Sample records for adjacent noncancerous 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. 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

  3. Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers

    NASA Astrophysics Data System (ADS)

    Brozek-Pluska, B.; Kopec, M.

    2016-12-01

    Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed.

  4. Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers.

    PubMed

    Brozek-Pluska, B; Kopec, M

    2016-12-05

    Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Label-free determination of lipid composition and secondary protein structure of human salivary noncancerous and cancerous tissues by Raman microspectroscopy.

    PubMed

    Brozek-Pluska, Beata; Kopec, Monika; Niedzwiecka, Izabela; Morawiec-Sztandera, Alina

    2015-04-07

    The applications of optical spectroscopic methods in cancer detection open new possibilities in oncological diagnostics. Raman spectroscopy and Raman imaging represent noninvasive, label-free, and rapidly developing tools in cancer diagnosis. In the study described in this paper Raman microspectroscopy has been employed to examine noncancerous and cancerous human salivary gland tissues of the same patient. The most significant differences between noncancerous and cancerous tissues were found in regions typical for the vibrations of lipids and proteins. The detailed analysis of secondary structures of proteins contained in the cancerous and the noncancerous tissues is also presented.

  6. 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.

  7. 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).

  8. 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.

  9. Distribution of phthalocyanines and Raman reporters in human cancerous and noncancerous breast tissue as studied by Raman imaging.

    PubMed

    Brozek-Pluska, Beata; Jarota, Arkadiusz; Jablonska-Gajewicz, Joanna; Kordek, Radzislaw; Czajkowski, Wojciech; Abramczyk, Halina

    2012-08-01

    There is a considerable interest in the developing new diagnostic techniques allowing noninvasive tracking of the progress of therapies used to treat a cancer. Raman imaging of distribution of phthalocyanine photosensitizers may open new possibilities of Photodynamic Therapy (PDT) to treat a wide range of neoplastic lesions with improved effectiveness of treatment through precise identification of malignant areas. We have employed Raman imaging and Raman spectroscopy to analyze human breast cancer tissue that interacts with photosensitizers used in the photodynamic therapy of cancer. PCA (Principal Component Analysis) has been employed to analyze various areas of the noncancerous and cancerous breast tissues. The results show that the emission spectra combined with the Raman images are very sensitive indicators to specify the aggregation state and the distribution of phthalocyanines in the cancerous and noncancerous breast tissues. Our results provide experimental evidence on the role of aggregation of phthalocyanines as a factor of particular significance in differentiation of the normal and tumourous (cancerous or benign pathology) breast tissues. We conclude that the Raman imaging reported here has a potential to be a novel and effective photodynamic therapeutic method with improved selectivity for the treatment of breast cancer.

  10. 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

  11. 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.

  12. 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

  13. Ultrafast dynamics and Raman imaging of metal complexes of tetrasulphonated phthalocyanines in human cancerous and noncancerous breast tissues

    NASA Astrophysics Data System (ADS)

    Abramczyk, H.; Jarota, A.; Brozek-Pluska, B.; Tondusson, M.; Freysz, E.; Musial, J.; Kordek, R.

    2013-03-01

    A promising material in medicine, electronics, optoelectronics, electrochemistry, catalysis and photophysics, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) is investigated at biological interfaces of human breast tissue by means of time-resolved spectroscopy. The nature of fast processes and pathways of the competing relaxation mechanisms from the initially excited electronic states of a photosensitizer at biological interfaces have been studied. Comparison between the results in the biological environment of the breast tissues and in aqueous solutions demonstrates that the photochemical mechanisms become dramatically different. The presented results provide a basis for a substantial revision of the commonly accepted assumption that photochemistry of the bulk properties of photosensitizers in solutions can be translated to the interfacial region. First, in solution the dynamics of the photosensitizer is much slower than that at the biological interface. Second, the dynamics of the photosensitizer in the cancerous tissue is dramatically slower than that in noncancerous tissue. Our results provide evidence that molecular structures responsible for harvesting of the light energy in biological tissue find their ways for a recovery through some special features of the potential energy surfaces such as conical intersections, which facilitate the rate of radiationless transitions and maintain the photostability in the biological systems.

  14. Raman microspectroscopy of noncancerous and cancerous human breast tissues. Identification and phase transitions of linoleic and oleic acids by Raman low-temperature studies.

    PubMed

    Brozek-Pluska, Beata; Kopec, Monika; Surmacki, Jakub; Abramczyk, Halina

    2015-04-07

    We present the results of Raman studies in the temperature range of 293-77 K on vibrational properties of linoleic and oleic acids and Raman microspectroscopy of human breast tissues at room temperature. Our results confirmed the significant role of unsaturated fatty acids in differentiation of noncancerous and cancerous breast tissues and the role of vibrational spectroscopy in phase transition identification. We have found that vibrational properties are very sensitive indicators to specify phases and phase transitions typical of unsaturated fatty acids at the molecular level. Using Raman spectroscopy we have identified high-temperature, middle-temperature and low-temperature phases of linoleic acid. Results obtained for linoleic acid were compared with parameters characteristic of α and γ phases of oleic acid - the parent compound of polyunsaturated fatty acids.

  15. 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.

  16. 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

  17. Advancements in Pharmacotherapy for Noncancerous Manifestations of HPV

    PubMed Central

    Kollipara, Ramya; Ekhlassi, Erfon; Downing, Christopher; Guidry, Jacqueline; Lee, Michael; Tyring, Stephen K.

    2015-01-01

    Human papillomavirus (HPV) is the most common sexually transmitted disease. Via infection of the basal epithelial cells, HPV causes numerous malignancies and noncancerous cutaneous manifestations. Noncancerous cutaneous manifestations of HPV, including common, plantar, plane, and anogenital warts, are among the most common reasons for an office visit. Although there are various therapies available, they are notoriously difficult to treat. HPV treatments can be grouped into destructive (cantharidin, salicylic acid), virucidal (cidofovir, interferon-α), antimitotic (bleomycin, podophyllotoxin, 5-fluorouracil), immunotherapy (Candida antigen, contact allergen immunotherapy, imiquimod) or miscellaneous (trichloroacetic acid, polyphenon E). The mechanism of action, recent efficacy data, safety profile and recommended regimen for each of these treatment modalities is discussed. PMID:26239450

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue

    PubMed Central

    Shinn, Helen Ki; Yan, Chunri; Kim, Tae-Hwan; Kim, Sang Tae; Kim, Won Tae; Lee, Ok-Jun; Moon, Sung-Kwon; Kim, Nam-Hyung; Kim, Jayoung; Cha, Eun-Jong

    2016-01-01

    Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). Conclusions: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections. PMID:27377944

  6. Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue.

    PubMed

    Yun, Seok Joong; Jeong, Pildu; Kang, Ho Won; Shinn, Helen Ki; Kim, Ye-Hwan; Yan, Chunri; Choi, Young-Ki; Kim, Dongho; Ryu, Dong Hee; Ha, Yun-Sok; Kim, Tae-Hwan; Kwon, Tae Gyun; Kim, Jung Min; Suh, Sang Heon; Kim, Seon-Kyu; Kim, Seon-Young; Kim, Sang Tae; Kim, Won Tae; Lee, Ok-Jun; Moon, Sung-Kwon; Kim, Nam-Hyung; Kim, Isaac Yi; Kim, Jayoung; Cha, Hee-Jae; Choi, Yung-Hyun; Cha, Eun-Jong; Kim, Wun-Jae

    2016-06-01

    Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.

  7. 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.

  8. 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

  9. 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.

  10. Phase transitions in oleic acid and in human breast tissue as studied by Raman spectroscopy and Raman imaging.

    PubMed

    Brozek-Pluska, Beata; Jablonska-Gajewicz, Joanna; Kordek, Radzislaw; Abramczyk, Halina

    2011-05-12

    We present the results of differential scanning calorimetry (DSC) and Raman studies in the temperature range of 293-77 K on vibrational properties of the oleic acid and the human breast tissue as a function of temperature. We have found that vibrational properties are very sensitive indicators to specify phases and phase transitions at the molecular level. We have found that water content confined in the cancerous tissue is markedly different from that in the noncancerous tissue. The OH stretching vibrations of water are useful as potential Raman biomarkers to distinguish between the cancerous and the noncancerous human breast tissues. Our results provide experimental evidence on the role of lipid profile and cell hydration as factors of particular significance in differentiation of the noncancerous and cancerous breast tissues.

  11. 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.

  12. 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

  13. 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.

  14. Size-Based Enrichment Technologies for Non-cancerous Tumor-Derived Cells in Blood.

    PubMed

    Mong, Jamie; Tan, Min-Han

    2018-05-01

    Enumeration of circulating tumor cells (CTCs) in the bloodstream can predict prognosis and survival in cancer patients. However, CTC rarity and heterogeneity pose challenges in using them as biomarkers. Recent publications have reported new classes of circulating, non-cancerous tumor-derived cells present in cancer patients but not in healthy controls; these include cancer-associated macrophages, tumor-endothelial clusters (TECs), and cancer-associated fibroblasts (CAFs). Well-established marker-dependent CTC enrichment technologies will miss this group of circulating cells. To maximize our chance of finding useful circulating biomarkers in cancer patients, we propose the use of size-based enrichment technologies to isolate both cancerous and non-cancerous cells in circulation. We review their biological properties and discuss device features to consider in their enrichment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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

  17. Oncologic photodynamic diagnosis and therapy: confocal Raman/fluorescence imaging of metal phthalocyanines in human breast cancer tissue in vitro.

    PubMed

    Abramczyk, Halina; Brozek-Pluska, Beata; Surmacki, Jakub; Musial, Jacek; Kordek, Radzislaw

    2014-11-07

    Raman microspectroscopy and confocal Raman imaging combined with confocal fluorescence were used to study the distribution and aggregation of aluminum tetrasulfonated phthalocyanine (AlPcS4) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and aggregation of aluminum phthalocyanine, which is a potential photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. We have observed that the distribution of aluminum tetrasulfonated phthalocyanine confined in cancerous tissue is markedly different from that in noncancerous tissue. We have concluded that Raman imaging can be treated as a new and powerful technique useful in cancer photodynamic therapy, increasing our understanding of the mechanisms and efficiency of photosensitizers by better monitoring localization in cancer cells as well as the clinical assessment of the therapeutic effects of PDT and PIT.

  18. Protective effects of sodium selenite supplementation against irradiation-induced damage in non-cancerous human esophageal cells.

    PubMed

    Puspitasari, Irma M; Yamazaki, Chiho; Abdulah, Rizky; Putri, Mirasari; Kameo, Satomi; Nakano, Takashi; Koyama, Hiroshi

    2017-01-01

    The administration of radioprotective compounds is one approach to preventing radiation damage in non-cancerous tissues. Therefore, radioprotective compounds are crucial in clinical radiotherapy. Selenium is a radioprotective compound that has been used in previous clinical studies of radiotherapy. However, evidence regarding the effectiveness of selenium in radiotherapy and the mechanisms underlying the selenium-induced reduction of the side effects of radiotherapy remains insufficient. To further investigate the effectiveness of selenium in radiotherapy, the present study examined the protective effects of sodium selenite supplementation administered prior to X-ray radiation treatment in CHEK-1 non-cancerous human esophageal cells. Sodium selenite supplementation increased glutathione peroxidase 1 (GPx-1) activity in a dose- and time-dependent manner. The sodium selenite dose that induced the highest GPx-1 activity was determined to be 50 nM for 72 h prior to radiotherapy. The half-maximal inhibitory concentration of sodium selenite in CHEK-1 cells was 3.6 µM. Sodium selenite supplementation increased the survival rate of the cells in a dose-dependent manner and enhanced the degree of cell viability at 72 h post-irradiation (P<0.05). Combined treatment with 50 nM sodium selenite and 2 gray (Gy) X-ray irradiation decreased the number of sub-G 1 cells from 5.9 to 4.2% (P<0.05) and increased the proportion of G 1 cells from 58.8 to 62.1%, compared with 2 Gy X-ray irradiation alone; however, this difference was not statistically significant (P=1.00). Western blot analysis revealed that treatment with 2 Gy X-ray irradiation significantly increased the expression levels of cleaved poly (ADP-ribose) polymerase (PARP; P<0.05). In addition, combined treatment with 50 nM sodium selenite and 2 Gy X-ray irradiation reduced the expression levels of cleaved PARP protein, compared with 2 Gy X-ray irradiation alone; however, this reduction was not statistically significant (P=0

  19. 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.

  20. 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.

  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. Potential of epigenetic therapies in non-cancerous conditions

    PubMed Central

    Mau, Theresa; Yung, Raymond

    2014-01-01

    There has been an explosion of knowledge in the epigenetics field in the past 20 years. The first epigenetic therapies have arrived in the clinic for cancer treatments. In contrast, much of the promise of epigenetic therapies for non-cancerous conditions remains in the laboratories. The current review will focus on the recent progress that has been made in understanding the pathogenic role of epigenetics in immune and inflammatory conditions, and how the knowledge may provide much needed new therapeutic targets for many autoimmune diseases. Dietary factors are increasingly recognized as potential modifiers of epigenetic marks that can influence health and diseases across generations. The current epigenomics revolution will almost certainly complement the explosion of personal genetics medicine to help guide treatment decisions and disease risk stratification. PMID:25566322

  3. A novel Trojan-horse targeting strategy to reduce the non-specific uptake of nanocarriers by non-cancerous cells.

    PubMed

    Shen, Zheyu; Wu, Hao; Yang, Sugeun; Ma, Xuehua; Li, Zihou; Tan, Mingqian; Wu, Aiguo

    2015-11-01

    One big challenge with active targeting of nanocarriers is non-specific binding between targeting molecules and non-target moieties expressed on non-cancerous cells, which leads to non-specific uptake of nanocarriers by non-cancerous cells. Here, we propose a novel Trojan-horse targeting strategy to hide or expose the targeting molecules of nanocarriers on-demand. The non-specific uptake by non-cancerous cells can be reduced because the targeting molecules are hidden in hydrophilic polymers. The nanocarriers are still actively targetable to cancer cells because the targeting molecules can be exposed on-demand at tumor regions. Typically, Fe3O4 nanocrystals (FN) as magnetic resonance imaging (MRI) contrast agents were encapsulated into albumin nanoparticles (AN), and then folic acid (FA) and pH-sensitive polymers (PP) were grafted onto the surface of AN-FN to construct PP-FA-AN-FN nanoparticles. Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), transmission electron microscope (TEM) and gel permeation chromatography (GPC) results confirm successful construction of PP-FA-AN-FN. According to difference of nanoparticle-cellular uptake between pH 7.4 and 5.5, the weight ratio of conjugated PP to nanoparticle FA-AN-FN (i.e. graft density) and the molecular weight of PP (i.e. graft length) are optimized to be 1.32 and 5.7 kDa, respectively. In vitro studies confirm that the PP can hide ligand FA to prevent it from binding to cells with FRα at pH 7.4 and shrink to expose FA at pH 5.5. In vivo studies demonstrate that our Trojan-horse targeting strategy can reduce the non-specific uptake of the PP-FA-AN-FN by non-cancerous cells. Therefore, our PP-FA-AN-FN might be used as an accurately targeted MRI contrast agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

  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. HOXB9 Expression Correlates with Histological Grade and Prognosis in LSCC

    PubMed Central

    2017-01-01

    The purpose of this study was to investigate the HOX gene expression profile in laryngeal squamous cell carcinoma (LSCC) and assess whether some genes are associated with the clinicopathological features and prognosis in LSCC patients. The HOX gene levels were tested by microarray and validated by qRT-PCR in paired cancerous and adjacent noncancerous LSCC tissue samples. The microarray testing data of 39 HOX genes revealed 15 HOX genes that were at least 2-fold upregulated and 2 that were downregulated. After qRT-PCR evaluation, the three most upregulated genes (HOXB9, HOXB13, and HOXD13) were selected for tissue microarray (TMA) analysis. The correlations between the HOXB9, HOXB13, and HOXD13 expression levels and both clinicopathological features and prognosis were analyzed. Three HOX gene expression levels were markedly increased in LSCC tissues compared with adjacent noncancerous tissues (P < 0.001). HOXB9 was found to correlate with histological grade (P < 0.01) and prognosis (P < 0.01) in LSCC. In conclusion, this study revealed that HOXB9, HOXB13, and HOXD13 were upregulated and may play important roles in LSCC. Moreover, HOXB9 may serve as a novel marker of poor prognosis and a potential therapeutic target in LSCC patients. PMID:28808656

  6. 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.

  7. CTP synthase forms the cytoophidium in human hepatocellular carcinoma.

    PubMed

    Chang, Chia-Chun; Jeng, Yung-Ming; Peng, Min; Keppeke, Gerson Dierley; Sung, Li-Ying; Liu, Ji-Long

    2017-12-15

    CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma. Copyright © 2017. Published by Elsevier Inc.

  8. 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.

  9. Methylselenol, a selenium metabolite, plays common and different roles in cancerous colon HCT116 cell and noncancerous NCM460 colon cell proliferation.

    PubMed

    Zeng, Huawei; Briske-Anderson, Mary; Wu, Min; Moyer, Mary P

    2012-01-01

    Methylselenol is hypothesized to be a critical selenium metabolite for anticancer action, and differential chemopreventive effects of methylselenol on cancerous and noncancerous cells may play an important role. In this study, the submicromolar concentrations of methylselenol were generated by incubating methionase with seleno-L methionine, and colon-cancer-derived HCT-116 cells and noncancerous colon NCM460 cells were exposed to methylselenol. Methylselenol exposure inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase and an induction of apoptosis in HCT116, but to a much lesser extent in NCM460 colon cells. Similarly, the examination of mitogen-activated protein kinase (MAPK) and cellular myelocytomatosis oncogene (c-Myc) signaling status revealed that methylselenol inhibited the phosphorylation of extracellular-regulated kinase1/2 and p38 mitogen-activated protein kinase and the expression of c-Myc in HCT116 cells, but also to a lesser extent in NCM460 cells. The other finding is that methylselenol inhibits sarcoma kinase phosphorylation in HCT116 cells. In contrast, methylselenol upregulated the phosphorylation of sarcoma and focal adhesion kinase survival signals in the noncancerous NCM460 cells. Collectively, methylselenol's stronger potential of inhibiting cell proliferation/survival signals in the cancerous HCT116 cells when compared with that in noncancerous NCM460 cells may partly explain the potential of methylselenol's anticancer action.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Butyrate plays differential roles in cellular signaling in cancerous HCT116 and noncancerous NCM460 colon cells

    USDA-ARS?s Scientific Manuscript database

    Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects in colon. However, the mechanistic action of butyrate at the cellular level remains to be determined. We hypothesize that butyrate plays differential roles in cancerous and non-cancerous cells through si...

  16. Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells.

    PubMed

    Zeng, Huawei; Taussig, David P; Cheng, Wen-Hsing; Johnson, LuAnn K; Hakkak, Reza

    2017-01-01

    Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.

  17. Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells

    PubMed Central

    Zeng, Huawei; Taussig, David P.; Cheng, Wen-Hsing; Johnson, LuAnn K.; Hakkak, Reza

    2017-01-01

    Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells. PMID:28045428

  18. 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

  19. 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.

  20. Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer.

    PubMed

    Wang, Wei-Xin; Lin, Qing-Feng; Shen, Dong; Liu, Shao-Ping; Mao, Wei-Dong; Ma, Gui; Qi, Wei-Dong

    2014-01-01

    Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P = 0.019), clinical stage (P = 0.001), and lymph node metastasis (P = 0.026). The Kaplan-Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.

  1. 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.

  2. 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.

  3. 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

  4. Blood and Tissue Enzymatic Activities of GDH and LDH, Index of Glutathione, and Oxidative Stress among Breast Cancer Patients Attending Referral Hospitals of Addis Ababa, Ethiopia: Hospital-Based Comparative Cross-Sectional Study

    PubMed Central

    Seyoum, Nebiyou; Bekele, Mahteme; Tigeneh, Wondimagegn; Seifu, Daniel

    2018-01-01

    The exact cause of breast cancer is unknown; it is a multifactorial disease. It is the most diagnosed and the second killer cancer among women. Breast cancer can be originated from tissues of breast or secondary from other organs via metastasis. Generally, cancer cells show aberrant metabolism and oxidative stress when compared to noncancerous tissues of breast cancer patients. The current study aims at evaluating glutamate and glucose metabolism through GDH and LDH enzyme activities, oxidant, and antioxidative status among breast cancer patients attending referral hospitals of Addis Ababa, Ethiopia. Result. Catalytic activities of glutamate dehydrogenase, lactate dehydrogenase, and oxidative stress index were significantly increased in both serum (4.2 mU/ml, 78.6 mU/ml, and 3.3 : 1, resp.) and cancerous tissues (1.4 mU/ml, 111.7 mU/ml, and 2.15 : 1, resp.) of breast cancer patients as compared to those in serum of control group (3.15 mU/ml, 30.4 mU/ml, and 2.05 : 1, resp.) and noncancerous tissues of breast cancer patients (0.92 mU/ml, 70.5 mU/ml, and 1.1 : 1, resp.) (P ≤ 0.05). Correspondingly, ratios of reduced to oxidized glutathione were significantly decreased in both serum (20 : 1) and cancerous tissues (23.5 : 1) of breast cancer patients when compared to those in serum of control group (104.5 : 1) and noncancerous tissues of breast cancer patients (70.9 : 1) (P ≤ 0.05). Conclusion. Catalytic activities of GDH and LDH, ratios of GSH to GSSG, and concentration of TOS among breast cancer patients were significantly higher than were those among control group and noncancerous tissues of breast cancer patients, while TAC of breast cancer patients is significantly lower than that of control group and normal tissues of breast cancer patients. PMID:29770168

  5. Blood and Tissue Enzymatic Activities of GDH and LDH, Index of Glutathione, and Oxidative Stress among Breast Cancer Patients Attending Referral Hospitals of Addis Ababa, Ethiopia: Hospital-Based Comparative Cross-Sectional Study.

    PubMed

    Mehdi, Mohammed; Menon, M K C; Seyoum, Nebiyou; Bekele, Mahteme; Tigeneh, Wondimagegn; Seifu, Daniel

    2018-01-01

    The exact cause of breast cancer is unknown; it is a multifactorial disease. It is the most diagnosed and the second killer cancer among women. Breast cancer can be originated from tissues of breast or secondary from other organs via metastasis. Generally, cancer cells show aberrant metabolism and oxidative stress when compared to noncancerous tissues of breast cancer patients. The current study aims at evaluating glutamate and glucose metabolism through GDH and LDH enzyme activities, oxidant, and antioxidative status among breast cancer patients attending referral hospitals of Addis Ababa, Ethiopia. Result . Catalytic activities of glutamate dehydrogenase, lactate dehydrogenase, and oxidative stress index were significantly increased in both serum (4.2 mU/ml, 78.6 mU/ml, and 3.3 : 1, resp.) and cancerous tissues (1.4 mU/ml, 111.7 mU/ml, and 2.15 : 1, resp.) of breast cancer patients as compared to those in serum of control group (3.15 mU/ml, 30.4 mU/ml, and 2.05 : 1, resp.) and noncancerous tissues of breast cancer patients (0.92 mU/ml, 70.5 mU/ml, and 1.1 : 1, resp.) ( P ≤ 0.05). Correspondingly, ratios of reduced to oxidized glutathione were significantly decreased in both serum (20 : 1) and cancerous tissues (23.5 : 1) of breast cancer patients when compared to those in serum of control group (104.5 : 1) and noncancerous tissues of breast cancer patients (70.9 : 1) ( P ≤ 0.05). Conclusion . Catalytic activities of GDH and LDH, ratios of GSH to GSSG, and concentration of TOS among breast cancer patients were significantly higher than were those among control group and noncancerous tissues of breast cancer patients, while TAC of breast cancer patients is significantly lower than that of control group and normal tissues of breast cancer patients.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. Sexual steroids in serum and prostatic tissue of human non-cancerous prostate (STERPROSER trial).

    PubMed

    Neuzillet, Yann; Raynaud, Jean-Pierre; Radulescu, Camélia; Fiet, Jean; Giton, Franck; Dreyfus, Jean-François; Ghoneim, Tarek P; Lebret, Thierry; Botto, Henry

    2017-11-01

    The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume. Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI). Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates. STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase. © 2017 Wiley Periodicals, Inc.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Diffusing-wave polarimetry for tissue diagnostics

    NASA Astrophysics Data System (ADS)

    Macdonald, Callum; Doronin, Alexander; Peña, Adrian F.; Eccles, Michael; Meglinski, Igor

    2014-03-01

    We exploit the directional awareness of circularly and/or elliptically polarized light propagating within media which exhibit high numbers of scattering events. By tracking the Stokes vector of the detected light on the Poincaŕe sphere, we demonstrate its applicability for characterization of anisotropy of scattering. A phenomenological model is shown to have an excellent agreement with the experimental data and with the results obtained by the polarization tracking Monte Carlo model, developed in house. By analogy to diffusing-wave spectroscopy we call this approach diffusing-wave polarimetry, and illustrate its utility in probing cancerous and non-cancerous tissue samplesin vitro for diagnostic purposes.

  4. Raman spectroscopy and imaging: applications in human breast cancer diagnosis.

    PubMed

    Brozek-Pluska, Beata; Musial, Jacek; Kordek, Radzislaw; Bailo, Elena; Dieing, Thomas; Abramczyk, Halina

    2012-08-21

    The applications of spectroscopic methods in cancer detection open new possibilities in early stage diagnostics. Raman spectroscopy and Raman imaging represent novel and rapidly developing tools in cancer diagnosis. In the study described in this paper Raman spectroscopy has been employed to examine noncancerous and cancerous human breast tissues of the same patient. The most significant differences between noncancerous and cancerous tissues were found in regions characteristic for the vibrations of carotenoids, lipids and proteins. Particular attention was paid to the role played by unsaturated fatty acids in the differentiation between the noncancerous and the cancerous tissues. Comparison of Raman spectra of the noncancerous and the cancerous tissues with the spectra of oleic, linoleic, α-linolenic, γ-linolenic, docosahexaenoic and eicosapentaenoic acids has been presented. The role of sample preparation in the determination of cancer markers is also discussed in this study.

  5. Detection of brain tumor margins using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Juarez-Chambi, Ronald M.; Kut, Carmen; Rico-Jimenez, Jesus; Campos-Delgado, Daniel U.; Quinones-Hinojosa, Alfredo; Li, Xingde; Jo, Javier

    2018-02-01

    In brain cancer surgery, it is critical to achieve extensive resection without compromising adjacent healthy, noncancerous regions. Various technological advances have made major contributions in imaging, including intraoperative magnetic imaging (MRI) and computed tomography (CT). However, these technologies have pros and cons in providing quantitative, real-time and three-dimensional (3D) continuous guidance in brain cancer detection. Optical Coherence Tomography (OCT) is a non-invasive, label-free, cost-effective technique capable of imaging tissue in three dimensions and real time. The purpose of this study is to reliably and efficiently discriminate between non-cancer and cancerinfiltrated brain regions using OCT images. To this end, a mathematical model for quantitative evaluation known as the Blind End-Member and Abundances Extraction method (BEAE). This BEAE method is a constrained optimization technique which extracts spatial information from volumetric OCT images. Using this novel method, we are able to discriminate between cancerous and non-cancerous tissues and using logistic regression as a classifier for automatic brain tumor margin detection. Using this technique, we are able to achieve excellent performance using an extensive cross-validation of the training dataset (sensitivity 92.91% and specificity 98.15%) and again using an independent, blinded validation dataset (sensitivity 92.91% and specificity 86.36%). In summary, BEAE is well-suited to differentiate brain tissue which could support the guiding surgery process for tissue resection.

  6. Detection of brain tumor margins using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Juarez-Chambi, Ronald M.; Kut, Carmen; Rico-Jimenez, Jesus; Campos-Delgado, Daniel U.; Quinones-Hinojosa, Alfredo; Li, Xingde; Jo, Javier

    2018-02-01

    In brain cancer surgery, it is critical to achieve extensive resection without compromising adjacent healthy, non-cancerous regions. Various technological advances have made major contributions in imaging, including intraoperative magnetic imaging (MRI) and computed tomography (CT). However, these technologies have pros and cons in providing quantitative, real-time and three-dimensional (3D) continuous guidance in brain cancer detection. Optical Coherence Tomography (OCT) is a non-invasive, label-free, cost-effective technique capable of imaging tissue in three dimensions and real time. The purpose of this study is to reliably and efficiently discriminate between non-cancer and cancer-infiltrated brain regions using OCT images. To this end, a mathematical model for quantitative evaluation known as the Blind End- Member and Abundances Extraction method (BEAE). This BEAE method is a constrained optimization technique which extracts spatial information from volumetric OCT images. Using this novel method, we are able to discriminate between cancerous and non-cancerous tissues and using logistic regression as a classifier for automatic brain tumor margin detection. Using this technique, we are able to achieve excellent performance using an extensive cross-validation of the training dataset (sensitivity 92.91% and specificity 98.15%) and again using an independent, blinded validation dataset (sensitivity 92.91% and specificity 86.36%). In summary, BEAE is well-suited to differentiate brain tissue which could support the guiding surgery process for tissue resection.

  7. 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.

  8. 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

  9. L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study

    PubMed Central

    2012-01-01

    Background Head and neck squamous cell carcinoma (HNSCC) represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients’ prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients. Methods 53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2-ddCt) method. Results DDC mRNA levels were lower in squamous cell carcinomas (SCCs) of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts. Conclusion This is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases. PMID:23083099

  10. L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study.

    PubMed

    Geomela, Panagiota-Aikaterini; Kontos, Christos K; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

    2012-10-20

    Head and neck squamous cell carcinoma (HNSCC) represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients' prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients. 53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2-ddCt) method. DDC mRNA levels were lower in squamous cell carcinomas (SCCs) of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts. This is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases.

  11. Decreased expression of hsa_circ_0137287 predicts aggressive clinicopathologic characteristics in papillary thyroid carcinoma.

    PubMed

    Lan, Xiabin; Cao, Jun; Xu, Jiajie; Chen, Chao; Zheng, Chuanming; Wang, Jiafeng; Zhu, Xuhang; Zhu, Xin; Ge, Minghua

    2018-05-22

    Circular RNA (circRNA) is a new type of noncoding RNA that can serve as ideal biomarkers. Evidence has showed that circRNAs play an important role in carcinogenesis and cancer development. However, little is known about the diagnostic value of circRNAs in papillary thyroid carcinoma (PTC) as well as their associations with clinicopathologic characteristics of patients with PTC. The expression levels of hsa_circ_0137287 were detected in 120 PTC and 60 adjacent noncancerous thyroid tissues by quantitative real-time polymerase chain reaction. The relationships between the expression of hsa_circ_0137287 in PTC and the clinicopathologic factors were analyzed. Finally, receiver operating characteristic (ROC) curves were generated to assess the diagnostic value of hsa_circ_0137287 as a biomarker for PTC. The expression of hsa_circ_0137287 was significantly downregulated in PTC tissues compared with adjacent noncancerous tissues (P < .0001). Downregulation of hsa_circ_0137287 correlated with aggressive clinicopathologic characteristics of PTC such as extrathyroidal extension (P < .001), lymph node metastasis (P = .022), advanced T stage (P < .001) and larger tumor size (P < .001). The ROC curves revealed that hsa_circ_0137287 had a potential diagnostic value in predicting malignancy, extrathyroidal extension and lymph node metastasis. The area under curves were 0.8973 (95% CI = 0.8452-0.9494, P < .0001), 0.6885 (95%CI = 0.5908-0.7862, P = .0009), and 0.6691(95%CI = 0.5641-0.7742, P = .0034), respectively. Our findings suggest that hsa_circ_0137287 may serve as a novel biomarker for PTC. © 2018 Wiley Periodicals, Inc.

  12. Fluorescence-labeled methylation-sensitive amplified fragment length polymorphism (FL-MS-AFLP) analysis for quantitative determination of DNA methylation and demethylation status.

    PubMed

    Kageyama, Shinji; Shinmura, Kazuya; Yamamoto, Hiroko; Goto, Masanori; Suzuki, Koichi; Tanioka, Fumihiko; Tsuneyoshi, Toshihiro; Sugimura, Haruhiko

    2008-04-01

    The PCR-based DNA fingerprinting method called the methylation-sensitive amplified fragment length polymorphism (MS-AFLP) analysis is used for genome-wide scanning of methylation status. In this study, we developed a method of fluorescence-labeled MS-AFLP (FL-MS-AFLP) analysis by applying a fluorescence-labeled primer and fluorescence-detecting electrophoresis apparatus to the existing method of MS-AFLP analysis. The FL-MS-AFLP analysis enables quantitative evaluation of more than 350 random CpG loci per run. It was shown to allow evaluation of the differences in methylation level of blood DNA of gastric cancer patients and evaluation of hypermethylation and hypomethylation in DNA from gastric cancer tissue in comparison with adjacent non-cancerous tissue.

  13. 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

  14. Association of microRNA-21 expression with clinicopathological characteristics and the risk of progression in advanced prostate cancer patients receiving androgen deprivation therapy.

    PubMed

    Guan, Yangbo; Wu, You; Liu, Yifei; Ni, Jian; Nong, Shaojun

    2016-08-01

    Despite androgen deprivation therapy (ADT) remains the mainstay therapy for advanced prostate cancer (PCa), the patients have widely variable durations of response to ADT. Unfortunately, there is limited knowledge of pre-treatment prognostic factors for response to ADT. Recently, microRNA-21 (miR-21) has been reported to play an important role in development of castration resistance of CaP. However, little is known about the expression of miR-21 in advanced PCa biopsy tissues, and data on its potential predictive value in advanced PCa are completely lacking. In this study, paraffin-embedded prostate carcinoma tissues obtained by needle biopsy from 85 advanced PCa patients were evaluated for the expression levels of miR-21 by quantitative real-time PCR (qRT-PCR). In situ hybridization (ISH) analysis was performed to further confirm the qRT-PCR results. Kaplan-Meier analysis and Cox proportional hazards regression models were performed to investigate the correlation between miR-21 expression and time to progression of advanced PCa patients. Compared with adjacent non-cancerous prostate tissues, the expression level of miR-21 was significantly increased in PCa tissues (PCa vs. non-cancerous prostate: 1.3273 ± 0.3207 vs. 0.9970 ± 0.2054, P < 0.001). By and large, in ISH analysis miR-21 was expressed at a higher level in tumor areas than in adjacent non-cancerous areas. Additionally, PCa patients with higher expression of miR-21 were significantly more likely to be of high Gleason score and high clinical stage (P < 0.05). There was no significant association between miR-21 expression and the initial prostate-specific antigen (PSA) level or age at diagnosis. Moreover, Kaplan-Meier survival analysis found that PCa patients with high miR-21 expression have shorter progression-free survival than those with low miR-21 expression. Furthermore, Multivariate Cox analysis revealed both miR-21 expression status (P = 0.040) and clinical stage (P = 0

  15. Investigation of relationship between precursor of miRNA-944 and its mature form in lung squamous-cell carcinoma - the diagnostic value.

    PubMed

    Powrózek, Tomasz; Mlak, Radosław; Dziedzic, Marcin; Małecka-Massalska, Teresa; Sagan, Dariusz

    2018-03-01

    MicroRNA (miRNA) are attractive markers of lung cancer, due to their regulatory role in cell cycle. However, we know more about function of miRNA in cancer development, there is still little known about role of their precursors (primary miRNA; pri-miRNA) in tumorgenesis. In present study we investigated potential role of miRNA-944 and its precursor pri-miRNA-944 in development of squamous-cell lung cancer (SCC) and explored interdependence between miRNA precursor and its mature form. This is a first available literature report analyzing pri-miRNA as a cancer diagnostic marker. Expression of miRNA-944 and its precursor was analyzed in 58 fresh-frozen tissues of non-small cell lung cancer and corresponding adjacent non-cancerous tissues using qRT-PCR. Expression of pri-miRNA-944 was correlated with TP63 and miRNA-944. Using ROC analysis diagnostic accuracy of studied markers was evaluated. miRNA-944 and its precursor were significantly overexspressed in SCC compared to adenocarcinoma (AC) and non-cancerous tissue. pri-miRNA-944 strongly and positively correlated with TP63 (r = 0.739, p < 0.001) and with mature miRNA-944 expression (r = 0.691, p < 0.001). Also, TP63 expression significantly correlated with mature miRNA (r = 0.785, p < 0.001). Combined analysis of pri-miRNA-944 and mature miRNA-944 allowed to distinguish SCC tissue form AC with sensitivity of 93.3% and specificity of 100% (AUC = 0.978), and SCC from non-cancerous tissue with 92.9% sensitivity and 100% specificity (AUC = 0.992). We assumed that pri-miRNA-944 and miRNA-944 may be involved in early squamous-type differentiation of lung tumors. Moreover, analysis of both markers provided high diagnostic accuracy for SCC detection. Copyright © 2018 Elsevier GmbH. All rights reserved.

  16. 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.

  17. 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

  18. 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

  19. Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer.

    PubMed

    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; Martinez Outschoorn, Ubaldo; Curry, Joseph

    2015-12-01

    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). Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer [PTC], and eight non-cancerous thyroid) and nine 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. MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (P<.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (P<.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (P<.001). These xenograft tumors have high (13)C- pyruvate uptake. ATC 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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Multimodality stereotactic brain tissue identification: the NASA smart probe project

    NASA Technical Reports Server (NTRS)

    Andrews, R.; Mah, R.; Aghevli, A.; Freitas, K.; Galvagni, A.; Guerrero, M.; Papsin, R.; Reed, C.; Stassinopoulos, D.

    1999-01-01

    Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures. Copyright 2000 S. Karger AG, Basel.

  1. Clinical role and biological function of CDK5 in hepatocellular carcinoma: A study based on immunohistochemistry, RNA-seq and in vitro investigation.

    PubMed

    Zhang, Rui; Lin, Peng; Yang, Hong; He, Yun; Dang, Yi-Wu; Feng, Zhen-Bo; Chen, Gang

    2017-12-12

    To investigate the clinical role and biological function of cyclin-dependent kinase 5 (CDK5) in hepatocellular carcinoma (HCC), 412 surgically resected tissue samples (HCC, n=171; non-HCC=241) were obtained and analyzed with immunohistochemistry. The diagnostic and prognostic values of CDK5 expression levels in HCC were clarified. Moreover, RNA-seq data or microarray datasets from The Cancer Genome Atlas (TCGA) (HCC, n=374; normal, n=50) or other public databases (HCC, n=1864; non-tumor=1995) regarding CDK5 in HCC were extracted and examined. Several bioinformatic methods were performed to identify CDK5-regulated pathways. In vitro experiments were adopted to measure proliferation and apoptosis in HCC cells after CDK5 mRNA was inhibited in the HCC cell lines HepG2 and HepB3. Based on immunohistochemistry, CDK5 expression levels were notably increased in HCC tissues (n=171) compared with normal (n=33, P <0.001), cirrhosis (n=37, P <0.001), and adjacent non-cancerous liver (n=171, P <0.001) tissues. The up-regulation of CDK5 was associated with higher differentiation ( P <0.001), metastasis ( P <0.001), advanced clinical TNM stages ( P <0.001), portal vein tumor embolus ( P =0.003) and vascular invasion ( P =0.004). Additionally, TCGA data analysis also revealed significantly increased CDK5 expression in HCC compared with non-cancerous hepatic tissues ( P <0.001). The pooled standard mean deviation (SMD) based on 36 included datasets (HCC, n=2238; non-cancerous, n=2045) indicated that CDK5 was up-regulated in HCC (SMD=1.23, 95% CI: 1.00-1.45, P <0.001). The area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve was 0.88. Furthermore, CDK5 knock-down inhibited proliferation and promoted apoptosis. In conclusion, CDK5 plays an essential role in the initiation and progression of HCC, most likely via accelerating proliferation and suppressing apoptosis in HCC cells by regulating the cell cycle and DNA replication pathways.

  2. 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.

  3. Patient Navigation Improves Subsequent Breast Cancer Screening After a Noncancerous Result: Evidence from the Patient Navigation in Medically Underserved Areas Study.

    PubMed

    Molina, Yamile; Kim, Sage J; Berrios, Nerida; Glassgow, Anne Elizabeth; San Miguel, Yazmin; Darnell, Julie S; Pauls, Heather; Vijayasiri, Ganga; Warnecke, Richard B; Calhoun, Elizabeth A

    2018-03-01

    Past efforts to assess patient navigation on cancer screening utilization have focused on one-time uptake, which may not be sufficient in the long term. This is partially due to limited resources for in-person, longitudinal patient navigation. We examine the effectiveness of a low-intensity phone- and mail-based navigation on multiple screening episodes with a focus on screening uptake after receiving noncancerous results during a previous screening episode. The is a secondary analysis of patients who participated in a randomized controlled patient navigation trial in Chicago. Participants include women referred for a screening mammogram, aged 50-74 years, and with a history of benign/normal screening results. Navigation services focused on identification of barriers and intervention via shared decision-making processes. A multivariable logistic regression intent-to-treat model was used to examine differences in odds of obtaining a screening mammogram within 2 years of the initial mammogram (yes/no) between navigated and non-navigated women. Sensitivity analyses were conducted to explore patterns across subsets of participants (e.g., navigated women successfully contacted before the initial appointment; women receiving care at Hospital C). The final sample included 2,536 women (741 navigated, 1,795 non-navigated). Navigated women exhibited greater odds of obtaining subsequent screenings relative to women in the standard care group in adjusted models and analyses including women who received navigation before the initial appointment. Our findings suggest that low-intensity navigation services can improve follow-up screening among women who receive a noncancerous result. Further investigation is needed to confirm navigation's impacts on longitudinal screening.

  4. 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

  5. Evaluation of a multi-fibre needle Raman probe for tissue analysis

    NASA Astrophysics Data System (ADS)

    Fullwood, Leanne M.; Iping Petterson, Ingeborg E.; Dudgeon, Alexander P.; Lloyd, Gavin R.; Kendall, Catherine; Hall, Charlie; Day, John C. C.; Stone, Nick

    2016-03-01

    Raman spectroscopy is a rapid technique for the identification of cancers. Its coupling with a hypodermic needle provides a minimally invasive instrument with the potential to aid real time assessment of suspicious lesions in vivo and guide surgery. A fibre optic Raman needle probe was utilised in this study to evaluate the classification ability of the instrument as a diagnostic tool together with multivariate analysis, through measurements of tissues from different animal species as well as various different porcine tissue types. Cross validation was performed and preliminary classification accuracies were calculated as 100% for the identification of tissue type and 97.5% for the identification of animal species. A lymph node sample was also measured using the needle probe to assess the use of the technique for human tissue and hence its efficiency as a clinical instrument. This needle probe has been demonstrated to have the capabilities to classify tissue samples based on their biochemical components. The Raman needle probe also has the potential to act as a diagnostic and surgical tool to delineate cancerous from non-cancerous cells in real time, thus assisting complete removal of a tumour.

  6. Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival.

    PubMed

    Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

    2015-10-20

    Stomatin-like protein 2 (SLP-2, also known as STOML2) is a stomatin homologue of uncertain function. SLP-2 overexpression has been suggested to be associated with cancer progression, resulting in adverse clinical outcomes in patients. Our study aim to investigate SLP-2 expression in epithelial ovarian cancer cells and its correlation with patient survival. SLP-2 mRNA and protein expression levels were analysed in five epithelial ovarian cancer cell lines and normal ovarian epithelial cells using real-time PCR and western blotting analysis. SLP-2 expression was investigated in eight matched-pair samples of epithelial ovarian cancer and adjacent noncancerous tissues from the same patients. Using immunohistochemistry, we examined the protein expression of paraffin-embedded specimens from 140 patients with epithelial ovarian cancer, 20 cases with borderline ovarian tumours, 20 cases with benign ovarian tumours, and 20 cases with normal ovarian tissues. Statistical analyses were applied to evaluate the clinicopathological significance of SLP-2 expression. SLP-2 mRNA and protein expression levels were significantly up-regulated in epithelial ovarian cancer cell lines and cancer tissues compared with normal ovarian epithelial cells and adjacent noncancerous ovarian tissues. Immunohistochemistry analysis revealed that the relative overexpression of SLP-2 was detected in 73.6 % (103/140) of the epithelial ovarian cancer specimens, 45.0 % (9/20) of the borderline ovarian specimens, 30.0 % (6/20) of the benign ovarian specimens and none of the normal ovarian specimens. SLP-2 protein expression in epithelial ovarian cancer was significantly correlated with the tumour stage (P < 0.001). Epithelial ovarian cancer patients with higher SLP-2 protein expression levels had shorter progress free survival and overall survival times compared to patients with lower SLP-2 protein expression levels. Multivariate analyses showed that SLP-2 expression levels were an independent

  7. 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.

  8. 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.

  9. SIRT3 functions as a tumor suppressor in hepatocellular carcinoma.

    PubMed

    Zeng, Xianchun; Wang, Nanzhu; Zhai, Hui; Wang, Rongpin; Wu, Jiahong; Pu, Wei

    2017-03-01

    Hepatocellular carcinoma is one of the leading causes for cancer-related mortality worldwide. SIRT3 may function as either oncogene or tumor suppressor in a panel of cancers; however, the role of SIRT3 in hepatocellular carcinoma remains unclear. In this study, we assayed the expression level of SIRT3 in hepatocellular carcinoma tissues by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. A loss-of-function approach was used to examine the effects of SIRT3 on biological activity, including cell proliferative activity and invasive potential. The results demonstrated that the expression levels of SIRT3 protein in hepatocellular carcinoma tissues were significantly downregulated compared with those in adjacent non-cancerous tissues. Furthermore, SIRT3 could decrease cell proliferation and inhibit cell migration/invasion in hepatocellular carcinoma cell line. Taken together, these results elucidated the function of SIRT3 in hepatocellular carcinoma development and suggested that SIRT3 might function as tumor suppressor in hepatocellular carcinoma by targeting PI3K/Akt pathway.

  10. Variability in physical and biological exchange among coastal wetlands and their adjacent Great Lakes

    EPA Science Inventory

    Hydrology is a major governor of physically-driven exchange among coastal wetlands and the adjacent Great Lake, whereas fish movement is a major governor of biologically-driven exchange. We use data describing coastal wetland morphology, hydrology, water quality, and fish tissue...

  11. Laboratory and in vivo transport characterization of hollow fiber membranes and adjacent scar tissue that forms following their implantation in the central nervous system

    NASA Astrophysics Data System (ADS)

    Bridge, Michael John

    Hollow fiber membrane (HFM) cell encapsulation devices use a semipermeable membrane to physically immunoisolate transplanted secretory cells from host tissues and high molecular weight solutes. Advantages inherent to macroencapsulation technology have led to extensive research towards their utilization for treating a wide range of disorders including a number of neurodegenerative diseases and diabetes. Although feasibility studies have already established the therapeutic potential of macroencapsulation technology, a common observation among these and later studies is diminishing therapeutic efficacy over a span of a few weeks following implantation of devices. Progress towards fulfilling the therapeutic potential of this technology initially recognized by investigators has potentially been hampered by inadequate diffusive transport characterization of membranes employed in studies. In addition, the potential effects of host tissue responses following central nervous system (CNS) implantation of these devices is completely unknown. To address these issues a membrane characterization instrument capable of efficiently characterizing the diffusive and convective transport properties of individual HFM segments, such as they are used in devices, was developed. The instrument was then employed to study the effects of ethanol exposure, a common sterilization method, on PAN-PVC membranes commonly used in CNS implantation macro encapsulation device studies. Lastly, the solute diffusivity properties of tissue that forms adjacent to the membranes of brain implanted transcranial access devices were investigated. Coinciding with this investigation was the development of a novel technique for examining the solute diffusivity properties in the extracellular spaces of CNS tissue.

  12. 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.

  13. Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma.

    PubMed

    Jin, Haojie; Zhang, Yurong; You, Haiyan; Tao, Xuemei; Wang, Cun; Jin, Guangzhi; Wang, Ning; Ruan, Haoyu; Gu, Dishui; Huo, Xisong; Cong, Wenming; Qin, Wenxin

    2015-06-23

    Kynurenine 3-monooxygenase (KMO) is a pivotal enzyme in the kynurenine pathway of tryptophan degradation and plays a critical role in Huntington's and Alzheimer's diseases. This study aimed to examine the expression of KMO in human hepatocellular carcinoma (HCC) and investigate the relationship between its expression and prognosis of HCC patients. We first analyzed KMO expression in 120 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), and 205 clinical HCC specimens using immunohistochemistry (IHC). Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. The results of IHC analysis showed that KMO expression was significantly higher in HCC tissues than that in normal liver tissues (all p < 0.05). Survival and recurrence analyses showed that KMO was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR) (both p<0.01). And in vitro studies revealed that KMO positively regulated proliferation, migration, and invasion of HCC cells. These results suggest that KMO exhibits tumor-promoting effects towards HCC and it may serve as a novel prognostic marker in HCC.

  14. Treatment of multiple adjacent Miller Class I and II gingival recessions with collagen matrix and the modified coronally advanced tunnel technique.

