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  1. Independent Tumor Origin in Two Cases of Synchronous Bilateral Clear Cell Renal Cell Carcinoma

    PubMed Central

    Ji, Zhengguo; Zhao, Jialu; Zhao, Tian; Han, Yuying; Zhang, Yujun; Ye, Haihong

    2016-01-01

    Bilateral renal cell carcinomas (RCCs) pose a challenge for clinical treatment and management. Most bilateral RCCs are sporadic, and do not show a hereditary pattern indicative of VHL syndrome or other inherited cancers. The origin and evolution of these sporadic bilateral RCCs remains elusive. We obtained normal and tumor samples from two male patients suffering from early stage synchronous bilateral clear cell RCC (ccRCC), and analyzed genomic DNA using whole exome sequencing and bisulfite pyrosequencing. We detected distinct 3p loss of heterozygosity (LOH) in both tumors in each patient. Two tumors within the same patient harbored distinct driver mutations and different CpG hypermethylation sites in the VHL promoter. Moreover, tumors exhibit independent evolutionary trajectories. Therefore, distinct 3p LOH, combined with contingent driver gene mutations and independent VHL hypermethylation, led to independent tumor origin and parallel evolution of bilateral ccRCC in these two patients. Our results indicate that tumors in these two cases were not due to common germline oncogenic mutations. They were results of multiple de novo mutations in each kidney, rather than primary ccRCC with contralateral renal metastasis. Therefore, histopathologic and genetic profiling from single tumor specimen may underestimate the mutational burden and somatic heterogeneity of bilateral ccRCCs. PMID:27383411

  2. Independent Tumor Origin in Two Cases of Synchronous Bilateral Clear Cell Renal Cell Carcinoma.

    PubMed

    Ji, Zhengguo; Zhao, Jialu; Zhao, Tian; Han, Yuying; Zhang, Yujun; Ye, Haihong

    2016-01-01

    Bilateral renal cell carcinomas (RCCs) pose a challenge for clinical treatment and management. Most bilateral RCCs are sporadic, and do not show a hereditary pattern indicative of VHL syndrome or other inherited cancers. The origin and evolution of these sporadic bilateral RCCs remains elusive. We obtained normal and tumor samples from two male patients suffering from early stage synchronous bilateral clear cell RCC (ccRCC), and analyzed genomic DNA using whole exome sequencing and bisulfite pyrosequencing. We detected distinct 3p loss of heterozygosity (LOH) in both tumors in each patient. Two tumors within the same patient harbored distinct driver mutations and different CpG hypermethylation sites in the VHL promoter. Moreover, tumors exhibit independent evolutionary trajectories. Therefore, distinct 3p LOH, combined with contingent driver gene mutations and independent VHL hypermethylation, led to independent tumor origin and parallel evolution of bilateral ccRCC in these two patients. Our results indicate that tumors in these two cases were not due to common germline oncogenic mutations. They were results of multiple de novo mutations in each kidney, rather than primary ccRCC with contralateral renal metastasis. Therefore, histopathologic and genetic profiling from single tumor specimen may underestimate the mutational burden and somatic heterogeneity of bilateral ccRCCs. PMID:27383411

  3. High incidence of oral squamous cell carcinoma independent of HPV infection after allogeneic hematopoietic SCT in Taiwan.

    PubMed

    Chen, M H; Chang, P M; Li, W Y; Hsiao, L T; Hong, Y C; Liu, C Y; Gau, J P; Liu, J H; Chen, P M; Chiou, T J; Tzeng, C H

    2011-04-01

    Hematopoietic SCT (HSCT) is a well-recognized therapeutic procedure to prolong life and cure patients with life-threatening hematological malignancies; however, the risk of developing secondary carcinoma may increase in long-term survivors. The objective of this study was to determine the incidence and risk factors for secondary squamous carcinoma after HSCT. Between 1984 and 2004, 170 allogeneic HSCT recipients aged >15 years, who had survived for >5 years were enrolled. Demographic data and the characteristics of secondary carcinoma were collected and analyzed for the determination of the incidence and risk of developing secondary carcinoma. Eight patients developed secondary carcinoma, including five oral squamous cell carcinomas, one esophageal, one gastric and one ovarian carcinoma, but no cutaneous carcinomas were detected at a median follow-up of 14.1 years (range, 5.1-23.3 years) after HSCT. The accrual 10-year cumulative incidence of secondary carcinoma was 2.89%. In univariate and multivariate analyses, chronic GVHD and age >40 years at the time of HSCT were both significant risk factors independently associated with the development of secondary carcinoma. Thus, the occurrence of secondary carcinoma is one of the late complications in patients undergoing HSCT. Oral squamous cell carcinoma was more common in our patients after HSCT, indicating the need for lifelong surveillance of the oral cavity. Moreover, because of the relatively long latency in developing secondary carcinoma, extended follow-up is required for a thorough understanding of the incidence and characteristics of secondary carcinoma after HSCT. PMID:20622906

