing dye concentration and irradiation parameters to achieve optimal thermal effects in cancer treatment.

  7. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

    PubMed

    Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

    2015-01-01

    To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

  8. Correlation between the methylation of APC gene promoter and colon cancer.

    PubMed

    Li, Bing-Qiang; Liu, Peng-Peng; Zhang, Cai-Hua

    2017-08-01

    The present study was planned to explore the correlation between the methylation of APC (adenomatous polyposis coli) and colon carcinogenesis. Colon cancer tissues and tumor-adjacent normal tissues of 60 colon cancer patients (who received surgical operation in our hospital from January 2012 to December 2014) were collected. SW1116 cells in human colon cancer tissues were selected for culturing. 5-aza-2c-deoxycytidine (5-aza-dC) was utilized as an inhibitor of the methylation for APC gene. Methylation specific PCR (MSP) was utilized for detection of APC methylation in SW1116 cells. The MTT and Transwell assays were performed to detect the effect of the methylation of APC gene on the proliferation and invasive abilities of SW1116 cells. The correlation between the methylation of APC gene and pathological parameters of colon cancer patients was analyzed. MSP results revealed that 41 cases (68.33%) showed methylation of APC gene in colon cancer tissues. No methylation of APC gene was found in tumor-adjacent normal tissues. 5-aza-dC was able to inhibit the methylation of APC gene in SW1116 cells. APC gene methylation was correlated with tumor size, differentiation degree, lymph node metastasis and Dukes staging. In conclusion, the levels of the methylation of APC in colon cancer tissues and SW1116 cells are relatively high. The methylation of APC promoted the proliferation and invasion abilities of SW1116 cells. Furthermore, methylation is correlated with a variety of clinicopathological features of colon cancer patients.

  9. Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non-Small Cell Lung Cancer Patients.

    PubMed

    Bruno, Tullia C; Ebner, Peggy J; Moore, Brandon L; Squalls, Olivia G; Waugh, Katherine A; Eruslanov, Evgeniy B; Singhal, Sunil; Mitchell, John D; Franklin, Wilbur A; Merrick, Daniel T; McCarter, Martin D; Palmer, Brent E; Kern, Jeffrey A; Slansky, Jill E

    2017-10-01

    Effective immunotherapy options for patients with non-small cell lung cancer (NSCLC) are becoming increasingly available. The immunotherapy focus has been on tumor-infiltrating T cells (TILs); however, tumor-infiltrating B cells (TIL-Bs) have also been reported to correlate with NSCLC patient survival. The function of TIL-Bs in human cancer has been understudied, with little focus on their role as antigen-presenting cells and their influence on CD4 + TILs. Compared with other immune subsets detected in freshly isolated primary tumors from NSCLC patients, we observed increased numbers of intratumoral B cells relative to B cells from tumor-adjacent tissues. Furthermore, we demonstrated that TIL-Bs can efficiently present antigen to CD4 + TILs and alter the CD4 + TIL phenotype using an in vitro antigen-presentation assay. Specifically, we identified three CD4 + TIL responses to TIL-Bs, which we categorized as activated, antigen-associated, and nonresponsive. Within the activated and antigen-associated CD4 + TIL population, activated TIL-Bs (CD19 + CD20 + CD69 + CD27 + CD21 + ) were associated with an effector T-cell response (IFNγ + CD4 + TILs). Alternatively, exhausted TIL-Bs (CD19 + CD20 + CD69 + CD27 - CD21 - ) were associated with a regulatory T-cell phenotype (FoxP3 + CD4 + TILs). Our results demonstrate a new role for TIL-Bs in NSCLC tumors in their interplay with CD4 + TILs in the tumor microenvironment, establishing them as a potential therapeutic target in NSCLC immunotherapy. Cancer Immunol Res; 5(10); 898-907. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    PubMed

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  11. Prostate-specific antigen (PSA) as a possible biomarker in non-prostatic cancer: A review.

    PubMed

    Pérez-Ibave, Diana Cristina; Burciaga-Flores, Carlos Horacio; Elizondo-Riojas, Miguel-Ángel

    2018-06-01

    Prostate-specific antigen (PSA) is a serine protease produced by epithelial prostatic cells and its main function is to liquefy seminal coagulum. Currently, PSA is a biomarker for the diagnosis and screening of prostate cancer and it was the first cancer biomarker approved by the FDA. The quantity and serum isoforms of male PSA, allows distinguishing between carcinoma and benign inflammatory disease of the prostate. Initially, it was thought that PSA was produced only by the prostate, and thus, a protein that was expressed exclusively in men. However, several authors report that PSA is a protein that is expressed by multiple non-prostatic tissues not only in men but also in women. Some authors also report that in women, the expression of this protein is highly related to breast and colon cancer and therefore can act as a possible biomarker for early detection, diagnosis and prognosis of these cancers in women. In this review, we will focus on the characteristics of the PSA at a molecular level, its current clinical implications, the expression of this protein in non-prostatic tissues, and its relationship with cancer, especially in women. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Genomic profiling of 766 cancer-related genes in archived esophageal normal and carcinoma tissues.

    PubMed

    Chen, Jing; Guo, Liping; Peiffer, Daniel A; Zhou, Lixin; Chan, Owen Tsan Mo; Bibikova, Marina; Wickham-Garcia, Eliza; Lu, Shih-Hsin; Zhan, Qimin; Wang-Rodriguez, Jessica; Jiang, Wei; Fan, Jian-Bing

    2008-05-15

    We employed the BeadArraytrade mark technology to perform a genetic analysis in 33 formalin-fixed, paraffin-embedded (FFPE) human esophageal carcinomas, mostly squamous-cell-carcinoma (ESCC), and their adjacent normal tissues. A total of 1,432 single nucleotide polymorphisms (SNPs) derived from 766 cancer-related genes were genotyped with partially degraded genomic DNAs isolated from these samples. This directly targeted genomic profiling identified not only previously reported somatic gene amplifications (e.g., CCND1) and deletions (e.g., CDKN2A and CDKN2B) but also novel genomic aberrations. Among these novel targets, the most frequently deleted genomic regions were chromosome 3p (including tumor suppressor genes FANCD2 and CTNNB1) and chromosome 5 (including tumor suppressor gene APC). The most frequently amplified genomic region was chromosome 3q (containing DVL3, MLF1, ABCC5, BCL6, AGTR1 and known oncogenes TNK2, TNFSF10, FGF12). The chromosome 3p deletion and 3q amplification occurred coincidently in nearly all of the affected cases, suggesting a molecular mechanism for the generation of somatic chromosomal aberrations. We also detected significant differences in germline allele frequency between the esophageal cohort of our study and normal control samples from the International HapMap Project for 10 genes (CSF1, KIAA1804, IL2, PMS2, IRF7, FLT3, NTRK2, MAP3K9, ERBB2 and PRKAR1A), suggesting that they might play roles in esophageal cancer susceptibility and/or development. Taken together, our results demonstrated the utility of the BeadArray technology for high-throughput genetic analysis in FFPE tumor tissues and provided a detailed genetic profiling of cancer-related genes in human esophageal cancer. (c) 2008 Wiley-Liss, Inc.

  13. Imaging of non-osteochondral tissues in osteoarthritis.

    PubMed

    Guermazi, A; Roemer, F W; Crema, M D; Englund, M; Hayashi, D

    2014-10-01

    The aim of this review is to describe imaging techniques for evaluation of non-osteochondral structures such as the synovium, menisci in the knee, labrum in the hip, ligaments and muscles and to review the literature from recent clinical and epidemiological studies of OA. This is a non-systematic narrative review of published literature on imaging of non-osteochondral tissues in OA. PubMed and MEDLINE search for articles published up to 2014, using the keywords osteoarthritis, synovitis, meniscus, labrum, ligaments, plica, muscles, magnetic resonance imaging (MRI), ultrasound, computed tomography (CT), scintigraphy, and positron emission tomography (PET). Published literature showed imaging of non-osteochondral tissues in OA relies primarily on MRI and ultrasound. The use of semiquantitative and quantitative imaging biomarkers of non-osteochondral tissues in clinical and epidemiological OA studies is reported. We highlight studies that have compared both imaging methodologies directly, and those that have established a relationship between imaging biomarkers and clinical outcomes. We provide recommendations as to which imaging protocols should be used to assess disease-specific changes regarding synovium, meniscus in the knee, labrum in the hip, and ligaments, and highlight potential pitfalls in their usage. MRI and ultrasound are currently the most useful imaging modalities for evaluation of non-osteochondral tissues in OA. MRI evaluation of any tissue needs to be performed using appropriate MR pulse sequences. Ultrasound may be particularly useful for evaluation of small joints of the hand. Nuclear medicine and CT play a limited role in imaging of non-osteochondral tissues in OA. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Identification of Specific miRNA Signature in Paired Sera and Tissue Samples of Indian Women with Triple Negative Breast Cancer

    PubMed Central

    Thakur, Seema; Grover, Rajesh K.; Gupta, Sanjay; Yadav, Ajay K.; Das, Bhudev C.

    2016-01-01

    Of several subtypes of breast cancer, triple negative breast cancer (TNBC) is a highly aggressive tumor that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor receptor 2 and shows a worst prognosis. The small noncoding RNAs (miRNAs) considered as master regulator of gene expression play a key role in cancer initiation, progression and drug resistance and have emerged as attractive molecular biomarkers for diagnosis, prognosis and treatment targets in cancer. We have done expression profiling of selected miRNAs in paired serum and tissue samples of TNBC patients and corresponding cell lines and compared with that of other subtypes, in order to identify novel serum miRNA biomarkers for early detection and progression of TNBC. A total of 85 paired tumor tissues and sera with an equal number of adjacent normal tissue margins and normal sera from age matched healthy women including tissue and sera samples from 15 benign fibroadenomas were employed for the study. We report for the first time an extremely high prevalence (73.9%) of TNBC in premenopausal women below 35 years of age and a significant altered expression of a panel of three specific oncogenic miRNAs- miR-21, miR-221, miR-210, and three tumor suppressor miRNAs- miR-195, miR-145 and Let-7a in both tissues and corresponding sera of TNBC patients when compared with triple positive breast cancer (TPBC) patients. While miR-21, miR-221 and miR-210 showed significant over-expression, miR-195 and miR-145 were downregulated and well correlated with various clinicopathological and demographic risk factors, tumor grade, clinical stage and hormone receptor status. Interestingly, despite being a known tumor suppressor, Let-7a showed a significant overexpression in TNBCs. It is suggested that this panel of six miRNA signature may serve as a minimally invasive biomarker for an early detection of TNBC patients. PMID:27404381

  15. A Non-Invasive Deep Tissue PH Monitor.

    DTIC Science & Technology

    1995-08-11

    disturbances in acid-base regulation may have serious effects on metabolic activity, circulation, and the central nervous system. Currently, acid-base...to tissue ischemia than is arterial pH. Consequently, a non-invasive deep tissue pH monitor has enormous value as a mechanism for rapid and effective ...achieved, and improve our understanding of what physical effects are important to successful non-invasive deep tissue pH monitoring. This last statement

  16. Migration-stimulating factor (MSF) is over-expressed in non-small cell lung cancer and promotes cell migration and invasion in A549 cells over-expressing MSF

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Deng, Xuefeng, E-mail: dengxfdoctor@hotmail.com; Department of Cardio-thoracic Surgery, Affiliated Hospital of Academy of Military Medical Sciences; Ma, Qunfeng

    Migration-stimulating factor (MSF), an oncofetal truncated isoform of fibronectin, is a potent stimulator of cell invasion. However, its distribution and motogenic role in non-small cell lung cancer (NSCLC) have never been identified. In this study, real-time PCR and immunohistochemical staining (IHC) were performed to detect MSF mRNA and protein levels in tumor tissues and matched adjacent tumor-free tissues. Furthermore, to examine the effect of MSF on invasiveness, MSF was upregulated in A549 cells. The invasiveness and viability of A549 cells were then determined using a transwell migration assay and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assays, respectively. The expression level ofmore » MSF in NSCLC tissue was markedly higher than in matched adjacent tumor-free tissue. Additionally, the level of MSF protein expression in stage III and IV NSCLC samples was higher than in stage I and II NSCLC samples. More importantly, we also demonstrated that migration and invasion of A549 cells increased substantially after upregulating MSF, although proliferation remained unchanged. Meanwhile, we found no correlation between increasing motility and invasiveness of MSF-overexpressing cells and expression levels and activities of matrix metalloprotease MMP-2 and MMP-9. Our current study shows that MSF plays a role in migration and invasion of A549 cells and suggests that MSF may be a potential biomarker of NSCLC progression. - Highlights: • MSF expression was upregulated in NSCLC and correlated with TNM stages. • MSF may be a new biomarker for NSCLC progression. • MSF promoted migration and invasion in A549 cells, independent of MMP-2/MMP-9 expression.« less

  17. Spectroscopic analysis of bladder cancer tissues using Fourier transform infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Al-Muslet, Nafie A.; Ali, Essam E.

    2012-03-01

    Bladder cancer is one of the most common cancers in Africa. It takes several days to reach a diagnosis using histological examinations of specimens obtained by endoscope, which increases the medical expense. Recently, spectroscopic analysis of bladder cancer tissues has received considerable attention as a diagnosis technique due to its sensitivity to biochemical variations in the samples. This study investigated the use of Fourier transform infrared (FTIR) spectroscopy to analyze a number of bladder cancer tissues. Twenty-two samples were collected from 11 patients diagnosed with bladder cancer from different hospitals without any pretreatment. From each patient two samples were collected, one normal and another cancerous. FTIR spectrometer was used to differentiate between normal and cancerous bladder tissues via changes in spectra of these samples. The investigations detected obvious changes in the bands of proteins (1650, 1550 cm-1), lipids (2925, 2850 cm-1), and nucleic acid (1080, 1236 cm-1). The results show that FTIR spectroscopy is promising as a rapid, accurate, nondestructive, and easy to use alternative method for identification and diagnosis of bladder cancer tissues.

  18. Effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice.

    PubMed

    Song, Lin; Zhou, Xin; Jia, Hong-Jun; Du, Mei; Zhang, Jin-Ling; Li, Liang

    2016-08-01

    To study the effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. hGC-MSCs group were given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, mRNA expression of proliferation, invasion, EMT-related molecules were determined. 4, 8, 12, 16, 20 d after intervention, tumor tissue volume of hGC-MSCs group were significantly higher than those of PBS group and the more the number of hGC-MSCs, the higher the tumor tissue volume; mRNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of hGC-MSCs group were higher than those of PBS group, and mRNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group. hGC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  19. The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial Pathology Tissue Resource.

    PubMed

    Zhu, Claire S; Huang, Wen-Yi; Pinsky, Paul F; Berg, Christine D; Sherman, Mark; Yu, Kelly J; Carrick, Danielle M; Black, Amanda; Hoover, Robert; Lenz, Petra; Williams, Craig; Hawkins, Laura; Chaloux, Matthew; Yurgalevitch, Susan; Mathew, Sunitha; Miller, Amy; Olivo, Vanessa; Khan, Asia; Pretzel, Shannon M; Multerer, Deborah; Beckmann, Patricia; Broski, Karen G; Freedman, Neal D

    2016-12-01

    Pathology tissue specimens with associated epidemiologic and clinical data are valuable for cancer research. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial undertook a large-scale effort to create a public resource of pathology tissues from PLCO participants who developed a cancer during the trial. Formalin-fixed paraffin-embedded tissue blocks were obtained from pathology laboratories on a loan basis for central processing of tissue microarrays, with additional free-standing tissue cores collected for nucleic acid extraction. Pathology tissue specimens were obtained for prostate cancer (n = 1,052), lung cancer (n = 434), colorectal cancer (n = 675) and adenoma (n = 658), ovarian cancer and borderline tumors (n = 212), breast cancer (n = 870), and bladder cancer (n = 204). The process of creating this resource was complex, involving multidisciplinary teams with expertise in pathology, epidemiology, information technology, project management, and specialized laboratories. Creating the PLCO tissue resource required a multistep process, including obtaining medical records and contacting pathology departments where pathology materials were stored after obtaining necessary patient consent and authorization. The potential to link tissue biomarkers to prospectively collected epidemiologic information, screening and clinical data, and matched blood or buccal samples offers valuable opportunities to study etiologic heterogeneity, mechanisms of carcinogenesis, and biomarkers for early detection and prognosis. The methods and protocols developed for this effort, and the detailed description of this resource provided here, will be useful for those seeking to use PLCO pathology tissue specimens for their research and may also inform future tissue collection efforts in other settings. Cancer Epidemiol Biomarkers Prev; 25(12); 1635-42. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. Cancer metabolism, stemness and tumor recurrence

    PubMed Central

    Curry, Joseph M.; Tuluc, Madalina; Whitaker-Menezes, Diana; Ames, Julie A.; Anantharaman, Archana; Butera, Aileen; Leiby, Benjamin; Cognetti, David M.; Sotgia, Federica; Lisanti, Michael P.; Martinez-Outschoorn, Ubaldo E.

    2013-01-01

    Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed to determine the metabolic state of proliferative cancer cells. Interestingly, cell proliferation in cancer cells, as marked by Ki-67 immunostaining, was strictly correlated with oxidative mitochondrial metabolism (OXPHOS) and the uptake of mitochondrial fuels, as detected via MCT1 expression (p < 0.001). More specifically, three metabolic tumor compartments were delineated: (1) proliferative and mitochondrial-rich cancer cells (Ki-67+/TOMM20+/COX+/MCT1+); (2) non-proliferative and mitochondrial-poor cancer cells (Ki-67−/TOMM20−/COX−/MCT1−); and (3) non-proliferative and mitochondrial-poor stromal cells (Ki-67−/TOMM20−/COX−/MCT1−). In addition, high oxidative stress (MCT4+) was very specific for cancer tissues. Thus, we next evaluated the prognostic value of MCT4 in a second independent patient cohort (n = 40). Most importantly, oxidative stress (MCT4+) in non-proliferating epithelial cancer cells predicted poor clinical outcome (tumor recurrence; p < 0.0001; log-rank test), and was functionally associated with FDG-PET avidity (p < 0.04). Similarly, oxidative stress (MCT4+) in tumor stromal cells was specifically associated with higher tumor stage (p < 0.03), and was a highly specific marker for cancer-associated fibroblasts (p < 0.001). We propose that oxidative stress is a key hallmark of tumor tissues that drives high-energy metabolism in adjacent proliferating mitochondrial-rich cancer cells, via the paracrine transfer of mitochondrial fuels (such as L-lactate and ketone bodies). New antioxidants and MCT4 inhibitors should be developed to metabolically target “three-compartment tumor metabolism” in head and neck cancers. It is remarkable that two “non-proliferating” populations of cells (Ki-67−/MCT4+) within the

  1. Evidence that breast tissue stiffness is associated with risk of breast cancer.

    PubMed

    Boyd, Norman F; Li, Qing; Melnichouk, Olga; Huszti, Ella; Martin, Lisa J; Gunasekara, Anoma; Mawdsley, Gord; Yaffe, Martin J; Minkin, Salomon

    2014-01-01

    Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer. Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors. After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements. An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement.

  2. Evidence That Breast Tissue Stiffness Is Associated with Risk of Breast Cancer

    PubMed Central

    Boyd, Norman F.; Li, Qing; Melnichouk, Olga; Huszti, Ella; Martin, Lisa J.; Gunasekara, Anoma; Mawdsley, Gord; Yaffe, Martin J.; Minkin, Salomon

    2014-01-01

    Background Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer. Methods Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors. Results After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements. Conclusion An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement. PMID:25010427

  3. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

    PubMed Central

    Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

    2015-01-01

    ABSTRACT Objective To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Methods Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. Results The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). Conclusion The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues. PMID:26761548

  4. BCCTBbp: the Breast Cancer Campaign Tissue Bank bioinformatics portal.

    PubMed

    Cutts, Rosalind J; Guerra-Assunção, José Afonso; Gadaleta, Emanuela; Dayem Ullah, Abu Z; Chelala, Claude

    2015-01-01

    BCCTBbp (http://bioinformatics.breastcancertissue bank.org) was initially developed as the data-mining portal of the Breast Cancer Campaign Tissue Bank (BCCTB), a vital resource of breast cancer tissue for researchers to support and promote cutting-edge research. BCCTBbp is dedicated to maximising research on patient tissues by initially storing genomics, methylomics, transcriptomics, proteomics and microRNA data that has been mined from the literature and linking to pathways and mechanisms involved in breast cancer. Currently, the portal holds 146 datasets comprising over 227,795 expression/genomic measurements from various breast tissues (e.g. normal, malignant or benign lesions), cell lines and body fluids. BCCTBbp can be used to build on breast cancer knowledge and maximise the value of existing research. By recording a large number of annotations on samples and studies, and linking to other databases, such as NCBI, Ensembl and Reactome, a wide variety of different investigations can be carried out. Additionally, BCCTBbp has a dedicated analytical layer allowing researchers to further analyse stored datasets. A future important role for BCCTBbp is to make available all data generated on BCCTB tissues thus building a valuable resource of information on the tissues in BCCTB that will save repetition of experiments and expand scientific knowledge. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. [Expression of Rictor and mTOR in colorectal cancer and their clinical significance].

    PubMed

    Wang, Li-Feng; Chen, Hai-Jin; Yu, Jin-Long; Qi, Jia; Lin, Xiao-Hua; Zou, Zhao-Wei

    2016-03-01

    To explore the expression of Rictor and mTOR in the colorectal cancer and their clinical significance. The expression levels of Rictor and mTOR in HCT116, SW480, LoVo and HCoEpiC cells were detected by indirect immunofluorescence and Western blotting. Sixty-two paraffin-embedded surgical specimens of colorectal cancer tissue and adjacent tissues were examined for Rictor expression using immunohistochemistry. The association of the expression levels of Rictor protein with the clinicopathologic features and the overall survival of the patients was analyzed. The expression level of Rictor was significantly higher in colorectal cancer tissues than in the adjacent tissues (P<0.05). The expression levels of Rictor and mTOR in the colon cancer cell lines were higher than those in human normal colon epithelial cell line HCoEpiC. The expression of Rictor was correlated with Dukes stage and lymphatic metastasis of the tumors but not with other clinicopathological parameter (P>0.05). Patients with Rictor expression had a lower overall survival rate than those without Rictor expression. Rictor overexpression is associated with the carcinogenesis and progression of colorectal cancer and can be an independent indicator for evaluating the prognosis of colorectal cancer patients.

  6. Identifying DNA Methylation Features that Underlie Prostate Cancer Disparities

    DTIC Science & Technology

    2016-10-01

    Report We will continue to recruit African American patients and bank their prostate tissue . We will continue dissecting tumor samples into tumor...in prostate tumors and adjacent normal tissue derived from both AA and EA individuals. We will determine if DNA methylation patterns in prostate... tissue (both cancerous and normal tissue ) differ between AA and EA individuals. We will also identify methylation features that differ between tumor

  7. Differential expression of VEGF ligands and receptors in prostate cancer.

    PubMed

    Woollard, David J; Opeskin, Kenneth; Coso, Sanja; Wu, Di; Baldwin, Megan E; Williams, Elizabeth D

    2013-05-01

    Prostate cancer disseminates to regional lymph nodes, however the molecular mechanisms responsible for lymph node metastasis are poorly understood. The vascular endothelial growth factor (VEGF) ligand and receptor family have been implicated in the growth and spread of prostate cancer via activation of the blood vasculature and lymphatic systems. The purpose of this study was to comprehensively examine the expression pattern of VEGF ligands and receptors in the glandular epithelium, stroma, lymphatic vasculature and blood vessels in prostate cancer. The localization of VEGF-A, VEGF-C, VEGF-D, VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 was examined in cancerous and adjacent benign prostate tissue from 52 subjects representing various grades of prostate cancer. Except for VEGFR-2, extensive staining was observed for all ligands and receptors in the prostate specimens. In epithelial cells, VEGF-A and VEGFR-1 expression was higher in tumor tissue compared to benign tissue. VEGF-D and VEGFR-3 expression was significantly higher in benign tissue compared to tumor in the stroma and the endothelium of lymphatic and blood vessels. In addition, the frequency of lymphatic vessels, but not blood vessels, was lower in tumor tissue compared with benign tissue. These results suggest that activation of VEGFR-1 by VEGF-A within the carcinoma, and activation of lymphatic endothelial cell VEGFR-3 by VEGF-D within the adjacent benign stroma may be important signaling mechanisms involved in the progression and subsequent metastatic spread of prostate cancer. Thus inhibition of these pathways may contribute to therapeutic strategies for the management of prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

  8. Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma.

    PubMed

    Gan, Yuanyuan; Han, Nana; He, Xiaoqin; Yu, Jiajun; Zhang, Meixia; Zhou, Yujie; Liang, Huiling; Deng, Junjian; Zheng, Yongfa; Ge, Wei; Long, Zhixiong; Xu, Ximing

    2017-06-01

    Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, especially cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in hepatocellular carcinoma have not been extensively studied. The long non-coding RNA CASC2 (cancer susceptibility candidate 2) has been characterised as a tumour suppressor in endometrial cancer and gliomas. However, the role and function of CASC2 in hepatocellular carcinoma remain unknown. In this study, using quantitative real-time polymerase chain reaction, we confirmed that CASC2 expression was downregulated in 50 hepatocellular carcinoma cases (62%) and in hepatocellular carcinoma cell lines compared with the paired adjacent tissues and normal liver cells. In vitro experiments further demonstrated that overexpressed CASC2 decreased hepatocellular carcinoma cell proliferation, migration and invasion as well as promoted apoptosis via inactivating the mitogen-activated protein kinase signalling pathway. Our findings demonstrate that CASC2 could be a useful tumour suppressor factor and a promising therapeutic target for hepatocellular carcinoma.

  9. Testes-specific protease 50 as an independent risk factor for poor prognosis in patients with non-small cell lung cancer

    PubMed Central

    Qiao, Wen-Liang; Shi, Bo-Wen; Han, Yu-Dong; Tang, Hua-Mei; Lin, Jun; Hu, Hai-Yang; Lin, Qiang

    2018-01-01

    Testes-specific protease 50 (TSP50) is normally expressed in the testes and is overexpressed in various types of human cancers, including breast cancer, colorectal carcinoma and laryngocarcinoma. However, little has been reported on the association between TSP50 and non-small cell lung cancer (NSCLC). The present study aimed to detect TSP50 expression in 198 strict follow-up cases of paired NSCLC and 15 cases of normal lung parenchymal specimens using immunohistochemical staining. The expression levels of TSP50 were then correlated with the clinicopathological factors of NSCLC to assess its potential diagnostic and prognostic value. The relationship between TSP50 expression and the clinicopathological parameters of NSCLC was evaluated using χ2 and Fisher's exact tests. Survival rates for the overall population (n=198) were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox's proportional hazards regression model. P<0.05 was considered to indicate a statistically significant difference. The expression of TSP50 was significantly increased in NSCLC tissue compared with in adjacent non-tumor or normal lung parenchymal tissue (P<0.001). A significant association was revealed between high expression levels of TSP50 and clinicopathological characteristics including tumor differentiation (P=0.012), late tumor status (P=0.004) and late tumor node metastasis stage (P=0.026), as well as a reduced disease free survival (P=0.009) and overall survival rate (P=0.002) in all patients with NSCLC. Multivariate analyses demonstrated that high TSP50 expression in tumor tissues was significantly associated with a shorter disease-free survival rate [hazard ratio (HR) =1.590, 95% confidence interval (CI): 1.035–2.441], and with a shorter overall survival rate (HR=1.814; 95% CI: 1.156–2.846). In conclusion, the present data demonstrated that increased TSP50 protein expression may be a potential predictor of early recurrence

  10. The nanomechanical signature of liver cancer tissues and its molecular origin

    NASA Astrophysics Data System (ADS)

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

    2015-07-01

    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus

  11. Dynamic biochemical tissue analysis detects functional L-selectin ligands on colon cancer tissues

    PubMed Central

    Carlson, Grady E.; Martin, Eric W.; Shirure, Venktesh S.; Malgor, Ramiro; Resto, Vicente A.; Goetz, Douglas J.; Burdick, Monica M.

    2017-01-01

    A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions. In this investigation, DBTA was used to probe human colon tissues for L-selectin ligand activity. The detection of L-selectin ligands using DBTA was highly specific. Furthermore, DBTA reproducibly detected functional L-selectin ligands on diseased, e.g., cancerous or inflamed, tissues but not on noncancerous tissues. In addition, DBTA revealed a heterogeneous distribution of functional L-selectin ligands on colon cancer tissues. Most notably, detection of L-selectin ligands by immunostaining using HECA-452 antibody only partially correlated with functional L-selectin ligands detected by DBTA. In summation, the results of this study demonstrate that DBTA detects functional selectin ligands to provide a unique characterization of pathological tissue. PMID:28282455

  12. Dynamic biochemical tissue analysis detects functional L-selectin ligands on colon cancer tissues.

    PubMed

    Carlson, Grady E; Martin, Eric W; Shirure, Venktesh S; Malgor, Ramiro; Resto, Vicente A; Goetz, Douglas J; Burdick, Monica M

    2017-01-01

    A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions. In this investigation, DBTA was used to probe human colon tissues for L-selectin ligand activity. The detection of L-selectin ligands using DBTA was highly specific. Furthermore, DBTA reproducibly detected functional L-selectin ligands on diseased, e.g., cancerous or inflamed, tissues but not on noncancerous tissues. In addition, DBTA revealed a heterogeneous distribution of functional L-selectin ligands on colon cancer tissues. Most notably, detection of L-selectin ligands by immunostaining using HECA-452 antibody only partially correlated with functional L-selectin ligands detected by DBTA. In summation, the results of this study demonstrate that DBTA detects functional selectin ligands to provide a unique characterization of pathological tissue.

  13. SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lindsay, WD; Oncora Medical, LLC, Philadelphia, PA; Berlind, CG

    Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013more » was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more

  14. [Relationships between the enrichment of ETBF, Fn, Hp in intestinal and colorectal cancer].

    PubMed

    Zhang, J; Lu, X L; Zhao, G; Shi, H T; Geng, Y; Zhong, W T; Dong, L

    2018-02-23

    Objective: To explore relationships between the enrichment of ETBF, Fn, Hp in feces, tissues and colorectal cancer. Methods: Feces, lesion tissue and adjacent tissue from 24 patients with colorectal cancer and 31 patients with adenomas were collected, and we collected Feces and tissue of 20 healthy control persons. Then the copy numbers of enterotoxigenic B. fragilis (ETBF), Fusobacterium nucleatum (Fn) and Helicobacter pylori (Hp) were determined by quantitative real-time PCR. Immunohistochemical method was used to examine the expression intensity of EGFR and p53, and the relationships between different expression intensity of EGFR, p53 and the numbers of three bacterias. Results: In the feces, copy numbers of ETBF and Fn were as follous: colorectal cancer group>adenomas group>healthy control group ( P <0.05). Copy numbers of Hp were as follous: colorectal cancer group>healthy control group ( P <0.01); adenomas group>healthy control group ( P <0.01). In the tissue, copy numbers of ETBF, Fn were as follows: colorectal cancer group>adenomas group>healthy control group ( P <0.05). Copy numbers of Hp were as follows: colorectal cancer group>healthy control group ( P <0.01); adenomas group>healthy control group ( P <0.01). Copy numbers of those three bacteria in the lesion tissue and the adjacent tissue had no significant difference. This happened both in colorectal cancer group and adenomas group. The different expression intensity of EGFR, p53 and the number of three bacteria showed no obviously statistical correlation( P >0.05). Conclusion: Adenomatous polyp and colorectal cancer patients show high enrichment of ETBF, Fn and Hp in both feces and tissues. ETBF, Fn and Hp probably contribute to the development of adenomatous polyp and colorectal cancer. Trial registration Chinese Clinical Trial Registry, ChiCTR-BOC-17012509.