    PubMed

    Molnár, Bálint; Aroca, Sofia; Keglevich, Tibor; Gera, István; Windisch, Péter; Stavropoulos, Andreas; Sculean, Anton

    2013-01-01

    To clinically evaluate the treatment of Miller Class I and II multiple adjacent gingival recessions using the modified coronally advanced tunnel technique combined with a newly developed bioresorbable collagen matrix of porcine origin. Eight healthy patients exhibiting at least three multiple Miller Class I and II multiple adjacent gingival recessions (a total of 42 recessions) were consecutively treated by means of the modified coronally advanced tunnel technique and collagen matrix. The following clinical parameters were assessed at baseline and 12 months postoperatively: full mouth plaque score (FMPS), full mouth bleeding score (FMBS), probing depth (PD), recession depth (RD), recession width (RW), keratinized tissue thickness (KTT), and keratinized tissue width (KTW). The primary outcome variable was complete root coverage. Neither allergic reactions nor soft tissue irritations or matrix exfoliations occurred. Postoperative pain and discomfort were reported to be low, and patient acceptance was generally high. At 12 months, complete root coverage was obtained in 2 out of the 8 patients and 30 of the 42 recessions (71%). Within their limits, the present results indicate that treatment of Miller Class I and II multiple adjacent gingival recessions by means of the modified coronally advanced tunnel technique and collagen matrix may result in statistically and clinically significant complete root coverage. Further studies are warranted to evaluate the performance of collagen matrix compared with connective tissue grafts and other soft tissue grafts.

  15. 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

  16. Biomaterials for tissue engineering applications.

    PubMed

    Keane, Timothy J; Badylak, Stephen F

    2014-06-01

    With advancements in biological and engineering sciences, the definition of an ideal biomaterial has evolved over the past 50 years from a substance that is inert to one that has select bioinductive properties and integrates well with adjacent host tissue. Biomaterials are a fundamental component of tissue engineering, which aims to replace diseased, damaged, or missing tissue with reconstructed functional tissue. Most biomaterials are less than satisfactory for pediatric patients because the scaffold must adapt to the growth and development of the surrounding tissues and organs over time. The pediatric community, therefore, provides a distinct challenge for the tissue engineering community. Copyright © 2014. Published by Elsevier Inc.

  17. 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.

  18. 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

  19. Role of serine/threonine kinase 33 methylation in colorectal cancer and its clinical significance

    PubMed Central

    Yin, Ming-Di; Ma, Si-Ping; Liu, Fang; Chen, Yu-Ze

    2018-01-01

    Serine/threonine kinase 33 (STK33) is a novel protein that has been the focus of an increasing number of studies in recent years; however, the role of STK33 in tumorigenesis remains controversial. Previous studies have demonstrated that STK33 is overexpressed in several human cancers and exerts a pro-tumorigenic effect through the promotion of cell proliferation. However, the role of STK33 in colorectal cancer (CRC), which is one of the most aggressive human malignancies, remains unclear. The aim of the current study was to investigate the methylation status of STK33 in CRC and to determine its clinical significance. The results demonstrated that STK33 was hypermethylated in CRC cell lines and promoted the proliferation of CRC cells. In addition, the methylation status and expression of STK33 in 94 pairs of cancer and noncancerous tissues obtained from patients with CRC was investigated. STK33 methylation was significantly increased in cancer tissues when compared with adjacent noncancerous tissues (P<0.001). STK33 methylation was associated with lymph node metastasis (P<0.05), tumor invasion (P<0.05), distant metastases (P<0.01) and tumor stage (P<0.01). Reduced STK33 mRNA and protein expression in CRC was associated with STK33 hypermethylation (P<0.001). In addition, patients with hypermethylated STK33 exhibited shorter overall survival rates when compared with those with unmethylated STK33 (P<0.01). In conclusion, the results of the current study suggest that STK33 hypermethylation may be a promising novel biomarker for the diagnosis, prognosis and suitable treatment of CRC. PMID:29434919

  20. Size cues and the adjacency principle.

    DOT National Transportation Integrated Search

    1963-11-01

    The purpose of the present study was to apply the adjacency principle to the perception of relative depth from size cues. In agreement with the adjacency principle, it was found that the size cue between adjacent objects was more effective than the s...

  1. Effects of radiotherapy on uveal melanomas and adjacent tissues

    PubMed Central

    Groenewald, C; Konstantinidis, L; Damato, B

    2013-01-01

    Most uveal melanomas are treated with radiotherapy. An adequate understanding of the effects of radiation on the tumour and the healthy ocular tissues is necessary. Ionizing radiation damages cell membranes, organelles, and DNA. Irradiated cells are lysed or undergo apoptosis, necrosis, and senescence. These effects occur in tumour cells and vascular endothelial cells, resulting in tumour shrinkage, ischaemia, infarction, exudation, and fibrosis, which can cause exudative maculopathy, serous retinal detachment, rubeosis, and neovascular glaucoma (ie, ‘toxic tumour syndrome'). Such abnormalities must be distinguished from collateral damage to healthy ocular tissues that receive high doses of radiation, and these include radiation-induced retinopathy, optic neuropathy, choroidopathy, cataract, and scleral necrosis. Radiation retinopathy can be treated effectively with photodynamic therapy, anti-angiogenic agents, and intravitreal steroid injections. In some patients, optic neuropathy may improve with intravitreal steroids or anti-angiogenic agents. Neovascular glaucoma resolves with intra-cameral bevacizumab. Exudative retinal detachment can regress with intra-vitreal steroid injections. Cataract is treated in the usual manner. Scleral necrosis, if severe, may require grafting, possibly using a lamellar flap from the same eye. Depending on the bulk of the residual toxic tumour, treatment can consist of intra-vitreal steroids and/or anti-angiogenic agents, transpupillary thermotherapy or photodynamic therapy to the tumour, or surgical removal of the tumour by endo- or exo-resection. Measures aimed at preventing collateral damage include eccentric placement of ruthenium plaques or iodine seeds and delivery of a notched proton beam. The decision to treat a uveal melanoma with radiotherapy requires the ability to manage iatrogenic side effects and complications. PMID:23196647

  2. Is the stripping technique a tissue-sparing procedure in large simple ovarian cysts in children?

    PubMed

    Arena, Francesco; Romeo, Carmelo; Castagnetti, Marco; Scalfari, GianFranco; Cimador, Marcello; Impellizzeri, Pietro; Villari, Daniela; Zimbaro, Fabrizio; DeGrazia, Enrico

    2008-07-01

    Stripping of the cystic wall is performed by gynecologists to treat large ovarian cysts. Information in the pediatric population is poor. We prospectively evaluated the pathologic specimens of large ovarian cyst to determine whether the stripping technique is a tissue-sparing procedure even in this age. We evaluated 5 patients. Samples were taken from the intermediate part of the cystic wall and from the layer covering the cyst during excision. The presence of ovarian tissue adjacent to the cyst wall, and the morphological features of the surrounding tissue were both evaluated. Pelvic ultrasound follow-up was also performed. Patients' mean age was 4.5 years (7 days to 12 years). All cysts were removed because all were symptomatic. The mean diameter was 86.6 mm (74-100 mm). Cysts were follicular in 2 cases, serous in other two, and endometriotic in 1 case. Adjacent ovarian tissue was present in 1 of 5 specimens and was approximately 1 to 2 mm in thickness. The layer adjacent to the cystic wall always appeared as normal ovarian tissue. Ultrasound scans at follow-up revealed presence of ovarian tissue. The stripping procedure for large ovarian cyst excision allows to spare the adjacent normal ovarian tissue even in pediatric age because ovarian tissue is rarely excised with the cyst wall during the procedure.

  3. The expression of MACC1 and its role in the proliferation and apoptosis of salivary adenoid cystic carcinoma.

    PubMed

    Li, Haifeng; Liao, Xiaoying; Liu, Yeqing; Shen, Zhuojian; Gan, Xiangfeng; Li, Haigang; Huang, Zhiquan

    2015-11-01

    The objective of this study was to investigate the relationship between metastasis-associated in colon cancer-1 and patient clinical characteristics. We also examined the role of metastasis-associated in colon cancer-1 in the proliferation and apoptosis in adenoid cystic carcinoma. Metastasis-associated in colon cancer-1 expression was analysed in 65 paraffin-embedded tissue specimens of salivary adenoid cystic carcinoma and 25 adjacent non-cancerous tissues by immunohistochemistry (IHC). We used RNA interference technology to silence metastasis-associated in colon cancer-1 expression in ACCM cells. Cell Counting Kit-8 tests, transwell experiments and flow cytometry were used to test the proliferation, cisplatin resistance, migration, invasion and apoptosis of ACCM cells. Metastasis-associated in colon cancer-1 nuclear and cytoplasmic expression in salivary adenoid cystic carcinoma tissue was higher than in the adjacent normal salivary tissue. The expression level was closely associated with tumour histological grading, perineural invasion and surrounding tumour invasion. The downregulation of metastasis-associated in colon cancer-1 expression inhibited proliferation and induced apoptosis in ACCM cells. The knock-down of metastasis-associated in colon cancer-1 expression had no effect on migration, invasion and chemoresistance. Metastasis-associated in colon cancer-1 may have an important role in tumour development in adenoid cystic carcinoma. Metastasis-associated in colon cancer-1 is a potential biomarker for adenoid cystic carcinoma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by natural...

  5. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by natural...

  6. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by natural...

  7. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by natural...

  8. 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

  9. 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.

  10. Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells.

    PubMed

    Kuan, Emma L; Ivanov, Stoyan; Bridenbaugh, Eric A; Victora, Gabriel; Wang, Wei; Childs, Ed W; Platt, Andrew M; Jakubzick, Claudia V; Mason, Robert J; Gashev, Anatoliy A; Nussenzweig, Michel; Swartz, Melody A; Dustin, Michael L; Zawieja, David C; Randolph, Gwendalyn J

    2015-06-01

    Collecting lymphatic vessels (CLVs), surrounded by fat and endowed with contractile muscle and valves, transport lymph from tissues after it is absorbed into lymphatic capillaries. CLVs are not known to participate in immune responses. In this study, we observed that the inherent permeability of CLVs allowed broad distribution of lymph components within surrounding fat for uptake by adjacent macrophages and dendritic cells (DCs) that actively interacted with CLVs. Endocytosis of lymph-derived Ags by these cells supported recall T cell responses in the fat and also generated Ag-bearing DCs for emigration into adjacent lymph nodes (LNs). Enhanced recruitment of DCs to inflammation-reactive LNs significantly relied on adipose tissue DCs to maintain sufficient numbers of Ag-bearing DCs as the LN expanded. Thus, CLVs coordinate inflammation and immunity within adipose depots and foster the generation of an unexpected pool of APCs for Ag transport into the adjacent LN. Copyright © 2015 by The American Association of Immunologists, Inc.

  11. 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.

  12. Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma

    PubMed Central

    Jin, Haojie; Zhang, Yurong; You, Haiyan; Tao, Xuemei; Wang, Cun; Jin, Guangzhi; Wang, Ning; Ruan, Haoyu; Gu, Dishui; Huo, Xisong; Cong, Wenming; Qin, Wenxin

    2015-01-01

    Kynurenine 3-monooxygenase (KMO) is a pivotal enzyme in the kynurenine pathway of tryptophan degradation and plays a critical role in Huntington’s and Alzheimer’s diseases. This study aimed to examine the expression of KMO in human hepatocellular carcinoma (HCC) and investigate the relationship between its expression and prognosis of HCC patients. We first analyzed KMO expression in 120 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), and 205 clinical HCC specimens using immunohistochemistry (IHC). Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. The results of IHC analysis showed that KMO expression was significantly higher in HCC tissues than that in normal liver tissues (all p < 0.05). Survival and recurrence analyses showed that KMO was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR) (both p<0.01). And in vitro studies revealed that KMO positively regulated proliferation, migration, and invasion of HCC cells. These results suggest that KMO exhibits tumor-promoting effects towards HCC and it may serve as a novel prognostic marker in HCC. PMID:26099564

  13. 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.

  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. Effects of holmium:YAG laser on equine articular cartilage and subchondral bone adjacent to traumatic lesions

    NASA Astrophysics Data System (ADS)

    Collier, Michael A.; Haugland, L. Mark; Bellamy, Janine; Johnson, Lanny L.; Rohrer, Michael D.; Walls, Robert C.; Bartels, Kenneth E.

    1994-09-01

    The effects of Ho:YAG laser energy on articular cartilage and subchondral bone adjacent to traumatically created cartilage lesions in a continuous weight-bearing model were investigated. The 2.1 micrometers wavelength was delivered in hand-controlled contact and near-contact hard tissue arthroscopic surgery in a saline medium. Bilateral arthroscopy was performed on normal antebrachiocarpal and intercarpal joints of four adult horses. One-hundred twenty traumatic lesions were created on three weight-bearing articular surfaces with a knife, curette, or a motorized burr. Depths of the lesions were partial and full thickness. Configurations of the lesions were lacerations, scrapes, and craters. Left limbs were used as controls. Right limb lesions were treated with various intensities of laser energy. Animals were sacrificed at intervals of 1, 3, and 8 weeks. Gross microscopic anatomy was documented, and tissue sections were subjected to blind review by a pathologist. Mankin grading for cellularity and proteoglycan content was used to qualitatively evaluate cartilage response. Cartilage adjacent to all lesions exposed to laser energy had better cellularity and proteoglycan content than corresponding controls by Mankin grading.

  16. 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.

  17. UV-fluorescence spectroscopic technique in the diagnosis of breast, ovarian, uterus, and cervix cancer

    NASA Astrophysics Data System (ADS)

    Das, Bidyut B.; Glassman, Wenling S.; Alfano, Robert R.; Cleary, Joseph; Prudente, R.; Celmer, Edward J.; Lubicz, Stephanie

    1991-06-01

    Malignant breast tumors can be separated from benign and normal tissues using uv-fluorescence spectroscopic technique. Using the same method one can also distinguish cancerous tissues from noncancerous ones in case of cervix, uterus and ovary.

  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. 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.

  20. Comparison of computed tomography and high-field (3.0 T) magnetic resonance imaging of age-related variances in selected equine maxillary cheek teeth and adjacent tissues.

    PubMed

    Schoppe, Christin; Hellige, Maren; Rohn, Karl; Ohnesorge, Bernhard; Bienert-Zeit, Astrid

    2017-09-06

    Modern imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) have the advantage of producing images without superimposition. Whilst CT is a well-established technique for dental diagnostics, MRI examinations are rarely used for the evaluation of dental diseases in horses. Regarding equine endodontic therapies which are increasingly implemented, MRI could help to portray changes of the periodontal ligament and display gross pulpar anatomy. Knowledge of age-related changes is essential for diagnosis, as cheek teeth and surrounding structures alter with increasing age. The aim of the present study was to highlight the advantages of CT and MRI regarding age-related changes in selected equine cheek teeth and their adjacent structures. The CT and MRI appearances of the maxillary 08 s and 09 s and adjacent structures were described by evaluation of post-mortem examinations of nine horses of different ages (Group A: <6 years, B: 6-15 years, C: ≥16 years). Most of the tissues selected were imaged accurately with MRI and CT. Magnetic resonance imaging gives an excellent depiction of soft endo- and periodontal units, and CT of hard dental and bony tissues. Negative correlation between dental age and pulpar sizes was found: 71.3% of the changes in pulp dimensions can be explained by teeth aging. Pulpar sizes ranged from 14.3 to 1.3 mm and were significantly smaller in older horses (p < 0.05). A common pulp chamber was present in 33% of the teeth with a mean dental age of 2.25 years. Ninety-four percent of the 08 and 09 alveoli of all groups were in direct contact with the maxillary sinus. An age-related regression was found (R 2  = 0.88) for the distance between alveoli and the infraorbital canal. The present study provides information about the dental and periodontal age-related morphology and its visibility using different imaging techniques. These results aid in evaluating diagnostic images and in deciding which is the

  1. Maize endosperm secretes a novel antifungal protein into adjacent maternal tissue.

    PubMed

    Serna, A; Maitz, M; O'Connell, T; Santandrea, G; Thevissen, K; Tienens, K; Hueros, G; Faleri, C; Cai, G; Lottspeich, F; Thompson, R D

    2001-03-01

    A series of endosperm transfer layer-specific transcripts has been identified in maize by differential screening of a cDNA library of transcripts at 10 days after pollination. Sequence comparisons revealed among this class of cDNAs a novel, small gene family of highly diverged sequences encoding basal layer antifungal proteins (BAPs). The bap genes mapped to two loci on chromosomes 4 and 10. So far, bap-homologous sequences have been detected only in maize, teosinte and sorghum, and are not present in grasses outside the Andropogoneae tribe. BAP2 is synthesized as a pre-proprotein, and is processed by successive removal of a signal peptide and a 29-residue prodomain. The proprotein can be detected exclusively in microsomal membrane-containing fractions of kernel extracts. Immunolocalization reveals BAP2 to be predominantly located in the placentochalazal cells of the pedicel, adjacent to the basal endosperm transfer layer (BETL) cells, although the BAP2 transcript is found only in the BETL cells. The biological roles of BAP2 propeptide and mature peptide have been investigated by heterologous expression of the proprotein in Escherichia coli, and by tests of its fungistatic activity and that of the fully processed form in vitro. The mature BAP2 peptide exhibits potent broad-range activity against a range of filamentous fungi, including several plant pathogens.

  2. Treatment of Osteomyelitis: A Case for Disruption of the Affected Adjacent Periosteum.

    PubMed

    Hudson, John W; Daly, Austin P; Foster, Michael

    2017-10-01

    To evaluate the response of mandibular osteomyelitis treated by surgical decortication with disruption of the affected adjacent periosteum in concert with long-term targeted antibiotic therapy. The hypothesis is that, by removing the buccal cortical plate and disrupting the hypertrophically inflamed adjacent periosteum, the medullary bone will be brought in contact with bleeding tissue and circulating immunologic factors and antibiotics, which will promote definitive resolution. A retrospective review was conducted of 7 patient charts with associated radiographs from November 2010 to August 2016 treated by the first author at the University of Tennessee Medical Center (Knoxville, TN). Patients with chronic suppurative or nonsuppurative osteomyelitis of the mandible without condylar involvement or pathologic fracture were selected and treated with decortication with periosteal disruption in combination with long-term targeted antibiotic therapy. Seven patients (3 women and 4 men; mean age, 60 yr) underwent decortication with periosteal disruption of the affected area and received at least 6 weeks of targeted intravenous antibiotics. Computed tomography was performed preoperatively and a repeat study was performed after completion of antibiotics. In each case, post-treatment imaging showed definitive resolution after treatment with decortication in concert with disruption of the inflamed hypertrophic periosteum and intravenous antibiotics. Debridement of the infected cortical bone with restoration of the blood supply through disruption of the adjacent periosteum provided definitive resolution of mandibular osteomyelitis in the 7 patients treated. The hypothesis is that disruption of the affected adjacent periosteum reintroduces an immune-mediated response in concert with improved antibiotic delivery to and penetrance of the diseased mandible, aiding in definitive resolution. Decortication with periosteal disruption allows for preservation of the inferior alveolar

  3. Trends in trace organic and metal concentrations in the Pechora and Kara Seas and adjacent rivers

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

    Brooks, J.M.; Champ, M.A.; Wade, T.L.

    1995-12-31

    Trace organic (pesticides, PCBs, PAHs and dioxin/furan) and trace metal concentrations have been measured in surficial sediment and tissue (i.e., clam, fish liver and flesh) samples from the Pechora and Kara Seas and their adjacent rivers -- Pechora, Ob and Yenisey Rivers. Total PAH, PCB and total DDT and chlordane concentrations ranged in surficial sediments from n.d. to 810 ppb, n.d.--8.7 ppb, n.d.--1.2 ppb, and n.d.--1.2 ppb, respectively, in a suite of 40 samples from the Kara Sea and its adjacent rivers. The highest concentrations of many of the trace organic and metal contaminants were found in the lower partmore » of the Yenisey River below the salt wedge. Some trace metals (As for example) were elevated in the Pechora River dispositional plume region. Dioxin ranged from 1.36 to 413 ppt in a subset of 20 sediment samples. Higher trace organic contaminant concentrations compared to sediments were found in tissue samples from the region, especially fish liver samples. Concentrations as high as 1,114 ppb total PAHs, 89 ppb chlordane, 1,011 ppb for total DDT and 663 ppb PCBs were found in some fish liver samples. Dioxin concentrations in tissue samples ranged from 11.7 to 61 ppt. Concentrations of many trace organic and metal contaminants in these Russian marginal seas are influenced by inputs from these large Arctic rivers. Many organic contaminant concentrations in sediments are low, however detecting these compounds in tissue show they are bioavailable.« less

  4. 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.

  5. 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

  6. Performance assessment of automated tissue characterization for prostate H and E stained histopathology

    NASA Astrophysics Data System (ADS)

    DiFranco, Matthew D.; Reynolds, Hayley M.; Mitchell, Catherine; Williams, Scott; Allan, Prue; Haworth, Annette

    2015-03-01

    Reliable automated prostate tumor detection and characterization in whole-mount histology images is sought in many applications, including post-resection tumor staging and as ground-truth data for multi-parametric MRI interpretation. In this study, an ensemble-based supervised classification algorithm for high-resolution histology images was trained on tile-based image features including histogram and gray-level co-occurrence statistics. The algorithm was assessed using different combinations of H and E prostate slides from two separate medical centers and at two different magnifications (400x and 200x), with the aim of applying tumor classification models to new data. Slides from both datasets were annotated by expert pathologists in order to identify homogeneous cancerous and non-cancerous tissue regions of interest, which were then categorized as (1) low-grade tumor (LG-PCa), including Gleason 3 and high-grade prostatic intraepithelial neoplasia (HG-PIN), (2) high-grade tumor (HG-PCa), including various Gleason 4 and 5 patterns, or (3) non-cancerous, including benign stroma and benign prostatic hyperplasia (BPH). Classification models for both LG-PCa and HG-PCa were separately trained using a support vector machine (SVM) approach, and per-tile tumor prediction maps were generated from the resulting ensembles. Results showed high sensitivity for predicting HG-PCa with an AUC up to 0.822 using training data from both medical centres, while LG-PCa showed a lower sensitivity of 0.763 with the same training data. Visual inspection of cancer probability heatmaps from 9 patients showed that 17/19 tumors were detected, and HG-PCa generally reported less false positives than LG-PCa.

  7. Combined surface-enhanced Raman spectroscopy biotags and microfluidic platform for quantitative ratiometric discrimination between noncancerous and cancerous cells in flow

    NASA Astrophysics Data System (ADS)

    Pallaoro, Alessia; Hoonejani, Mehran R.; Braun, Gary B.; Meinhart, Carl; Moskovits, Martin

    2013-01-01

    Surface-enhanced Raman spectroscopy (SERS) biotags (SBTs) that carry peptides as cell recognition moieties were made from polymer-encapsulated silver nanoparticle dimers, infused with unique Raman reporter molecules. We previously demonstrated their potential use for identification of malignant cells, a central goal in cancer research, through a multiplexed, ratiometric method that can confidently distinguish between cancerous and noncancerous epithelial prostate cells in vitro based on receptor overexpression. Progress has been made toward the application of this quantitative methodology for the identification of cancer cells in a microfluidic flow-focusing device. Beads are used as cell mimics to evaluate the devices. Cells (and beads) are simultaneously incubated with two sets of SBTs while in suspension, then injected into the device for laser interrogation under flow. Each cell event is characterized by a composite Raman spectrum, deconvoluted into its single components to ultimately determine their relative contribution. We have found that using SBTs ratiometrically can provide cell identification in flow, insensitive to normal causes of uncertainty in optical measurements such as variations in focal plane, cell concentration, autofluorescence, and turbidity.

  8. A biological approach to assembling tissue modules through endothelial capillary network formation.

    PubMed

    Riesberg, Jeremiah J; Shen, Wei

    2015-09-01

    To create functional tissues having complex structures, bottom-up approaches to assembling small tissue modules into larger constructs have been emerging. Most of these approaches are based on chemical reactions or physical interactions at the interface between tissue modules. Here we report a biological assembly approach to integrate small tissue modules through endothelial capillary network formation. When adjacent tissue modules contain appropriate extracellular matrix materials and cell types that support robust endothelial capillary network formation, capillary tubules form and grow across the interface, resulting in assembly of the modules into a single, larger construct. It was shown that capillary networks formed in modules of dense fibrin gels seeded with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs); adjacent modules were firmly assembled into an integrated construct having a strain to failure of 117 ± 26%, a tensile strength of 2208 ± 83 Pa and a Young's modulus of 2548 ± 574 Pa. Under the same culture conditions, capillary networks were absent in modules of dense fibrin gels seeded with either HUVECs or MSCs alone; adjacent modules disconnected even when handled gently. This biological assembly approach eliminates the need for chemical reactions or physical interactions and their associated limitations. In addition, the integrated constructs are prevascularized, and therefore this bottom-up assembly approach may also help address the issue of vascularization, another key challenge in tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

    PubMed Central

    Xuan, Shi-Ying; Xin, Yong-Ning; Chen, Hua; Shi, Guang-Jun; Guan, Hua-Shi; Li, Yang

    2007-01-01

    AIM: To investigate the correlation between hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) expression in hepatocellular carcinoma (HCC), the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein (AFP) level. METHODS: The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immuno-histochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index (HAI) score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups: patients positive for HBsAg (HBsAg group), patients positive for HCV (HCV group), patients negative for both HCV and HBsAg (NBNC group) and patients positive for both HBsAg and HCV (BC group). RESULTS: The BC group had significantly higher HAI scores than the other three groups. (BC > HCV > HBsAg > NBNC). HBV and HCV virus infection was positively correlated with HAI (rs = 0.39, P = 0.0001). The positive rate of AFP (85.7%) and the value of AFP (541.2 ng/mL) in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate (53.3%) of AFP and the value of AFP ( 53.3 ng/mL) in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP(rs = 0.38, P = 0.0001). CONCLUSION: The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman’s rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with

  10. Induction of angiogenesis and neovascularization in adjacent tissue of plasma-collagen-coated silicone implants.

    PubMed

    Ring, Andrej; Langer, Stefan; Tilkorn, Daniel; Goertz, Ole; Henrich, Lena; Stricker, Ingo; Steinau, Hans-Ulrich; Steinstraesser, Lars; Hauser, Joerg

    2010-09-28

    Formation of encapsulating, avascular fibrous tissue is deemed to decrease implant's biocompatibility and versatility. We investigated whether plasma-mediated collagen coating possesses the ability to enhance neovascularization in the vicinity of silicone implants. Plasma-treated collagen-I-coated silicone samples were placed into the dorsal skinfold chambers of female balb/c mice (n = 10). Conventional silicone served as control (n = 10). Intravital microscopy was performed within implant's surrounding tissue on days 1, 5, and 10. Functional vessel density, intervascular distance, vessel diameter, microvascular permeability, red blood cell velocity, and leukocyte-endothelium interaction were determined. Enhanced angiogenesis in the tissue surrounding plasma-pretreated collagen-coated implants was noted. Significant increase of functional vessel density due to vascular new development was observed (t test, P < .05). Analyses of microvascular permeability and red blood cell velocity displayed stable perfusion of the vascular network neighboring the surface-modified implants. Intensified vascularity due to induced angiogenesis and neovascularization in the tissue surrounding plasma-collagen-coated samples were observed. These results indicate that plasma-mediated collagen coating might be a promising technology in order to improve the biocompatibility and versatility of silicone implants.

  11. Induction of Angiogenesis and Neovascularization in Adjacent Tissue of Plasma-Collagen–Coated Silicone Implants

    PubMed Central

    Ring, Andrej; Langer, Stefan; Tilkorn, Daniel; Goertz, Ole; Henrich, Lena; Stricker, Ingo; Steinau, Hans-Ulrich; Steinstraesser, Lars; Hauser, Joerg

    2010-01-01

    Objective: Formation of encapsulating, avascular fibrous tissue is deemed to decrease implant's biocompatibility and versatility. We investigated whether plasma-mediated collagen coating possesses the ability to enhance neovascularization in the vicinity of silicone implants. Methods: Plasma-treated collagen-I–coated silicone samples were placed into the dorsal skinfold chambers of female balb/c mice (n = 10). Conventional silicone served as control (n = 10). Intravital microscopy was performed within implant's surrounding tissue on days 1, 5, and 10. Functional vessel density, intervascular distance, vessel diameter, microvascular permeability, red blood cell velocity, and leukocyte-endothelium interaction were determined. Results: Enhanced angiogenesis in the tissue surrounding plasma-pretreated collagen-coated implants was noted. Significant increase of functional vessel density due to vascular new development was observed (t test, P < .05). Analyses of microvascular permeability and red blood cell velocity displayed stable perfusion of the vascular network neighboring the surface-modified implants. Conclusion: Intensified vascularity due to induced angiogenesis and neovascularization in the tissue surrounding plasma-collagen–coated samples were observed. These results indicate that plasma-mediated collagen coating might be a promising technology in order to improve the biocompatibility and versatility of silicone implants. PMID:20936137

  12. 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

  13. 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.

  14. 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

  15. Variability of adjacency effects in sky reflectance measurements.

    PubMed

    Groetsch, Philipp M M; Gege, Peter; Simis, Stefan G H; Eleveld, Marieke A; Peters, Steef W M

    2017-09-01

    Sky reflectance R sky (λ) is used to correct in situ reflectance measurements in the remote detection of water color. We analyzed the directional and spectral variability in R sky (λ) due to adjacency effects against an atmospheric radiance model. The analysis is based on one year of semi-continuous R sky (λ) observations that were recorded in two azimuth directions. Adjacency effects contributed to R sky (λ) dependence on season and viewing angle and predominantly in the near-infrared (NIR). For our test area, adjacency effects spectrally resembled a generic vegetation spectrum. The adjacency effect was weakly dependent on the magnitude of Rayleigh- and aerosol-scattered radiance. The reflectance differed between viewing directions 5.4±6.3% for adjacency effects and 21.0±19.8% for Rayleigh- and aerosol-scattered R sky (λ) in the NIR. Under which conditions in situ water reflectance observations require dedicated correction for adjacency effects is discussed. We provide an open source implementation of our method to aid identification of such conditions.

  16. MicroRNA-124-3p expression and its prospective functional pathways in hepatocellular carcinoma: A quantitative polymerase chain reaction, gene expression omnibus and bioinformatics study.

    PubMed

    He, Rong-Quan; Yang, Xia; Liang, Liang; Chen, Gang; Ma, Jie

    2018-04-01

    The present study aimed to explore the potential clinical significance of microRNA (miR)-124-3p expression in the hepatocarcinogenesis and development of hepatocellular carcinoma (HCC), as well as the potential target genes of functional HCC pathways. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the expression of miR-124-3p in 101 HCC and adjacent non-cancerous tissue samples. Additionally, the association between miR-124-3p expression and clinical parameters was also analyzed. Differentially expressed genes identified following miR-124-3p transfection, the prospective target genes predicted in silico and the key genes of HCC obtained from Natural Language Processing (NLP) were integrated to obtain potential target genes of miR-124-3p in HCC. Relevant signaling pathways were assessed with protein-protein interaction (PPI) networks, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein Annotation Through Evolutionary Relationships (PANTHER) pathway enrichment analysis. miR-124-3p expression was significantly reduced in HCC tissues compared with expression in adjacent non-cancerous liver tissues. In HCC, miR-124-3p was demonstrated to be associated with clinical stage. The mean survival time of the low miR-124-3p expression group was reduced compared with that of the high expression group. A total of 132 genes overlapped from differentially expressed genes, miR-124-3p predicted target genes and NLP identified genes. PPI network construction revealed a total of 109 nodes and 386 edges, and 20 key genes were identified. The major enriched terms of three GO categories included regulation of cell proliferation, positive regulation of cellular biosynthetic processes, cell leading edge, cytosol and cell projection, protein kinase activity, transcription activator activity and enzyme binding. KEGG analysis revealed pancreatic cancer, prostate cancer and non-small cell lung cancer as the

  17. Application of a flexible CO(2) laser fiber for neurosurgery: laser-tissue interactions.

    PubMed

    Ryan, Robert W; Wolf, Tamir; Spetzler, Robert F; Coons, Stephen W; Fink, Yoel; Preul, Mark C

    2010-02-01

    The CO(2) laser has an excellent profile for use in neurosurgery. Its high absorption in water results in low thermal spread, sparing adjacent tissue. Use of this laser has been limited to line-of-sight applications because no solid fiber optic cables could transmit its wavelength. Flexible photonic bandgap fiber technology enables delivery of CO(2) laser energy through a flexible fiber easily manipulated in a handheld device. The authors examined and compared the first use of this CO(2) laser fiber to conventional methods for incising neural tissue. Carbon dioxide laser energy was delivered in pulsed or continuous wave settings for different power settings, exposure times, and distances to cortical tissue of 6 anesthetized swine. Effects of CO(2) energy on the tissue were compared with bipolar cautery using a standard pial incision technique, and with scalpel incisions without cautery. Tissue was processed for histological analysis (using H & E, silver staining, and glial fibrillary acidic protein immunohistochemistry) and scanning electron microscopy, and lesion measurements were made. Light microscopy and scanning electron microscopy revealed laser incisions of consistent shape, with central craters surrounded by limited zones of desiccated and edematous tissue. Increased laser power resulted in deeper but not significantly wider incisions. Bipolar cautery lesions showed desiccated and edematous zones but did not incise the pia, and width increased more than depth with higher power. Incisions made without using cautery produced hemorrhage but minimal adjacent tissue damage. The photonic bandgap fiber CO(2) laser produced reliable cortical incisions, adjustable over a range of settings, with minimal adjacent thermal tissue damage. Ease of application under the microscope suggests this laser system has reached true practicality for neurosurgery.

  18. Downregulated miR-23b-3p expression acts as a predictor of hepatocellular carcinoma progression: A study based on public data and RT-qPCR verification

    PubMed Central

    Xiang, Xue-Lian; Yang, Xia; Liang, Hai-Wei; Qiu, Xiao-Hui; Yang, Li-Hua; Peng, Zhi-Gang; Chen, Gang

    2018-01-01

    Mounting evidence has shown that miR-23b-3p, which is associated with cell proliferation, invasion, and apoptosis, acts as a biomarker for diagnosis and outcomes in numerous cancers. However, the clinicopathological implication of miR-23b-3p in hepatocellular carcinoma (HCC) remains unclear. Our study evaluated the role of miR-23b-3p in HCC and investigated its potential application as a marker for preliminary diagnosis and therapy in HCC. High-throughput data from the NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were collected and analyzed. One hundred and one tissue sections of HCC were paired with adjacent non-cancerous HCC as further supplements. miR-23b-3p expression was detected using quantitative real-time PCR. Additionally, the relationship between miR-23b-3p expression and HCC progression and Time-to-recurrence (months) was explored. Ten algorithms were applied to predict the prospective target genes of miR-23b-3p. Next, we conducted bioinformatics analysis for further study. miR-23b-3p expression was pronouncedly decreased in HCC tissues in contrast with their paired adjacent non-cancerous HCC (P<0.001) with RT-qPCR. In total, 405 targets, acquired with consistent prediction from at least five databases, were used for the bioinformatics analysis. According to the Gene Ontology (GO) analysis, all targets were classified into biological processes, cellular components and molecular functions. In the pathway analysis, targets of miR-23b-3p were primarily enriched in the signaling pathways of renal cell carcinoma, hepatitis B and pancreatic cancer (corrected P-value <0.05). In the protein-protein interaction (PPI) network for miR-23b-3p, a total of 8 targets, including SRC, AKT1, EGFR, CTNNB1, BCL2, SMAD3, PTEN and KDM6A, were located in the key nodes with high degree (>35). In conclusion, this study provides impressive illumination of the potential role of miR-23b-3p in HCC tumorigenesis and progression. Furthermore, miR-23b-3p may

  19. A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer

    NASA Astrophysics Data System (ADS)

    Auslander, Noam; Yizhak, Keren; Weinstock, Adam; Budhu, Anuradha; Tang, Wei; Wang, Xin Wei; Ambs, Stefan; Ruppin, Eytan

    2016-07-01

    Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured.

  20. 47 CFR 101.1421 - Coordination of adjacent area MVDDS stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Multichannel Video Distribution and Data Service Rules for... compatible with adjacent and co-channel operations in the adjacent areas on all its frequencies; and (2... adjacent and co-channel operations in adjacent areas. (b) Harmful interference to public safety stations...

  1. 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.

  2. 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.

  3. Oral mucosa tissue response to titanium cover screws.

    PubMed

    Olmedo, Daniel G; Paparella, María L; Spielberg, Martín; Brandizzi, Daniel; Guglielmotti, María B; Cabrini, Rómulo L

    2012-08-01

    Titanium is the most widely used metal in dental implantology. The release of particles from metal structures into the biologic milieu may be the result of electrochemical processes (corrosion) and/or mechanical disruption during insertion, abutment connection, or removal of failing implants. The aim of the present study is to evaluate tissue response of human oral mucosa adjacent to titanium cover screws. One hundred fifty-three biopsies of the supra-implant oral mucosa adjacent to the cover screw of submerged dental implants were analyzed. Histologic studies were performed to analyze epithelial and connective tissue as well as the presence of metal particles, which were identified using microchemical analysis. Langerhans cells, macrophages, and T lymphocytes were studied using immunohistochemical techniques. The surface of the cover screws was evaluated by scanning electron microscopy (SEM). Forty-one percent of mucosa biopsies exhibited metal particles in different layers of the section thickness. Particle number and size varied greatly among specimens. Immunohistochemical study confirmed the presence of macrophages and T lymphocytes associated with the metal particles. Microchemical analysis revealed the presence of titanium in the particles. On SEM analysis, the surface of the screws exhibited depressions and irregularities. The biologic effects seen in the mucosa in contact with the cover screws might be associated with the presence of titanium or other elements, such as aluminum or vanadium. The potential long-term biologic effects of particles on soft tissues adjacent to metallic devices should be further investigated because these effects might affect the clinical outcome of the implant.

  4. [Morphology of collagen matrices for tissue engineering (biocompatibility, biodegradation, tissue response)].

    PubMed

    Shekhter, A B; Guller, A E; Istranov, L P; Istranova, E V; Butnaru, D V; Vinarov, A Z; Zakharkina, O L; Kurkov, A V; Kantimerov, D F; Antonov, E N; Marisov, L V; Glybochko, P V

    2015-01-01

    to perform a comparative morphological study of biocompatibility, biodegradation, and tissue response to implantation of collagen matrices (scaffolds) for tissue engineering in urology and other areas of medicine. Nine matrix types, such as porous materials reconstructed from collagen solution; a collagen sponge-vicryl mesh composite; decellularized and freeze-dried bovine, equine, and fish dermis; small intestinal submucosa, decellularized bovine dura mater; and decellularized human femoral artery, were implanted subcutaneously in 225 rats. The tissues at the implantation site were investigated for a period of 5 to 90 days. Classical histology and nonlinear optical microscopy (NLOM) were applied. The investigations showed no rejection of all the collagen materials. The period of matrix bioresorption varied from 10 days for collagen sponges to 2 months for decellularized and freeze-dried vessels and vicryl meshes. Collagen was prone to macrophage resorption and enzymatic lysis, being replaced by granulation tissue and then fibrous tissue, followed by its involution. NLOM allowed the investigators to study the number, density, interposition, and spatial organization of collagen structures in the matrices and adjacent tissues, and their change over time during implantation. The performed investigation could recommend three matrices: hybrid collagen/vicryl composite; decellularized bovine dermis; and decellularized porcine small intestinal submucosa, which are most adequate for tissue engineering in urology. These and other collagen matrices may be used in different areas of regenerative medicine.

  5. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake Union...

  6. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake Union...

  7. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake Union...

  8. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake Union...

  9. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake Union...

  10. 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.

  11. 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.

  12. Correlation analysis of expressions of PTEN and p53 with the value obtained by magnetic resonance spectroscopy and apparent diffusion coefficient in the tumor and the tumor-adjacent area in magnetic resonance imaging for glioblastoma.

    PubMed

    Li, Yunyun; Ji, Feng; Jiang, Yuzhi; Zhao, Ting; Xu, Chongfu

    2018-01-01

    To explore the correlation of the expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) and p53 of glioblastoma multiforme (GBM) with the value obtained by magnetic resonance spectroscopy (MRS) and apparent diffusion coefficient (ADC) in the tumor and the tumor-adjacent area in magnetic resonance imaging (MRI). A total of 38 patients were operated for GBM. All the patients had received diffusion-weighted imaging (DWI) and MRS prior to surgery. ADC of water molecules and values of metabolite indexes of MRS, including n-acetyl aspartate (NAA), choline (Cho) and creatine (Cr), were recorded, and the ratios of Cho/NAA, Cho/Cr and NAA/Cr were calculated. Hematoxylin-eosin (H&E) staining was done to examine the morphology of tumor and of tumor-adjacent tissues; immunohistochemistry (IHC) was performed to examine the expressions of PTEN and p53 in the tumor and the tumor-adjacent area. Finally, the correlations of the expressions of PTEN and p53 with ADC, Cho/NAA, Cho/Cr and NAA/Cr of the tumor and the tumor-adjacent area were analyzed. H&E staining showed that GBM tissues had disordered morphology, different sizes of cells, large cell nuclei and significant cell heterogeneity. IHC indicated that the expression level of p53 protein in the tumor was significantly higher than in the tumor-adjacent tissues (p<0.05). The expression level of PTEN protein was high in the tumor-adjacent tissues, but significantly deficient in the tumor. DWI showed that the signal of DWI in the tumor was significantly increased, but ADC was decreased compared with the tumor-adjacent area. MRS indicated that the wave band of Cho in the tumor was significantly increased, NAA was significantly lowered, and Cr section was decreased compared with the tumor-adjacent area, while NAA/Cr in the tumor was significantly decreased compared with the tumoradjacent area (p<0.05). Correlation analysis indicated that PTEN levels in the tumor and the tumor-adjacent area were

  13. 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 .

  14. Blocking of the EGFR-STAT3 signaling pathway through afatinib treatment inhibited the intrahepatic cholangiocarcinoma

    PubMed Central

    Zhang, Changhe; Xu, Hong; Zhou, Zhenping; Tian, Ye; Cao, Xiaofei; Cheng, Guochang; Liu, Qinghong

    2018-01-01

    Epidermal growth factor receptor (EGFR) and downstream signal transducer and activator of transcription 3 (STAT3) signaling have been extensively implicated in various human neoplasms. Recently, a novel EGFR inhibitor, known as afatinib, has exhibited broad antitumor activities in a variety of tumors. Therefore, the present study attempted to investigate the impact of this agent on intrahepatic cholangiocarcinoma (ICC). Initially, immunohistochemical assays were performed on 15 human ICC specimens and their adjacent tissues in order to assess the protein levels of phosphorylated EGFR (pEGFR) and pSTAT3. Subsequently, the human ICC cell lines JCK and OZ were exposed to different doses of afatinib, and then cell viability and apoptosis were determined by MTT assay and flow cytometry, respectively. Furthermore, immunoblotting was applied to detect any variations in the phosphorylated protein levels of EGFR and STAT3 in afatinib-treated ICC cells. The results of the current study demonstrated that ICC specimens had evidently increased pEGFR and pSTAT3 protein levels as compared with the adjacent noncancerous tissues. Further in vitro experiments indicated that afatinib evidently blocked ICC cell growth and induced cell apoptosis. At the protein level, pEGFR and pSTAT3 were evidently attenuated by afatinib-administration. In conclusion, the present study clearly determined that afatinib exerts an antitumor effect on ICC cells by silencing the EGFR-STAT3 signaling pathway. This novel agent deserves further investigation as a potential therapeutic strategy for ICC. PMID:29805522

  15. 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

  16. The endothelial lipase protein is promising urinary biomarker for diagnosis of gastric cancer.

    PubMed

    Dong, Xueyan; Wang, Guoqing; Zhang, Guoqing; Ni, Zhaohui; Suo, Jian; Cui, Juan; Cui, Ai; Yang, Qing; Xu, Ying; Li, Fan

    2013-03-19

    Gastric cancer is one of the most common malignant tumors in the world. Finding effective diagnostic biomarkers in urine or serum would represent the most ideal solution to detecting gastric cancer during annual physical examination. This study was to evaluate the potential of endothelial lipase (EL) as a urinary biomarker for diagnosis of gastric cancer. The expression levels of EL was measured using Western blotting and immunohistochemical staining experiments on (tissue, serum, and urine) samples of gastric cancer patients versus healthy people. We also checked the EL levels in the urine samples of other cancer types (lung, colon and rectum cancers) and benign lesions (gastritis and gastric leiomyoma) to check if EL was specific to gastric cancer. We observed a clear separation between the EL expression levels in the urine samples of 90 gastric cancer patients and of 57 healthy volunteers. It was approximately 9.9 fold average decrease of the EL expression levels in the urine samples of gastric cancer compared to the healthy controls (P <0.0001), achieving a 0.967 AUC value for the ROC (receiver operating characteristic) curve, demonstrating it's highly accurate as a diagnostic marker for gastric cancer. Interestingly, the expression levels of EL in tissue and serum samples were not nearly as discriminative as in urine samples (P = 0.90 and P = 0.79). In immunohistochemical experiments, positive expression of the EL protein was found in 67% (8/12) of gastric adjacent noncancerous and in 58% (7/12) of gastric cancer samples. There was no significant statistical in the expression levels of this protein between the gastric cancer and the matching noncancerous tissues (P =0.67). The urinary EL as a highly accurate gastric cancer biomarker that is potentially applicable to the general screening with high sensitivity and specificity. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4527331618757552.

  17. The endothelial lipase protein is promising urinary biomarker for diagnosis of gastric cancer

    PubMed Central

    2013-01-01

    Background Gastric cancer is one of the most common malignant tumors in the world. Finding effective diagnostic biomarkers in urine or serum would represent the most ideal solution to detecting gastric cancer during annual physical examination. This study was to evaluate the potential of endothelial lipase (EL) as a urinary biomarker for diagnosis of gastric cancer. Methods The expression levels of EL was measured using Western blotting and immunohistochemical staining experiments on (tissue, serum, and urine) samples of gastric cancer patients versus healthy people. We also checked the EL levels in the urine samples of other cancer types (lung, colon and rectum cancers) and benign lesions (gastritis and gastric leiomyoma) to check if EL was specific to gastric cancer. Result We observed a clear separation between the EL expression levels in the urine samples of 90 gastric cancer patients and of 57 healthy volunteers. It was approximately 9.9 fold average decrease of the EL expression levels in the urine samples of gastric cancer compared to the healthy controls (P <0.0001), achieving a 0.967 AUC value for the ROC (receiver operating characteristic) curve, demonstrating it’s highly accurate as a diagnostic marker for gastric cancer. Interestingly, the expression levels of EL in tissue and serum samples were not nearly as discriminative as in urine samples (P = 0.90 and P = 0.79). In immunohistochemical experiments, positive expression of the EL protein was found in 67% (8/12) of gastric adjacent noncancerous and in 58% (7/12) of gastric cancer samples. There was no significant statistical in the expression levels of this protein between the gastric cancer and the matching noncancerous tissues (P =0.67). Conclusions The urinary EL as a highly accurate gastric cancer biomarker that is potentially applicable to the general screening with high sensitivity and specificity. Virtual Slides The virtual slide(s) for this article can be found here: http

  18. Raman imaging at biological interfaces: applications in breast cancer diagnosis

    PubMed Central

    2013-01-01

    Background One of the most important areas of Raman medical diagnostics is identification and characterization of cancerous and noncancerous tissues. The methods based on Raman scattering has shown significant potential for probing human breast tissue to provide valuable information for early diagnosis of breast cancer. A vibrational fingerprint from the biological tissue provides information which can be used to identify, characterize and discriminate structures in breast tissue, both in the normal and cancerous environment. Results The paper reviews recent progress in understanding structure and interactions at biological interfaces of the human tissue by using confocal Raman imaging and IR spectroscopy. The important differences between the noncancerous and cancerous human breast tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives as well as carotenoids and interfacial water. Conclusions We demonstrate that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The results presented in the paper may have serious implications on understanding mechanisms of interactions in living cells under realistically crowded conditions of biological tissue. PMID:23705882

  19. Raman imaging at biological interfaces: applications in breast cancer diagnosis.

    PubMed

    Surmacki, Jakub; Musial, Jacek; Kordek, Radzislaw; Abramczyk, Halina

    2013-05-24

    One of the most important areas of Raman medical diagnostics is identification and characterization of cancerous and noncancerous tissues. The methods based on Raman scattering has shown significant potential for probing human breast tissue to provide valuable information for early diagnosis of breast cancer. A vibrational fingerprint from the biological tissue provides information which can be used to identify, characterize and discriminate structures in breast tissue, both in the normal and cancerous environment. The paper reviews recent progress in understanding structure and interactions at biological interfaces of the human tissue by using confocal Raman imaging and IR spectroscopy. The important differences between the noncancerous and cancerous human breast tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives as well as carotenoids and interfacial water. We demonstrate that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The results presented in the paper may have serious implications on understanding mechanisms of interactions in living cells under realistically crowded conditions of biological tissue.

  20. Microwave processing of gustatory tissues for immunohistochemistry

    PubMed Central

    Bond, Amanda; Kinnamon, John C.