  4. Serum Adiponectin Level May be an Independent Predictor of Clear Cell Renal Cell Carcinoma

    PubMed Central

    Wang, Hongkai; Wu, Junlong; Gu, Weijie; Wang, Beihe; Wan, Fangning; Dai, Bo; Zhang, Hailiang; Shi, Guohai; Shen, Yijun; Zhu, Yiping; Zhu, Yao; Ye, Dingwei

    2016-01-01

    Objectives: To examine whether serum adiponectin or leptin level has the ability to differentiate clear cell renal cell carcinoma (ccRCC) from other subtypes of renal cell carcinoma (RCC) in a Chinese population. Patients and methods: We recruited 198 consecutive patients who were treated with radical or partial nephrectomy in our department from September 2011 to June 2013. Their histological types were all malignant, including clear cell, papillary, chromophobe and unclassified RCC. We also enrolled 86 people with no cancer or cancer-related diseases as normal controls. We measured patients' preoperative blood samples for plasma adiponectin and leptin concentrations using an enzyme-linked immunosorbent assay method. Statistical methods were used to analyze ccRCC and other subtypes as they relate to serum adiponectin/leptin level and other factors such as body mass index or visceral fat area. Results: In our database, normal controls had significantly higher circulating adiponectin (p < 0.001) and leptin levels (p < 0.001) than patients with RCC. Among the 198 RCC patients, 156 patients had ccRCC while 42 patients had other histological types. Serum adiponectin levels were lower in ccRCC patients than in non-clear-cell RCC patients (p = 0.004). However, the plasma leptin level was not differently distributed between ccRCC and non-ccRCC patients (p = 0.940). In multivariate analysis, we found that serum adiponectin level may be an independent predictor for discriminating ccRCC patients from others (p = 0.004). Furthermore, in the ccRCC subgroup, we observed that men with ccRCC had lower leptin (p < 0.001) and adiponectin (p = 0.002) levels, and diabetic patients had lower plasma adiponectin levels (p = 0.001). Conclusions: Lower plasma adiponectin concentration was related to an increased incidence of ccRCC and may act as an independent predictor for ccRCC. Our study may help define the process from obesity to adipose tissue, to cytokines and finally to ccRCC. PMID

  5. Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53

    SciTech Connect

    Ho, T.-F.; Ma, C.-J.; Lu, C.-H.; Tsai, Yo-Ting; Wei, Y.-H.; Chang, J.-S.; Lai, J.-K.; Cheuh, Pin-Ju; Yeh, C.-T.; Tang, P.-C.; Jingua, T.C.; Ko, J.-L.; Liu, F.-S.; Yen, H.E.

    2007-12-15

    Undecylprodigiosin (UP) is a bacterial bioactive metabolite produced by Streptomyces and Serratia. In this study, we explored the anticancer effect of UP. Human breast carcinoma cell lines BT-20, MCF-7, MDA-MB-231 and T47D and one nonmalignant human breast epithelial cell line, MCF-10A, were tested in this study. We found that UP exerted a potent cytotoxicity against all breast carcinoma cell lines in a dose- and time-dependent manner. In contrast, UP showed limited toxicity to MCF-10A cells, indicating UP's cytotoxic effect is selective for malignant cells. UP's cytotoxic effect was due to apoptosis, as confirmed by positive TUNEL signals, annexin V-binding, caspase 9 activation and PARP cleavage. Notably, UP-induced apoptosis was blocked by the pan-caspase inhibitor z-VAD.fmk, further indicating the involvement of caspase activity. Moreover, UP caused a marked decrease of the levels of antiapoptotic BCL-X{sub L}, Survivin and XIAP while enhancing the levels of proapoptotic BIK, BIM, MCL-1S and NOXA, consequently favoring induction of apoptosis. Additionally, we found that cells with functional p53 (MCF-7, T47D) or mutant p53 (BT-20, MDA-MB-231) were both susceptible to UP's cytotoxicity. Importantly, UP was able to induce apoptosis in MCF-7 cells with p53 knockdown by RNA interference, confirming the dispensability of p53 in UP-induced apoptosis. Overall, our results establish that UP induces p53-independent apoptosis in breast carcinoma cells with no marked toxicity to nonmalignant cells, raising the possibility of its use as a new chemotherapeutic drug for breast cancer irrespective of p53 status.

  6. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells.

    PubMed

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-09

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting.

  7. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells

    PubMed Central

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-01

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting. PMID:25571970

  8. c-Myc protein expression is not an independent prognostic predictor in cervical squamous cell carcinoma.

    PubMed

    Brenna, S M F; Zeferino, L C; Pinto, G A; Souza, R A; Andrade, L A L; Vassalo, J; Martinez, E Z; Syrjanen, K J

    2002-04-01

    The c-myc protein is known to regulate the cell cycle, and its down-regulation can lead to cell death by apoptosis. The role of c-myc protein as an independent prognostic determinant in cervical cancer is controversial. In the present study, a cohort of 220 Brazilian women (mean age 53.4 years) with FIGO stage I, II and III (21, 28 and 51%, respectively) cervical squamous cell carcinomas was analyzed for c-myc protein expression using immunohistochemistry. The disease-free survival and relapse-rate were analyzed using univariate (Kaplan-Meier) survival analysis for 116 women who completed the standard FIGO treatment and were followed up for 5 years. Positive c-myc staining was detected in 40% of carcinomas, 29% being grade 1, 9% grade 2, and 2% grade 3. The distribution of positive c-myc according to FIGO stage was 19% (17 women) in stage I, 33% (29) in stage II, and 48% (43) in stage III of disease. During the 60-month follow-up, disease-free survival in univariate (Kaplan-Meier) survival analysis (116 women) was lower for women with c-myc-positive tumors, i.e., 60.5, 47.5 and 36.6% at 12, 36, and 60 months, respectively (not significant). The present data suggest that immunohistochemical demonstration of c-myc does not possess any prognostic value independent of FIGO stage, and as such is unlikely to be a useful prognostic marker in cervical squamous cell carcinoma.