  15. Inflammatory process induced by carrageenan in adjacent tissue triggers the acute inflammation in deep digital flexor tendon of rats.

    PubMed

    Vieira, Cristiano Pedrozo; De Aro, Andrea Aparecida; Da Ré Guerra, Flávia; De Oliveira, Letícia Prado; De Almeida, Marcos Dos Santos; Pimentel, Edson Rosa

    2013-08-01

    Tendinopathy is a pathology found mainly in the rotator cuff, patellar, Achilles and flexor tendons. Tendinopathy is a significant impediment to performance in athletes and in workers in the labor market. Some studies have indicated that inflammation in adjacent tissues may affect the rotator cuff and Achilles tendon. In this study alterations were verified in the extracellular matrix (ECM) of the deep digital flexor tendon after two periods (12 and 24 hr) of induction inflammation in rat paw. Wistar rats were divided into three groups: those that received injection of 1% carrageenan; those that received 0.9% NaCl; and those that received no application. The tendon was divided into distal (d), proximal (p), and intermediate (i) regions. Biochemical analyses were performed and included non-collagenous proteins (NCP), glycosaminoglycans (GAGs), hydroxyproline (HoPro) and metalloproteinases 2 and 9. Tissue sections were stained with toluidine blue, hematoxylin-eosin, and Ponceau SS and observed under polarization microscopy. Remarkable results were detected that included the presence of MMP-9, degradation of NCP and GAG and the presence of cellular infiltrate closer to digits in d region. The different concentrations of HoPro, as well as alterations in the organization of the collagen fibers showed the collagenous matrix undergoing some alterations. The results indicated that the induced inflammation in rat paw exhibited characteristics similar to the typical acute inflammatory process observed in tendons. Copyright © 2013 Wiley Periodicals, Inc.

  16. The Christchurch Tissue Bank to support cancer research.

    PubMed

    Morrin, Helen; Gunningham, Sarah; Currie, Margaret; Dachs, Gabi; Fox, Stephen; Robinson, Bridget

    2005-11-11

    To report on the development of a central resource of consented cancer tissues for researchers to use for ethically approved projects, and to describe the banking process. The development of tissue banking in Christchurch, New Zealand is described, including the number and main types of samples collected. The consent forms have evolved with several new donor options added between 1996 and 2004. Since June 2004, disposal of tissues by a karakia (blessing) has been offered. Characteristics of each tissue including amount, location in the bank, and relevant clinicopathological data have been recorded prospectively in a detailed secure relational database. The changes in the consent form and donor options are described. Most donors (99.6%) consented to allow access to medical records (since May 2002); 98.3% to tissue being sent overseas (since May 2003), 97.4% to commercial research (since May 2003), and 35.6% requested disposal with a karakia. Since May 2003, 87% of donors have been Caucasian, 5.1% Maori, and the remainder composed of other categories as stated on the 2001 New Zealand census format. By March 2005, samples have been banked from more than 2000 donors. For each of the last 4 years, samples have been collected from more than 300 donors, including fresh-frozen tissue, DNA preparations, serum, plasma, and paraffin blocks. The predominant tissues are from donors with cancers of the breast, colon, urological, and gynaecological sites. The Christchurch Tissue Bank is a successful model for potential New Zealand-wide application, providing quality tissue samples for cancer research whilst appropriately addressing ethical, legal, and cultural aspects of their collection.

  17. Characterizing viscoelastic properties of breast cancer tissue in a mouse model using indentation.

    PubMed

    Qiu, Suhao; Zhao, Xuefeng; Chen, Jiayao; Zeng, Jianfeng; Chen, Shuangqing; Chen, Lei; Meng, You; Liu, Biao; Shan, Hong; Gao, Mingyuan; Feng, Yuan

    2018-03-01

    Breast cancer is one of the leading cancer forms affecting females worldwide. Characterizing the mechanical properties of breast cancer tissue is important for diagnosis and uncovering the mechanobiology mechanism. Although most of the studies were based on human cancer tissue, an animal model is still describable for preclinical analysis. Using a custom-build indentation device, we measured the viscoelastic properties of breast cancer tissue from 4T1 and SKBR3 cell lines. A total of 7 samples were tested for each cancer tissue using a mouse model. We observed that a viscoelastic model with 2-term Prony series could best describe the ramp and stress relaxation of the tissue. For long-term responses, the SKBR3 tissues were stiffer in the strain levels of 4-10%, while no significant differences were found for the instantaneous elastic modulus. We also found tissues from both cell lines appeared to be strain-independent for the instantaneous elastic modulus and for the long-term elastic modulus in the strain level of 4-10%. In addition, by inspecting the cellular morphological structure of the two tissues, we found that SKBR3 tissues had a larger volume ratio of nuclei and a smaller volume ratio of extracellular matrix (ECM). Compared with prior cellular mechanics studies, our results indicated that ECM could contribute to the stiffening the tissue-level behavior. The viscoelastic characterization of the breast cancer tissue contributed to the scarce animal model data and provided support for the linear viscoelastic model used for in vivo elastography studies. Results also supplied helpful information for modeling of the breast cancer tissue in the tissue and cellular levels. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Tryptophan as key biomarker to detect gastrointestinal tract cancer using non-negative biochemical analysis of native fluorescence and Stokes Shift spectroscopy

    NASA Astrophysics Data System (ADS)

    Wang, Leana; Zhou, Yan; Liu, Cheng-hui; Zhou, Lixin; He, Yong; Pu, Yang; Nguyen, Thien An; Alfano, Robert R.

    2015-03-01

    The objective of this study was to find out the emission spectral fingerprints for discrimination of human colorectal and gastric cancer from normal tissue in vitro by applying native fluorescence. The native fluorescence (NFL) and Stokes shift spectra of seventy-two human cancerous and normal colorectal (colon, rectum) and gastric tissues were analyzed using three selected excitation wavelengths (e.g. 300 nm, 320 nm and 340 nm). Three distinct biomarkers, tryptophan, collagen and reduced nicotinamide adenine dinucleotide hydrate (NADH), were found in the samples of cancerous and normal tissues from eighteen subjects. The spectral profiles of tryptophan exhibited a sharp peak in cancerous colon tissues under a 300 nm excitation when compared with normal tissues. The changes in compositions of tryptophan, collagen, and NADH were found between colon cancer and normal tissues under an excitation of 300 nm by the non-negative basic biochemical component analysis (BBCA) model.

  19. Long non-coding RNA CRNDE promotes tumor growth in medulloblastoma.

    PubMed

    Song, H; Han, L-M; Gao, Q; Sun, Y

    2016-06-01

    Medulloblastoma is the most common malignant brain tumor in children. Despite remarkable advances over the past decades, a novel therapeutic strategy is urgently required to increase long-term survival. This study aimed to understand the role of a long non-coding RNA (lncRNA), colorectal neoplasia differentially expressed (CRNDE), in medulloblastoma tumor growth. The transcript level of CRNDE was initially examined in dissected clinical tissues and cultured cancerous cells. Effects of CRNDE knockdown on cell viability and colony formation in vitro were assessed using the CCK-8 and colony formation assays, respectively. Cell cycle progression and survival were also determined after CRNDE knockdown. A xenograft mouse model of human medulloblastoma was established by injecting nude mice with medulloblastoma cells stably depleted of CRNDE expression. Our data suggest that transcript levels of CRNDE are elevated in clinical medulloblastoma tissues instead of in adjacent non-cancerous tissues. Knockdown of CRNDE significantly slowed cell proliferation rates and inhibited colony formation in Daoy and D341 cells. Tumor growth in vivo was also inhibited after CRNDE knockdown. Moreover, after knockdown of CRNDE, cell cycle progression was arrested in S phase and apoptosis was promoted by 15-20% in Daoy and D341 cells. In vivo data further showed that proliferating cell nuclei antigen (PCNA) was decreased, whereas the apoptosis initiator cleaved-caspase-3 was increased upon CRNDE knockdown in cancerous tissues from the mouse model. All these data suggest that CRNDE promotes tumor growth both in vitro and in vivo. This growth-promotion effect might be achieved via arresting cell cycle progression and inhibiting apoptosis. Therapeutics against CRNDE may be a novel strategy for the treatment of medulloblastoma.

  20. Tissue preservation with mass spectroscopic analysis: Implications for cancer diagnostics.

    PubMed

    Hall, O Morgan; Peer, Cody J; Figg, William D

    2018-05-17

    Surgical intervention is a common treatment modality for localized cancer. Post-operative analysis involves evaluation of surgical margins to assess whether all malignant tissue has been resected because positive surgical margins lead to a greater likelihood of recurrence. Secondary treatments are utilized to minimize the negative effects of positive surgical margins. Recently, in Science Translational Medicine, Zhang et al describe a new mass spectroscopic technique that could potentially decrease the likelihood of positive surgical margins. Their nondestructive in vivo tissue sampling leads to a highly accurate and rapid cancer diagnosis with great precision between healthy and malignant tissue. This new tool has the potential to improve surgical margins and accelerate cancer diagnostics by analyzing biomolecular signatures of various tissues and diseases.

  1. Clinical evaluation of expanded mesh connective tissue graft in the treatment for multiple adjacent gingival recessions in the esthetic zone

    PubMed Central

    Shanmugam, M.; Shivakumar, B.; Meenapriya, B.; Anitha, V.; Ashwath, B.

    2015-01-01

    Background: Multiple approaches have been used to replace lost, damaged or diseased gingival tissues. The connective tissue graft (CTG) procedure is the golden standard method for root coverage. Although multiple sites often need grafting, the palatal mucosa supplies only a limited area of grafting material. To overcome this limitation, expanded mesh graft provides a method whereby a graft can be stretched to cover a large area. The aim of this study was to evaluate the effectiveness and the predictability of expanded mesh CTG (e-MCTG) in the treatment of adjacent multiple gingival recessions. Materials and Methods: Sixteen patients aged 20–50 years contributed to 55 sites, each site falling into at least three adjacent Miller's Class 1 or Class 2 gingival recession. The CTG obtained from the palatal mucosa was expanded to cover the recipient bed, which was 1.5 times larger than the graft. Clinical measurements were recorded at baseline and 3 months, 12 months postoperatively. Results: A mean coverage of 1.96 mm ± 0.66 mm and 2.22 mm ± 0.68 mm was obtained at the end of 3rd and 12th month, respectively. Twelve months after surgery a statistically significant increase in CAL (2.2 mm ± 0.68 mm, P < 0.001) and increasing WKT (1.75 ± 0.78, P < 0.001) were obtained. In 80% of the treated sites, 100% root coverage was achieved (mean 93.5%). Conclusions: The results of this study demonstrated that multiple adjacent recessions were treated by using e-MCTG technique can be applied and highly predictable root coverage can be achieved. PMID:26321829

  2. Comparison of EGFR signaling pathway somatic DNA mutations derived from peripheral blood and corresponding tumor tissue of patients with advanced non-small-cell lung cancer using liquidchip technology.

    PubMed

    Zhang, Hui; Liu, Deruo; Li, Shanqing; Zheng, Yongqing; Yang, Xinjie; Li, Xi; Zhang, Quan; Qin, Na; Lu, Jialin; Ren-Heidenreich, Lifen; Yang, Huiyi; Wu, Yuhua; Zhang, Xinyong; Nong, Jingying; Sun, Yifen; Zhang, Shucai

    2013-11-01

    Somatic DNA mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway are known to predict responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. We evaluated a sensitive liquidchip platform for detecting EGFR, KRAS (alias Ki-ras), proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations in plasma samples, which were highly correlated with matched tumor tissues from 86 patients with advanced non-small-cell lung cancers. Either EGFR exon 19 or 21 mutations were detected in 36 patients: 23 of whom had identical mutations in both their blood and tissue samples; whereas mutations in the remaining 13 were found only in their tumor samples. These EGFR mutations occurred at a significantly higher frequency in females, never-smokers, and in patients with adenocarcinomas (P ≤ 0.001). The EGFR exon 20 T790M mutation was detected in only one of the paired samples [100% (95% CI, 96% to 100%) agreement]. For KRAS, proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations, the overall agreements were 97% (95% CI, 90% to 99%), 98% (95% CI, 92% to 99%), and 97% (95% CI, 90% to 99%), respectively, and these were not associated with age, sex, smoking history, or histopathologic type. In conclusion, mutations detected in plasma correlated strongly with mutation profiles in each respective tumor sample, suggesting that this liquidchip platform may offer a rapid and noninvasive method for predicting tumor responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  3. Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer.

    PubMed

    Kalsbeek, Anton M F; Chan, Eva K F; Grogan, Judith; Petersen, Desiree C; Jaratlerdsiri, Weerachai; Gupta, Ruta; Lyons, Ruth J; Haynes, Anne-Maree; Horvath, Lisa G; Kench, James G; Stricker, Phillip D; Hayes, Vanessa M

    2018-01-01

    Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra-glandular as well as inter-patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue. DNA was extracted and qPCR performed to quantify the total amount of mtDNA as a ratio to genomic DNA. Differences in mtDNA content were compared for prostate cancer pathology features and disease outcomes. We showed a significantly reduced mtDNA content in prostate cancer compared with normal adjacent prostate tissue (mean difference 1.73-fold, P-value <0.001). Prostate cancer with increased mtDNA content showed unfavorable pathologic characteristics including, higher disease stage (PT2 vs PT3 P-value = 0.018), extracapsular extension (P-value = 0.02) and a trend toward an increased Gleason score (P-value = 0.064). No significant association was observed between changes in mtDNA content and biochemical recurrence (median follow up of 107 months). Contrary to other cancer types, prostate cancer tissue shows no universally depleted mtDNA content. Rather, the change in mtDNA content is highly variable, mirroring known prostate cancer genome heterogeneity. Patients with high mtDNA content have an unfavorable pathology, while a high mtDNA content in normal adjacent prostate tissue is associated with worse prognosis. © 2017 Wiley Periodicals, Inc.

  4. MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2.

    PubMed

    Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

    2015-01-01

    MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer.

  5. MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2

    PubMed Central

    Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

    2015-01-01

    MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer. PMID:26722475

  6. Defining Genomic Changes in Triple-Negative Breast Cancer in Women of African Descent

    DTIC Science & Technology

    2012-06-01

    Triple negative breast cancer • Ethnic disparities • Breast cancer amongst African Americans and Africans • Gene expression profiling • Array... negative cases seen in both African and African - American breast cancer cases. Gene Expression Array Studies The 31 triple negative Kijabe... African - American Adjacent Normal Breast Tissue PI: Pegram &

  7. Visualization of risk of radiogenic second cancer in the organs and tissues of the human body.

    PubMed

    Zhang, Rui; Mirkovic, Dragan; Newhauser, Wayne D

    2015-04-28

    Radiogenic second cancer is a common late effect in long term cancer survivors. Currently there are few methods or tools available to visually evaluate the spatial distribution of risks of radiogenic late effects in the human body. We developed a risk visualization method and demonstrated it for radiogenic second cancers in tissues and organs of one patient treated with photon volumetric modulated arc therapy and one patient treated with proton craniospinal irradiation. Treatment plans were generated using radiotherapy treatment planning systems (TPS) and dose information was obtained from TPS. Linear non-threshold risk coefficients for organs at risk of second cancer incidence were taken from the Biological Effects of Ionization Radiation VII report. Alternative risk models including linear exponential model and linear plateau model were also examined. The predicted absolute lifetime risk distributions were visualized together with images of the patient anatomy. The risk distributions of second cancer for the two patients were visually presented. The risk distributions varied with tissue, dose, dose-risk model used, and the risk distribution could be similar to or very different from the dose distribution. Our method provides a convenient way to directly visualize and evaluate the risks of radiogenic second cancer in organs and tissues of the human body. In the future, visual assessment of risk distribution could be an influential determinant for treatment plan scoring.

  8. SU-E-J-31: Biodynamic Imaging of Cancer Tissue and Response to Chemotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nolte, D; Turek, J; Childress, M

    2014-06-01

    Purpose: To measure intracellular motions inside three-dimensional living cancer tissue samples to establish a novel set of biodynamic biomarkers that assess tissue proliferative activity and sensitivity or resistance to chemotherapy. Methods: Biodynamic imaging (BDI) uses digital holography with low-coherence low-intensity light illumination to construct 3D holograms from depths up to a millimeter deep inside cancer tissue models that include multicellular tumor spheroids and ex vivo cancer biopsies from canine non-Hodgkins lymphoma and epithelial ovarian cancer (EOC) mouse explants. Intracellular motions modulate the holographic intensity with frequencies related to the Doppler effect caused by the motions of a wide variety ofmore » intracellular components. These motions are affected by applied therapeutic agents, and BDI produces unique fingerprints of the action of specific drugs on the motions in specific cell types. In this study, chemotherapeutic agents (doxorubicin for canine lymphoma and oxoplatin for ovarian) are applied to the living tissue models and monitored over 10 hours by BDI. Results: Multicellular spheroids and patient biopsies are categorized as either sensitive or insensitive to applied therapeutics depending on the intracellular Doppler signatures of chemotherapy response. For both lymphoma and EOC there is strong specificity to the two types of sensitivities, with sensitive cell lines and biopsies exhibiting a global cessation of proliferation and strong suppression of metabolic activity, while insensitive cell lines and biopsies show moderate activation of Doppler frequencies associated with membrane processes and possible membrane trafficking. Conclusion: This work supports the hypothesis that biodynamic biomarkers from three-dimensional living tumor tissue, that includes tissue heterogeneity and measured within 24 hours of surgery, is predictive of near-term patient response to therapy. Future work will correlate biodynamic biomarkers

  9. Metabolome analysis of esophageal cancer tissues using capillary electrophoresis-time-of-flight mass spectrometry.

    PubMed

    Tokunaga, Masanori; Kami, Kenjiro; Ozawa, Soji; Oguma, Junya; Kazuno, Akihito; Miyachi, Hayato; Ohashi, Yoshiaki; Kusuhara, Masatoshi; Terashima, Masanori

    2018-06-01

    Reports of the metabolomic characteristics of esophageal cancer are limited. In the present study, we thus conducted metabolome analysis of paired tumor tissues (Ts) and non-tumor esophageal tissues (NTs) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The Ts and surrounding NTs were surgically excised pair-wise from 35 patients with esophageal cancer. Following tissue homogenization and metabolite extraction, a total of 110 compounds were absolutely quantified by CE-TOFMS. We compared the concentrations of the metabolites between Ts and NTs, between pT1 or pT2 (pT1-2) and pT3 or pT4 (pT3-4) stage, and between node-negative (pN-) and node-positive (pN+) samples. Principal component analysis and hierarchical clustering analysis revealed clear metabolomic differences between Ts and NTs. Lactate and citrate levels in Ts were significantly higher (P=0.001) and lower (P<0.001), respectively, than those in NTs, which corroborated with the Warburg effect in Ts. The concentrations of most amino acids apart from glutamine were higher in Ts than in NTs, presumably due to hyperactive glutaminolysis in Ts. The concentrations of malic acid (P=0.015) and citric acid (P=0.008) were significantly lower in pT3-4 than in pT1-2, suggesting the downregulation of tricarboxylic acid (TCA) cycle activity in pT3-4. On the whole, in this study, we demonstrate significantly different metabolomic characteristics between tumor and non-tumor tissues and identified a novel set of metabolites that were strongly associated with the degree of tumor progression. A further understanding of cancer metabolomics may enable the selection of more appropriate treatment strategies, thereby contributing to individualized medicine.

  10. Prostate Cancer: Serum and Tissue Markers

    PubMed Central

    Miller, Gary J; Brawer, Michael K; Sakr, Wael A; Thrasher, J Brantley; Townsend, Ronald

    2001-01-01

    The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the “gold standard,” has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and the clinical emergence of prostate cancer; the possible correlation of serum insulin-like growth factor levels with the risk for developing prostate cancer; and the latest advances in radiologic staging. PMID:16985995

  11. Tissue-based biomarkers in prostate cancer

    PubMed Central

    Clinton, Timothy N.; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Raj, Ganesh V; Woldu, Solomon L

    2017-01-01

    Introduction Prostate cancer is a heterogeneous disease. Existing risk stratification tools based on standard clinlicopathologic variables (prostate specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree of predictive ability. Advances in high-throughput sequencing has led to the development of several novel tissue-based biomarkers that can improve prognostication in prostate cancer management. Areas Covered The authors review commercially-available, tissue-based biomarker assays that improve upon existing risk-stratification tools in several areas of prostate cancer management, including the appropriateness of active surveillance and aiding in decision making regarding the use of adjuvant therapy. Additionally, some of the obstacles to the widespread adoption of these biomarkers and discuss several investigational sources of new biomarkers are discussed. Expert Commentary Work is ongoing to answer pertinent clinical questions in prostate cancer management including which patients should undergo biopsy, active surveillance, receive adjuvant therapy, and what systemic therapy is best in the first-line. Incorporation into novel biomarkers may allow for the incorporation of a ‘personalized’ approach to management. Further validation will be required and questions of cost must be considered before wide scale adoption of these biomarkers. Tumor heterogeneity may impose a ceiling on the prognostic ability of biomarkers using currently available techniques. PMID:29226251

  12. Evaluation of altered expression of miR-9 and miR-106a as an early diagnostic approach in gastric cancer.

    PubMed

    Shirmohammadi, Khadije; Sohrabi, Sareh; Jafarzadeh Samani, Zahra; Effatpanah, Hosein; Yadegarazari, Reza; Saidijam, Massoud

    2018-02-01

    The role of microRNAs (miRNAs) in cellular processes such as growth, apoptosis, differentiation and proliferation verifies the importance of miRNAs in carcinogenesis. Moreover, levels of miRNAs are dysregulated in cancer cells, so they could be used as novel classes of biomarkers for diagnosing cancer. The oncogenic role of miR-106a and its increased expression have been demonstrated in some cancers. In contrast, there is no consensus for miR-9 expression rate in different cancers. Therefore, this study was done to investigate the role of miR-106a and miR-9 in gastric cancer (GC). The current study was performed on 31 GC tissues as case, and 31 healthy adjacent tissues as a control group. Quantitative reverse transcriptase (q-RT) PCR was used for studying the expression rate of both miR-106a and miR-9 . The expression rate of both miRNAs in cancerous tissues was significantly higher than healthy adjacent tissues (≈10 folds) (P<0.05). The results showed that the expression rate of both markers was significantly increased in cancerous tissues. Therefore, they can be suggested as potential biomarkers for cancer diagnosis and prognosis as well as targets for therapy.

  13. Knockdown of long non-coding RNA MAP3K20 antisense RNA 1 inhibits gastric cancer growth through epigenetically regulating miR-375.

    PubMed

    Quan, Yongsheng; Zhang, Yan; Lin, Wei; Shen, Zhaohua; Wu, Shuai; Zhu, Changxin; Wang, Xiaoyan

    2018-03-04

    Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis of gastric cancer. LncRNA MAP3K20 antisense RNA 1 (MLK7-AS1) has been identified as one of gastric cancer-specific lncRNAs. However, its precise role in gastric cancer remains unknown. In this study, we found that lncRNA MLK7-AS1 was significantly increased in gastric cancer tissues compared with in adjacent tissues. Gastric cancer patients with high MLK7-AS1 expression had a shorter survival and poorer prognosis. By loss-function assay, we demonstrated that knockdown of MLK7-AS1 inhibited cell proliferation and induced apoptosis in HGC27and MKN-45 cells. Furthermore, we identified miR-375 as a target of MLK7-AS1. MLK7-AS1 interacted with Dnmt1 and recruited it to miR-375 promotor, hyper-methylating miR-375 promotor and repressing miR-375 expression. Taken together, our findings demonstrate that knockdown of MLK7-AS1 by siRNA inhibits gastric cancer growth by epigenetically regulating miR-375. Thus, MLK7-AS1 may be a useful prognostic marker and therapeutic target for gastric cancer patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Electromechanical Coupling Factor of Breast Tissue as a Biomarker for Breast Cancer.

    PubMed

    Park, Kihan; Chen, Wenjin; Chekmareva, Marina A; Foran, David J; Desai, Jaydev P

    2018-01-01

    This research aims to validate a new biomarker of breast cancer by introducing electromechanical coupling factor of breast tissue samples as a possible additional indicator of breast cancer. Since collagen fibril exhibits a structural organization that gives rise to a piezoelectric effect, the difference in collagen density between normal and cancerous tissue can be captured by identifying the corresponding electromechanical coupling factor. The design of a portable diagnostic tool and a microelectromechanical systems (MEMS)-based biochip, which is integrated with a piezoresistive sensing layer for measuring the reaction force as well as a microheater for temperature control, is introduced. To verify that electromechanical coupling factor can be used as a biomarker for breast cancer, the piezoelectric model for breast tissue is described with preliminary experimental results on five sets of normal and invasive ductal carcinoma (IDC) samples in the 25-45 temperature range. While the stiffness of breast tissues can be captured as a representative mechanical signature which allows one to discriminate among tissue types especially in the higher strain region, the electromechanical coupling factor shows more distinct differences between the normal and IDC groups over the entire strain region than the mechanical signature. From the two-sample -test, the electromechanical coupling factor under compression shows statistically significant differences ( 0.0039) between the two groups. The increase in collagen density in breast tissue is an objective and reproducible characteristic of breast cancer. Although characterization of mechanical tissue property has been shown to be useful for differentiating cancerous tissue from normal tissue, using a single parameter may not be sufficient for practical usage due to inherent variation among biological samples. The portable breast cancer diagnostic tool reported in this manuscript shows the feasibility of measuring multiple

  15. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post- chemotherapy tissues

    PubMed Central

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-01-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens. PMID:26515599

  16. Quantitative proteomic analysis of microdissected oral epithelium for cancer biomarker discovery.

    PubMed

    Xiao, Hua; Langerman, Alexander; Zhang, Yan; Khalid, Omar; Hu, Shen; Cao, Cheng-Xi; Lingen, Mark W; Wong, David T W

    2015-11-01

    Specific biomarkers are urgently needed for the detection and progression of oral cancer. The objective of this study was to discover cancer biomarkers from oral epithelium through utilizing high throughput quantitative proteomics approaches. Morphologically malignant, epithelial dysplasia, and adjacent normal epithelial tissues were laser capture microdissected (LCM) from 19 patients and used for proteomics analysis. Total proteins from each group were extracted, digested and then labelled with corresponding isobaric tags for relative and absolute quantitation (iTRAQ). Labelled peptides from each sample were combined and analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) for protein identification and quantification. In total, 500 proteins were identified and 425 of them were quantified. When compared with adjacent normal oral epithelium, 17 and 15 proteins were consistently up-regulated or down-regulated in malignant and epithelial dysplasia, respectively. Half of these candidate biomarkers were discovered for oral cancer for the first time. Cornulin was initially confirmed in tissue protein extracts and was further validated in tissue microarray. Its presence in the saliva of oral cancer patients was also explored. Myoglobin and S100A8 were pre-validated by tissue microarray. These data demonstrated that the proteomic biomarkers discovered through this strategy are potential targets for oral cancer detection and salivary diagnostics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. A universal method for the mutational analysis of K-ras and p53 gene in non-small-cell lung cancer using formalin-fixed paraffin-embedded tissue.

    PubMed

    Sarkar, F H; Valdivieso, M; Borders, J; Yao, K L; Raval, M M; Madan, S K; Sreepathi, P; Shimoyama, R; Steiger, Z; Visscher, D W

    1995-12-01

    The p53 tumor suppressor gene has been found to be altered in almost all human solid tumors, whereas K-ras gene mutations have been observed in a limited number of human cancers (adenocarcinoma of colon, pancreas, and lung). Studies of mutational inactivation for both genes in the same patient's sample on non-small-cell lung cancer have been limited. In an effort to perform such an analysis, we developed and compared methods (for the mutational detection of p53 and K-ras gene) that represent a modified and universal protocol, in terms of DNA extraction, polymerase chain reaction (PCR) amplification, and nonradioisotopic PCR-single-strand conformation polymorphism (PCR-SSCP) analysis, which is readily applicable to either formalin-fixed, paraffin-embedded tissues or frozen tumor specimens. We applied this method to the evaluation of p53 (exons 5-8) and K-ras (codon 12 and 13) gene mutations in 55 cases of non-small-cell lung cancer. The mutational status in the p53 gene was evaluated by radioisotopic PCR-SSCP and compared with PCR-SSCP utilizing our standardized nonradioisotopic detection system using a single 6-microns tissue section. The mutational patterns observed by PCR-SSCP were subsequently confirmed by PCR-DNA sequencing. The mutational status in the K-ras gene was similarly evaluated by PCR-SSCP, and the specific mutation was confirmed by Southern slot-blot hybridization using 32P-labeled sequence-specific oligonucleotide probes for codons 12 and 13. Mutational changes in K-ras (codon 12) were found in 10 of 55 (18%) of non-small-cell lung cancers. Whereas adenocarcinoma showed K-ras mutation in 33% of the cases at codon 12, only one mutation was found at codon 13. As expected, squamous cell carcinoma samples (25 cases) did not show K-ras mutations. Mutations at exons 5-8 of the p53 gene were documented in 19 of 55 (34.5%) cases. Ten of the 19 mutations were single nucleotide point mutations, leading to amino acid substitution. Six showed insertional

  18. RBFOX2 Is an Important Regulator of Mesenchymal Tissue-Specific Splicing in both Normal and Cancer Tissues

    PubMed Central

    Venables, Julian P.; Brosseau, Jean-Philippe; Gadea, Gilles; Klinck, Roscoe; Prinos, Panagiotis; Beaulieu, Jean-François; Lapointe, Elvy; Durand, Mathieu; Thibault, Philippe; Tremblay, Karine; Rousset, François; Tazi, Jamal; Abou Elela, Sherif

    2013-01-01

    Alternative splicing provides a critical and flexible layer of regulation intervening in many biological processes to regulate the diversity of proteins and impact cell phenotype. To identify alternative splicing differences that distinguish epithelial from mesenchymal tissues, we have investigated hundreds of cassette exons using a high-throughput reverse transcription-PCR (RT-PCR) platform. Extensive changes in splicing were noted between epithelial and mesenchymal tissues in both human colon and ovarian tissues, with many changes from mostly one splice variant to predominantly the other. Remarkably, many of the splicing differences that distinguish normal mesenchymal from normal epithelial tissues matched those that differentiate normal ovarian tissues from ovarian cancer. Furthermore, because splicing profiling could classify cancer cell lines according to their epithelial/mesenchymal characteristics, we used these cancer cell lines to identify regulators for these specific splicing signatures. By knocking down 78 potential splicing factors in five cell lines, we provide an extensive view of the complex regulatory landscape associated with the epithelial and mesenchymal states, thus revealing that RBFOX2 is an important driver of mesenchymal tissue-specific splicing. PMID:23149937

  19. P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer.

    PubMed

    Kato, Shinichiro; Yokoyama, Satoru; Hayakawa, Yoshihiro; Li, Luhui; Iwakami, Yusuke; Sakurai, Hiroaki; Saiki, Ikuo

    2016-10-01

    Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non-small-cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC-14, A549, and PC-9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  20. [Chymotripsin-like activity and subunit composition of proteasomes in human cancers].

    PubMed

    Kondakova, I V; Spirina, L V; Koval, V D; Shashova, E E; Choinzonov, E L; Ivanova, E V; Kolomiets, L A; Chernyshova, A L; Slonimskaya, E M; Usynin, E A; Afanasyev, S G

    2014-01-01

    Activity of the proteasome, polyfunctional enzymatic complex, is known to undergo changes during cancer development. This phenomenon is, probably, caused by the changes in subunit composition of proteasomes. In present work, we studied chymotrypsin-like activity of proteasomes, subunit composition and their association in breast cancer, head and neck squamous cell carcinoma, endometrial cancer, renal cancer, bladder cancer, stomach cancer and colorectal cancer. The increase of proteasome activity was revealed in most cancer tissues compared with adjacent tissues except for the renal cell carcinoma. Changes in proteasome activity in cancer tissues compared with correspondent normal tissues were accompanied by modification of its subunit composition. High proteasome activity was observed in combination with an increased expression of immune subunits and/or proteasome activator PA28, associated with activity of 20S proteasome. In breast cancer, head and neck squamous cell carcinoma, bladder cancer, stomach cancer and colorectal cancer we additionally found higher expression of Rpt6 subunit of 26S proteasome. Correlations between chymotrypsin like proteasome activity and subunit expressions were found in human cancer tissues. In summary, we suggest that proteasome ac- tivation and changes in its subunit composition plays an important role in cancer pathogenesis.