    2013-01-01

    We use immunohistochemistry to study taste cell structure and function as a means to elucidate how taste receptor cells communicate with nerve fibers and adjacent taste cells. This conventional method, however, is time consuming. In the present study we used taste buds from rat circumvallate papillae to compare conventional immunohistochemical tissue processing with microwave processing for the colocalization of several biochemical pathway markers (PLCβ2, syntaxin-1, IP3R3, α-gustducin) and the nuclear stain, Sytox. The results of our study indicate that in microwave versus conventional immunocytochemistry: (1) fixation quality is improved; (2) the amount of time necessary for processing tissue is decreased; (3) antigen retrieval is no longer needed; (4) image quality is superior. In sum, microwave tissue processing of gustatory tissues is faster and superior to conventional immunohistochemical tissue processing for many applications. PMID:23473796

  1. Development of improved connection details for adjacent prestressed member bridges.

    DOT National Transportation Integrated Search

    2017-06-01

    Adjacent prestressed member girder bridges are economical systems for short spans and generally come in two types: adjacent box beam bridges and adjacent voided slab bridges. Each type provides the advantages of having low clearances because of their...

  2. Generation of Chimeric RNAs by cis-splicing of adjacent genes (cis-SAGe) in mammals.

    PubMed

    Zhuo, Jian-Shu; Jing, Xiao-Yan; Du, Xin; Yang, Xiu-Qin

    2018-02-20

    Chimeric RNA molecules, possessing exons from two or more independent genes, are traditionally believed to be produced by chromosome rearrangement. However, recent studies revealed that cis-splicing of adjacent genes (cis- SAGe) is one of the major mechanisms underlying the formation of chimeric RNAs. cis-SAGe refers to intergenic splicing of directly adjacent genes with the same transcriptional orientation, resulting in read-through transcripts, termed chimeric RNAs, which contain sequences from two or more parental genes. cis-SAGe was first identified in tumor cells, since then its potential in carcinogenesis has attracted extensive attention. More and more scientists are focusing on it. With the development of research, cis-SAGe was found to be ubiquitous in various normal tissues, and might make a crucial contribution to the formation of novel genes in the evolution of genomes. In this review, we summarize the splicing pattern, expression characteristics, possible mechanisms, and significance of cis-SAGe in mammals. This review will be helpful for general understanding of the current status and development tendency of cis-SAGe.

  3. 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...

  4. MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell carcinoma arising from oral submucous fibrosis.

    PubMed

    Xie, Xiaoyan; Jiang, Yuchen; Yuan, Yao; Wang, Peiqi; Li, Xinyi; Chen, Fangman; Sun, Chongkui; Zhao, Hang; Zeng, Xin; Jiang, Lu; Zhou, Yu; Dan, Hongxia; Feng, Mingye; Liu, Rui; Chen, Qianming

    2016-09-13

    Oral squamous cell carcinoma (OSCC) ranks among the most common cancer worldwide, and is associated with severe morbidity and high mortality. Oral submucous fibrosis (OSF), characterized by fibrosis of the mucosa of the upper digestive tract, is a pre-malignant lesion, but the molecular mechanisms underlying this malignant transformation remains to be elucidated. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was employed to profile the differentially expressed peptides/proteins between OSCC tissues and the corresponding adjacent non-cancerous OSF tissues. Sixty-five unique peptide peaks and nine proteins were identified with altered expression levels. Of them, expression of NCOA7 was found to be up-regulated in OSCC tissues by immunohistochemistry staining and western blotting, and correlated with a pan of clinicopathologic parameters, including lesion site, tumor differentiation status and lymph node metastasis. Further, we show that overexpression of NCOA7 promotes OSCC cell proliferation in either in vitro or in vivo models. Mechanistic study demonstrates that NCOA7 induces OSCC cell proliferation probably by activating aryl hydrocarbon receptor (AHR). The present study suggests that NCOA7 is a potential biomarker for early diagnosis of OSF malignant transformation, and leads to a better understanding of the molecular mechanisms responsible for OSCC development.

  5. The influence of monoamine oxidase variants on the risk of betel quid-associated oral and pharyngeal cancer.

    PubMed

    Chen, Ping-Ho; Huang, Bin; Shieh, Tien-Yu; Wang, Yan-Hsiung; Chen, Yuk-Kwan; Wu, Ju-Hui; Huang, Jhen-Hao; Chen, Chun-Chia; Lee, Ka-Wo

    2014-01-01

    Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS.

  6. The Influence of Monoamine Oxidase Variants on the Risk of Betel Quid-Associated Oral and Pharyngeal Cancer

    PubMed Central

    Huang, Bin; Shieh, Tien-Yu; Wang, Yan-Hsiung; Chen, Yuk-Kwan; Wu, Ju-Hui; Huang, Jhen-Hao; Chen, Chun-Chia; Lee, Ka-Wo

    2014-01-01

    Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS. PMID:25389533

  7. Use of the tunnel technique and an acellular dermal matrix in the treatment of multiple adjacent teeth with gingival recession in the esthetic zone.

    PubMed

    Mahn, Douglas H

    2010-12-01

    The proper management of gingival recession is critical to the establishment of a natural-appearing soft tissue architecture. Subepithelial connective tissue grafts have been considered the "gold standard" but are limited by the availability of palatal donor tissue. Tunnel techniques have improved the esthetic results of connective tissue grafting. Acellular dermal matrices have been successful in the treatment of gingival recession and are not limited by the palatal anatomy. The aim of this report is to describe the application of the tunnel technique, with use of an acellular dermal matrix, in the correction of gingival recession affecting multiple adjacent teeth in the esthetic zone.

  8. Isolation and culture of primary human pancreatic stellate cells that reflect the context of their tissue of origin.

    PubMed

    Strobel, Oliver; Dadabaeva, Nigora; Felix, Klaus; Hackert, Thilo; Giese, Nathalia A; Jesenofsky, Ralf; Werner, Jens

    2016-02-01

    Pancreatic stellate cells (PSCs) play a critical role in pancreatic ductal adenocarcinoma (PDAC). Activated PSCs are the main source of fibrosis in chronic pancreatitis and of desmoplasia in PDAC. The majority of studies on PSC are based on in vitro experiments relying on immortalized cell lines derived from diseased human pancreas or from animal models. These PSCs are usually activated and may not represent the biological context of their tissue of origin. (1) To isolate and culture primary human PSC from different disease contexts with minimal impact on their state of activation. (2) To perform a comparative analysis of phenotypes of PSC derived from different contexts. PSCs were isolated from normal pancreas, chronic pancreatitis, and PDAC using a hybrid method of digestion and outgrowth. To minimize activation by serum compounds, cells were cultured in a low-serum environment (2.5 % fetal bovine serum (FBS)). Expression patterns of commonly used markers for PSC phenotype and activity were compared between primary PSC lines derived from different contexts and correlated to expression in their original tissues. Isolation was successful from 14 of 17 tissues (82 %). Isolated PSC displayed stable viability and phenotype in low-serum environment. Expression profiles of isolated PSC and matched original tissues were closely correlated. PDAC-derived PSC tended to have a higher status of activation if compared to PSC derived from non-cancerous tissues. Primary human PSCs isolated from different contexts and cultured in a low-serum environment maintain a phenotype that reflects the stromal activity present in their tissue of origin.

  9. 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

  10. 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

  11. Histone Deacetylase Inhibitor Trichostatin a Promotes the Apoptosis of Osteosarcoma Cells through p53 Signaling Pathway Activation

    PubMed Central

    Deng, Zhantao; Liu, Xiaozhou; Jin, Jiewen; Xu, Haidong; Gao, Qian; Wang, Yong; Zhao, Jianning

    2016-01-01

    Purpose: The purpose of this study was to investigate the profile of histone deacetylase (HDAC) activity and expression in osteosarcoma cells and tissues from osteosarcoma patients and to examine the mechanism by which a histone deacetylase (HDAC) inhibitor, Trichostatin A (TSA), promotes the apoptosis of osteosarcoma cells. Methods: HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of MG63 cells, hFOB 1.19 cells and tissues from 6 patients with primary osteosarcoma. The protein expression of Class I HDACs (1, 2, 3 and 8) and the activation of the p53 signaling pathway were examined by Western blot. Cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. Results: Nuclear HDAC activity and class I HDAC expression were significantly higher in MG63 cells than in hFOB 1.19 cells, and a similar trend was observed in the human osteosarcoma tissues compared with the paired adjacent non-cancerous tissues. TSA significantly inhibited the growth of MG63 cells and promoted apoptosis in a dose-dependent manner through p53 signaling pathway activation. Conclusion: Class I HDACs play a central role in the pathogenesis of osteosarcoma, and HDAC inhibitors may thus have promise as new therapeutic agents against osteosarcoma. PMID:27877082

  12. Downregulated SASH1 expression indicates poor clinical prognosis in gastric cancer.

    PubMed

    Zhou, Nan; Liu, Can; Wang, Xudong; Mao, Qinsheng; Jin, Qin; Li, Peng

    2018-04-01

    SASH1 (SAM- and SH3-domain containing 1), a novel candidate tumor suppressor, has attracted attention due to its role in intracellular signal transduction and its tumor prognostic value in diverse cancers. Reports have demonstrated that reduced SASH1 expression correlates with tumor proliferation, invasion, and metastasis. However, the expression and prognostic significance of SASH1 in gastric cancer (GC) remain unclear. In this study, 8 paired fresh-frozen GC tissues and corresponding gastric mucosal tissues were examined by Western blot to analyze the protein expression of SASH1. Seven hundred twenty-six formalin-fixed, paraffin-embedded (FFPE) gastric tissue samples were evaluated by immunohistochemical (IHC) to determine the correlations of SASH1 expression with clinicopathological factors and prognosis. Compared with adjacent noncancerous tissues, SASH1 was significantly downregulated in GC specimens. Analysis using the χ 2 test revealed that low SASH1 expression was significantly associated with advanced TNM stage (P < .001) in GC. Cox regression multivariable analyses demonstrated that SASH1 expression (P < .001), TNM stage (P < .001), preoperative CEA level (P = .003) and preoperative CA19-9 level (P = .002) were independent prognostic factors. Our clinical findings suggest that downregulated SASH1 expression could be used as an independent biomarker for poor prognosis in GC. Copyright © 2018. Published by Elsevier Inc.

  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. Origin of the subepidermal tissue in Piper L. leaves.

    PubMed

    Nakamura, A T; Simão, E; Silva, L; Torres, G A

    2015-05-01

    Studies on the anatomy of Piper leaves demonstrate the presence of a subepidermal tissue distinct from the adjacent epidermis, which cells show thin walls and hyaline contents. Some authors consider such cells a hypodermal tissue, while others refer to them as components of a multiple epidermis. In this study, the nature of this subepidermal tissue was investigated through the analysis of leaf ontogeny in three Piper species. The analysis showed that the referred tissue originates from the ground meristem and, thus, should be considered a hypodermis. The studied species suggests that the role of the hypodermis would be to protect the photosynthetic apparatus from excess light, regulating the intensity of light reaching the chlorophyll parenchyma.

  15. 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.

  16. 75 FR 42729 - Cellu Tissue Corporation; Notice of Application Accepted for Filing, Soliciting Motions To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2851-016] Cellu Tissue... the right bank of the river; (5) a 570-foot-long bypassed reach; (6) a powerhouse containing three... adjacent to the north wall of the Powerhouse; and (8) other appurtenances. Cellu Tissue Corporation...

  17. 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…

  18. 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

  19. Study on expression of CDH4 in lung cancer.

    PubMed

    Li, Zhupeng; Su, Dan; Ying, Lisha; Yu, Guangmao; Mao, Weimin

    2017-01-17

    The human CDH4 gene, which encodes the R-cadherin protein, has an important role in cell migration and cell adhesion, sorting, tissue morphogenesis, and tumor genesis. This study analyzed the relationship of CDH4 mRNA expression with lung cancer. Real time PCR was applied to detect CDH4 mRNA transcription in 142 paired cases of lung cancer and noncancerous regions. No correlation was identified between CDH4 mRNA expression and gender, age, lymphnode metastasis, TNM stage, family history, smoking state, drinking state (P > 0.05), but grade and histotype (P < 0.05). The relative CDH4 mRNA value was remarkably decreased in lung cancer tissues compared with noncancerous tissues (P = 0.001). We found that CDH4 mRNA expression was associated with grade and histotype. What is more, the relative CDH4 mRNA value was decreased in the lung cancer tissues. Our results suggested that CDH4 might be a putative tumor suppressor gene (TSG) in lung cancer.

  20. 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.

  1. A Review of the Positive Influence of Crown Contours on Soft-Tissue Esthetics.

    PubMed

    Kinsel, Richard P; Pope, Bryan I; Capoferri, Daniele

    2015-05-01

    Successful crown restorations duplicate the natural tooth in hue, chroma, value, maverick colors, and surface texture. Equally important is the visual harmony of the facial and proximal soft-tissue contours, which requires the collaborative skills of the restorative dentist, periodontist, and dental technician. The treatment team must understand the biologic structures adjacent to natural dentition and dental implants. This report describes the potential for specifically designed restorative contours to dictate the optimal gingival profile for tooth-supported and implant-supported crowns. Showing several cases, the article explains how esthetic soft-tissue contours enhance the definitive crown restoration, highlights the importance of clinical evaluation of adjacent biologic structures, and discusses keys to predicting when the proximal papilla has the potential to return to a favorable height and shape.

  2. Soft tissue hemangioma with osseous extension: a case report and review of the literature.

    PubMed

    Daoud, Alexander; Olivieri, Brandon; Feinberg, Daniel; Betancourt, Michel; Bockelman, Brian

    2015-04-01

    Soft tissue hemangiomas are commonly encountered lesions, accounting for 7-10 % of all benign soft tissue masses (Mitsionis et al. J Foot Ankle Surg 16(2):27-9, 2010). While the literature describes the great majority of hemangiomas as asymptomatic and discovered only as incidental findings, they do have the potential to induce reactive changes in neighboring structures (Pastushyn et al. Surg Neurol 50(6):535-47, 1998). When these variants occur in close proximity to bone, they may elicit a number of well-documented reactive changes in osseous tissue (Mitsionis et al. J Foot Ankle Surg 16(2):27-9, 2010; DeFilippo et al. Skelet Radiol 25(2):174-7, 1996; Ly et al. AJR Am J Roentgenol 180(6):1695-700, 2003; Sung et al. Skelet Radiol 27(4):205-10, 1998). However, instances of direct extension into bone by soft tissue hemangiomas--that is, infiltration of the mass's vascular components into nearby osseous tissue--are currently undocumented in the literature. In these cases, imaging plays an important role in differentiating hemangiomas from malignant lesions (Mitsionis et al. J Foot Ankle Surg 16(2):27-9, 2010; Sung et al. Skelet Radiol 27(4):205-10, 1998; Pourbagher, Br J Radiol 84(1008):1100-8, 2011). In this article, we present such a case that involved the sacral spine. Imaging revealed a soft tissue mass with direct extension of vascular components into osseous tissue of the adjacent sacral vertebrae. Biopsy and subsequent histopathologic examination led to definitive diagnosis of soft tissue hemangioma. While MRI is widely regarded as the gold standard imaging modality for evaluating hemangiomas, in this report we describe how CT can aid in narrowing the differential diagnosis when one encounters a vascular lesion with adjacent osseous changes. Furthermore, we review the literature as it pertains to the imaging of soft tissue hemangiomas that occur in proximity to osseous tissue, as well as correlate this case to current theories on the pathogenesis of hemangiomas

  3. A systematic review of definitions and classification systems of adjacent segment pathology.

    PubMed

    Kraemer, Paul; Fehlings, Michael G; Hashimoto, Robin; Lee, Michael J; Anderson, Paul A; Chapman, Jens R; Raich, Annie; Norvell, Daniel C

    2012-10-15

    Systematic review. To undertake a systematic review to determine how "adjacent segment degeneration," "adjacent segment disease," or clinical pathological processes that serve as surrogates for adjacent segment pathology are classified and defined in the peer-reviewed literature. Adjacent segment degeneration and adjacent segment disease are terms referring to degenerative changes known to occur after reconstructive spine surgery, most commonly at an immediately adjacent functional spinal unit. These can include disc degeneration, instability, spinal stenosis, facet degeneration, and deformity. The true incidence and clinical impact of degenerative changes at the adjacent segment is unclear because there is lack of a universally accepted classification system that rigorously addresses clinical and radiological issues. A systematic review of the English language literature was undertaken and articles were classified using the Grades of Recommendation Assessment, Development, and Evaluation criteria. RESULTS.: Seven classification systems of spinal degeneration, including degeneration at the adjacent segment, were identified. None have been evaluated for reliability or validity specific to patients with degeneration at the adjacent segment. The ways in which terms related to adjacent segment "degeneration" or "disease" are defined in the peer-reviewed literature are highly variable. On the basis of the systematic review presented in this article, no formal classification system for either cervical or thoracolumbar adjacent segment disorders currently exists. No recommendations regarding the use of current classification of degeneration at any segments can be made based on the available literature. A new comprehensive definition for adjacent segment pathology (ASP, the now preferred terminology) has been proposed in this Focus Issue, which reflects the diverse pathology observed at functional spinal units adjacent to previous spinal reconstruction and balances

  4. 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.

  5. 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…

  6. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    PubMed

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

  7. Combined SERS biotags (SBTs) and microfluidic platform for the quantitative ratiometric discrimination between noncancerous and cancerous cells in flow

    NASA Astrophysics Data System (ADS)

    Pallaoro, Alessia; Hoonejani, Mehran R.; Braun, Gary B.; Meinhart, Carl; Moskovits, Martin

    2012-10-01

    SERS biotags are made from polymer-encapsulated silver nanoparticle dimers infused with unique Raman reporter molecules, and carry peptides as cell recognition moieties. We demonstrate their potential use for early and rapid identification of malignant cells, a central goal in cancer research. SERS biotags (SBTs) can be routinely synthesized and simultaneously excited with a single, low intensity laser source, making the determination of the relative contribution of the individual SBTs to the overall spectrum tractable. Importantly for biomedical applications, SERS employs tissuepenetrating lasers in the red to near-infrared range resulting in low autofluorescence. We have previously described a multiplexed, ratiometric method that can confidently distinguish between cancerous and noncancerous epithelial prostate cells in vitro based on receptor overexpression. Here we present the progress towards the application of this quantitative methodology for the identification of cancer cells in a microfluidic flow-focusing device. Beads are used as cell mimics to characterize the devices. Cells (and beads) are simultaneously incubated with two sets of SBTs while in suspension (simulating cells' capture from blood), then injected into the device for laser interrogation under flow. Each cell event is characterized by a composite Raman spectrum, deconvoluted into its single components to ultimately determine their relative contribution. We show that using SBTs ratiometrically can provide cell identification insensitive to normal causes of uncertainty in optical measurements such as variations in focal plane, cell concentration, autofluorescence, and turbidity.

  8. Uremia Induces Dental Pulp Ossification but Reciprocally Inhibits Adjacent Alveolar Bone Osteogenesis.

    PubMed

    Yang, Chih-Yu; Chang, Zee-Fen; Chau, Yat-Pang; Chen, Ann; Lee, Oscar Kuang-Sheng; Yang, An-Hang

    2015-11-01

    Uremic patients are predisposed to atrophy of the alveolar bone and narrowing of the dental pulp chamber. Such pulp chamber changes have only been diagnosed radiologically; however, this has not been supported by any pathological evidence. We used a uremic rat model with secondary hyperparathyroidism induced by 5/6 nephrectomy surgery and high-phosphate diet to examine the dental pulp and adjacent alveolar bone pathology. In addition, we collected pulp tissues for real-time PCR. We found an opposite histopathological presentation of the ossified dental pulp and the osteomalacic adjacent alveolar bone. Furthermore, pulp cells with positive staining for Thy-1, a surrogate stem cell marker, were significantly reduced in the pulp of uremic rats compared to the controls, indicating a paucity of stem cells. This was further evidenced by the reduced pulp expression of dickkopf-1 (Dkk-1), a Wnt/β-catenin signaling inhibitor produced by mesenchymal stem cells. In contrast, expressions of receptor activator of nuclear factor κB ligand (RANKL) and RANK in uremic pulp were up-regulated, probably to counteract the ossifying process of uremic pulp. In conclusion, uremic pulp ossifications were associated with a paucity of stem cells and dysregulated Dkk-1 and RANKL signaling systems, further shifting the imbalance toward osteogenesis. Strategies to counteract such an imbalance may offer a potential therapeutic target to improve dental health in uremic patients, which warrants further interventional studies.

  9. Automatic segmentation and supervised learning-based selection of nuclei in cancer tissue images.

    PubMed

    Nandy, Kaustav; Gudla, Prabhakar R; Amundsen, Ryan; Meaburn, Karen J; Misteli, Tom; Lockett, Stephen J

    2012-09-01

    Analysis of preferential localization of certain genes within the cell nuclei is emerging as a new technique for the diagnosis of breast cancer. Quantitation requires accurate segmentation of 100-200 cell nuclei in each tissue section to draw a statistically significant result. Thus, for large-scale analysis, manual processing is too time consuming and subjective. Fortuitously, acquired images generally contain many more nuclei than are needed for analysis. Therefore, we developed an integrated workflow that selects, following automatic segmentation, a subpopulation of accurately delineated nuclei for positioning of fluorescence in situ hybridization-labeled genes of interest. Segmentation was performed by a multistage watershed-based algorithm and screening by an artificial neural network-based pattern recognition engine. The performance of the workflow was quantified in terms of the fraction of automatically selected nuclei that were visually confirmed as well segmented and by the boundary accuracy of the well-segmented nuclei relative to a 2D dynamic programming-based reference segmentation method. Application of the method was demonstrated for discriminating normal and cancerous breast tissue sections based on the differential positioning of the HES5 gene. Automatic results agreed with manual analysis in 11 out of 14 cancers, all four normal cases, and all five noncancerous breast disease cases, thus showing the accuracy and robustness of the proposed approach. Published 2012 Wiley Periodicals, Inc.

  10. Increased Frequency of CpG Island Methylator Phenotype and CDH1 Methylation in a Gastric Cancer High-Risk Region of China1

    PubMed Central

    Zhang, Kai-Li; Sun, Yuan; Li, Yan; Liu, Ming; Qu, Bo; Cui, Shu-Hong; Kong, Qing-You; Chen, Xiao-Yan; Li, Hong; Liu, Jia

    2008-01-01

    This study aimed to profile the methylation statuses of CDH1/E-cadherin and five CpG island methylator phenotype (CIMP)-associated genes (p16, hMLH1, MINT1, MINT2, and MINT31) in gastric specimens of 47 Dalian long-term residents with and 31 without gastric cancers (GCs). CIMP patterns were classified as CIMP-H with over three methylated genes, CIMP-L with one to two methylated genes, and CIMP-N without methylation. Of 47 GC cases, 24 (51.1%) were CIMP-H, 18 (38.3%) were CIMP-L, and 5 (10.6%) were CIMP-N, whereas 5 of 21 (23.8%) premalignant lesions were CIMP-H and 15 (71.4%) were CIMP-L. CIMP-L was found in 75% (12/16) of GC-adjacent mucosa and in 38.7% (12/31) of mucosa from GC-free patients. CDH1 methylation occurred in 48.9% (23/47) of cancer, in 23.8% (5/21) of premalignant, and in 25% (4/16) of noncancerous tissues and was correlated with patients' age (P = .01), lymph node metastasis, and CIMP severity (P = .000–.028). Our results demonstrated that the frequencies of CIMP-H in Dalian GCs, CIMP-L, and p16 methylation in GC-adjacent tissues and in GC-free mucosa were much higher than those reported previously, indicating the elevated methylation pressure in this GC high-risk region. The close correlation between CDH1 methylation and CIMP severity suggests the necessity of their combination in GC prevention and earlier diagnosis. PMID:18607505

  11. Objectifying the adjacent and opposite angles: a cultural historical analysis

    NASA Astrophysics Data System (ADS)

    Daher, Wajeeh; Musallam, Nadera

    2018-02-01

    The angle topic is central to the development of geometric knowledge. Two of the basic concepts associated with this topic are the adjacent and opposite angles. It is the goal of the present study to analyze, based on the cultural historical semiotics framework, how high-achieving seventh grade students objectify the adjacent and opposite angles' concepts. We videoed the learning of a group of three high-achieving students who used technology, specifically GeoGebra, to explore geometric relations related to the adjacent and opposite angles' concepts. To analyze students' objectification of these concepts, we used the categories of objectification of knowledge (attention and awareness) and the categories of generalization (factual, contextual and symbolic), developed by Radford. The research results indicate that teacher's and students' verbal and visual signs, together with the software dynamic tools, mediated the students' objectification of the adjacent and opposite angles' concepts. Specifically, eye and gestures perceiving were part of the semiosis cycles in which the participating students were engaged and which related to the mathematical signs that signified the adjacent and the opposite angles. Moreover, the teacher's suggestions/requests/questions included/suggested semiotic signs/tools, including verbal signs that helped the students pay attention, be aware of and objectify the adjacent and opposite angles' concepts.

  12. Phytoparasitic Nematodes Adjacent to Established Strawberry Plantations

    PubMed Central

    Crow, R. V.; MacDonald, D. H.

    1978-01-01

    Plant-nematode populations associated with uncultivated vegetation, adjacent strawberry plants, and alternate crop sites were studied at three locations in Minnesota. At one site (Forest Lake), Paratylenchus projectus, Meloidogyne hapla, and Pratylenchus tenuis were frequently associated with the roots of native vegetation. These nematode species were also present in adjacent strawberry beds. Among alternate crops observed, oats and muskmelon usually supported the fewest nematodes although moderate densities of Xiphinema americanum and P. tenuis were found at one location in plots planted to oats. Pratylenchus tenuis was also found on rye at one location. PMID:19305841

  13. 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.

  14. In vivo outcomes of tissue-engineered osteochondral grafts.

    PubMed

    Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

    2010-04-01

    Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

  15. 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.

  16. Mutant p53 expression in kidney tubules adjacent to renal cell carcinoma: evidence of a precursor lesion.

    PubMed

    Lai, R; el Dabbagh, L; Mourad, W A

    1996-06-01

    Neoplastic transformation can be associated with mutations of the p53 gene. This leads to stabilization of its protein product and to its accumulation, which allows immunohistochemical detection. Mutant p53 expression has been seen in many neoplasms, including renal cell carcinoma (RCC). We recently described putative precursor lesions of RCC. The lesions were defined as intratubular epithelial dysplasia (IED) of kidney tubules adjacent to RCC. They were seen in one-third of the cases studied. The findings were based only on light microscopic analysis. We hypothesized that neoplastic transformation would be manifested by mutant p53 expression in the kidney tubules adjacent to RCC and not in nonneoplastic kidneys. Immunohistochemical staining for p53 in 24 cases of RCC with adjacent kidneys was performed. We used the DO-7 monoclonal antibody reactive for the N-terminal of the p53 protein on formalin-fixed paraffin-embedded tissue. Sections from 14 kidneys resected for nonneoplastic conditions were used as controls. Twenty-one (87%) of the 24 cases of RCC had nuclear p53 expression in the tumor cells. This included 14 cases (58%) with intense reactivity and 7 cases (29%) with weaker p53 immunoreactivity. Of the 24 cases of RCC, IED was identified in 13 cases (54%). Immunoreactivity for p53 was focally seen in tubules of all the lesions, as well as in the nonlesional areas. Six of the lesions exhibited intense nuclear staining. The kidneys adjacent to the RCC, with no evidence of IED, showed focally intense positive p53 nuclear staining in four cases. None of the control specimens showed p53 expression. Our findings provide supportive evidence that previously described IED in kidneys adjacent to RCC are most likely precursor lesions of the neoplasm. Aberrant expression of p53 in areas without evidence of IED may suggest that neoplastic transformation manifested by p53 mutation in kidney tubules may be seen before the development of the morphologic features of

  17. Variable length adjacent partitioning for PTS based PAPR reduction of OFDM signal

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

    Ibraheem, Zeyid T.; Rahman, Md. Mijanur; Yaakob, S. N.

    2015-05-15

    Peak-to-Average power ratio (PAPR) is a major drawback in OFDM communication. It leads the power amplifier into nonlinear region operation resulting into loss of data integrity. As such, there is a strong motivation to find techniques to reduce PAPR. Partial Transmit Sequence (PTS) is an attractive scheme for this purpose. Judicious partitioning the OFDM data frame into disjoint subsets is a pivotal component of any PTS scheme. Out of the existing partitioning techniques, adjacent partitioning is characterized by an attractive trade-off between cost and performance. With an aim of determining effects of length variability of adjacent partitions, we performed anmore » investigation into the performances of a variable length adjacent partitioning (VL-AP) and fixed length adjacent partitioning in comparison with other partitioning schemes such as pseudorandom partitioning. Simulation results with different modulation and partitioning scenarios showed that fixed length adjacent partition had better performance compared to variable length adjacent partitioning. As expected, simulation results showed a slightly better performance of pseudorandom partitioning technique compared to fixed and variable adjacent partitioning schemes. However, as the pseudorandom technique incurs high computational complexities, adjacent partitioning schemes were still seen as favorable candidates for PAPR reduction.« less

  18. 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

  19. A review of the natural history of adult Cetoniinae (Coleoptera: Scarabaeidae) from Argentina and adjacent countries.

    PubMed

    Di Iorio, Osvaldo

    2014-04-17

    A compilation of the known natural history of adult Cetoniinae (Coleoptera: Scarabaeidae) from Argentina and adjacent countries is provided. Food items of adult Cetoniinae include pollen and/or nectar (flower visitors), sap and/or slime flux, ripened fruits on plants, green tissues and leaves, and honey. Of the 36 species of Cetoniinae from Argentina, food items are known only for 11 species (30.5%). Attraction to light and bait-traps, adult activity periods, vertebrate predators, and the occurrence in bird nests are presented and discussed. Other insects that share the same food sources and bait-traps with Cetoniinae are mentioned.

  20. MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis

    PubMed Central

    Shang, Runze; Zhou, Liang; Wang, Xing; Duan, Juanli; Ruan, Bai; Gao, Yuan; Dai, Bin; Qu, Shibin; Liu, Wei; Ding, Rui; Wang, Lin; Wang, Desheng; Dou, Kefeng

    2016-01-01

    MicroRNA-150 (miR-150) is frequently dysregulated in cancer and is involved in carcinogenesis and cancer progression. In this study, we found that miR-150 was significantly downregulated in hepatocellular carcinoma (HCC) tissues compared to adjacent noncancerous tissues. Low levels of miR-150 were significantly associated with worse clinicopathological characteristics and a poor prognosis for patients with HCC. miR-150 overexpression inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Further experiments indicated that Grb2-associated binding protein 1 (GAB1) was a direct target of miR-150 in HCC cells. In addition, GAB1 expression was increased in HCC tissues and inversely correlated with miR-150 levels. Knockdown of GAB1 mimicked the tumor-suppressive effects of miR-150 overexpression on HCC cells, whereas restoration of GAB1 expression partially abolished the inhibitory effects. Moreover, miR-150 overexpression decreased GAB1 expression, subsequently downregulated phospho-ERK1/2 and suppressed epithelial-mesenchymal-transition (EMT). These effects caused by miR-150 overexpression were alleviated by exogenous GAB1 expression. Taken together, this study demonstrates that miR-150 may be useful as a prognostic marker and that the identified miR-150-GAB1-ERK axis is a potential therapeutic target for HCC. PMID:26871477

  1. Blockade of the CXCR6 signaling inhibits growth and invasion of hepatocellular carcinoma cells through inhibition of the VEGF expression.

    PubMed

    Xu, J M; Weng, M Z; Song, F B; Chen, J Y; Zhang, J Y; Wu, J Y; Qin, J; Jin, T; Wang, X L

    2014-01-01

    Chemokines have been shown to play a critical role in tumor development and progression. However, little is known about the function and molecular mechanisms of CXCR6 in multiple malignancies. In the present study, we aimed to investigate the role of CXCR6 in human hepatocellular carcinoma (HCC). The expression of CXCR6 was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentivirus-mediated CXCR6 shRNA (shCXCR6) on cell proliferation and invasive potential by MTT and Transwell assays in HCC cell line (SMMC-7721). It was found that the expression of CXCR6 protein was significantly increased in HCC tissues compared with that in adjacent non-cancerous tissues (ANCT) (63.04% vs 36.96%, P=0.019), and correlated with the lymph-vascular space invasion in HCC patients (P=0.038). Knockdown of CXCR6 repressed cell proliferation and invasion of HCC cells followed by the down-regulation of vascular endothelial growth factor (VEGF). Taken together, our findings show that high expression of CXCR6 is positively associated with distant invasion of HCC patients, and blockade of CXCR6 signaling suppresses the growth and invasion of HCC cells through inhibition of the VEGF expression, suggesting that CXCR6 may represent a promising therapeutic target for the treatment of HCC.

  2. Reduced miR-300 expression predicts poor prognosis in patients with laryngeal squamous cell carcinoma.

    PubMed

    He, F-Y; Liu, H-J; Guo, Q; Sheng, J-L

    2017-02-01

    miR-300 has been demonstrated to play an important role in the progression of several tumors, but its role in tumorigenesis of laryngeal squamous cell carcinoma (LSCC) is still unclear. The purpose of this study was to explore miR-300 expression in LSCC patients and analyze its association with clinicopathological factors and prognosis. In the present study, we measured the expression level of miR-300 in LSCC tissues by RT-PCR. Associations between miRNA-300 expressions and various clinicopathological characteristics were analyzed. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. The univariate and multivariate analysis were performed using the Cox proportional hazard analysis. miR-300 expression was significantly increased in LSCC tissues compared with that in adjacent non-cancerous tissues (p < 0.01). In addition, lymph node metastasis (p = 0.004) and TNM stage (p = 0.001) were obvious influence factors for the expression of miR-300. More importantly, Kaplan-Meier analysis showed that LSCC patients with low miR-300 expression tended to have shorter overall survival (p < 0.001). Finally, multivariate analysis revealed that miR-300 expression was an independent prognostic factor for LSCC patients. Our results pointed to miR-300 as a powerful prognostic marker in LSCC and as a novel target for tumor-suppressive therapy.

  3. Long-term effects of vertebroplasty: adjacent vertebral fractures.

    PubMed

    Baroud, Gamal; Vant, Christianne; Wilcox, Ruth

    2006-01-01

    In today's aging population, osteoporosis-related fractures are an ever-growing concern. Vertebroplasty, a promising yet cost-effective treatment for vertebral compression fractures, has an increasing role. The first vertebroplasty procedures were reported by Deramond and Galibert in France in 1987, and international interest grew with continued development of clinical techniques and augmentation materials in Europe and the United States. Initial publications and presentations at peer review meetings demonstrated 60-90% success rates in providing immediate and significant pain relief. The objective of this review is to assemble experimental and computational biomechanical research whose goal is determining and preventing the negative long-term effects ofvertebroplasty, with a specific focus on adjacent vertebral fractures. Biomechanical studies using isolated cancellous bone cylinders have shown that osteoporotic cancellous bone samples augmented by the rigid bone cement were at least 12 times stiffer and 35 times stronger than the untreated osteoporotic cancellous bone samples. The biomechanical efficacy of the procedure to repair the fractured vertebrae and prevent further collapse is determined using single-vertebra models. The strength or load-bearing capacity of a single vertebra is significantly increased following augmentation when compared to the intact strength. However, there is no dear result regarding the overall stiffness of the single vertebra, with studies reporting contradictorily that the stiffness increases, decreases, or does not significantly alter following augmentation. The effects of vertebroplasty on adjacent structures are studied via multisegment models, whose results plainly oppose the findings of the single-vertebra and intravertebral models. Here, augmentation was shown to decrease the overall segment strength by 19% when compared to the matched controls. As well, there is a significant increase in disc pressure compared to the pre

  4. Tissue adhesion to bioactive glass-coated silicone tubing in a rat model of peritoneal dialysis catheters and catheter tunnels.

    PubMed

    Ross, Edward A; Batich, Christopher D; Clapp, William L; Sallustio, Judith E; Lee, Nadeen C

    2003-02-01

    Silicone peritoneal dialysis catheters do not develop tissue ingrowth, lack a mechanical barrier to periluminal bacterial migration and need cuffs for anchorage. We hypothesized that a bioactive glass coating composed of silicon, calcium, sodium and phosphorous oxides would cause a beneficial tissue reaction causing catheter adhesion, and tested this in a rat model. A hexane solvent-based method of coating silicone tubes with Bioglass powder was used, which maintained flexibility, and then the ultrastructure was confirmed with scanning electron microscopy (EM). Segments 2.5 cm were implanted subcutaneously in 8 Sprague-Dawley rats, with uncoated tubes as a contralateral control, and histology was done at 2, 4 and 6 weeks, including special stains and EM. The uncoated segments grossly had no adherence to surrounding tissue, and were physically separate from a thin fibrous capsule of approximately 50 micro width. Trichrome stains demonstrated the capsule was rich in collagen. There was minimal adjacent tissue reaction. In contrast, the coated tubes were palpably fixed to the soft tissues, and sections demonstrated an adjacent prominent layer of macrophages and multinucleated giant cells. Small numbers of lymphocytes were noted. This cellular reaction increased over the 6-week implant duration, and was also associated with neovascularization of the tissue adjacent to the segments (33 vessels in coated vs. 20 in controls per x 200 field, P < 0.0001). Many refractile silicone particles and prominent multinucleated giant cells were present, with small numbers of lymphocytes and macrophages. Stains showed scattered discontinuous calcific deposits. These findings are consistent with reports that the Bioglass(R) silicon oxide leads to the formation of a layer of hydroxyapatite, which binds to collagen and induces a tissue cellular reaction. In summary, bioactive glass coatings can improve the tissue retention of silicone tubing by promoting adhesion by collagen and cell

  5. Explaining large mortality differences between adjacent counties: a cross-sectional study.

    PubMed

    Schootman, M; Chien, L; Yun, S; Pruitt, S L

    2016-08-02

    Extensive geographic variation in adverse health outcomes exists, but global measures ignore differences between adjacent geographic areas, which often have very different mortality rates. We describe a novel application of advanced spatial analysis to 1) examine the extent of differences in mortality rates between adjacent counties, 2) describe differences in risk factors between adjacent counties, and 3) determine if differences in risk factors account for the differences in mortality rates between adjacent counties. We conducted a cross-sectional study in Missouri, USA with 2005-2009 age-adjusted all-cause mortality rate as the outcome and county-level explanatory variables from a 2007 population-based survey. We used a multi-level Gaussian model and a full Bayesian approach to analyze the difference in risk factors relative to the difference in mortality rates between adjacent counties. The average mean difference in the age-adjusted mortality rate between any two adjacent counties was -3.27 (standard deviation = 95.5) per 100,000 population (maximum = 258.80). Six variables were associated with mortality differences: inability to obtain medical care because of cost (β = 2.6), hospital discharge rate (β = 1.03), prevalence of fair/poor health (β = 2.93), and hypertension (β = 4.75) and poverty prevalence (β = 6.08). Examining differences in mortality rates and associated risk factors between adjacent counties provides additional insight for future interventions to reduce geographic disparities.

  6. Local adjacency metric dimension of sun graph and stacked book graph

    NASA Astrophysics Data System (ADS)

    Yulisda Badri, Alifiah; Darmaji

    2018-03-01

    A graph is a mathematical system consisting of a non-empty set of nodes and a set of empty sides. One of the topics to be studied in graph theory is the metric dimension. Application in the metric dimension is the navigation robot system on a path. Robot moves from one vertex to another vertex in the field by minimizing the errors that occur in translating the instructions (code) obtained from the vertices of that location. To move the robot must give different instructions (code). In order for the robot to move efficiently, the robot must be fast to translate the code of the nodes of the location it passes. so that the location vertex has a minimum distance. However, if the robot must move with the vertex location on a very large field, so the robot can not detect because the distance is too far.[6] In this case, the robot can determine its position by utilizing location vertices based on adjacency. The problem is to find the minimum cardinality of the required location vertex, and where to put, so that the robot can determine its location. The solution to this problem is the dimension of adjacency metric and adjacency metric bases. Rodrguez-Velzquez and Fernau combine the adjacency metric dimensions with local metric dimensions, thus becoming the local adjacency metric dimension. In the local adjacency metric dimension each vertex in the graph may have the same adjacency representation as the terms of the vertices. To obtain the local metric dimension of values in the graph of the Sun and the stacked book graph is used the construction method by considering the representation of each adjacent vertex of the graph.

  7. Constrained and Unconstrained Partial Adjacent Category Logit Models for Ordinal Response Variables

    ERIC Educational Resources Information Center

    Fullerton, Andrew S.; Xu, Jun

    2018-01-01

    Adjacent category logit models are ordered regression models that focus on comparisons of adjacent categories. These models are particularly useful for ordinal response variables with categories that are of substantive interest. In this article, we consider unconstrained and constrained versions of the partial adjacent category logit model, which…

  8. 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.

  9. Overexpression of karyopherin-α2 in cholangiocarcinoma correlates with poor prognosis and gemcitabine sensitivity via nuclear translocation of DNA repair proteins

    PubMed Central

    Tsukagoshi, Mariko; Araki, Kenichiro; Yokobori, Takehiko; Altan, Bolag; Suzuki, Hideki; Kubo, Norio; Watanabe, Akira; Ishii, Norihiro; Hosouchi, Yasuo; Nishiyama, Masahiko; Shirabe, Ken; Kuwano, Hiroyuki

    2017-01-01

    Cholangiocarcinoma is a highly malignant tumor, and the development of new therapeutic strategies is critical. Karyopherin-α2 (KPNA2) functions as an adaptor that mediates nucleocytoplasmic transport. Specifically, KPNA2 transports one of the important DNA repair machineries, the MRE11-RAD50-NBS1 (MRN) complex, to the nucleus. In this study, we clarified the significance of KPNA2 in cholangiocarcinoma. KPNA2 expression evaluated by immunohistochemical analysis was common in malignant tissue but rare in adjacent noncancerous tissues. KPNA2 overexpression was significantly correlated with poor prognosis and was an independent prognostic factor after surgery. In patients with cholangiocarcinoma who received gemcitabine after surgery, KPNA2 overexpression tended to be a prognostic indicator of poor overall survival. In KPNA2-depleted cholangiocarcinoma cells, proliferation was significantly decreased and gemcitabine sensitivity was enhanced in vitro and in vivo. Expression of KPNA2 and the MRN complex displayed colocalization in the nucleus. In addition, nuclear localization of the MRN complex was regulated by KPNA2 in vitro. These results suggest that KPNA2 expression may be a useful prognostic and predictive marker of gemcitabine sensitivity and survival. The regulation of KPNA2 expression may be a new therapeutic strategy for cholangiocarcinoma. PMID:28178675

  10. Overexpression of karyopherin-α2 in cholangiocarcinoma correlates with poor prognosis and gemcitabine sensitivity via nuclear translocation of DNA repair proteins.

    PubMed

    Tsukagoshi, Mariko; Araki, Kenichiro; Yokobori, Takehiko; Altan, Bolag; Suzuki, Hideki; Kubo, Norio; Watanabe, Akira; Ishii, Norihiro; Hosouchi, Yasuo; Nishiyama, Masahiko; Shirabe, Ken; Kuwano, Hiroyuki

    2017-06-27

    Cholangiocarcinoma is a highly malignant tumor, and the development of new therapeutic strategies is critical. Karyopherin-α2 (KPNA2) functions as an adaptor that mediates nucleocytoplasmic transport. Specifically, KPNA2 transports one of the important DNA repair machineries, the MRE11-RAD50-NBS1 (MRN) complex, to the nucleus. In this study, we clarified the significance of KPNA2 in cholangiocarcinoma. KPNA2 expression evaluated by immunohistochemical analysis was common in malignant tissue but rare in adjacent noncancerous tissues. KPNA2 overexpression was significantly correlated with poor prognosis and was an independent prognostic factor after surgery. In patients with cholangiocarcinoma who received gemcitabine after surgery, KPNA2 overexpression tended to be a prognostic indicator of poor overall survival. In KPNA2-depleted cholangiocarcinoma cells, proliferation was significantly decreased and gemcitabine sensitivity was enhanced in vitro and in vivo. Expression of KPNA2 and the MRN complex displayed colocalization in the nucleus. In addition, nuclear localization of the MRN complex was regulated by KPNA2 in vitro. These results suggest that KPNA2 expression may be a useful prognostic and predictive marker of gemcitabine sensitivity and survival. The regulation of KPNA2 expression may be a new therapeutic strategy for cholangiocarcinoma.

  11. Synergistic Effect of MiR-146a Mimic and Cetuximab on Hepatocellular Carcinoma Cells

    PubMed Central

    Huang, Suning; Rong, Minhua; Dang, Yiwu

    2014-01-01

    Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC. PMID:24895573

  12. Synergistic effect of MiR-146a mimic and cetuximab on hepatocellular carcinoma cells.

    PubMed

    Huang, Suning; He, Rongquan; Rong, Minhua; Dang, Yiwu; Chen, Gang

    2014-01-01

    Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.

  13. Diffusion-Weighted MRI Assessment of Adjacent Disc Degeneration After Thoracolumbar Vertebral Fractures

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

    Noriega, David C., E-mail: dcnoriega1970@gmail.com; Marcia, Stefano, E-mail: stemarcia@gmail.com; Ardura, Francisco, E-mail: fardura@ono.com

    ObjectiveThe purpose of this study was to assess, by the mean apparent diffusion coefficient (ADC), if a relationship exists between disc ADC and MR findings of adjacent disc degeneration after thoracolumbar fractures treated by anatomic reduction using vertebral augmentation (VAP).Materials and MethodsTwenty non-consecutive patients (mean age 50.7 years; range 45–56) treated because of vertebral fractures, were included in this study. There were 10 A3.1 and 10 A1.2 fractures (AO classification). Surgical treatment using VAP was applied in 14 cases, and conservative in 6 patients. MRI T2-weighted images and mapping of apparent diffusion coefficient (ADC) of the intervertebral disc adjacent to themore » fractured segment were performed after a mean follow-up of 32 months. A total of 60 discs, 3 per patient, were analysed: infra-adjacent, supra-adjacent and a control disc one level above the supra-adjacent.ResultsNo differences between patients surgically treated and those following a conservative protocol regarding the average ADC values obtained in the 20 control discs analysed were found. Considering all discs, average ADC in the supra-adjacent level was lower than in the infra-adjacent (1.35 ± 0.12 vs. 1.53 ± 0.06; p < 0.001). Average ADC values of the discs used as a control were similar to those of the infra-adjacent level (1.54 ± 0.06). Compared to surgically treated patients, discs at the supra-adjacent fracture level showed statistically significant lower values in cases treated conservatively (p < 0.001). The variation in the delay of surgery had no influence on the average values of ADC at any of the measured levels.ConclusionsADC measurements of the supra-adjacent discs after a mean follow-up of 32 months following thoracolumbar fractures, showed that restoration of the vertebral collapse by minimally invasive VAP prevents posttraumatic disc degeneration.« less

  14. Tissue biocompatibility of kevlar aramid fibers and polymethylmethacrylate, composites in rabbits.

    PubMed

    Henderson, J D; Mullarky, R H; Ryan, D E

    1987-01-01

    Two groups of female NZW rabbits were implanted in the paravertebral muscles with aramid (du Pont Kevlar aramid 49) fibers and aramid-polymethylmethacrylate (PMMA) composites for 14 and 28 days. Rabbits were killed at these times periods, necropsies performed, sites scored for gross tissue response, and tissue specimens containing the implants removed for histopathological evaluation. A mild fibrous tissue reaction was observed around all implants containing aramid fiber similar to that observed around the silicone control implant. Some foreign body giant cells were also present adjacent to the fibers. An intense necrotic inflammatory reaction was present around the positive control material (PVC Y-78). The tissue response to implantation of aramid fiber and fiber-PMMA composites indicates that aramid is a biocompatible material.

  15. 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

  16. 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.

  17. Adjacent-level arthroplasty following cervical fusion.

    PubMed

    Rajakumar, Deshpande V; Hari, Akshay; Krishna, Murali; Konar, Subhas; Sharma, Ankit

    2017-02-01

    OBJECTIVE Adjacent-level disc degeneration following cervical fusion has been well reported. This condition poses a major treatment dilemma when it becomes symptomatic. The potential application of cervical arthroplasty to preserve motion in the affected segment is not well documented, with few studies in the literature. The authors present their initial experience of analyzing clinical and radiological results in such patients who were treated with arthroplasty for new or persistent arm and/or neck symptoms related to neural compression due to adjacent-segment disease after anterior cervical discectomy and fusion (ACDF). METHODS During a 5-year period, 11 patients who had undergone ACDF anterior cervical discectomy and fusion (ACDF) and subsequently developed recurrent neck or arm pain related to adjacent-level cervical disc disease were treated with cervical arthroplasty at the authors' institution. A total of 15 devices were implanted (range of treated levels per patient: 1-3). Clinical evaluation was performed both before and after surgery, using a visual analog scale (VAS) for pain and the Neck Disability Index (NDI). Radiological outcomes were analyzed using pre- and postoperative flexion/extension lateral radiographs measuring Cobb angle (overall C2-7 sagittal alignment), functional spinal unit (FSU) angle, and range of motion (ROM). RESULTS There were no major perioperative complications or device-related failures. Statistically significant results, obtained in all cases, were reflected by an improvement in VAS scores for neck/arm pain and NDI scores for neck pain. Radiologically, statistically significant increases in the overall lordosis (as measured by Cobb angle) and ROM at the treated disc level were observed. Three patients were lost to follow-up within the first year after arthroplasty. In the remaining 8 cases, the duration of follow-up ranged from 1 to 3 years. None of these 8 patients required surgery for the same vertebral level during the follow

  18. 49 CFR 214.107 - Working over or adjacent to water.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Working over or adjacent to water. 214.107 Section 214.107 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD WORKPLACE SAFETY Bridge Worker Safety Standards § 214.107 Working over or adjacent to water. (a)...