  9. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    PubMed

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

  10. Independent bilateral primary bronchial carcinomas

    PubMed Central

    Chaudhuri, M. Ray

    1971-01-01

    Independent bilateral primary bronchial carcinomas are not common. Since Beyreuther's description in 1924, 16 well-documented cases of independent primary bronchial carcinomas of different histology have been described. From 1965 to 1970, eight cases were seen at the London Chest Hospital. In order to make the diagnosis of a second primary bronchial carcinoma, each tumour should be malignant and neither should be a metastasis from the other. To meet this last criterion, the histopathological features of the two tumours must be different. Many cases have been described in the literature as double primary bronchial carcinomas where the second primary had the same histological features as the first. Images PMID:4327711

  11. Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides.

    PubMed

    Liu, Jung-Sen; Chiang, Tzu-Hsuan; Wang, Jinn-Shyan; Lin, Li-Ju; Chao, Wei-Chih; Inbaraj, Baskaran Stephen; Lu, Jyh-Feng; Chen, Bing-Huei

    2015-07-01

    The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50 ) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s). PMID:25781909

  12. Retention of prolyl hydroxylase PHD2 in the cytoplasm prevents PHD2-induced anchorage-independent carcinoma cell growth

    SciTech Connect

    Jokilehto, Terhi; Hoegel, Heidi; Heikkinen, Pekka; Rantanen, Krista; Elenius, Klaus; Sundstroem, Jari; Jaakkola, Panu M.

    2010-04-15

    Cellular oxygen tension is sensed by a family of prolyl hydroxylases (PHD1-3) that regulate the degradation of hypoxia-inducible factors (HIF-1{alpha} and -2{alpha}). The PHD2 isoform is considered as the main downregulator of HIF in normoxia. Our previous results have shown that nuclear translocation of PHD2 associates with poorly differentiated tumor phenotype implying that nuclear PHD2 expression is advantageous for tumor growth. Here we show that a pool of PHD2 is shuttled between the nucleus and the cytoplasm. In line with this, accumulation of wild type PHD2 in the nucleus was detected in human colon adenocarcinomas and in cultured carcinoma cells. The PHD2 isoforms showing high nuclear expression increased anchorage-independent carcinoma cell growth. However, retention of PHD2 in the cytoplasm inhibited the anchorage-independent cell growth. A region that inhibits the nuclear localization of PHD2 was identified and the deletion of the region promoted anchorage-independent growth of carcinoma cells. Finally, the cytoplasmic PHD2, as compared with the nuclear PHD2, less efficiently downregulated HIF expression. Forced HIF-1{alpha} or -2{alpha} expression decreased and attenuation of HIF expression increased the anchorage-independent cell growth. However, hydroxylase-inactivating mutations in PHD2 had no effect on cell growth. The data imply that nuclear PHD2 localization promotes malignant cancer phenotype.

  13. FLOT-2 is an independent prognostic marker in oral squamous cell carcinoma.

    PubMed

    Wen, Qiuyuan; Alnemah, Mohannad Ma; Luo, Jiadi; Wang, Weiyuan; Chu, Shuzhou; Chen, Lingjiao; Li, Jiao; Xu, Lina; Li, Meirong; Zhou, Jianhua; Fan, Songqing

    2015-01-01

    Flotillin-2 (Flot-2) is an important component of cellular membrane, which involves in various cellular processes and recent studies have revealed that Flot-2 played important roles in cancer progression. The expression and prognostic impact of Flot-2 in oral squamous cell carcinoma (OSCC) have not been well studied. So, a tissue microarray (TMA) based on immunohistochemical analysis of surgical resection of tumor tissues of 78 cases of OSCC patients and 27 cases of adjacent non-cancerous squamous epithelium tissues was conducted. This study focused on detecting Flot-2 expression and analyzing its prognostic impact on OSCC. The result showed that the positive percentage of Flot-2 expression in OSCC (74.4%, 58/78) was significantly higher than that in adjacent non-cancerous squamous epithelium tissues (25.9%, 7/27) (P<0.001). Additionally, the positive expression of Flot-2 in OSCC patients with a history of alcohol consumption was significantly higher than those nonusers (P=0.027). Both univariate and multivariate survival analysis indicated that increased expression Flot-2 protein was significantly correlated inversely with overall survival rates in OSCC patients (P=0.046, P=0.002). Taken together, positive expression of Flot-2 protein may be an independent biomarker for poor prognosis in OSCC. PMID:26339392

  14. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy.