  1. Cellular phone enabled non-invasive tissue classifier.

    PubMed

    Laufer, Shlomi; Rubinsky, Boris

    2009-01-01

    Cellular phone technology is emerging as an important tool in the effort to provide advanced medical care to the majority of the world population currently without access to such care. In this study, we show that non-invasive electrical measurements and the use of classifier software can be combined with cellular phone technology to produce inexpensive tissue characterization. This concept was demonstrated by the use of a Support Vector Machine (SVM) classifier to distinguish through the cellular phone between heart and kidney tissue via the non-invasive multi-frequency electrical measurements acquired around the tissues. After the measurements were performed at a remote site, the raw data were transmitted through the cellular phone to a central computational site and the classifier was applied to the raw data. The results of the tissue analysis were returned to the remote data measurement site. The classifiers correctly determined the tissue type with a specificity of over 90%. When used for the detection of malignant tumors, classifiers can be designed to produce false positives in order to ensure that no tumors will be missed. This mode of operation has applications in remote non-invasive tissue diagnostics in situ in the body, in combination with medical imaging, as well as in remote diagnostics of biopsy samples in vitro.

  2. Cellular Phone Enabled Non-Invasive Tissue Classifier

    PubMed Central

    Laufer, Shlomi; Rubinsky, Boris

    2009-01-01

    Cellular phone technology is emerging as an important tool in the effort to provide advanced medical care to the majority of the world population currently without access to such care. In this study, we show that non-invasive electrical measurements and the use of classifier software can be combined with cellular phone technology to produce inexpensive tissue characterization. This concept was demonstrated by the use of a Support Vector Machine (SVM) classifier to distinguish through the cellular phone between heart and kidney tissue via the non-invasive multi-frequency electrical measurements acquired around the tissues. After the measurements were performed at a remote site, the raw data were transmitted through the cellular phone to a central computational site and the classifier was applied to the raw data. The results of the tissue analysis were returned to the remote data measurement site. The classifiers correctly determined the tissue type with a specificity of over 90%. When used for the detection of malignant tumors, classifiers can be designed to produce false positives in order to ensure that no tumors will be missed. This mode of operation has applications in remote non-invasive tissue diagnostics in situ in the body, in combination with medical imaging, as well as in remote diagnostics of biopsy samples in vitro. PMID:19365554

  3. Visualization and tissue classification of human breast cancer images using ultrahigh-resolution OCT.

    PubMed

    Yao, Xinwen; Gan, Yu; Chang, Ernest; Hibshoosh, Hanina; Feldman, Sheldon; Hendon, Christine

    2017-03-01

    Breast cancer is one of the most common cancers, and recognized as the third leading cause of mortality in women. Optical coherence tomography (OCT) enables three dimensional visualization of biological tissue with micrometer level resolution at high speed, and can play an important role in early diagnosis and treatment guidance of breast cancer. In particular, ultra-high resolution (UHR) OCT provides images with better histological correlation. This paper compared UHR OCT performance with standard OCT in breast cancer imaging qualitatively and quantitatively. Automatic tissue classification algorithms were used to automatically detect invasive ductal carcinoma in ex vivo human breast tissue. Human breast tissues, including non-neoplastic/normal tissues from breast reduction and tumor samples from mastectomy specimens, were excised from patients at Columbia University Medical Center. The tissue specimens were imaged by two spectral domain OCT systems at different wavelengths: a home-built ultra-high resolution (UHR) OCT system at 800 nm (measured as 2.72 μm axial and 5.52 μm lateral) and a commercial OCT system at 1,300 nm with standard resolution (measured as 6.5 μm axial and 15 μm lateral), and their imaging performances were analyzed qualitatively. Using regional features derived from OCT images produced by the two systems, we developed an automated classification algorithm based on relevance vector machine (RVM) to differentiate hollow-structured adipose tissue against solid tissue. We further developed B-scan based features for RVM to classify invasive ductal carcinoma (IDC) against normal fibrous stroma tissue among OCT datasets produced by the two systems. For adipose classification, 32 UHR OCT B-scans from 9 normal specimens, and 28 standard OCT B-scans from 6 normal and 4 IDC specimens were employed. For IDC classification, 152 UHR OCT B-scans from 6 normal and 13 IDC specimens, and 104 standard OCT B-scans from 5 normal and 8 IDC specimens

  4. GAB2 Amplification in Squamous Cell Lung Cancer of Non-Smokers

    PubMed Central

    2017-01-01

    Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers. PMID:28960030

  5. Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer.

    PubMed

    Rohan, Thomas E; Miller, Christopher A; Li, Tiandao; Wang, Yihong; Loudig, Olivier; Ginsberg, Mindy; Glass, Andrew; Mardis, Elaine

    2018-06-06

    Insights into the molecular pathogenesis of breast cancer might come from molecular analysis of tissue from early stages of the disease. We conducted a case-control study nested in a cohort of women who had biopsy-confirmed benign breast disease (BBD) diagnosed between 1971 and 2006 at Kaiser Permanente Northwest and who were followed to mid-2015 to ascertain subsequent invasive breast cancer (IBC); cases (n = 218) were women with BBD who developed subsequent IBC and controls, individually matched (1:1) to cases, were women with BBD who did not develop IBC in the same follow-up interval as that for the corresponding case. Targeted sequence capture and sequencing were performed for 83 genes of importance in breast cancer. There were no significant case-control differences in mutation burden overall, for non-silent mutations, for individual genes, or with respect either to the nature of the gene mutations or to mutational enrichment at the pathway level. For seven subjects with DNA from the BBD and ipsilateral IBC, virtually no mutations were shared. This study, the first to use a targeted multi-gene sequencing approach on early breast cancer precursor lesions to investigate the genomic basis of the disease, showed that somatic mutations detected in BBD tissue were not associated with breast cancer risk.

  6. Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.

    PubMed

    Guimond, Marie-Odile; Battista, Marie-Claude; Nikjouitavabi, Fatemeh; Carmel, Maude; Barres, Véronique; Doueik, Alexandre A; Fazli, Ladan; Gleave, Martin; Sabbagh, Robert; Gallo-Payet, Nicole

    2013-07-01

    Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture. AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate. AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells. AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance. Copyright © 2013 Wiley Periodicals, Inc.

  7. SOX17 promoter methylation in plasma circulating tumor DNA of patients with non-small cell lung cancer.

    PubMed

    Balgkouranidou, Ioanna; Chimonidou, Maria; Milaki, Georgia; Tsaroucha, Emily; Kakolyris, Stylianos; Georgoulias, Vasilis; Lianidou, Evi

    2016-08-01

    SOX17 belongs to the high-mobility group-box transcription factor superfamily and down-regulates the Wnt pathway. The aim of our study was to evaluate the prognostic significance of SOX17 promoter methylation in circulating tumor DNA (ctDNA) in plasma of non-small cell lung cancer (NSCLC) patients. We examined the methylation status of SOX17 promoter in 57 operable NSCLC primary tumors and paired adjacent non-cancerous tissues and in ctDNA isolated from 48 corresponding plasma samples as well as in plasma from 74 patients with advanced NSCLC and 49 healthy individuals. SOX17 promoter methylation was examined by Methylation Specific PCR (MSP). In operable NSCLC, SOX17 promoter was fully methylated in primary tumors (57/57, 100%), and in corresponding ctDNA (27/48, 56.2%) while it was detected in only 1/49 (2.0%) healthy individuals. In advanced NSCLC, SOX17 promoter was methylated in ctDNA in 27/74 (36.4%) patients and OS was significantly different in favor of patients with non-methylated SOX17 promoter (p=0.012). Multivariate analysis revealed that SOX17 promoter methylation in ctDNA was an independent prognostic factor associated with OS in patients with advanced but not operable NSCLC. Our results show that SOX17 promoter is highly methylated in primary tumors and in corresponding plasma samples both in operable and advanced NSCLC. In the advanced setting, SOX17 promoter methylation in plasma ctDNA has a statistical significant influence on NSCLC patient's survival time. Detection of SOX17 promoter methylation in plasma provides prognostic information and merits to be further evaluated as a circulating tumor biomarker in patients with operable and advanced NSCLC.

  8. Deformable anatomical templates for brachytherapy treatment planning in radiotherapy of cervical cancer

    NASA Astrophysics Data System (ADS)

    Christensen, Gary E.; Williamson, Jeffrey F.; Chao, K. S. C.; Miller, Michael I.; So, F. B.; Vannier, Michael W.

    1997-10-01

    This paper describes a new method to register serial, volumetric x-ray computed tomography (CT) data sets for tracking soft-tissue deformation caused by insertion of intracavity brachytherapy applicators to treat cervical cancer. 3D CT scans collected from the same patient with and without a brachytherapy applicator are registered to aid in computation of the radiation dose to tumor and normal tissue. The 3D CT image volume of pelvic anatomy with the applicator. Initial registration is accomplished by rigid alignment of the pelvic bones and non-rigid alignment of gray scale CT data and hand segmentations of the vagina, cervix, bladder, and rectum. A viscous fluid transformation model is used for non-rigid registration to allow for local, non-linear registration of the vagina, cervix, bladder, and rectum without disturbing the rigid registration of the bony pelvis and adjacent structures. Results are presented in which two 3D CT data sets of the same patient - imaged with and without a brachytherapy applicator - are registered.

  9. Evaulation of cancer and non-cancer effects of cumene ...

    EPA Pesticide Factsheets

    Cumene, also known as isopropyl benzene, is a volatile liquid. We have systematically reviewed published literature to evaluate cancer and noncancer effects of cumene. Cumene, readily absorbed via inhalation is distributed in several tissues, metabolized extensively by cytochrome P-450 isozymes within hepatic and extra-hepatic tissues and excreted through urine. Although, there are no epidemiological cancer studies for humans, chronic inhalation exposure studies in rat and mouse have shown increased nasal lesions including atrophy, basal cell hyperplasia, atypical hyperplasia and hyperplasia of the olfactory epithelium glands. To present the information at the Society of Toxicology Meeting.

  10. TRIM28, a new molecular marker predicting metastasis and survival in early-stage non-small cell lung cancer.

    PubMed

    Liu, Lei; Zhao, Enhong; Li, Chunhui; Huang, Liang; Xiao, Lijun; Cheng, Luyang; Huang, Xu; Song, Youxin; Xu, Dawei

    2013-02-01

    TRIM28 is a universal corepressor for Kruppel-associated box zinc finger proteins. In this study, we demonstrated the expression of TRIM28 gene was significantly higher in cancerous tissues than in noncancerous tissues (P < 0.001). TRIM28 knockdown resulted in a decrease in cell proliferation in liquid media as well as in soft agar. The proliferation rate was impaired and the cell cycle progression was inhibited after knockdown of TRIM28 in non-small cell lung cancer cell lines PAa and SK-MES-1. We used real-time polymerase chain reaction to detect circulating cancer cells in 138 non-small cell lung cancer patients. The overall positive detection rate was 30.4% (42 of 138) in peripheral blood of NSCLC patients and was 29.9% (29 of 97) in early-stage patients. In a 70-month follow-up study, 20 of 29 patients (69.0%) in TRIM28 positive group had recurrence and/or metastasis, significantly higher (P = 0.004) than in the TRIM28 negative group (25 of 68, 36.8%). In addition, non-small cell lung cancer patients whose circulating cancer cells expressed TRIM28 suffered shorter tumor-specific survival compared with those with absent TRIM28 expression (P < 0.001). Results of our study showed that TRIM28 provides a survival advantage to lung cancer cells and may be a new marker to predict metastasis and prognosis in early-stage non-small cell lung cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing

    PubMed Central

    Radovich, Milan; Clare, Susan E.; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A.; Solzak, Jeffrey P.; Kassem, Nawal; Mathieson, Theresa; Storniolo, Anna Maria V.; Rufenbarger, Connie; Lillemoe, Heather A.; Blosser, Rachel J.; Choi, Mi Ran; Sauder, Candice A.; Doxey, Diane; Henry, Jill E.; Hilligoss, Eric E.; Sakarya, Onur; Hyland, Fiona C.; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W.; Schneider, Bryan P.

    2014-01-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER−,PR−,HER2−). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90% of TNBCs revealing an over-expressed central network. In conclusion, Use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos. PMID:24292813

  12. Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing.

    PubMed

    Radovich, Milan; Clare, Susan E; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A; Solzak, Jeffrey P; Kassem, Nawal; Mathieson, Theresa; Storniolo, Anna Maria V; Rufenbarger, Connie; Lillemoe, Heather A; Blosser, Rachel J; Choi, Mi Ran; Sauder, Candice A; Doxey, Diane; Henry, Jill E; Hilligoss, Eric E; Sakarya, Onur; Hyland, Fiona C; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W; Schneider, Bryan P

    2014-01-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.

  13. Developmental tumors and adjacent cortical dysplasia: single or dual pathology?

    PubMed

    Palmini, André; Paglioli, Eliseu; Silva, Vinicius Duval

    2013-12-01

    Developmental tumors often lead to refractory partial seizures and constitute a well-defined, surgically remediable epilepsy syndrome. Dysplastic features are often associated with these tumors, and their significance carries both practical and conceptual relevance. If associated focal cortical dysplasia (FCD) relates to the extent of the epileptogenic tissue, then presurgical evaluation and surgical strategies should target both the tumor and the surrounding dyslaminated cortex. Furthermore, the association has been included in the recently revised classification of FCD and the epileptogenicity of this associated dysplastic tissue is crucial to validate such revision. In addition to the possibility of representing dual pathology, the association of developmental tumors and adjacent dysplasia may instead represent a single developmental lesion with distinct parts distributed along a histopathologic continuum. Moreover, the possibility that this adjacent dyslamination is of minor epileptogenic relevance should also be entertained. Surgical data show that complete resection of the solid tumors and immediately adjacent tissue harboring satellites may disrupt epileptogenic networks and lead to high rates of seizure freedom, challenging the epileptogenic relevance of more extensive adjacent dyslaminated cortex. Whether the latter is a primary or secondary abnormality and whether dyslaminated cortex in the context of a second lesion may produce seizures after complete resection of the main lesion is still to be proven. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  14. DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons.

    PubMed

    Fish, Trevor J; Benninghoff, Abby D

    2017-11-01

    Polycyclic aromatic hydrocarbons (PAHs) comprise an important class of environmental pollutants that are known to cause lung cancer in animals and are suspected lung carcinogens in humans. Moreover, evidence from cell-based studies points to PAHs as modulators of the epigenome. The objective of this work was to assess patterns of genome-wide DNA methylation in lung tissues of adult offspring initiated in utero with the transplacental PAH carcinogens dibenzo [def,p]chrysene (DBC) or benzo [a]pyrene (BaP). Genome-wide methylation patterns for normal (not exposed), normal adjacent and lung tumor tissues obtained from adult offspring were determined using methylated DNA immunoprecipitation (MeDIP) with the NimbleGen mouse DNA methylation CpG island array. Lung tumor incidence in 45-week old mice initiated with BaP was 32%, much lower than that of the DBC-exposed offspring at 96%. Also, male offspring appeared more susceptible to BaP as compared to females. Distinct patterns of DNA methylation were associated with non-exposed, normal adjacent and adenocarcinoma lung tissues, as determined by principal components, hierarchical clustering and gene ontology analyses. From these methylation profiles, a set of genes of interest was identified that includes potential important targets for epigenetic modification during the process of lung tumorigenesis in animals exposed to environmental PAHs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Esophageal cancer detection based on tissue surface-enhanced Raman spectroscopy and multivariate analysis

    NASA Astrophysics Data System (ADS)

    Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Chen, Weisheng; Wang, Yue; Chen, Rong; Zeng, Haishan

    2013-01-01

    The capability of using silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) spectroscopy combined with principal component analysis (PCA) and linear discriminate analysis (LDA) to differentiate esophageal cancer tissue from normal tissue was presented. Significant differences in Raman intensities of prominent SERS bands were observed between normal and cancer tissues. PCA-LDA multivariate analysis of the measured tissue SERS spectra achieved diagnostic sensitivity of 90.9% and specificity of 97.8%. This exploratory study demonstrated great potential for developing label-free tissue SERS analysis into a clinical tool for esophageal cancer detection.

  16. Bioactive compounds produced by gut microbial tannase: implications for colorectal cancer development

    PubMed Central

    López de Felipe, Félix; de las Rivas, Blanca; Muñoz, Rosario

    2014-01-01

    The microorganisms in the human gastrointestinal tract have a profound influence on the transformation of food into metabolites which can impact human health. Gallic acid (GA) and pyrogallol (PG) are bioactive compounds displaying diverse biological properties, including carcinogenic inhibiting activities. However, its concentration in fruits and vegetables is generally low. These metabolites can be also generated as final products of tannin metabolism by microbes endowed with tannase, which opens up the possibility of their anti-cancer potential being increased. Patients with colorectal cancer (CRC) display an imbalanced gut microbiota respect to healthy population. The recent use of next generation sequencing technologies has greatly improved knowledge of the identity of bacterial species that colonize non-tumorous and tumorous tissues of CRC patients. This information provides a unique opportunity to shed light on the role played by gut microorganisms in the different stages of this disease. We here review the recently published gut microbiome associated to CRC patients and highlight tannase as an underlying gene function of bacterial species that selectively colonize tumorous tissues, but not adjacent non-malignant tissues. Given the anti-carcinogenic roles of GA and PG produced by gut tannin-degrading bacteria, we provide an overview of the possible consequences of this intriguing coincidence for CRC development. PMID:25538697

  17. Bioactive compounds produced by gut microbial tannase: implications for colorectal cancer development.

    PubMed

    López de Felipe, Félix; de Las Rivas, Blanca; Muñoz, Rosario

    2014-01-01

    The microorganisms in the human gastrointestinal tract have a profound influence on the transformation of food into metabolites which can impact human health. Gallic acid (GA) and pyrogallol (PG) are bioactive compounds displaying diverse biological properties, including carcinogenic inhibiting activities. However, its concentration in fruits and vegetables is generally low. These metabolites can be also generated as final products of tannin metabolism by microbes endowed with tannase, which opens up the possibility of their anti-cancer potential being increased. Patients with colorectal cancer (CRC) display an imbalanced gut microbiota respect to healthy population. The recent use of next generation sequencing technologies has greatly improved knowledge of the identity of bacterial species that colonize non-tumorous and tumorous tissues of CRC patients. This information provides a unique opportunity to shed light on the role played by gut microorganisms in the different stages of this disease. We here review the recently published gut microbiome associated to CRC patients and highlight tannase as an underlying gene function of bacterial species that selectively colonize tumorous tissues, but not adjacent non-malignant tissues. Given the anti-carcinogenic roles of GA and PG produced by gut tannin-degrading bacteria, we provide an overview of the possible consequences of this intriguing coincidence for CRC development.

  18. In vivo determination of optical properties and fluorophore characteristics of non-melanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Rajaram, Narasimhan; Kovacic, Dianne; Migden, Michael F.; Reichenberg, Jason S.; Nguyen, Tri H.; Tunnell, James W.

    2009-02-01

    Diffuse optical spectroscopy (DOS) and laser-induced fluorescence (LIF) techniques have widely been used as noninvasive tools for early cancer detection in several organs including the cervix, oral cavity and gastrointestinal tract. Using a combined DOS/LIF approach, one can simultaneously measure the morphology and biochemical composition of tissue and use these features to diagnose malignancy. We report for the first time to our knowledge both the optical properties and native fluorophore characteristics of non-melanoma skin cancer in the UV-visible range. We collected in vivo diffuse reflectance and intrinsic fluorescence measurements from 44 skin lesions on 37 patients. The skin sites were further categorized into three groups of non-melanoma skin cancer according to histopathology: 1) pre-cancerous actinic keratosis 2) malignant squamous cell carcinoma (SCC) and 3) basal cell carcinoma (BCC). We used a custom-built probe-based clinical system that collects both white light reflectance and laser-induced fluorescence in the wavelength range of 350-700 nm. We extracted the blood volume fraction, oxygen saturation, blood vessel size, tissue microarchitecture and melanin content from diffuse reflectance measurements. In addition, we determined the native fluorophore contributions of NADH, collagen and FAD from laser-induced fluorescence for all groups. The scattering from tissue decreased with progression from clinically normal to precancerous actinic keratosis to malignant SCC. A similar trend was observed for clinically normal skin and malignant BCC. Statistically significant differences were observed in the collagen contributions, which were lower in malignant SCC and BCC as compared to normal skin. Our data demonstrates that the mean optical properties and fluorophore contributions of normal, benign and malignant nonmelanoma cancers are significantly different from each other and can potentially be used as biomarkers for the early detection of skin cancer.

  19. Detection of oral squamous-cell cancer and precancerous lesions by fluorescence imaging in a hamster cheek-pouch model

    NASA Astrophysics Data System (ADS)

    Lam, Stephen; Kluftinger, A. M.; Hung, J.; Davis, N. L.; Quenville, N. F.; Palcic, Branko

    1993-03-01

    The role of non-skin phototoxic dose of Photofrin in the detection of dysplasia and carcinoma in situ was assessed in a small animal model of oral squamous cell cancer (SCC). Nine,10-dimethyl 1,2-benzanthracene (DMBA) impregnated cotton sutures, covered with a silicone sheath, were sewn into the hamster cheek pouch to produce dysplasia, carcinoma in situ, and invasive cancer. The yield of SCC was 83% by 20 weeks. Fluorescence imaging was performed using a specially designed device that exploits differences of fluorescence properties of normal, precancerous, and cancerous tissues with and without Photofrin. The fluorescence was induced by a helium-cadmium laser (442 nm) and then measured at two different wavelengths by an image intensified camera. Computed images using a mathematical transformation of fluorescence data were then displayed on a video monitor. Areas with dysplasia and both in situ and invasive cancers could be clearly delineated from the adjacent normal tissues. Lesions as small as 2 mm in diameter could be identified. Because of the presence of endogenous porphyrins, the addition of a non-skin phototoxic dose of Photofrin (0.25 mg/kg iv) did not enhance the signal to noise ratio. Our results suggest that fluorescence imaging can accurately detect both precancerous and cancerous lesions in the oral mucosa without exogenous porphyrins. It may have an important role as a non-invasive, clinical diagnostic tool in oropharyngeal cancer.

  20. A new mild hyperthermia device to treat vascular involvement in cancer surgery.

    PubMed

    Ware, Matthew J; Nguyen, Lam P; Law, Justin J; Krzykawska-Serda, Martyna; Taylor, Kimberly M; Cao, Hop S Tran; Anderson, Andrew O; Pulikkathara, Merlyn; Newton, Jared M; Ho, Jason C; Hwang, Rosa; Rajapakshe, Kimal; Coarfa, Cristian; Huang, Shixia; Edwards, Dean; Curley, Steven A; Corr, Stuart J

    2017-09-12

    Surgical margin status in cancer surgery represents an important oncologic parameter affecting overall prognosis. The risk of disease recurrence is minimized and survival often prolonged if margin-negative resection can be accomplished during cancer surgery. Unfortunately, negative margins are not always surgically achievable due to tumor invasion into adjacent tissues or involvement of critical vasculature. Herein, we present a novel intra-operative device created to facilitate a uniform and mild heating profile to cause hyperthermic destruction of vessel-encasing tumors while safeguarding the encased vessel. We use pancreatic ductal adenocarcinoma as an in vitro and an in vivo cancer model for these studies as it is a representative model of a tumor that commonly involves major mesenteric vessels. In vitro data suggests that mild hyperthermia (41-46 °C for ten minutes) is an optimal thermal dose to induce high levels of cancer cell death, alter cancer cell's proteomic profiles and eliminate cancer stem cells while preserving non-malignant cells. In vivo and in silico data supports the well-known phenomena of a vascular heat sink effect that causes high temperature differentials through tissues undergoing hyperthermia, however temperatures can be predicted and used as a tool for the surgeon to adjust thermal doses delivered for various tumor margins.

  1. Non-invasive Assessments of Adipose Tissue Metabolism In Vitro.

    PubMed

    Abbott, Rosalyn D; Borowsky, Francis E; Quinn, Kyle P; Bernstein, David L; Georgakoudi, Irene; Kaplan, David L

    2016-03-01

    Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with non-invasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored.

  2. Up-regulated expression of type II very low density lipoprotein receptor correlates with cancer metastasis and has a potential link to β-catenin in different cancers.

    PubMed

    He, Lei; Lu, Yanjun; Wang, Peng; Zhang, Jun; Yin, Chuanchang; Qu, Shen

    2010-11-03

    Very low density lipoprotein receptor (VLDLR) has been considered as a multiple function receptor due to binding numerous ligands, causing endocytosis and regulating cellular signaling. Our group previously reported that enhanced activity of type II VLDLR (VLDLR II), one subtype of VLDLR, promotes adenocarcinoma SGC7901 cells proliferation and migration. The aim of this study is to explore the expression levels of VLDLR II in human gastric, breast and lung cancer tissues, and to investigate its relationship with clinical characteristics and β-catenin expression status. VLDLR II expression was examined using immunohistochemistry (IHC) and Western blot in tumor tissues from 213 gastric, breast and lung cancer patients, tumor adjacent noncancerous tissues by same methods. Correlations between VLDLR II and clinical features, as well as β-catenin expression status were evaluated by statistical analysis. The immunohistochemical staining of VLDLR II showed statistical difference between tumor tissues and tumor adjacent noncancerous tissues in gastric, breast and lung cancers (P = 0.034, 0.018 and 0.043, respectively). Moreover, using Western, we found higher VLDLR II expression levels were associated with lymph node and distant metastasis in gastric and breast cancer (P < 0.05). Furthermore, highly significant positive correlations were found between VLDLR II and β-catenin in gastric cancer (r = 0.689; P < 0.001)breast cancer (r = 0.594; P < 0.001). According to the results of the current study, high VLDLR II expression is correlated with lymph node and distant metastasis in gastric and breast cancer patients, the data suggest that VLDLR II may be a clinical marker in cancers, and has a potential link with β-catenin signaling pathway. This is the first to reveal the closer relationship of VLDLR II with clinical information.

  3. Nanoparticle-based photodynamic therapy on non-melanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; Arce-Diego, J. L.

    2018-02-01

    There are several advantages of Photodynamic Therapy (PDT) for nonmelanoma skin cancer treatment compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages its noninvasive nature, the use of non ionizing radiation and its high selectivity can be mentioned. Despite all these advantages, the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. An adequate dosimetry is needed in order to personalize the protocol. There are strategies that try to overcome the current PDT shortcomings, such as the improvement of the photosensitizer accumulation in the target tissue, optical radiation distribution optimization or photochemical reactions maximization. These strategies can be further complemented by the use of nanostructures with conventional PDT. Customized dosimetry for nanoparticle-based PDT requires models in order to adjust parameters of different nature to get an optimal tumor removal. In this work, a predictive model of nanoparticle-based PDT is proposed and analyzed. Dosimetry in nanoparticle-based PDT is going to be influenced by photosensitizer-nanoparticle distribution in the malignant tissue, its influence in the optical radiation distribution and the subsequent photochemical reactions. Nanoparticles are considered as photosensitizer carriers on several types of non-melanoma skin cancer. Shielding effects are taken into account. The results allow to compare the estimated treatment outcome with and without nanoparticles.

  4. Physical non-viral gene delivery methods for tissue engineering.

    PubMed

    Mellott, Adam J; Forrest, M Laird; Detamore, Michael S

    2013-03-01

    The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that "fits-all" cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications.

  5. Physical non-viral gene delivery methods for tissue engineering

    PubMed Central

    Mellott, Adam J.; Forrest, M. Laird; Detamore, Michael S.

    2016-01-01

    The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that “fits-all” cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications. PMID:23099792

  6. Development and validation of a MRgHIFU non-invasive tissue acoustic property estimation technique.

    PubMed

    Johnson, Sara L; Dillon, Christopher; Odéen, Henrik; Parker, Dennis; Christensen, Douglas; Payne, Allison

    2016-11-01

    MR-guided high-intensity focussed ultrasound (MRgHIFU) non-invasive ablative surgeries have advanced into clinical trials for treating many pathologies and cancers. A remaining challenge of these surgeries is accurately planning and monitoring tissue heating in the face of patient-specific and dynamic acoustic properties of tissues. Currently, non-invasive measurements of acoustic properties have not been implemented in MRgHIFU treatment planning and monitoring procedures. This methods-driven study presents a technique using MR temperature imaging (MRTI) during low-temperature HIFU sonications to non-invasively estimate sample-specific acoustic absorption and speed of sound values in tissue-mimicking phantoms. Using measured thermal properties, specific absorption rate (SAR) patterns are calculated from the MRTI data and compared to simulated SAR patterns iteratively generated via the Hybrid Angular Spectrum (HAS) method. Once the error between the simulated and measured patterns is minimised, the estimated acoustic property values are compared to the true phantom values obtained via an independent technique. The estimated values are then used to simulate temperature profiles in the phantoms, and compared to experimental temperature profiles. This study demonstrates that trends in acoustic absorption and speed of sound can be non-invasively estimated with average errors of 21% and 1%, respectively. Additionally, temperature predictions using the estimated properties on average match within 1.2 °C of the experimental peak temperature rises in the phantoms. The positive results achieved in tissue-mimicking phantoms presented in this study indicate that this technique may be extended to in vivo applications, improving HIFU sonication temperature rise predictions and treatment assessment.

  7. Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer.