  19. 49 CFR 214.107 - Working over or adjacent to water.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Working over or adjacent to water. 214.107 Section 214.107 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD WORKPLACE SAFETY Bridge Worker Safety Standards § 214.107 Working over or adjacent to water. (a)...

  20. 49 CFR 214.107 - Working over or adjacent to water.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Working over or adjacent to water. 214.107 Section 214.107 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD WORKPLACE SAFETY Bridge Worker Safety Standards § 214.107 Working over or adjacent to water. (a)...

  1. Pyrosequencing reveals the microbial communities in the Red Sea sponge Carteriospongia foliascens and their impressive shifts in abnormal tissues.

    PubMed

    Gao, Zhao-Ming; Wang, Yong; Lee, On On; Tian, Ren-Mao; Wong, Yue Him; Bougouffa, Salim; Batang, Zenon; Al-Suwailem, Abdulaziz; Lafi, Feras F; Bajic, Vladimir B; Qian, Pei-Yuan

    2014-10-01

    Abnormality and disease in sponges have been widely reported, yet how sponge-associated microbes respond correspondingly remains inconclusive. Here, individuals of the sponge Carteriospongia foliascens under abnormal status were collected from the Rabigh Bay along the Red Sea coast. Microbial communities in both healthy and abnormal sponge tissues and adjacent seawater were compared to check the influences of these abnormalities on sponge-associated microbes. In healthy tissues, we revealed low microbial diversity with less than 100 operational taxonomic units (OTUs) per sample. Cyanobacteria, affiliated mainly with the sponge-specific species "Candidatus Synechococcus spongiarum," were the dominant bacteria, followed by Bacteroidetes and Proteobacteria. Intraspecies dynamics of microbial communities in healthy tissues were observed among sponge individuals, and potential anoxygenic phototrophic bacteria were found. In comparison with healthy tissues and the adjacent seawater, abnormal tissues showed dramatic increase in microbial diversity and decrease in the abundance of sponge-specific microbial clusters. The dominated cyanobacterial species Candidatus Synechococcus spongiarum decreased and shifted to unspecific cyanobacterial clades. OTUs that showed high similarity to sequences derived from diseased corals, such as Leptolyngbya sp., were found to be abundant in abnormal tissues. Heterotrophic Planctomycetes were also specifically enriched in abnormal tissues. Overall, we revealed the microbial communities of the cyanobacteria-rich sponge, C. foliascens, and their impressive shifts under abnormality.

  2. Prevention and treatment of breast cancer by suppressing aromatase activity and expression.

    PubMed

    Chen, Shiuan; Zhou, Dujin; Okubo, Tomoharu; Kao, Yeh-Chih; Eng, Elizabeth T; Grube, Baiba; Kwon, Annette; Yang, Chun; Yu, Bin

    2002-06-01

    Estrogen promotes the proliferation of breast cancer cells. Aromatase is the enzyme that converts androgen to estrogen. In tumors, expression of aromatase is upregulated compared to that of surrounding noncancerous tissue. Tumor aromatase is thought to stimulate breast cancer growth in both an autocrine and a paracrine manner. A treatment strategy for breast cancer is to abolish in situ estrogen formation with aromatase inhibitors. In addition, aromatase suppression in postmenapausal women is being evaluated as a potential chemopreventive modality against breast cancer. One area of aromatase research in this laboratory is the identification of foods and dietary compounds that can suppress aromatase activity. In vitro and in vivo studies have found that grapes and mushrooms contain chemicals that can inhibit aromatase. Therefore, a diet that includes grapes and mushrooms would be considered preventative against breast cancer. Another area of our aromatase research is the elucidation of the regulatory mechanism of aromatase expression in breast cancer tissue. Increased aromatase expression in breast tumors is attributed to changes in the transcriptional control of aromatase expression. Whereas promoter I.4 is the main promoter that controls aromatase expression in noncancerous breast tissue, promoters II and I.3 are the dominant promoters that drive aromatase expression in breast cancer tissue. Our recent gene regulation studies revealed that in cancerous versus normal tissue, several positive regulatory proteins (e.g., nuclear receptors and CREB1) are present at higher levels and several negative regulatory proteins (e.g., snail and slug proteins) are present at lower levels. This may explain why the activity of promoters II and I.3 is upregulated in cancerous tissue. In addition, our in vitro transcription/translation analysis using plasmids containing T7 promoter and the human snail gene as a reporter capped with different untranslated exon Is revealed that exon

  3. Effects of coating materials on nanoindentation hardness of enamel and adjacent areas.

    PubMed

    Alsayed, Ehab Z; Hariri, Ilnaz; Nakashima, Syozi; Shimada, Yasushi; Bakhsh, Turki A; Tagami, Junji; Sadr, Alireza

    2016-06-01

    Materials that can be applied as thin coatings and actively release fluoride or other bioavailable ions for reinforcing dental hard tissue deserve further investigation. In this study we assessed the potential of resin coating materials in protection of underlying and adjacent enamel against demineralization challenge using nanoindentation. Enamel was coated using Giomer (PRG Barrier Coat, PBC), resin-modified glass-ionomer (Clinpro XT Varnish, CXT), two-step self-etch adhesive (Clearfil SE Protect, SEP) or no coating (control). After 5000 thermal cycles and one-week demineralization challenge, Martens hardness of enamel beneath the coating, uncoated area and intermediate areas was measured using a Berkovich tip under 2mN load up to 200μm depth. Integrated hardness and 10-μm surface zone hardness were compared among groups. Nanoindentation and scanning electron microscopy suggested that all materials effectively prevented demineralization in coated area. Uncoated areas presented different hardness trends; PBC showed a remarkable peak at the surface zone before reaching as low as the control, while CXT showed relatively high hardness values at all depths. Ion-release from coating materials affects different layers of enamel. Coatings with fluoride-releasing glass fillers contributed to reinforcement of adjacent enamel. Surface prereacted glass filler-containing PBC superficially protected neighboring enamel against demineralization, while resin-modified glass-ionomer with calcium (CXT) improved in-depth protection. Cross-sectional hardness mapping of enamel on a wide range of locations revealed minute differences in its structure. Copyright © 2016 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  4. Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics.

    PubMed

    Hatzfeld, Mechthild; Keil, René; Magin, Thomas M

    2017-06-01

    Adherens junctions (AJs) and desmosomes connect the actin and keratin filament networks of adjacent cells into a mechanical unit. Whereas AJs function in mechanosensing and in transducing mechanical forces between the plasma membrane and the actomyosin cytoskeleton, desmosomes and intermediate filaments (IFs) provide mechanical stability required to maintain tissue architecture and integrity when the tissues are exposed to mechanical stress. Desmosomes are essential for stable intercellular cohesion, whereas keratins determine cell mechanics but are not involved in generating tension. Here, we summarize the current knowledge of the role of IFs and desmosomes in tissue mechanics and discuss whether the desmosome-keratin scaffold might be actively involved in mechanosensing and in the conversion of chemical signals into mechanical strength. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. Early Verb Constructions in French: Adjacency on the Left Edge

    ERIC Educational Resources Information Center

    Veneziano, Edy; Clark, Eve V.

    2016-01-01

    Children acquiring French elaborate their early verb constructions by adding adjacent morphemes incrementally at the left edge of core verbs. This hypothesis was tested with 2657 verb uses from four children between 1;3 and 2;7. Consistent with the Adjacency Hypothesis, children added clitic subjects frst only to present tense forms (as in…

  6. Adjacent bin stability evaluating for feature description

    NASA Astrophysics Data System (ADS)

    Nie, Dongdong; Ma, Qinyong

    2018-04-01

    Recent study improves descriptor performance by accumulating stability votes for all scale pairs to compose the local descriptor. We argue that the stability of a bin depends on the differences across adjacent pairs more than the differences across all scale pairs, and a new local descriptor is composed based on the hypothesis. A series of SIFT descriptors are extracted from multiple scales firstly. Then the difference value of the bin across adjacent scales is calculated, and the stability value of a bin is calculated based on it and accumulated to compose the final descriptor. The performance of the proposed method is evaluated with two popular matching datasets, and compared with other state-of-the-art works. Experimental results show that the proposed method performs satisfactorily.

  7. Repair of Craniomaxillofacial Traumatic Soft Tissue Defects With Tissue Expansion in the Early Stage.

    PubMed

    Han, Yan; Zhao, Jianhui; Tao, Ran; Guo, Lingli; Yang, Hongyan; Zeng, Wei; Song, Baoqiang; Xia, Wensen

    2017-09-01

    Craniomaxillofacial traumatic soft tissue defects severely affect the function and appearance of the patients. The traditional skin grafting or free flap transplantation can only close the defects in the early stage of operation but cannot ensure similar color, texture, and relative aesthetic contour. In the present study, the authors have explored a novel strategy to repair craniomaxillofacial traumatic soft tissue defects by tissue expansion in the early stage and have obtained satisfactory results. Eighteen patients suffering large craniomaxillofacial traumatic soft tissue defects were treated by thorough debridement leaving the wounds unclosed or simply closed with thin split-thickness scalp grafts, adjacent expander implantation in the first stage, and expanded flap transposition in the second stage. There were 11 male patients and 7 female patients ranging in age from 3.5 to 40 years (mean, 19.4 ± 12.2 years), with average 15 months follow-up (range, 3-67 months). The average expansion time was 74.3 days (range, 53-96 days). The 18 patients with a total of 22 expanders were treated with satisfactory results. All the flaps survived and the skin color, texture, and contour well matched those of the peripheral tissue. Only 1 complication of infection happened in the 18 cases (5.56%) and the 22 expanders (4.55%), which was similar to the rate reported in the literature. No other complications related to the expanders occurred. Debridement and tissue expansion in the early stage has been proved to be a more effective strategy to repair craniomaxillofacial traumatic soft tissue defects. This strategy can not only achieve satisfactory color, unbulky and well-matched texture similar to normal, but also avoid unnecessary donor site injuries.

  8. Soft tissue grafting to improve implant esthetics

    PubMed Central

    Kassab, Moawia M

    2010-01-01

    Dental implants are becoming the treatment of choice to replace missing teeth, especially if the adjacent teeth are free of restorations. When minimal bone width is present, implant placement becomes a challenge and often resulting in recession and dehiscence around the implant that leads to subsequent gingival recession. To correct such defect, the author turned to soft tissue autografting and allografting to correct a buccal dehiscence around tooth #24 after a malpositioned implant placed by a different surgeon. A 25-year-old woman presented with the chief complaint of gingival recession and exposure of implant threads around tooth #24. The patient received three soft tissue grafting procedures to augment the gingival tissue. The first surgery included a connective tissue graft to increase the width of the keratinized gingival tissue. The second surgery included the use of autografting (connective tissue graft) to coronally position the soft tissue and achieve implant coverage. The third and final surgery included the use of allografting material Alloderm to increase and mask the implant from showing through the gingiva. Healing period was uneventful for the patient. After three surgical procedures, it appears that soft tissue grafting has increased the width and height of the gingiva surrounding the implant. The accomplished thickness of gingival tissue appeared to mask the showing of implant threads through the gingival tissue and allowed for achieving the desired esthetic that the patient desired. The aim of the study is to present a clinical case with soft tissue grafting procedures. PMID:23662087

  9. System and method for moving a probe to follow movements of tissue

    NASA Technical Reports Server (NTRS)

    Feldstein, C.; Andrews, T. W.; Crawford, D. W.; Cole, M. A. (Inventor)

    1981-01-01

    An apparatus is described for moving a probe that engages moving living tissue such as a heart or an artery that is penetrated by the probe, which moves the probe in synchronism with the tissue to maintain the probe at a constant location with respect to the tissue. The apparatus includes a servo positioner which moves a servo member to maintain a constant distance from a sensed object while applying very little force to the sensed object, and a follower having a stirrup at one end resting on a surface of the living tissue and another end carrying a sensed object adjacent to the servo member. A probe holder has one end mounted on the servo member and another end which holds the probe.

  10. Objectifying the Adjacent and Opposite Angles: A Cultural Historical Analysis

    ERIC Educational Resources Information Center

    Daher, Wajeeh; Musallam, Nadera

    2018-01-01

    The angle topic is central to the development of geometric knowledge. Two of the basic concepts associated with this topic are the adjacent and opposite angles. It is the goal of the present study to analyze, based on the cultural historical semiotics framework, how high-achieving seventh grade students objectify the adjacent and opposite angles'…

  11. The Volpe Center GPS Adjacent Band Compatibility Program Plan : GPS Adjacent Band Compatibility Workshop, Volpe Center, Cambridge MA

    DOT National Transportation Integrated Search

    2014-09-18

    Approach to DOT GPS Adjacent Band Compatibility Assessment. Identify forums and provide public outreach to make sure the progress and work are as open and transparent as possible. Develop an implementation plan that incorporates aspects from the DOT ...

  12. Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome.

    PubMed

    Schucht, Philippe; Seidel, Kathleen; Beck, Jürgen; Murek, Michael; Jilch, Astrid; Wiest, Roland; Fung, Christian; Raabe, Andreas

    2014-12-01

    Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)-guided surgery in patients with glioblastoma adjacent to eloquent tissue. The authors prospectively studied 72 consecutive patients who underwent 5-ALA-guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11-20 mA, n = 13; 6-10 mA, n = 10; 4-5 mA, n = 13; and 1-3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST. A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for

  13. Do Mangroves Subsidize Carbon to Adjacent Mudflat Fish Communities?

    NASA Astrophysics Data System (ADS)

    Henkel, S.; Kasten, S.; Hartmann, J.; Staubwasser, M.; Hernandez, M. F.; West, L.; Midway, S. R.; Polito, M. J.

    2017-12-01

    Mangroves are often implicated as energetic sources for fisheries productivity. However, the validity of this connection still remains in contention. Stable isotopes may provide answers by tracking the use of specific basal carbon sources in fish and invertebrates living in mangrove-mudflat habitat mosaics. We analyzed 307 consumer samples representing n=44 fish and invertebrate species collected from mangrove forest creeks and adjacent mudflats in coastal Tanzania using bulk carbon and nitrogen stable isotope analysis. Given the proposed high productivity of mangrove habitats, we hypothesize that mudflat communities will have carbon stable isotope values similar to mangrove communities either through the flux of mangrove carbon into adjacent mudflats and/or via the movement of mudflat fish communities into and out of mangrove habitats. Alternatively, mangrove carbon is often refractory, which may result in mudflat communities with isotopic values that differ from those found in adjacent mangrove communities. This scenario would suggest limited carbon flow between mudflat and mangrove food webs and that the movement of fish into and out of mangrove habitats is related to shelter from predation more than feeding. Data analysis is ongoing to test these competing hypotheses. By understanding the contribution of mangrove carbon to adjacent habitats, managers in Tanzania can make better informed decisions regarding the protection of mangroves and the local fisheries, which are a crucial source of income and food.

  14. 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.

  15. Delta-like ligand 4: A predictor of poor prognosis in clear cell renal cell carcinoma

    PubMed Central

    WANG, WEI; YU, YI; WANG, YA; LI, XIAOMING; BAO, JUNSHENG; WU, GONGJIN; CHANG, HONG; SHI, TINGKAI; YUE, ZHONGJIN

    2014-01-01

    Delta-like ligand 4 (Dll4)-Notch signaling is important in tumor angiogenesis; however, the prognostic value of D114 detection in patients with clear cell renal cell carcinoma (CCRCC) remains unclear. The present study aimed to determine whether the presence of high Dll4 expression levels was correlated with poor prognosis in CCRCC following curative resection. The D114 expression levels in four paired samples of CCRCC tissues and adjacent normal renal tissues were assayed by western blotting. Surgical specimens comprised 121 CCRCC tissue samples and 65 normal renal tissue samples, obtained from patients with CCRCC. The specimens were immunohistochemically assessed to determine Dll4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression levels. The prognostic significance of Dll4 expression levels was evaluated by the Kaplan-Meier method and Cox regression analysis. The correlation between Dll4 expression levels and VEGFR-2 expression levels, tumor stage, tumor grade and metastasis, was examined by χ2 test and multivariate logistic regression. As determined by the western blotting results, Dll4 protein expression levels were significantly increased in CCRCC tissues compared with those in adjacent non-cancerous tissues. From the analysis of the surgical specimens, 53 (43.8%) CCRCC patients exhibited immunohistochemically high Dll4 expression levels and 68 (56.2%) patients exhibited low Dll4 expression levels. The survival curves revealed that the patients with high Dll4 expression levels had significantly shorter survival times than the patients with low Dll4 expression levels (P<0.001). Multivariate survival analysis demonstrated that the presence of high Dll4 expression levels was independently associated with reduced overall survival and progression-free survival times (P=0.021 and 0.034, respectively). A positive correlation was also identified between Dll4 and VEGFR-2 expression levels (P=0.001). In conclusion, the results show that the

  16. Adjacent-Categories Mokken Models for Rater-Mediated Assessments

    PubMed Central

    Wind, Stefanie A.

    2016-01-01

    Molenaar extended Mokken’s original probabilistic-nonparametric scaling models for use with polytomous data. These polytomous extensions of Mokken’s original scaling procedure have facilitated the use of Mokken scale analysis as an approach to exploring fundamental measurement properties across a variety of domains in which polytomous ratings are used, including rater-mediated educational assessments. Because their underlying item step response functions (i.e., category response functions) are defined using cumulative probabilities, polytomous Mokken models can be classified as cumulative models based on the classifications of polytomous item response theory models proposed by several scholars. In order to permit a closer conceptual alignment with educational performance assessments, this study presents an adjacent-categories variation on the polytomous monotone homogeneity and double monotonicity models. Data from a large-scale rater-mediated writing assessment are used to illustrate the adjacent-categories approach, and results are compared with the original formulations. Major findings suggest that the adjacent-categories models provide additional diagnostic information related to individual raters’ use of rating scale categories that is not observed under the original formulation. Implications are discussed in terms of methods for evaluating rating quality. PMID:29795916

  17. 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

  18. 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.

  19. Biomechanical performance of rigid compared to dynamic anterior cervical plating: analysis of adjacent upper and lower level compressive forces.

    PubMed

    Connor, David E; Shamieh, Khader Samer; Ogden, Alan L; Mukherjee, Debi P; Sin, Anthony; Nanda, Anil

    2012-12-01

    Dynamic anterior cervical plating is well established as a means of enhancing graft loading and subsequent arthrodesis. Current concerns center on the degree of adjacent-level stress induced by these systems. The aim of this study was to evaluate and compare the load transferred to adjacent levels for single-level anterior cervical discectomy and fusion utilizing rigid compared to dynamic anterior plating systems. Nine cadaveric adult human cervical spine specimens were subjected to range-of-motion testing prior to and following C5-C6 anterior cervical discectomy and fusion procedures. Interbody grafting was performed with human fibula tissue. Nondestructive biomechanical testing included flexion/extension and lateral bending loading modes. A constant displacement of 5mm was applied in each direction and the applied load was measured in newtons (N). Specimens were tested in the following order: intact, following discectomy, after rigid plating, then after dynamic plating. Adjacent level (C4-C5 [L(S)] and C6-C7 [L(I)]) compressive forces were measured using low profile load cells inserted into each disc space. The measured load values for plating systems were then normalized using values measured for the intact specimens. Mean loads transferred to L(S) and L(I) during forced flexion in specimens with rigid plating were 23.47 N and 8.76 N, respectively; while the corresponding values in specimens with dynamic plating were 18.55 N and 1.03 N, respectively. Dynamic plating yielded no significant change at L(I) and a 21.0% decrease in load at L(S) when compared with rigid plating, although the difference was not significant. The observed trend suggests that dynamic plating may diminish superior adjacent level compressive stresses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. [The chemical action of gun powder gases on biological tissues in a point-blank shot].

    PubMed

    Popov, V L; Isakov, V D; Babakhanian, R V; Karnasevich, Iu A

    1992-01-01

    Chemical effect of gun powder gas on the biologic tissues manifests by red-brown staining of the tissues, mainly at the expense of methemoglobin and sulfhemoglobin. Scarlet staining of the tissues at the edges of gun-shot wounds is not a specific marker of a shot made from a short distance; it may emerge several hours after wounding at the expense of hydroxy-hemoglobin and is not at all related to the chemical effect of gun powder gas. The conditions conducive to scarlet staining are an open wound permitting free oxygenation by air oxygen and hemoglobin transfer from the injured red cells into blood plasma and adjacent tissues.

  1. 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. 

  2. 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.

  3. Cytotoxic consequences of Halloysite nanotube/iron oxide nanocomposite and iron oxide nanoparticles upon interaction with bacterial, non-cancerous and cancerous cells.

    PubMed

    Abhinayaa, R; Jeevitha, G; Mangalaraj, D; Ponpandian, N; Vidhya, Kalieswaran; Angayarkanni, Jayaraman

    2018-05-19

    Cytotoxic effects of iron oxide (Fe 3 O 4 ) nanoparticles and Halloysite nanotube/iron oxide (HNT/Fe 3 O 4 ) nanocomposite are compared based on their interaction with Gram-negative bacteria Escherichia coli and Gram-positive bacteria Bacillus subtilis. Similarly, the action of these two nanomaterials on non-cancerous Vero cell lines and human lung cancerous (A-549) cell lines are compared. The cytotoxicity studies on Fe 3 O 4 nanoparticles and HNT/Fe 3 O 4 nanocomposite showed difference in the rate of killing of bacterial cells. This is reflected in differential cell growth, cell membrane integrity loss, lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production. These factors are measured over a range of concentrations of Fe 3 O 4 nanoparticles and HNT/Fe 3 O 4 nanocomposite and at specified time intervals, to test if there is any statistically significant difference between the toxicity of the two nanomaterials. Between the two nanomaterials, HNT/Fe 3 O 4 nanocomposite is found to be less toxic to bacterial cells than Fe 3 O 4 nanoparticles. HNT, when attached to the Fe 3 O 4 nanoparticles, changes their surface characteristics and suppresses their inherent toxicity on bacteria. In the study on the effect on cell lines, Fe 3 O 4 nanoparticles and HNT/Fe 3 O 4 nanocomposite are both seen to be biocompatible with Vero cell lines. However, HNT/Fe 3 O 4 nanocomposite showed more cytotoxicity than Fe 3 O 4 nanoparticles on A-549 cell lines. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Long non-coding RNA biomarker for human laryngeal squamous cell carcinoma prognosis.

    PubMed

    Chen, Jingjing; Shen, Zhisen; Deng, Hongxia; Zhou, Wei; Liao, Qi; Mu, Ying

    2018-05-15

    Long non-coding RNAs (lncRNA) were discovered in tumors. The regulation of lncRNA in human laryngeal squamous cell carcinoma (LSCC) remains incomplete. Uncovering the potential of lncRNA to stratify the prognosis of LSCC and streamline the vast amount of clinical information will affect medical interventions. The surgical resected LSCC tissues, adjacent non-cancerous tissues (ANCT) and lymph node metastatic tissue (LNM) were collected from 76 patients for lncRNA AC008440.10 expression assay. The stages of LSCC and LNM were classified accordingly. We integrated the epigenetic information with enhanced CT imaging and pathological evaluations to predict the patients' survival by comprehensive statistical algorithms using equal weighting. Significant downregulation of lncRNA AC008440.10 was detected in LSCC tumor and metastatic lymph node in advanced stage of patient samples compared with those in early stage. The pattern of differentially expressed AC008440.10 displayed a clear trend that significantly related to tumor progression. The downregulation of lncRNA AC008440.10 correlates with increasing risk of metastasis, poor prognosis and patient survival. The potential for lncRNA AC008440.10 to be developed as a novel biomarker for stratification of the prognosis was especially promising when clinic parameters were hybridized with equal weight, and using a panel of complementary parameters yielded a more powerful predictability of LSCC prognosis than any single parameter individually. Copyright © 2017. Published by Elsevier B.V.

  5. Gene and protein expression of oestrogen-β and progesterone receptors in facial melasma and adjacent healthy skin in women.

    PubMed

    Tamega, A de A; Miot, H A; Moço, N P; Silva, M G; Marques, M E A; Miot, L D B

    2015-04-01

    Compare gene and protein expression for oestrogen receptor-β (ER-β) and progesterone receptor (PR) in facial melasma and adjacent healthy skin. A cross-sectional study including 42 women with facial melasma, conducted at the Dermatology Service of Botucatu Medical School of São Paulo State University, Brazil. Biopsies of the melasma skin were performed, together with healthy surrounding skin. The gene expression (real-time PCR) of the hormone receptors in the tissue was evaluated. Subsequently, skin fragments were immunostained for nuclear ER-β and PR, evaluated according to their HSCORE (epidermis) and percentage of staining per microscopic field (dermis). Messenger RNA tissue expression for ER-β and PR showed no difference between melasma-affected skin fragments and the healthy perilesional areas (P > 0.2). Median nuclear epithelial expression for ER-β and PR was higher in lesioned skin (HSCORE 157 and 58) than in the healthy perilesional skin (HSCORE 97 and 19; P < 0.01), with no difference in dermal immunostaining. Nuclear histological expression for ER-β was associated to sun-induced melasma and negative familiar background; PR expression was associated to sun-induced melasma and darker phototypes. No difference was observed in gene expression for oestrogen-β and progesterone receptors in melasma-affected skin compared with adjacent healthy skin. However, the higher protein expression of these receptors in melasma-affected epithelia suggests hormonal participation in the pathogenesis of this disease. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  6. Reaction of the rat tissues to implantation of polyhydroxyalkanoate films and ultrafine fibers.

    PubMed

    Maiborodin, I V; Shevela, A I; Morozov, V V; Novikova, Ya V; Matveeva, V A; Drovosekov, M N; Barannik, M I

    2013-01-01

    The reaction of various tissues of rats to implantation of polyhydroxyalkanoate films and ultrafine fibers was studied by optic microscopy. Implantation of polyhydroxyalkanoate films into the abdominal cavity caused a peritoneal reaction, leading after 1 month to the formation of fibrous adhesions between polyhydroxyalkanoate and intestinal loops. Under the skin and in the muscle tissue polyhydroxyalkanoate films were encapsulated in a thick fibrous capsule. Implantation of polyhydroxyalkanoate ultrathin fibers led to formation of foreign body granulomas in all tissues with perifocal inflammation and sclerosis of the adjacent tissues. The polymer was fragmented in these granulomas and phagocytosed by macrophages with the formation of giant foreign body cells. Hence, polyhydroxyalkanoate materials implanted in vivo caused chronic granulomatous inflammatory reaction and were very slowly destroyed by macrophages.

  7. Biexponential Characterization of Prostate Tissue Water Diffusion Decay Curves Over an Extended b-factor Range

    PubMed Central

    Mulkern, Robert V.; Barnes, Agnieszka Szot; Haker, Steven J.; Hung, Yin P.; Rybicki, Frank J.; Maier, Stephan E.; Tempany, Clare M.C.

    2006-01-01

    Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging exams at 1.5 T, a single 10 mm thick axial slice was scanned with a line scan diffusion imaging (LSDI) sequence in which 14 equally spaced b- factors from 5 to 3500 s/mm2 were sampled along three orthogonal diffusion sensitization directions in 6 minutes. Due to the combination of long scan time and limited volume coverage associated with the multi-b- factor, multi-directional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed non-cancerous regions of interest (ROI’s) within the central gland (CG) and peripheral zone (PZ). Histology from pre-scan biopsy (N = 9) and post-surgical resection (N = 4) was subsequently employed to help confirm that the ROIs sampled were non-cancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia (BPH) which is prevalent in this population. The water signal decays with b- factor from all ROI’s were clearly non-monoexponential and better served with bi- vs monoexponential fits, as tested using λ2 based F-test analyses. Fits to biexponential decay functions yielded inter-subject fast diffusion component fractions on the order of 0.73 ± 0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68 ± 0.39 and 2.52 ± 0.38 μm2/ms and slow diffusion coefficients of 0.44 ± 0.16 and 0.23 ± 0.16 um2/ms for CG and PZ ROI’s, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney non-parametric test (P < 0.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when

  8. Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range.

    PubMed

    Mulkern, Robert V; Barnes, Agnieszka Szot; Haker, Steven J; Hung, Yin P; Rybicki, Frank J; Maier, Stephan E; Tempany, Clare M C

    2006-06-01

    Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging examinations at 1.5 T, a single 10-mm-thick axial slice was scanned with a line scan diffusion imaging sequence in which 14 equally spaced b factors from 5 to 3,500 s/mm(2) were sampled along three orthogonal diffusion sensitization directions in 6 min. Due to the combination of long scan time and limited volume coverage associated with the multi-b-factor, multidirectional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed noncancerous regions of interest (ROIs) within the central gland (CG) and peripheral zone (PZ). Histology from prescan biopsy (n=9) and postsurgical resection (n=4) was subsequently employed to help confirm that the ROIs sampled were noncancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia, which is prevalent in this population. The water signal decays with b factor from all ROIs were clearly non-monoexponential and better served with bi- vs. monoexponential fits, as tested using chi(2)-based F test analyses. Fits to biexponential decay functions yielded intersubject fast diffusion component fractions in the order of 0.73+/-0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68+/-0.39 and 2.52+/-0.38 microm(2)/ms and slow diffusion coefficients of 0.44+/-0.16 and 0.23+/-0.16 um(2)/ms for CG and PZ ROIs, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney nonparametric test (P<.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b

  9. Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

    PubMed

    Fahlén, M; Zhang, H; Löfgren, L; Masironi, B; von Schoultz, E; von Schoultz, B; Sahlin, L

    2017-05-01

    Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

  10. Chloroformate derivatization for tracing the fate of Amino acids in cells and tissues by multiple stable isotope resolved metabolomics (mSIRM).

    PubMed

    Yang, Ye; Fan, Teresa W-M; Lane, Andrew N; Higashi, Richard M

    2017-07-11

    applied this method to profile amino acids and their labeling patterns in 13 C and 2 H doubly labeled PC9 cell extracts, cancerous and non-cancerous tissue extracts from a lung cancer patient and their protein hydrolysates as well as plasma extracts from mice fed with a liquid diet containing 13 C 6 -glucose (Glc). The multi-element isotopologue distributions provided key insights into amino acid metabolism and intracellular pools in human lung cancer tissues in high detail. The 13 C labeling of Asp and Glu revealed de novo synthesis of these amino acids from 13 C 6 -Glc via the Krebs cycle, specifically the elevated level of 13 C 3 -labeled Asp and Glu in cancerous versus non-cancerous lung tissues was consistent with enhanced pyruvate carboxylation. In addition, tracking the fate of double tracers, ( 13 C 6 -Glc +  2 H 2 -Gly or 13 C 6 -Glc +  2 H 3 -Ser) in PC9 cells clearly resolved pools of Ser and Gly synthesized de novo from 13 C 6 -Glc ( 13 C 3 -Ser and 13 C 2 -Gly) versus Ser and Gly derived from external sources ( 2 H 3 -Ser, 2 H 2 -Gly). Moreover the complex 2 H labeling patterns of the latter were results of Ser and Gly exchange through active Ser-Gly one-carbon metabolic pathway in PC9 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Extra-embryonic tissue spreading directs early embryo morphogenesis in killifish

    PubMed Central

    Reig, Germán; Cerda, Mauricio; Sepúlveda, Néstor; Flores, Daniela; Castañeda, Victor; Tada, Masazumi; Härtel, Steffen; Concha, Miguel L.

    2017-01-01

    The spreading of mesenchymal-like cell layers is critical for embryo morphogenesis and tissue repair, yet we know little of this process in vivo. Here we take advantage of unique developmental features of the non-conventional annual killifish embryo to study the principles underlying tissue spreading in a simple cellular environment, devoid of patterning signals and major morphogenetic cell movements. Using in vivo experimentation and physical modelling we reveal that the extra-embryonic epithelial enveloping cell layer, thought mainly to provide protection to the embryo, directs cell migration and the spreading of embryonic tissue during early development. This function relies on the ability of embryonic cells to couple their autonomous random motility to non-autonomous signals arising from the expansion of the extra-embryonic epithelium, mediated by cell membrane adhesion and tension. Thus, we present a mechanism of extra-embryonic control of embryo morphogenesis that couples the mechanical properties of adjacent tissues in the early killifish embryo. PMID:28580937

  12. Environmental characteristics of the Grand Fir Mosaic and adjacent habitat types

    Treesearch

    Dennis E. Ferguson; John C. Byrne

    2000-01-01

    Grand Fir Mosaic habitats differ from adjacent forest habitats in their slow rate of secondary succession to woody vegetation. Remote monitoring stations were used to sample the environment at a Grand Fir Mosaic site and three adjacent habitat types. The Grand Fir Mosaic site has shorter growing seasons, cooler temperatures, and more soil moisture than the other sites...

  13. 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

  14. GFRA3 promoter methylation may be associated with decreased postoperative survival in gastric cancer.

    PubMed

    Eftang, Lars Lohne; Klajic, Jovana; Kristensen, Vessela N; Tost, Jörg; Esbensen, Qin Ying; Blom, Gustav Peter; Bukholm, Ida Rashida Khan; Bukholm, Geir

    2016-03-16

    A large number of epigenetic alterations has been found to be implicated in the etiology of gastric cancer. We have studied the DNA methylation status of 27 500 gene promoter regions in 24 gastric adenocarcinomas from a Norwegian cohort, and aimed at identifying the hypermethylated regions. We have compared our findings to the gene expression in the same tissue, and linked our results to prognosis and survival. Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 24 patients following surgical resection of the tumor. Genome-wide DNA methylation profiling of the tumor and matched non-cancerous mucosa was performed. The results were compared to whole transcriptome cDNA microarray analysis of the same material. Most of the gene promoter regions in both types of tissue showed a low degree of methylation, however there was a small, but significant hypermethylation of the tumors. Hierarchical clustering showed separate grouping of the tumor and normal tissue. Hypermethylation of the promoter region of the GFRA3 gene showed a strong correlation to post-operative survival and several of the clinicopathological parameters, however no difference was found between the two main histological types of gastric cancer. There was only a modest correlation between the DNA methylation status and gene expression. The different DNA methylation clusters of the tumors and normal tissue indicate that aberrant DNA methylation is a distinct feature of gastric cancer, although there is little difference in the overall, and low, methylation levels between the two tissue types. The GFRA3 promoter region showed marked hypermethylation in almost all tumors, and its correlation with survival and other clinicopathological parameters may have important prognostic significance.

  15. Creation of a virtual cutaneous tissue bank

    NASA Astrophysics Data System (ADS)

    LaFramboise, William A.; Shah, Sujal; Hoy, R. W.; Letbetter, D.; Petrosko, P.; Vennare, R.; Johnson, Peter C.

    2000-04-01

    Cellular and non-cellular constituents of skin contain fundamental morphometric features and structural patterns that correlate with tissue function. High resolution digital image acquisitions performed using an automated system and proprietary software to assemble adjacent images and create a contiguous, lossless, digital representation of individual microscope slide specimens. Serial extraction, evaluation and statistical analysis of cutaneous feature is performed utilizing an automated analysis system, to derive normal cutaneous parameters comprising essential structural skin components. Automated digital cutaneous analysis allows for fast extraction of microanatomic dat with accuracy approximating manual measurement. The process provides rapid assessment of feature both within individual specimens and across sample populations. The images, component data, and statistical analysis comprise a bioinformatics database to serve as an architectural blueprint for skin tissue engineering and as a diagnostic standard of comparison for pathologic specimens.

  16. MINARETS WILDERNESS AND ADJACENT AREAS, CALIFORNIA.

    USGS Publications Warehouse

    Huber, N. King; Thurber, Horace K.

    1984-01-01

    A mineral survey of the Minarets Wilderness and adjacent areas in the central Sierra Nevada, California was conducted. The results of the survey indicate that the study area has a substantiated resource potential for small deposits of copper, silver, zinc, lead, and iron, and a probable mineral-resource potential for molybdenum. No energy-resource potential was identified in the study.

  17. Trace contaminant concentrations in the Kara Sea and its adjacent rivers, Russia.

    PubMed

    Sericano, J L; Brooks, J M; Champ, M A; Kennicutt, M C; Makeyev, V V

    2001-11-01

    Trace organic (chlorinated pesticides, PCBs, PAHs and dioxins/furans) and trace metal concentrations were measured in surficial sediment and biological tissues (i.e., worms, crustaceans, bivalve molluscs, and fish livers) collected from the Russian Arctic. Total DDT, chlordane, PCB and PAH concentrations ranged from ND to 1.2, ND to <0.1, ND to 1.5 and <20-810 ng g(-1), respectively, in a suite of 40 surficial sediment samples from the Kara Sea and the adjacent Ob and Yenisey Rivers. High sedimentary concentrations of contaminants were found in the lower part of the Yenisey River below the salt wedge. Total dioxins/furans were analysed in a subset of 20 sediment samples and ranged from 1.4 to 410 pg g(-1). The highest trace organic contaminant concentrations were found in organisms, particularly fish livers. Concentrations as high as 89 ng g(-1) chlordane; 1010 ng g(-1) total DDTs; 460 ng g(-1) total PCBs; and 1110 ng g(-1) total PAH, were detected. A subset of 11 tissue samples was analysed for dioxins and furans with total concentrations ranging from 12 to 61 pg g(-1). Concentrations of many trace organic and metal contaminants in the Kara Sea appear to originate from riverine sources and atmospheric transport from more temperate areas. Most organic contaminant concentrations in sediments were low; however, contaminants are being concentrated in organisms and may pose a health hazard for inhabitants of coastal villages.

  18. Downregulation of gasdermin D promotes gastric cancer proliferation by regulating cell cycle-related proteins.

    PubMed

    Wang, Wei Jie; Chen, Di; Jiang, Ming Zuo; Xu, Bing; Li, Xiao Wei; Chu, Yi; Zhang, Yu Jie; Mao, Ren; Liang, Jie; Fan, Dai Ming

    2018-02-01

    To explore the relationship between gasdermin D (GSDMD) and gastric cancer (GC) cell proliferation, and to determine whether the downregulated expression of GSDMD contributed to the tumorigenesis and proliferation of GC cells. GSDMD expressions in GC tissues and matched adjacent non-cancerous tissues were assessed by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. The effect of GSDMD on cell proliferation in vitro was assessed by the colony formation assay and cell viability assays. In vivo, xenografted tumors in nude mice were evaluated. The cell cycle was analyzed by flow cytometry. In addition, the alterations of several cell cycle-related and cell signaling pathway proteins were analyzed by Western blot. GSDMD expression was decreased in GC, and the decreased expression of GSDMD could markedly promote the proliferation of tumors in vivo and in vitro. The downregulation of GSDMD accelerated S/G 2 cell transition by activating extracellular signal regulated kinase, signal transducer and activator of transcription 3 and phosphatidylinositol 3 kinase/protein kinase B signaling pathways and regulating cell cycle-related proteins in GC. GSDMD may protect against cell proliferation of GC, and it may be used as a diagnostic and treatment strategy for GC. © 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  19. Roles of Perivascular Adipose Tissue in the Pathogenesis of Atherosclerosis

    PubMed Central

    Tanaka, Kimie; Sata, Masataka

    2018-01-01

    Traditionally, it is believed that white adipose tissues serve as energy storage, heat insulation, and mechanical cushion, whereas non-shivering thermogenesis occurs in brown adipose tissue. Recent evidence revealed that adipose tissue secretes many types of cytokines, called as adipocytokines, which modulate glucose metabolism, lipid profile, appetite, fibrinolysis, blood pressure, and inflammation. Most of the arteries are surrounded by perivascular adipose tissue (PVAT). PVAT has been thought to be simply a structurally supportive tissue for vasculature. However, recent studies showed that PVAT influences vasodilation and vasocontraction, suggesting that PVAT regulates vascular tone and diameter. Adipocytokines secreted from PVAT appear to have direct access to the adjacent arterial wall by diffusion or via vasa vasorum. In fact, PVAT around atherosclerotic lesions and mechanically-injured arteries displayed inflammatory cytokine profiles, suggesting that PVAT functions to promote vascular lesion formation. Many clinical studies revealed that increased accumulation of epicardial adipose tissue (EAT), which surrounds coronary arteries, is associated with coronary artery disease. In this review article, we will summarize recent findings about potential roles of PVAT in the pathogenesis of atherosclerosis, particularly focusing on a series of basic and clinical studies from our laboratory. PMID:29487532

  20. Obesity Decreases Perioperative Tissue Oxygenation

    PubMed Central

    Kabon, Barbara; Nagele, Angelika; Reddy, Dayakar; Eagon, Chris; Fleshman, James W.; Sessler, Daniel I.; Kurz, Andrea

    2005-01-01

    Background: Obesity is an important risk factor for surgical site infections. The incidence of surgical wound infections is directly related to tissue perfusion and oxygenation. Fat tissue mass expands without a concomitant increase in blood flow per cell, which might result in a relative hypoperfusion with decreased tissue oxygenation. Consequently, we tested the hypotheses that perioperative tissue oxygen tension is reduced in obese surgical patients. Furthermore, we compared the effect of supplemental oxygen administration on tissue oxygenation in obese and non-obese patients. Methods: Forty-six patients undergoing major abdominal surgery were assigned to one of two groups according to their body mass index (BMI): BMI < 30 kg/m2 (non-obese) and BMI ≥ 30 kg/m2 (obese). Intraoperative oxygen administration was adjusted to arterial oxygen tensions of ≈150 mmHg and ≈300 mmHg in random order. Anesthesia technique and perioperative fluid management were standardized. Subcutaneous tissue oxygen tension was measured with a polarographic electrode positioned within a subcutaneous tonometer in the lateral upper arm during surgery, in the recovery room, and on the first postoperative day. Postoperative tissue oxygen was also measured adjacent to the wound. Data were compared with unpaired two tailed t-tests and Wilcoxon rank-sum tests; P < 0.05 was considered statistically significant. Results: Intraoperative subcutaneous tissue oxygen tension was significantly less in the obese patients at baseline (36 vs. 57 mmHg, P = 0.002) and with supplemental oxygen administration (47 vs. 76 mmHg, P = 0.014). Immediate postoperative tissue oxygen tension was also significantly less in subcutaneous tissue of the upper arm (43 vs. 54 mmHg, P = 0.011) as well as near the incision (42 vs. 62 mmHg, P = 0.012) in obese patients. In contrast, tissue oxygen tension was comparable in each group on the first postoperative morning. Conclusion: Wound and tissue hypoxia were common in obese

  1. Impact of Somatic Mutations in the D-Loop of Mitochondrial DNA on the Survival of Oral Squamous Cell Carcinoma Patients

    PubMed Central

    Lin, Jin-Ching; Wang, Chen-Chi; Jiang, Rong-San; Wang, Wen-Yi; Liu, Shih-An

    2015-01-01

    Objectives The aim of this study was to investigate somatic mutations in the D-loop of mitochondrial DNA (mtDNA) and their impact on survival in oral squamous cell carcinoma patients. Materials and Methods Surgical specimen confirmed by pathological examination and corresponding non-cancerous tissues were collected from 120 oral squamous cell carcinoma patients. The sequence in the D-loop of mtDNA from non-cancerous tissues was compared with that from paired cancer samples and any sequence differences were recognized as somatic mutations. Results Somatic mutations in the D-loop of mtDNA were identified in 75 (62.5%) oral squamous cell carcinoma patients and most of them occurred in the poly-C tract. Although there were no significant differences in demographic and tumor-related features between participants with and without somatic mutation, the mutation group had a better survival rate (5 year disease-specific survival rate: 64.0% vs. 43.0%, P = 0.0266). Conclusion Somatic mutation in D-loop of mtDNA was associated with a better survival in oral squamous cell carcinoma patients. PMID:25906372

  2. Analysis of proximal contact loss between implant-supported fixed dental prostheses and adjacent teeth in relation to influential factors and effects. A cross-sectional study.

    PubMed

    Byun, Soo-Jung; Heo, Seok-Mo; Ahn, Seung-Geun; Chang, Moontaek

    2015-06-01

    The aim was to analyze influential factors and effects of proximal contact loss between implant-supported fixed dental prostheses (FDP) and adjacent teeth. Ninety-four subjects treated with 135 FDPs supported by 188 implants were included. Degree of proximal contact tightness, food impaction, and periodontal/peri-implant tissue conditions were assessed in 191 proximal embrasures between implant-supported FDPs and adjacent teeth. Potential factors influencing proximal contact loss were estimated with the generalized estimation equation (GEE) procedure. Thirty-four percent of the proximal embrasures between implant-supported FDPs and teeth lost a proximal contact. The proximal contact loss rate continuously increased over the follow-up periods. A longer follow-up period, splinted implants, and mesial aspect of proximal contact were significant factors influencing the proximal contact loss in the univariate GEE analysis, whereas a longer follow-up period was the only significant factor in the multivariate GEE analysis. Food impaction was more frequently reported in the proximal contact loss group than the proximal contact group (odds ratio: 2.2). However, the proximal contact loss did not appear to affect the periodontal/peri-implant tissue conditions. Proximal contact loss between implant-supported FDPs and teeth occurred frequently and increased continuously over the follow-up period. The proximal contact loss significantly affected food impaction, but not the periodontal/peri-implant tissue conditions. Proximal contact loss should be carefully monitored during follow-up examinations in relation to food impaction. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Soft Tissue Injections in the Athlete

    PubMed Central

    Nepple, Jeffrey J.; Matava, Matthew J.

    2009-01-01

    Background: Injections into or adjacent to soft tissue structures, including muscle, tendon, bursa, and fascia, for pain relief and an earlier return to play have become common in the field of sports medicine. Study Design: Clinical review. Results: Corticosteroids, local anesthetics, and ketorolac tromethamine (Toradol) are the most commonly used injectable agents in athletes. The use of these injectable agents have proven efficacy in some disorders, whereas the clinical benefit for others remain questionable. All soft tissue injections performed for pain control and/or an anti-inflammatory effect have potentially serious side effects, which must be considered, especially in the pregame setting. Conclusions: The primary concern regarding corticosteroid and local anesthetic injections is an increased risk of tendon rupture associated with the direct injection into the tendon. Intramuscular Toradol injections provide significant analgesia, as well as an anti-inflammatory effect via its inhibitory effect on the cyclooxygenase pathway. The risk of bleeding associated with Toradol use is recognized but not accurately quantified. PMID:23015899

  4. Raman molecular imaging of brain frozen tissue sections.

    PubMed

    Kast, Rachel E; Auner, Gregory W; Rosenblum, Mark L; Mikkelsen, Tom; Yurgelevic, Sally M; Raghunathan, Aditya; Poisson, Laila M; Kalkanis, Steven N

    2014-10-01

    Raman spectroscopy provides a molecular signature of the region being studied. It is ideal for neurosurgical applications because it is non-destructive, label-free, not impacted by water concentration, and can map an entire region of tissue. The objective of this paper is to demonstrate the meaningful spatial molecular information provided by Raman spectroscopy for identification of regions of normal brain, necrosis, diffusely infiltrating glioma and solid glioblastoma (GBM). Five frozen section tissues (1 normal, 1 necrotic, 1 GBM, and 2 infiltrating glioma) were mapped in their entirety using a 300-µm-square step size. Smaller regions of interest were also mapped using a 25-µm step size. The relative concentrations of relevant biomolecules were mapped across all tissues and compared with adjacent hematoxylin and eosin-stained sections, allowing identification of normal, GBM, and necrotic regions. Raman peaks and peak ratios mapped included 1003, 1313, 1431, 1585, and 1659 cm(-1). Tissue maps identified boundaries of grey and white matter, necrosis, GBM, and infiltrating tumor. Complementary information, including relative concentration of lipids, protein, nucleic acid, and hemoglobin, was presented in a manner which can be easily adapted for in vivo tissue mapping. Raman spectroscopy can successfully provide label-free imaging of tissue characteristics with high accuracy. It can be translated to a surgical or laboratory tool for rapid, non-destructive imaging of tumor margins.

  5. MicroRNA meta-signature of oral cancer: evidence from a meta-analysis.

    PubMed

    Zeljic, Katarina; Jovanovic, Ivan; Jovanovic, Jasmina; Magic, Zvonko; Stankovic, Aleksandra; Supic, Gordana

    2018-03-01

    It was the aim of the study to identify commonly deregulated miRNAs in oral cancer patients by performing a meta-analysis of previously published miRNA expression profiles in cancer and matched normal non-cancerous tissue in such patients. Meta-analysis included seven independent studies analyzed by a vote-counting method followed by bioinformatic enrichment analysis. Amongst seven independent studies included in the meta-analysis, 20 miRNAs were found to be deregulated in oral cancer when compared with non-cancerous tissue. Eleven miRNAs were consistently up-regulated in three or more studies (miR-21-5p, miR-31-5p, miR-135b-5p, miR-31-3p, miR-93-5p, miR-34b-5p, miR-424-5p, miR-18a-5p, miR-455-3p, miR-450a-5p, miR-21-3p), and nine were down-regulated (miR-139-5p, miR-30a-3p, miR-376c-3p, miR-885-5p, miR-375, miR-486-5p, miR-411-5p, miR-133a-3p, miR-30a-5p). The meta-signature of identified miRNAs was functionally characterized by KEGG enrichment analysis. Twenty-four KEGG pathways were significantly enriched, and TGF-beta signaling was the most enriched signaling pathway. The highest number of meta-signature miRNAs was involved in the sphingolipid signaling pathway. Natural killer cell-mediated cytotoxicity was the pathway with most genes regulated by identified miRNAs. The rest of the enriched pathways in our miRNA list describe different malignancies and signaling. The identified miRNA meta-signature might be considered as a potential battery of biomarkers when distinguishing oral cancer tissue from normal, non-cancerous tissue. Further mechanistic studies are warranted in order to confirm and fully elucidate the role of deregulated miRNAs in oral cancer.