    PubMed

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol's efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  15. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy

    PubMed Central

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  16. Development and evaluation of an anchorage-independent agar-based clonal assay for human primary breast carcinoma cells

    SciTech Connect

    Besch, G.J.

    1985-01-01

    The development and evaluation of an anchorage-independent clonal cytotoxic assay for primary human breast carcinoma cells is described in this thesis. This assay was developed in three stages which include: (1) the optimization of the production of a monodispersed cell suspension from solid breast carcinomas, (2) the systematic development of a growth medium for the clonal growth of these cells, and (3) the adaptation of these methods for use in the quantitation of cytotoxicity. The results of these studies indicated that hydrocortisone, fetal bovine serum and red blood cells stimulated the clonal growth of breast carcinoma cells. The optimal concentrations of these three factors were simultaneously determined using response surface methodology. These culture conditions were then used to develop radiation-cytotoxicity assays for both primary and recurrent breast carcinomas. The methodology developed and evaluated in this thesis may be useful to: (1) study the biology and radiobiology of human breast cancer, (2) customize the treatment of individual breast cancer patients, and (3) identify and/or develop new drugs and/or other treatment modalities for breast cancer.

  17. Inhibition of focal adhesion kinase (FAK) activity prevents anchorage-independent ovarian carcinoma cell growth and tumor progression

    PubMed Central

    Ward, Kristy K.; Tancioni, Isabelle; Lawson, Christine; Miller, Nichol L.G.; Jean, Christine; Chen, Xiao Lei; Uryu, Sean; Kim, Josephine; Tarin, David; Stupack, Dwayne G.; Plaxe, Steven C.; Schlaepfer, David D.

    2013-01-01

    Recurrence and spread of ovarian cancer is the 5th leading cause of death for women in the United States. Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase located on chromosome 8q24.3 (gene is Ptk2), a site commonly amplified in serous ovarian cancer. Elevated FAK mRNA levels in serous ovarian carcinoma are associated with decreased (logrank P = 0.0007, hazard ratio 1.43) patient overall survival, but how FAK functions in tumor progression remains undefined. We have isolated aggressive ovarian carcinoma cells termed ID8-IP after intraperitoneal (IP) growth of murine ID8 cells in C57Bl6 mice. Upon orthotopic implantation within the periovarian bursa space, ID8-IP cells exhibit greater tumor growth, local and distant metastasis, and elevated numbers of ascites-associated cells compared to parental ID8 cells. ID8-IP cells exhibit enhanced growth under non-adherent conditions with elevated FAK and c-Src tyrosine kinase activation compared to parental ID8 cells. In vitro, the small molecule FAK inhibitor (Pfizer, PF562,271, PF-271) at 0.1 uM selectively prevented anchorage-independent ID8-IP cell growth with the inhibition of FAK tyrosine (Y)397 but not c-Src Y416 phosphorylation. Oral PF-271 administration (30 mg/kg, twice daily) blocked FAK but not c-Src tyrosine phosphorylation in ID8-IP tumors. This was associated with decreased tumor size, prevention of peritoneal metastasis, reduced tumor-associated endothelial cell number, and increased tumor cell-associated apoptosis. FAK knockdown and re-expression assays showed that FAK activity selectively promoted anchorage-independent ID8-IP cell survival. These results support the continued evaluation of FAK inhibitors as a promising clinical treatment for ovarian cancer. PMID:23275034

  18. KU-0060648 inhibits hepatocellular carcinoma cells through DNA-PKcs-dependent and DNA-PKcs-independent mechanisms.

    PubMed

    Chen, Min-Bin; Zhou, Zhen-Tao; Yang, Lan; Wei, Mu-Xin; Tang, Min; Ruan, Ting-Yan; Xu, Jun-Ying; Zhou, Xiao-Zhong; Chen, Gang; Lu, Pei-Hua

    2016-03-29

    Here we tested anti-tumor activity of KU-0060648 in preclinical hepatocellular carcinoma (HCC) models. Our results demonstrated that KU-0060648 was anti-proliferative and pro-apoptotic in established (HepG2, Huh-7 and KYN-2 lines) and primary human HCC cells, but was non-cytotoxic to non-cancerous HL-7702 hepatocytes. DNA-PKcs (DNA-activated protein kinase catalytic subunit) is an important but not exclusive target of KU-0060648. DNA-PKcs knockdown or dominant negative mutation inhibited HCC cell proliferation. On the other hand, overexpression of wild-type DNA-PKcs enhanced HepG2 cell proliferation. Importantly, KU-0060648 was still cytotoxic to DNA-PKcs-silenced or -mutated HepG2 cells, although its activity in these cells was relatively weak. Further studies showed that KU-0060648 inhibited PI3K-AKT-mTOR activation, independent of DNA-PKcs. Introduction of constitutively-active AKT1 (CA-AKT1) restored AKT-mTOR activation after KU-0060648 treatment in HepG2 cells, and alleviated subsequent cytotoxicity. In vivo, intraperitoneal (i.p.) injection of KU-0060648 significantly inhibited HepG2 xenograft growth in nude mice. AKT-mTOR activation was also inhibited in xenografted tumors. Finally, we showed that DNA-PKcs expression was significantly upregulated in human HCC tissues. Yet miRNA-101, an anti-DNA-PKcs miRNA, was downregulated. Over-expression of miR-101 in HepG2 cells inhibited DNA-PKcs expression and cell proliferation. Together, these results indicate that KU-0060648 inhibits HCC cells through DNA-PKcs-dependent and -independent mechanisms.