    PubMed

    Curry, Joseph M; Tuluc, Madalina; Whitaker-Menezes, Diana; Ames, Julie A; Anantharaman, Archana; Butera, Aileen; Leiby, Benjamin; Cognetti, David M; Sotgia, Federica; Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E

    2013-05-01

    Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed to determine the metabolic state of proliferative cancer cells. Interestingly, cell proliferation in cancer cells, as marked by Ki-67 immunostaining, was strictly correlated with oxidative mitochondrial metabolism (OXPHOS) and the uptake of mitochondrial fuels, as detected via MCT1 expression (p < 0.001). More specifically, three metabolic tumor compartments were delineated: (1) proliferative and mitochondrial-rich cancer cells (Ki-67+/TOMM20+/COX+/MCT1+); (2) non-proliferative and mitochondrial-poor cancer cells (Ki-67-/TOMM20-/COX-/MCT1-); and (3) non-proliferative and mitochondrial-poor stromal cells (Ki-67-/TOMM20-/COX-/MCT1-). In addition, high oxidative stress (MCT4+) was very specific for cancer tissues. Thus, we next evaluated the prognostic value of MCT4 in a second independent patient cohort (n = 40). Most importantly, oxidative stress (MCT4+) in non-proliferating epithelial cancer cells predicted poor clinical outcome (tumor recurrence; p < 0.0001; log-rank test), and was functionally associated with FDG-PET avidity (p < 0.04). Similarly, oxidative stress (MCT4+) in tumor stromal cells was specifically associated with higher tumor stage (p < 0.03), and was a highly specific marker for cancer-associated fibroblasts (p < 0.001). We propose that oxidative stress is a key hallmark of tumor tissues that drives high-energy metabolism in adjacent proliferating mitochondrial-rich cancer cells, via the paracrine transfer of mitochondrial fuels (such as L-lactate and ketone bodies). New antioxidants and MCT4 inhibitors should be developed to metabolically target "three-compartment tumor metabolism" in head and neck cancers. It is remarkable that two "non-proliferating" populations of cells (Ki-67-/MCT4+) within the tumor can actually

  8. Targeted expression of suicide gene by tissue-specific promoter and microRNA regulation for cancer gene therapy.

    PubMed

    Danda, Ravikanth; Krishnan, Gopinath; Ganapathy, Kalaivani; Krishnan, Uma Maheswari; Vikas, Khetan; Elchuri, Sailaja; Chatterjee, Nivedita; Krishnakumar, Subramanian

    2013-01-01

    In order to realise the full potential of cancer suicide gene therapy that allows the precise expression of suicide gene in cancer cells, we used a tissue specific Epithelial cell adhesion molecule (EpCAM) promoter (EGP-2) that directs transgene Herpes simplex virus-thymidine kinase (HSV-TK) expression preferentially in EpCAM over expressing cancer cells. EpCAM levels are considerably higher in retinoblastoma (RB), a childhood eye cancer with limited expression in normal cells. Use of miRNA regulation, adjacent to the use of the tissue-specific promoter, would provide the second layer of control to the transgene expression only in the tumor cells while sparing the normal cells. To test this hypothesis we cloned let-7b miRNA targets in the 3'UTR region of HSV-TK suicide gene driven by EpCAM promoter because let-7 family miRNAs, including let-7b, were found to be down regulated in the RB tumors and cell lines. We used EpCAM over expressing and let-7 down regulated RB cell lines Y79, WERI-Rb1 (EpCAM (+ve)/let-7b(down-regulated)), EpCAM down regulated, let-7 over expressing normal retinal Müller glial cell line MIO-M1(EpCAM (-ve)/let-7b(up-regulated)), and EpCAM up regulated, let-7b up-regulated normal thyroid cell line N-Thy-Ori-3.1(EpCAM (+ve)/let-7b(up-regulated)) in the study. The cell proliferation was measured by MTT assay, apoptosis was measured by probing cleaved Caspase3, EpCAM and TK expression were quantified by Western blot. Our results showed that the EGP2-promoter HSV-TK (EGP2-TK) construct with 2 or 4 copies of let-7b miRNA targets expressed TK gene only in Y79, WERI-Rb-1, while the TK gene did not express in MIO-M1. In summary, we have developed a tissue-specific, miRNA-regulated dual control vector, which selectively expresses the suicide gene in EpCAM over expressing cells.

  9. Trace elemental analysis in cancer-afflicted tissues of penis and testis by PIXE technique

    NASA Astrophysics Data System (ADS)

    Naga Raju, G. J.; John Charles, M.; Bhuloka Reddy, S.; Sarita, P.; Seetharami Reddy, B.; Rama Lakshmi, P. V. B.; Vijayan, V.

    2005-04-01

    PIXE technique was employed to estimate the trace elemental concentrations in the biological samples of cancerous penis and testis. A 3 MeV proton beam was employed to excite the samples. From the present results it can be seen that the concentrations of Cl, Fe and Co are lower in the cancerous tissue of the penis when compared with those in normal tissue while the concentrations of Cu, Zn and As are relatively higher. The concentrations of K, Ca, Ti, Cr, Mn, Br, Sr and Pb are in agreement within standard deviations in both cancerous and normal tissues. In the cancerous tissue of testis, the concentrations of K, Cr and Cu are higher while the concentrations of Fe, Co and Zn are lower when compared to those in normal tissue of testis. The concentrations of Cl, Ca, Ti and Mn are in agreement in both cancerous and normal tissues of testis. The higher levels of Cu lead to the development of tumor. Our results also support the underlying hypothesis of an anticopper, antiangiogenic approach to cancer therapy. The Cu/Zn ratios of both penis and testis were higher in cancer tissues compared to that of normal.

  10. Assessing the extent of non-aggressive cancer in clinically detected stage I non-small cell lung cancer.

    PubMed

    Kale, Minal S; Sigel, Keith; Mhango, Grace; Wisnivesky, Juan P

    2018-05-01

    Overdiagnosis among clinically detected lung cancers likely consists of cases that are non-aggressive and slowly progressive and will never disseminate, cause symptoms or be a threat to a subject's survival, even if untreated. In this study, we estimate the prevalence of non-aggressive lung cancers from a large, population-based cancer registry. We identified individuals ≥65 years with histologically confirmed, untreated stage I non-small cell lung cancers (NSCLCs) from the Surveillance, Epidemiology, and End Results-Medicare registry. We estimated the rate of non-aggressive lung cancers by determining the point at which the cumulative lung cancer-specific survival curve no longer changed (ie, the slope approaches zero). At this point, there are no additional deaths due to progressive lung cancer observed among untreated patients after adjusting for deaths from competing risks (these long-term survivors can be considered 'non-aggressive cases). The overall rate of non-aggressive cancers among 2197 clinically detected cases of untreated stage I NSCLC was 2.4%, 95% CI: 1.0% to 3.8%. The rate of non-aggressive cancer was 1.9% (95% CI: 0.0% to 4.9%) for women and 2.4% (95% CI: 0.7% to 4.1%) for men (p=0.84). When stratifying by tumour size, non-aggressive cancer rates were 10.2% (95% CI: 0.0% to 29.3%), 2.1% (95% CI: 0.0% to 9.2%), 4.9% (95% CI: 0.0% to 10.3%), 1.8% (95% CI: 0.0% to 5.2%) and 0.0% (95% CI: 0.0% to 1.0%) for tumour sizes <15 mm, 15-24 mm, 25-34 mm, 35-44 mm and ≥45 mm, respectively. In comparison with the smallest tumour sizes (<15 mm), the rates of non-aggressive cancers were not statistically significantly different for tumour sizes 15-24 mm (p=0.36), 25-34 mm (p=0.57), 35-44 mm (p=0.38) and tumour sizes >45 mm (p=0.30). We found relatively low rates of non-aggressive cancers among clinically detected, stage I NSCLC regardless of sex or size. Our findings suggest that most clinically diagnosed early stage cancers should be treated with

  11. 42 CFR 81.30 - Non-radiogenic cancers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Non-radiogenic cancers. 81.30 Section 81.30 Public... Causation § 81.30 Non-radiogenic cancers. The following cancers are considered non-radiogenic for the... cancers: (a) Chronic lymphocytic leukemia (ICD-9 code: 204.1) (b) [Reserved] ...

  12. 42 CFR 81.30 - Non-radiogenic cancers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Non-radiogenic cancers. 81.30 Section 81.30 Public... Causation § 81.30 Non-radiogenic cancers. The following cancers are considered non-radiogenic for the... cancers: (a) Chronic lymphocytic leukemia (ICD-9 code: 204.1) (b) [Reserved] ...

  13. European Organisation for Research and Treatment of Cancer (EORTC) Pathobiology Group standard operating procedure for the preparation of human tumour tissue extracts suited for the quantitative analysis of tissue-associated biomarkers.

    PubMed

    Schmitt, Manfred; Mengele, Karin; Schueren, Elisabeth; Sweep, Fred C G J; Foekens, John A; Brünner, Nils; Laabs, Juliane; Malik, Abha; Harbeck, Nadia

    2007-03-01

    With the new concept of 'individualized treatment and targeted therapies', tumour tissue-associated biomarkers have been given a new role in selection of cancer patients for treatment and in cancer patient management. Tumour biomarkers can give support to cancer patient stratification and risk assessment, treatment response identification, or to identifying those patients who are expected to respond to certain anticancer drugs. As the field of tumour-associated biomarkers has expanded rapidly over the last years, it has become increasingly apparent that a strong need exists to establish guidelines on how to easily disintegrate the tumour tissue for assessment of the presence of tumour tissue-associated biomarkers. Several mechanical tissue (cell) disruption techniques exist, ranging from bead mill homogenisation and freeze-fracturing through to blade or pestle-type homogenisation, to grinding and ultrasonics. Still, only a few directives have been given on how fresh-frozen tumour tissues should be processed for the extraction and determination of tumour biomarkers. The PathoBiology Group of the European Organisation for Research and Treatment of Cancer therefore has devised a standard operating procedure for the standardised preparation of human tumour tissue extracts which is designed for the quantitative analysis of tumour tissue-associated biomarkers. The easy to follow technical steps involved require 50-300 mg of deep-frozen cancer tissue placed into small size (1.2 ml) cryogenic tubes. These are placed into the shaking flask of a Mikro-Dismembrator S machine (bead mill) to pulverise the tumour tissue in the capped tubes in the deep-frozen state by use of a stainless steel ball, all within 30 s of exposure. RNA is isolated from the pulverised tissue following standard procedures. Proteins are extracted from the still frozen pulverised tissue by addition of Tris-buffered saline to obtain the cytosol fraction of the tumour or by the Tris buffer supplemented with

  14. Cancer-adipose tissue interaction and fluid flow synergistically modulate cell kinetics, HER2 expression, and trastuzumab efficacy in gastric cancer.

    PubMed

    Akutagawa, Takashi; Aoki, Shigehisa; Yamamoto-Rikitake, Mihoko; Iwakiri, Ryuichi; Fujimoto, Kazuma; Toda, Shuji

    2018-04-25

    Early local tumor invasion in gastric cancer results in likely encounters between cancer cells and submucosal and subserosal adipose tissue, but these interactions remain to be clarified. Microenvironmental mechanical forces, such as fluid flow, are known to modulate normal cell kinetics, but the effects of fluid flow on gastric cancer cells are poorly understood. We analyzed the cell kinetics and chemosensitivity in gastric cancer using a simple in vitro model that simultaneously replicated the cancer-adipocyte interaction and physical microenvironment. Gastric cancer cells (MKN7 and MKN74) were seeded on rat adipose tissue fragment-embedded discs or collagen discs alone. To generate fluid flow, samples were placed on a rotatory shaker in a CO 2 incubator. Proliferation, apoptosis, invasion, and motility-related molecules were analyzed by morphometry and immunostaining. Proteins were evaluated by western blot analysis. Chemosensitivity was investigated by trastuzumab treatment. Adipose tissue and fluid flow had a positive synergistic effect on the proliferative potential and invasive capacity of gastric cancer cells, and adipose tissue inhibited apoptosis in these cells. Adipose tissue upregulated ERK1/2 signaling in gastric cancer cells, but downregulated p38 signaling. Notably, adipose tissue and fluid flow promoted membranous and cytoplasmic HER2 expression and modulated chemosensitivity to trastuzumab in gastric cancer cells. We have demonstrated that cancer-adipocyte interaction and physical microenvironment mutually modulate gastric cancer cell kinetics. Further elucidation of the microenvironmental regulation in gastric cancer will be very important for the development of strategies involving molecular targeted therapy.

  15. miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Yunda; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102; Xu, Guoxing

    miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasionmore » while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. - Highlights: • miR-411-5p is downregulated in breast cancer tissues and cell lines. • miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro. • GRB2 is a direct target of miR-411-5p in breast cancer. • GRB2 is overexpressed in breast cancer and associates with disease outcome. • miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.« less

  16. GAB2 Amplification in Squamous Cell Lung Cancer of Non-Smokers.

    PubMed

    Park, Yu Rang; Bae, Soo Hyeon; Ji, Wonjun; Seo, Eul Ju; Lee, Jae Cheol; Kim, Hyeong Ryul; Jang, Se Jin; Choi, Chang Min

    2017-11-01

    Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers. © 2017 The Korean Academy of Medical Sciences.

  17. Improved connection details for adjacent prestressed bridge beams.

    DOT National Transportation Integrated Search

    2015-03-01

    Bridges with adjacent box beams and voided slabs are simply and rapidly constructed, and are well suited to : short to medium spans. The traditional connection between the adjacent members is a shear key lled with a : conventional non-shrink grout...

  18. Vorinostat differentially alters 3D nuclear structure of cancer and non-cancerous esophageal cells.

    PubMed

    Nandakumar, Vivek; Hansen, Nanna; Glenn, Honor L; Han, Jessica H; Helland, Stephanie; Hernandez, Kathryn; Senechal, Patti; Johnson, Roger H; Bussey, Kimberly J; Meldrum, Deirdre R

    2016-08-09

    The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an 'epigenetic' drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat's differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action.

  19. Stages of Non-Small Cell Lung Cancer

    MedlinePlus

    ... Cancer Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key ...

  20. Non-invasive label-free investigation and typing of head and neck cancers by multimodal nonlinear microscopy

    NASA Astrophysics Data System (ADS)

    Meyer, Tobias; Vogler, Nadine; Dietzek, Benjamin; Akimov, Denis; Inhestern, Johanna; Guntinas-Lichius, Orlando; Popp, Jürgen

    2012-06-01

    Early detection and typing of tumors is pressing matter in clinical research with important impacts for prognosis and successful treatment. Currently, staining is the golden standard in histopathology but requires surgical removal of tissue. In order to avoid resection of non-diseased tissue a non-invasive real-time imaging method is required which can be applied ideally intrasurgically. In this proceeding a combination of second harmonic generation (SHG), two photon excited fluorescence (TPEF) and coherent anti-Stokes Raman (CARS) imaging has been employed to investigate tissue sections of head and neck carcinomas focussing on laryngeal carcinoma. Primary laryngeal and other head and neck carcinomas consist to 99% of squamous cell carcinoma. By fusing the various imaging methods it is possible to measure the thickness of the epithelial cell layer as a marker for dysplastic or cancerous tissue degradation and to differentiate keratinizing and nonkeratininzing squamous cell carcinomas (SCC). As nonkeratinizing SCCs of the oropharynx correlate with a human papillomavirus (HPV) infection as a subentity of head and neck cancer, and HPV related tumors are associated with a better clinical prognosis, the differentiation between keratinizing and non-keratinizing forms of SCCs is of high diagnostic value. TPEF is capable of displaying cell nuclei, therefore, morphologic information as cell density, cell to cytoplasm ratio, size and shape of cell nuclei can be obtained. SHG - on the other hand - selectively reveals the collagen matrix of the connective tissue, which is useful for determination of tumor-islets boundaries within epithelial tissue - a prerequisite for precise resection. Finally CARS in the CH-stretching region visualizes the lipid content of the tissue, which can be correlated with the dysplastic grade of the tissue.

  1. Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

    PubMed

    Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

    2016-12-01

    Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Viscoelastic properties of normal and cancerous human breast cells are affected differently by contact to adjacent cells.

    PubMed

    Schierbaum, Nicolas; Rheinlaender, Johannes; Schäffer, Tilman E

    2017-06-01

    Malignant transformation drastically alters the mechanical properties of the cell and its response to the surrounding cellular environment. We studied the influence of the physical contact between adjacent cells in an epithelial monolayer on the viscoelastic behavior of normal MCF10A, non-invasive cancerous MCF7, and invasive cancerous MDA-MB-231 human breast cells. Using an atomic force microscopy (AFM) imaging technique termed force clamp force mapping (FCFM) to record images of the viscoelastic material properties, we found that normal MCF10A cells are stiffer and have a lower fluidity at confluent than at sparse density. Contrarily, cancerous MCF7 and MDA-MB-231 cells do not stiffen and do not decrease their fluidity when progressing from sparse to confluent density. The behavior of normal MCF10A cells appears to be governed by the formation of stable cell-cell contacts, because their disruption with a calcium-chelator (EGTA) causes the stiffness and fluidity values to return to those at sparse density. In contrast, EGTA-treatment of MCF7 and MDA-MB-231 cells does not change their viscoelastic properties. Confocal fluorescence microscopy showed that the change of the viscoelastic behavior in MCF10A cells when going from sparse to confluent density is accompanied by a remodeling of the actin cytoskeleton into thick stress fiber bundles, while in MCF7 and MDA-MB-231 cells the actin cytoskeleton is only composed of thin and short fibers, regardless of cell density. While the observed behavior of normal MCF10A cells might be crucial for providing mechanical stability and thus in turn integrity of the epithelial monolayer, the dysregulation of this behavior in cancerous MCF7 and MDA-MB-231 cells is possibly a central aspect of cancer progression in the epithelium. We measured the viscoelastic properties of normal and cancerous human breast epithelial cells in different states of confluency using atomic force microscopy. We found that confluent normal cells are

  3. Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis

    PubMed Central

    Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

    2018-01-01

    The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I–II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919–0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments. PMID:29616090

  4. Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis.

    PubMed

    Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

    2018-04-01

    The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I-II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919-0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments.

  5. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shi, Yongguo, E-mail: 1138303166@qq.com; Lu, Jianwei, E-mail: jianwei2010077@163.com; Zhou, Jing, E-mail: 2310848@163.com

    2014-04-04

    Highlights: • First, we have shown that upregulated of the Loc554202 in breast cancer tissues. • Second, we demonstrated the function of Loc554202 in breast cancer cell. • Finally, we demonstrated that LOC554202 knockdown could inhibit tumor growth in vivo. - Abstract: Data derived from massive cloning and traditional sequencing methods have revealed that long non-coding RNAs (lncRNA) play important roles in the development and progression of cancer. Although many studies suggest that the lncRNAs have different cellular functions, many of them are not yet to be identified and characterized for the mechanism of their functions. To address this question,more » we assay the expression level of lncRNAs–Loc554202 in breast cancer tissues and find that Loc554202 is significantly increased compared with normal control, and associated with advanced pathologic stage and tumor size. Moreover, knockdown of Loc554202 decreased breast cancer cell proliferation, induced apoptosis and inhibits migration/invasion in vitro and impeded tumorigenesis in vivo. These data suggest an important role of Loc554202 in breast tumorigenesis.« less

  6. Synergistic effect of sequential administration of mitoguazone (MGBG) and gemcitabine in treating tissue cultured human breast cancer cells and mammary rat tumors.

    PubMed

    Ishmael, D Richard; Chen, Wei R; Nordquist, John A; Liu, Hong; Nordquist, Robert E

    2003-04-01

    Modulation of cancer chemotherapeutic drugs has been attempted to increase efficacy and overcome resistance to the chemotherapeutic agent. Studies have shown schedule-dependent interactions in combined use of chemotherapeutic drugs. Mitoguazone (MGBG), an old drug with possible modulating activity, was used in combination with gemcitabine, a relatively new cancer drug, in treating tissue cultured human breast cancer cells and mammary rat tumors. Tissue cultured BOT-2 cancer cells were first treated with varying concentrations of gemcitabine and MGBG, independently. Combinations of the two drugs were then used with different scheduled administrations. Marked synergistic activity was found between gemcitabine and MGBG when the MGBG was given first, followed by gemcitabine 24 hours later. A non-toxic dose of MGBG enhanced the toxicity of gemcitabine by eight orders of magnitude using MTT assays in the tissue cultured human breast cancer cell study. The sequential administration of MGBG and gemcitabine also increased the survival rate of rats bearing mammary tumors in our pilot animal study.

  7. The role of adipose tissue in cancer-associated cachexia.

    PubMed

    Vaitkus, Janina A; Celi, Francesco S

    2017-03-01

    Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing

  8. Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk.

    PubMed

    Samoli, E; Lagiou, A; Zourna, P; Barbouni, A; Georgila, C; Tsikkinis, A; Vassilarou, D; Minaki, P; Sfikas, C; Spanos, E; Trichopoulos, D; Lagiou, P

    2015-04-01

    Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ERα(+) breast cancer and compared their IGF-1 blood levels with those of 178 ERα(+) and 83 ERα(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. ERα(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ERα status of women with BBD was taken into account, the difference in IGF-1 levels between ERα(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ERα(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ERα(+) breast cancer patients were compared with ERα(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. We found evidence in support of an interaction of IGF-1 with the expression of ERα in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer. Published by Oxford University Press on behalf of the European Society for Medical Oncology 2014.

  9. Laser induced autofluorescence for diagnosis of non-melanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Drakaki, E.; Makropoulou, M.; Serafetinides, A. A.; Merlemis, N.; Kalatzis, I.; Sianoudis, I. A.; Batsi, O.; Christofidou, E.; Stratigos, A. J.; Katsambas, A. D.; Antoniou, Ch.

    2015-01-01

    Non melanoma skin cancer is one of the most frequent malignant tumors among humans. A non-invasive technique, with high sensitivity and high specificity, would be the most suitable method for basal cell carcinoma (BCC) or other malignancies diagnostics, instead of the well established biopsy and histopathology examination. In the last decades, a non-invasive, spectroscopic diagnostic method was introduced, the laser induced fluorescence (LIF), which could generate an image contrast between different states of skin tissue. The noninvasiveness consists in that this biophotonic method do not require tissue sample excision, what is necessary in histopathology characterization and biochemical analysis of the skin tissue samples, which is worldwide used as an evaluation gold standard. The object of this study is to establish the possibilities of a relatively portable system for laser induced skin autofluorescence to differentiate malignant from nonmalignant skin lesions. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a Nd:YAG-3ω laser (λ=355 nm, 6 ns), used as an excitation source for the autofluorescence measurements. A portable fiber-based spectrometer was used to record fluorescence spectra of the sites of interest. The ex vivo results, obtained with this spectroscopic technique, were correlated with the histopathology results. After the analysis of the fluorescence spectra of almost 60 skin tissue areas, we developed an algorithm to distinguish different types of malignant lesions, including inflammatory areas. Optimization of the data analysis and potential use of LIF spectroscopy with 355 nm Nd:YAG laser excitation of tissue autofluorescence for clinical applications are discussed.

  10. CDC25AQ110del: A Novel Cell Division Cycle 25A Isoform Aberrantly Expressed in Non-Small Cell Lung Cancer

    PubMed Central

    Younis, Rania H.; Cao, Wei; Lin, Ruxian; Xia, Ronghui; Liu, Zhenqiu; Edelman, Martin J.; Mei, Yuping; Mao, Li; Ren, Hening

    2012-01-01

    Objective Lung cancer remains number one cause of cancer related deaths worldwide. Cell cycle deregulation plays a major role in the pathogenesis of Non-Small Cell Lung Cancer (NSCLC). CDC25A represents a critical cell cycle regulator that enhances cell cycle progression. In this study we aimed to investigate the role of a novel CDC25A transcriptional variant, CDC25AQ110del, on the regulation of the CDC25A protein, and its impact on prognosis of NSCLC patients. Methodology/Principal Findings Here we report a novel CDC25A transcript variant with codon 110 (Glutamine) deletion, that we termed CDC25AQ110del in NSCLC cells. In 9 (75%) of the 12 NSCLC cell lines, CDC25AQ110del expression accounted for more than 20% of the CDC25A transcripts. Biological effects of CDC25AQ110del were investigated in H1299 and HEK-293F cells using UV radiation, flowcytometry, cyclohexamide treatment, and confocal microscopy. Compared to CDC25Awt, CDC25AQ110del protein had longer half-life; cells expressing CDC25AQ110del were more resistant to UV irradiation and showed more mitotic activity. Taqman-PCR was used to quantify CDC25AQ110del expression levels in 88 primary NSCLC tumor/normal tissue pairs. In patients with NSCLC, Kaplan Meier curves showed tumors expressing higher levels of CDC25AQ110del relative to the adjacent lung tissues to have significantly inferior overall survival (P = .0018). Significance Here we identified CDC25AQ110del as a novel transcriptional variant of CDC25A in NSCLC. The sequence-specific nature of the abnormality could be a prognostic indicator in NSCLC patients as well as a candidate target for future therapeutic strategies. PMID:23071577

  11. Deep learning for tissue microarray image-based outcome prediction in patients with colorectal cancer

    NASA Astrophysics Data System (ADS)

    Bychkov, Dmitrii; Turkki, Riku; Haglund, Caj; Linder, Nina; Lundin, Johan

    2016-03-01

    Recent advances in computer vision enable increasingly accurate automated pattern classification. In the current study we evaluate whether a convolutional neural network (CNN) can be trained to predict disease outcome in patients with colorectal cancer based on images of tumor tissue microarray samples. We compare the prognostic accuracy of CNN features extracted from the whole, unsegmented tissue microarray spot image, with that of CNN features extracted from the epithelial and non-epithelial compartments, respectively. The prognostic accuracy of visually assessed histologic grade is used as a reference. The image data set consists of digitized hematoxylin-eosin (H and E) stained tissue microarray samples obtained from 180 patients with colorectal cancer. The patient samples represent a variety of histological grades, have data available on a series of clinicopathological variables including long-term outcome and ground truth annotations performed by experts. The CNN features extracted from images of the epithelial tissue compartment significantly predicted outcome (hazard ratio (HR) 2.08; CI95% 1.04-4.16; area under the curve (AUC) 0.66) in a test set of 60 patients, as compared to the CNN features extracted from unsegmented images (HR 1.67; CI95% 0.84-3.31, AUC 0.57) and visually assessed histologic grade (HR 1.96; CI95% 0.99-3.88, AUC 0.61). As a conclusion, a deep-learning classifier can be trained to predict outcome of colorectal cancer based on images of H and E stained tissue microarray samples and the CNN features extracted from the epithelial compartment only resulted in a prognostic discrimination comparable to that of visually determined histologic grade.

  12. Low junctional adhesion molecule A expression correlates with poor prognosis in gastric cancer.

    PubMed

    Huang, Jin-Yu; Xu, Ying-Ying; Sun, Zhe; Wang, Zhen-Ning; Zhu, Zhi; Song, Yong-Xi; Luo, Yang; Zhang, Xue; Xu, Hui-Mian

    2014-12-01

    The aberrant expression of junctional adhesion molecule A (JAM-A), which has a close correlation with the development, progression, metastasis, and prognosis of cancer, has been frequently reported. However, neither JAM-A expression nor its correlation with clinicopathologic variables and patient survival has been defined in gastric cancers. Moreover, little is known about the role of JAM-A in gastric cancer progression. We carried out the present study to investigate the prognostic value of JAM-A expression in gastric cancer patients. Furthermore, the biological roles of JAM-A in gastric cancer progression were also investigated. We determined JAM-A expression in 167 primary gastric cancer tissues and 94 matched adjacent non-tumor tissues by immunohistochemistry. Transwell migration assays and matrigel invasion assays were used to explore the role of JAM-A in gastric cancer cells migration and invasion. CCK-8 assays were used to examine the effect of JAM-A on the proliferation of gastric cancer cells. JAM-A was downregulated in gastric cancer tissues. Low JAM-A expression was significantly associated with tumor size, lymphatic vessel invasion, lymph node metastasis, and TNM stage. Low JAM-A expression was also significantly associated with poor disease-specific survival in gastric cancer patients. Multivariate analysis demonstrated low JAM-A expression as an independent factor predicting poor survival. In addition, JAM-A had the effect on inhibition of gastric cancer cells migration and invasion. However, JAM-A had no significant effects on proliferation of gastric cancer cells. Low JAM-A expression correlates with poor clinical outcome and promotes cell migration and invasion in gastric cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. NON-INVASIVE RADIOFREQUENCY ABLATION OF CANCER TARGETED BY GOLD NANOPARTICLES

    PubMed Central

    Cardinal, Jon; Klune, John Robert; Chory, Eamon; Jeyabalan, Geetha; Kanzius, John S.; Nalesnik, Michael; Geller, David A.

    2008-01-01

    Introduction Current radiofrequency ablation (RFA) techniques require invasive needle placement and are limited by accuracy of targeting. The purpose of this study was to test a novel non-invasive radiowave machine that uses RF energy to thermally destroy tissue. Gold nanoparticles were designed and produced to facilitate tissue heating by the radiowaves. Methods A solid state radiowave machine consisting of a power generator and transmitting/receiving couplers which transmit radiowaves at 13.56 MHz was used. Gold nanoparticles were produced by citrate reduction and exposed to the RF field either in solutions testing or after incubation with HepG2 cells. A rat hepatoma model using JM-1 cells and Fisher rats was employed using direct injection of nanoparticles into the tumor to focus the radiowaves for select heating. Temperatures were measured using a fiber-optic thermometer for real-time data. Results Solutions containing gold nanoparticles heated in a time- and power-dependent manner. HepG2 liver cancer cells cultured in the presence of gold nanoparticles achieved adequate heating to cause cell death upon exposure to the RF field with no cytotoxicity attributable to the gold nanoparticles themselves. In vivo rat exposures at 35W using gold nanoparticles for tissue injection resulted in significant temperature increases and thermal injury at subcutaneous injection sites as compared to vehicle (water) injected controls. Discussion These data show that non-invasive radiowave thermal ablation of cancer cells is feasible when facilitated by gold nanoparticles. Future studies will focus on tumor selective targeting of nanoparticles for in vivo tumor destruction. PMID:18656617

  14. Promoter methylation and expression of DNA repair genes MGMT and ERCC1 in tissue and blood of rectal cancer patients.

    PubMed

    Shalaby, Sally M; El-Shal, Amal S; Abdelaziz, Lobna A; Abd-Elbary, Eman; Khairy, Mostafa M

    2018-02-20

    Rectal cancer involves one-third of colorectal cancers (CRCs). Recently, data supported that DNA methylation have a role in CRC pathogenesis. In the present study we aimed to analyze the methylation status of MGMT and ERCC1 promoter regions in blood and tissue of patients with benign and malignant rectal tumors. We also studied the methylated MGMT and ERCC1 genes and their relations with clinicopathological features. Furthermore, we suggested that methylation may play a critical function in the regulation of MGMT and ERCC1 expression. Fifty patients with non-metastatic cancer rectum and 43 patients with benign rectal lesions were involved in the study. DNA extraction from blood and rectal specimens was done to analyze the methylation status of MGMT and ERCC1 genes by methylation-specific PCR method. RNA was extracted also to determine the expression levels of these genes by real time-PCR. The frequency of MGMT and ERCC1 methylation was significantly higher in rectum cancers than in benign tumors both for the tissue and the blood (p<0.001). There was no relation between MGMT or ERCC1 methylation and clinicopathological features; while they were correlated with the response to therapy. An interesting finding that the agreement of the methylation levels in the blood and rectal tissue was classified as good (κ=0.78) for MGMT gene and as very good (κ=0.85) for ERCC1. Lastly, the MGMT and ERCC1 genes methylation was associated with down-regulation of their mRNA expression when compared with the non-methylated status. Our findings provided evidence that both blood and tumor tissue MGMT and ERCC1 methylation were associated with cancer rectum. MGMT or ERCC1 methylation in blood could be suitable non-invasive biomarkers differentiating benign and malignant rectal tumors. Furthermore, the methylation of the MGMT and ERCC1 promoter regions was associated with down-regulation of their mRNA expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Decreased expression of dual specificity phosphatase 22 in colorectal cancer and its potential prognostic relevance for stage IV CRC patients.

    PubMed

    Yu, Dan; Li, Zhenli; Gan, Meifu; Zhang, Hanyun; Yin, Xiaoyang; Tang, Shunli; Wan, Ledong; Tian, Yiping; Zhang, Shuai; Zhu, Yimin; Lai, Maode; Zhang, Dandan

    2015-11-01

    Dual specificity phosphatase 22 (DUSP22) is a novel dual specificity phosphatase that has been demonstrated to be a cancer suppressor gene associated with numerous biological and pathological processes. However, little is known of DUSP22 expression profiling in colorectal cancer and its prognostic value. Our study aims to investigate the role of DUSP22 expression in the prognosis of colorectal cancer. We detected the mRNA expression in 92 paired primary colorectal cancer tissues and the corresponding adjacent normal tissues by using QuantiGenePlex assay. The Friedman test was used to determine the statistical difference of gene expression. Kaplan-Meier survival analysis was performed. Mann-Whitney test and Kruskal-Wallis test were used to conduct data analyses to determine the prognostic value. Statistical significance was set at P < 0.05. In 74 of 92 cases, DUSP22 mRNA was reduced in primary colorectal cancer tissues, compared to the adjacent normal tissues. The mRNA levels of DUSP22 were significantly lower in colorectal cancer tissues than in adjacent normal tissues (0.0290 vs. 0.0658; P < 0.001). Low expression of DUSP22 correlated significantly with large tumor size (P = 0.013). No association was observed between DUSP22 mRNA expression and differentiation, histopathological type, tumor invasion, lymph node metastases, metastases, TNM stage, and Duke's phase (all P > 0.05). Kaplan-Meier analysis indicated that DUSP22 expression had no significant relationship with overall survival in all patients (P > 0.05). Interestingly, low expression level of DUSP22 in stage IV patients had a poor survival measures with a marginal P value (P = 0.07). Reduced DUSP22 expression was found in colorectal cancer specimens. Low expression level of DUSP22 in stage IV patients had a poor survival outcome. Further study is required for the investigation of the role of DUSP22 in colorectal cancer.