  6. Murine tissue-engineered stomach demonstrates epithelial differentiation.

    PubMed

    Speer, Allison L; Sala, Frederic G; Matthews, Jamil A; Grikscheit, Tracy C

    2011-11-01

    Gastric cancer remains the second largest cause of cancer-related mortality worldwide. Postgastrectomy morbidity is considerable and quality of life is poor. Tissue-engineered stomach is a potential replacement solution to restore adequate food reservoir and gastric physiology. In this study, we performed a detailed investigation of the development of tissue-engineered stomach in a mouse model, specifically evaluating epithelial differentiation, proliferation, and the presence of putative stem cell markers. Organoid units were isolated from <3 wk-old mouse glandular stomach and seeded onto biodegradable scaffolds. The constructs were implanted into the omentum of adult mice. Implants were harvested at designated time points and analyzed with histology and immunohistochemistry. Tissue-engineered stomach grows as an expanding sphere with a simple columnar epithelium organized into gastric glands and an adjacent muscularis. The regenerated gastric epithelium demonstrates differentiation of all four cell types: mucous, enteroendocrine, chief, and parietal cells. Tissue-engineered stomach epithelium proliferates at a rate comparable to native glandular stomach and expresses two putative stem cell markers: DCAMKL-1 and Lgr5. This study demonstrates the successful generation of tissue-engineered stomach in a mouse model for the first time. Regenerated gastric epithelium is able to appropriately proliferate and differentiate. The generation of murine tissue-engineered stomach is a necessary advance as it provides the transgenic tools required to investigate the molecular and cellular mechanisms of this regenerative process. Delineating the mechanism of how tissue-engineered stomach develops in vivo is an important precursor to its use as a human stomach replacement therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. 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

  8. 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

  9. Overlapping and differential localization of Bmp-2, Bmp-4, Msx-2 and apoptosis in the endocardial cushion and adjacent tissues of the developing mouse heart.

    PubMed

    Abdelwahid, E; Rice, D; Pelliniemi, L J; Jokinen, E

    2001-07-01

    The bone morphogenetic proteins BMP-2 and BMP-4 and the homeobox gene MSX-2 are required for normal development of many embryonic tissues. To elucidate their possible roles during the remodeling of the tubular heart into a fully septated four-chambered heart, we have localized the mRNA of Bmp-2, Bmp-4, Msx-2 and apoptotic cells in the developing mouse heart from embryonic day (E)11 to E17. mRNA was localized by in situ hybridization, and apoptotic cells by TUNEL (TDT-mediated dUTP-biotin nick end-labeling) as well as by transmission electron microscopy. By analyzing adjacent serial sections, we demonstrated that the expression of Msx-2 and Bmp-2 strikingly overlapped in the atrioventricular canal myocardium, in the atrioventricular junctional myocardium, and in the maturing myocardium of the atrioventricular valves. Bmp-4 was expressed in the outflow tract myocardium and in the endocardial cushion of the outflow tract ridges from E12 to E14. Msx-2 appeared in the mesenchyme of the atrioventricular endocardial cushion from E11 to E14, while Bmp-2 and Bmp-4 were detected between E11 and E14. Apoptotic cells were also detected in the mesenchyme of the endocardial cushion between E12 and E14. Our results suggest that BMP-2 and MSX-2 are tightly linked to the formation of the atrioventricular junction and valves and that BMP-4 is involved in the development of the outflow tract myocardium and of the endocardial cushion. In addition, BMP-2, BMP-4 and MSX-2 and apoptosis seem to be associated with differentiation of the endocardial cushion.

  10. Safe and targeted anticancer therapy for ovarian cancer using a novel class of curcumin analogs

    PubMed Central

    2013-01-01

    A diagnosis of advanced ovarian cancer is the beginning of a long and arduous journey for a patient. Worldwide, approximately half of the individuals undergoing therapy for advanced cancer will succumb to the disease, or consequences of treatment. Well-known and widely-used chemotherapeutic agents such as cisplatin, paclitaxel, 5-fluorouracil, and doxorubicin are toxic to both cancer and non-cancerous cells, and have debilitating side effects Therefore, development of new targeted anticancer therapies that can selectively kill cancer cells while sparing the surrounding healthy tissues is essential to develop more effective therapies. We have developed a new class of synthetic curcumin analogs, diarylidenyl-piperidones (DAPs), which have higher anticancer activity and enhanced bio-absorption than curcumin. The DAP backbone structure exhibits cytotoxic (anticancer) activity, whereas the N-hydroxypyrroline (-NOH) moiety found on some variants functions as a cellular- or tissue-specific modulator (antioxidant) of cytotoxicity. The anticancer activity of the DAPs has been evaluated using a number of ovarian cancer cell lines, and the safety has been evaluated in a number of non-cancerous cell lines. Both variations of the DAP compounds showed similar levels of cell death in ovarian cancer cells, however the compounds with the -NOH modification were less toxic to non-cancerous cells. The selective cytotoxicity of the DAP–NOH compounds suggests that they will be useful as safe and effective anticancer agents. This article reviews some of the key findings of our work with the DAP compounds, and compares this to some of the targeted therapies currently used in ovarian cancer therapy. PMID:23663277

  11. Community conservation adjacent to Ruaha National Park, Tanzania

    Treesearch

    Sue Stolberger

    2007-01-01

    In the areas adjacent to Ruaha National Park where rural communities exist, much more work and education is required to enable them to benefit directly and indirectly from tourism and managing their own natural resources.

  12. Optimizing Soft Tissue Management and Spacer Design in Segmental Bone Defects

    DTIC Science & Technology

    2014-10-01

    the time of the “Pre-Procedure”. Autogenous Cancellous Bone Graft (ACBG harvested from the sternum at the time of the treatment surgery is used as...will receive more specialized training and orientation to microCT analysis, both on a theoretical and practical level. He will work with raw CT...adjacent to the PMMA) composed of mononuclear cells and exhibited extensive, diffuse fibrous connective tissue.  Performed histology on goat autogenous

  13. [Elevated expression of CLOCK is associated with poor prognosis in hepatocellular carcinoma].

    PubMed

    Li, Bo; Yang, Xiliang; Li, Jiaqi; Yang, Yi; Yan, Zhaoyong; Zhang, Hongxin; Mu, Jiao

    2018-02-01

    Objective To evaluate the expression of circadian locomotor output cycles kaput (CLOCK) and its effects on cell growth in hepatocellular carcinoma (HCC). Methods The expression of CLOCK in 158 pairs of human HCC tissues and matched noncancerous samples was detected by immunohistochemical (IHC) staining. The expression of CLOCK in HCC patients was also verified using the data from GEO and TCGA (a total of 356 cases). The relationship between CLOCK expression and clinicopathological features of HCC patients was analyzed by single factor statistical analysis. Kaplan-Meier survival curves of HCC patients were drawn to study the relationship between the expression level of CLOCK and the survival state. The effect of CLOCK on the growth of HepG2 cells was detected by MTS assay. Results The expression of CLOCK in HCC tissues was significantly higher than that in the adjacent tissues, and the up-regulation of CLOCK expression in HCC tissue was also confirmed in the public data of HCC (356 cases). HCC patients were divided into low CLOCK expression group and high CLOCK expression group. Univariate analysis showed that the expression of CLOCK was related to tumor size, TNM stage, and portal vein invasion in HCC patients. HCC patients with low CLOCK expression had longer overall survival time and relapse-free survival time than those with high CLOCK expression. The proliferation of cells significantly decreased after the expression of CLOCK was knocked down in HepG2 cells. Conclusion The expression of CLOCK in HCC tissues was much higher than that in normal liver tissues, and the high expression of CLOCK indicated the poor prognosis. The knockdown of CLOCK in HCC cells could inhibit the proliferation of HepG2 cells.

  14. Uplink scheduling and adjacent-channel coupling loss analysis for TD-LTE deployment.

    PubMed

    Yeo, Woon-Young; Moon, Sung Ho; Kim, Jae-Hoon

    2014-01-01

    TD-LTE, one of the two duplexing modes in LTE, operates in unpaired spectrum and has the advantages of TDD-based technologies. It is expected that TD-LTE will be more rapidly deployed in near future and most of WiMax operators will upgrade their networks to TD-LTE gradually. Before completely upgrading to TD-LTE, WiMax may coexist with TD-LTE in an adjacent frequency band. In addition, multiple TD-LTE operators may deploy their networks in adjacent bands. When more than one TDD network operates in adjacent frequency bands, severe interference may happen due to adjacent channel interference (ACI) and unsynchronized operations. In this paper, coexistence issues between TD-LTE and other systems are analyzed and coexistence requirements are provided. This paper has three research objectives. First, frame synchronization between TD-LTE and WiMax is discussed by investigating possible combinations of TD-LTE and WiMax configurations. Second, an uplink scheduling algorithm is proposed to utilize a leakage pattern of ACI in synchronized operations. Third, minimum requirements for coexistence in unsynchronized operations are analyzed by introducing a concept of adjacent-channel coupling loss. From the analysis and simulation results, we can see that coexistence of TD-LTE with other TDD systems is feasible if the two networks are synchronized. For the unsynchronized case, some special cell-site engineering techniques may be required to reduce the ACI.

  15. DNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma

    PubMed Central

    Liu, Hongyan; Dong, Huijia; Robertson, Keith; Liu, Chen

    2011-01-01

    Carbamoyl phosphate synthetase 1 (CPS1) is a liver-specific, intramitochondrial, rate-limiting enzyme in the urea cycle. A previous study showed that CPS1 is the antigen for hepatocyte paraffin 1 antibody, a commonly used antibody in surgical pathology practice; and CPS1 expression appears to be down-regulated in liver cancer tissue and cell lines. The aim of this study is to understand how the CPS1 gene is regulated in liver carcinogenesis. In this report, we show that human hepatocellular carcinoma (HCC) cells do not express CPS1, whereas cultured human primary hepatocytes express abundant levels. In addition, CPS1 was silenced or down-regulated in liver tumor tissues compared with the matched noncancerous tissues. The expression of CPS1 in HCC cells was restored with a demethylation agent, 5-azacytidine. We show that two CpG dinucleotides, located near the transcription start site, and a CpG-rich region in the first intron were hypermethylated in HCC cells. The hypermethylation of the two CpG dinucleotides was also detected in HCC tumor tissues compared with noncancerous tissues. Further molecular analysis with mutagenesis indicated that the two CpG dinucleotides play a role in promoter activity of the CPS1 gene. In conclusion, our study demonstrates that DNA methylation is a key mechanism of silencing CPS1 expression in human HCC cells, and CPS1 gene hypermethylation of the two CpG dinucleotides is a potential biomarker for HCC. PMID:21281797

  16. Sacroiliac Joint Fusion Minimally Affects Adjacent Lumbar Segment Motion: A Finite Element Study

    PubMed Central

    Kiapour, Ali; Yerby, Scott A.; Goel, Vijay K.

    2015-01-01

    Background Adjacent segment disease is a recognized consequence of fusion in the spinal column. Fusion of the sacroiliac joint is an effective method of pain reduction. Although effective, the consequences of sacroiliac joint fusion and the potential for adjacent segment disease for the adjacent lumbar spinal levels is unknown. The objective of this study was to quantify the change in range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments due to sacroiliac joint fusion and compare these changes to previous literature to assess the potential for adjacent segment disease in the lumbar spine. Methods An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the sacroiliac joint using three laterally placed triangular implants (iFuse Implant System, SI-BONE, Inc., San Jose, CA). The range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments were calculated using a hybrid loading protocol and compared with the intact range of motion in flexion, extension, lateral bending, and axial rotation. Results The range of motions of the treated sacroiliac joints were reduced in flexion, extension, lateral bending, and axial rotation, by 56.6%, 59.5%, 27.8%, and 53.3%, respectively when compared with the intact condition. The stiffening of the sacroiliac joint resulted in increases at the adjacent lumbar motion segment (L5-S1) for flexion, extension, lateral bending, and axial rotation, of 3.0%, 3.7%, 1.1%, and 4.6%, respectively. Conclusions Fusion of the sacroiliac joint resulted in substantial (> 50%) reductions in flexion, extension, and axial rotation of the sacroiliac joint with minimal (< 5%) increases in range of motion in the lumbar spine. Although the predicted increases in lumbar range of motion are minimal after sacroiliac joint fusion, the long-term clinical results remain to be investigated. PMID:26767156

  17. Sacroiliac Joint Fusion Minimally Affects Adjacent Lumbar Segment Motion: A Finite Element Study.

    PubMed

    Lindsey, Derek P; Kiapour, Ali; Yerby, Scott A; Goel, Vijay K

    2015-01-01

    Adjacent segment disease is a recognized consequence of fusion in the spinal column. Fusion of the sacroiliac joint is an effective method of pain reduction. Although effective, the consequences of sacroiliac joint fusion and the potential for adjacent segment disease for the adjacent lumbar spinal levels is unknown. The objective of this study was to quantify the change in range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments due to sacroiliac joint fusion and compare these changes to previous literature to assess the potential for adjacent segment disease in the lumbar spine. An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the sacroiliac joint using three laterally placed triangular implants (iFuse Implant System, SI-BONE, Inc., San Jose, CA). The range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments were calculated using a hybrid loading protocol and compared with the intact range of motion in flexion, extension, lateral bending, and axial rotation. The range of motions of the treated sacroiliac joints were reduced in flexion, extension, lateral bending, and axial rotation, by 56.6%, 59.5%, 27.8%, and 53.3%, respectively when compared with the intact condition. The stiffening of the sacroiliac joint resulted in increases at the adjacent lumbar motion segment (L5-S1) for flexion, extension, lateral bending, and axial rotation, of 3.0%, 3.7%, 1.1%, and 4.6%, respectively. Fusion of the sacroiliac joint resulted in substantial (> 50%) reductions in flexion, extension, and axial rotation of the sacroiliac joint with minimal (< 5%) increases in range of motion in the lumbar spine. Although the predicted increases in lumbar range of motion are minimal after sacroiliac joint fusion, the long-term clinical results remain to be investigated.

  18. UNITED STATES DEPARTMENT OF TRANSPORTATION GLOBAL POSITIONING SYSTEM (GPS) ADJACENT BAND COMPATIBILITY ASSESSMENT

    DOT National Transportation Integrated Search

    2018-04-01

    The goal of the U.S. Department of Transportation (DOT) Global Positioning System (GPS) Adjacent Band Compatibility Assessment is to evaluate the maximum transmitted power levels of adjacent band radiofrequency (RF) systems that can be tolerated by G...

  19. Adjacent segment disease after instrumented fusion for adult lumbar spondylolisthesis: Incidence and risk factors.

    PubMed

    Zhong, Zhao-Ming; Deviren, Vedat; Tay, Bobby; Burch, Shane; Berven, Sigurd H

    2017-05-01

    A potential long-term complication of lumbar fusion is the development of adjacent segment disease (ASD), which may necessitate second surgery and adversely affect outcomes. The objective of this is to determine the incidence of ASD following instrumented fusion in adult patients with lumbar spondylolisthesis and to identify the risk factors for this complication. We retrospectively assessed adult patients who had undergone decompression and instrumented fusion for lumbar spondylolisthesis between January 2006 and December 2012. The incidence of ASD was analyzed. Potential risk factors included the patient-related factors, surgery-related factors, and radiographic variables such as sagittal alignment, preexisting disc degeneration and spinal stenosis at the adjacent segment. A total of 154 patients (mean age, 58.4 years) were included. Mean duration of follow-up was 28.6 months. Eighteen patients (11.7%) underwent a reoperation for ASD; 15 patients had reoperation at cranial ASD and 3 at caudal ASD. The simultaneous decompression at adjacent segment (p=0.002) and preexisting spinal stenosis at cranial adjacent segment (p=0.01) were identified as risk factors for ASD. The occurrence of ASD was not affected by patient-related factors, the types, grades and levels of spondylolisthesis, surgical approach, fusion procedures, levels of fusion, number of levels fused, types of bone graft, use of bone morphogenetic proteins, sagittal alignment, preexisting adjacent disc degeneration and preexisting spinal stenosis at caudal adjacent segments. Our findings suggest the overall incidence of ASD is 11.7% in adult patients with lumbar spondylolisthesis after decompression and instrumented fusion at a mean follow-up of 28.6 months, the simultaneous decompression at the adjacent segment and preexisting spinal stenosis at cranial adjacent segment are risk factors for ASD. Copyright © 2017. Published by Elsevier B.V.

  20. Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms.

    PubMed

    Siennicka, Aldona; Zuchowski, Marta; Kaczmarczyk, Mariusz; Cnotliwy, Miłosław; Clark, Jeremy Simon; Jastrzębska, Maria

    2018-03-20

    The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Factor levels were measured using enzyme-linked immunosorbent assay of protein extract. Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001; B vs B1, P = .001). Significantly higher tissue plasminogen activator was found in thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of α 2 -antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  1. [Influence of ambient light and adjacent tooth in anterior tooth color measurement].

    PubMed

    Wang, Si-qian; Sean, S Lee; Wu, Zhang; Li, Yiming; Ma, Jian-feng

    2007-10-01

    To investigate the influence of different intensity and directions of ambient light and adjacent tooth in anterior tooth color measurement by using colorimeter. Fiber lite MI-150 was used as ambient illuminant and it irradiated from three or twelve o'clock direction through 45 degrees angle above. The light magnitude 0, 50, 75, 100, 125, 150 W were applied in this experiment. The values of CIE L* a* b* were measured by Minolta Chroma meter CR-321 colorimeter on the center labial surface of ten extracted human maxillary central incisors with or without adjacent teeth, then those data were analyzed statistically by using SPSS 11.5. Neither different intensities nor different directions of ambient light could influence the results of color measurement by using Minolta Chroma meter CR-321 colorimeter, so did the adjacent teeth whether those were exist or not. There is no influence of ambient light and adjacent teeth in the color measurement of anterior teeth under this experiment condition, and Minolta Chroma meter CR-321 colorimeter can be used to measure the color directly aside the chair with light.

  2. Flow and transport within a coastal aquifer adjacent to a stratified water body

    NASA Astrophysics Data System (ADS)

    Oz, Imri; Yechieli, Yoseph; Eyal, Shalev; Gavrieli, Ittai; Gvirtzman, Haim

    2016-04-01

    The existence of a freshwater-saltwater interface and the circulation flow of saltwater beneath the interface is a well-known phenomenon found at coastal aquifers. This flow is a natural phenomenon that occurs due to density differences between fresh groundwater and the saltwater body. The goals of this research are to use analytical, numerical, and physical models in order to examine the configuration of the freshwater-saltwater interface and the density-driven flow patterns within a coastal aquifer adjacent to long-term stratified saltwater bodies (e.g. meromictic lake). Such hydrological systems are unique, as they consist of three different water types: the regional fresh groundwater, and low and high salinity brines forming the upper and lower water layers of the stratified water body, respectively. This research also aims to examine the influence of such stratification on hydrogeological processes within the coastal aquifer. The coastal aquifer adjacent to the Dead Sea, under its possible future meromictic conditions, serves as an ideal example to examine these processes. The results show that adjacent to a stratified saltwater body three interfaces between three different water bodies are formed, and that a complex flow system, controlled by the density differences, is created, where three circulation cells are developed. These results are significantly different from the classic circulation cell that is found adjacent to non-stratified water bodies (lakes or oceans). In order to obtain a more generalized insight into the groundwater behavior adjacent to a stratified water body, we used the numerical model to perform sensitivity analysis. The hydrological system was found be sensitive to three dimensionless parameters: dimensionless density (i.e. the relative density of the three water bodies'); dimensionless thickness (i.e. the ratio between the relative thickness of the upper layer and the whole thickness of the lake); and dimensionless flux. The results

  3. Coordinating cell and tissue behavior during zebrafish neural tube morphogenesis.

    PubMed

    Araya, Claudio; Ward, Laura C; Girdler, Gemma C; Miranda, Miguel

    2016-03-01

    The development of a vertebrate neural epithelium with well-organized apico-basal polarity and a central lumen is essential for its proper function. However, how this polarity is established during embryonic development and the potential influence of surrounding signals and tissues on such organization has remained less understood. In recent years the combined superior transparency and genetics of the zebrafish embryo has allowed for in vivo visualization and quantification of the cellular and molecular dynamics that govern neural tube structure. Here, we discuss recent studies revealing how co-ordinated cell-cell interactions coupled with adjacent tissue dynamics are critical to regulate final neural tissue architecture. Furthermore, new findings show how the spatial regulation and timing of orientated cell division is key in defining precise lumen formation at the tissue midline. In addition, we compare zebrafish neurulation with that of amniotes and amphibians in an attempt to understand the conserved cellular mechanisms driving neurulation and resolve the apparent differences among animals. Zebrafish neurulation not only offers fundamental insights into early vertebrate brain development but also the opportunity to explore in vivo cell and tissue dynamics during complex three-dimensional animal morphogenesis. © 2015 Wiley Periodicals, Inc.

  4. Uplink Scheduling and Adjacent-Channel Coupling Loss Analysis for TD-LTE Deployment

    PubMed Central

    Yeo, Woon-Young; Moon, Sung Ho

    2014-01-01

    TD-LTE, one of the two duplexing modes in LTE, operates in unpaired spectrum and has the advantages of TDD-based technologies. It is expected that TD-LTE will be more rapidly deployed in near future and most of WiMax operators will upgrade their networks to TD-LTE gradually. Before completely upgrading to TD-LTE, WiMax may coexist with TD-LTE in an adjacent frequency band. In addition, multiple TD-LTE operators may deploy their networks in adjacent bands. When more than one TDD network operates in adjacent frequency bands, severe interference may happen due to adjacent channel interference (ACI) and unsynchronized operations. In this paper, coexistence issues between TD-LTE and other systems are analyzed and coexistence requirements are provided. This paper has three research objectives. First, frame synchronization between TD-LTE and WiMax is discussed by investigating possible combinations of TD-LTE and WiMax configurations. Second, an uplink scheduling algorithm is proposed to utilize a leakage pattern of ACI in synchronized operations. Third, minimum requirements for coexistence in unsynchronized operations are analyzed by introducing a concept of adjacent-channel coupling loss. From the analysis and simulation results, we can see that coexistence of TD-LTE with other TDD systems is feasible if the two networks are synchronized. For the unsynchronized case, some special cell-site engineering techniques may be required to reduce the ACI. PMID:24707214

  5. Use of cryostat sections from snap-frozen nervous tissue for combining stereological estimates with histological, cellular, or molecular analyses on adjacent sections.

    PubMed

    Schmitz, C; Dafotakis, M; Heinsen, H; Mugrauer, K; Niesel, A; Popken, G J; Stephan, M; Van de Berg, W D; von Hörsten, S; Korr, H

    2000-10-01

    Adequate tissue preparation is essential for both modern stereological and immunohistochemical investigations. However, combining these methodologies in a single study presents a number of obstacles pertaining to optimal histological preparation. Tissue shrinkage and loss of nuclei/nucleoli from the unprotected section surfaces of unembedded tissue used for immunohistochemistry may be problematic with regard to adequate stereological design. In this study, frozen cryostat sections from hippocampal and cerebellar regions of two rat strains and cerebellar and cerebral regions from a human brain were analyzed to determine the potential impact of these factors on estimates of neuron number obtained using the optical disector. Neuronal nuclei and nucleoli were clearly present in thin sections of snap-frozen rat (3 microm) and human (6 microm) tissue, indicating that neuronal nuclei/nucleoli are not unavoidably lost from unprotected section surfaces of unembedded tissue. In order to quantify the potential impact of any nuclear loss, optical fractionator estimates of rat hippocampal pyramidal cells in areas CA1-3 and cerebellar granule and Purkinje cells were made using minimal (1 microm) upper guard zones. Estimates did not differ from data reported previously in the literature. This data indicates that cryostat sections of snap-frozen nervous tissue may successfully be used for estimating total neuronal numbers using optical disectors.

  6. Constructing an optimal facility layout to maximize adjacency as a function of common boundary length

    NASA Astrophysics Data System (ADS)

    Ghassemi Tari, Farhad; Neghabi, Hossein

    2018-03-01

    An effective facility layout implies that departments with high flow are laid adjacent. However, in the case of a very narrow boundary length between the neighbouring departments, the adjacency would actually be useless. In traditional layout design methods, a score is generally assigned independent of the department's boundary length. This may result in a layout design with a restricted material flow. This article proposes a new concept of adjacency in which the department pairs are laid adjacent with a wider path. To apply this concept, a shop with unequal rectangular departments is contemplated and a mathematical programming model with the objective of maximizing the sum of the adjacency degrees is proposed. A computational experiment is conducted to demonstrate the efficiency of the layout design. It is demonstrated that the new concept provides a more efficient and a more realistic layout design.

  7. 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...

  8. 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.

  9. Lumbar intervertebral disc allograft transplantation: long-term mobility and impact on the adjacent segments.

    PubMed

    Huang, Yong-Can; Xiao, Jun; Lu, William W; Leung, Victor Y L; Hu, Yong; Luk, Keith D K

    2017-03-01

    Fresh-frozen intervertebral disc (IVD) allograft transplantation has been successfully performed in the human cervical spine. Whether this non-fusion technology could truly decrease adjacent segment disease is still unknown. This study evaluated the long-term mobility of the IVD-transplanted segment and the impact on the adjacent spinal segments in a goat model. Twelve goats were used. IVD allograft transplantation was performed at lumbar L4/L5 in 5 goats; the other 7 goats were used as the untreated control (5) and for the supply of allografts (2). Post-operation lateral radiographs of the lumbar spine in the neutral, full-flexion and full-extension positions were taken at 1, 3, 6, 9 and 12 months. Disc height (DH) of the allograft and the adjacent levels was calculated and range of motion (ROM) was measured using the Cobb's method. The anatomy of the adjacent discs was observed histologically. DH of the transplanted segment was decreased significantly after 3 months but no further reduction was recorded until the final follow-up. No obvious alteration was seen in the ROM of the transplanted segment at different time points with the ROM at 12 months being comparable to that of the untreated control. The DH and ROM in the adjacent segments were well maintained during the whole observation period. At post-operative 12 months, the ROM of the adjacent levels was similar to that of the untreated control and the anatomical morphology was well preserved. Lumbar IVD allograft transplantation in goats could restore the segmental mobility and did not negatively affect the adjacent segments after 12 months.

  10. 33 CFR 110.168 - Hampton Roads, Virginia and adjacent waters (Datum: NAD 83).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Hampton Roads, Virginia and adjacent waters (Datum: NAD 83). 110.168 Section 110.168 Navigation and Navigable Waters COAST GUARD..., Virginia and adjacent waters (Datum: NAD 83). (a) Anchorage Grounds—(1) Anchorage A [Naval Anchorage]. The...

  11. Cell interactions in bone tissue engineering.

    PubMed

    Pirraco, R P; Marques, A P; Reis, R L

    2010-01-01

    Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and new bottom-up approaches are needed. The study of the cellular interactions between the cells relevant for bone biology can be of essential importance to that. In living bone, cells are in a context where communication with adjacent cells is almost permanent. Many fundamental works have been addressing these communications nonetheless, in a bone TE approach, the 3D perspective, being part of the microenvironment of a bone cell, is as crucial. Works combining the study of cell-to-cell interactions in a 3D environment are not as many as expected. Therefore, the bone TE field should not only gain knowledge from the field of fundamental Biology but also contribute for further understanding the biology of bone. In this review, a summary of the main works in the field of bone TE, aiming at studying cellular interactions in a 3D environment, and how they contributed towards the development of a functional engineered bone tissue, is presented.

  12. 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.

  13. [Experimental-morphologic study of bone tissue reaction to carbon-containing material implantation with initiated X-ray contrast property].

    PubMed

    Grigorian, A S; Nabiev, F Kh; Golovin, R V

    2005-01-01

    In experimental study on 15 rabbits (chinchilla) influence of titanium plates implanted lapped on adjacent tissues in the region of the lower jaw body (comparison group) and carbon material with added boron in the concentrations of 8 and 15% (the study group) was studied. Results of the experimental-morphological investigation show that carbon-based materials with boron addition (with its content 8 and 15%) did not impede adaptive rebuilding of bone tissues and in particular bone structure regeneration in the process of reactive rebuilding of the "maternal" bone. Moreover, as the result of reactive processes developing in osseous tissues after implantation of the tested materials their successful integration in surrounding tissue structures was detected.

  14. Near-infrared spectroscopy of the adult head: effect of scattering and absorbing obstructions in the cerebrospinal fluid layer on light distribution in the tissue.

    PubMed

    Dehghani, H; Delpy, D T

    2000-09-01

    Previous modeling of near-infrared (NIR) light distribution in models of the adult head incorporating a clear nonscattering cerebrospinal fluid (CSF) layer have shown the latter to have a profound effect on the resulting photon measurement density function (PMDF). In particular, the presence of the CSF limits the PMDF largely to the outer cortical gray matter with little signal contribution from the deeper white matter. In practice, the CSF is not a simple unobstructed clear layer but contains light-scattering membranes and is crossed by various blood vessels. Using a radiosity-diffusion finite-element model, we investigated the effect on the PMDF of introducing intrusions within the clear layer. The results show that the presence of such obstructions does not significantly increase the light penetration into the brain tissue, except immediately adjacent to the obstruction and that its presence also increases the light sampling of the adjacent skull tissues, which would lead to additional contamination of the NIR spectroscopy signal by the surface tissue layers.

  15. Regenerating Articular Tissue by Converging Technologies

    PubMed Central

    Paoluzzi, Luca; Pieper, Jeroen; de Wijn, Joost R.; van Blitterswijk, Clemens A.

    2008-01-01

    Scaffolds for osteochondral tissue engineering should provide mechanical stability, while offering specific signals for chondral and bone regeneration with a completely interconnected porous network for cell migration, attachment, and proliferation. Composites of polymers and ceramics are often considered to satisfy these requirements. As such methods largely rely on interfacial bonding between the ceramic and polymer phase, they may often compromise the use of the interface as an instrument to direct cell fate. Alternatively, here, we have designed hybrid 3D scaffolds using a novel concept based on biomaterial assembly, thereby omitting the drawbacks of interfacial bonding. Rapid prototyped ceramic particles were integrated into the pores of polymeric 3D fiber-deposited (3DF) matrices and infused with demineralized bone matrix (DBM) to obtain constructs that display the mechanical robustness of ceramics and the flexibility of polymers, mimicking bone tissue properties. Ostechondral scaffolds were then fabricated by directly depositing a 3DF structure optimized for cartilage regeneration adjacent to the bone scaffold. Stem cell seeded scaffolds regenerated both cartilage and bone in vivo. PMID:18716660

  16. On the Circulation Manifold for Two Adjacent Lifting Sections

    NASA Technical Reports Server (NTRS)

    Zannetti, Luca; Iollo, Angelo

    1998-01-01

    The circulation functional relative to two adjacent lifting sections is studied for two cases. In the first case we consider two adjacent circles. The circulation is computed as a function of the displacement of the secondary circle along the axis joining the two centers and of the angle of attack of the secondary circle, The gradient of such functional is computed by deriving a set of elliptic functions with respect both to their argument and to their Period. In the second case studied, we considered a wing-flap configuration. The circulation is computed by some implicit mappings, whose differentials with respect to the variation of the geometrical configuration in the physical space are found by divided differences. Configurations giving rise to local maxima and minima in the circulation manifold are presented.

  17. 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.

  18. Co-expression networks reveal the tissue-specific regulation of transcription and splicing

    PubMed Central

    Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D.H.; Jo, Brian; Gao, Chuan; McDowell, Ian C.; Engelhardt, Barbara E.

    2017-01-01

    Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. PMID:29021288

  19. Potential interactions among disease, pesticides, water quality and adjacent land cover in amphibian habitats in the United States.

    PubMed

    Battaglin, W A; Smalling, K L; Anderson, C; Calhoun, D; Chestnut, T; Muths, E

    2016-10-01

    To investigate interactions among disease, pesticides, water quality, and adjacent land cover, we collected samples of water, sediment, and frog tissue from 21 sites in 7 States in the United States (US) representing a variety of amphibian habitats. All samples were analyzed for >90 pesticides and pesticide degradates, and water and frogs were screened for the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) using molecular methods. Pesticides and pesticide degradates were detected frequently in frog breeding habitats (water and sediment) as well as in frog tissue. Fungicides occurred more frequently in water, sediment, and tissue than was expected based upon their limited use relative to herbicides or insecticides. Pesticide occurrence in water or sediment was not a strong predictor of occurrence in tissue, but pesticide concentrations in tissue were correlated positively to agricultural and urban land, and negatively to forested land in 2-km buffers around the sites. Bd was detected in water at 45% of sites, and on 34% of swabbed frogs. Bd detections in water were not associated with differences in land use around sites, but sites with detections had colder water. Frogs that tested positive for Bd were associated with sites that had higher total fungicide concentrations in water and sediment, but lower insecticide concentrations in sediments relative to frogs that were Bd negative. Bd concentrations on frog swabs were positively correlated to dissolved organic carbon, and total nitrogen and phosphorus, and negatively correlated to pH and water temperature. Data were collected from a range of locations and amphibian habitats and represent some of the first field-collected information aimed at understanding the interactions between pesticides, land use, and amphibian disease. These interactions are of particular interest to conservation efforts as many amphibians live in altered habitats and may depend on wetlands embedded in these landscapes to survive

  20. Potential interactions among disease, pesticides, water quality and adjacent land cover in amphibian habitats in the United States

    USGS Publications Warehouse

    Battaglin, William A.; Smalling, Kelly L.; Anderson, Chauncey; Calhoun, Daniel L.; Chestnut, Tara E.; Muths, Erin L.

    2016-01-01

    To investigate interactions among disease, pesticides, water quality, and adjacent land cover, we collected samples of water, sediment, and frog tissue from 21 sites in 7 States in the United States (US) representing a variety of amphibian habitats. All samples were analyzed for > 90 pesticides and pesticide degradates, and water and frogs were screened for the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) using molecular methods. Pesticides and pesticide degradates were detected frequently in frog breeding habitats (water and sediment) as well as in frog tissue. Fungicides occurred more frequently in water, sediment, and tissue than was expected based upon their limited use relative to herbicides or insecticides. Pesticide occurrence in water or sediment was not a strong predictor of occurrence in tissue, but pesticide concentrations in tissue were correlated positively to agricultural and urban land, and negatively to forested land in 2-km buffers around the sites. Bd was detected in water at 45% of sites, and on 34% of swabbed frogs. Bd detections in water were not associated with differences in land use around sites, but sites with detections had colder water. Frogs that tested positive for Bd were associated with sites that had higher total fungicide concentrations in water and sediment, but lower insecticide concentrations in sediments relative to frogs that were Bd negative. Bd concentrations on frog swabs were positively correlated to dissolved organic carbon, and total nitrogen and phosphorus, and negatively correlated to pH and water temperature.Data were collected from a range of locations and amphibian habitats and represent some of the first field-collected information aimed at understanding the interactions between pesticides, land use, and amphibian disease. These interactions are of particular interest to conservation efforts as many amphibians live in altered habitats and may depend on wetlands embedded in these landscapes to

  1. 33 CFR 165.1303 - Puget Sound and adjacent waters, WA-regulated navigation area.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Puget Sound and adjacent waters... § 165.1303 Puget Sound and adjacent waters, WA—regulated navigation area. (a) The following is a... Light to New Dungeness Light and all points in the Puget Sound area north and south of these lights. (b...

  2. 33 CFR 165.1303 - Puget Sound and adjacent waters, WA-regulated navigation area.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Puget Sound and adjacent waters... § 165.1303 Puget Sound and adjacent waters, WA—regulated navigation area. (a) The following is a... Light to New Dungeness Light and all points in the Puget Sound area north and south of these lights. (b...

  3. 33 CFR 165.1303 - Puget Sound and adjacent waters, WA-regulated navigation area.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Puget Sound and adjacent waters... § 165.1303 Puget Sound and adjacent waters, WA—regulated navigation area. (a) The following is a... Light to New Dungeness Light and all points in the Puget Sound area north and south of these lights. (b...

  4. 33 CFR 165.1303 - Puget Sound and adjacent waters, WA-regulated navigation area.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Puget Sound and adjacent waters... § 165.1303 Puget Sound and adjacent waters, WA—regulated navigation area. (a) The following is a... Light to New Dungeness Light and all points in the Puget Sound area north and south of these lights. (b...

  5. Modeling the Morphogenesis of Epidermal Tissues on the Surface of a 3D Last

    NASA Astrophysics Data System (ADS)

    McCleery, W. Tyler; Crews, Sarah M.; Mashburn, David N.; Veldhuis, Jim; Brodland, G. Wayne; Hutson, M. Shane

    2014-03-01

    Embryogenesis in the fruit fly Drosophila melanogaster is coordinated by the interaction of cells in adjacent tissues. For some events of embryogenesis, e.g., dorsal closure, two-dimensional models have been sufficient to elucidate the relevant cell and tissue mechanics. Here, we describe a new three-dimensional cell-level finite element model for investigating germ band retraction - a morphogenetic event where one epidermal tissue, the germ band, initially wraps around the posterior end of the ellipsoidal embryo. This tissue then retracts with a mechanical assist from contraction of cells in a second epidermal tissue, the amnioserosa. To speed simulation run times and focus on the relevant tissues, we only model epidermal tissue interactions. Epidermal cells are defined as polygons constrained to lie on the surface of the ellipsoidal last, but have adjustable parameters such as edge tensions and cell pressures. Tissue movements are simulated by balancing these dynamic cell-level forces with viscous resistance and allowing cells to exchange neighbors. Our choice of modeling parameters is informed by in vivo measurements of cell-level forces using laser microsurgery. We use this model to investigate the multicellular stress fields in normal and aberrant development.

  6. Influence of cantilevered sheet pile deflection on adjacent roadways.

    DOT National Transportation Integrated Search

    2009-06-01

    Cantilevered sheet pile walls are often used adjacent roadways as temporary support during construction. Excess movement of these walls has led to excessive roadway distress causing additional repairs to be necessary. This study assessed the effects ...

  7. Experimental verification of the Acuros XB and AAA dose calculation adjacent to heterogeneous media for IMRT and RapidArc of nasopharygeal carcinoma.

    PubMed

    Kan, Monica W K; Leung, Lucullus H T; So, Ronald W K; Yu, Peter K N

    2013-03-01

    To compare the doses calculated by the Acuros XB (AXB) algorithm and analytical anisotropic algorithm (AAA) with experimentally measured data adjacent to and within heterogeneous medium using intensity modulated radiation therapy (IMRT) and RapidArc(®) (RA) volumetric arc therapy plans for nasopharygeal carcinoma (NPC). Two-dimensional dose distribution immediately adjacent to both air and bone inserts of a rectangular tissue equivalent phantom irradiated using IMRT and RA plans for NPC cases were measured with GafChromic(®) EBT3 films. Doses near and within the nasopharygeal (NP) region of an anthropomorphic phantom containing heterogeneous medium were also measured with thermoluminescent dosimeters (TLD) and EBT3 films. The measured data were then compared with the data calculated by AAA and AXB. For AXB, dose calculations were performed using both dose-to-medium (AXB_Dm) and dose-to-water (AXB_Dw) options. Furthermore, target dose differences between AAA and AXB were analyzed for the corresponding real patients. The comparison of real patient plans was performed by stratifying the targets into components of different densities, including tissue, bone, and air. For the verification of planar dose distribution adjacent to air and bone using the rectangular phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 98.7%, 99.5%, and 97.7% on the axial plane for AAA, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans, while they were 97.6%, 98.2%, and 97.7%, respectively, on the coronal plane. For the verification of planar dose distribution within the NP region of the anthropomorphic phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 95.1%, 91.3%, and 99.0% for AAA, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans. Within the NP region where air and bone were present, the film measurements represented the dose close to unit density water

  8. High Rab27A expression indicates favorable prognosis in CRC.

    PubMed

    Shi, Chuanbing; Yang, Xiaojun; Ni, Yijiang; Hou, Ning; Xu, Li; Zhan, Feng; Zhu, Huijun; Xiong, Lin; Chen, Pingsheng

    2015-06-13

    Rab27A is a peculiar member in Rab family and has been suggested to play essential roles in the development of human cancers. However, the association between Rab27A expression and clinicopathological characteristics of colorectal cancer (CRC) has not been elucidated yet. One-step quantitative real-time polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 112 CRC cases were executed to evaluate the relationship between Rab27A expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for 112 CRC patients. The results specified that the expression levels of Rab27A mRNA and protein were significantly higher in CRC tissues than that in matched non-cancerous tissues, in both qPCR test (p = 0.029) and IHC analysis (p = 0.020). The IHC data indicated that the Rab27A protein expression in CRC was statistically correlated with lymph node metastasis (p = 0.022) and TNM stage (p = 0.026). Cox multi-factor analysis and Kaplan-Meier method suggested Rab27A protein expression (p = 0.012) and tumor differentiation (p = 0.004) were significantly associated with the overall survival of CRC patients. The data indicated the differentiate expression of Rab27A in CRC tissues and matched non-cancerous tissues. Rab27A may be used as a valuable prognostic biomarker for CRC patients.

  9. Spillover from adjacent crop and forest habitats shapes carabid beetle assemblages in fragmented semi-natural grasslands.

    PubMed

    Schneider, Gudrun; Krauss, Jochen; Boetzl, Fabian A; Fritze, Michael-Andreas; Steffan-Dewenter, Ingolf

    2016-12-01

    Semi-natural grasslands in Europe are insect biodiversity hotspots and important source habitats delivering ecosystem services to adjacent agricultural land by species spillover. However, this spillover might also occur in the opposite direction, affecting the diversity of semi-natural grasslands. This opposite spillover has got little attention in scientific literature even though generalist species penetrating into the grasslands can affect local biotic interactions, community composition and the conservation value of grassland habitats. In this study, we examined spillover effects from two different adjacent habitat types on carabid beetle assemblages in 20 semi-natural calcareous grasslands. The grasslands were either adjacent to a cereal crop field or to a coniferous forest. We found distinct differences in carabid beetle assemblages in calcareous grasslands depending on adjacent habitat type. Species richness and activity density were higher, but the evenness was lower in calcareous grasslands adjacent to crop fields compared with calcareous grasslands adjacent to coniferous forests. Further, we found a strong spillover of carabid beetles from adjacent crop fields after crop harvest, which may result in transiently increased predation pressure and resource competition in calcareous grasslands. Our results highlight that species composition, diversity and presumably ecosystem functions within semi-natural habitats are affected by the type and management of surrounding habitats. This needs to be considered by nature conservation measures, which aim to protect the unique insect communities of semi-natural European grasslands.

  10. DYSTOCIA DUE TO SOFT TISSUE

    PubMed Central

    DeCarle, Donald W.

    1954-01-01

    In dystocia caused by abnormal conditions of the soft parts, the etiologic changes may be either in the genital tissues or in adjacent soft structures. Broadly, the conditions causing the difficulty may be grouped as follows: (1) anomalies or congenital modifications; (2) tumors; (3) modifications due to age, accident or surgical operations; (4) modification of the expulsive forces; (5) abnormalities of the products of conception. Often in such circumstances cesarean section is necessary. Sometimes when tumor is present it can be removed before it interferes with delivery, but decision to excise the growth must be guided by such factors as the location of the lesion and the stage of gestation. This would determine to what extent the maintenance of pregnancy would be jeopardized by surgical intervention before term. PMID:13190430

  11. Colonization and Movement of Xanthomonas fragariae in Strawberry Tissues.

    PubMed

    Wang, Hehe; McTavish, Christine; Turechek, William W

    2018-06-01

    Xanthomonas fragariae causes angular leaf spot of strawberry, an important disease in strawberry growing regions worldwide. To better understand how X. fragariae multiplies and moves in strawberry plants, a green fluorescent protein (GFP)-labeled strain was constructed and used to monitor the pathogen's presence in leaf, petiole, and crown tissue with fluorescence microscopy following natural and wound inoculation in three strawberry cultivars. Taqman PCR was used to quantify bacterial densities in these same tissues regardless of the presence of GFP signal. Results showed X. fragariae colonized leaf mesophyll, the top 1 cm portion of the petiole adjacent to the leaf blade, and was occasionally found colonizing xylem vessels down to the middle of the petioles. The colonization of vascular bundles and the limited systemic movement that was observed appeared to be a passive process, of which the frequency increased with wounding and direct infiltration of bacteria into leaf veins. X. fragariae was able to directly enter petioles and colonize the space under the epidermis. Systemic movement of the bacteria into crown and other uninoculated tissues was not detected visually by GFP. However, X. fragariae was occasionally detected in these tissues by qPCR, but at quantities very near the qPCR detection limit. Petiole tissue harboring bacteria introduced either by direct entry through natural openings or wounds, or by systemic movement from infected foliar tissue, likely serves as a main source of initial inoculum in field plantings.

  12. 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

  13. Metamorphosis of mesothelial cells with active horizontal motility in tissue culture.

    PubMed

    Nagai, Hirotaka; Chew, Shan Hwu; Okazaki, Yasumasa; Funahashi, Satomi; Namba, Takashi; Kato, Takuya; Enomoto, Atsushi; Jiang, Li; Akatsuka, Shinya; Toyokuni, Shinya

    2013-01-01

    Mesothelial cells, which have diverse roles in physiology and pathology, constitute the mesothelium along with connective tissue and the basement membrane; the mesothelium serves to shield the somatic cavities. After mesothelial injury, mesothelial cells undergo tissue recovery. However, the mechanism of mesothelial regeneration remains poorly understood. In this study, we used confocal time-lapse microscopy to demonstrate that transformed mesothelial cells (MeT5A) and mouse peritoneal mesothelial cells can randomly migrate between cells in cell culture and in ex vivo tissue culture, respectively. Moreover, peritoneal mesothelial cells changed their morphology from a flattened shape to a cuboidal one prior to the migration. Conversely, MDCKII epithelial cells forming tight cell-cell contacts with one another do not alter the arrangement of adjacent cells during movement. Our evidence complements the current hypotheses of mesothelial regeneration and suggests that certain types of differentiated mesothelial cells undergo morphological changes before initiating migration to repair injured sites.

  14. Metal and transuranic records in mussel shells, byssal threads and tissues

    NASA Astrophysics Data System (ADS)

    Koide, Minoru; Lee, Dong Soo; Goldberg, Edward D.

    1982-12-01

    Bivalve shells offer several advantages over tissues for the monitoring of heavy metal pollutants in the marine environment. They are easier to handle and to store. The problem of whether to depurate the animals before analyses is avoided. The shells appear to be more sensitive to environmental heavy metals levels over the long term than do the soft parts. Of the substances examined (Cd, Cu, Zn, Pb, Ag, Ni, 238Pu and 239 + 240Pu) only Pb and Pu displayed a strong covariance between soft tissue and shell concentrations. There were strong correlations between metals in the shell but not in the soft tissues in general. The byssal threads, because of their enrichment of transuranic elements and of their ease in handling, may be useful in monitoring these metals. A very weak discharge of 238Pu to marine waters adjacent to a nuclear reactor was detected in the byssal threads of mussels.

  15. Decreased Expression of EHD2 Promotes Tumor Metastasis and Indicates Poor Prognosis in Hepatocellular Carcinoma.

    PubMed

    Liu, Jinxia; Ni, Wenkai; Qu, Lishuai; Cui, Xiaopeng; Lin, Zhipeng; Liu, Qingqing; Zhou, Huiling; Ni, Runzhou

    2016-09-01

    Metastasis remains the most common cause of lethal outcomes in hepatocellular carcinoma (HCC) after curative resection. Understanding molecular mechanisms that regulate metastasis process is crucial for improving treatment of hepatocellular carcinoma. In this article, we examined whether Eps15 homology domain-containing 2 (EHD2) played a critical role in hepatocellular carcinoma metastasis and explored the possible mechanism. EHD2 and E-cadherin expression levels in hepatocellular carcinoma patients were examined using Western blotting and immunohistochemistry. The cell migration and invasion were evaluated by wound-healing assay and trans-well assay. Epithelial-mesenchymal transition was analyzed by immunofluorescence, and the vital markers were detected by Western blotting. The correlation of EHD2 and E-cadherin was confirmed by co-immunoprecipitation. EHD2 expression, along with the epithelial marker E-cadherin, was markedly reduced in tumor tissues than in adjacent noncancerous tissues. Moreover, EHD2 was positively correlated with E-cadherin, histological grade, tumor metastasis, and microvascular invasion. Kaplan-Meier survival analysis showed that hepatocellular carcinoma patients with decreased EHD2 expression had shorter overall survival times than those with higher EHD2 expression. Knockdown of EHD2 induced an increase in cell invasion and changes characteristic of epithelial-mesenchymal transition, while overexpression of EHD2 inhibited these processes. Molecular data indicated that EHD2 inhibited migration and invasion of hepatocellular carcinoma probably by interacting with E-cadherin and it might be an independent, significant risk factor for survival after curative resection.