  19. Basal Cell Carcinoma (BCC)

    MedlinePlus

    ... carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive than other types of basal ... to treat them early and with slightly more aggressive techniques. Excision – The basal cell carcinoma is cut ...

  20. Matrine induces caspase-independent program cell death in hepatocellular carcinoma through bid-mediated nuclear translocation of apoptosis inducing factor.

    PubMed

    Zhou, Huan; Xu, Minying; Gao, Ya; Deng, Zhigang; Cao, Hanwei; Zhang, Wenqing; Wang, Qiao; Zhang, Bing; Song, Gang; Zhan, Yanyan; Hu, Tianhui

    2014-03-16

    Matrine, a clinical drug in China, has been used to treat viral hepatitis, cardiac arrhythmia and skin inflammations. Matrine also exhibits chemotherapeutic potential through its ability to trigger cancer cell death. However, the mechanisms involved are still largely unknown. The objective of this study was to investigate the major determinant for the cell death induced by matrine in human hepatocellular carcinoma. We use human hepatocellular carcinoma cell line HepG2 and human hepatocellular carcinoma xenograft in nude mice as models to study the action of matrine in hepatocellular cancers. We found that caspase-dependent and -independent Program Cell Death (PCD) occurred in matrine-treated HepG2 cells, accompanied by the decreasing of mitochondrial transmembrane potential and the increasing ROS production. Further studies showed that AIF released from the mitochondria to the nucleus, and silencing of AIF reduced the caspase-independent PCD induced by matrine. What's more, AIF nuclear translocation, and the subsequent cell death as well, was prevented by Bid inhibitor BI-6C9, Bid-targeted siRNA and ROS scavenger Tiron. In the in vivo study, matrine significantly attenuated tumor growth with AIF release from mitochondria into nucleus in nude mice. These data imply that matrine potently induce caspase-independent PCD in HepG2 cells through Bid-mediated AIF translocation.

  1. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  2. Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status

    PubMed Central

    Chen, Yuan; Sun, Yin; Rao, Qun; Xu, Hua; Li, Lei; Chang, Chawnshang

    2015-01-01

    Mutational inactivation of the VHL tumor suppressor plays key roles in the development of renal cell carcinoma (RCC), and mutated VHL-mediated VEGF induction has become the main target for the current RCC therapy. Here we identified a signal pathway of VEGF induction by androgen receptor (AR)/miRNA-145 as a new target to suppress RCC progression. Mechanism dissection revealed that AR might function through binding to the androgen receptor element (ARE) located on the promoter region of miRNA-145 to suppress p53's ability to induce expression of miRNA-145 that normally suppresses expression of HIF2α/VEGF/MMP9/CCND1. Suppressing AR with AR-shRNA or introducing exogenous miRNA-145 mimic can attenuate RCC progression independent of VHL status. MiR-145 mimic in preclinical RCC orthotopic xenograft mouse model revealed its efficacy in suppression of RCC progression. These results together identified signals by AR-suppressed miRNA-145 as a key player in the RCC progression via regulating HIF2α/VEGF/MMP9/CCND1 expression levels. Blockade of the newly identified signal by AR inhibition or miRNA-145 mimics has promising therapeutic benefit to suppress RCC progression. PMID:26304926

  3. Circulating miR-21 as an independent predictive biomarker for chemoresistance in esophageal squamous cell carcinoma

    PubMed Central

    Komatsu, Shuhei; Ichikawa, Daisuke; Kawaguchi, Tsutomu; Miyamae, Mahito; Okajima, Wataru; Ohashi, Takuma; Imamura, Taisuke; Kiuchi, Jun; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Okamoto, Kazuma; Otsuji, Eigo

    2016-01-01

    Only a few studies indentified the significance of circulating microRNAs in blood as a predictive biomarker for chemoresistance in esophageal squamous cell carcinoma (ESCC). In this study, we tested whether oncogenic miR-21 promoted chemoresistance in ESCC and served as a biomarker for predicting chemoresistance in plasma of patients with ESCC. All consecutive patients underwent the preoperative chemotherapy regimen (JCOG9907 trial) with cisplatin plus 5-fluorouracil. As a result, pretreatment plasma concentrations of miR-21 were significantly higher in ESCC patients with a low histopathological response than in those with a high histopathological response (P = 0.0416). Multivariate analysis revealed that a high pretreatment plasma concentration of miR-21 was an independent risk factor of chemoresistance (p = 0.0150; Odds Ratio 9.95 (range: 1.56-63.4)). The expression of miR-21 was also significantly higher in pretreatment ESCC tissues with a low histopathological response than in those with a high histopathological response (P = 0.0409). In vitro, although the growth of KYSE 170 ESCC cells transfected with the control mimics was markedly inhibited by the 5-fluorouracil or cisplatin treatment, the inhibitory effects of 5-FU (P < 0.05) or cisplatin (P < 0.05) were significantly reduced in KYSE170 cells that overexpressed miR-21. Taken together, the overexpression of miR-21 contributed to chemoresistance and circulating miR-21 in plasma of patients with ESCC could be a useful biomarker for predicting chemoresistance. PMID:27508093