  16. Investigation of Epstein-Barr virus DNA in formalin-fixed and paraffin- embedded breast cancer tissues.

    PubMed

    Kalkan, Ahmet; Ozdarendeli, Aykut; Bulut, Yasemin; Yekeler, Hayrettin; Cobanoglu, Bengu; Doymaz, Mehmet Z

    2005-01-01

    To investigate etiological role of Epstein-Barr virus (EBV) DNA in breast cancer. The presence of EBV DNA in 57 breast cancer tissues was investigated with a sensitive PCR assay. The breast cancer tissues were from invasive ductular (n=28), lobular (n=20) and other miscellaneous carcinomas (n=9). Tissues from normal breasts and patients with various benign breast diseases (n=55): fibrocystic disease (n=34), fibroadenoma (n=16), hyperplasia, and granulomatous mastitis (n=5), were used as control samples. EBV DNA was detected in 13 (23%) cancerous tissues (7 ductular, 4 lobular, 2 other carcinoma) and 19 (35%) in the control tissues. The difference between EBV presence in malignant and benign tissues was not statistically significant (p>0.05). The presence of EBV DNA was detected almost equally in both breast cancer and normal tissues, which indicates no etiological role for EBV in breast cancer. We suggest further etiological studies. Copyright (c) 2005 S. Karger AG, Basel.

  17. Protocol for HER2 FISH Using a Non-cross-linking, Formalin-free Tissue Fixative to Combine Advantages of Cryo-preservation and Formalin Fixation

    PubMed Central

    Loibner, Martina; Oberauner-Wappis, Lisa; Viertler, Christian; Groelz, Daniel; Zatloukal, Kurt

    2017-01-01

    Morphologic assessment of formalin-fixed, paraffin-embedded (FFPE) tissue samples has been the gold standard for cancer diagnostics for decades due to its excellent preservation of morphology. Personalized medicine increasingly provides individually adapted and targeted therapies for characterized individual diseases enabled by combined morphological and molecular analytical technologies and diagnostics. Performance of morphologic and molecular assays from the same FFPE specimen is challenging because of the negative impact of formalin due to chemical modification and cross-linking of nucleic acids and proteins. A non-cross-linking, formalin-free tissue fixative has been recently developed to fulfil both requirements, i.e., to preserve morphology like FFPE and biomolecules like cryo-preservation. Since FISH is often required in combination with histopathology and molecular diagnostics, we tested the applicability of FISH protocols on tissues treated with this new fixative. We found that formalin post-fixation of histological sections of non-cross-linking, formalin-free and paraffin-embedded (NCFPE) breast cancer tissue generated equivalent results to those with FFPE tissue in human epidermal growth factor receptor 2 (HER2) FISH analysis. This protocol describes how a FISH assay originally developed and validated for FFPE tissue can be used for NCFPE tissues by a simple post-fixation step of histological sections. PMID:29364207

  18. Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

    PubMed

    Tsoli, Maria; Swarbrick, Michael M; Robertson, Graham R

    2016-06-01

    Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  19. Thermal therapy techniques for skin and superficial tissue disease

    NASA Astrophysics Data System (ADS)

    Stauffer, Paul R.

    2000-01-01

    There are numerous diseases and abnormal growths and conditions that afflict the skin and underlying superficial tissues. In addition to cancers such as primary, recurrent, and metastatic melanomas and carcinomas, there are many non-malignant conditions such as psoriasis plaques, port wine stains, warts, and superficial cut and bum wounds. Many of these clinical conditions have been shown responsive to treatment with thermal therapy - either low temperature freezing (cryotherapy),. moderate temperature warming to about 41-45°C (hyperthermia), or high temperature (>50°C) ablation or coagulation necrosis therapy. Because both very low and very high temperature therapies are for the most part non-selectively destructive in nature, they normally are used for applications where therapy can be localized precisely in the desired target and some necrosis of adjacent normal tissues is acceptable. With the exception of precision controlled cryotherapy or laser surgery (e.g. wart, mole, tattoo and port wine stain removal) or focal thermal surgery of small deep-seated nodules, it is generally preferred to use moderate thermal therapy (hyperthermia) in the treatment of skin and subcutaneous tissue disease in order to preserve the protective barrier characteristic of intact skin within the target region while inducing more subtle long term therapeutic improvement in the disease condition. This type of subtle thermal therapy is usually administered in combination with one or more other therapies such as radiation or chemotherapy - something with a differential effect on the target and surrounding normal tissues that can be magnified by the adjuvant use of heat.

  20. MicroRNA-137 Contributes to Dampened Tumorigenesis in Human Gastric Cancer by Targeting AKT2

    PubMed Central

    Wu, Liping; Chen, Jingtao; Ding, Chunsheng; Wei, Shutang; Zhu, Yanhong; Yang, Wenyi; Zhang, Xiaoyang; Wei, Xuejv; Han, Dazheng

    2015-01-01

    MiRNAs play important roles in tumorigenesis. This study focused on exploring the effects and regulation mechanism of miRNA-137 on the biological behaviors of gastric cancer. Total RNA was extracted from tissues of 100 patients with gastric cancer and from four gastric cancer cell lines. Expression of miR-137 was detected by real-time PCR from 100 patients. The effects of miR-137 overexpression on gastric cancer cells’ proliferation, apoptosis, migration and invasion ability were investigated in vitro and in vivo. The target gene of miR-137 was predicted by Targetscan on line software, screened by dual luciferase reporter gene assay and demonstrated by western blot. As a result, the expression of miR-137 was significant reduced in gastric cancer cell line HGC-27, HGC-803, SGC-7901 and MKN-45 as well as in gastric cancer tissues compared with GES-1 cell or matched adjacent non-neoplastic tissues (p<0.001). The re-introduction of miR-137 into gastric cancer cells was able to inhibit cell proliferation, migration and invasion. The in vivo experiments demonstrated that the miR-137 overexpression can reduce the gastric cancer cell proliferation and metastasis. Bioinformatic and western blot analysis indicated that the miR-137 acted as tumor suppressor roles on gastric cancer cells through targeting AKT2 and further affecting the Bad and GSK-3β. In conclusion, the miR-137 which is frequently down-regulated in gastric cancer is potentially involved in gastric cancer tumorigenesis and metastasis by regulating AKT2 related signal pathways. PMID:26102366

  1. An Examination of Ultrasound Measured Tissue Perfusion on Breast Cancer

    DTIC Science & Technology

    1998-12-01

    is similar to those of the study by Ivey et al. [9] in which high intensity fields were used to produce cavitation bubbles for ultrasound contrast...ft * * AD AWARD NUMBER DAMD17-94-J-4144 TITLE: ^ Examination of Ultrasound Measured Tissue Perfusion on Breast Cancer...Examination of Ultrasound Measured Tissue Perfusion on Breast Cancer 3. REPORT TYPE AND DATES COVERED Final (1 Jun 94 - 30 Nov 98) 5. FUNDING

  2. Hyperspectral Stimulated Raman Scattering Microscopy Unravels Aberrant Accumulation of Saturated Fat in Human Liver Cancer.

    PubMed

    Yan, Shuai; Cui, Sishan; Ke, Kun; Zhao, Bixing; Liu, Xiaolong; Yue, Shuhua; Wang, Ping

    2018-06-05

    Lipid metabolism is dysregulated in human cancers. The analytical tools that could identify and quantitatively map metabolites in unprocessed human tissues with submicrometer resolution are highly desired. Here, we implemented analytical hyperspectral stimulated Raman scattering microscopy to map the lipid metabolites in situ in normal and cancerous liver tissues from 24 patients. In contrast to the conventional wisdom that unsaturated lipid accumulation enhances tumor cell survival and proliferation, we unexpectedly visualized substantial amount of saturated fat accumulated in cancerous liver tissues, which was not seen in majority of their adjacent normal tissues. Further analysis by mass spectrometry confirmed significant high levels of glyceryl tripalmitate specifically in cancerous liver. These findings suggest that the aberrantly accumulated saturated fat may have great potential to be a metabolic biomarker for liver cancer.

  3. Immune biomarkers for chronic inflammation related complications in non-cancerous and cancerous diseases.

    PubMed

    Meirow, Yaron; Baniyash, Michal

    2017-08-01

    Chronic inflammation arising in a diverse range of non-cancerous and cancerous diseases, dysregulates immunity and exposes patients to a variety of complications. These include immunosuppression, tissue damage, cardiovascular diseases and more. In cancer, chronic inflammation and related immunosuppression can directly support tumor growth and dramatically reduce the efficacies of traditional treatments, as well as novel immune-based therapies, which require a functional immune system. Nowadays, none of the immune biomarkers, regularly used by clinicians can sense a developing chronic inflammation, thus complications can only be detected upon their appearance. This review focuses on the necessity for such immune status biomarkers, which could predict complications prior to their appearance. Herein we bring examples for the use of cellular and molecular biomarkers in diagnosis, prognosis and follow-up of patients suffering from various cancers, for prediction of response to immune-based anti-cancer therapy and for prediction of cardiovascular disease in type 2 diabetes patients. Monitoring such biomarkers is expected to have a major clinical impact in addition to unraveling of the entangled complexity underlying dysregulated immunity in chronic inflammation. Thus, newly discovered biomarkers and those that are under investigation are projected to open a new era towards combating the silent damage induced by chronic inflammation.

  4. Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer.

    PubMed

    Wang, Yuan-Yuan; Lehuédé, Camille; Laurent, Victor; Dirat, Béatrice; Dauvillier, Stéphanie; Bochet, Ludivine; Le Gonidec, Sophie; Escourrou, Ghislaine; Valet, Philippe; Muller, Catherine

    2012-11-28

    Among the many different cell types surrounding breast cancer cells, the most abundant are those that compose mammary adipose tissue, mainly mature adipocytes and progenitors. New accumulating recent evidences bring the tumor-surrounding adipose tissue into the light as a key component of breast cancer progression. The purpose of this review is to emphasize the role that adipose tissue might play by locally affecting breast cancer cell behavior and subsequent clinical consequences arising from this dialog. Two particular clinical aspects are addressed: obesity that was identified as an independent negative prognostic factor in breast cancer and the oncological safety of autologous fat transfer used in reconstructive surgery for breast cancer patients. This is preceded by the overall description of adipose tissue composition and function with special emphasis on the specificity of adipose depots and the species differences, key experimental aspects that need to be taken in account when cancer is considered. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Deep learning based tissue analysis predicts outcome in colorectal cancer.

    PubMed

    Bychkov, Dmitrii; Linder, Nina; Turkki, Riku; Nordling, Stig; Kovanen, Panu E; Verrill, Clare; Walliander, Margarita; Lundin, Mikael; Haglund, Caj; Lundin, Johan

    2018-02-21

    Image-based machine learning and deep learning in particular has recently shown expert-level accuracy in medical image classification. In this study, we combine convolutional and recurrent architectures to train a deep network to predict colorectal cancer outcome based on images of tumour tissue samples. The novelty of our approach is that we directly predict patient outcome, without any intermediate tissue classification. We evaluate a set of digitized haematoxylin-eosin-stained tumour tissue microarray (TMA) samples from 420 colorectal cancer patients with clinicopathological and outcome data available. The results show that deep learning-based outcome prediction with only small tissue areas as input outperforms (hazard ratio 2.3; CI 95% 1.79-3.03; AUC 0.69) visual histological assessment performed by human experts on both TMA spot (HR 1.67; CI 95% 1.28-2.19; AUC 0.58) and whole-slide level (HR 1.65; CI 95% 1.30-2.15; AUC 0.57) in the stratification into low- and high-risk patients. Our results suggest that state-of-the-art deep learning techniques can extract more prognostic information from the tissue morphology of colorectal cancer than an experienced human observer.

  6. In situ detection of cancerous kidney tissue by means of fiber ATR-FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Sablinskas, Valdas; Velicka, Martynas; Pucetaite, Milda; Urboniene, Vidita; Ceponkus, Justinas; Bandzeviciute, Rimante; Jankevicius, Feliksas; Sakharova, Tatiana; Bibikova, Olga; Steiner, Gerald

    2018-02-01

    The crucial goal of kidney-sparing surgical resection of a malignant tumor is complete removal of the cancerous tissue. The exact border between the cancerous and normal tissues is not always possible to identify by naked eye, therefore, a supplementary intraoperative diagnosis is needed. Unfortunately, intraoperative pathology methods used nowadays are time consuming and of inadequate quality rendering not definitive diagnosis. It has recently been shown that ATR-FTIR spectroscopy can be used for fast discrimination between cancerous and normal kidney tissues by analyzing the collected spectra of the tissue touch imprint smears. Most prominent differences are obtained in the wavenumber region from 950 cm-1 to 1250 cm-1, where the spectral bands due to the molecular vibrations of glycogen arise in the spectra of cancerous tissue smears. Such method of detection of cancerous tissue is limited by requirement to transfer the suspected tissue from the body to the FTIR instrument and stamp it on an ATR crystal of the spectrometer. We propose a spectroscopic tool which exploits the same principle of detection of cancerous cells as mentioned above, but does not require the tissue to be transferred from the body to the spectrometer. The portable spectrometer used in this design is equipped with fiber ATR probe and a sensitive liquid nitrogen cooled MCT detector. The design of the fiber probe allows the ATR tip to be changed easily in order to use only new sterilized tips for each measurement point of the tissue. It also enables sampling multiple areas of the suspected tissue with high lateral resolution which, in turn, increases accuracy with which the marginal regions between normal and cancerous tissues can be identified. Due to the loss of optical signal in the fiber probe the spectra have lower signal-to-noise ratio than in the case of standard ATR sampling setup. However, software for the spectral analysis used with the fiber probe design is still able to distinguish

  7. Food Impaction and Periodontal/Peri-Implant Tissue Conditions in Relation to the Embrasure Dimensions Between Implant-Supported Fixed Dental Prostheses and Adjacent Teeth: A Cross-Sectional Study.

    PubMed

    Jeong, Jin-Seok; Chang, Moontaek

    2015-12-01

    Food impaction and periodontal/peri-implant tissue conditions were evaluated in relation to the embrasure dimensions between implant-supported fixed dental prostheses (FDPs) and adjacent teeth. A total of 215 embrasures of 150 FDPs in 100 patients (55 males and 45 females, aged 27 to 83 years; mean age: 56 years) were included in the study. Clinical assessments of the periodontal/peri-implant mucosal conditions, radiographic assessments of embrasure dimensions, and overall patient satisfaction were used as explanatory variables for the food impaction and periodontal/peri-implant tissue conditions adjacent to implant-supported FDPs in the generalized estimating equation (GEE) analysis. Food impaction was reported in 96 (44.7%) of 215 embrasures between implant-supported FDPs and adjacent teeth. Food impaction was reported more frequently in the embrasures with proximal contact loss than in those with tight contact (P = 0.009). Overall patient satisfaction was influenced negatively by food impaction in the proximal embrasures (P = 0.01). Among embrasure dimensions, only the embrasure surface area (ESA) significantly influenced food impaction (P = 0.03). Significant influences of various embrasure dimensions on the periodontal/peri-implant mucosal conditions and bone level at the implant were found in the univariate and multivariate GEE analyses. Food impaction between implant-supported FDPs and adjacent teeth occurred more frequently when proximal contact was lost and ESA increased. Food impaction negatively affected overall patient satisfaction. Embrasure dimensions influenced the periodontal/peri-implant mucosal conditions and bone level at the implant.

  8. Distinction of gastric cancer tissue based on surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Ma, Jun; Zhou, Hanjing; Gong, Longjing; Liu, Shu; Zhou, Zhenghua; Mao, Weizheng; Zheng, Rong-er

    2012-12-01

    Gastric cancer is one of the most common malignant tumors with high recurrence rate and mortality rate in China. This study aimed to evaluate the diagnostic capability of Surface-enhanced Raman spectroscopy (SERS) based on gold colloids for distinguishing gastric tissues. Gold colloids were directly mixed with the supernatant of homogenized tissues to heighten the Raman signal of various biomolecule. A total of 56 samples were collected from normal (30) and cancer (26). Raman spectra were obtained with a 785nm excitation in the range of 600-1800 cm-1. Significant spectral differences in SERS mainly belong to nucleic acid, proteins and lipids, particularly in the range of 653, 726, 828, 963, 1004, 1032, 1088, 1130, 1243, 1369, 1474, 1596, 1723 cm-1. PCA-LDA algorithms with leave-one-patient-out cross validation yielded diagnostic sensitivities of 90% (27/30), specificities of 88.5% (23/26), and accuracy of 89.3% (50/56), for classification of normal and cancer tissues. The receiver operating characteristic (ROC) surface is 0.917, illustrating the diagnostic utility of SERS together with PCA-LDA to identify gastric cancer from normal tissue. This work demonstrated the SERS techniques can be useful for gastric cancer detection, and it is also a potential technique for accurately identifying cancerous tumor, which is of considerable clinical importance to real-time diagnosis.

  9. TPX2 expression is associated with poor survival in gastric cancer.

    PubMed

    Tomii, Chiharu; Inokuchi, Mikito; Takagi, Yoko; Ishikawa, Toshiaki; Otsuki, Sho; Uetake, Hiroyuki; Kojima, Kazuyuki; Kawano, Tatsuyuki

    2017-01-09

    Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for microtubule formation in human cells. Several studies have demonstrated that TPX2 is overexpressed in multiple tumor types and promotes tumor growth and metastasis. However, there have been few reports regarding its role in gastric cancer. In this study, we evaluated TPX2 expression and investigated its correlations with gastric cancer clinicopathological features and prognosis. Tumor samples were obtained from 290 patients with gastric adenocarcinoma who had undergone gastrectomy. The expression of TPX2 protein was examined using immunohistochemical staining. TPX2 messenger RNA (mRNA) levels were evaluated using real-time quantitative reverse transcription PCR in 19 of the gastric cancer tumors and adjacent normal tissues. The mRNA levels of TPX2 were significantly higher in gastric cancer tissues than in matched adjacent normal tissues (p = 0.004). In the immunohistochemical analysis, TPX2 overexpression was found in 123 (42.4%) of 290 patients. High TPX2 expression was positively associated with age, type of histology, depth of tumor, lymph node metastasis, stage, and remote metastasis or recurrence. High TPX2 expression was significantly associated with poorer disease-specific survival (p = 0.004) and relapse-free interval (p = 0.013). Our results indicated that high TPX2 expression was associated with tumor progression and poor survival in gastric cancer.

  10. No association between Epstein-Barr Virus and Mouse Mammary Tumor Virus with Breast Cancer in Mexican Women

    NASA Astrophysics Data System (ADS)

    Morales-Sánchez, Abigail; Molina-Muñoz, Tzindilú; Martínez-López, Juan L. E.; Hernández-Sancén, Paulina; Mantilla, Alejandra; Leal, Yelda A.; Torres, Javier; Fuentes-Pananá, Ezequiel M.

    2013-10-01

    Breast cancer is the most frequent malignancy affecting women worldwide. It has been suggested that infection by Epstein Barr Virus (EBV), Mouse Mammary Tumor Virus or a similar virus, MMTV-like virus (MMTV-LV), play a role in the etiology of the disease. However, studies looking at the presence of these viruses in breast cancer have produced conflicting results, and this possible association remains controversial. Here, we used polymerase chain reaction assay to screen specific sequences of EBV and MMTV-LV in 86 tumor and 65 adjacent tissues from Mexican women with breast cancer. Neither tumor samples nor adjacent tissue were positive for either virus in a first round PCR and only 4 tumor samples were EBV positive by a more sensitive nested PCR. Considering the study's statistical power, these results do not support the involvement of EBV and MMTV-LV in the etiology of breast cancer.

  11. Non-Invasive Prostate Cancer Characterization with Diffusion-Weighted MRI: Insight from In silico Studies of a Transgenic Mouse Model

    PubMed Central

    Hill, Deborah K.; Heindl, Andreas; Zormpas-Petridis, Konstantinos; Collins, David J.; Euceda, Leslie R.; Rodrigues, Daniel N.; Moestue, Siver A.; Jamin, Yann; Koh, Dow-Mu; Yuan, Yinyin; Bathen, Tone F.; Leach, Martin O.; Blackledge, Matthew D.

    2017-01-01

    Diffusion-weighted magnetic resonance imaging (DWI) enables non-invasive, quantitative staging of prostate cancer via measurement of the apparent diffusion coefficient (ADC) of water within tissues. In cancer, more advanced disease is often characterized by higher cellular density (cellularity), which is generally accepted to correspond to a lower measured ADC. A quantitative relationship between tissue structure and in vivo measurements of ADC has yet to be determined for prostate cancer. In this study, we establish a theoretical framework for relating ADC measurements with tissue cellularity and the proportion of space occupied by prostate lumina, both of which are estimated through automatic image processing of whole-slide digital histology samples taken from a cohort of six healthy mice and nine transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. We demonstrate that a significant inverse relationship exists between ADC and tissue cellularity that is well characterized by our model, and that a decrease of the luminal space within the prostate is associated with a decrease in ADC and more aggressive tumor subtype. The parameters estimated from our model in this mouse cohort predict the diffusion coefficient of water within the prostate-tissue to be 2.18 × 10−3 mm2/s (95% CI: 1.90, 2.55). This value is significantly lower than the diffusion coefficient of free water at body temperature suggesting that the presence of organelles and macromolecules within tissues can drastically hinder the random motion of water molecules within prostate tissue. We validate the assumptions made by our model using novel in silico analysis of whole-slide histology to provide the simulated ADC (sADC); this is demonstrated to have a significant positive correlation with in vivo measured ADC (r2 = 0.55) in our mouse population. The estimation of the structural properties of prostate tissue is vital for predicting and staging cancer aggressiveness, but prostate

  12. Tissue spray ionization mass spectrometry for rapid recognition of human lung squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Wei, Yiping; Chen, Liru; Zhou, Wei; Chingin, Konstantin; Ouyang, Yongzhong; Zhu, Tenggao; Wen, Hua; Ding, Jianhua; Xu, Jianjun; Chen, Huanwen

    2015-05-01

    Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue samples has been shown to provide highly specific molecular information. In this study, we apply this method to the analysis of 38 pairs of human lung squamous cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z 757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z 832.43), were identified using high-resolution tandem mass spectrometry. Monte Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was used to distinguish full-mass-range mass spectra of cancer samples from the mass spectra of normal tissues. With 5 principal components and 30 - 40 Monte Carlo samplings, the accuracy of cancer identification in matched tissue samples reached 94.42%. Classification of a tissue sample required less than 1 min, which is much faster than the analysis of frozen sections. The rapid, in situ diagnosis with minimal sample consumption provided by TSI-MS is advantageous for surgeons. TSI-MS allows them to make more informed decisions during surgery.

  13. Doublecortin and CaM kinase-like-1 expression in pathological stage I non-small cell lung cancer.

    PubMed

    Tao, Hiroyuki; Tanaka, Toshiki; Okabe, Kazunori

    2017-08-01

    Doublecortin and CaM kinase-like-1 (DCLK1) regulates microtubule polymerization in migrating neurons. Recently, DCLK1 has been reported to act as an intestinal tumor stem cell marker and has been shown to be expressed in cancer cells and in the stroma of breast, colon, pancreatic, and prostate cancers. Here, we studied DCLK1 expression in non-small cell lung cancer (NSCLC) by immunohistochemistry in association with clinicopathological factors and patient prognosis. DCLK1 expression was analyzed by immunohistochemical staining of surgical specimens from 232 patients with pathological stage I NSCLC, including 187 adenocarcinomas. Relationships between the expression status of DCLK1 and clinicopathological factors were examined. The impact of DCLK1 expression status and other clinicopathological factors on survival was evaluated by univariate and multivariate analyses. Thirty-three (14.2%) of 232 patients had DCLK1-positive cancer cells. DCLK1 was also expressed in the tumor stroma in most of the specimens and was significantly associated with DCLK1 expression in cancer cells. DCLK1-positive cancer cells were more common in non-adenocarcinoma tissues (44.4%) than in adenocarcinoma tissues (7.0%). Moreover, positive DCLK1 expression in cancer cells and stromal cells was correlated with a worse prognosis. Histological analyses revealed that the presence of DCLK1-positive cancer cells was an independent risk factor for poor prognosis in adenocarcinoma, but was not significantly associated with prognosis in non-adenocarcinoma. DCLK1 expression was observed in tumor cells in patients with pathological stage I NSCLC and was correlated with adverse prognosis, especially in patients with adenocarcinoma. DCLK1 may be a potential new therapeutic target.

  14. Differentiating characteristic microstructural features of cancerous tissues using Mueller matrix microscope.

    PubMed

    Wang, Ye; He, Honghui; Chang, Jintao; Zeng, Nan; Liu, Shaoxiong; Li, Migao; Ma, Hui

    2015-12-01

    Polarized light imaging can provide rich microstructural information of samples, and has been applied to the detections of various abnormal tissues. In this paper, we report a polarized light microscope based on Mueller matrix imaging by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission optical microscope. The maximum errors for the absolute values of Mueller matrix elements are reduced to 0.01 after calibration. This Mueller matrix microscope has been used to examine human cervical and liver cancerous tissues with fibrosis. Images of the transformed Mueller matrix parameters provide quantitative assessment on the characteristic features of the pathological tissues. Contrast mechanism of the experimental results are backed up by Monte Carlo simulations based on the sphere-cylinder birefringence model, which reveal the relationship between the pathological features in the cancerous tissues at the cellular level and the polarization parameters. Both the experimental and simulated data indicate that the microscopic transformed Mueller matrix parameters can distinguish the breaking down of birefringent normal tissues for cervical cancer, or the formation of birefringent surrounding structures accompanying the inflammatory reaction for liver cancer. With its simple structure, fast measurement and high precision, polarized light microscope based on Mueller matrix shows a good diagnosis application prospect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Long non-coding RNA ZEB1-AS1 is associated with poor prognosis in gastric cancer and promotes cancer cell metastasis.

    PubMed

    Liu, X-J; Li, S-L; Li, J-S; Lu, H; Yin, L-L; Zheng, W-F; Wang, W-C

    2018-05-01

    To investigate the expression of long non-coding RNA zinc-finger E-box binding homeobox 1-AS1 (lncRNA ZEB1-AS1) in gastric cancer cells and tissues, to study its effect on the gastric cancer cell metastasis capacity, and analyze its clinical significance. The relative expression level of lncRNA ZEB1-AS1 in gastric cancer cells was detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transwell assay was used to detect the effects of lncRNA ZEB1-AS1 on the invasion and metastasis capacities of gastric cancer cells. qRT-PCR was used to detect the relative expression level of lncRNA ZEB1-AS1 in 75 pairs of gastric cancer tissues, and the correlations of its expression with the pathological characteristics and prognosis of patients were statistically analyzed. qRT-PCR showed that compared with that in the normal gastric epithelial cell (GES-1), the expression level of lncRNA ZEB1-AS1 was up-regulated in gastric cancer cells (MKN28, MKN45, BGC823, MGC803, KATOIII, and SGC7901). LncRNA ZEB1-AS1 interfering sequence was transfected into model cells, and Transwell assay showed that the cell invasion and migration capacities were significantly inhibited. qRT-PCR also revealed that the expression of lncRNA ZEB1-AS1 was up-regulated in 55 out of 75 cases of gastric cancer and para-carcinoma tissues (fold change > 1). Statistical analysis showed that the high expression of lncRNA ZEB1-AS1 was positively correlated with TNM staging (p = 0.002), lymph node metastasis (p = 0.002), and invasion degree (p = 0.004). The survival time of patients with high expression of lncRNA ZEB1-AS1 in gastric cancer tissues was shorter than that of patients with low expression (p = 0.004). LncRNA ZEB1-AS1 is highly expressed in gastric cancer tissues and cells, and it is expected to be a new prognostic marker of gastric cancer used for the clinical diagnosis and prognostic evaluation. After intervention in lncRNA ZEB1-AS1 expression, the cell invasion and migration

  16. Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2016-10-01

    Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

  17. Reduced expression of the long non-coding RNA AI364715 in gastric cancer and its clinical significance.

    PubMed

    Zhu, Shengqian; Mao, Jinqin; Shao, Yongfu; Chen, Fang; Zhu, Xiaoqin; Xu, Dingli; Zhang, Xinjun; Guo, Junming

    2015-09-01

    Long non-coding RNA (lncRNA), which is greater than 200 nucleotides, is a class of RNA molecules without protein coding function. In recent years, studies have shown that lncRNAs are associated with cancers. They are affecting the occurrence and development of cancers. However, the diagnostic significances of lncRNAs in gastric cancer are largely unknown. In this study, we focused on AI364715, one typical lncRNA. A total of 186 samples were collected from two cancer centers. To find the potential association between its level and gastric cancer, we first collected 75 paired gastric cancer tissues and normal tissues, which are 5 cm away from the edge of carcinoma. Besides, 18 human healthy gastric mucosa and 18 gastric precancerous lesions (dysplasia) were also collected. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was first used to detect the expression level of AI364715 at multiple stages of gastric tumorigenesis. Then, the relationships between AI364715 level and the clinicopathological factors of patients with gastric cancer were analyzed. The results showed that the expression level of AI364715 in gastric cancer tissues was downregulated. Meanwhile, its expression level was closely associated with tumor size and differentiation. More importantly, AI364715 expression level was significantly changed in dysplasia, the typical precancerous lesions. Taken together, AI364715 may be a potential biomarker for the diagnosis of gastric cancer.

  18. The aluminium content of breast tissue taken from women with breast cancer.

    PubMed

    House, Emily; Polwart, Anthony; Darbre, Philippa; Barr, Lester; Metaxas, George; Exley, Christopher

    2013-10-01

    The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48 μg/L. Method blanks were used to estimate background levels of contamination of 14.80 μg/L. The mean concentration of aluminium across all tissues was 0.39 μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content

  19. Distribution of erlotinib in rash and normal skin in cancer patients receiving erlotinib visualized by matrix assisted laser desorption/ionization mass spectrometry imaging.

    PubMed

    Nishimura, Meiko; Hayashi, Mitsuhiro; Mizutani, Yu; Takenaka, Kei; Imamura, Yoshinori; Chayahara, Naoko; Toyoda, Masanori; Kiyota, Naomi; Mukohara, Toru; Aikawa, Hiroaki; Fujiwara, Yasuhiro; Hamada, Akinobu; Minami, Hironobu

    2018-04-06

    The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed. Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs. 120 ± 103 ions/mm 2 ; P = 0.009 in paired t -test). LC-MS/MS confirmed that the concentration of erlotinib in the skin rashes was higher than that in normal skin in the superficial skin layer (1946 ± 1258 vs. 1174 ± 662 ng/cm 3 ; P = 0.028 in paired t -test). The results of MALDI-MSI and LC-MS/MS were well correlated (coefficient of correlation 0.879, P < 0.0001). Focal distribution of erlotinib in the skin tissue was visualized using non-labeled MALDI-MSI. Erlotinib concentration in the superficial layer of the skin rashes was higher than that in the adjacent normal skin. We examined patients with advanced pancreatic cancer who developed skin rashes after treatment with erlotinib and gemcitabine. We biopsied both the rash and adjacent normal skin tissues, and visualized and compared the distribution of erlotinib within the skin using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The tissue concentration of erlotinib was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with laser microdissection.