  16. Tissues viability and blood flow sensing based on a new nanophotonics method

    NASA Astrophysics Data System (ADS)

    Yariv, Inbar; Haddad, Menashe; Duadi, Hamootal; Motiei, Menachem; Fixler, Dror

    2018-02-01

    Extracting optical parameters of turbid medium (e.g. tissue) by light reflectance signals is of great interest and has many applications in the medical world, life science, material analysis and biomedical optics. The reemitted light from an irradiated tissue is affected by the light's interaction with the tissue components and contains the information about the tissue structure and physiological state. In this research we present a novel noninvasive nanophotonics technique, i.e., iterative multi-plane optical property extraction (IMOPE) based on reflectance measurements. The reflectance based IMOPE was applied for tissue viability examination, detection of gold nanorods (GNRs) within the blood circulation as well as blood flow detection using the GNRs presence within the blood vessels. The basics of the IMOPE combine a simple experimental setup for recording light intensity images with an iterative Gerchberg-Saxton (G-S) algorithm for reconstructing the reflected light phase and computing its standard deviation (STD). Changes in tissue composition affect its optical properties which results in changes in the light phase that can be measured by its STD. This work presents reflectance based IMOPE tissue viability examination, producing a decrease in the computed STD for older tissues, as well as investigating their organic material absorption capability. Finally, differentiation of the femoral vein from adjacent tissues using GNRs and the detection of their presence within blood circulation and tissues are also presented with high sensitivity (better than computed tomography) to low quantities of GNRs (<3 mg).

  17. 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.

  18. 33 CFR 150.35 - How may an adjacent coastal State request an amendment to the operations manual?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... provide equivalent or improved protection and safety. The adjacent coastal State may petition the... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false How may an adjacent coastal State... § 150.35 How may an adjacent coastal State request an amendment to the operations manual? (a) An...

  19. 33 CFR 150.35 - How may an adjacent coastal State request an amendment to the operations manual?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... provide equivalent or improved protection and safety. The adjacent coastal State may petition the... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false How may an adjacent coastal State... § 150.35 How may an adjacent coastal State request an amendment to the operations manual? (a) An...

  20. 33 CFR 150.35 - How may an adjacent coastal State request an amendment to the operations manual?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... provide equivalent or improved protection and safety. The adjacent coastal State may petition the... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false How may an adjacent coastal State... § 150.35 How may an adjacent coastal State request an amendment to the operations manual? (a) An...

  1. Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA.

    PubMed

    Guo, Shicheng; Diep, Dinh; Plongthongkum, Nongluk; Fung, Ho-Lim; Zhang, Kang; Zhang, Kun

    2017-04-01

    Adjacent CpG sites in mammalian genomes can be co-methylated owing to the processivity of methyltransferases or demethylases, yet discordant methylation patterns have also been observed, which are related to stochastic or uncoordinated molecular processes. We focused on a systematic search and investigation of regions in the full human genome that show highly coordinated methylation. We defined 147,888 blocks of tightly coupled CpG sites, called methylation haplotype blocks, after analysis of 61 whole-genome bisulfite sequencing data sets and validation with 101 reduced-representation bisulfite sequencing data sets and 637 methylation array data sets. Using a metric called methylation haplotype load, we performed tissue-specific methylation analysis at the block level. Subsets of informative blocks were further identified for deconvolution of heterogeneous samples. Finally, using methylation haplotypes we demonstrated quantitative estimation of tumor load and tissue-of-origin mapping in the circulating cell-free DNA of 59 patients with lung or colorectal cancer.

  2. View of deck truss span over creek and adjacent trestle, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of deck truss span over creek and adjacent trestle, looking due south. - Pennsylvania Railroad, Brandywine Valley Viaduct, Spanning Brandywine Creek & U.S. Route 322, Downingtown, Chester County, PA

  3. FACILITY 802B, BEDROOM ADJACENT TO BATHROOM, VIEW FACING NORTH. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FACILITY 802B, BEDROOM ADJACENT TO BATHROOM, VIEW FACING NORTH. - Schofield Barracks Military Reservation, Bachelor Officers' Quarters Type, Between Grimes & Tidball Streets near Ayres Avenue, Wahiawa, Honolulu County, HI

  4. EAGLE CAP WILDERNESS AND ADJACENT AREAS, OREGON.

    USGS Publications Warehouse

    Kilsgaard, Thor H.; Tuchek, Ernest T.

    1984-01-01

    On the basis of a mineral survey of the Eagle Cap Wilderness and adjacent areas a probable mineral-resources potential was identified in five areas in the eastern part of the wilderness. Mineral resources are most likely to occur in tactite deposits in sedimentary rocks at or near contacts with intrusive granitic rocks that could contain copper and small amounts of other metals; however, there is little promise for the occurrence of energy resources.

  5. Co-expression networks reveal the tissue-specific regulation of transcription and splicing.

    PubMed

    Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D H; Jo, Brian; Gao, Chuan; McDowell, Ian C; Engelhardt, Barbara E; Battle, Alexis

    2017-11-01

    Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. © 2017 Saha et al.; Published by Cold Spring Harbor Laboratory Press.

  6. Is an attention-based associative account of adjacent and nonadjacent dependency learning valid?

    PubMed

    Pacton, Sébastien; Sobaco, Amélie; Perruchet, Pierre

    2015-05-01

    Pacton and Perruchet (2008) reported that participants who were asked to process adjacent elements located within a sequence of digits learned adjacent dependencies but did not learn nonadjacent dependencies and conversely, participants who were asked to process nonadjacent digits learned nonadjacent dependencies but did not learn adjacent dependencies. In the present study, we showed that when participants were simply asked to read aloud the same sequences of digits, a task demand that did not require the intentional processing of specific elements as in standard statistical learning tasks, only adjacent dependencies were learned. The very same pattern was observed when digits were replaced by syllables. These results show that the perfect symmetry found in Pacton and Perruchet was not due to the fact that the processing of digits is less sensitive to their distance than the processing of syllables, tones, or visual shapes used in most statistical learning tasks. Moreover, the present results, completed with a reanalysis of the data collected in Pacton and Perruchet (2008), demonstrate that participants are highly sensitive to violations involving the spacing between paired elements. Overall, these results are consistent with the Pacton and Perruchet's single-process account of adjacent and nonadjacent dependencies, in which the joint attentional processing of the two events is a necessary and sufficient condition for learning the relation between them, irrespective of their distance. However, this account should be completed to encompass the notion that the presence or absence of an intermediate event is an intrinsic component of the representation of an association. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. PMC's Florida Bay & Adjacent Marine Systems Science Program

    Science.gov Websites

    Florida Bay and Adjacent Marine Systems Science Program Inverted image, click link below to view actual image and caption click to display actual image and caption Program Overview Management & - January 2002 >For more, click here to view the What's New Page... | Main | Overview | Management &

  8. Detail of fire alarm boxes located adjacent to the entrance ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of fire alarm boxes located adjacent to the entrance of the northwest wing - Mare Island Naval Shipyard, Guard House & Barracks, Railroad Avenue near Eighteenth Street, Vallejo, Solano County, CA

  9. 52. EASTSIDE PLANT: GENERAL VIEW OF GOVERNOR ADJACENT TO GENERATOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. EASTSIDE PLANT: GENERAL VIEW OF GOVERNOR ADJACENT TO GENERATOR - American Falls Water, Power & Light Company, Island Power Plant, Snake River, below American Falls Dam, American Falls, Power County, ID

  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. Ultrastructural effects on gill tissues induced in red tilapia Oreochromis sp. by a waterborne lead exposure.

    PubMed

    Aldoghachi, Mohammed A; Azirun, Mohd Sofian; Yusoff, Ismail; Ashraf, Muhammad Aqeel

    2016-09-01

    Experiments on hybrid red tilapia Oreochromis sp. were conducted to assess histopathological effects induced in gill tissues of 96 h exposure to waterborne lead (5.5 mg/L). These tissues were investigated by light and scanning electron microscopy. Results showed that structural design of gill tissues was noticeably disrupted. Major symptoms were changes of epithelial cells, fusion in adjacent secondary lamellae, hypertrophy and hyperplasia of chloride cells and coagulate necrosis in pavement cells with disappearance of its microridges. Electron microscopic X-ray microanalysis of fish gills exposed to sublethal lead revealed that lead accumulated on the surface of the gill lamella. This study confirmed that lead exposure incited a difference of histological impairment in fish, supporting environmental watch over aquatic systems when polluted by lead.

  12. Image-guided genomic analysis of tissue response to laser-induced thermal stress

    NASA Astrophysics Data System (ADS)

    Mackanos, Mark A.; Helms, Mike; Kalish, Flora; Contag, Christopher H.

    2011-05-01

    The cytoprotective response to thermal injury is characterized by transcriptional activation of ``heat shock proteins'' (hsp) and proinflammatory proteins. Expression of these proteins may predict cellular survival. Microarray analyses were performed to identify spatially distinct gene expression patterns responding to thermal injury. Laser injury zones were identified by expression of a transgene reporter comprised of the 70 kD hsp gene and the firefly luciferase coding sequence. Zones included the laser spot, the surrounding region where hsp70-luc expression was increased, and a region adjacent to the surrounding region. A total of 145 genes were up-regulated in the laser irradiated region, while 69 were up-regulated in the adjacent region. At 7 hours the chemokine Cxcl3 was the highest expressed gene in the laser spot (24 fold) and adjacent region (32 fold). Chemokines were the most common up-regulated genes identified. Microarray gene expression was successfully validated using qRT- polymerase chain reaction for selected genes of interest. The early response genes are likely involved in cytoprotection and initiation of the healing response. Their regulatory elements will benefit creating the next generation reporter mice and controlling expression of therapeutic proteins. The identified genes serve as drug development targets that may prevent acute tissue damage and accelerate healing.

  13. Relevance of adjacent joint imaging in the evaluation of ankle fractures.

    PubMed

    Antoci, Valentin; Patel, Shaun P; Weaver, Michael J; Kwon, John Y

    2016-10-01

    Routinely obtaining adjacent joint radiographs when evaluating patients with ankle fractures may be of limited clinical utility and an unnecessary burden, particularly in the absence of clinical suspicion for concomitant injuries. One thousand, three hundred and seventy patients who sustained ankle fractures over a 5-year period presenting to two level 1 trauma centers were identified. Medical records were retrospectively reviewed for demographics, physical examination findings, and radiographic information. Analyses included descriptive statistics along with sensitivity and predictive value calculations for the presence of adjacent joint fracture. Adjacent joint imaging (n=1045 radiographs) of either the knee or foot was obtained in 873 patients (63.7%). Of those, 75/761 patients (9.9%) demonstrated additional fractures proximal to the ankle joint, most commonly of the proximal fibula. Twenty-two of 284 (7.7%) demonstrated additional fractures distal to the ankle joint, most commonly of the metatarsals. Tenderness to palpation demonstrated sensitivities of 0.92 and 0.77 and positive predictive values of 0.94 and 0.89 for the presence of proximal and distal fractures, respectively. Additionally, 19/22 (86.4%) of patients sustaining foot fractures had their injury detectable on initial ankle X-rays. Overall, only 5.5% (75/1370) of patients sustained fractures proximal to the ankle and only 0.2% (3/1370) of patients had additional foot fractures not evident on initial ankle X-rays. The addition of adjacent joint imaging for the evaluation of patients sustaining ankle fractures is low yield. As such, patient history, physical examination, and clinical suspicion should direct the need for additional X-rays. Level IV. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 3. DODGEVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR DODGEVILLE, BRISTOL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. DODGEVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR DODGEVILLE, BRISTOL CO., MA. Sec. 4116, MP 195.55. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  15. 1. HEBRONVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR. HEBRONVILLE, BRISTOL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. HEBRONVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR. HEBRONVILLE, BRISTOL CO., MA. Sec. 4116, MP 193.75. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  16. VIEW OF LAMP FIXTURE (EXTERIOR) ADJACENT TO ENTRANCE AT SOUTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF LAMP FIXTURE (EXTERIOR) ADJACENT TO ENTRANCE AT SOUTHWEST CORNER OF BUILDING 23, FACING NORTH - Roosevelt Base, Auditorium-Gymnasium, West Virginia Street between Richardson & Reeves Avenues, Long Beach, Los Angeles County, CA

  17. 5. VIEW OF CENTER PIER AND ADJACENT STRUCTURE, SHOWING PIER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF CENTER PIER AND ADJACENT STRUCTURE, SHOWING PIER STONE MASONRY AND LOWER PIN CONNECTIONS, LOOKING SOUTH - Emlenton Bridge, Spanning Allegheny River, Travel Route 38 (Legislative Route 75), Emlenton, Venango County, PA

  18. 24. INTERIOR VIEW, WILLIAM GRAY AT SIZING GUAGE ADJACENT TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. INTERIOR VIEW, WILLIAM GRAY AT SIZING GUAGE ADJACENT TO BRADLEY HAMMER; NOTE THIS IS THE SAME TOOL AS BEING FORGED ABOVE - Warwood Tool Company, Foot of Nineteenth Street, Wheeling, Ohio County, WV

  19. Identification of the collagen type 1 alpha 1 gene (COL1A1) as a candidate survival-related factor associated with hepatocellular carcinoma

    PubMed Central

    2014-01-01

    Background Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death especially among Asian and African populations. It is urgent that we identify carcinogenesis-related genes to establish an innovative treatment strategy for this disease. Methods Triple-combination array analysis was performed using one pair each of HCC and noncancerous liver samples from a 68-year-old woman. This analysis consists of expression array, single nucleotide polymorphism array and methylation array. The gene encoding collagen type 1 alpha 1 (COL1A1) was identified and verified using HCC cell lines and 48 tissues from patients with primary HCC. Results Expression array revealed that COL1A1 gene expression was markedly decreased in tumor tissues (log2 ratio –1.1). The single nucleotide polymorphism array showed no chromosomal deletion in the locus of COL1A1. Importantly, the methylation value in the tumor tissue was higher (0.557) than that of the adjacent liver tissue (0.008). We verified that expression of this gene was suppressed by promoter methylation. Reactivation of COL1A1 expression by 5-aza-2′-deoxycytidine treatment was seen in HCC cell lines, and sequence analysis identified methylated CpG sites in the COL1A1 promoter region. Among 48 pairs of surgical specimens, 13 (27.1%) showed decreased COL1A1 mRNA expression in tumor sites. Among these 13 cases, 10 had promoter methylation at the tumor site. The log-rank test indicated that mRNA down-regulated tumors were significantly correlated with a poor overall survival rate (P = 0.013). Conclusions Triple-combination array analysis successfully identified COL1A1 as a candidate survival-related gene in HCCs. Epigenetic down-regulation of COL1A1 mRNA expression might have a role as a prognostic biomarker of HCC. PMID:24552139

  20. 21. VIEW OF AXLE AND WHEEL ASSEMBLY STORAGE AREA, adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. VIEW OF AXLE AND WHEEL ASSEMBLY STORAGE AREA, adjacent to Erecting Shop and Machine Shop. - Juniata Shops, Erecting Shop & Machine Shop, East of Fourth Avenue, between Fourth & Fifth Streets, Altoona, Blair County, PA

  1. OBLIQUE OF SOUTHWEST END AND SOUTHEAST SIDE, WITH ADJACENT FACILITY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    OBLIQUE OF SOUTHWEST END AND SOUTHEAST SIDE, WITH ADJACENT FACILITY 391 IN THE FOREGROUND. - U.S. Naval Base, Pearl Harbor, Joint Intelligence Center, Makalapa Drive in Makalapa Administration Area, Pearl City, Honolulu County, HI

  2. 33. HISTORIC PLAQUE MARKING WHERE JOHNSTON DIED, ADJACENT TO PATHWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. HISTORIC PLAQUE MARKING WHERE JOHNSTON DIED, ADJACENT TO PATHWAY WITH CONCRETE CULVERT LEADING NORTH OUT OF RAVINE TOWARD JOHNSTON MEMORIAL SITE. VIEW NW. - Shiloh National Military Park Tour Roads, Shiloh, Hardin County, TN

  3. View from water showing south facade and adjacent boat slips ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View from water showing south facade and adjacent boat slips (Facility Nos. S375 & S376) - U.S. Naval Base, Pearl Harbor, Boat House, Hornet Avenue at Independence Street, Pearl City, Honolulu County, HI

  4. Feeding feedlot steers fish oil alters the fatty acid composition of adipose and muscle tissue.

    PubMed

    Wistuba, T J; Kegley, E B; Apple, J K; Rule, D C

    2007-10-01

    Sixteen steers (441±31.7kg initial body weight) consumed two high concentrate diets with either 0 or 3% fish oil to determine the impact of fish oil, an omega-3 fatty acid source, on the fatty acid composition of beef carcasses. Collected tissue samples included the Longissimus thoracis from the 6th to 7th rib section, ground 10th to 12th rib, liver, subcutaneous adipose tissue adjacent to the 12th rib, intramuscular adipose tissue in the 6th to 7th rib sections, perirenal adipose tissue, and brisket adipose tissue. Including fish oil in the diet increased most of the saturated fatty acids (P<0.01) and proportions of polyunsaturated fatty acids (P<0.06), and decreased (P<0.01) proportions of monounsaturated fatty acids. Dietary fish oil increased (P<0.01) levels of omega-3 fatty acids in sampled tissues, resulting in lower (P<0.01) omega-6:omega-3 ratios. The weight percentages of C20:5 and C22:6 in tissue may provide the recommended daily allowance for humans. Fish oil may have a role in beef niche marketing if there are no deleterious effects on consumer satisfaction.

  5. Real-time confocal laser endomicroscopic evaluation of primary liver cancer based on human liver autofluorescence.

    PubMed

    Maki, Harufumi; Kawaguchi, Yoshikuni; Arita, Junichi; Akamatsu, Nobuhisa; Kaneko, Junichi; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Harihara, Yasushi; Kokudo, Norihiro

    2017-02-01

    Confocal laser endomicroscopy (CLE) is available for real-time microscopic examination. This study aims to evaluate the usefulness of intraoperative CLE examination as a modality to evaluate surgical margins in surgery for primary liver cancer. A probe-based CLE system (Cellvizio 100, Mauna Kea Technologies, Paris, France) was used. The subjects comprised seven specimens obtained from six patients with primary liver cancer in November 2015. The probe was manually attached to the surfaces of specimens, and images were collected without external fluorophores. CLE images were compared with hematoxylin and eosin-stained slides. Fluorescence intensity (FI) values of the CLE images were assessed using luminance-analyzing software. CLE examination visualized non-cancerous regions in the background liver as regular structures with high fluorescence because of human liver autofluorescence. Conversely, hepatocellular carcinoma and intrahepatic cholangiocarcinoma were depicted as irregular structures with low fluorescence. The median FI values of the non-cancerous regions and the cancerous regions were 104 (79.8-156) and 74.9 (60.6-106), respectively, and were significantly different (P = 0.031). The probe-based CLE enables real-time differentiation of cancerous regions from non-cancerous tissues in surgical specimens because of human liver autofluorescence. CLE can be used to confirm negative surgical margins in the operating room. J. Surg. Oncol. 2017;115:151-157. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Comparative study on laser tissue ablation between PV and HPS lasers

    NASA Astrophysics Data System (ADS)

    Kang, Hyun Wook; Jebens, David; Mitchell, Gerald; Koullick, Ed

    2008-02-01

    Laser therapy for obstructive benign prostatic hyperplasia (BPH) has gained broad adoption due to effective tissue removal, immediate hemostasis, and minor complications. The aim of this study is to quantitatively compare ablation characteristics of PV (Photoselective Vaporization) and the newly introduced HPS (High Performance System) 532 nm lasers. Bovine prostatic tissues were ablated in vitro, using a custom-made scanning system. Laser-induced volume produced by two lasers was quantified as a function of applied power, fiber working distance (WD), and treatment speed. Given the same power of 80 W and speed of 4 mm/s, HPS created up to 50 % higher tissue ablation volume than PV did. PV induced a rapid decrease of ablation volume when WD increased from 0.5 mm to 3 mm while HPS yielded almost constant tissue removal up to 3 mm for both 80 W and 120 W. As the treatment speed increased, both lasers reached saturation in tissue ablation volume. Lastly, both PV and HPS lasers exhibited approximately 1 mm thick heat affected zone (HAZ) in this study although HPS created twice deeper ablation channels with a depth of up to 4 mm. Due to a smaller beam size and a higher output power, HPS maximized tissue ablation rate with minimal thermal effects to the adjacent tissue. Furthermore, more collimated beam characteristics provides more spatial flexibility and may even help to decrease the rate of fiber degradation associated with thermal damage from debris reattachment to the tip.

  7. 6. Detail, vertical guides adjacent to east portal of Tunnel ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Detail, vertical guides adjacent to east portal of Tunnel 28, view to southwest, 135mm lens with electronic flash fill. - Central Pacific Transcontinental Railroad, Tunnel No. 28, Milepost 134.75, Applegate, Placer County, CA

  8. Gene-expression signatures can distinguish gastric cancer grades and stages.

    PubMed

    Cui, Juan; Li, Fan; Wang, Guoqing; Fang, Xuedong; Puett, J David; Xu, Ying

    2011-03-18

    Microarray gene-expression data of 54 paired gastric cancer and adjacent noncancerous gastric tissues were analyzed, with the aim to establish gene signatures for cancer grades (well-, moderately-, poorly- or un-differentiated) and stages (I, II, III and IV), which have been determined by pathologists. Our statistical analysis led to the identification of a number of gene combinations whose expression patterns serve well as signatures of different grades and different stages of gastric cancer. A 19-gene signature was found to have discerning power between high- and low-grade gastric cancers in general, with overall classification accuracy at 79.6%. An expanded 198-gene panel allows the stratification of cancers into four grades and control, giving rise to an overall classification agreement of 74.2% between each grade designated by the pathologists and our prediction. Two signatures for cancer staging, consisting of 10 genes and 9 genes, respectively, provide high classification accuracies at 90.0% and 84.0%, among early-, advanced-stage cancer and control. Functional and pathway analyses on these signature genes reveal the significant relevance of the derived signatures to cancer grades and progression. To the best of our knowledge, this represents the first study on identification of genes whose expression patterns can serve as markers for cancer grades and stages.

  9. Overexpressed PTOV1 associates with tumorigenesis and progression of esophageal squamous cell carcinoma.

    PubMed

    Li, Rong; Leng, Ai-Min; Liu, Xiao-Ming; Hu, Ting-Zi; Zhang, Lin-Fang; Li, Ming; Jiang, Xiao-Xia; Zhou, Yan-Wu; Xu, Can-Xia

    2017-06-01

    PTOV1 has been demonstrated to play an extensive role in many types of cancers. This study takes the first step to clarify the potential relationship between esophageal squamous cell carcinoma and PTOV1 expression and highlight the link between PTOV1 and the tumorigenesis, progression, and prognosis of esophageal squamous cell carcinoma. PTOV1 expression was detected by quantitative reverse transcription polymerase chain reaction and western blotting or immunohistochemical staining in esophageal squamous cell carcinoma cell lines, esophageal squamous cell carcinoma tissues, and its paired adjacent non-cancerous tissues. Moreover, we have analyzed the relationship between PTOV1 expression and clinicopathological features of esophageal squamous cell carcinoma. Survival analysis and Cox regression analysis were used to assess its prognostic significance. We found that PTOV1 expression was significantly higher in the esophageal squamous cell carcinoma cell lines and tissues at messenger RNA level (p < 0.001) and protein level (p < 0.001). Gender, tumor size, or differentiation was tightly associated with the PTOV1 expression. Lymph node involvement (p < 0.001) and TNM stage (p < 0.001) promoted a high PTOV1 expression. A prognostic significance of PTOV1 was also found by Log-rank method, and the overexpression of PTOV1 was related to a shorter OS and DFS. Multiple Cox regression analysis indicated overexpressed PTOV1 as an independent indicator for adverse prognosis. In conclusion, this study takes the lead to demonstrate that the overexpressed PTOV1 plays a vital role in the tumorigenesis and progression of esophageal squamous cell carcinoma, and it is potentially a valuable prognostic predicator and new chemotherapeutic target for esophageal squamous cell carcinoma.

  10. Instabilities of mixed convection flows adjacent to inclined plates

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

    Abu-Mulaweh, H.I.; Armaly, B.F.; Chen, T.S.

    1987-11-01

    The measurements by Sparrow and Husar and by Lloyd and Sparrow established that the onset of instability (transition from laminar to turbulent) in free convection boundary layer flow above an inclined heated plate is predominated by the wave mode of instability for inclination angles less than 14 deg, as measured from the vertical, and by the vortex mode of instability for angles greater than 17 deg. The transition Grashof number deceased as the angle of inclination increased. The predictions of Chen and Tzuoo for this flow provide trends that are similar to measured values, but the predicted critical Grashof numbersmore » deviate significantly (three orders of magnitude smaller) from measured values. The instability of mixed convection boundary layer flow adjacent to inclined heated plates have also been treated numerically by Chen and Mucoglu for wave instability and by Chen et al. for vortex instability. Comparisons with measurements of instability in mixed convection flow adjacent to inclined plates were not available in the literature. It is anticipated, however, that these predictions will underestimate the actual onset of instability, as in the free convection case. The lack of measurements in this flow domain for this geometry has motivated the present study. The onset of instability in mixed convection flow adjacent to an isothermally heated inclined plate was determined in this study through flow visualization. The buoyancy-assisting and buoyancy-opposing flow cases were examined for the flow both above and below the heated plate. The critical Grashof-Reynolds number relationships for the onset of instability in this flow domain are reported in this paper.« less

  11. 14. Charles Acey Cobb standing adjacent to the fish screen ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Charles Acey Cobb standing adjacent to the fish screen he designed and installed in the Congdon Canal, facing southeast. Photo dates ca. late 1920's. - Congdon Canal, Fish Screen, Naches River, Yakima, Yakima County, WA

  12. Massive haemothorax after pulmonary endostapling preloaded with bioabsorbable tissue reinforcement material.

    PubMed

    Kanai, Yoshihiko; Endo, Shunsuke; Tetsuka, Kenji; Yamamoto, Shinichi

    2012-03-01

    Reinforced endostapling can prevent postoperative air leakage from surgical stumps. We herein present a 58-year old woman with idiopathic interstitial pneumonia who developed lethal haemothorax after a thoracoscopic lung biopsy with the use of an endostapler preloaded with bioabsorbable tissue reinforcement material. This lethal haemothorax, which occurred on the day after the lung biopsy, required an emergency operation. The bleeding point was an intercostal artery of the inferior chest wall adjacent to the surgical stump. The operative findings suggested that the reinforced material on the surgical stump scratched the chest wall through respiratory movement.

  13. Autofluorescence of seborrheic keratosis (warts) and of tissue surrounding malignant tumors

    NASA Astrophysics Data System (ADS)

    Lohmann, Wolfgang; Schill, Wolf-Bernhard; Bohle, Rainer M.; Dreyer, Thomas

    1997-12-01

    Autofluorescence measurements on human tissue have revealed a decrease in intensity in malignant tumors and an increase in the healthy region adjacent to the tumor. This latter event might serve as a protective wall against the invasive tumor cells. The composition of this wall is still unknown. Antioxidants such as NADH might be involved. In the case of seborrheic keratosis (wart), the intensity is increased in the pigmented spots. Care must be taken, therefore, when warts are attached to malignant tumors. The resulting value is, then, not indicative for the condition of the system.

  14. Time-dependent micromechanical responses of breast cancer cells and adjacent fibroblasts to electric treatment.

    PubMed

    Yizraeli, Maayan Lia; Weihs, Daphne

    2011-12-01

    Direct-current, low-intensity, electric fields were suggested as a minimally invasive treatment for various cancers. The tumor microenvironment may affect treatment efficacy, albeit it has not generally been considered when evaluating novel anti-cancer treatments. We evaluate the effects of electric treatment on epithelial, breast-cancer cells, co-cultured with non-cancerous fibroblasts, a simplified model for the tumor-microenvironment. We evaluate changes in morphology, cytoskeleton, and focus on dynamic intracellular structure and mechanics. Multiple-particle tracking was used within living cells to quantify time-dependent structural and mechanical changes. Cancer cells suffer severe cell death and exhibit transient rounding and changes in internal structural and mechanics. Interestingly, treating cancer cells in co-culture with fibroblasts delays and reduces their responses to treatment. Our particle-tracking data indicates a mechanism relating the observed changes in intracellular transport to transient changes in the microtubule network and its motors. In contrast, fibroblasts are only minimally affected by treatment, separately or in co-culture. To conclude, intracellular mechanics reveal time-dependent responses after treatment, unavailable by bulk measurements. This time-dependence could provide a window of opportunity for continued treatment. We demonstrate the importance of evaluating anti-cancer treatments within their microenvironment, which can affect response magnitude and time-course.

  15. The enhanced anti-tissue adhesive effect of injectable pluronic-HA hydrogel by poly(γ-glutamic acid).

    PubMed

    Kim, Manse; Hwang, Youngmin; Tae, Giyoong

    2016-12-01

    The stability of tissue barrier in physiological condition is a key factor to isolate the damaged site from adjacent tissue for anti-tissue adhesion. Although pluronic or pluronic-hyaluronic acid (HA) hydrogel as an injectable formulation can prevent tissue adhesion at the injection site, the anti-tissue adhesion effect is limited due to its poor stability. Herein, we prepared tissue barrier formulations composed of pluronic F127 (F127) and HA mixture (F127-HA) and the effect of the addition of poly(γ-glutamic acid) (PGA) was characterized. All of F127, HA, and F127-HA mixture showed the poor in vitro residence stability less than 3 days. However, by adding PGA into F127-HA mixture, their stability was significantly enhanced by the control of the molecular weight and concentration of PGA. Thus, F127-HA with 10wt% PGA (2000kDa) showed the long-term stability over 10 days. Similarly, the enhanced stability of F127-HA with PGA resulted in the enhanced and excellent in vivo anti-tissue adhesion effect, evidenced by histological analysis and grading of tissue adhesion. Therefore, F127-HA containing PGA could be applied as an efficient injectable tissue barrier for anti-tissue adhesion. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. 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.

  17. Vertebral Augmentation can Induce Early Signs of Degeneration in the Adjacent Intervertebral Disc: Evidence from a Rabbit Model.

    PubMed

    Feng, Zhiyun; Chen, Lunhao; Hu, Xiaojian; Yang, Ge; Wang, Yue; Chen, Zhong

    2018-04-11

    An experimental study. The aim of this study was to determine the effect of polymethylmethacrylate (PMMA) augmentation on the adjacent disc. Vertebral augmentation with PMMA reportedly may predispose the adjacent vertebra to fracture. The influence of PMMA augmentation on the adjacent disc, however, remains unclear. Using a retroperitoneal approach, PMMA augmentation was performed for 23 rabbits. For each animal, at least one vertebra was augmented with 0.2 to 0.3 mL PMMA. The disc adjacent to the augmented vertebra and a proximal control disc were studied using magnetic resonance (MR) imaging, histological and molecular level evaluation at 1, 3, and 6 months postoperatively. Marrow contact channels in the endplate were quantified in histological slices and number of invalid channels (those without erythrocytes inside) was rated. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was performed to determine disc cell apoptosis. On MR images, the signal and height of the adjacent disc did not change 6 months after vertebral augmentation. Histological scores of the adjacent disc increased over time, particularly for the nucleus pulposus. The adjacent disc had greater nucleus degeneration score than the control disc at 3 months (5.7 vs. 4.5, P < 0.01) and 6 months (6.9 vs. 4.4, P < 0.001). There were more invalid marrow contact channels in the endplate of augmented vertebra than the control (43.3% vs. 11.1%, P < 0.01). mRNA of ADAMTS-5, MMP-13, HIF-1α, and caspase-3 were significantly upregulated in the adjacent disc at 3 and 6 months (P < 0.05 for all). In addition, there were more TUNEL-positive cells in the adjacent disc than in the control disc (43.4% vs. 24.0%, P < 0.05) at 6 months postoperatively. Vertebral augmentation can induce early degenerative signs in the adjacent disc, which may be due to impaired nutrient supply to the disc. N/A.

  18. A Voronoi interior adjacency-based approach for generating a contour tree

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Qiao, Chaofei; Zhao, Renliang

    2004-05-01

    A contour tree is a good graphical tool for representing the spatial relations of contour lines and has found many applications in map generalization, map annotation, terrain analysis, etc. A new approach for generating contour trees by introducing a Voronoi-based interior adjacency set concept is proposed in this paper. The immediate interior adjacency set is employed to identify all of the children contours of each contour without contour elevations. It has advantages over existing methods such as the point-in-polygon method and the region growing-based method. This new approach can be used for spatial data mining and knowledge discovering, such as the automatic extraction of terrain features and construction of multi-resolution digital elevation model.

  19. 33 CFR 165.1301 - Puget Sound and Adjacent Waters in Northwestern Washington-Regulated Navigation Area.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Puget Sound and Adjacent Waters... Areas Thirteenth Coast Guard District § 165.1301 Puget Sound and Adjacent Waters in Northwestern... northwestern Washington waters under the jurisdiction of the Captain of the Port, Puget Sound: Puget Sound...

  20. Anterior cement augmentation of adjacent levels after vertebral body replacement leads to superior stability of the corpectomy cage under cyclic loading-a biomechanical investigation.

    PubMed

    Oberkircher, Ludwig; Krüger, Antonio; Hörth, Dominik; Hack, Juliana; Ruchholtz, Steffen; Fleege, Christoph; Rauschmann, Michael; Arabmotlagh, Mohammad

    2018-03-01

    In the operative treatment of osteoporotic vertebral body fractures, a dorsal stabilization in combination with a corpectomy of the fractured vertebral body might be necessary with respect to the fracture morphology, whereby the osteoporotic bone quality may possibly increase the risk of implant failure. To achieve better stability, it is recommended to use cement-augmented screws for dorsal instrumentation. Besides careful end plate preparation, cement augmentation of the adjacent end plates has also been reported to lead to less reduction loss. The aim of the study was to evaluate biomechanically under cyclic loading whether an additional cement augmentation of the adjacent end plates leads to improved stability of the inserted cage. Methodical cadaver study. Fourteen fresh frozen human thoracic spines with proven osteoporosis were used (T2-T7). After removal of the soft tissues, the spine was embedded in Technovit (Kulzer, Germany). Subsequently, a corpectomy of T5 was performed, leaving the dorsal ligamentary structures intact. After randomization with respect to bone quality, two groups were generated: Dorsal instrumentation (cemented pedicle screws, Medtronic, Minneapolis, MN, USA)+cage implantation (CAPRI Corpectomy Cage, K2M, Leesburg, VA, USA) without additional cementation of the adjacent endplates (Group A) and dorsal instrumentation+cage implantation with additional cement augmentation of the adjacent end plates (Group B). The subsequent axial and cyclic loading was performed at a frequency of 1 Hz, starting at 400 N and increasing the load within 200 N after every 500 cycles up to a maximum of 2,200 N. Load failure was determined when the cages sintered macroscopically into the end plates (implant failure) or when the maximum load was reached. One specimen in Group B could not be clamped appropriately into the test bench for axial loading because of a pronounced scoliotic misalignment and had to be excluded. The mean strength for implant

  1. Detail exterior view looking north showing piping system adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail exterior view looking north showing piping system adjacent to engine house. Gas cooling system is on far right. - Burnsville Natural Gas Pumping Station, Saratoga Avenue between Little Kanawha River & C&O Railroad line, Burnsville, Braxton County, WV

  2. 2. DETAIL OF CONTROL GATE ADJACENT TO LIFT LOCK NO. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. DETAIL OF CONTROL GATE ADJACENT TO LIFT LOCK NO. 7; THIS CONTROL GATE IS A 1980s RECONSTRUCTION. - Illinois & Michigan Canal, Lift Lock No. 7 & Control Gate, East side of DuPage River, Channahon, Will County, IL

  3. Tissue Expanders and Proton Beam Radiotherapy: What You Need to Know

    PubMed Central

    Howarth, Ashley L.; Niska, Joshua R.; Brooks, Kenneth; Anand, Aman; Bues, Martin; Vargas, Carlos E.

    2017-01-01

    Summary: Proton beam radiotherapy (PBR) has gained acceptance for the treatment of breast cancer because of unique beam characteristics that allow superior dose distributions with optimal dose to the target and limited collateral damage to adjacent normal tissue, especially to the heart and lungs. To determine the compatibility of breast tissue expanders (TEs) with PBR, we evaluated the structural and dosimetric properties of 2 ex vivo models: 1 model with internal struts and another model without an internal structure. Although the struts appeared to have minimal impact, we found that the metal TE port alters PBR dynamics, which may increase proton beam range uncertainty. Therefore, submuscular TE placement may be preferable to subcutaneous TE placement to reduce the interaction of the TE and proton beam. This will reduce range uncertainty and allow for more ideal radiation dose distribution. PMID:28740794

  4. Matrix Intensification Alters Avian Functional Group Composition in Adjacent Rainforest Fragments

    PubMed Central

    Deikumah, Justus P.; McAlpine, Clive A.; Maron, Martine

    2013-01-01

    Conversion of farmland land-use matrices to surface mining is an increasing threat to the habitat quality of forest remnants and their constituent biota, with consequences for ecosystem functionality. We evaluated the effects of matrix type on bird community composition and the abundance and evenness within avian functional groups in south-west Ghana. We hypothesized that surface mining near remnants may result in a shift in functional composition of avifaunal communities, potentially disrupting ecological processes within tropical forest ecosystems. Matrix intensification and proximity to the remnant edge strongly influenced the abundance of members of several functional guilds. Obligate frugivores, strict terrestrial insectivores, lower and upper strata birds, and insect gleaners were most negatively affected by adjacent mining matrices, suggesting certain ecosystem processes such as seed dispersal may be disrupted by landscape change in this region. Evenness of these functional guilds was also lower in remnants adjacent to surface mining, regardless of the distance from remnant edge, with the exception of strict terrestrial insectivores. These shifts suggest matrix intensification can influence avian functional group composition and related ecosystem-level processes in adjacent forest remnants. The management of matrix habitat quality near and within mine concessions is important for improving efforts to preserveavian biodiversity in landscapes undergoing intensification such as through increased surface mining. PMID:24058634

  5. Matrix intensification alters avian functional group composition in adjacent rainforest fragments.

    PubMed

    Deikumah, Justus P; McAlpine, Clive A; Maron, Martine

    2013-01-01

    Conversion of farmland land-use matrices to surface mining is an increasing threat to the habitat quality of forest remnants and their constituent biota, with consequences for ecosystem functionality. We evaluated the effects of matrix type on bird community composition and the abundance and evenness within avian functional groups in south-west Ghana. We hypothesized that surface mining near remnants may result in a shift in functional composition of avifaunal communities, potentially disrupting ecological processes within tropical forest ecosystems. Matrix intensification and proximity to the remnant edge strongly influenced the abundance of members of several functional guilds. Obligate frugivores, strict terrestrial insectivores, lower and upper strata birds, and insect gleaners were most negatively affected by adjacent mining matrices, suggesting certain ecosystem processes such as seed dispersal may be disrupted by landscape change in this region. Evenness of these functional guilds was also lower in remnants adjacent to surface mining, regardless of the distance from remnant edge, with the exception of strict terrestrial insectivores. These shifts suggest matrix intensification can influence avian functional group composition and related ecosystem-level processes in adjacent forest remnants. The management of matrix habitat quality near and within mine concessions is important for improving efforts to preserveavian biodiversity in landscapes undergoing intensification such as through increased surface mining.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Soft tissue remodeling technique as a non-invasive alternative to second implant surgery.

    PubMed

    Vela, Xavier; Méndez, Víctor; Rodríguez, Xavier; Segalà, Maribel; Gil, Jaime A

    2012-01-01

    It is currently accepted that success in implant-supported restorations is based not only on osseointegration, but also on achieving the esthetic outcome of natural teeth and healthy soft tissues. The socalled "pink esthetic" has become the main challenge with implant-supported rehabilitations in the anterior area. This is especially difficult in the cases with two adjacent implants. Two components affect the final periimplant gingiva: a correct bone support, and a sufficient quantity and quality of soft tissues. Several papers have emphasized the need to regenerate and preserve the bone after extractions, or after the exposure of the implants to the oral environment. The classical implantation protocol entails entering the working area several times and always involves the surgical manipulation of peri-implant tissues. Careful surgical handling of the soft tissues when exposing the implants and placing the healing abutments (second surgery) helps the clinician to obtain the best possible results, but even so there is a loss of volume of the tissues as they become weaker and more rigid after each procedure. The present study proposes a new protocol that includes the connective tissue graft placement and the soft tissues remodeling technique, which is based on the use of the ovoid pontics. This technique may help to minimize the logical scar reaction after the second surgery and to improve the final emergence profile.

  11. 3. View of side of house facing north from adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. View of side of house facing north from adjacent property. Original wood siding and trim is visible. Note: later addition to rear of house is shown in right side of photograph. - 322 South Fifteenth Street (House), Louisville, Jefferson County, KY

  12. 1. Ninth Street (west) facade. Adjacent on the north is ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Ninth Street (west) facade. Adjacent on the north is the 9th Street facade of 816 E Street. Both buildings were originally one property. - Riley Building, Rendezvous Adult Magazines & Films, 437 Ninth Street, Northwest, Washington, District of Columbia, DC

  13. LEHR NO. 2 AND LEHR NO. 3 ADJACENT TO FURNACE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    LEHR NO. 2 AND LEHR NO. 3 ADJACENT TO FURNACE ROOM; THE PIPES AT THE BOTTOM ARE PART OF THE RADIANT HEATING SYSTEM USED FOR HEATING THE FACTORY DURING COLD WEATHER. - Westmoreland Glass Company, Seventh & Kier Streets, Grapeville, Westmoreland County, PA

  14. 20. LOOKING NORTH AT MAIN SPAN, FROM FIELD ADJACENT TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. LOOKING NORTH AT MAIN SPAN, FROM FIELD ADJACENT TO 100TH STREET BRIDGE, USING 600-mm TELEPHOTO LENS. - Chicago Skyway Toll Bridge, I-90, for 7.8 miles from South State Street to Indiana state line, Chicago, Cook County, IL

  15. Interior building details of Building A, dungeon cell adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Interior building details of Building A, dungeon cell adjacent to northwest cell: granite and brick threshold, poured concrete floors, plastered finished walls, vaulted veiling; northwesterly view - San Quentin State Prison, Building 22, Point San Quentin, San Quentin, Marin County, CA

  16. Wide excision of soft tissues adjacent to the ovary and fallopian tube does not impair the ovarian reserve in women undergoing prophylactic bilateral salpingectomy: results from a randomized, controlled trial.

    PubMed

    Venturella, Roberta; Morelli, Michele; Lico, Daniela; Di Cello, Annalisa; Rocca, Morena; Sacchinelli, Angela; Mocciaro, Rita; D'Alessandro, Pietro; Maiorana, Antonio; Gizzo, Salvatore; Zullo, Fulvio

    2015-11-01

    To study the effects of the wide excision of soft tissues adjacent to the ovary and fallopian tube on ovarian function and surgical outcomes in women undergoing laparoscopic bilateral prophylactic salpingectomy. Randomized, controlled trial. Teaching hospital. One hundred eighty-six women undergoing laparoscopic surgery for uterine myoma (n = 143) or tubal surgical sterilization (n = 43). Patients were randomly divided into two groups. In group A (n = 91), standard salpingectomy was performed. In group B (n = 95), the mesosalpinx was removed within the tubes. Prior to and 3 months after surgery, antimüllerian hormone (AMH), FSH, three-dimensional antral follicle count (AFC), vascular index (VI), flow index (FI), vascular-flow index (VFI), and OvAge were recorded for each patient. Ovarian reserve modification (Δ) before and after surgery was assessed as the primary outcome. Operative time, variation of the hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were assessed as secondary outcomes. No significant difference was observed between groups for ΔAMH, ΔFSH, ΔAFC, ΔVI, ΔFI, ΔVFI, and ΔOvAge. Moreover, the groups were similar for operative time, ΔHb, postoperative hospital stay, postoperative return to normal activity, and complication rate. Even when the surgical excision includes the removal of the mesosalpinx, salpingectomy does not damage the ovarian reserve. Moreover, wide salpingectomy with excision of the mesosalpinx did not alter blood loss, hospitalization stay, or return to normal activities. NCT02086370. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Herpetology of the American Madrean Archipelago and adjacent valleys

    Treesearch

    Lawrence L. C. Jones

    2005-01-01

    Approximately 110 species of amphibians (18 frogs and toads, and 1 salamander) and reptiles (47 snakes, 39 lizards, and 5 turtles) are known from the American Madrean Archipelago and adjacent valleys. The high diversity of the herpetofauna comes from a variety of factors, including a convergence of biotic communities representing deserts, grasslands, and mountains....

  18. Coexistence Analysis of Adjacent Long Term Evolution (LTE) Systems

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

    Aulama, Mohannad M.; Olama, Mohammed M

    As the licensing and deployment of Long term evolution (LTE) systems are ramping up, the study of coexistence of LTE systems is an essential topic in civil and military applications. In this paper, we present a coexistence study of adjacent LTE systems aiming at evaluating the effect of inter-system interference on system capacity and performance as a function of some of the most common mitigation techniques: frequency guard band, base station (BS) antenna coupling loss, and user equipment (UE) antenna spacing. A system model is constructed for two collocated macro LTE networks. The developed model takes into consideration the RFmore » propagation environment, power control scheme, and adjacent channel interference. Coexistence studies are performed for a different combination of time/frequency division duplex (TDD/FDD) systems under three different guard-bands of 0MHz, 5MHz, and 10MHz. Numerical results are presented to advice the minimum frequency guard band, BS coupling loss, and UE antenna isolation required for a healthy system operation.« less

  19. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin

    PubMed Central

    Brines, Michael; Patel, Nimesh S. A.; Villa, Pia; Brines, Courtenay; Mennini, Tiziana; De Paola, Massimiliano; Erbayraktar, Zubeyde; Erbayraktar, Serhat; Sepodes, Bruno; Thiemermann, Christoph; Ghezzi, Pietro; Yamin, Michael; Hand, Carla C.; Xie, Qiao-wen; Coleman, Thomas; Cerami, Anthony

    2008-01-01

    Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the β common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58–82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia–reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure. PMID:18676614

  20. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin.

    PubMed

    Brines, Michael; Patel, Nimesh S A; Villa, Pia; Brines, Courtenay; Mennini, Tiziana; De Paola, Massimiliano; Erbayraktar, Zubeyde; Erbayraktar, Serhat; Sepodes, Bruno; Thiemermann, Christoph; Ghezzi, Pietro; Yamin, Michael; Hand, Carla C; Xie, Qiao-wen; Coleman, Thomas; Cerami, Anthony

    2008-08-05

    Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the beta common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58-82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia-reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.

  1. The dynamics of innovation through the expansion in the adjacent possible

    NASA Astrophysics Data System (ADS)

    Tria, F.

    2016-03-01

    The experience of something new is part of our daily life. At different scales, innovation is also a crucial feature of many biological, technological and social systems. Recently, large databases witnessing human activities allowed the observation that novelties -such as the individual process of listening a song for the first time- and innovation processes -such as the fixation of new genes in a population of bacteria- share striking statistical regularities. We here indicate the expansion into the adjacent possible as a very general and powerful mechanism able to explain such regularities. Further, we will identify statistical signatures of the presence of the expansion into the adjacent possible in the analyzed datasets, and we will show that our modeling scheme is able to predict remarkably well these observations.

  2. Identification of DEP domain-containing proteins by a machine learning method and experimental analysis of their expression in human HCC tissues

    NASA Astrophysics Data System (ADS)

    Liao, Zhijun; Wang, Xinrui; Zeng, Yeting; Zou, Quan

    2016-12-01

    The Dishevelled/EGL-10/Pleckstrin (DEP) domain-containing (DEPDC) proteins have seven members. However, whether this superfamily can be distinguished from other proteins based only on the amino acid sequences, remains unknown. Here, we describe a computational method to segregate DEPDCs and non-DEPDCs. First, we examined the Pfam numbers of the known DEPDCs and used the longest sequences for each Pfam to construct a phylogenetic tree. Subsequently, we extracted 188-dimensional (188D) and 20D features of DEPDCs and non-DEPDCs and classified them with random forest classifier. We also mined the motifs of human DEPDCs to find the related domains. Finally, we designed experimental verification methods of human DEPDC expression at the mRNA level in hepatocellular carcinoma (HCC) and adjacent normal tissues. The phylogenetic analysis showed that the DEPDCs superfamily can be divided into three clusters. Moreover, the 188D and 20D features can both be used to effectively distinguish the two protein types. Motif analysis revealed that the DEP and RhoGAP domain was common in human DEPDCs, human HCC and the adjacent tissues that widely expressed DEPDCs. However, their regulation was not identical. In conclusion, we successfully constructed a binary classifier for DEPDCs and experimentally verified their expression in human HCC tissues.