  4. Novel monofunctional platinum (II) complex Mono-Pt induces apoptosis-independent autophagic cell death in human ovarian carcinoma cells, distinct from cisplatin

    PubMed Central

    Guo, Wen-Jie; Zhang, Yang-Miao; Zhang, Li; Huang, Bin; Tao, Fei-Fei; Chen, Wei; Guo, Zi-Jian; Xu, Qiang; Sun, Yang

    2013-01-01

    Failure to engage apoptosis appears to be a leading mechanism of resistance to traditional platinum drugs in patients with ovarian cancer. Therefore, an alternative strategy to induce cell death is needed for the chemotherapy of this apoptosis-resistant cancer. Here we report that autophagic cell death, distinct from cisplatin-induced apoptosis, is triggered by a novel monofunctional platinum (II) complex named Mono-Pt in human ovarian carcinoma cells. Mono-Pt-induced cell death has the following features: cytoplasmic vacuolation, caspase-independent, no nuclear fragmentation or chromatin condensation, and no apoptotic bodies. These characteristics integrally indicated that Mono-Pt, rather than cisplatin, initiated a nonapoptotic cell death in Caov-3 ovarian carcinoma cells. Furthermore, incubation of the cells with Mono-Pt but not with cisplatin produced an increasing punctate distribution of microtubule-associated protein 1 light chain 3 (LC3), and an increasing ratio of LC3-II to LC3-I. Mono-Pt also caused the formation of autophagic vacuoles as revealed by monodansylcadaverine staining and transmission electron microscopy. In addition, Mono-Pt-induced cell death was significantly inhibited by the knockdown of either BECN1 or ATG7 gene expression, or by autophagy inhibitors 3-methyladenine, chloroquine and bafilomycin A1. Moreover, the effect of Mono-Pt involved the AKT1-MTOR-RPS6KB1 pathway and MAPK1 (ERK2)/MAPK3 (ERK1) signaling, since the MTOR inhibitor rapamycin increased, while the MAPK1/3 inhibitor U0126 decreased Mono-Pt-induced autophagic cell death. Taken together, our results suggest that Mono-Pt exerts anticancer effect via autophagic cell death in apoptosis-resistant ovarian cancer. These findings lead to increased options for anticancer platinum drugs to induce cell death in cancer. PMID:23580233

  5. Squamous Cell Carcinoma (SCC)

    MedlinePlus

    ... A A Squamous cell carcinoma typically develops in sun-damaged skin in fair-skinned patients. Overview Squamous ... skin cancer. Squamous cell carcinoma usually occurs on sun-damaged skin, especially in light-skinned individuals with ...

  6. Apoptotic-like death occurs through a caspase-independent route in colon carcinoma cells undergoing mitotic catastrophe.

    PubMed

    Llovera, Laia; Mansilla, Sylvia; Portugal, José

    2012-12-29

    We have examined the relationship between chemotherapy-induced mitotic catastrophe and cell death by apoptosis in both wild-type and p53(-/-) HCT116 human colon carcinoma cells treated with nanomolar concentrations of paclitaxel (PTX), a drug that acts on tubulin altering the normal development of mitosis. After treatment, HCT116 cells entered mitosis regardless of the presence of functional p53, which resulted in changes in the distribution of cells in the different phases of the cell cycle, and in cell death. In the presence of PTX, the percentage of polyploid cells observed was higher in p53-deficient cells, indicating that mitotic slippage was favored compared to wild-type cells, with the presence of large multinucleate cells. PTX caused mitotic catastrophe and about 50-60% cells that were entering an aberrant mitosis died through an apoptotic-like pathway characterized by the presence of phosphatidylserine in the outer cell membrane, which occurred in the absence of significant activation of caspases. Lack of p53 facilitated endoreduplication and polyploidy in PTX-treated cells, but cells were still killed with similar efficacy through the same apoptotic-like mechanism in the absence of caspase activity. PMID:22885806

  7. Analysis of the invasive edge in primary and secondary oral squamous cell carcinoma: An independent prognostic marker: A retrospective study

    PubMed Central

    Nadaf, Afreen; Bavle, Radhika M; Soumya, M; D'mello, Sarah; Kuriakose, Moni Abraham; Govindan, Sindhu