  20. Distribution of erlotinib in rash and normal skin in cancer patients receiving erlotinib visualized by matrix assisted laser desorption/ionization mass spectrometry imaging

    PubMed Central

    Mizutani, Yu; Takenaka, Kei; Imamura, Yoshinori; Chayahara, Naoko; Toyoda, Masanori; Kiyota, Naomi; Mukohara, Toru; Aikawa, Hiroaki; Fujiwara, Yasuhiro; Hamada, Akinobu; Minami, Hironobu

    2018-01-01

    Background The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed. Results Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs. 120 ± 103 ions/mm2; P = 0.009 in paired t-test). LC-MS/MS confirmed that the concentration of erlotinib in the skin rashes was higher than that in normal skin in the superficial skin layer (1946 ± 1258 vs. 1174 ± 662 ng/cm3; P = 0.028 in paired t-test). The results of MALDI-MSI and LC-MS/MS were well correlated (coefficient of correlation 0.879, P < 0.0001). Conclusions Focal distribution of erlotinib in the skin tissue was visualized using non-labeled MALDI-MSI. Erlotinib concentration in the superficial layer of the skin rashes was higher than that in the adjacent normal skin. Methods We examined patients with advanced pancreatic cancer who developed skin rashes after treatment with erlotinib and gemcitabine. We biopsied both the rash and adjacent normal skin tissues, and visualized and compared the distribution of erlotinib within the skin using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The tissue concentration of erlotinib was also measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS) with laser microdissection. PMID:29719624

  1. Mastl overexpression is associated with epithelial to mesenchymal transition and predicts a poor clinical outcome in gastric cancer.

    PubMed

    Sun, Xian-Jun; Li, Yan-Liang; Wang, Long-Gang; Liu, Li-Qing; Ma, Heng; Hou, Wen-Hong; Yu, Jin-Ming

    2017-12-01

    Microtubule-associated serine/threonine kinase like (Mastl) is deregulated in a number of types of human malignancy and may be a kinase target for cancer treatment. The aim of the present study was to determine the Mastl expression in gastric cancer and to clarify its clinical and prognostic significance. Immunohistochemistry was performed on a cohort of 126 postoperative gastric cancer samples to detect the expression of Mastl and two epithelial to mesenchymal transition (EMT) markers, epithelial-cadherin and Vimentin. The χ 2 test, Kaplan-Meier estimator analysis and Cox's regression model were used to analyze the data. Upregulated Mastl protein expression was observed in the gastric cancer tissues compared with that in the adjacent non-cancerous gastric tissues. Increased Mastl expression was identified in 54/126 (42.9%) gastric cancer samples, and was significantly associated with lymph node metastasis, tumor relapse, EMT status and poor overall survival. Additional analysis demonstrated that the Mastl expression level stratified the patient outcome in stage III, but not stage II tumor subgroups. Cox's regression analysis revealed that increased Mastl expression was an independent prognostic factor for patients with gastric cancer. Mastl expression may be a valuable prognostic marker and a potential target for patients with gastric cancer.

  2. Monoclonal antibodies targeting non-small cell lung cancer stem-like cells by multipotent cancer stem cell monoclonal antibody library.

    PubMed

    Cao, Kaiyue; Pan, Yunzhi; Yu, Long; Shu, Xiong; Yang, Jing; Sun, Linxin; Sun, Lichao; Yang, Zhihua; Ran, Yuliang

    2017-02-01

    Cancer stem cells (CSCs) are a rare subset of cancer cells that play a significant role in cancer initiation, spreading, and recurrence. In this study, a subpopulation of lung cancer stem-like cells (LCSLCs) was identified from non-small cell lung carcinoma cell lines, SPCA-1 and A549, using serum-free suspension sphere-forming culture method. A monoclonal antibody library was constructed using immunized BLAB/c mice with the multipotent CSC cell line T3A-A3. Flow cytometry analysis showed that 33 mAbs targeted antigens can be enriched in sphere cells compared with the parental cells of SPCA-1 and A549 cell lines. Then, we performed functional antibody screening including sphere-forming inhibiting and invasion inhibiting assay. The results showed that two antibodies, 12C7 and 9B8, notably suppressed the self-renewal and invasion of LCSLCs. Fluorescence-activated cell sorting (FACs) found that the positive cells recognized by mAbs, 12C7 or 9B8, displayed features of LCSLCs. Interestingly, we found that these two antibodies recognized different subsets of cells and their combination effect was superior to the individual effect both in vitro and in vivo. Tissue microarrays were applied to detect the expression of the antigens targeted by these two antibodies. The positive expression of 12C7 and 9B8 targeted antigen was 84.4 and 82.5%, respectively, which was significantly higher than that in the non-tumor lung tissues. In conclusion, we screened two potential therapeutic antibodies that target different subsets of LCSLCs.

  3. An informatics model for tissue banks--lessons learned from the Cooperative Prostate Cancer Tissue Resource.

    PubMed

    Patel, Ashokkumar A; Gilbertson, John R; Parwani, Anil V; Dhir, Rajiv; Datta, Milton W; Gupta, Rajnish; Berman, Jules J; Melamed, Jonathan; Kajdacsy-Balla, Andre; Orenstein, Jan; Becich, Michael J

    2006-05-05

    Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for calculating PSA recurrence

  4. Regulatory role of tumor necrosis factor receptor-associated factor 6 in breast cancer by activating the protein kinase B/glycogen synthase kinase 3β signaling pathway.

    PubMed

    Shen, Hongyu; Li, Liangpeng; Yang, Sujin; Wang, Dandan; Zhou, Siying; Chen, Xiu; Tang, Jinhai

    2017-08-01

    Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an endogenous adaptor of innate and adaptive immune responses, and serves a crucial role in tumor necrosis factor receptor and toll‑like/interleukin‑1 receptor signaling. Although studies have demonstrated that TRAF6 has oncogenic activity, its potential contributions to breast cancer in human remains largely uninvestigated. The present study examined the expression levels and function of TRAF6 in breast carcinoma (n=32) and adjacent healthy (n=25) tissue samples. Compared with adjacent healthy tissues, TRAF6 protein expression levels were significantly upregulated in breast cancer tissues. Reverse transcription‑quantitative polymerase chain reaction analysis revealed a significant upregulation of the cellular proliferative marker Ki‑67 and proliferation cell nuclear antigen expression levels in breast carcinoma specimens. Furthermore, protein expression levels of the accessory molecule, transforming growth factor β‑activated kinase 1 (TAK1), were significantly increased in breast cancer patients, as detected by western blot analysis. As determined by MTT assay, TRAF6 exerted profoundly proliferative effects in the MCF‑7 breast cancer cell line; however, these detrimental effects were ameliorated by TAK1 inhibition. Notably, protein kinase B (AKT)/glycogen synthase kinase (GSK)3β phosphorylation levels were markedly upregulated in breast cancer samples, compared with adjacent healthy tissues. In conclusion, an altered TRAF6‑TAK1 axis and its corresponding downstream AKT/GSK3β signaling molecules may contribute to breast cancer progression. Therefore, TRAF6 may represent a potential therapeutic target for the treatment of breast cancer.

  5. Circular RNA hsa_circ_0000745 may serve as a diagnostic marker for gastric cancer.

    PubMed

    Huang, Mei; He, Yi-Ren; Liang, Li-Chuan; Huang, Qiang; Zhu, Zhi-Qiang

    2017-09-14

    To determine whether circular RNAs (circRNAs) are involved in pathological processes of gastric cancer (GC). Three circRNAs with differential expression in GC and colorectal cancer were randomly selected for validation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using 20 pairs of gastric tissues and normal tissues. Based on the predicted circRNA-miRNA network, we then focused on hsa_circ_0000745, which was found to be down-regulated in 20 GC tissues compared with normal tissues. The hsa_circ_0000745 levels were further analyzed by qRT-PCR in 60 GC tissues and paired adjacent non-tumor tissues, as well as 60 plasma samples from GC patients and 60 plasma samples from healthy controls. The associations between the levels of hsa_circ_0000745 and the clinicopathological features of GC patients were statistically assessed. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_0000745 in GC. Hsa_circ_0000745 was down-regulated in GC tissues vs non-tumorous tissues ( P < 0.001) and in plasma samples from patients with GC vs healthy controls ( P < 0.001). The expression level of hsa_circ_0000745 in GC tissues correlated with tumor differentiation, while the expression level in plasma correlated with tumor-node-metastasis stage. The area under the ROC curve (AUC) of hsa_circ_0000745 in plasma was 0.683, suggesting good diagnostic value. Plasma hsa_circ_0000745 level combined with carcinoembryogenic antigen (CEA) level increased the AUC to 0.775. Hsa_circ_0000745 plays an important role in GC and its expression level in plasma in combination with CEA level is a promising diagnostic marker for this malignancy.

  6. Non-invasive spectroscopic techniques in the diagnosis of non-melanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Drakaki, E.; Sianoudis, IA; Zois, EN; Makropoulou, M.; Serafetinides, AA; Dessinioti, C.; Stefanaki, E.; Stratigos, AJ; Antoniou, C.; Katsambas, A.; Christofidou, E.

    2017-11-01

    The number of non-melanoma skin cancers is increasing worldwide and has become an important health and economic issue. Early detection and treatment of skin cancer can significantly improve patient outcome. Therefore there is an increase in the demand for proper management and effective non-invasive diagnostic modalities in order to avoid relapses or unnecessary treatments. Although the gold standard of diagnosis for non-melanoma skin cancers is biopsy followed by histopathology evaluation, optical non-invasive diagnostic tools have obtained increased attention. Emerging non-invasive or minimal invasive techniques with possible application in the diagnosis of non-melanoma skin cancers include high-definition optical coherence tomography, fluorescence spectroscopy, oblique incidence diffuse reflectance spectrometry among others spectroscopic techniques. Our findings establish how those spectrometric techniques can be used to more rapidly and easily diagnose skin cancer in an accurate and automated manner in the clinic.

  7. Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

    PubMed Central

    Uno, K; Homma, S; Satoh, T; Nakanishi, K; Abe, D; Matsumoto, K; Oki, A; Tsunoda, H; Yamaguchi, I; Nagasawa, T; Yoshikawa, H; Aonuma, K

    2007-01-01

    Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE. PMID:17211468

  8. MicroRNA-138 inhibits proliferation of cervical cancer cells by targeting c-Met.

    PubMed

    Li, B; Yang, X-X; Wang, D; Ji, H-K

    2016-01-01

    MicroRNAs (miRNAs) function as important post-transcriptional regulators involved in a wide range of biological behaviors. MicroRNA-138 (miR-138) has been shown to play a critical role in tumor pathogenesis, the present study aimed to investigate the role of miR-138 in cervical cancer. CCK-8 assay was performed to measure the viabilities of cancer cells. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the mRNA and protein expression, respectively. Moreover, the miRNA target genes were validated with luciferase activity assay. In the current study, we found that the expression of miR-138 was significantly down-regulated in cervical cancer tissues compared to the adjacent non-cancer tissues. CCK-8 assay showed that over-expression of miR-138 suppressed the proliferation of four cervical cancer cell lines including HeLa, SiHa, C33A and CaSki. By contrast, down-regulation of miR-138 promoted the growth of cervical cancer cells. In addition, increased expression of miR-138 led to a reduction in c-Met expression, whereas inhibition of miR-138 enhanced c-Met levels in cervical cancer cells. The luciferase reporter assay showed that c-Met was a direct target of miR-138 in cervical cancer cells. These findings demonstrated that miR-138 inhibited cervical cancer cells proliferation via c-Met, providing a novel target for the molecular treatment of cervical cancer.

  9. Comparative Proteomics of Tumor and Paired Normal Breast Tissue Highlights Potential Biomarkers in Breast Cancer.

    PubMed

    Da Costa, Gustavo Góes; Gomig, Talita Helen Bombardelli; Kaviski, Rodrigo; Santos Sousa, Karla; Kukolj, Caroline; De Lima, Rubens Silveira; De Andrade Urban, Cicero; Cavalli, Iglenir J; Ribeiro, Enilze M S F

    2015-01-01

    Breast cancer is the most common type of cancer among women worldwide, and about 57,000 new cases are expected for the Brazilian population in 2015. Elucidation of protein expression and modification is essential for the biological understanding, early diagnosis and therapeutics of breast cancer. The main objectives of the study are comparison between the proteome of tumor and paired non-tumor breast cancer tissues, describing all identified proteins, highlighting the ones most differentially expressed and comparing the data with existing literature. The five paired samples from patients with invasive ductal carcinoma were analyzed by 2-DE and MS. We collected 161 identified spots corresponding to 110 distinct proteins. Forty-three differentially-expressed spots were common to at least two samples, and the ten proteins with the highest-fold changes were CASPE, ENOG, TPM1, CAPG, VIME, TPM3, TRFE, PDIA6, WDR61 and PDIA3. Metabolic enzymes and proteins with binding functions were the most representative functional classes of proteins with increased and decreased expression in tumor tissue respectively. Taking the fold change as a parameter, we point to future targets to be studied by functional methods in a search for biomarkers for initiation and progress of breast cancer. Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  10. Low dose of continuous – wave microwave irradiation did not cause temperature increase in muscles tissue adjacent to titanium alloy implants – an animal study

    PubMed Central

    2013-01-01

    Background Research studies on the influence of radiofrequency electromagnetic radiation on implants in vitro have failed to investigate temperature changes in the tissues adjacent to the implants under microwave therapy. We therefore, used a rabbit model in an effort to determine the impact of microwave therapy on temperature changes in tissues adjacent to the titanium alloy implants and the safety profile thereof. Methods Titanium alloy internal fixation plates were implanted in New Zealand rabbits in the middle of femur. Microwave therapy was performed by a 2450 MHz microwave generator 3 days after the surgery. Temperature changes of muscles adjacent to the implants were recorded under exposure to dose-gradient microwave radiation from 20w to 60w. Results Significant difference between control and microwave treatment group at peak temperatures (Tpeak) and temperature gap (Tgap= Tpeak-Tvally) were observed in deep muscles (Tpeak, 41.63 ± 0.21°C vs. 44.40 ± 0.17°C, P < 0.01; Tgap, 5.33 ± 0.21°C vs. 8.10 ± 0.36°C, P < 0.01) and superficial muscles (Tpeak, 41.53 ± 0.15°C vs. 42.03 ± 0.23°C, P = 0.04; Tgap, 5.23 ± 0.21°C vs. 5.80 ± 0.17°C, P = 0.013) under 60 w, and deep muscles (Tpeak, 40.93 ± 0.25°C vs. 41.87 ± 0.23°C, P = 0.01; Tgap, 4.73 ± 0.20°C vs. 5.63 ± 0.35°C, P = 0.037) under 50w, but not under 20, 30 and 40w. Conclusion Our results suggest that low-dose (20w-40w) continuous-wave microwave irradiation delivered by a 2450 MHz microwave generator might be a promising treatment for patients with titanium alloy internal fixation, as it did not raise temperature in muscle tissues adjacent to the titanium alloy implant. PMID:24365389

  11. Tissue modification with feedback: the smart scalpel

    NASA Astrophysics Data System (ADS)

    Sebern, Elizabeth L.; Brenan, Colin J. H.; Anderson, R. Rox; Hunter, Ian W.

    1998-10-01

    While feedback control is widespread throughout many engineering fields, there are almost no examples of surgical instruments that utilize a real-time detection and intervention strategy. This concept of closed loop feedback can be applied to the development of autonomous or semi- autonomous minimally invasive robotic surgical systems for efficient excision or modification of diseased tissue. Spatially localized regions of the tissue are first probed to distinguish pathological from healthy tissue based on differences in histochemical and morphological properties. Energy is directed to only the diseased tissue, minimizing collateral damage by leaving the adjacent healthy tissue intact. Continuous monitoring determines treatment effectiveness and, if needed, enables real-time treatment modifications to produce optimal therapeutic outcomes. The present embodiment of this general concept is a microsurgical instrument we call the Smart Scalpel, designed to treat skin angiodysplasias such as port wine stains. Other potential Smart Scalpel applications include psoriasis treatment and early skin cancer detection and intervention.

  12. Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium

    NASA Technical Reports Server (NTRS)

    Shim, Veronica; Gauthier, Mona L.; Sudilovsky, Daniel; Mantei, Kristin; Chew, Karen L.; Moore, Dan H.; Cha, Imok; Tlsty, Thea D.; Esserman, Laura J.

    2003-01-01

    Cyclooxygenase-2 (COX-2) is emerging as an important cancer biomarker and is now an experimental target for solid tumor treatment.However, no study has exclusively focused on COX-2 expression in early lesions such as ductal carcinoma in situ (DCIS). We examined COX-2 expression by immunohistochemistry in 46 cases of women undergoing surgical resection for DCIS. We found that COX-2 expression was detected in 85% of all DCIS specimens, with increased COX-2 staining correlating with higher nuclear grade. Strikingly, COX-2 staining intensity in the normal adjacent epithelium was stronger than in the DCIS lesion itself. Our observations demonstrate that COX-2 is up-regulated in the normal adjacent epithelium and supports the hypothesis that the surrounding epithelial tissue is part of the disease process in DCIS.

  13. Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer.

    PubMed

    Cui, X Y; Tinholt, M; Stavik, B; Dahm, A E A; Kanse, S; Jin, Y; Seidl, S; Sahlberg, K K; Iversen, N; Skretting, G; Sandset, P M

    2016-02-01

    ESSENTIALS: A hypoxic microenvironment is a common feature of tumors that may influence activation of coagulation. MCF-7 and SK-BR-3 breast cancer cells and breast cancer tissue samples were used. The results showed transcriptional repression of tissue factor pathway inhibitor expression in hypoxia. Hypoxia-inducible factor 1α may be a target for the therapy of cancer-related coagulation and thrombosis. Activation of coagulation is a common finding in patients with cancer, and is associated with an increased risk of venous thrombosis. As a hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia-inducible factor (HIF)-1α in breast cancer cells and their correlation in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. Time-dependent and dose-dependent downregulation of TFPI mRNA (quantitative RT-PCR) and of free TFPI protein (ELISA) were observed in hypoxia. Western blotting showed parallel increases in the levels of HIF-1α protein and TF. HIF-1α inhibitor abolished or attenuated the hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and HIF-1α overexpression caused strong repression of TFPI promoter activity. Subsequent chromatin immunoprecipitation and mutagenesis analysis demonstrated a functional hypoxia response element within the TFPI promoter, located at -1065 to -1060 relative to the transcriptional start point. In breast cancer tissue samples, gene expression analyses showed a positive correlation between the mRNA expression of TFPI and that of HIF-1α. This study demonstrates that HIF-1α is involved in the transcriptional regulation of the TFPI gene, and suggests that a hypoxic microenvironment inside a breast tumor may

  14. The Network Organization of Cancer-associated Protein Complexes in Human Tissues

    PubMed Central

    Zhao, Jing; Lee, Sang Hoon; Huss, Mikael; Holme, Petter

    2013-01-01

    Differential gene expression profiles for detecting disease genes have been studied intensively in systems biology. However, it is known that various biological functions achieved by proteins follow from the ability of the protein to form complexes by physically binding to each other. In other words, the functional units are often protein complexes rather than individual proteins. Thus, we seek to replace the perspective of disease-related genes by disease-related complexes, exemplifying with data on 39 human solid tissue cancers and their original normal tissues. To obtain the differential abundance levels of protein complexes, we apply an optimization algorithm to genome-wide differential expression data. From the differential abundance of complexes, we extract tissue- and cancer-selective complexes, and investigate their relevance to cancer. The method is supported by a clustering tendency of bipartite cancer-complex relationships, as well as a more concrete and realistic approach to disease-related proteomics. PMID:23567845

  15. Accurate Characterization of Benign and Cancerous Breast Tissues: Aspecific Patient Studies using Piezoresistive Microcantilevers

    PubMed Central

    PANDYA, HARDIK J.; ROY, RAJARSHI; CHEN, WENJIN; CHEKMAREVA, MARINA A.; FORAN, DAVID J.; DESAI, JAYDEV P.

    2014-01-01

    Breast cancer is the largest detected cancer amongst women in the US. In this work, our team reports on the development of piezoresistive microcantilevers (PMCs) to investigate their potential use in the accurate detection and characterization of benign and diseased breast tissues by performing indentations on the micro-scale tissue specimens. The PMCs used in these experiments have been fabricated using laboratory-made silicon-on-insulator (SOI) substrate, which significantly reduces the fabrication costs. The PMCs are 260 μm long, 35 μm wide and 2 μm thick with resistivity of order 1.316 X 10−3 Ω-cm obtained by using boron diffusion technique. For indenting the tissue, we utilized 8 μm thick cylindrical SU-8 tip. The PMC was calibrated against a known AFM probe. Breast tissue cores from seven different specimens were indented using PMC to identify benign and cancerous tissue cores. Furthermore, field emission scanning electron microscopy (FE-SEM) of benign and cancerous specimens showed marked differences in the tissue morphology, which further validates our observed experimental data with the PMCs. While these patient aspecific feasibility studies clearly demonstrate the ability to discriminate between benign and cancerous breast tissues, further investigation is necessary to perform automated mechano-phenotyping (classification) of breast cancer: from onset to disease progression. PMID:25128621

  16. LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma.

    PubMed

    Strazisar, Mojca; Mlakar, Vid; Glavac, Damjan

    2009-06-01

    LATS2 is a new member of the LATS tumour suppressor family. The human LATS2 gene is located at chromosome 13q11-12, a hot spot (67%) for loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). We screened 129 non-small cell lung cancer samples and 13 lung cancer cell lines, initially for mutations in the LATS2 gene and subsequently for mutations in P53 and K-RAS genes. Either polymorphisms or mutations were identified in over 50 percent of analysed tumours. A novel missense mutation, S1073R, and a large deletion of 8 amino acids in the PAPA-repeat region were detected in 9 and 2 NSCLC tumours, respectively. Those mutations were not identified in the 13 lung cancer cell lines. Mutations were tumour specific and were absent from adjacent normal tissue and healthy controls. Down-regulation of the LATS2 gene was observed in most NSCLC tumours but was not related to any mutation or polymorphism. Tumours with a LATS2 mutation often also harbour a P53 but not K-RAS gene mutation and were mostly in an advanced stage of development, with regional lymph node involvement.

  17. Cancer-specific production of N-acetylaspartate via NAT8L overexpression in non-small cell lung cancer and its potential as a circulating biomarker

    PubMed Central

    Lou, Tzu-Fang; Sethuraman, Deepa; Dospoy, Patrick; Srivastva, Pallevi; Kim, Hyun Seok; Kim, Joongsoo; Ma, Xiaotu; Chen, Pei-Hsuan; Huffman, Kenneth E.; Frink, Robin E.; Larsen, Jill E.; Lewis, Cheryl; Um, Sang-Won; Kim, Duk-Hwan; Ahn, Jung-Mo; DeBerardinis, Ralph J.; White, Michael A.; Minna, John D.; Yoo, Hyuntae

    2015-01-01

    In order to identify new cancer-associated metabolites that may be useful for early detection of lung cancer, we performed a global metabolite profiling of a non-small cell lung cancer (NSCLC) line and immortalized normal lung epithelial cells from the same patient. Among several metabolites with significant cancer/normal differences, we identified a unique metabolic compound, N-acetylaspartate (NAA) in cancer cells — undetectable in normal lung epithelium. NAA’s cancer-specific detection was validated in additional cancer and control lung cells as well as selected NSCLC patient tumors and control tissues. NAA’s cancer-specificity was further supported in our analysis of NAA synthetase (gene symbol: NAT8L) gene expression levels in The Cancer Genome Atlas: elevated NAT8L expression in approximately 40% of adenocarcinoma and squamous cell carcinoma cases (N=577), with minimal expression in all non-malignant lung tissues (N=74). We then showed that NAT8L is functionally involved in NAA production of NSCLC cells through siRNA-mediated suppression of NAT8L, which caused selective reduction of intracellular and secreted NAA. Our cell culture experiments also indicated that NAA biosynthesis in NSCLC cells depends on glutamine availability. For preliminary evaluation of NAA’s clinical potential as a circulating biomarker, we developed a sensitive NAA blood assay and found that NAA blood levels were elevated in 46% of NSCLC patients (N=13) in comparison with age-matched healthy controls (N=21) among individuals aged 55 years or younger. Taken together, these results indicate that NAA is produced specifically in NSCLC tumors through NAT8L overexpression and its extracellular secretion can be detected in blood. PMID:26511490

  18. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    PubMed

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  19. Prostate specific membrane antigen (PSMA) expression in non-small cell lung cancer

    PubMed Central

    Heitkötter, Birthe; Schulze, Arik B.; Schliemann, Christoph; Steinestel, Konrad; Trautmann, Marcel; Marra, Alessandro; Hillejan, Ludger; Mohr, Michael; Evers, Georg; Wardelmann, Eva; Rahbar, Kambiz; Görlich, Dennis; Lenz, Georg; Berdel, Wolfgang E.; Hartmann, Wolfgang; Wiewrodt, Rainer; Huss, Sebastian

    2017-01-01

    Objectives PSMA (prostate-specific membrane antigen) is overexpressed in prostate cancer cells and is reported to be a promising target for antibody-based radioligand therapy in patients with metastasized prostate cancer. Since PSMA expression is not restricted to prostate cancer, the underlying study investigates PSMA expression in non-small cell lung cancer (NSCLC). Material and methods Immunohistochemistry was used to identify PSMA expression in n = 275 samples of NSCLC tissue specimens. By means of CD34 co-expression, the level of PSMA expression in tumor associated neovasculature was investigated. The impact of PSMA expression on clinicopathologic parameters and prognosis was evaluated. Results PSMA tumor cell expression in NSCLC is as low as 6% and was predominantly found in squamous cell carcinoma (p = 0.002). Neovascular PSMA expression was found in 49% of NSCLC. High neovascular PSMA expression was associated with higher tumor grading (G3/G4) (p < 0.001). Neither for PSMA tumor cell expression, nor for PSMA neovascular cell expression prognostic effects were found for the investigated NSCLC cases. Conclusion Here, we report on the expression of PSMA in NSCLC tissue samples. Against the background of a potential treatment with radiolabeled PSMA ligands, our data might serve for the future identification of patients who could benefit from this therapeutic option. PMID:29077706

  20. Non-invasive assessments of adipose tissue metabolism in vitro

    PubMed Central

    Abbott, Rosalyn D.; Borowsky, Francis E.; Quinn, Kyle P.; Bernstein, David L.; Georgakoudi, Irene; Kaplan, David L.

    2015-01-01

    Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with noninvasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored. PMID:26399988

  1. Use of shear waves for diagnosis and ablation monitoring of prostate cancer: a feasibility study

    NASA Astrophysics Data System (ADS)

    Gomez, A.; Rus, G.; Saffari, N.

    2016-01-01

    Prostate cancer remains as a major healthcare issue. Limitations in current diagnosis and treatment monitoring techniques imply that there is still a need for improvements. The efficacy of prostate cancer diagnosis is still low, generating under and over diagnoses. High intensity focused ultrasound ablation is an emerging treatment modality, which enables the noninvasive ablation of pathogenic tissue. Clinical trials are being carried out to evaluate its longterm efficacy as a focal treatment for prostate cancer. Successful treatment of prostate cancer using non-invasive modalities is critically dependent on accurate diagnostic means and is greatly benefited by a real-time monitoring system. While magnetic resonance imaging remains the gold standard for prostate imaging, its wider implementation for prostate cancer diagnosis remains prohibitively expensive. Conventional ultrasound is currently limited to guiding biopsy. Elastography techniques are emerging as a promising real-time imaging method, as cancer nodules are usually stiffer than adjacent healthy prostatic tissue. In this paper, a new transurethral approach is proposed, using shear waves for diagnosis and ablation monitoring of prostate cancer. A finite-difference time domain model is developed for studying the feasibility of the method, and an inverse problem technique based on genetic algorithms is proposed for reconstructing the location, size and stiffness parameters of the tumour. Preliminary results indicate that the use of shear waves for diagnosis and monitoring ablation of prostate cancer is feasible.

  2. Quantifying collagen orientation in breast tissue biopsies using SLIM (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Majeed, Hassaan; Okoro, Chukwuemeka; Balla, Andre; Toussaint, Kimani C.; Popescu, Gabriel

    2017-02-01

    Breast cancer is a major public health problem worldwide, being the most common type of cancer among women according to the World Health Organization (WHO). The WHO has further stressed the importance of an early determination of the disease course through prognostic markers. Recent studies have shown that the alignment of collagen fibers in tumor adjacent stroma correlate with poorer health outcomes in patients. Such studies have typically been carried out using Second-Harmonic Generation (SHG) microscopy. SHG images are very useful for quantifying collagen fiber orientation due their specificity to non-centrosymmetric structures in tissue, leading to high contrast in collagen rich areas. However, the imaging throughput in SHG microscopy is limited by its point scanning geometry. In this work, we show that SLIM, a wide-field high-throughput QPI technique, can be used to obtain the same information on collagen fiber orientation as is obtainable through SHG microscopy. We imaged a tissue microarray containing both benign and malignant cores using both SHG microscopy and SLIM. The cellular (non-collagenous) structures in the SLIM images were next segmented out using an algorithm developed in-house. Using the previously published Fourier Transform Second Harmonic Generation (FT-SHG) tool, the fiber orientations in SHG and segmented SLIM images were then quantified. The resulting histograms of fiber orientation angles showed that both SHG and SLIM generate similar measurements of collagen fiber orientation. The SLIM modality, however, can generate these results at much higher throughput due to its wide-field, whole-slide scanning capabilities.

  3. A decrease in miR-150 regulates the malignancy of pancreatic cancer by targeting c-Myb and MUC4.

    PubMed

    Yang, Ke; He, Miaoxia; Cai, Zailong; Ni, Canrong; Deng, Jingjing; Ta, Na; Xu, Jingjing; Zheng, Jianming

    2015-04-01

    Pancreatic cancer is an aggressive cancer with high mortality. Conventional treatments have little impact on its progression. Limited research investigating the role of oncogene miR-150 specifically in pancreatic cancer has been published. The purpose of this study was to determine the tumorigenesis of miR-150 in pancreatic cancer. One hundred six pancreatic ductal adenocarcinomas were analyzed together with their adjacent benign pancreatic tissues. The associations of miR-150, c-Myb, and MUC4 expression with survival rates were determined. Functional studies on miR-150 in pancreatic cancer were used to assess its effect on proliferation and malignancy in several pancreatic cell lines. miR-150 expression was significantly down-regulated in pancreatic ductal adenocarcinoma tissues compared with adjacent benign pancreatic tissues. Patients with low miR-150 expression had significantly higher mortality rates than those with high miR-150 expression. The in vitro and in vivo assays of pancreatic cancer cells showed that miR-150 overexpression leads to reduced cell growth, clonogenicity, migration, invasion, modular cell cycles, and induced apoptosis. Moreover, miR-150 expression was inversely correlated with c-Myb and MUC4 activities in pancreatic tissue, cell lines, and nude mouse model. miR-150 is an important suppressor of pancreatic ductal carcinoma and acts as a regulator of c-Myb and MUC4 in aggressive progress.

  4. A 4-gene panel as a marker at chromosome 8q in Asian gastric cancer patients.

    PubMed

    Cheng, Lei; Zhang, Qing; Yang, Sheng; Yang, Yanqing; Zhang, Wen; Gao, Hengjun; Deng, Xiaxing; Zhang, Qinghua

    2013-10-01

    A widely held viewpoint is that the use of multiple markers, combined in some type of algorithm, will be necessary to provide high enough discrimination between diseased cases and non-diseased. We applied stepwise logistic regression analysis to identify the best combination of the 32 biomarkers at chromosome 8q on an independent public microarray test set of 80 paired gastric samples. A combination of SULF1, INTS8, ATP6V1C1, and GPR172A was identified with a prediction accuracy of 98.0% for discriminating carcinomas from adjacent noncancerous tissues in our previous 25 paired samples. Interestingly, the overexpression of SULF1 was associated with tumor invasion and metastasis. Function prediction analysis revealed that the 4-marker panel was mainly associated with acidification of intracellular compartments. Taken together, we found a 4-gene panel that accurately discriminated gastric carcinomas from adjacent noncancerous tissues and these results had potential clinical significance in the early diagnosis and targeted treatment of gastric cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages.