  3. 8. Exterior view, showing tank and associated piping adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Exterior view, showing tank and associated piping adjacent to Test Cell 6, Systems Integration Laboratory Building (T-28), looking south. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  4. 12. VIEW LOOKING WEST FROM THE PARKING LOT ADJACENT TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. VIEW LOOKING WEST FROM THE PARKING LOT ADJACENT TO THE STEEL PLANT OFFICES. BAR AND BILLET MILLS AND, IN THE DISTANCE, THE BASIC OXYGEN FURNACES MAY BE SEEN. - Corrigan, McKinney Steel Company, 3100 East Forty-fifth Street, Cleveland, Cuyahoga County, OH

  5. PRDM1 expression on the epithelial component but not on ectopic lymphoid tissues of Warthin tumour.

    PubMed

    Wang, Y; Zhou, J; Zhang, Y; Wang, L; Liu, Y; Fan, L; Zhu, J; Xu, X; Huang, G; Li, X; Xun, W

    2015-05-01

    To determine the role of PRDM1, a key molecule for modulating the immune cells, in Warthin tumour (WT) pathogenesis. Forty paraffin-embedded parotid tissues of patients (mean age: 62.08 ± 11.90) with WT were retrieved from the pathology archives of Qindu Hospital from January 2012 to December 2012. The PRDM1 expression was investigated in a cohort of WT by immunohistochemistry. PRDM1 was expressed only on the epithelial component but not on ectopic lymphoid tissue of the tumour. Statistically, PRDM1 expression rates between WT glandular epithelial cells (40/40 cases) and the tumour-adjacent tissues (0/9 cases), and WT germinal centres (0/34 cases) and tonsil tissues (10/10 cases) were significantly different (P < 0.001), respectively. The PRDM1 expression appeared to play an essential role in WT pathogenesis. A better understanding of it might give options for revealing possible novel management strategies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Two Distinct Processes of Bone-like Tissue Formation by Dental Pulp Cells after Tooth Transplantation

    PubMed Central

    Yukita, Akira; Yoshiba, Kunihiko; Yoshiba, Nagako; Takahashi, Masafumi; Nakamura, Hiroaki

    2012-01-01

    Dental pulp is involved in the formation of bone-like tissue in response to external stimuli. However, the origin of osteoblast-like cells constructing this tissue and the mechanism of their induction remain unknown. We therefore evaluated pulp mineralization induced by transplantation of a green fluorescent protein (GFP)–labeled tooth into a GFP-negative hypodermis of host rats. Five days after the transplantation, the upper pulp cavity became necrotic; however, cell-rich hard tissue was observed adjacent to dentin at the root apex. At 10 days, woven bone-like tissue was formed apart from the dentin in the upper pulp. After 20 days, these hard tissues expanded and became histologically similar to bone. GFP immunoreactivity was detected in the hard tissue-forming cells within the root apex as well as in the upper pulp. Furthermore, immunohistochemical observation of α–smooth muscle actin, a marker for undifferentiated cells, showed a positive reaction in cells surrounding this bone-like tissue within the upper pulp but not in those within the root apex. Immunoreactivities of Smad4, Runx2, and Osterix were detected in the hard tissue-forming cells within both areas. These results collectively suggest that the dental pulp contains various types of osteoblast progenitors and that these cells might thus induce bone-like tissue in severely injured pulp. PMID:22899860

  7. Reconstruction of maxillectomy and midfacial defects with free tissue transfer.

    PubMed

    Santamaria, Eric; Cordeiro, Peter G

    2006-11-01

    The maxillary bones are part of the midfacial skeleton and are closely related to the eyeglobe, nasal airway, and oral cavity. Together with the overlying soft tissues, the two maxillae are responsible to a large extent for facial contour. Maxillectomy defects become more complex when critical structures such as the orbit, globe, and cranial base are resected, and reconstruction with distant tissues become essential. In this article, we describe a classification system and algorithm for reconstruction of these complex defects using various pedicled and free flaps. Most defects that involve resection of the maxilla and adjacent soft tissues may be classified into one of the following four types: Type I defects, Limited maxillectomy; Type II defects, Subtotal maxillectomy; Type III defects, Total maxillectomy; and Type IV defects, Orbitomaxillectomy. Using this classification, reconstruction of maxillectomy and midfacial defects may be approached considering the relationship between volume and surface area requirements, that is, addressing the bony defect first, followed by assessment of the associated soft tissue, skin, palate, and cheek-lining deficits. In our experience, most complex maxillectomy defects are best reconstructed using free tissue transfer. The rectus abdominis and radial forearm free flap in combination with immediate bone grafting or as an osteocutaneous flap reliably provide the best aesthetic and functional results. A temporalis muscle pedicled flap is used for reconstruction of maxillectomy defects only in those patients who are not candidates for a microsurgical procedure.

  8. 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.

  9. 22. Float located adjacent to entry stair in filtration bed. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Float located adjacent to entry stair in filtration bed. The float actuates a valve that maintains water level over the bed. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  10. 7. VIEW OF WATER TREATMENT PLANT, ADJACENT TO THE COAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. VIEW OF WATER TREATMENT PLANT, ADJACENT TO THE COAL CONVEYOR; IN THE DISTANCE IS THE FREQUENCY CHANGER HOUSE, WHICH IS ATTACHED TO SWITCH HOUSE NO. 1; LOOKING WEST. - Commonwealth Electric Company, Fisk Street Electrical Generating Station, 1111 West Cermak Avenue, Chicago, Cook County, IL

  11. 11. Interior detail, Boiler Room, fire door to the adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Interior detail, Boiler Room, fire door to the adjacent Blacksmith Shop, Roundhouse Machine Shop Extension, Southern Pacific Railroad Carlin Shops, view to southwest (90mm lens). - Southern Pacific Railroad, Carlin Shops, Roundhouse Machine Shop Extension, Foot of Sixth Street, Carlin, Elko County, NV

  12. Impacted maxillary canines and root resorption of adjacent teeth: A retrospective observational study.

    PubMed

    Guarnieri, R; Cavallini, C; Vernucci, R; Vichi, M; Leonardi, R; Barbato, E

    2016-11-01

    The prevalence of impacted maxillary canine is reported to be between 1% and 3%. The lack of monitoring and the delay in the treatment of the impacted canine can cause different complications such as: displacement of adjacent teeth, loss of vitality of neighbouring teeth, shortening of the dental arch, follicular cysts, canine ankylosis, recurrent infections, recurrent pain, internal resorption of the canine and the adjacent teeth, external resorption of the canine and the adjacent teeth, combination of these factors. An appropriate diagnosis, accurate predictive analysis and early intervention are likely to prevent such undesirable effects. The objective is to evaluate, by means of a retrospective observational study, the possibility of carrying out a predictive analysis of root resorption adjacent to the impacted canines by means of orthopantomographs, so as to limit the prescription of additional 3D radiography. 120 subjects with unilateral or bilateral maxillary impacted canine were examined and 50 patients with 69 impacted maxillary canine (22 male, 28 female; mean age: 11.7 years) satisfied the inclusion criteria of the study. These patients were subjected to a basic clinical and radiographic investigation (orthopantomographs and computerized tomography). All panoramic films were viewed under standardized conditions for the evaluation of two main variables: maxillary canine angulations (a, b, g angles) and the overlapping between the impacted teeth and the lateral incisor (Analysis of Lindauer). Binary logistic regression was used to estimate the likelihood of resorbed lateral incisors depending on sector location and angle measurements. Results indicated that b angle has the greatest influence on the prediction of root resorption (predictive value of b angle = 76%). If β angle <18° and Lindauer = I, the probability of resorption is 0.06. Evaluation of b angle and superimposition lateral incisor/impacted canine analysed on orthopantomographs could be one of

  13. Histologic effects of a high-repetition pulsed Nd:YAG laser on intraoral soft tissue

    NASA Astrophysics Data System (ADS)

    White, Joel M.; Goodis, Harold E.; Yessik, Michael J.; Myers, Terry D.

    1995-05-01

    High-repetition rate, fiberoptic-delivered Nd:YAG lasers have increased oral soft tissue laser applications. This study focused on three parameters: the temperature rise occurring in deeper tissue during excision, the histology of thermal coagulation during excision of oral tissue, and effects of accidental exposure to adjacent hard tissue. Thermocouples were placed 5.0 +/- 0.5 mm in bone below fresh bovine gingiva and at the same depth in tongue; temperatures in the underlying tissue were measured during laser excision. An Nd:YAG laser with 100 microsecond(s) pulse duration was used to excise the tissue using a 200 or 300 micrometers diameter fiber in contact with the tissue. The soft tissue was excised using constant force and rate with laser powers of 1.5, 3, 5, and 10 W, and a variety of pulse rates. The tissue was bioprepared, sectioned and stained with hematoxylin and eosin. The width and depth of the tissue removed as well as lateral and deep thermal coagulation were measured in histologic sections with a measuring microscope (10x). Multifactor randomized ANOVA showed that probe diameter and repetition rates were not significant variables (p tissue.

  14. Effectiveness of noise barriers installed adjacent to transverse grooved concrete pavement.

    DOT National Transportation Integrated Search

    2009-10-16

    In recent years the Ohio Department of Transportation (ODOT) has reconstructed a number of roadways where asphalt pavements were replaced with random transverse grooved concrete pavements. Upon completion, residents living adjacent to the reconstruct...

  15. 33 CFR 150.35 - How may an Adjacent Coastal State request an amendment to the deepwater port operations manual?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... equivalent or improved protection and safety. The Adjacent Coastal State may petition the Commandant (CG-5P... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false How may an Adjacent Coastal State...: OPERATIONS General § 150.35 How may an Adjacent Coastal State request an amendment to the deepwater port...

  16. 33 CFR 150.35 - How may an Adjacent Coastal State request an amendment to the deepwater port operations manual?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... equivalent or improved protection and safety. The Adjacent Coastal State may petition the Commandant (CG-5P... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false How may an Adjacent Coastal State...: OPERATIONS General § 150.35 How may an Adjacent Coastal State request an amendment to the deepwater port...

  17. Massive haemothorax after pulmonary endostapling preloaded with bioabsorbable tissue reinforcement material

    PubMed Central

    Kanai, Yoshihiko; Endo, Shunsuke; Tetsuka, Kenji; Yamamoto, Shinichi

    2012-01-01

    Reinforced endostapling can prevent postoperative air leakage from surgical stumps. We herein present a 58-year old woman with idiopathic interstitial pneumonia who developed lethal haemothorax after a thoracoscopic lung biopsy with the use of an endostapler preloaded with bioabsorbable tissue reinforcement material. This lethal haemothorax, which occurred on the day after the lung biopsy, required an emergency operation. The bleeding point was an intercostal artery of the inferior chest wall adjacent to the surgical stump. The operative findings suggested that the reinforced material on the surgical stump scratched the chest wall through respiratory movement. PMID:22184467

  18. 30 CFR 57.14218 - Movement of equipment on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Movement of equipment on adjacent tracks. 57.14218 Section 57.14218 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... MINES Machinery and Equipment Safety Practices and Operational Procedures § 57.14218 Movement of...

  19. 30 CFR 56.14218 - Movement of equipment on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Movement of equipment on adjacent tracks. 56.14218 Section 56.14218 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Machinery and Equipment Safety Practices and Operational Procedures § 56.14218 Movement of equipment on...

  20. 12. LOG FOUNDATION ELEMENTS OF THE SAWMILL ADJACENT TO THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. LOG FOUNDATION ELEMENTS OF THE SAWMILL ADJACENT TO THE CANAL, LOOKING EAST. BARREN AREA IN FOREGROUND IS DECOMPOSING SAWDUST. DIRT PILE IN BACKGROUND IS THE EDGE OF THE SUMMIT COUNTY LANDFILL. - Snake River Ditch, Headgate on north bank of Snake River, Dillon, Summit County, CO

  1. 33 CFR 165.1313 - Security zone regulations, tank ship protection, Puget Sound and adjacent waters, Washington

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ship protection, Puget Sound and adjacent waters, Washington 165.1313 Section 165.1313 Navigation and... Sound and adjacent waters, Washington (a) Notice of enforcement or suspension of enforcement. The tank... Port Puget Sound. Captain of the Port Puget Sound will cause notice of the enforcement of the tank ship...

  2. 33 CFR 165.1313 - Security zone regulations, tank ship protection, Puget Sound and adjacent waters, Washington

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ship protection, Puget Sound and adjacent waters, Washington 165.1313 Section 165.1313 Navigation and... Sound and adjacent waters, Washington (a) Notice of enforcement or suspension of enforcement. The tank... Port Puget Sound. Captain of the Port Puget Sound will cause notice of the enforcement of the tank ship...

  3. Preneoplastic lesion growth driven by the death of adjacent normal stem cells

    PubMed Central

    Chao, Dennis L.; Eck, J. Thomas; Brash, Douglas E.; Maley, Carlo C.; Luebeck, E. Georg

    2008-01-01

    Clonal expansion of premalignant lesions is an important step in the progression to cancer. This process is commonly considered to be a consequence of sustaining a proliferative mutation. Here, we investigate whether the growth trajectory of clones can be better described by a model in which clone growth does not depend on a proliferative advantage. We developed a simple computer model of clonal expansion in an epithelium in which mutant clones can only colonize space left unoccupied by the death of adjacent normal stem cells. In this model, competition for space occurs along the frontier between mutant and normal territories, and both the shapes and the growth rates of lesions are governed by the differences between mutant and normal cells' replication or apoptosis rates. The behavior of this model of clonal expansion along a mutant clone's frontier, when apoptosis of both normal and mutant cells is included, matches the growth of UVB-induced p53-mutant clones in mouse dorsal epidermis better than a standard exponential growth model that does not include tissue architecture. The model predicts precancer cell mutation and death rates that agree with biological observations. These results support the hypothesis that clonal expansion of premalignant lesions can be driven by agents, such as ionizing or nonionizing radiation, that cause cell killing but do not directly stimulate cell replication. PMID:18815380

  4. Pelvic incidence-lumbar lordosis mismatch predisposes to adjacent segment disease after lumbar spinal fusion.

    PubMed

    Rothenfluh, Dominique A; Mueller, Daniel A; Rothenfluh, Esin; Min, Kan

    2015-06-01

    Several risk factors and causes of adjacent segment disease have been debated; however, no quantitative relationship to spino-pelvic parameters has been established so far. A retrospective case-control study was carried out to investigate spino-pelvic alignment in patients with adjacent segment disease compared to a control group. 45 patients (ASDis) were identified that underwent revision surgery for adjacent segment disease after on average 49 months (7-125), 39 patients were selected as control group (CTRL) similar in the distribution of the matching variables, such as age, gender, preoperative degenerative changes, and numbers of segments fused with a mean follow-up of 84 months (61-142) (total n = 84). Several radiographic parameters were measured on pre- and postoperative radiographs, including lumbar lordosis measured (LL), sacral slope, pelvic incidence (PI), and tilt. Significant differences between ASDis and CTRL groups on preoperative radiographs were seen for PI (60.9 ± 10.0° vs. 51.7 ± 10.4°, p = 0.001) and LL (48.1 ± 12.5° vs. 53.8 ± 10.8°, p = 0.012). Pelvic incidence was put into relation to lumbar lordosis by calculating the difference between pelvic incidence and lumbar lordosis (∆PILL = PI-LL, ASDis 12.5 ± 16.7° vs. CTRL 3.4 ± 12.1°, p = 0.001). A cutoff value of 9.8° was determined by logistic regression and ROC analysis and patients classified into a type A (∆PILL <10°) and a type B (∆PILL ≥10°) alignment according to pelvic incidence-lumbar lordosis mismatch. In type A spino-pelvic alignment, 25.5 % of patients underwent revision surgery for adjacent segment disease, whereas 78.3 % of patients classified as type B alignment had revision surgery. Classification of patients into type A and B alignments yields a sensitivity for predicting adjacent segment disease of 71 %, a specificity of 81 % and an odds ratio of 10.6. In degenerative disease of the lumbar spine a high pelvic incidence with diminished lumbar lordosis seems

  5. Microwave thermal radiation effects on skin tissues

    NASA Astrophysics Data System (ADS)

    Yoon, Hargsoon; Song, Kyo D.; Lee, Uhn; Choi, Sang H.

    2012-10-01

    Microwave/RF energy has been used for wireless power transmission including many therapeutic applications, such as transurethral microwave therapy (TUMT). For safe uses of RF power, it is important to know how to deliver microwave energy on focused area and control the temperature changes not to drastically increase on adjacent areas. Graphical analysis of thermal loading factor is important to understand how to achieve effective transmission of microwave through the tissue. The loss mechanism while transmission often appears as thermal effects due to absorption of microwave, especially for materials such as human skin, muscles, and other organic parts including brain. In this paper, microwave thermal effects are investigated to measure temperatures, penetration depth through animal skins in terms of input power and various frequencies. This result will be compare with the case of human applications.

  6. 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

  7. IGFBP3, a transcriptional target of homeobox D10, is correlated with the prognosis of gastric cancer.

    PubMed

    Xue, Meng; Fang, Yanfei; Sun, Guoming; Zhuo, Wei; Zhong, Jing; Qian, Cuijuan; Wang, Lan; Wang, Liangjing; Si, Jianmin; Chen, Shujie

    2013-01-01

    Homeobox D10 (HoxD10) plays important roles in the differentiation of embryonic cells and progression of breast cancer. Our previous report revealed that insulin-like growth factor binding protein-3 (IGFBP3) was regulated by HoxD10 in gastric cancer cells; however, the functional roles and underlying mechanisms of IGFBP3 in gastric cancer remain unclear. Here, we found that the expression of IGFBP3 were upregulated after ectopic expression of HoxD10 in gastric cancer cells. Chromatin immunoprecipitation assay showed that HoxD10 bound to three potential regions of IGFBP3 promoter. Exogenous HoxD10 significantly enhanced the activity of luciferase reporter containing these binding regions in gastric cancer cells. Further data showed that all of these binding sites had Hox binding element "TTAT". Immunohistochemical staining results revealed that IGFBP3 expression was significantly downregulated in 86 gastric adenocarcinomas tissues relative to their adjacent non-cancerous tissues (p<0.001). Moreover, IGFBP3 expression was significantly lower in gastric tumor with lymph node metastasis compared with that without lymph node metastasis (p=0.045). Patients with high expression level of IGFBP3 showed favorable 5 year overall survival (p=0.011). Knockdown of IGFBP3 accelerated gastric cancer cell migration and invasion and induced the expression of invasive factors including MMP14, uPA and uPAR. Thus, our data suggest that HoxD10-targeted gene IGFBP3 may suppress gastric cancer cell invasion and favors the survival of gastric cancer patients.

  8. Prognostic value of transformer 2β expression in prostate cancer.

    PubMed

    Diao, Yan; Wu, Dong; Dai, Zhijun; Kang, Huafeng; Wang, Ziming; Wang, Xijing

    2015-01-01

    Deregulation of transformer 2β (Tra2β) has been implicated in several cancers. However, the role of Tra2β expression in prostate cancer (PCa) is unclear. Therefore, this study was to investigate the expression of Tra2β in PCa and evaluated its association with clinicopathological variables and prognosis. Thirty paired fresh PCa samples were analyzed for Tra2β expression by Western blot analysis. Immunohistochemistry (IHC) assay was performed in 160 PCa samples after radical prostatectomy and adjacent non-cancerous tissues. Tra2β protein expression was divided into high expression group and low expression group by IHC. We also investigated the association of Tra2β expression with clinical and pathologic parameters. Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the association between Tra2β protein expression and prognosis of PCa patients. Our results showed that Tra2β was significantly upregulated in PCa tissues by western blot and IHC. Our data indicated that high expression of Tra2β was significantly associated with lymph node metastasis (P=0.002), clinical stage (P=0.015), preoperative prostate-specific antigen (P=0.003), Gleason score (P=0.001), and biochemical recurrence (P=0.021). High Tra2β expression was a significant predictor of poor biochemical recurrence free survival and overall survival both in univariate and multivariate analysis. We show that Tra2β was significantly upregulated in PCa patients after radical prostatectomy, and multivariate analysis confirmed Tra2β as an independent prognostic factor.

  9. Summary geochemical maps, Hoover Wilderness and adjacent study area, Mono and Tuolumne counties, California

    USGS Publications Warehouse

    Chaffee, M.A.; Hill, R.H.; Sutley, S.J.

    1984-01-01

    The Hoover Wilderness and the adjacent Hoover Extension (East), Hoover Extension (West), and Cherry Creek A Roadless Areas (the adjacent study area) encompass approximately 153,900 acres (241 mi2; 623 km2) in the Inyo, Stanislaus, and Toiyabe Naitonal Forests, Mono and Tuolumne Counties, Calif. These two areas lie along and mostly east of the crest of the Sierra Nevada, along the north and east sides of Yosemite National Park. Elevations vary from a high of 12,446 ft (3,793 m) on the crest of the Sierra Nevada to a low of about 6,500 ft (1,981 m) near the Bridgeport Ranger Station. Access to the Hoover Wilderness and adjacent study area is by U.S. Highway 395, California State Highways 108 (Sonora Pass) and 120 (Tioga Pass), and by other paved and graded roads that lead off of these U.S. and State highways.

  10. A Standardized Rat Model of Volumetric Muscle Loss Injury for the Development of Tissue Engineering Therapies

    DTIC Science & Technology

    2012-12-01

    isometric tetanic force (Po) of 28.4% and 32.5% at 2 and 4 months. Importantly, Po corrected for differences in body weight and muscle wet weights were...development, we removed progres- sively larger amounts of muscle tissue followed by a mea- surement of maximal isometric force (Po). The final model, and...indicated by increased collagen deposition (Fig. 2). The scarred area and the area immediately adjacent to it contained disorganized muscle fibers

  11. Novel Applications of Ultrasound Technology to Visualize and Characterize Myofascial Trigger Points and Surrounding Soft Tissue

    PubMed Central

    Sikdar, Siddhartha; Shah, Jay P.; Gebreab, Tadesse; Yen, Ru-Huey; Gilliams, Elizabeth; Danoff, Jerome; Gerber, Lynn H.

    2009-01-01

    Objective Apply ultrasound (US) imaging techniques to better describe the characteristics of myofascial trigger points (MTrPs) and the immediately adjacent soft tissue. Design Descriptive (exploratory) study. Setting Biomedical research center. Participants 9 subjects meeting Travell and Simons’s criteria for MTrPs in a taut band in the upper trapezius. Interventions (None) Main Outcome Measures MTrPs were evaluated by 1) physical examination, 2) pressure algometry, and 3) three types of ultrasound imaging including grayscale (2D US), vibration sonoelastography (VSE), and Doppler. Methods Four sites in each patient were labeled based on physical examination as either active MTrP (spontaneously-painful, A-MTrP), latent MTrP (non-painful, L-MTrP), or normal myofascial tissue. US examination was performed on each subject by a team blinded to the physical findings. A 12-5 MHz US transducer was used. VSE was performed by color Doppler variance imaging while simultaneously inducing vibrations (~92Hz) with a handheld massage vibrator. Each site was assigned a tissue imaging score (TIS) as follows: 0 = uniform echogenicity and stiffness; 1 = focal hypoechoic region with stiff nodule; 2 = multiple hypoechoic regions with stiff nodules. Blood flow in the neighborhood of MTrPs was assessed using Doppler imaging. Each site was assigned a blood flow waveform score (BFS) as follows: 0 = normal arterial flow in muscle; 1 = elevated diastolic flow; 2 = high-resistance flow waveform with retrograde diastolic flow. Results MTrPs appeared as focal, hypoechoic regions on 2D US, indicating local changes in tissue echogenicity, and as focal regions of reduced vibration amplitude on VSE, indicating a localized stiff nodule. MTrPs were elliptical in shape, with a size of 0.16 ± 0.11 cm2. There were no significant differences in size between A-MTrPs and L-MTrPs. Sites containing MTrPs were more likely to have higher TIS compared to normal myofascial tissue (p<0.002). Small arteries (or

  12. The relative influence of road characteristics and habitat on adjacent lizard populations in arid shrublands

    USGS Publications Warehouse

    Hubbard, Kaylan A.; Chalfoun, Anna D.; Gerow, Kenneth G.

    2016-01-01

    As road networks continue to expand globally, indirect impacts to adjacent wildlife populations remain largely unknown. Simultaneously, reptile populations are declining worldwide and anthropogenic habitat loss and fragmentation are frequently cited causes. We evaluated the relative influence of three different road characteristics (surface treatment, width, and traffic volume) and habitat features on adjacent populations of Northern Sagebrush Lizards (Sceloporus graciosus graciosus), Plateau Fence Lizards (S. tristichus), and Greater Short-Horned Lizards (Phrynosoma hernandesi) in mixed arid shrubland habitats in southwest Wyoming. Neither odds of lizard presence nor relative abundance was significantly related to any of the assessed road characteristics, although there was a trend for higher Sceloporus spp. abundance adjacent to paved roads. Sceloporus spp. relative abundance did not vary systematically with distance to the nearest road. Rather, both Sceloporus spp. and Greater Short-Horned Lizards were associated strongly with particular habitat characteristics adjacent to roads. Sceloporus spp. presence and relative abundance increased with rock cover, relative abundance was associated positively with shrub cover, and presence was associated negatively with grass cover. Greater Short-Horned Lizard presence increased with bare ground and decreased marginally with shrub cover. Our results suggest that habitat attributes are stronger correlates of lizard presence and relative abundance than individual characteristics of adjacent roads, at least in our system. Therefore, an effective conservation approach for these species may be to consider the landscape through which new roads and their associated development would occur, and the impact that placement could have on fragment size and key habitat elements.

  13. Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI.

    PubMed

    Hu, Houchun H; Yin, Larry; Aggabao, Patricia C; Perkins, Thomas G; Chia, Jonathan M; Gilsanz, Vicente

    2013-10-01

    To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity. Copyright © 2013 Wiley Periodicals, Inc.

  14. Tissue-engineered tracheal reconstruction using three-dimensionally printed artificial tracheal graft: preliminary report.

    PubMed

    Chang, Jae Won; Park, Su A; Park, Ju-Kyeong; Choi, Jae Won; Kim, Yoo-Suk; Shin, Yoo Seob; Kim, Chul-Ho

    2014-06-01

    Three-dimensional printing has come into the spotlight in the realm of tissue engineering. We intended to evaluate the plausibility of 3D-printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial tracheal defects. MSCs from rabbit bone marrow were expanded and cultured. A half-pipe-shaped 3DP polycaprolactone scaffold was coated with the MSCs seeded in fibrin. The half-pipe tracheal graft was implanted on a 10 × 10-mm artificial tracheal defect in four rabbits. Four and eight weeks after the operation, the reconstructed sites were evaluated bronchoscopically, radiologically, histologically, and functionally. None of the four rabbits showed any sign of respiratory distress. Endoscopic examination and computed tomography showed successful reconstruction of trachea without any collapse or blockage. The replaced tracheas were completely covered with regenerated respiratory mucosa. Histologic analysis showed that the implanted 3DP tracheal grafts were successfully integrated with the adjacent trachea without disruption or granulation tissue formation. Neo-cartilage formation inside the implanted graft was sufficient to maintain the patency of the reconstructed trachea. Scanning electron microscope examination confirmed the regeneration of the cilia, and beating frequency of regenerated cilia was not different from those of the normal adjacent mucosa. The shape and function of reconstructed trachea using 3DP scaffold coated with MSCs seeded in fibrin were restored successfully without any graft rejection. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  15. Microwave treatment of renal cell carcinoma adjacent to renal sinus.

    PubMed

    Gao, Yongyan; Liang, Ping; Yu, Xiaoling; Yu, Jie; Cheng, Zhigang; Han, Zhiyu; Duan, Shaobo; Huang, Hui

    2016-11-01

    To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4cm (100%, 29/29) and RCCs >4cm (75%, 9/12, p=0.021). During the median follow-up of 37.6 (range, 3.0-97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. US-guided percutaneous MWA appears to be a promising method for RCCs adjacent to renal sinus, especially for tumors ≤4cm. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Response Funtions for Computing Absorbed Dose to Skeletal Tissues from Photon Irradiation

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

    Eckerman, Keith F; Bolch, W E; Zankl, M

    2007-01-01

    The calculation of absorbed dose in skeletal tissues at radiogenic risk has been a difficult problem because the relevant structures cannot be represented in conventional geometric terms nor can they be visualised in the tomographic image data used to define the computational models of the human body. The active marrow, the tissue of concern in leukaemia induction, is present within the spongiosa regions of trabecular bone, whereas the osteoprogenitor cells at risk for bone cancer induction are considered to be within the soft tissues adjacent to the mineral surfaces. The International Commission on Radiological Protection (ICRP) recommends averaging the absorbedmore » energy over the active marrow within the spongiosa and over the soft tissues within 10 mm of the mineral surface for leukaemia and bone cancer induction, respectively. In its forthcoming recommendation, it is expected that the latter guidance will be changed to include soft tissues within 50 mm of the mineral surfaces. To address the computational problems, the skeleton of the proposed ICRP reference computational phantom has been subdivided to identify those voxels associated with cortical shell, spongiosa and the medullary cavity of the long bones. It is further proposed that the Monte Carlo calculations with these phantoms compute the energy deposition in the skeletal target tissues as the product of the particle fluence in the skeletal subdivisions and applicable fluence-to-dose response functions. This paper outlines the development of such response functions for photons.« less

  17. Drilling electrode for real-time measurement of electrical impedance in bone tissues.

    PubMed

    Dai, Yu; Xue, Yuan; Zhang, Jianxun

    2014-03-01

    In order to prevent possible damages to soft tissues, reliable monitoring methods are required to provide valuable information on the condition of the bone being cut. This paper describes the design of an electrical impedance sensing drill developed to estimate the relative position between the drill and the bone being drilled. The two-electrode method is applied to continuously measure the electrical impedance during a drill feeding movement: two copper wire brushes are used to conduct electricity in the rotating drill and then the drill is one electrode; a needle is inserted into the soft tissues adjacent to the bone being drilled and acts as another electrode. Considering that the recorded electrical impedance is correlated with the insertion depth of the drill, we theoretically calculate the electrode-tissue contact impedance and prove that the rate of impedance change varies considerably when the drill bit crosses the boundary between two different bone tissues. Therefore, the rate of impedance change is used to determine whether the tip of the drill is located in one of cortical bone, cancellous bone, and cortical bone near a boundary with soft tissue. In vitro experiments in porcine thoracic spines were performed to demonstrate the feasibility of the impedance sensing drill. The experimental results indicate that the drill, used with the proposed data-processing method, can provide accurate and reliable breakthrough detection in the bone-drilling process.

  18. Forecasters Handbook for Japan and Adjacent Sea Areas

    DTIC Science & Technology

    1988-06-01

    a strengthening Siberian high pressure cell. 4.5.1.1 Synoptic Patterns Summer is a season of reduced extratropical storm activity over the East China...the waters adjacent to eastern Asia, summer is a period of reduced extratropical storm activity over the Yellow Sea. Figure 2-6 (page 2-23) depicts...since the southeastern part of the sea is 6-15 closer to the extratropical storm tracks discussed in section 6.3.1.1 above. 6.3.1.3 Upper Level Winds

  19. Automatic registration of multi-modal microscopy images for integrative analysis of prostate tissue sections.

    PubMed

    Lippolis, Giuseppe; Edsjö, Anders; Helczynski, Leszek; Bjartell, Anders; Overgaard, Niels Chr

    2013-09-05

    Prostate cancer is one of the leading causes of cancer related deaths. For diagnosis, predicting the outcome of the disease, and for assessing potential new biomarkers, pathologists and researchers routinely analyze histological samples. Morphological and molecular information may be integrated by aligning microscopic histological images in a multiplex fashion. This process is usually time-consuming and results in intra- and inter-user variability. The aim of this study is to investigate the feasibility of using modern image analysis methods for automated alignment of microscopic images from differently stained adjacent paraffin sections from prostatic tissue specimens. Tissue samples, obtained from biopsy or radical prostatectomy, were sectioned and stained with either hematoxylin & eosin (H&E), immunohistochemistry for p63 and AMACR or Time Resolved Fluorescence (TRF) for androgen receptor (AR). Image pairs were aligned allowing for translation, rotation and scaling. The registration was performed automatically by first detecting landmarks in both images, using the scale invariant image transform (SIFT), followed by the well-known RANSAC protocol for finding point correspondences and finally aligned by Procrustes fit. The Registration results were evaluated using both visual and quantitative criteria as defined in the text. Three experiments were carried out. First, images of consecutive tissue sections stained with H&E and p63/AMACR were successfully aligned in 85 of 88 cases (96.6%). The failures occurred in 3 out of 13 cores with highly aggressive cancer (Gleason score ≥ 8). Second, TRF and H&E image pairs were aligned correctly in 103 out of 106 cases (97%).The third experiment considered the alignment of image pairs with the same staining (H&E) coming from a stack of 4 sections. The success rate for alignment dropped from 93.8% in adjacent sections to 22% for sections furthest away. The proposed method is both reliable and fast and therefore well suited

  20. Mechanistic background and clinical applications of indocyanine green fluorescence imaging of hepatocellular carcinoma.

    PubMed

    Ishizawa, Takeaki; Masuda, Koichi; Urano, Yasuteru; Kawaguchi, Yoshikuni; Satou, Shouichi; Kaneko, Junichi; Hasegawa, Kiyoshi; Shibahara, Junji; Fukayama, Masashi; Tsuji, Shingo; Midorikawa, Yutaka; Aburatani, Hiroyuki; Kokudo, Norihiro

    2014-02-01

    Although clinical applications of intraoperative fluorescence imaging of liver cancer using indocyanine green (ICG) have begun, the mechanistic background of ICG accumulation in the cancerous tissues remains unclear. In 170 patients with hepatocellular carcinoma cells (HCC), the liver surfaces and resected specimens were intraoperatively examined by using a near-infrared fluorescence imaging system after preoperative administration of ICG (0.5 mg/kg i.v.). Microscopic examinations, gene expression profile analysis, and immunohistochemical staining were performed for HCCs, which showed ICG fluorescence in the cancerous tissues (cancerous-type fluorescence), and HCCs showed fluorescence only in the surrounding non-cancerous liver parenchyma (rim-type fluorescence). ICG fluorescence imaging enabled identification of 273 of 276 (99%) HCCs in the resected specimens. HCCs showed that cancerous-type fluorescence was associated with higher cancer cell differentiation as compared with rim-type HCCs (P < 0.001). Fluorescence microscopy identified the presence of ICG in the canalicular side of the cancer cell cytoplasm, and pseudoglands of the HCCs showed a cancerous-type fluorescence pattern. The ratio of the gene and protein expression levels in the cancerous to non-cancerous tissues for Na(+)/taurocholate cotransporting polypeptide (NTCP) and organic anion-transporting polypeptide 8 (OATP8), which are associated with portal uptake of ICG by hepatocytes that tended to be higher in the HCCs that showed cancerous-type fluorescence than in those that showed rim-type fluorescence. Preserved portal uptake of ICG in differentiated HCC cells by NTCP and OATP8 with concomitant biliary excretion disorders causes accumulation of ICG in the cancerous tissues after preoperative intravenous administration. This enables highly sensitive identification of HCC by intraoperative ICG fluorescence imaging.

  1. Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

    PubMed Central

    2010-01-01

    Background Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Methods Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Results Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p < 0.05) expression in ONJ-adjacent periodontal tissue. ONJ tissue also exhibited decreased relative gene expression for Msx-1 (p < 0.03) and RANKL (p < 0.03) and increased BMP-2/4 expression (p < 0.02) compared to control. Conclusions These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in

  2. Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.

    PubMed

    Wehrhan, Falk; Hyckel, Peter; Ries, Jutta; Stockmann, Phillip; Nkenke, Emeka; Schlegel, Karl A; Neukam, Friedrich W; Amann, Kerstin

    2010-10-13

    Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p < 0.05) expression in ONJ-adjacent periodontal tissue. ONJ tissue also exhibited decreased relative gene expression for Msx-1 (p < 0.03) and RANKL (p < 0.03) and increased BMP-2/4 expression (p < 0.02) compared to control. These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred

  3. 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

  4. LOOKING NORTH AT MAIN SPAN, FROM FIELD ADJACENT TO 100TH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    LOOKING NORTH AT MAIN SPAN, FROM FIELD ADJACENT TO 100TH STREET BRIDGE, USING 600-mm TELEPHOTO LENS - Chicago Skyway Toll Bridge, I-90, for 7.8 miles from South State Street to Indiana state line, Chicago, Cook County, IL

  5. MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma.

    PubMed

    Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Wang, Xiao-Jing; Zhang, Bing; Chen, Hua

    2016-10-23

    BACKGROUND This study investigated the mechanism of miR-145 in targeting connective tissue growth factor (CTGF), which affects the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells. MATERIAL AND METHODS A total of 50 ESCC tissues and their corresponding normal adjacent esophageal tissue samples were collected. Then, miR-145 expression in both ESCC clinical specimens and cell lines was detected using quantitative real-time PCR. CTGF protein was detected using immunohistochemistry. Dual luciferase reporter gene assay was employed to assess the effect of miR-145 on the 3'UTR luciferase activity of CTGF. Eca109 cells were transfected with miR-145 mimics and CTGF siRNA, respectively, and changes in cellular proliferation, migration, and invasion were detected via MTT assay, wound-healing assay, and Transwell assay, respectively. Western blotting assay was used to detect the expression of marker genes related to EMT. RESULTS MiR-145 was significantly down-regulated in ESCC tissues and cell lines compared with normal tissues and cell lines (P<0.05). We found significantly more positively expressed CTGF protein in ESCC tissues was than in normal adjacent esophageal tissues (P<0.01). Dual luciferase reporter gene assay showed that miR-145 can specifically bind with the 3'UTR of CTGF and significantly inhibit the luciferase activity by 55% (P<0.01). Up-regulation of miR-145 or down-regulation of CTGF can suppress the proliferation, migration, invasion, and EMT process of ESCC cells. CONCLUSIONS MiR-145 was significantly down-regulated in ESCC tissues and cell lines, while the protein expression of CTGF exhibited the opposite trend. MiR-145 inhibited the proliferation, migration, invasiveness, and the EMT process of ESCC cells through targeted regulation of CTGF expression.

  6. Tissue Sodium Concentration in Myocardial Infarction in Humans: A Quantitative 23Na MR Imaging Study1

    PubMed Central

    Ouwerkerk, Ronald; Bottomley, Paul A.; Solaiyappan, Meiyappan; Spooner, Amy E.; Tomaselli, Gordon F.; Wu, Katherine C.; Weiss, Robert G.

    2008-01-01

    Purpose: To prospectively determine whether the absolute tissue sodium concentration (TSC) increases in myocardial infarctions (MIs) in humans and whether TSC is related to infarct size, infarct age, ventricular dysfunction, and/or electrophysiologic inducibility of ventricular arrhythmias. Materials and Methods: Delayed contrast material–enhanced 1.5-T hydrogen 1 (1H) magnetic resonance (MR) imaging was used to measure the size and location of nonacute MIs in 20 patients (18 men, two women; mean age, 63 years ± 9 [standard deviation]; age range, 48–82 years) examined at least 90 days after MI. End-systolic and end-diastolic volumes, ejection fraction, and left ventricle (LV) mass were measured with cine MR imaging. The TSC in normal, infarcted, and adjacent myocardial tissue was measured on sodium 23 (23Na) MR images coregistered with delayed contrast-enhanced 1H MR images. Programmed electric stimulation to induce monomorphic ventricular tachycardia (MVT) was used to assess arrhythmic potential, and myocardial TSC was compared between the inducible MVT and noninducible MVT patient groups. Results: The mean TSC for MIs (59 μmol/g wet weight ± 10) was 30% higher than that for noninfarcted (remote) LV regions (45 μmol/g wet weight ± 5, P < .001) and that for healthy control subjects, and TSC did not correlate with infarct age or functional and morphologic indices. The mean TSC for tissue adjacent to the MI (50 μmol/g wet weight ± 6) was intermediate between that for the MI and that for remote regions. The elevated TSC measured in the MI at 23Na MR imaging lacked sufficient contrast and spatial resolution for routine visualization of MI. Cardiac TSC did not enable differentiation between patients in whom MVT was inducible and those in whom it was not. Conclusion: Absolute TSC is measurable with 23Na MR imaging and is significantly elevated in human MI; however, TSC increase is not related to infarct age, infarct size, or global ventricular function. In

  7. 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.

  8. Assessment of penetrating thermal tissue damage/spread associated with PhotonBlade™, Valleylab™ Pencil, Valleylab™ EDGE™ Coated Pencil, PlasmaBlade® 3.0S and PlasmaBlade® 4.0 for intraoperative tissue dissection using the fresh extirpated porcine muscle model

    NASA Astrophysics Data System (ADS)

    Bennett, Haydon E.; Taylor, Scott D.; Fugett, James H.; Shrout, Joshua L.; Davison, Paul O.; Ryan, S. Eric; Coad, James E.

    2017-02-01

    Penetrating thermal tissue damage/spread is an important aspect of many electrosurgical devices and correlates with effective tissue cutting, hemostasis, preservation of adjacent critical structures and tissue healing. This study compared the thermal damage/spread associated with the PhotonBlade, Valleylab Pencil, Valleylab EDGE Coated Pencil, PlasmaBlade 3.0S and PlasmaBlade 4.0, when performing a single pass dynamic tissue cut in fresh extirpated porcine longissimus muscle. These devices were used in a fashion that emulated their use in the clinical setting. Each device's thermal damage/spread, at Minimum, Median and Maximum power input settings, was assessed with nitroblue tetrazolium viability staining in the WVU Pathology Laboratory for Translational Medicine. The thermal damage/spread associated with the PhotonBlade was compared with the other devices tested based on the individual treatment results (n=179 cuts combined). In summary, the PhotonBlade overall demonstrated the least penetrating thermal tissue damage/spread, followed by the PlasmaBlade 4.0, then Valleylab Pencil and PlasmaBlade 3.0S and then Valleylab EDGE Coated Pencil in order of increasing thermal damage/spread depths.

  9. A Poroelastic Fluid/Structure-Interaction Model of Cerebrospinal Fluid Dynamics in the Cord With Syringomyelia and Adjacent Subarachnoid-Space Stenosis.

    PubMed

    Bertram, C D; Heil, M

    2017-01-01

    An existing axisymmetric fluid/structure-interaction (FSI) model of the spinal cord, pia mater, subarachnoid space, and dura mater in the presence of syringomyelia and subarachnoid-space stenosis was modified to include porous solids. This allowed investigation of a hypothesis for syrinx fluid ingress from cerebrospinal fluid (CSF). Gross model deformation was unchanged by the addition of porosity, but pressure oscillated more in the syrinx and the subarachnoid space below the stenosis. The poroelastic model still exhibited elevated mean pressure in the subarachnoid space below the stenosis and in the syrinx. With realistic cord permeability, there was slight oscillatory shunt flow bypassing the stenosis via the porous tissue over the syrinx. Weak steady streaming flow occurred in a circuit involving craniocaudal flow through the stenosis and back via the syrinx. Mean syrinx volume was scarcely altered when the adjacent stenosis bisected the syrinx, but increased slightly when the syrinx was predominantly located caudal to the stenosis. The fluid content of the tissues over the syrinx oscillated, absorbing most of the radial flow seeping from the subarachnoid space so that it did not reach the syrinx. To a lesser extent, this cyclic swelling in a boundary layer of cord tissue just below the pia occurred all along the cord, representing a mechanism for exchange of interstitial fluid (ISF) and cerebrospinal fluid which could explain recent tracer findings without invoking perivascular conduits. The model demonstrates that syrinx volume increase is possible when there is subarachnoid-space stenosis and the cord and pia are permeable.

  10. 33 CFR 165.1317 - Security and Safety Zone; Large Passenger Vessel Protection, Puget Sound and adjacent waters...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Passenger Vessel Protection, Puget Sound and adjacent waters, Washington. 165.1317 Section 165.1317... Vessel Protection, Puget Sound and adjacent waters, Washington. (a) Notice of enforcement or suspension... be enforced only upon notice by the Captain of the Port Puget Sound. Captain of the Port Puget Sound...

  11. 33 CFR 165.1317 - Security and Safety Zone; Large Passenger Vessel Protection, Puget Sound and adjacent waters...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Passenger Vessel Protection, Puget Sound and adjacent waters, Washington. 165.1317 Section 165.1317... Vessel Protection, Puget Sound and adjacent waters, Washington. (a) Notice of enforcement or suspension... be enforced only upon notice by the Captain of the Port Puget Sound. Captain of the Port Puget Sound...

  12. 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.

  13. 14-3-3ζ and aPKC-ι synergistically facilitate epithelial-mesenchymal transition of cholangiocarcinoma via GSK-3β/Snail signaling pathway.

    PubMed

    Yang, Yan; Liu, Yan; He, Jun-Chuang; Wang, Jian-Ming; Schemmer, Peter; Ma, Chao-Qun; Qian, Ya-Wei; Yao, Wei; Zhang, Jian; Qi, Wei-Peng; Fu, Yang; Feng, Wei; Yang, Tao

    2016-08-23

    Cholangiocarcinoma (CCA) invasion and metastasis are the primary causes of poor survival rates in patients. The epithelial-mesenchymal transition (EMT) is a crucial step in cancer invasion and metastasis. However, it is still unclear of the molecular mechanism. In this study, the expression of 14-3-3ζ and atypical protein kinase C-ι (aPKC-ι) was further detected in CCA tissues and cell lines. Meanwhile, we established the EMT model of CCA cells and investigated 14-3-3ζ and aPKC-ι co-regulatory effect on the EMT in vitro and in vivo. Further, we identified the downstream molecular glycogen synthase kinase 3 beta (GSK-3β)/Snail signalling pathway that contribute to regulating the EMT. Our data showed that the expression of 14-3-3ζ and aPKC-ι was synergistically increased in CCA tissues compared with adjacent noncancerous tissues and was intimately associated with differentiation and the tumour-node-metastasis (TNM) stage. Multivariate Cox regression analysis indicated that high 14-3-3ζ and aPKC-ι expression separately predicted a poor prognosis and were independent prognostic indicators in patients with CCA. The CO-IP experiment confirmed that the mutual binding relationship between 14-3-3ζ and aPKC-ι. Small interfering RNAs and siRNA rescue experiment demonstrated that 14-3-3ζ and aPKC-ι regulated each other. In addition, 14-3-3ζ and aPKC-ι pretreatment by si-RNA inhibit the phosphorylated GSK-3β and Snail expression during EMT. Meanwhile, silence of 14-3-3ζ or aPKC-ι suppressed CCA cells migration, metastasis and proliferation in vitro and in vivo. Our study demonstrates that 14-3-3ζ and aPKC-ι synergistically facilitate EMT of CCA via GSK-3β/Snail signalling pathway, and may be potential therapeutic target for CCA.

  14. 14-3-3ζ and aPKC-ι synergistically facilitate epithelial-mesenchymal transition of cholangiocarcinoma via GSK-3β/snail signaling pathway

    PubMed Central

    He, Jun-chuang; Wang, Jian-ming; Schemmer, Peter; Ma, Chao-qun; Qian, Ya-wei; Yao, Wei; Zhang, Jian; Qi, Wei-peng; Fu, Yang; Feng, Wei; Yang, Tao

    2016-01-01

    Cholangiocarcinoma (CCA) invasion and metastasis are the primary causes of poor survival rates in patients. The epithelial-mesenchymal transition (EMT) is a crucial step in cancer invasion and metastasis. However, it is still unclear of the molecular mechanism. In this study, the expression of 14-3-3ζ and atypical protein kinase C-ι (aPKC-ι) was further detected in CCA tissues and cell lines. Meanwhile, we established the EMT model of CCA cells and investigated 14-3-3ζ and aPKC-ι co-regulatory effect on the EMT in vitro and in vivo. Further, we identified the downstream molecular glycogen synthase kinase 3 beta (GSK-3β)/Snail signalling pathway that contribute to regulating the EMT. Our data showed that the expression of 14-3-3ζ and aPKC-ι was synergistically increased in CCA tissues compared with adjacent noncancerous tissues and was intimately associated with differentiation and the tumour-node-metastasis (TNM) stage. Multivariate Cox regression analysis indicated that high 14-3-3ζ and aPKC-ι expression separately predicted a poor prognosis and were independent prognostic indicators in patients with CCA. The CO-IP experiment confirmed that the mutual binding relationship between 14-3-3ζ and aPKC-ι. Small interfering RNAs and siRNA rescue experiment demonstrated that 14-3-3ζ and aPKC-ι regulated each other. In addition, 14-3-3ζ and aPKC-ι pretreatment by si-RNA inhibit the phosphorylated GSK-3β and Snail expression during EMT. Meanwhile, silence of 14-3-3ζ or aPKC-ι suppressed CCA cells migration, metastasis and proliferation in vitro and in vivo. Our study demonstrates that 14-3-3ζ and aPKC-ι synergistically facilitate EMT of CCA via GSK-3β/Snail signalling pathway, and may be potential therapeutic target for CCA. PMID:27409422

  15. Epithelial alterations adjacent to invasive squamous carcinoma of the vulva.

    PubMed

    Gómez Rueda, N; García, A; Vighi, S; Belardi, M G; Cardinal, L; di Paola, G

    1994-07-01

    The slides of 64 vulvectomy specimens from vulvar squamous carcinoma were reviewed in order to study the histopathologic changes adjacent to the neoplasia. Normal epithelium was found in 7 cases (11%) and epithelial alterations adjacent to carcinoma in 59 (89%). The epithelial alterations found were: nonneoplastic epithelial disorder (NNDV) in 38 cases (59%) and vulvar intraepithelial neoplasia (VIN) in 19 (30%). The distribution of NNDV was: 20 cases of epithelial hyperplasia (EH) (31%), 6 of lichen sclerosus (9%) and 12 of the mixed type (19%). Sixteen cases of VIN 3 (25%) were undifferentiated, and three cases were differentiated VIN. Eighteen of 19 VIN cases were associated with NNDV, and 8 cases of undifferentiated VIN were associated with human papillomavirus infection. There was no apparent relationship between the associated lesions and tumor size, depth of invasion, lymph node metastases and clinical stage. Nevertheless, we found a significantly higher frequency of associated lesions in poorly differentiated tumors (P > .01). The most important finding was a high association between EH (50%) and VIN (30%) with carcinoma. VIN cases were almost always (95%) associated with EH.