    2016-01-01

    Background and Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck carcinomas and corresponds to 95% of all oral cancers with an increasing morbidity and mortality. Its prognosis is affected by several clinicopathologic factors, one of which is pattern of invasion (POI). The histological features of OSCC may differ widely, but there is general agreement that the most useful prognostic information can be deduced from the invasive front of the tumor. In this retrospective study, our aim was to compare the POI, the status of connective tissue and the status of inflammation at the tumor–host interface in primary and recurrent (secondary) OSCC and test the validity of POI, to serve as a potential marker to assess the prognosis of the patient. Materials and Methods: Differentiation of tumors, POI, status of connective tissue and inflammation was assessed in 168 cases of primary and recurrent cases of OSCC. Statistical Analysis: Fisher's exact test was used to determine the statistical significance and P < 0.05 was considered to be statistically significant. Results: Our study showed that majority of the primary and secondary tumors were well differentiated, 117 [95.9%] and 34 [73.9%], respectively. Predominant POI in the primary and secondary tumor group was Pattern II and least was Pattern V. Worst pattern in primary tumor and highest distribution was seen for Pattern III (53.3%), and least for Pattern V (0.00%). In secondary tumors, the predominant worst pattern was Pattern IV (50.0%) and least distribution was seen for Pattern I (0.00%). Connective tissue status for both primary and secondary tumors showed the predominance of loose type (85.2% and 79.2%) and least was variable type (0.8% and 0.6%), respectively. Status of inflammation in the primary tumor group showed a predominance of moderate grade of inflammation (50.0%) and very mild grade of inflammation (6.6%) was the least type. In the secondary tumor group, moderate grade

  8. Analysis of the invasive edge in primary and secondary oral squamous cell carcinoma: An independent prognostic marker: A retrospective study

    PubMed Central

    Nadaf, Afreen; Bavle, Radhika M; Soumya, M; D'mello, Sarah; Kuriakose, Moni Abraham; Govindan, Sindhu

    2016-01-01

    Background and Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck carcinomas and corresponds to 95% of all oral cancers with an increasing morbidity and mortality. Its prognosis is affected by several clinicopathologic factors, one of which is pattern of invasion (POI). The histological features of OSCC may differ widely, but there is general agreement that the most useful prognostic information can be deduced from the invasive front of the tumor. In this retrospective study, our aim was to compare the POI, the status of connective tissue and the status of inflammation at the tumor–host interface in primary and recurrent (secondary) OSCC and test the validity of POI, to serve as a potential marker to assess the prognosis of the patient. Materials and Methods: Differentiation of tumors, POI, status of connective tissue and inflammation was assessed in 168 cases of primary and recurrent cases of OSCC. Statistical Analysis: Fisher's exact test was used to determine the statistical significance and P < 0.05 was considered to be statistically significant. Results: Our study showed that majority of the primary and secondary tumors were well differentiated, 117 [95.9%] and 34 [73.9%], respectively. Predominant POI in the primary and secondary tumor group was Pattern II and least was Pattern V. Worst pattern in primary tumor and highest distribution was seen for Pattern III (53.3%), and least for Pattern V (0.00%). In secondary tumors, the predominant worst pattern was Pattern IV (50.0%) and least distribution was seen for Pattern I (0.00%). Connective tissue status for both primary and secondary tumors showed the predominance of loose type (85.2% and 79.2%) and least was variable type (0.8% and 0.6%), respectively. Status of inflammation in the primary tumor group showed a predominance of moderate grade of inflammation (50.0%) and very mild grade of inflammation (6.6%) was the least type. In the secondary tumor group, moderate grade

  9. Squamous cell carcinoma

    Cancer.gov

    The hallmarks of squamous cell carcinoma are the differentiation features of the squamous epithelium: keratinization and intercellular bridges. Large central masses of keratin, individual cell keratinization, and/or keratin pearls may form. Necrosis of tumor cell nests and accumulation of acute inflammatory cells are frequent features of poorly differentiated squamous cell carcinoma.

  10. L-3-Phosphoserine Phosphatase (PSPH) Regulates Cutaneous Squamous Cell Carcinoma Proliferation Independent of L-serine Biosynthesis

    PubMed Central

    Bachelor, Michael A.; Lu, Yan; Owens, David M.

    2011-01-01

    Background L-3-phosphoserine phosphatase (Psph) is a highly conserved and widely expressed member of the haloacid dehalogenase superfamily and the rate-limiting enzyme in L-serine biosynthesis. We previously found Psph expression to be uniquely upregulated in a α6β4 integrin transgenic mouse model that is predisposed to epidermal hyperproliferation and squamous cell carcinoma (SCC) formation implicating a role for Psph in epidermal homeostasis. Objective We examined the status of PSPH in normal skin epidermis and skin tumors along with its sub-cellular localization in epidermal keratinocytes and its requirement for squamous cell carcinoma (SCC) proliferation. Methods First, an immunohistochemical study was performed for PSPH in normal skin and skin cancer specimens and in cultured keratinocytes. Next, biochemical analyses were performed to confirm localization of PSPH and to identify candidate binding proteins. Finally, proliferation and apoptosis studies were performed in human SCC and normal keratinocytes, respectively, transduced with vectors encoding small hairpin RNAs targeting PSPH or overexpressing a phosphatase-deficient PSPH mutant. Results PSPH is expressed throughout the proliferative layer of the epidermis and hair follicles in rodent and human skin and is highly induced in SCC. In keratinocytes, PSPH is a cytoplasmic protein that primarily localizes to endosomes and is present primarily as a homodimer. Knock down of PSPH dramatically diminished SCC cell proliferation and cyclin D1 levels in the presence of exogenous of L-serine production suggesting a non-canonical role for PSPH in epithelial carcinogenesis. Conclusions Psph is highly induced in proliferative normal keratinocytes and in skin tumors. PSPH appears to be critical for the proliferation of SCC cells; however, this phenomenon may not involve the phosphoserine metabolic pathway. PMID:21726982