    PubMed

    Al Obeed, Omar A; Alkhayal, Khayal A; Al Sheikh, Abdulmalik; Zubaidi, Ahmad M; Vaali-Mohammed, Mansoor-Ali; Boushey, Robin; Mckerrow, James H; Abdulla, Maha-Hamadien

    2014-12-28

    To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC.

  6. Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages

    PubMed Central

    Al Obeed, Omar A; Alkhayal, Khayal A; Al Sheikh, Abdulmalik; Zubaidi, Ahmad M; Vaali-Mohammed, Mansoor-Ali; Boushey, Robin; Mckerrow, James H; Abdulla, Maha-Hamadien

    2014-01-01

    AIM: To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. METHODS: Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. RESULTS: The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. CONCLUSION: High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC. PMID:25561807

  7. [Roles of Y box-binding protein 1 in SK-BR-3 breast cancer proliferation].

    PubMed

    Shi, Jianhong; Lü, Xinrui; Wang, Bing; Daudan, Lin; Yanan, Wang; Yuhui, Bu; Zhenfeng, Ma

    2014-09-30

    To explore the roles of Y box-binding protein 1 (YB-1) in breast cancer cell proliferation. Twenty cases of surgical removal of breast cancer tissue (diagnosed with invasive ductal carcinoma, stage II, by postoperative paraffin pathology) and normal breast tissues adjacent to carcinoma were collected during June 2013 to August 2013.Quantitative real-time PCR (qRT-PCR) was performed to detect the YB1 mRNA levels. Cultured mammary epithelial cells (HBL-100) and breast cancer cells (MCF7, MDA-MB-231 & SK-BR-3 cells) were harvested and qRT-PCR was performed to detect the YB1 mRNA levels.SK-BR-3 cells were stimulated with various concentrations of PDGF-BB and YB1 expression levels were detected by qRT-PCR. Down-regulation or over-expression of YB1 by si-YB1 or Ad-GFP-YB1 was detected in SK-BR-3 cells. And MTS cell proliferation assay kit was used to detect cell proliferation. YB1 mRNA levels were significantly higher in breast cancer tissues and MDA-MB-231 and SK-BR-3 breast cancer cell lines than that in adjacent normal breast tissues and HBL-100 mammary epithelial cells respectively (P < 0.05).YB1 expression levels increased in PDGF-BB stimulated SK-BR-3 cells in a dose-dependent manner. A down-regulation of endogenous YB1 decreases and an over-expression of exogenous YB1 promotes the proliferation activity in SK-BR-3 cells.

  8. BTG2 Is Down-Regulated and Inhibits Cancer Stem Cell-Like Features of Side Population Cells in Hepatocellular Carcinoma.

    PubMed

    Huang, Chen-Song; Zhai, Jing-Ming; Zhu, Xiao-Xu; Cai, Jian-Peng; Chen, Wei; Li, Jian-Hui; Yin, Xiao-Yu

    2017-12-01

    Our previous study found that B cell translocation gene 2 (BTG2) was hyper-methylated and down-regulated in side population (SP) cells of hepatocellular carcinoma (HCC) cell line. However, its clinical significances and biological impacts on HCC SP cells remained unclear. To investigate the prognostic value of BTG2 gene in HCC and its influences on cancer stem cells (CSCs)-like traits of HCC cell line SP cells. BTG2 expression in human HCC and adjacent non-cancerous tissues was detected by immunohistochemical staining and quantitative real-time PCR, and also obtained from GEO and TCGA data. Its prognostic values were assessed. Its biological influences on HCC cell line SP cells were evaluated using cell viability, cell cycle, plate clone-forming assay, and chemoresistance in vitro and tumorigenicity in vivo. BTG2 expression was significantly suppressed in human HCC compared to adjacent non-cancerous tissues. BTG2 expression was correlated with TNM stage, tumor size and vascular invasion. Lower expression of BTG2 was associated with poorer overall survival and disease-free survival. In vitro, overexpression of BTG2 substantially suppressed cell proliferation and accumulation of HCC cell line SP cells in G0/G1 phase. Colony formation ability was markedly suppressed by BTG2 overexpression. Moreover, sensitivity of HCC cell line SP cells to 5-fluorouracil was substantially increased by overexpression of BTG2. Furthermore, tumorigenicity of HCC cell line SP cells transfected with BTG2 plasmids was significantly reduced in vivo. BTG2 gene could regulate the CSC-like traits of HCC cell line SP cells, and it represented as a molecular prognostic marker for HCC.

  9. Tissue redox activity as a hallmark of carcinogenesis: from early to terminal stages of cancer.

    PubMed

    Bakalova, Rumiana; Zhelev, Zhivko; Aoki, Ichio; Saga, Tsuneo

    2013-05-01

    The study aimed to clarify the dynamics of tissue redox activity (TRA) in cancer progression and assess the importance of this parameter for therapeutic strategies. The experiments were carried out on brain tissues of neuroblastoma-bearing, glioma-bearing, and healthy mice. TRA was visualized in vivo by nitroxide-enhanced MRI on anesthetized animals or in vitro by electron paramagnetic resonance spectroscopy on isolated tissue specimens. Two biochemical parameters were analyzed in parallel: tissue total antioxidant capacity (TTAC) and plasma levels of matrix metalloproteinases (MMP). In the early stage of cancer, the brain tissues were characterized by a shorter-lived MRI signal than that from healthy brains (indicating a higher reducing activity for the nitroxide radical), which was accompanied by an enhancement of TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both hemispheres were characterized by a longer-lived MRI signal than in healthy brains (indicating a high-oxidative activity) that was accompanied by a decrease in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also affected the redox potential of tissues distant from the primary tumor locus (liver and lung). Their oxidative status increased in both stages of cancer. The study shows that tissue redox balance is very sensitive to the progression of cancer and can be used as a diagnostic marker of carcinogenesis. The study also suggests that the noncancerous tissues of a cancer-bearing organism are susceptible to oxidative damage and should be considered a therapeutic target. ©2013 AACR.

  10. Analysis of Tissue and Serum MicroRNA Expression in Patients with Upper Urinary Tract Urothelial Cancer

    PubMed Central

    Kriebel, Stephanie; Schmidt, Doris; Holdenrieder, Stefan; Goltz, Diane; Kristiansen, Glen; Moritz, Rudolf; Fisang, Christian; Müller, Stefan C.; Ellinger, Jörg

    2015-01-01

    Introduction MicroRNAs play an important role in many human malignancies; so far, their expression remains to be studied in upper urinary tract urothelial cancer (UUTUC). Materials and Methods The expression of eleven microRNAs (miR-10a, miR-21, miR-96, miR-135, miR-141, miR-182, miR-200b, miR-205, miR-429, miR-520b, miR-1244) formerly shown to be upregulated in urothelial bladder cancer were studied in corresponding normal and cancerous tissue samples of patients undergoing nephroureterectomy for UUTUC. Upregulated microRNAs were then measured in serum samples of patients with UUTUC and patients with non-malignant urological diseases to evaluate their potential as non-invasive biomarkers for UUTUC. Results MicroRNA expression allowed differentiation of normal and cancerous tissue: miR-21, miR-96, miR-135, miR-141, miR-182, miR-205, miR-429 and miR-520b were significantly overexpressed. Furthermore, miR-205 was upregulated in poorly differentiated UUTUC. The analysis of circulating RNA in serum demonstrated an increase of miR-141 in patients with UUTUC; receiver operator characteristic analysis demonstrated an area under the curve of 0.726 for miR-141 as a diagnostic biomarker. Furthermore, we observed lower levels of miR-10a and miR-135 in UUTUC patients. Conclusions MicroRNA expression is altered in UUTUC. The analysis of circulating miR-141 may be useful to identify patients with UUTUC. PMID:25629698

  11. Analysis of tissue and serum microRNA expression in patients with upper urinary tract urothelial cancer.

    PubMed

    Kriebel, Stephanie; Schmidt, Doris; Holdenrieder, Stefan; Goltz, Diane; Kristiansen, Glen; Moritz, Rudolf; Fisang, Christian; Müller, Stefan C; Ellinger, Jörg

    2015-01-01

    MicroRNAs play an important role in many human malignancies; so far, their expression remains to be studied in upper urinary tract urothelial cancer (UUTUC). The expression of eleven microRNAs (miR-10a, miR-21, miR-96, miR-135, miR-141, miR-182, miR-200b, miR-205, miR-429, miR-520b, miR-1244) formerly shown to be upregulated in urothelial bladder cancer were studied in corresponding normal and cancerous tissue samples of patients undergoing nephroureterectomy for UUTUC. Upregulated microRNAs were then measured in serum samples of patients with UUTUC and patients with non-malignant urological diseases to evaluate their potential as non-invasive biomarkers for UUTUC. MicroRNA expression allowed differentiation of normal and cancerous tissue: miR-21, miR-96, miR-135, miR-141, miR-182, miR-205, miR-429 and miR-520b were significantly overexpressed. Furthermore, miR-205 was upregulated in poorly differentiated UUTUC. The analysis of circulating RNA in serum demonstrated an increase of miR-141 in patients with UUTUC; receiver operator characteristic analysis demonstrated an area under the curve of 0.726 for miR-141 as a diagnostic biomarker. Furthermore, we observed lower levels of miR-10a and miR-135 in UUTUC patients. MicroRNA expression is altered in UUTUC. The analysis of circulating miR-141 may be useful to identify patients with UUTUC.

  12. An Informatics-assisted Label-free Approach for Personalized Tissue Membrane Proteomics: Case Study on Colorectal Cancer*

    PubMed Central

    Han, Chia-Li; Chen, Jinn-Shiun; Chan, Err-Cheng; Wu, Chien-Peng; Yu, Kun-Hsing; Chen, Kuei-Tien; Tsou, Chih-Chiang; Tsai, Chia-Feng; Chien, Chih-Wei; Kuo, Yung-Bin; Lin, Pei-Yi; Yu, Jau-Song; Hsueh, Chuen; Chen, Min-Chi; Chan, Chung-Chuan; Chang, Yu-Sun; Chen, Yu-Ju

    2011-01-01

    We developed a multiplexed label-free quantification strategy, which integrates an efficient gel-assisted digestion protocol, high-performance liquid chromatography tandem MS analysis, and a bioinformatics alignment method to determine personalized proteomic profiles for membrane proteins in human tissues. This strategy provided accurate (6% error) and reproducible (34% relative S.D.) quantification of three independently purified membrane fractions from the same human colorectal cancer (CRC) tissue. Using CRC as a model, we constructed the personalized membrane protein atlas of paired tumor and adjacent normal tissues from 28 patients with different stages of CRC. Without fractionation, this strategy confidently quantified 856 proteins (≥2 unique peptides) across different patients, including the first and robust detection (Mascot score: 22,074) of the well-documented CRC marker, carcinoembryonic antigen 5 by a discovery-type proteomics approach. Further validation of a panel of proteins, annexin A4, neutrophils defensin A1, and claudin 3, confirmed differential expression levels and high occurrences (48–70%) in 60 CRC patients. The most significant discovery is the overexpression of stomatin-like 2 (STOML2) for early diagnostic and prognostic potential. Increased expression of STOML2 was associated with decreased CRC-related survival; the mean survival period was 34.77 ± 2.03 months in patients with high STOML2 expression, whereas 53.67 ± 3.46 months was obtained for patients with low STOML2 expression. Further analysis by ELISA verified that plasma concentrations of STOML2 in early-stage CRC patients were elevated as compared with those of healthy individuals (p < 0.001), suggesting that STOML2 may be a noninvasive serological biomarker for early CRC diagnosis. The overall sensitivity of STOML2 for CRC detection was 71%, which increased to 87% when combined with CEA measurements. This study demonstrated a sensitive, label-free strategy for differential

  13. Microbial Dysbiosis Is Associated with Human Breast Cancer

    PubMed Central

    Xuan, Caiyun; Shamonki, Jaime M.; Chung, Alice; DiNome, Maggie L.; Chung, Maureen; Sieling, Peter A.; Lee, Delphine J.

    2014-01-01

    Breast cancer affects one in eight women in their lifetime. Though diet, age and genetic predisposition are established risk factors, the majority of breast cancers have unknown etiology. The human microbiota refers to the collection of microbes inhabiting the human body. Imbalance in microbial communities, or microbial dysbiosis, has been implicated in various human diseases including obesity, diabetes, and colon cancer. Therefore, we investigated the potential role of microbiota in breast cancer by next-generation sequencing using breast tumor tissue and paired normal adjacent tissue from the same patient. In a qualitative survey of the breast microbiota DNA, we found that the bacterium Methylobacterium radiotolerans is relatively enriched in tumor tissue, while the bacterium Sphingomonas yanoikuyae is relatively enriched in paired normal tissue. The relative abundances of these two bacterial species were inversely correlated in paired normal breast tissue but not in tumor tissue, indicating that dysbiosis is associated with breast cancer. Furthermore, the total bacterial DNA load was reduced in tumor versus paired normal and healthy breast tissue as determined by quantitative PCR. Interestingly, bacterial DNA load correlated inversely with advanced disease, a finding that could have broad implications in diagnosis and staging of breast cancer. Lastly, we observed lower basal levels of antibacterial response gene expression in tumor versus healthy breast tissue. Taken together, these data indicate that microbial DNA is present in the breast and that bacteria or their components may influence the local immune microenvironment. Our findings suggest a previously unrecognized link between dysbiosis and breast cancer which has potential diagnostic and therapeutic implications. PMID:24421902

  14. Application of RT-PCR in formalin-fixed and paraffin-embedded lung cancer tissues.

    PubMed

    Zhang, Fan; Wang, Zhuo-min; Liu, Hong-yu; Bai, Yun; Wei, Sen; Li, Ying; Wang, Min; Chen, Jun; Zhou, Qing-hua

    2010-01-01

    To analyze gene expression in formalin-fixed, paraffin-embedded lung cancer tissues using modified method. Total RNA from frozen tissues was extracted using TRIZOL reagent. RNA was extracted from formalin-fixed, paraffin-embedded tissues by digestion with proteinase K before the acid-phenol:chloroform extraction and carrier precipitation. We modified this method by using a higher concentration of proteinase K and a longer digestion time, optimized to 16 hours. RT-PCR and real-time RT-PCR were used to check reproducibility and the concordance between frozen and paraffin-embedded samples. The results showed that the RNA extracted from the paraffin-embedded lung tissues had high quality with the most fragment length between 28S and 18S bands (about 1000 to 2000 bases). The housekeeping gene GUSB exhibited low variation of expression in frozen and paraffin-embedded lung tissues, whereas PGK1 had the lowest variation in lymphoma tissues. Furthermore, real-time PCR analysis of the expression of known prognostic genes in non-small cell lung carcinoma (NSCLC) demonstrated an extremely high correlation (r>0.880) between the paired frozen and formalin-fixed, paraffin-embedded specimens. This improved method of RNA extraction is suitable for real-time quantitative RT-PCR, and may be used for global gene expression profiling of paraffin-embedded tissues.

  15. Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer.

    PubMed

    Fletcher, Sabrina Johanna; Sacca, Paula Alejandra; Pistone-Creydt, Mercedes; Coló, Federico Andrés; Serra, María Florencia; Santino, Flavia Eliana; Sasso, Corina Verónica; Lopez-Fontana, Constanza Matilde; Carón, Rubén Walter; Calvo, Juan Carlos; Pistone-Creydt, Virginia

    2017-02-07

    Adipose microenvironment is involved in signaling pathways that influence breast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumor human breast epithelial cell lines when incubated with conditioned media (CMs) from human breast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants (hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. non tumor associated adipocytes. We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines. We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell lines or in the different CMs. In addition we evaluated changes in the morphology and expression of these factors in slices of the different adipose tissues. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post-hoc tests were performed within each individual treatment. hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breast cancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expression compared to hATN-CMs. In addition, we observed a loss of effect in cellular migration when we pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains bound to the versican core protein, thus losing the ability to bind to CD44. Adipocytes associated with the invasive front are reduced in size compared to adipocytes that are farther away. Also, hATT adipocytes express significantly higher amounts of versican, CD44 and Adipo R1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes. We conclude that hATT secrete a different set of proteins compared to hATN. Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared to hATN-CMs, might be involved in the tumorogenic behavior observed in both cell lines employed. In addition, we may conclude that adipocytes from the tumor microenvironment show a less differentiated

  16. Why might people donate tissue for cancer research? Insights from organ/tissue/blood donation and clinical research.

    PubMed

    Axler, Renata E; Irvine, Rob; Lipworth, Wendy; Morrell, Bronwen; Kerridge, Ian H

    2008-01-01

    Little is known about why patients with cancer do or do not donate their biopsied/cancerous tissue to research. A review of the literature on motivations to participate in clinical research and to donate tissues/organs for therapeutic use may provide some insights relevant to tumour banking research. While more research is necessary, a better understanding of the factors that motivate patients to give or refuse consent to tumour banking may ultimately improve consent practices, public trust and donation rates. Copyright 2008 S. Karger AG, Basel.

  17. Bacteriome and mycobiome associations in oral tongue cancer.

    PubMed

    Mukherjee, Pranab K; Wang, Hannah; Retuerto, Mauricio; Zhang, Huan; Burkey, Brian; Ghannoum, Mahmoud A; Eng, Charis

    2017-11-14

    Squamous cell carcinoma of the oral (mobile) tongue (OMTC), a non-human papilloma virus-associated oral cancer, is rapidly increasing without clear etiology. Poor oral hygiene has been associated with oral cancers, suggesting that oral bacteriome (bacterial community) and mycobiome (fungal community) could play a role. While the bacteriome is increasingly recognized as an active participant in health, the role of the mycobiome has not been studied in OMTC. Tissue DNA was extracted from 39 paired tumor and adjacent normal tissues from patients with OMTC. Microbiome profiling, principal coordinate, and dissimilarity index analyses showed bacterial diversity and richness, and fungal richness, were significantly reduced in tumor tissue (TT) compared to their matched non-tumor tissues (NTT, P <0.006). Firmicutes was the most abundant bacterial phylum, which was significantly increased in TT compared to NTT (48% vs. 40%, respectively; P =0.004). Abundance of Bacteroidetes and Fusobacteria were significantly decreased in TT compared to matched NTT ( P ≤0.003 for both). Abundance of 22 bacterial and 7 fungal genera was significantly different between the TT and NTT, including Streptococcus , which was the most abundant and significantly increased in the tumor group (34% vs. 22%, P <0.001). Abundance of fungal genus Aspergillus in TT correlated negatively with bacteria ( Actinomyces, Prevotella , Streptococcus) , but positively with Aggregatibacter . Patients with high T-stage disease had lower mean differences between TT and NTT compared with patients with low T-stage disease (0.07 vs. 0.21, P =0.04). Our results demonstrate differences in bacteriome and mycobiome between OMTC and their matched normal oral epithelium, and their association with T-stage.

  18. Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

    DOE PAGES

    Cucinotta, Francis A.; Cacao, Eliedonna

    2017-05-12

    Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

  19. Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cucinotta, Francis A.; Cacao, Eliedonna

    Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

  20. Oncogenic Activation of Fibroblast Growth Factor Receptor-3 and RAS Genes as Non-Overlapping Mutual Exclusive Events in Urinary Bladder Cancer.

    PubMed

    Pandith, Arshad A; Hussain, Aashaq; Khan, Mosin S; Shah, Zafar A; Wani, M Saleem; Siddiqi, Mushtaq A

    2016-01-01

    Urinary bladder cancer is a common malignancy in the West and ranks as the 7th most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

  1. Defining the steps that lead to cancer: replicative telomere erosion, aneuploidy and an epigenetic maturation arrest of tissue stem cells.

    PubMed

    Stindl, Reinhard

    2008-01-01

    Recently, an influential sequencing study found that more than 1700 genes had non-silent mutations in either a breast or colorectal cancer, out of just 11 breast and 11 colorectal tumor samples. This is not surprising given the fact that genomic instability is the hallmark of cancer cells. The plethora of genomic alterations found in every carcinoma does not obey the 'law of genotype-phenotype correlation', since the same histological subtype of cancer harbors different gene mutations and chromosomal aberrations in every patient. In an attempt to make sense out of the observed genetic and chromosomal chaos in cancer, I propose a cascade model. According to this model, tissue regeneration depends on the proliferation and serial activation of stem cells. Replicative telomere erosion limits the proliferative life span of adult stem cells and results in the Hayflick limit (M1). However, local tissue exhaustion or old age might promote the activation of M1-deficient tissue stem cells. Extended proliferation of these cells leads to telomere-driven chromosomal instability and aneuploidy (abnormal balance of chromosomes and/or chromosome material). Several of the aforementioned steps have been already described in the literature. However, in contrast to common theories, it is proposed here that the genomic damage blocks the epigenetic differentiation switch. As a result of aneuploidy, differentiation-specific genes cannot be activated by modification of methylation patterns. Consequently, the phenotype of cancer tissue is largely determined by the epigenetic maturation arrest of tissue stem cells, which in addition enables a fraction of cancer cells to proliferate, invade and metastasize, as normal adult stem cells do. The new model combines genetic and epigenetic alterations of cancer cells in one causative cascade and offers an explanation for why identical histologic cancer types harbor a confusing variety of chromosomal and gene aberrations. The Viennese Cascade, as

  2. MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing

    PubMed Central

    Zhang, Yuanwei; Xu, Bo; Zhou, Jun; Fan, Song; Hao, Zongyao; Shi, Haoqiang; Zhang, Xiansheng; Kong, Rui; Xu, Lingfan; Gao, Jingjing; Zou, Duohong; Liang, Chaozhao

    2015-01-01

    Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights

  3. Adipose tissue immunity and cancer

    PubMed Central

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

    2013-01-01

    Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete pro-inflammatory adipokines and cytokines providing a microenvironment favorable for tumor growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching toward M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumor growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumor cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumor microenvironment with more sophisticated and selective anti-tumoral drugs. PMID:24106481

  4. Quantitative analysis of collagen change between normal and cancerous thyroid tissues based on SHG method

    NASA Astrophysics Data System (ADS)

    Chen, Xiwen; Huang, Zufang; Xi, Gangqin; Chen, Yongjian; Lin, Duo; Wang, Jing; Li, Zuanfang; Sun, Liqing; Chen, Jianxin; Chen, Rong

    2012-03-01

    Second-harmonic generation (SHG) is proved to be a high spatial resolution, large penetration depth and non-photobleaching method. In our study, SHG method was used to investigate the normal and cancerous thyroid tissue. For SHG imaging performance, system parameters were adjusted for high-contrast images acquisition. Each x-y image was recorded in pseudo-color, which matches the wavelength range in the visible spectrum. The acquisition time for a 512×512-pixels image was 1.57 sec; each acquired image was averaged four frames to improve the signal-to-noise ratio. Our results indicated that collagen presence as determined by counting the ratio of the SHG pixels over the whole pixels for normal and cancerous thyroid tissues were 0.48+/-0.05, 0.33+/-0.06 respectively. In addition, to quantitatively assess collagen-related changes, we employed GLCM texture analysis to the SHG images. Corresponding results showed that the correlation both fell off with distance in normal and cancerous group. Calculated value of Corr50 (the distance where the correlation crossed 50% of the initial correlation) indicated significant difference. This study demonstrates that SHG method can be used as a complementary tool in thyroid histopathology.

  5. Highly Increased 125I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst2 Targeting in Human Cancers.

    PubMed

    Reubi, Jean Claude; Waser, Beatrice; Mäcke, Helmut; Rivier, Jean

    2017-02-01

    There is recent in vitro and in vivo evidence that somatostatin receptor subtype 2 (sst 2 ) antagonists are better tools to target neuroendocrine tumors (NETs) than sst 2 agonists. Indeed, antagonists bind to a greater number of sst 2 sites than agonists. Whether sst 2 antagonists could be used successfully to target non-NETs, expressing low sst 2 density, is unknown. Here, we compare quantitatively 125 I-JR11 sst 2 antagonist binding in vitro with that of the sst 2 agonist 125 I-Tyr 3 -octreotide in large varieties of non-NET and NET. In vitro receptor autoradiography was performed with 125 I-JR11 and 125 I-Tyr 3 -octreotide in cancers from prostate, breast, colon, kidney, thyroid, and lymphoid tissues as well as NETs as reference. In general, 125 I-JR11 binds to many more sst 2 sites than 125 I-Tyr 3 -octreotide. In 13 breast cancers, 8 had a low binding (mean density, 844 ± 168 dpm/mg of tissue) with the agonist whereas 12 had a high binding (mean density, 4,447 ± 1,128 dpm/mg of tissue) with the antagonist. All 12 renal cell cancers showed a low binding of sst 2 with the agonist (mean density, 348 ± 49 dpm/mg of tissue) whereas all cases had a high sst 2 binding with the antagonist (mean density, 3,777 ± 582 dpm/mg of tissue). One of 5 medullary thyroid cancers was positive with the agonist, whereas 5 of 5 were positive with the antagonist. In 15 non-Hodgkin lymphomas, many more sst 2 sites were labeled with the antagonist than with the agonist. In 14 prostate cancers, none had sst 2 binding with the agonist and only 4 had a weak binding with the antagonist. None of 17 colon cancers showed sst 2 sites with the agonist, and only 3 cases were weakly positive with the antagonist. In the various tumor types, adjacent sst 2 -expressing tissues such as vessels, lymphocytes, nerves, mucosa, or stroma were more strongly labeled with the antagonist than with the agonist. The reference NET cases, incubated with a smaller amount of tracer, were also found to have many

  6. [Expression and clinical significance of Pokemon in non-small cell lung cancer].

    PubMed

    Zhao, Zhihong; Wang, Shengfa; Zhang, Tiewa

    2007-12-20

    Proto-oncogene Pokemon is the special transcription inhibitor of ARF,which can regulate cell growth and differentiation by ARF-P53 path.It may be the important monitoring target of tumor because of being upstream region of many tumor suppressor genes and proto-oncogenes.The aim of this study is to explore the clinical significance of Pokemon gene in non-small cell lung cancer(NSCLC). Immunohistochemistry was applied to detect the expression of Pokemon protein in 92 cases of NSCLC and 20 cases of paracancerous lung tissues.Correlation between abnormal expression of Pokemon with pathologic characteristics and prognosis of NSCLC was analyzed. Pokemon was not expressed in paracancerous lung tissues and was found in 66 of 92(71.7%) cases of lung cancer tissues.Expression of Pokemon was closely related to TNM stages(P=0.011).Survival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression(P=0.0015).Pokemon expression was demonstrated as independent prognostic factor of NSCLC. Pokemon is expressed in NSCLC and it may be identified as a new diagnostic marker.High expression of Pokemon may indicate poor prognosis of patients with NSCLC.

  7. Relationship between transmembrane serine protease expression and prognosis of esophageal squamous cell carcinoma.

    PubMed

    Liu, G T; Shen, C; Ren, X H; Yang, L; Yu, Y M; Xiu, Y X; Li, R H; Jiang, L; Zhang, C L; Li, Y W

    2017-01-01

    Esophageal squamous cell carcinoma is the most common type of esophageal cancer in Eastern Europe and Asia, being the 6th most common cause of cancer deaths worldwide. The aim of this study was to analyze the expression of transmembrane serine protein in esophageal squamous cell carcinoma, and to correlate it with the clinical biological features of esophageal cancer. The expression of transmembrane protease serine 4 (TMPRSS4) mRNA and protein in carcinoma tissues and corresponding adjacent tissues and non-tumorous esophageal tissues was determined using PCR (qRT-PCR). The results show that both TMPRSS4 mRNA and protein expression were remarkably lower in adjacent normal tissues than in tumorous tissues. TMPRSS4 protein expression in esophageal carcinoma was correlated with patient demographic characteristics, tumor type, high TNM stages and overall survival (OS). Based on the experimental results, we conclude that TMPRSS4 is closely related to the occurrence, development and metastasis of esophageal squamous cell carcinoma.

  8. HOXA9 inhibits migration of lung cancer cells and its hypermethylation is associated with recurrence in non-small cell lung cancer.

    PubMed

    Hwang, Jung-Ah; Lee, Bo Bin; Kim, Yujin; Hong, Seung-Hyun; Kim, Young-Ho; Han, Joungho; Shim, Young Mog; Yoon, Chae-Yeong; Lee, Yeon-Su; Kim, Duk-Hwan

    2015-06-01

    This study was aimed at understanding the clinicopathological significance of HOXA9 hypermethylation in non-small cell lung cancer (NSCLC). HOXA9 hypermethylation was characterized in six lung cancer cell lines, and its clinicopathological significance was analyzed using methylation-specific PCR in 271 formalin-fixed paraffin-embedded tissues and 27 fresh-frozen tumor and matched normal tissues from 298 NSCLC patients, and Ki-67 expression was analyzed using immunohistochemistry. The promoter region of HOXA9 was highly methylated in six lung cancer cell lines, but not in normal bronchial epithelial cells. The loss of expression was restored by treatment of the cells with a demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC). Transient transfection of HOXA9 into H23 lung cancer cells resulted in the inhibition of cell migration but not proliferation. Conversely, sequence-specific siRNA-mediated knockdown of HOXA9 enhanced cell migration. The mRNA levels of HOXA9 in 27 fresh-frozen tumor tissues were significantly lower than in matched normal tissues (P<0.0001; Wilcoxon signed-rank test). HOXA9 hypermethylation was found in 191 (70%) of 271 primary NSCLCs. HOXA9 hypermethylation was not associated with tumor size (P=0.12) and Ki-67 proliferation index (P=0.15). However, patients with HOXA9 hypermethylation had poor recurrence-free survival (hazard ratio=3.98, 95% confidence interval = 1.07-17.09, P=0.01) in never-smokers, after adjusting for age, sex, tumor size, adjuvant therapy, pathologic stage, and histology. In conclusion, the present study suggests that HOXA9 inhibits migration of lung cancer cells and its hypermethylation is an independent prognostic factor for recurrence-free survival in never-smokers with NSCLC. © 2014 Wiley Periodicals, Inc.

  9. Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis

    PubMed Central

    Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh

    2015-01-01

    Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer. PMID:25797243

  10. Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.

    PubMed

    Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh; Yamamoto, Hiroyuki; Shinomura, Yasuhisa

    2015-03-30

    Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.

  11. Combining polarimetry and spectropolarimetry techniques in diagnostics of cancer changes in biological tissues

    NASA Astrophysics Data System (ADS)

    Yermolenko, Sergey; Ivashko, Pavlo; Gruia, Ion; Gruia, Maria; Peresunko, Olexander; Zelinska, Natalia; Voloshynskyi, Dmytro; Fedoruk, Olexander; Zimnyakov, Dmitry; Alonova, Marina

    2015-02-01

    The aim of the study is combining polarimetry and spectropolarimetry techniques for identifying the changes of opticalgeometrical structure in different kinds of biotissues with solid tumours. It is researched that a linear dichroism appears in biotissues (human esophagus, muscle tissue of rats, human prostate tissue, cervical smear) with cancer diseases, magnitude of which depends on the type of the tissue and on the time of cancer process development.

  12. Hyperspectral Imaging and SPA-LDA Quantitative Analysis for Detection of Colon Cancer Tissue

    NASA Astrophysics Data System (ADS)

    Yuan, X.; Zhang, D.; Wang, Ch.; Dai, B.; Zhao, M.; Li, B.

    2018-05-01

    Hyperspectral imaging (HSI) has been demonstrated to provide a rapid, precise, and noninvasive method for cancer detection. However, because HSI contains many data, quantitative analysis is often necessary to distill information useful for distinguishing cancerous from normal tissue. To demonstrate that HSI with our proposed algorithm can make this distinction, we built a Vis-NIR HSI setup and made many spectral images of colon tissues, and then used a successive projection algorithm (SPA) to analyze the hyperspectral image data of the tissues. This was used to build an identification model based on linear discrimination analysis (LDA) using the relative reflectance values of the effective wavelengths. Other tissues were used as a prediction set to verify the reliability of the identification model. The results suggest that Vis-NIR hyperspectral images, together with the spectroscopic classification method, provide a new approach for reliable and safe diagnosis of colon cancer and could lead to advances in cancer diagnosis generally.