  16. 33 CFR 334.1080 - San Francisco Bay adjacent to northeast corner of Treasure Island; naval restricted area.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false San Francisco Bay adjacent to northeast corner of Treasure Island; naval restricted area. 334.1080 Section 334.1080 Navigation and... RESTRICTED AREA REGULATIONS § 334.1080 San Francisco Bay adjacent to northeast corner of Treasure Island...

  17. Stress Wave Interaction Between Two Adjacent Blast Holes

    NASA Astrophysics Data System (ADS)

    Yi, Changping; Johansson, Daniel; Nyberg, Ulf; Beyglou, Ali

    2016-05-01

    Rock fragmentation by blasting is determined by the level and state of stress in the rock mass subjected to blasting. With the application of electronic detonators, some researchers stated that it is possible to achieve improved fragmentation through stress wave superposition with very short delay times. This hypothesis was studied through theoretical analysis in the paper. First, the stress in rock mass induced by a single-hole shot was analyzed with the assumptions of infinite velocity of detonation and infinite charge length. Based on the stress analysis of a single-hole shot, the stress history and tensile stress distribution between two adjacent holes were presented for cases of simultaneous initiation and 1 ms delayed initiation via stress superposition. The results indicated that the stress wave interaction is local around the collision point. Then, the tensile stress distribution at the extended line of two adjacent blast holes was analyzed for a case of 2 ms delay. The analytical results showed that the tensile stress on the extended line increases due to the stress wave superposition under the assumption that the influence of neighboring blast hole on the stress wave propagation can be neglected. However, the numerical results indicated that this assumption is unreasonable and yields contrary results. The feasibility of improving fragmentation via stress wave interaction with precise initiation was also discussed. The analysis in this paper does not support that the interaction of stress waves improves the fragmentation.

  18. LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

    PubMed

    Leonard, B E; Lucas, A C

    2009-02-01

    Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to <10 cGy h(-1) and involve multiple patients to detect patient variability. Results may suggest a preference for high dose rate brachytherapy or LDR brachytherapy without permanent retention of the implant seeds (hence the dose rates in peripheral tissues and organs remain above IDRE thresholds).

  19. An overview of inverted colloidal crystal systems for tissue engineering.

    PubMed

    João, Carlos Filipe C; Vasconcelos, Joana Marta; Silva, Jorge Carvalho; Borges, João Paulo

    2014-10-01

    Scaffolding is at the heart of tissue engineering but the number of techniques available for turning biomaterials into scaffolds displaying the features required for a tissue engineering application is somewhat limited. Inverted colloidal crystals (ICCs) are inverse replicas of an ordered array of monodisperse colloidal particles, which organize themselves in packed long-range crystals. The literature on ICC systems has grown enormously in the past 20 years, driven by the need to find organized macroporous structures. Although replicating the structure of packed colloidal crystals (CCs) into solid structures has produced a wide range of advanced materials (e.g., photonic crystals, catalysts, and membranes) only in recent years have ICCs been evaluated as devices for medical/pharmaceutical and tissue engineering applications. The geometry, size, pore density, and interconnectivity are features of the scaffold that strongly affect the cell environment with consequences on cell adhesion, proliferation, and differentiation. ICC scaffolds are highly geometrically ordered structures with increased porosity and connectivity, which enhances oxygen and nutrient diffusion, providing optimum cellular development. In comparison to other types of scaffolds, ICCs have three major unique features: the isotropic three-dimensional environment, comprising highly uniform and size-controllable pores, and the presence of windows connecting adjacent pores. Thus far, this is the only technique that guarantees these features with a long-range order, between a few nanometers and thousands of micrometers. In this review, we present the current development status of ICC scaffolds for tissue engineering applications.

  20. Validation of a Radiography-Based Quantification Designed to Longitudinally Monitor Soft Tissue Calcification in Skeletal Muscle.

    PubMed

    Moore, Stephanie N; Hawley, Gregory D; Smith, Emily N; Mignemi, Nicholas A; Ihejirika, Rivka C; Yuasa, Masato; Cates, Justin M M; Liu, Xulei; Schoenecker, Jonathan G

    2016-01-01

    Soft tissue calcification, including both dystrophic calcification and heterotopic ossification, may occur following injury. These lesions have variable fates as they are either resorbed or persist. Persistent soft tissue calcification may result in chronic inflammation and/or loss of function of that soft tissue. The molecular mechanisms that result in the development and maturation of calcifications are uncertain. As a result, directed therapies that prevent or resorb soft tissue calcifications remain largely unsuccessful. Animal models of post-traumatic soft tissue calcification that allow for cost-effective, serial analysis of an individual animal over time are necessary to derive and test novel therapies. We have determined that a cardiotoxin-induced injury of the muscles in the posterior compartment of the lower extremity represents a useful model in which soft tissue calcification develops remote from adjacent bones, thereby allowing for serial analysis by plain radiography. The purpose of the study was to design and validate a method for quantifying soft tissue calcifications in mice longitudinally using plain radiographic techniques and an ordinal scoring system. Muscle injury was induced by injecting cardiotoxin into the posterior compartment of the lower extremity in mice susceptible to developing soft tissue calcification. Seven days following injury, radiographs were obtained under anesthesia. Multiple researchers applied methods designed to standardize post-image processing of digital radiographs (N = 4) and quantify soft tissue calcification (N = 6) in these images using an ordinal scoring system. Inter- and intra-observer agreement for both post-image processing and the scoring system used was assessed using weighted kappa statistics. Soft tissue calcification quantifications by the ordinal scale were compared to mineral volume measurements (threshold 450.7mgHA/cm3) determined by μCT. Finally, sample-size calculations necessary to discriminate

  1. Validation of a Radiography-Based Quantification Designed to Longitudinally Monitor Soft Tissue Calcification in Skeletal Muscle

    PubMed Central

    Moore, Stephanie N.; Hawley, Gregory D.; Smith, Emily N.; Mignemi, Nicholas A.; Ihejirika, Rivka C.; Yuasa, Masato; Cates, Justin M. M.; Liu, Xulei; Schoenecker, Jonathan G.

    2016-01-01

    Introduction Soft tissue calcification, including both dystrophic calcification and heterotopic ossification, may occur following injury. These lesions have variable fates as they are either resorbed or persist. Persistent soft tissue calcification may result in chronic inflammation and/or loss of function of that soft tissue. The molecular mechanisms that result in the development and maturation of calcifications are uncertain. As a result, directed therapies that prevent or resorb soft tissue calcifications remain largely unsuccessful. Animal models of post-traumatic soft tissue calcification that allow for cost-effective, serial analysis of an individual animal over time are necessary to derive and test novel therapies. We have determined that a cardiotoxin-induced injury of the muscles in the posterior compartment of the lower extremity represents a useful model in which soft tissue calcification develops remote from adjacent bones, thereby allowing for serial analysis by plain radiography. The purpose of the study was to design and validate a method for quantifying soft tissue calcifications in mice longitudinally using plain radiographic techniques and an ordinal scoring system. Methods Muscle injury was induced by injecting cardiotoxin into the posterior compartment of the lower extremity in mice susceptible to developing soft tissue calcification. Seven days following injury, radiographs were obtained under anesthesia. Multiple researchers applied methods designed to standardize post-image processing of digital radiographs (N = 4) and quantify soft tissue calcification (N = 6) in these images using an ordinal scoring system. Inter- and intra-observer agreement for both post-image processing and the scoring system used was assessed using weighted kappa statistics. Soft tissue calcification quantifications by the ordinal scale were compared to mineral volume measurements (threshold 450.7mgHA/cm3) determined by μCT. Finally, sample-size calculations necessary

  2. The change of adjacent segment after cervical disc arthroplasty compared with anterior cervical discectomy and fusion: a meta-analysis of randomized controlled trials.

    PubMed

    Dong, Liang; Xu, Zhengwei; Chen, Xiujin; Wang, Dongqi; Li, Dichen; Liu, Tuanjing; Hao, Dingjun

    2017-10-01

    Many meta-analyses have been performed to study the efficacy of cervical disc arthroplasty (CDA) compared with anterior cervical discectomy and fusion (ACDF); however, there are few data referring to adjacent segment within these meta-analyses, or investigators are unable to arrive at the same conclusion in the few meta-analyses about adjacent segment. With the increased concerns surrounding adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis) after anterior cervical surgery, it is necessary to perform a comprehensive meta-analysis to analyze adjacent segment parameters. To perform a comprehensive meta-analysis to elaborate adjacent segment motion, degeneration, disease, and reoperation of CDA compared with ACDF. Meta-analysis of randomized controlled trials (RCTs). PubMed, Embase, and Cochrane Library were searched for RCTs comparing CDA and ACDF before May 2016. The analysis parameters included follow-up time, operative segments, adjacent segment motion, ASDeg, ASDis, and adjacent segment reoperation. The risk of bias scale was used to assess the papers. Subgroup analysis and sensitivity analysis were used to analyze the reason for high heterogeneity. Twenty-nine RCTs fulfilled the inclusion criteria. Compared with ACDF, the rate of adjacent segment reoperation in the CDA group was significantly lower (p<.01), and the advantage of that group in reducing adjacent segment reoperation increases with increasing follow-up time by subgroup analysis. There was no statistically significant difference in ASDeg between CDA and ACDF within the 24-month follow-up period; however, the rate of ASDeg in CDA was significantly lower than that of ACDF with the increase in follow-up time (p<.01). There was no statistically significant difference in ASDis between CDA and ACDF (p>.05). Cervical disc arthroplasty provided a lower adjacent segment range of motion (ROM) than did ACDF, but the difference was not statistically significant. Compared with ACDF, the

  3. 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.

  4. Phosmet residues in an orchard and adjacent recreational area.

    PubMed

    MacNeil, J D; Hikichi, M

    1986-10-01

    Two cover sprays of phosmet were applied to an orchard adjoining a camping area and a bird sanctuary with a resident goose population. Insecticide residues were monitored on orchard leaves, orchard ground cover, ground cover in the camp-site and along the adjacent lakeshore. Despite attempts to minimize drift, significant spray residues were found outside the target area. Residues on ground cover and leaves were reduced by sprinkler irrigation subsequent to spray application.

  5. Adjacent Segment Disease After Cervical Spine Fusion: Evaluation of a 70 Patient Long-Term Follow-Up.

    PubMed

    Alhashash, Mohamed; Shousha, Mootaz; Boehm, Heinrich

    2018-05-01

    A retrospective study of 70 patients undergoing surgical treatment for adjacent segment disease (ASD) after anterior cervical decompression and fusion (ACDF). To analyze the risk factors for the development of ASD in patients who underwent ACDF. ACDF has provided a high rate of clinical success for the cervical degenerative disc disease; nevertheless, adjacent segment degeneration has been reported as a complication at the adjacent level secondary to the rigid fixation. Between January 2005 and December 2012, 70 consecutive patients underwent surgery for ASD after ACDF in our institution. In all patients thorough clinical and radiological examination was performed preoperatively, postoperatively, and at the final follow-up. The clinical data included the Neck Disability Index (NDI) and the Visual Analogue Scale (VAS). The radiological evaluation included x-rays and magnetic resonance imaging (MRI) for all patients. The duration of follow up after the adjacent segment operation ranged from 3 to 10 years. Surgery for ASD was performed after a mean period of 32 months from the primary ACDF. ASD occurred after single level ACDF in 54% of cases, most commonly after C5/6 fusion (28%). Risk factors for ASD were found to be preexisting radiological signs of degeneration at the primary surgery (74%) and bad sagittal profile after the primary ACDF (90%). ASD occurred predominantly in the middle cervical region (C4-6); especially in patients with preexisting evidence of radiological degeneration in the adjacent segment at the time of primary cervical fusion, notably when this surgery failed to restore or maintain the cervical lordosis. 4.

  6. Optical coherence tomography can assess skeletal muscle tissue from mouse models of muscular dystrophy by parametric imaging of the attenuation coefficient

    PubMed Central

    Klyen, Blake R.; Scolaro, Loretta; Shavlakadze, Tea; Grounds, Miranda D.; Sampson, David D.

    2014-01-01

    We present the assessment of ex vivo mouse muscle tissue by quantitative parametric imaging of the near-infrared attenuation coefficient µt using optical coherence tomography. The resulting values of the local total attenuation coefficient µt (mean ± standard error) from necrotic lesions in the dystrophic skeletal muscle tissue of mdx mice are higher (9.6 ± 0.3 mm−1) than regions from the same tissue containing only necrotic myofibers (7.0 ± 0.6 mm−1), and significantly higher than values from intact myofibers, whether from an adjacent region of the same sample (4.8 ± 0.3 mm−1) or from healthy tissue of the wild-type C57 mouse (3.9 ± 0.2 mm−1) used as a control. Our results suggest that the attenuation coefficient could be used as a quantitative means to identify necrotic lesions and assess skeletal muscle tissue in mouse models of human Duchenne muscular dystrophy. PMID:24761302

  7. Evaluation of different tissue de-paraffinization procedures for infrared spectral imaging.

    PubMed

    Nallala, Jayakrupakar; Lloyd, Gavin Rhys; Stone, Nicholas

    2015-04-07

    In infrared spectral histopathology, paraffin embedded tissues are often de-paraffinized using chemical agents such as xylene and hexane. These chemicals are known to be toxic and the routine de-waxing procedure is time consuming. A comparative study was carried out to identify alternate de-paraffinization methods by using paraffin oil and electronic de-paraffinization (using a mathematical computer algorithm) and their effectiveness was compared to xylene and hexane. Sixteen adjacent tissue sections obtained from a single block of a normal colon tissue were de-paraffinized using xylene, hexane and paraffin oil (+ hexane wash) at five different time points each for comparison. One section was reserved unprocessed for electronic de-paraffinization based on a modified extended multiplicative signal correction (EMSC). IR imaging was carried out on these tissue sections. Coefficients based on the fit of a pure paraffin model to the IR images were then calculated to estimate the amount of paraffin remaining after processing. Results indicate that on average xylene removes more paraffin in comparison to hexane and paraffin oil although the differences were small. This makes paraffin oil, followed by a hexane wash, an interesting and less toxic alternative method of de-paraffinization. However, none of the chemical methods removed paraffin completely from the tissues at any given time point. Moreover, paraffin was removed more easily from the glandular regions than the connective tissue regions indicating a form of differential paraffin retention based on the histology. In such cases, the use of electronic de-paraffinization to neutralize such variances across different tissue regions might be considered. Moreover it is faster, reduces scatter artefacts by index matching and enables samples to be easily stored for further analysis if required.

  8. Connective tissue growth factor is activated by gastrin and involved in gastrin-induced migration and invasion.

    PubMed

    Bhandari, Sabin; Bakke, Ingunn; Kumar, J; Beisvag, Vidar; Sandvik, Arne K; Thommesen, Liv; Varro, Andrea; Nørsett, Kristin G

    2016-06-17

    Connective tissue growth factor (CTGF) has been reported in gastric adenocarcinoma and in carcinoid tumors. The aim of this study was to explore a possible link between CTGF and gastrin in gastric epithelial cells and to study the role of CTGF in gastrin induced migration and invasion of AGS-GR cells. The effects of gastrin were studied using RT-qPCR, Western blot and assays for migration and invasion. We report an association between serum gastrin concentrations and CTGF abundancy in the gastric corpus mucosa of hypergastrinemic subjects and mice. We found a higher expression of CTGF in gastric mucosa tissue adjacent to tumor compared to normal control tissue. We showed that gastrin induced expression of CTGF in gastric epithelial AGS-GR cells via MEK, PKC and PKB/AKT pathways. CTGF inhibited gastrin induced migration and invasion of AGS-GR cells. We conclude that CTGF expression is stimulated by gastrin and involved in remodeling of the gastric epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Timber resources of the Kuskokwim flood plain and adjacent upland.

    Treesearch

    Karl M. Hegg; Harold. Sieverding

    1979-01-01

    The first intensive forest inventory of the Kuskokwim River flood plains and adjacent uplands was conducted in 1967. A commercial forest area of 252.5 thousand acres (102.2 thousand hectares) was identified with a growing-stock volume of 343.0 million cubic feet (9.7 million cubic meters). A noncommercial stratum was also examined that had substantial standing volume...

  10. Sound insulation property of membrane-type acoustic metamaterials carrying different masses at adjacent cells

    NASA Astrophysics Data System (ADS)

    Zhang, Yuguang; Wen, Jihong; Zhao, Honggang; Yu, Dianlong; Cai, Li; Wen, Xisen

    2013-08-01

    We present the experimental realization and theoretical understanding of membrane-type acoustic metamaterials embedded with different masses at adjacent cells, capable of increasing the transmission loss at low frequency. Owing to the reverse vibration of adjacent cells, Transmission loss (TL) peaks appear, and the magnitudes of the TL peaks exceed the predicted results of the composite wall. Compared with commonly used configuration, i.e., all cells carrying with identical mass, the nonuniformity of attaching masses causes another much low TL peak. Finite element analysis was employed to validate and provide insights into the TL behavior of the structure.

  11. The effects of tunnel horizontal distance on the vertical deformations of an adjacent building

    NASA Astrophysics Data System (ADS)

    Balkaya, Müge

    2015-12-01

    Due to the rapid development of urbanization and the need for effective transportation, it became a common application to construct subway tunnels in modern cities. However, these construction activities may lead to undesirable deformations on the adjacent buildings. In this study, the effect of tunnel horizontal distance on the deformations of an adjacent building is investigated using 2D finite element analysis. The results of the finite element analysis showed that, although high settlement values were not observed for the cases investigated in this study, the vertical deformations of the building decreased as the tunnel moved away from the building.

  12. Global Epigenetic Changes May Underlie Ethnic Differences and Susceptibility to Prostate Cancer

    DTIC Science & Technology

    2013-09-01

    malignancy and can often be found in non-cancerous tissues; in the prostate, hypermethylation of the GSTP1 CpG has been detected in PIA lesions [8]. DNA...methylcytosine (5-meC; [9, 10]). Since the recognition that the GSTP1 CpG island was frequently hypermethylated in PCa, more than 40 genes have been reported to...has also been identified for several genes. One study demonstrated that GSTP1 hypermethylation was significantly higher in PCa samples from AA men

  13. ArF excimer laser debrides burns without destruction of viable tissue: A pilot study.

    PubMed

    Prasad, Atulya; Sawicka, Katarzyna M; Pablo, Kelly B; Macri, Lauren K; Felsenstein, Jerome; Wynne, James J; Clark, Richard A F

    2018-05-01

    Recent evidence indicates that early removal of eschar by tangential debridement can promote healing. Laser debridement can be used for debridement of areas that prove challenging for debridement using tangential excision. In particular, irradiation with an ArF excimer laser ablates desiccated eschar and is self-terminating, preserving hydrated or viable tissue. Thermal burns were created on the flanks of two outbred, female Yorkshire pigs using aluminum bars heated to 70°C and applied for different lengths of time. Three days after injury, burns were debrided using an ArF excimer laser (193nm). Tissue was harvested immediately after debridement and 7days after debridement (10days after burn). Data from a pilot study demonstrates that ArF excimer laser irradiation removes burn eschar and promotes healing at 10days after burn. ArF excimer laser debridement is self-terminating and preserves underlying and adjacent perfused tissue. Potentially, this modality would be ideal for the complex curvilinear structures of the body. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  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. Carbon nanotubes with high bone-tissue compatibility and bone-formation acceleration effects.

    PubMed

    Usui, Yuki; Aoki, Kaoru; Narita, Nobuyo; Murakami, Narumichi; Nakamura, Isao; Nakamura, Koichi; Ishigaki, Norio; Yamazaki, Hiroshi; Horiuchi, Hiroshi; Kato, Hiroyuki; Taruta, Seiichi; Kim, Yoong Ahm; Endo, Morinobu; Saito, Naoto

    2008-02-01

    Carbon nanotubes (CNTs) have been used in various fields as composites with other substances or alone to develop highly functional materials. CNTs hold great interest with respect to biomaterials, particularly those to be positioned in contact with bone such as prostheses for arthroplasty, plates or screws for fracture fixation, drug delivery systems, and scaffolding for bone regeneration. Accordingly, bone-tissue compatibility of CNTs and CNT influence on bone formation are important issues, but the effects of CNTs on bone have not been delineated. Here, it is found that multi-walled CNTs adjoining bone induce little local inflammatory reaction, show high bone-tissue compatibility, permit bone repair, become integrated into new bone, and accelerate bone formation stimulated by recombinant human bone morphogenetic protein-2 (rhBMP-2). This study provides an initial investigational basis for CNTs in biomaterials that are used adjacent to bone, including uses to promote bone regeneration. These findings should encourage development of clinical treatment modalities involving CNTs.

  16. Shock-induced bubble jetting into a viscous fluid with application to tissue injury in shock-wave lithotripsy.

    PubMed

    Freund, J B; Shukla, R K; Evan, A P

    2009-11-01

    Shock waves in liquids are known to cause spherical gas bubbles to rapidly collapse and form strong re-entrant jets in the direction of the propagating shock. The interaction of these jets with an adjacent viscous liquid is investigated using finite-volume simulation methods. This configuration serves as a model for tissue injury during shock-wave lithotripsy, a medical procedure to remove kidney stones. In this case, the viscous fluid provides a crude model for the tissue. It is found that for viscosities comparable to what might be expected in tissue, the jet that forms upon collapse of a small bubble fails to penetrate deeply into the viscous fluid "tissue." A simple model reproduces the penetration distance versus viscosity observed in the simulations and leads to a phenomenological model for the spreading of injury with multiple shocks. For a reasonable selection of a single efficiency parameter, this model is able to reproduce in vivo observations of an apparent 1000-shock threshold before wide-spread tissue injury occurs in targeted kidneys and the approximate extent of this injury after a typical clinical dose of 2000 shock waves.

  17. Shock-induced bubble jetting into a viscous fluid with application to tissue injury in shock-wave lithotripsy

    PubMed Central

    Freund, J. B.; Shukla, R. K.; Evan, A. P.

    2009-01-01

    Shock waves in liquids are known to cause spherical gas bubbles to rapidly collapse and form strong re-entrant jets in the direction of the propagating shock. The interaction of these jets with an adjacent viscous liquid is investigated using finite-volume simulation methods. This configuration serves as a model for tissue injury during shock-wave lithotripsy, a medical procedure to remove kidney stones. In this case, the viscous fluid provides a crude model for the tissue. It is found that for viscosities comparable to what might be expected in tissue, the jet that forms upon collapse of a small bubble fails to penetrate deeply into the viscous fluid “tissue.” A simple model reproduces the penetration distance versus viscosity observed in the simulations and leads to a phenomenological model for the spreading of injury with multiple shocks. For a reasonable selection of a single efficiency parameter, this model is able to reproduce in vivo observations of an apparent 1000-shock threshold before wide-spread tissue injury occurs in targeted kidneys and the approximate extent of this injury after a typical clinical dose of 2000 shock waves. PMID:19894850

  18. Adjacent segment infection after surgical treatment of spondylodiscitis.

    PubMed

    Siam, Ahmed Ezzat; El Saghir, Hesham; Boehm, Heinrich

    2016-03-01

    This is the first case series to describe adjacent segment infection (ASI) after surgical treatment of spondylodiscitis (SD). Patients with SD, spondylitis who were surgically treated between 1994 and 2012 were included. Out of 1187 cases, 23 (1.94 %) returned to our institution (Zentralklinik Bad Berka) with ASI: 10 males, 13 females, with a mean age of 65.1 years and a mean follow-up of 69 months. ASI most commonly involved L3-4 (seven patients), T12-L1 (five) and L2-3 (four). The mean interval between operations of primary infection and ASI was 36.9 months. All cases needed surgical intervention, debridement, reconstruction and fusion with longer instrumentation, with culture and sensitivity-based postoperative antimicrobial therapy. At last follow-up, six patients (26.1 %) were mobilized in a wheelchair with a varying degree of paraplegia (three had pre-existing paralysis). Three patients died within 2 months after the ASI operation (13 %). Excellent outcomes were achieved in five patients, and good in eight. Adjacent segment infection after surgical treatment of spondylodiscitis is a rare complication (1.94 %). It is associated with multimorbidity and shows a high mortality rate and a high neurological affection rate. Possible explanations are: haematomas of repeated micro-fractures around screw loosening, haematogenous spread, direct inoculation or a combination of these factors. ASI may also lead to proximal junctional kyphosis, as found in this series. We suggest early surgical intervention with anterior debridement, reconstruction and fusion with posterior instrumentation, followed by antimicrobial therapy for 12 weeks. Level IV retrospective uncontrolled case series.

  19. Hybrid dynamic stabilization: a biomechanical assessment of adjacent and supraadjacent levels of the lumbar spine.

    PubMed

    Mageswaran, Prasath; Techy, Fernando; Colbrunn, Robb W; Bonner, Tara F; McLain, Robert F

    2012-09-01

    The object of this study was to evaluate the effect of hybrid dynamic stabilization on adjacent levels of the lumbar spine. Seven human spine specimens from T-12 to the sacrum were used. The following conditions were implemented: 1) intact spine; 2) fusion of L4-5 with bilateral pedicle screws and titanium rods; and 3) supplementation of the L4-5 fusion with pedicle screw dynamic stabilization constructs at L3-4, with the purpose of protecting the L3-4 level from excessive range of motion (ROM) and to create a smoother motion transition to the rest of the lumbar spine. An industrial robot was used to apply continuous pure moment (± 2 Nm) in flexion-extension with and without a follower load, lateral bending, and axial rotation. Intersegmental rotations of the fused, dynamically stabilized, and adjacent levels were measured and compared. In flexion-extension only, the rigid instrumentation at L4-5 caused a 78% decrease in the segment's ROM when compared with the intact specimen. To compensate, it caused an increase in motion at adjacent levels L1-2 (45.6%) and L2-3 (23.2%) only. The placement of the dynamic construct at L3-4 decreased the operated level's ROM by 80.4% (similar stability as the fusion at L4-5), when compared with the intact specimen, and caused a significant increase in motion at all tested adjacent levels. In flexion-extension with a follower load, instrumentation at L4-5 affected only a subadjacent level, L5-sacrum (52.0%), while causing a reduction in motion at the operated level (L4-5, -76.4%). The dynamic construct caused a significant increase in motion at the adjacent levels T12-L1 (44.9%), L1-2 (57.3%), and L5-sacrum (83.9%), while motion at the operated level (L3-4) was reduced by 76.7%. In lateral bending, instrumentation at L4-5 increased motion at only T12-L1 (22.8%). The dynamic construct at L3-4 caused an increase in motion at T12-L1 (69.9%), L1-2 (59.4%), L2-3 (44.7%), and L5-sacrum (43.7%). In axial rotation, only the placement of

  20. 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...

  1. CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

    PubMed

    El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E; Shay, Jerry W

    2014-01-01

    Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

  2. CDDO-Me Protects Normal Lung and Breast Epithelial Cells but Not Cancer Cells from Radiation

    PubMed Central

    El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E.; Shay, Jerry W.

    2014-01-01

    Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients. PMID:25536195

  3. Effect of Augmentation Material Stiffness on Adjacent Vertebrae after Osteoporotic Vertebroplasty Using Finite Element Analysis with Different Loading Methods.

    PubMed

    Cho, Ah-Reum; Cho, Sang-Bong; Lee, Jae-Ho; Kim, Kyung-Hoon

    2015-11-01

    Vertebroplasty is an effective treatment for osteoporotic vertebral fractures, which are one of the most common fractures associated with osteoporosis. However, clinical observation has shown that the risk of adjacent vertebral body fractures may increase after vertebroplasty. The mechanism underlying adjacent vertebral body fracture after vertebroplasty is not clear; excessive stiffness resulting from polymethyl methacrylate has been suspected as an important mechanism. The aim of our study was to compare the effects of bone cement stiffness on adjacent vertebrae after osteoporotic vertebroplasty under load-controlled versus displacement-controlled conditions. An experimental computer study using a finite element analysis. Medical research institute, university hospital, Korean. A three-dimensional digital anatomic model of L1/2 bone structure was reconstructed from human computed tomographic images. The reconstructed three-dimensional geometry was processed for finite element analysis such as meshing elements and applying material properties. Two boundary conditions, load-controlled and displacement-controlled methods, were applied to each of 5 deformation modes: compression, flexion, extension, lateral bending, and torsion. The adjacent L1 vertebra, irrespective of augmentation, revealed nearly similar maximum von Mises stresses under the load-controlled condition. However, for the displacement-controlled condition, the maximum von Mises stresses in the cortical bone and inferior endplate of the adjacent L1 vertebra increased significantly after cement augmentation. This increase was more significant than that with stiffer bone cement under all modes, except the torsion mode. The finite element model was simplified, excluding muscular forces and incorporating a large volume of bone cement, to more clearly demonstrate effects of bone cement stiffness on adjacent vertebrae after vertebroplasty. Excessive stiffness of augmented bone cement increases the risk of

  4. Assessing the multiscale architecture of muscular tissue with Q-space magnetic resonance imaging: Review.

    PubMed

    Hoffman, Matthew P; Taylor, Erik N; Aninwene, George E; Sadayappan, Sakthivel; Gilbert, Richard J

    2018-02-01

    Contraction of muscular tissue requires the synchronized shortening of myofibers arrayed in complex geometrical patterns. Imaging such myofiber patterns with diffusion-weighted MRI reveals architectural ensembles that underlie force generation at the organ scale. Restricted proton diffusion is a stochastic process resulting from random translational motion that may be used to probe the directionality of myofibers in whole tissue. During diffusion-weighted MRI, magnetic field gradients are applied to determine the directional dependence of proton diffusion through the analysis of a diffusional probability distribution function (PDF). The directions of principal (maximal) diffusion within the PDF are associated with similarly aligned diffusion maxima in adjacent voxels to derive multivoxel tracts. Diffusion-weighted MRI with tractography thus constitutes a multiscale method for depicting patterns of cellular organization within biological tissues. We provide in this review, details of the method by which generalized Q-space imaging is used to interrogate multidimensional diffusion space, and thereby to infer the organization of muscular tissue. Q-space imaging derives the lowest possible angular separation of diffusion maxima by optimizing the conditions by which magnetic field gradients are applied to a given tissue. To illustrate, we present the methods and applications associated with Q-space imaging of the multiscale myoarchitecture associated with the human and rodent tongues. These representations emphasize the intricate and continuous nature of muscle fiber organization and suggest a method to depict structural "blueprints" for skeletal and cardiac muscle tissue. © 2016 Wiley Periodicals, Inc.

  5. 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

  6. Extraction efficiency and implications for absolute quantitation of propranolol in mouse brain, liver and kidney thin tissue sections using droplet-based liquid microjunction surface sampling-HPLC ESI-MS/MS

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

    Kertesz, Vilmos; Weiskittel, Taylor M.; Vavek, Marissa

    Currently, absolute quantitation aspects of droplet-based surface sampling for thin tissue analysis using a fully automated autosampler/HPLC-ESI-MS/MS system are not fully evaluated. Knowledge of extraction efficiency and its reproducibility is required to judge the potential of the method for absolute quantitation of analytes from thin tissue sections. Methods: Adjacent thin tissue sections of propranolol dosed mouse brain (10- μm-thick), kidney (10- μm-thick) and liver (8-, 10-, 16- and 24- μm-thick) were obtained. Absolute concentration of propranolol was determined in tissue punches from serial sections using standard bulk tissue extraction protocols and subsequent HPLC separations and tandem mass spectrometric analysis. Thesemore » values were used to determine propranolol extraction efficiency from the tissues with the droplet-based surface sampling approach. Results: Extraction efficiency of propranolol using 10- μm-thick brain, kidney and liver thin tissues using droplet-based surface sampling varied between ~45-63%. Extraction efficiency decreased from ~65% to ~36% with liver thickness increasing from 8 μm to 24 μm. Randomly selecting half of the samples as standards, precision and accuracy of propranolol concentrations obtained for the other half of samples as quality control metrics were determined. Resulting precision ( ±15%) and accuracy ( ±3%) values, respectively, were within acceptable limits. In conclusion, comparative quantitation of adjacent mouse thin tissue sections of different organs and of various thicknesses by droplet-based surface sampling and by bulk extraction of tissue punches showed that extraction efficiency was incomplete using the former method, and that it depended on the organ and tissue thickness. However, once extraction efficiency was determined and applied, the droplet-based approach provided the required quantitation accuracy and precision for assay validations. Furthermore, this means that once the extraction

  7. Extraction efficiency and implications for absolute quantitation of propranolol in mouse brain, liver and kidney thin tissue sections using droplet-based liquid microjunction surface sampling-HPLC ESI-MS/MS

    DOE PAGES

    Kertesz, Vilmos; Weiskittel, Taylor M.; Vavek, Marissa; ...

    2016-06-22

    Currently, absolute quantitation aspects of droplet-based surface sampling for thin tissue analysis using a fully automated autosampler/HPLC-ESI-MS/MS system are not fully evaluated. Knowledge of extraction efficiency and its reproducibility is required to judge the potential of the method for absolute quantitation of analytes from thin tissue sections. Methods: Adjacent thin tissue sections of propranolol dosed mouse brain (10- μm-thick), kidney (10- μm-thick) and liver (8-, 10-, 16- and 24- μm-thick) were obtained. Absolute concentration of propranolol was determined in tissue punches from serial sections using standard bulk tissue extraction protocols and subsequent HPLC separations and tandem mass spectrometric analysis. Thesemore » values were used to determine propranolol extraction efficiency from the tissues with the droplet-based surface sampling approach. Results: Extraction efficiency of propranolol using 10- μm-thick brain, kidney and liver thin tissues using droplet-based surface sampling varied between ~45-63%. Extraction efficiency decreased from ~65% to ~36% with liver thickness increasing from 8 μm to 24 μm. Randomly selecting half of the samples as standards, precision and accuracy of propranolol concentrations obtained for the other half of samples as quality control metrics were determined. Resulting precision ( ±15%) and accuracy ( ±3%) values, respectively, were within acceptable limits. In conclusion, comparative quantitation of adjacent mouse thin tissue sections of different organs and of various thicknesses by droplet-based surface sampling and by bulk extraction of tissue punches showed that extraction efficiency was incomplete using the former method, and that it depended on the organ and tissue thickness. However, once extraction efficiency was determined and applied, the droplet-based approach provided the required quantitation accuracy and precision for assay validations. Furthermore, this means that once the extraction

  8. 20. Interior view of fuel storage pit or vault adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Interior view of fuel storage pit or vault adjacent to Test Cell 9 in Component Test Laboratory (T-27), looking west. Photograph shows upgraded instrumentation, piping, tanks, and technological modifications installed in 1997-99 to accommodate component testing requirements for the Atlas V missile. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  9. Determination of lateral effects of borrow pits on hydrology of adjacent wetlands.

    DOT National Transportation Integrated Search

    2007-09-28

    A three year research project was conducted to develop and test a method to predict the distance borrow pits should : be set back from adjacent wetlands to avoid detrimental impacts on wetland hydrology. The method is based on the : Boussinesq equati...

  10. Tumors of the skin and soft tissues

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

    Weller, R.E.

    1991-10-01

    The majority of the body surface is covered by the skin. Many internal disorders are reflected in the condition of the skin. One of the major functions of the skin is protection of the other organ systems from a variety of environmental insults. In this role, the skin itself is exposed to factors that can ultimately cause chronic diseases and cancer. Since it is relatively easy to recognize skin abnormalities, most skin cancers are brought to professional attention sooner than other types of cancer. However, due to the close resemblance between many skin neoplasms and noncancerous dermatologic disorders, these neoplasmsmore » may be mistreated for months or even years. In veterinary oncology, as in human medicine, most cancers can be effectively treated or cured following an accurate diagnosis. Once diagnosed, skin neoplasms should be aggressively treated. If causal factors are known, exposure to these factors should be limited through removal of the agent (for chemical carcinogens) or limiting exposure to the agent (for other carcinogens such as sunlight). 10 tabs. (MHB)« less

  11. Quantitative photoacoustic assessment of ex-vivo lymph nodes of colorectal cancer patients

    NASA Astrophysics Data System (ADS)

    Sampathkumar, Ashwin; Mamou, Jonathan; Saegusa-Beercroft, Emi; Chitnis, Parag V.; Machi, Junji; Feleppa, Ernest J.

    2015-03-01

    Staging of cancers and selection of appropriate treatment requires histological examination of multiple dissected lymph nodes (LNs) per patient, so that a staggering number of nodes require histopathological examination, and the finite resources of pathology facilities create a severe processing bottleneck. Histologically examining the entire 3D volume of every dissected node is not feasible, and therefore, only the central region of each node is examined histologically, which results in severe sampling limitations. In this work, we assess the feasibility of using quantitative photoacoustics (QPA) to overcome the limitations imposed by current procedures and eliminate the resulting under sampling in node assessments. QPA is emerging as a new hybrid modality that assesses tissue properties and classifies tissue type based on multiple estimates derived from spectrum analysis of photoacoustic (PA) radiofrequency (RF) data and from statistical analysis of envelope-signal data derived from the RF signals. Our study seeks to use QPA to distinguish cancerous from non-cancerous regions of dissected LNs and hence serve as a reliable means of imaging and detecting small but clinically significant cancerous foci that would be missed by current methods. Dissected lymph nodes were placed in a water bath and PA signals were generated using a wavelength-tunable (680-950 nm) laser. A 26-MHz, f-2 transducer was used to sense the PA signals. We present an overview of our experimental setup; provide a statistical analysis of multi-wavelength classification parameters (mid-band fit, slope, intercept) obtained from the PA signal spectrum generated in the LNs; and compare QPA performance with our established quantitative ultrasound (QUS) techniques in distinguishing metastatic from non-cancerous tissue in dissected LNs. QPA-QUS methods offer a novel general means of tissue typing and evaluation in a broad range of disease-assessment applications, e.g., cardiac, intravascular

  12. Magnetic Resonance Imaging of Human Tissue-Engineered Adipose Substitutes

    PubMed Central

    Proulx, Maryse; Aubin, Kim; Lagueux, Jean; Audet, Pierre; Auger, Michèle

    2015-01-01

    Adipose tissue (AT) substitutes are being developed to answer the strong demand in reconstructive surgery. To facilitate the validation of their functional performance in vivo, and to avoid resorting to excessive number of animals, it is crucial at this stage to develop biomedical imaging methodologies, enabling the follow-up of reconstructed AT substitutes. Until now, biomedical imaging of AT substitutes has scarcely been reported in the literature. Therefore, the optimal parameters enabling good resolution, appropriate contrast, and graft delineation, as well as blood perfusion validation, must be studied and reported. In this study, human adipose substitutes produced from adipose-derived stem/stromal cells using the self-assembly approach of tissue engineering were implanted into athymic mice. The fate of the reconstructed AT substitutes implanted in vivo was successfully followed by magnetic resonance imaging (MRI), which is the imaging modality of choice for visualizing soft ATs. T1-weighted images allowed clear delineation of the grafts, followed by volume integration. The magnetic resonance (MR) signal of reconstructed AT was studied in vitro by proton nuclear magnetic resonance (1H-NMR). This confirmed the presence of a strong triglyceride peak of short longitudinal proton relaxation time (T1) values (200±53 ms) in reconstructed AT substitutes (total T1=813±76 ms), which establishes a clear signal difference between adjacent muscle, connective tissue, and native fat (total T1 ∼300 ms). Graft volume retention was followed up to 6 weeks after implantation, revealing a gradual resorption rate averaging at 44% of initial substitute's volume. In addition, vascular perfusion measured by dynamic contrast-enhanced-MRI confirmed the graft's vascularization postimplantation (14 and 21 days after grafting). Histological analysis of the grafted tissues revealed the persistence of numerous adipocytes without evidence of cysts or tissue necrosis. This study

  13. 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.

  14. Dose equivalent near the bone-soft tissue interface from nuclear fragments produced by high-energy protons

    NASA Technical Reports Server (NTRS)

    Shavers, M. R.; Poston, J. W.; Cucinotta, F. A.; Wilson, J. W.

    1996-01-01

    During manned space missions, high-energy nucleons of cosmic and solar origin collide with atomic nuclei of the human body and produce a broad linear energy transfer spectrum of secondary particles, called target fragments. These nuclear fragments are often more biologically harmful than the direct ionization of the incident nucleon. That these secondary particles increase tissue absorbed dose in regions adjacent to the bone-soft tissue interface was demonstrated in a previous publication. To assess radiological risks to tissue near the bone-soft tissue interface, a computer transport model for nuclear fragments produced by high energy nucleons was used in this study to calculate integral linear energy transfer spectra and dose equivalents resulting from nuclear collisions of 1-GeV protons transversing bone and red bone marrow. In terms of dose equivalent averaged over trabecular bone marrow, target fragments emitted from interactions in both tissues are predicted to be at least as important as the direct ionization of the primary protons-twice as important, if recently recommended radiation weighting factors and "worst-case" geometry are used. The use of conventional dosimetry (absorbed dose weighted by aa linear energy transfer-dependent quality factor) as an appropriate framework for predicting risk from low fluences of high-linear energy transfer target fragments is discussed.

  15. A New Strategy to Enhance Cavitational Tissue Erosion Using a High-Intensity, Initiating Sequence

    PubMed Central

    Xu, Zhen; Fowlkes, J. Brian; Cain, Charles A.

    2009-01-01

    Our previous studies have shown that pulsed ultrasound can physically remove soft tissue through cavitation. A new strategy to enhance the cavitation-induced erosion is proposed wherein tissue erosion is initiated by a short, high-intensity sequence of pulses and sustained by lower intensity pulses. We investigated effects of the initiating sequence on erosion and cavitation sustained by lower intensity pulses. Multiple three-cycle pulses at a pulse repetition frequency of 20 kHz delivered by a 788-kHz focused transducer were used for tissue erosion. Fixing the initiating sequence at ISPPA of 9000 W/cm2, 16 combinations of different numbers of pulses within the initiating sequence and different sustaining pulse intensities were tested. Results showed: the initiating sequence increases the probability of erosion occurrence and the erosion rate with only slight overall increases in propagated energy; the initiating sequence containing more pulses does not increase the sustained cavitation period; and if extinguished and reinitiated, the sustained cavitation period becomes shorter after each initiation, although the waiting time between adjacent cavitation periods is random. The high-intensity, initiating sequence enhances cavitational tissue erosion and enables erosion at intensities significantly lower than what is required to initiate erosion. PMID:16921893

  16. Identification of oleoresin in epoxy-embedded slash pine tissue

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

    Birchem, R.; Brown, C.L.

    1978-01-01

    Sudan black B stains oleoresin blue-black in epoxy-embedded material as well as in living tissue. The Sudan black B staining properties of oleoresin are similar to those of lipid, but it can be distinguished from tannin, which stains brown. Practically all oleoresin present in resin ducts and intercellular spaces, and much of that contained in epithelial and ray cells, is extracted in preparatory procedures for electron microscopy. A fixation procedure is proposed which preserves significantly more oleoresin in situ. The use of Sudan black B enables one to localize oleoresin by light microscopy, and permits direct comparison of adjacent sectionsmore » of epoxy-embedded material at the ultrastructure level. Ultrastructurally oleoresin and lipid possess similar electron densities and can be distinguished from the highly electron-opaque tannin deposits.« less

  17. Tissue healing response following hyperthermic vapor ablation in the porcine longissimus muscle

    NASA Astrophysics Data System (ADS)

    Grantham, John T.; Grisez, Brian T.; Famoso, Justin; Hoey, Michael; Dixon, Chris; Coad, James E.

    2015-03-01

    As the use of hyperthermic ablation technologies has increased, so too has the need to understand their effects on tissue and their healing responses. This study was designed to characterize tissue injury and healing following hyperthermic vapor ablation in the in vivo porcine longissimus muscle model. The individual ablations were performed using the NxThera Vapor Delivery System (NxThera Inc., Minneapolis, MN). To assess the vapor ablation's evolution, the swine were euthanized post-treatment on Day 0, Day 3, Day 7, Day 14, Day 28, Day 45 and Day 90. Triphenyltetrazolium chloride viability staining (TTC staining) was used to macroscopically assess the extent of each vapor ablation within the tissue. The ablation associated healing responses were then histologically evaluated for acute inflammation, chronic inflammation, foreign body reaction and fibrosis. Two zones of tissue injury were initially identified in the ablations: 1) a central zone of complete coagulative necrosis and 2) an outer "transition zone" of viable and non-viable cells. The ablations initially increased in size from Day 0 to Day 7 and then progressively decreased in size though Day 45. The initial Day 3 healing changes originated in the transition zone with minimal acute and chronic inflammation. As time progressed, granulation tissue began to form by Day 7 and peaked around Day 14. Collagen formation, deposition and remodeling began in the adjacent healthy tissue by Day 28, replaced the ablation site by Day 45 and reorganized by Day 90. In conclusion, this vapor ablation technology provided a non-desiccating form of hyperthermic ablation that resulted in coagulative necrosis without a central thermally/heat-fixed tissue component, followed a classical wound healing pathway, and healed with minimal associated inflammation.

  18. Enamel remineralization on teeth adjacent to Class II glass ionomer restorations.

    PubMed

    Segura, A; Donly, K J; Stratmann, R G

    1997-10-01

    To examine the in vitro remineralization of incipient carious lesions on teeth adjacent interproximally to teeth with Class II glass ionomer cement restorations. Artificial carious lesions were created at the contact area of 30 teeth. Ten teeth had Class II glass ionomer cement/resin composite restorations placed, 10 teeth had Class II glass ionomer silver cermet restorations placed and 10 teeth had Class II amalgam restorations placed. Sections 100 microns thick were obtained longitudinally through the caries sites and polarized photomicrographs were taken in imbibition media of water and Thoulet's (R.I. 1.41 and 1.47) solutions, representing 5%, 10% and 25% pore volume respectively. Varnish was placed on the section, leaving only the external section site exposed, then sections were situated back into the original tooth. The restored teeth were abutted to the carious tooth so that the restorations came into contact with the adjacent restoration. The specimens were placed into closed environments of artificial saliva for 14 days, then were photographed again under polarized light and areas of the carious lesions were quantitated. An ANOVA indicated significant variance in adjacent tooth remineralization, when comparing the experimental groups, in imbibition media of water (P < 0.05), Thoulet's 1.41 solution (P < 0.008) and Thoulet's 1.47 solution (P < 0.006). Duncan's multiple range test demonstrated the glass ionomer cement/resin composite group to have significantly greater decrease in pore volume (P < 0.05) than the amalgam control group in water imbibition media and Thoulet's 1.47 media. There was no statistically significant difference between the glass ionomer cement/resin composite and glass ionomer silver cermet groups in these two imbibition media. The glass ionomer cement/resin composite group demonstrated significantly more (P < 0.05) decrease in pore volume than both the glass ionomer silver cermet group and amalgam control group in Thoulet's 1

  19. Tier-Adjacency Is Not a Necessary Condition for Learning Phonotactic Dependencies

    ERIC Educational Resources Information Center

    Koo, Hahn; Callahan, Lydia

    2012-01-01

    One hypothesis raised by Newport and Aslin to explain how speakers learn dependencies between nonadjacent phonemes is that speakers track bigram probabilities between two segments that are adjacent to each other within a tier of their own. The hypothesis predicts that a dependency between segments separated from each other at the tier level cannot…

  20. Thermal fixation of swine liver tissue after magnetic resonance-guided high-intensity focused ultrasound ablation.

    PubMed

    Courivaud, Frédéric; Kazaryan, Airazat M; Lund, Alice; Orszagh, Vivian C; Svindland, Aud; Marangos, Irina Pavlik; Halvorsen, Per Steinar; Jebsen, Peter; Fosse, Erik; Hol, Per Kristian; Edwin, Bjørn

    2014-07-01

    The aim of this study was to investigate experimental conditions for efficient and controlled in vivo liver tissue ablation by magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) in a swine model, with the ultimate goal of improving clinical treatment outcome. Histological changes were examined both acutely (four animals) and 1 wk after treatment (five animals). Effects of acoustic power and multiple sonication cycles were investigated. There was good correlation between target size and observed ablation size by thermal dose calculation, post-procedural MR imaging and histopathology, when temperature at the focal point was kept below 90°C. Structural histopathology investigations revealed tissue thermal fixation in ablated regions. In the presence of cavitation, mechanical tissue destruction occurred, resulting in an ablation larger than the target. Complete extra-corporeal MR-guided HIFU ablation in the liver is feasible using high acoustic power. Nearby large vessels were preserved, which makes MR-guided HIFU promising for the ablation of liver tumors adjacent to large veins. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.