  13. MFDFA and Lacunarity Analysis of Synthetic Multifractals and Pre-Cancerous Tissues

    NASA Astrophysics Data System (ADS)

    Roy, A.; Das, N.; Ghosh, N.

    2017-12-01

    Multifractal Detrended Fluctuation Analysis (MFDFA) has been employed for evaluating complex variations in the refractive index (RI) of human pre-cancerous tissues. While this was primarily aimed towards the early diagnosis of cancer in the human cervix, question remains whether multifractal analysis alone can be conclusively used for distinguishing between various grades of pre-cancerous tissues. Lacunarity is a parameter that was developed for multiscale analysis of data and has been shown to be theoretically related to the correlation dimension, D2, by dlog(L)/dlog(x) = D2 - 2. Further, research has proven that not only can Lacunarity be used as a preliminary indicator of multifractal behavior but it also distinguishes between images with similar correlation dimension values. In order to compare the efficacy of the two approaches namely, MFDFA and Lacunarity, in distinguishing between pre-cancerous tissues of various grades, we test these techniques on a set of 2-dimensional theoretical random multifractal fields. MFDFA is employed for computing the width of the singularity spectrum f(α), which is a measure of multifractal behavior. A weighted mean of the log-transformed lacunarity values at different scales is employed for differentiating between patterns with the same correlation dimension but differences in texture. The two different techniques are then applied to images containing RI values of biopsy samples from human cervical tissues that were histo-pathologically characterized as grade-I and grade-II pre-cancerous cells. The results show that the two approaches are complementary to one another when it comes to multi-scale analysis of complex natural patterns manifested in the images of such pre-cancerous cells.

  14. BRAF activated non-coding RNA (BANCR) promoting gastric cancer cells proliferation via regulation of NF-κB1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Zhi-Xin; Liu, Zhi-Qiang; Jiang, Biao

    Background and objective: Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1. Methods: Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer. Results: BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth andmore » promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3′UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis. Conclusion: BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis. - Highlights: • BANCR up-regulated in gastric cancer (GC) tissues and cell lines MGC803 and BGC823. • Down-regulation of BANCR inhibited GC cell growth and promoted cell apoptosis. • Down-regulation of BANCR contributed to decreased 3′UTR of NF-κB1 and its expression. • Overexpressed NF-κB1 reversed the effect of BANCR on GC cell growth. • miR-9 inhibitor reversed the effect of BANCR on cancer GC cell growth.« less

  15. Tissues from population-based cancer registries: a novel approach to increasing research potential.

    PubMed

    Goodman, Marc T; Hernandez, Brenda Y; Hewitt, Stephen; Lynch, Charles F; Coté, Timothy R; Frierson, Henry F; Moskaluk, Christopher A; Killeen, Jeffrey L; Cozen, Wendy; Key, Charles R; Clegg, Limin; Reichman, Marsha; Hankey, Benjamin F; Edwards, Brenda

    2005-07-01

    Population-based cancer registries, such as those included in the Surveillance, Epidemiology, and End-Results (SEER) Program, offer tremendous research potential beyond traditional surveillance activities. We describe the expansion of SEER registries to gather formalin-fixed, paraffin-embedded tissue from cancer patients on a population basis. Population-based tissue banks have the advantage of providing an unbiased sampling frame for evaluating the public health impact of genes or protein targets that may be used for therapeutic or diagnostic purposes in defined communities. Such repositories provide a unique resource for testing new molecular classification schemes for cancer, validating new biologic markers of malignancy, prognosis and progression, assessing therapeutic targets, and measuring allele frequencies of cancer-associated genetic polymorphisms or germline mutations in representative samples. The assembly of tissue microarrays will allow for the use of rapid, large-scale protein-expression profiling of tumor samples while limiting depletion of this valuable resource. Access to biologic specimens through SEER registries will provide researchers with demographic, clinical, and risk factor information on cancer patients with assured data quality and completeness. Clinical outcome data, such as disease-free survival, can be correlated with previously validated prognostic markers. Furthermore, the anonymity of the study subject can be protected through rigorous standards of confidentiality. SEER-based tissue resources represent a step forward in true, population-based tissue repositories of tumors from US patients and may serve as a foundation for molecular epidemiology studies of cancer in this country.

  16. Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Study.

    PubMed

    Vatrano, S; Righi, L; Vavalá, T; Rapa, I; Busso, M; Izzo, S; Cappia, S; Veltri, A; Papotti, M; Scagliotti, G V; Novello, S

    2016-04-01

    Recently, in advanced non-small cell lung cancer (NSCLC), standard chemotherapy was flanked by biological agents directed against genomic abnormalities, including EGFR and ALK alterations, that significantly improved patient outcome. Despite these achievements, tumour progression almost always occurs and a reassessment of the tumour genetic profile may contribute to modulating the therapeutic regimen. Resampling may provide tissue for additional tests to detect acquired resistance and/or new genetic alterations, but the currently available information is limited. Histological and genetic reassessments of biopsy or surgical tissue samples from 50 non-squamous NSCLC patients before and after at least one systemic treatment were performed. EGFR, KRAS, BRAF, PIK3CA and HER2 mutations were sequenced, p.T790M was identified with real-time PCR, and ALK and MET genomic alterations by fluorescence in situ hybridization. Overall in baseline biopsies, 37/50 (74 %) tumours had genetic alterations, either single (52 %) or multiple (22 %). Among them, 16 were EGFR mutations and 6 ALK rearrangements. In the second tissue sampling, 54 % of cases had additional genomic changes, including newly acquired alterations (81 %) or losses (18 %). The commonest changes were MET amplification and p.T790M mutation. One case had a histological shift from adenocarcinoma to small cell carcinoma. The remarkable number of molecular changes following systemic therapy and the genetic complexity of some cases underline the value of histological and molecular re-evaluation of lung cancer to tailor the most appropriate therapy during disease progression.

  17. Time Lapse to Colorectal Cancer: Telomere Dynamics Define the Malignant Potential of Polyps.

    PubMed

    Druliner, Brooke R; Ruan, Xiaoyang; Johnson, Ruth; Grill, Diane; O'Brien, Daniel; Lai, Tsung-Po; Rashtak, Shahrooz; Felmlee-Devine, Donna; Washechek-Aletto, Jill; Malykh, Andrei; Smyrk, Thomas; Oberg, Ann; Liu, Hongfang; Shay, Jerry W; Ahlquist, David A; Boardman, Lisa A

    2016-09-01

    Whereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free. Tissues were identified as cancer-adjacent polyp (CAP)-residual adenoma contiguous with cancer-and cancer-free polyp (CFP)-adenomas without malignancy. Telomere length, TMM, and expression were measured in 102 tissues including peripheral blood leukocytes (PBLs), normal colon epithelium, adenoma, and cancer (in CAP cases) from 31 patients. Telomere length was measured in a separate cohort of 342 PBL from CAP and CFP patients. The mean differences in telomere length between normal and adenoma were greater in CAP than in CFP cases, P=0.001; telomere length in PBL was 91.7 bp greater in CAP than in CFP, P=0.007. Each 100 bp telomere increase was associated with a 1.14 (1.04-1.26) increased odds of being a CAP, P=0.0063. The polyp tissue from CAP patients had shorter telomeres and higher Telomerase reverse transcriptase (hTERT) expression compared with polyps from CFP patients, P=0.05. There was a greater degree of alternative lengthening of telomere (ALT) level difference in CFP polyps than in CAP polyps. The polyp telomere lengths of aggressive CAPs were significantly different from the polyps of non-aggressive CAPs, P=0.01. Adenomas that progress to cancer exhibit distinct telomere length and TMM profiles. We report for the first time that PBL telomeres differ in patients with polyps that become malignant, and therefore may have clinical value in adenoma risk assessment and management.

  18. Tissue slide-based microRNA characterization of tumors: how detailed could diagnosis become for cancer medicine?

    PubMed Central

    Sempere, Lorenzo F

    2014-01-01

    miRNAs are short, non-coding, regulatory RNAs that exert cell type-dependent, context-dependent, transcriptome-wide gene expression control under physiological and pathological conditions. Tissue slide-based assays provide qualitative (tumor compartment) and semi-quantitative (expression levels) information about altered miRNA expression at single-cell resolution in clinical tumor specimens. Reviewed here are key technological advances in the last 5 years that have led to implementation of fully automated, robust and reproducible tissue slide-based assays for in situ miRNA detection on US FDA-approved instruments; recent tissue slide-based discovery studies that suggest potential clinical applications of specific miRNAs in cancer medicine are highlighted; and the challenges in bringing tissue slide-based miRNA assays into the clinic are discussed, including clinical validation, biomarker performance, biomarker space and integration with other biomarkers. PMID:25090088

  19. Analysis of Lung Tissue Using Ion Beams

    NASA Astrophysics Data System (ADS)

    Alvarez, J. L.; Barrera, R.; Miranda, J.

    2002-08-01

    In this work a comparative study is presented of the contents of metals in lung tissue from healthy patients and with lung cancer, by means of two analytical techniques: Particle Induced X-ray Emission (PIXE) and Rutherford Backscattering Spectrometry (RBS). The samples of cancerous tissue were taken from 26 autopsies made to individuals died in the National Institute of Respiratory Disease (INER), 22 of cancer and 4 of other non-cancer biopsies. When analyzing the entirety of the samples, in the cancerous tissues, there were increments in the concentrations of S (4%), K (635%), Co (85%) and Cu (13%). Likewise, there were deficiencies in the concentrations of Cl (59%), Ca (6%), Fe (26%) and Zn (7%). Only in the cancerous tissues there were appearances of P, Ca, Ti, V, Cr, Mn, Ni, Br and Sr. The tissue samples were classified according to cancer types (adenocarcinomas, epidermoides and of small cell carcinoma), personal habits (smokers and alcoholic), genetic predisposition and residence place. There was a remarkable decrease in the concentration of Ca and a marked increment in the Cu in the epidermoide tissue samples with regard to those of adenocarcinoma or of small cells cancer. Also, decrements were detected in K and increments of Fe, Co and Cu in the sample belonging to people that resided in Mexico City with regard to those that resided in the State of Mexico.

  20. Organoid culture systems for prostate epithelial tissue and prostate cancer tissue

    PubMed Central

    Drost, Jarno; Karthaus, Wouter R.; Gao, Dong; Driehuis, Else; Sawyers, Charles L.; Chen, Yu; Clevers, Hans

    2016-01-01

    Summary This protocol describes a recently developed strategy to generate 3D prostate organoid cultures from healthy mouse and human prostate (either bulk or FAC-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumour cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumour. The stepwise establishment of these cultures and the fully defined serum-free conditioned medium that is required to sustain organoid growth are outlined. Organoids established using this protocol can be used to study many different aspects of prostate biology, including homeostasis, tumorigenesis and drug discovery. PMID:26797458

  1. The magnitude of linear dichroism of biological tissues as a result of cancer changes

    NASA Astrophysics Data System (ADS)

    Bojchuk, T. M.; Yermolenko, S. B.; Fedonyuk, L. Y.; Petryshen, O. I.; Guminetsky, S. G.; Prydij, O. G.

    2012-01-01

    The results of studies of linear dichroism values of different types of biological tissues (human prostate, esophageal epithelial human muscle tissue in rats) both healthy and infected tumor at different stages of development are shown here. The significant differences in magnitude of linear dichroism and its spectral dependence in the spectral range λ = 330 - 750 nm both among the objects of study, and between biotissues: healthy (or affected by benign tumors) and cancer patients are established. It is researched that in all cases in biological tissues (prostate gland, esophagus, human muscle tissue in rats) with cancer the linear dichroism arises, the value of which depends on the type of tissue and time of the tumor process. As for healthy tissues linear dichroism is absent, the results may have diagnostic value for detecting and assessing the degree of development of cancer.

  2. The magnitude of linear dichroism of biological tissues as a result of cancer changes

    NASA Astrophysics Data System (ADS)

    Bojchuk, T. M.; Yermolenko, S. B.; Fedonyuk, L. Y.; Petryshen, O. I.; Guminetsky, S. G.; Prydij, O. G.

    2011-09-01

    The results of studies of linear dichroism values of different types of biological tissues (human prostate, esophageal epithelial human muscle tissue in rats) both healthy and infected tumor at different stages of development are shown here. The significant differences in magnitude of linear dichroism and its spectral dependence in the spectral range λ = 330 - 750 nm both among the objects of study, and between biotissues: healthy (or affected by benign tumors) and cancer patients are established. It is researched that in all cases in biological tissues (prostate gland, esophagus, human muscle tissue in rats) with cancer the linear dichroism arises, the value of which depends on the type of tissue and time of the tumor process. As for healthy tissues linear dichroism is absent, the results may have diagnostic value for detecting and assessing the degree of development of cancer.

  3. Down-regulation of adenosine monophosphate-activated protein kinase activity: A driver of cancer.

    PubMed

    He, Xiaoling; Li, Cong; Ke, Rong; Luo, Lingyu; Huang, Deqiang

    2017-04-01

    Adenosine monophosphate-activated protein kinase (AMPK), a serine/threonine protein kinase, is known as "intracellular energy sensor and regulator." AMPK regulates multiple cellular processes including protein and lipid synthesis, cell proliferation, invasion, migration, and apoptosis. Moreover, AMPK plays a key role in the regulation of "Warburg effect" in cancer cells. AMPK activity is down-regulated in most tumor tissues compared with the corresponding adjacent paracancerous or normal tissues, indicating that the decline in AMPK activity is closely associated with the development and progression of cancer. Therefore, understanding the mechanism of AMPK deactivation during cancer progression is of pivotal importance as it may identify AMPK as a valid therapeutic target for cancer treatment. Here, we review the mechanisms by which AMPK is down-regulated in cancer.

  4. Diffuse reflectance spectroscopy as a tool for real-time tissue assessment during colorectal cancer surgery

    NASA Astrophysics Data System (ADS)

    Baltussen, Elisabeth J. M.; Snaebjornsson, Petur; de Koning, Susan G. Brouwer; Sterenborg, Henricus J. C. M.; Aalbers, Arend G. J.; Kok, Niels; Beets, Geerard L.; Hendriks, Benno H. W.; Kuhlmann, Koert F. D.; Ruers, Theo J. M.

    2017-10-01

    Colorectal surgery is the standard treatment for patients with colorectal cancer. To overcome two of the main challenges, the circumferential resection margin and postoperative complications, real-time tissue assessment could be of great benefit during surgery. In this ex vivo study, diffuse reflectance spectroscopy (DRS) was used to differentiate tumor tissue from healthy surrounding tissues in patients with colorectal neoplasia. DRS spectra were obtained from tumor tissue, healthy colon, or rectal wall and fat tissue, for every patient. Data were randomly divided into training (80%) and test (20%) sets. After spectral band selection, the spectra were classified using a quadratic classifier and a linear support vector machine. Of the 38 included patients, 36 had colorectal cancer and 2 had an adenoma. When the classifiers were applied to the test set, colorectal cancer could be discriminated from healthy tissue with an overall accuracy of 0.95 (±0.03). This study demonstrates the possibility to separate colorectal cancer from healthy surrounding tissue by applying DRS. High classification accuracies were obtained both in homogeneous and inhomogeneous tissues. This is a fundamental step toward the development of a tool for real-time in vivo tissue assessment during colorectal surgery.

  5. Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection

    NASA Astrophysics Data System (ADS)

    Tate, Tyler; Baggett, Brenda; Rice, Photini; Watson, Jennifer; Orsinger, Gabe; Nymeyer, Ariel C.; Welge, Weston A.; Keenan, Molly; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth; Chambers, Setsuko; Black, John; Utzinger, Urs; Barton, Jennifer

    2015-03-01

    With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

  6. Silk fibroin-Thelebolan matrix: A promising chemopreventive scaffold for soft tissue cancer.

    PubMed

    Mukhopadhyay, Sourav K; Naskar, Deboki; Bhattacharjee, Promita; Mishra, Abheepsa; Kundu, Subhas C; Dey, Satyahari

    2017-07-01

    Research of improved functional bio-mimetic matrix for regenerative medicine is currently one of the rapidly growing fields in tissue engineering and medical sciences. This study reports a novel bio-polymeric matrix, which is fabricated using silk protein fibroin from Bombyx mori silkworm and fungal exopolysaccharide Thelebolan from Antarctic fungus Thelebolus sp. IITKGP-BT12 by solvent evaporation and freeze drying method. Natural cross linker genipin is used to imprison the Thelebolan within the fibroin network. Different cross-linked and non-cross-linked fibroin/Thelebolan matrices are fabricated and biophysically characterized. Cross-linked thin films show robustness, good mechanical strength and high temperature stability in comparison to non-cross-linked and pure matrices. The 3D sponge matrices demonstrate good cytocompatibility. Interestingly, sustained release of the Thelebolan from the cross-linked matrices induce apoptosis in colon cancer cell line (HT-29) in time dependent manner while it is nontoxic to the normal fibroblast cells (L929).The findings indicate that the cross-linked fibroin/Thelebolan matrices can be used as potential topical chemopreventive scaffold for preclusion of soft tissue carcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models.

    PubMed

    Carvalho, Mariana R; Lima, Daniela; Reis, Rui L; Oliveira, Joaquim M; Correlo, Vitor M

    2017-06-01

    Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current "state of art" on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their study.

  8. Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Li, Zhifang; Li, Hui

    2012-12-01

    In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

  9. Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation.

    PubMed

    Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

    2017-01-02

    Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model.

  10. Identification of the long non‑coding RNA LET as a novel tumor suppressor in gastric cancer.

    PubMed

    Tian, Jingjing; Hu, Xibao; Gao, Wei; Zhang, Jie; Chen, Ming; Zhang, Xinrong; Ma, Junhong; Yuan, Hongxia

    2017-04-01

    Long non-coding RNAs (lncRNAs) have emerged recently as important factors in regulating fundamental biological processes. Alterations in the expression and function of lncRNAs have been observed to promote tumor formation, progression and metastasis. Although downregulation of the expression levels of LET lncRNA in several tumors has been reported, its role in gastric cancer remains unknown. The aim of the present study was to investigate the expression and function of LET in gastric cancer development. The expression levels of LET in 37 pairs of gastric cancer and adjacent non‑tumor tissues were detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). In addition, LET expression in gastric cancer cell lines was analyzed by RT‑qPCR assay analysis. Furthermore, the impact of LET on cell proliferation, migration and apoptosis were detected using the cell counting kit‑8, wound scratch and ELISA assays, respectively. The results demonstrated that the expression level of LET was downregulated in gastric cancer tissues and cell lines (SGC‑7901 and MGC‑803) compared with normal tissues and a normal human gastric epithelial cell line (GES‑1). Restoration of LET expression using a synthesized recombinant overexpression vector transfected into SGC‑7901 and MGC‑803 cells, significantly inhibited cell proliferation and migration, and promoted cell apoptosis in vitro. The present study is the first to demonstrate that LET may function as a tumor suppressor in gastric cancer. The results indicate that LET may be a promising biomarker and/or a therapeutic target for gastric cancer.

  11. Association between P16INK4a Promoter Methylation and Non-Small Cell Lung Cancer: A Meta-Analysis

    PubMed Central

    Zhu, Siwei; Hua, Feng; Zhao, Hui; Xu, Hongrui; You, Jiacong; Sun, Linlin; Wang, Weiqiang; Chen, Jun; Zhou, Qinghua

    2013-01-01

    Background Aberrant methylation of CpG islands acquired in tumor cells in promoter regions plays an important role in carcinogenesis. Accumulated evidence demonstrates P16INK4a gene promoter hypermethylation is involved in non-small cell lung carcinoma (NSCLC), indicating it may be a potential biomarker for this disease. The aim of this study is to evaluate the frequency of P16INK4a gene promoter methylation between cancer tissue and autologous controls by summarizing published studies. Methods By searching Medline, EMBSE and CNKI databases, the open published studies about P16INK4a gene promoter methylation and NSCLC were identified using a systematic search strategy. The pooled odds of P16INK4A promoter methylation in lung cancer tissue versus autologous controls were calculated by meta-analysis method. Results Thirty-four studies, including 2 652 NSCLC patients with 5 175 samples were included in this meta-analysis. Generally, the frequency of P16INK4A promoter methylation ranged from 17% to 80% (median 44%) in the lung cancer tissue and 0 to 80% (median 15%) in the autologous controls, which indicated the methylation frequency in cancer tissue was much higher than that in autologous samples. We also find a strong and significant correlation between tumor tissue and autologous controls of P16INK4A promoter methylation frequency across studies (Correlation coefficient 0.71, 95% CI:0.51–0.83, P<0.0001). And the pooled odds ratio of P16INK4A promoter methylation in cancer tissue was 3.45 (95% CI: 2.63–4.54) compared to controls under random-effect model. Conclusion Frequency of P16INK4a promoter methylation in cancer tissue was much higher than that in autologous controls, indicating promoter methylation plays an important role in carcinogenesis of the NSCLC. Strong and significant correlation between tumor tissue and autologous samples of P16INK4A promoter methylation demonstrated a promising biomarker for NSCLC. PMID:23577085

  12. Epigenetic alterations are involved in the overexpression of glutathione S-transferase π-1 in human colorectal cancers.

    PubMed

    Zhang, Rui; Kang, Kyoung Ah; Piao, Mei Jing; Kim, Ki Cheon; Zheng, Jian; Yao, Cheng Wen; Cha, Ji Won; Maeng, Young Hee; Chang, Weon Young; Moon, Pyong-Gon; Baek, Moon-Chang; Hyun, Jin Won

    2014-09-01

    Glutathione S-transferase π-1 (GSTP-1) is a member of the glutathione S-transferase enzyme superfamily, which catalyzes the conjugation of electrophiles to glutathione during the process of detoxification. In this study, the epigenetic alterations of GSTP-1 expression in human colorectal cancers and the underlying mechanisms were investigated. In 10 colon cancer patients, proteomic analysis revealed that expression of GSTP-1 protein was higher in tumor tissues than in paired adjacent normal tissues. Likewise, in 7 of 10 colon cancer patients, GSTP-1 protein expression was more than 1.5-fold higher in tumor tissues than in adjacent normal tissues, as determined by western blotting. Immunohistochemical data confirmed that GSTP-1 protein was expressed at higher levels in colon cancer tissues compared to normal mucosa. GSTP-1 enzyme activity was closely correlated with GSTP-1 protein expression in colon cancer patients. Consistent with this, GSTP-1 mRNA, protein and activity levels were higher in the colorectal cancer cell lines Caco-2, HCT-116, HT-29, SNU-407 and SNU-1033 compared to the normal colon cell line FHC. Methylation-specific PCR results indicated that the high levels of GSTP-1 in human colorectal cancer cell lines were likely due to the lower degree of promoter methylation in colon cancer cell lines compared to the normal colon cell line, consistent with findings in colon cancer patients. Moreover, the levels of specific activator-protein complexes and histone marks were higher in human colorectal cancer cells compared to the normal human colon cell line, whereas the repressor protein complexes exhibited the opposite pattern. Furthermore, chromatin immunoprecipitation assays demonstrated that expression levels of the transcription factors AP-1 and SP-1 were correlated with the upregulation of GSTP-1 expression in colorectal cancer cells. Finally, knockdown of GSTP-1 promoted the sensitivity of SNU-407 cells to the anticancer agent 5-fluorouracil. These

  13. Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer

    PubMed Central

    Johnson, Jennifer M; Lai, Stephen Y.; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A.; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Outschoorn, Ubaldo Martinez; Curry, Joseph

    2015-01-01

    Aims Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically Monocarboxylate Transporter 1 (MCT1) and Translocase of the Outer Mitochondrial Membrane Member 20 (TOMM20). Methods Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer (PTC), and 8 non-cancerous thyroid) and 9 ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. Results MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (p<0.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (p<0.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (p<0.001). These xenograft tumors have high 13C- pyruvate uptake. Conclusions Anaplastic thyroid cancer has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. PMID:26615136

  14. Objective Diagnosis of Cervical Cancer by Tissue Protein Profile Analysis

    NASA Astrophysics Data System (ADS)

    Patil, Ajeetkumar; Bhat, Sujatha; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh

    2011-07-01

    Protein profiles of homogenized normal cervical tissue samples from hysterectomy subjects and cancerous cervical tissues from biopsy samples collected from patients with different stages of cervical cancer were recorded using High Performance Liquid Chromatography coupled with Laser Induced Fluorescence (HPLC-LIF). The Protein profiles were subjected to Principle Component Analysis to derive statistically significant parameters. Diagnosis of sample types were carried out by matching three parameters—scores of factors, squared residuals, and Mahalanobis Distance. ROC and Youden's Index curves for calibration standards were used for objective estimation of the optimum threshold for decision making and performance.

  15. Evaluation of serum lysyl oxidase as a blood test for colorectal cancer.

    PubMed

    Ward, S T; Weston, C J; Hepburn, E; Damery, S; Hejmadi, R K; Morton, D G; Middleton, G; Ismail, T; Adams, D H

    2014-06-01

    Lysyl oxidase (LOX) expression is elevated in colorectal cancer (CRC) tissue and associated with disease progression. A blood test may form a more acceptable diagnostic test for CRC although LOX has not previously been measured in the serum. We therefore sought to determine the clinical usefulness of a serum LOX test for CRC in a symptomatic population. Adult patients referred to a hospital colorectal clinic with bowel symptoms completed a questionnaire and provided a blood sample for serum LOX measurement. Associations between presenting symptoms, serum LOX concentrations and outcomes of investigations were tested by univariate and multivariate analyses to determine if serum LOX was clinically useful in the prediction of CRC. LOX expression in CRC and adjacent colon biopsies was evaluated by ELISA and immunohistochemistry. Thirty-one cases of colorectal cancer and 16 high-risk polyps were identified from a total of 962 participants. There was no association between serum LOX concentration and the presence of CRC, high-risk polyps or cancers at any site. LOX expression was significantly increased in CRC tissue compared to adjacent colon. Despite overexpression of LOX in CRC tissue, elevated serum levels could not be demonstrated. Serum LOX measurement is therefore not a clinically useful test for CRC. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Long non-coding RNAs in cancer metabolism.

    PubMed

    Xiao, Zhen-Dong; Zhuang, Li; Gan, Boyi

    2016-10-01

    Altered cellular metabolism is an emerging hallmark of cancer. Accumulating recent evidence links long non-coding RNAs (lncRNAs), a still poorly understood class of non-coding RNAs, to cancer metabolism. Here we review the emerging findings on the functions of lncRNAs in cancer metabolism, with particular emphasis on how lncRNAs regulate glucose and glutamine metabolism in cancer cells, discuss how lncRNAs regulate various aspects of cancer metabolism through their cross-talk with other macromolecules, explore the mechanistic conceptual framework of lncRNAs in reprogramming metabolism in cancers, and highlight the challenges in this field. A more in-depth understanding of lncRNAs in cancer metabolism may enable the development of novel and effective therapeutic strategies targeting cancer metabolism. © 2016 WILEY Periodicals, Inc.

  17. SPOP suppresses tumorigenesis by regulating Hedgehog/Gli2 signaling pathway in gastric cancer.

    PubMed

    Zeng, Chunyan; Wang, Yao; Lu, Quqin; Chen, Jiang; Zhang, Junyan; Liu, Tao; Lv, Nonghua; Luo, Shiwen

    2014-09-11

    Recent evidence suggests that aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas including gastric cancer. Speckle-type POZ protein, SPOP, is an E3 ubiquitin ligase adaptor, and it is found to inhibit oncogenic signaling. However, the molecular mechanisms are largely unknown. In this study, we characterized the expression of SPOP in 88 pairs of gastric cancer tissues and adjacent tissues by immunohistochemical staining and Western blotting. The relationship between SPOP expression and clinical pathologic factors was analyzed. Transfected gastric cancer cell lines were used in cell viability, wound healing and colony formation assays. The interaction of SPOP with Gli2 and other related apoptotic proteins was assessed by immunoprecipitation, Western blotting, real-time PCR and dual luciferase reporter assays. Intracellular interaction of SPOP and Gli2 was visualized by immunofluorescent staining in gastric cancer cells. Immunohistochemical staining of SPOP can be detected in gastric cancer tissues but much less than adjacent gastric tissues (P < 0.01). High SPOP expression is negatively correlated with lymph node metastasis, poor histological differentiation, and tumor malignancy according to TNM staging. In vitro experiments revealed that over-expression of SPOP prevented tumor cells from proliferation, migration and colony formation in gastric cancer cell lines. Likewise, repression of SPOP promoted cell viability, migration, proliferation, and attenuated apoptosis. Mechanistic studies revealed that increasing SPOP accelerated Gli2 degradation but regardless of Gli2 synthesis. Furthermore, cytoplasmic Gli2 decreased markedly along with the abundant expression of SPOP in MKN45 cells. Our findings indicate that SPOP plays critical roles in suppressing gastric tumorigenesis through inhibiting Hh/Gli2 signaling pathway. It may provide an alternative strategy for developing

  18. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    MedlinePlus

    ... Cancer Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key ...

  19. Differentiating fatty and non-fatty tissue using photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Pan, Leo; Rohling, Robert; Abolmaesumi, Purang; Salcudean, Septimiu; Tang, Shuo

    2014-03-01

    In this paper, we demonstrate a temporal-domain intensity-based photoacoustic imaging method that can differentiate between fatty and non-fatty tissues. PA pressure intensity is partly dependent on the tissue's speed of sound, which increases as temperature increases in non-fatty tissue and decreases in fatty tissue. Therefore, by introducing a temperature change in the tissue and subsequently monitoring the change of the PA intensity, it is possible to distinguish between the two types of tissue. A commercial ultrasound system with a 128-element 5-14 MHz linear array transducer and a tunable ND:YAG laser were used to produce PA images. Ex-vivo bovine fat and porcine liver tissues were precooled to below 10°C and then warmed to room-temperature over ~1 hour period. A thermocouple monitored the temperature rise while PA images were acquired at 0.5°C intervals. The averaged intensity of the illuminated tissue region at each temperature interval was plotted and linearly fitted. Liver samples showed a mean increase of 2.82 %/°C, whereas bovine fat had a mean decrease of 6.24 %/°C. These results demonstrate that this method has the potential to perform tissue differentiation in the temporal-domain.

  20. Correlation of HIWI and HILI Expression with Cancer Stem Cell Markers in Colorectal Cancer.

    PubMed

    Litwin, Monika; Dubis, Joanna; Arczyńska, Katarzyna; Piotrowska, Aleksandra; Frydlewicz, Anna; Karczewski, Maciej; Dzięgiel, Piotr; Witkiewicz, Wojciech

    2015-06-01

    Cancer stem cells (CSCs) constitute a sub-population of tumor cells that possess stem cell properties, such as self-renewal and the ability of differentiation. The presence of CSCs is associated with metastatic potential, treatment resistance and poor patient prognosis. Recently, aberrant expression of P-element induced wimpy testis proteins-PIWI (HIWI and HILI) has been identified in various types of tumors. The aim of the study was to evaluate the clinical significance of the HIWI and HILI expression and its relationship with cancer stem cells markers in 72 patients with colorectal carcinoma (CRC). The expression level of HIWI and HILI and cancer stem cells markers in paired cancerous and non-cancerous tissues was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Immunohistochemistry was performed to confirm the observed changes on mRNA level and detect tissue localization of PIWI proteins. Significantly higher mRNA levels of HIWI and decreased HILI mRNA were measured in colorectal cancer tissues compared to corresponding non-cancerous samples. The changes in HIWI mRNA level in cancer tissues were correlated with OCT4 expression. Positive correlations between HILI level and SOX2 were also observed in cancerous tissues. Our results indicate a reciprocal regulation between HIWI, HILI and some CSCs markers in colorectal cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.