  11. Involvement of phorbol-12-myristate-13-acetate-induced protein 1 in goniothalamin-induced TP53-dependent and -independent apoptosis in hepatocellular carcinoma-derived cells

    SciTech Connect

    Kuo, Kung-Kai; Chen, Yi-Ling; Chen, Lih-Ren; Li, Chien-Feng; Lan, Yu-Hsuan; Chang, Fang-Rong; Wu, Yang-Chang; Shiue, Yow-Ling

    2011-10-01

    The objective was to investigate the upstream apoptotic mechanisms that were triggered by a styrylpyrone derivative, goniothalamin (GTN), in tumor protein p53 (TP53)-positive and -negative hepatocellular carcinoma (HCC)-derived cells. Effects of GTN were evaluated by the flow cytometry, alkaline comet assay, immunocytochemistry, small-hairpin RNA interference, mitochondria/cytosol fractionation, quantitative reverse transcription-polymerase chain reaction, immunoblotting analysis and caspase 3 activity assays in two HCC-derived cell lines. Results indicated that GTN triggered phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, also known as NOXA)-mediated apoptosis via TP53-dependent and -independent pathways. In TP53-positive SK-Hep1 cells, GTN furthermore induced TP53 transcription-dependent and -independent apoptosis. After GTN treatment, accumulation of reactive oxygen species, formation of DNA double-strand breaks, transactivation of TP53 and/or PMAIP1 gene, translocation of TP53 and/or PMAIP1 proteins to mitochondria, release of cytochrome c from mitochondria, cleavage of caspases and induction of apoptosis in both cell lines were sustained. GTN might represent a novel class of anticancer drug that induces apoptosis in HCC-derived cells through PMAIP1 transactivation regardless of the status of TP53 gene. - Highlights: > Goniothalamin (GTN) induced apoptosis in hepatocellular carcinomas-derived cells. > The apoptosis induced by GTN is PMAIP1-dependent, regardless of TP53 status. > The apoptosis induced by GTN might be TP53 transcription-dependent or -independent. > GTN-induced apoptosis is mitochondria- and caspases-mediated.

  12. Basal Cell Carcinoma

    PubMed Central

    Lanoue, Julien

    2016-01-01

    Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

  13. [Merkel cell skin carcinoma].

    PubMed

    Krejcí, K; Zadrazil, J; Tichý, T; Horák, P; Ciferská, H; Hodulová, M; Zezulová, M; Zlevorová, M

    2010-01-01

    Merkel cell carcinoma is a rare tumour of the skin. It affects predominantly elderly Caucasian males on sun-exposed areas of the skin. Distinctively more frequent and at significantly lower age, its incidence is higher in immunocompromised patients. In these patients we often observe the highly aggressive course of Merkel cell carcinoma and a fatal outcome. The incidence of Merkel cell carcinoma has been rising in recent years and is more dramatic than the increased incidence of cutaneous melanoma. More than one-third of Merkel cell carcinoma patients will die from this cancer, making it twice as lethal as melanoma. The malignant transformation of Merkel cells is currently thought to be related to an infection with Merkel cell polyomavirus. In the early stage the discreet clinical picture may be contrary to extensive microscopic invasion and this seemingly benign appearance can delay diagnosis or increase the risk of insufficient tumour excision. The diagnosis is definitely confirmed by histological evaluation and immunohistochemical tests. A typical feature is the tendency of Merkel cell carcinoma to frequent local recurrence and early metastasizing into regional lymph nodes with subsequent tumour generalization. The mainstay of therapy is radical excision of the tumour and adjuvant radiotherapy targeted at the site of primary incidence and local draining lymph nodes. The efficacy of different chemotherapy protocols in Merkel cell carcinoma is limited and the median survival rate is measured in months. In the future, prophylaxis with vaccination against Merkel cell polyomavirus will hopefully be possible in high-risk patients, as well as therapeutic usage of antisense oligonucleotides or microRNAs, eventually complete Merkel cell carcinoma elimination by affecting the tumour suppressor gene Atonal homolog 1 expression. The staging of the tumour at time of diagnosis is the most important prognostic factor. In this respect, the importance of preventative skin

  14. Xenotransplanted human prostate carcinoma (DU145) cells develop into carcinomas and cribriform carcinomas: ultrastructural aspects.

    PubMed

    Gilloteaux, Jacques; Jamison, James M; Neal, Deborah R; Summers, Jack L; Taper, Henryk S

    2012-10-01

    Androgen-independent, human prostate carcinoma cells (DU145) develop into solid, carcinomatous xenotransplants on the diaphragm of nu/nu mice. Tumors encompass at least two poorly differentiated cell types: a rapidly dividing, eosinophilic cell comprises the main cell population and a few, but large basophilic cells able to invade the peritoneal stroma, the muscular tissue, lymph vessels. Poor cell contacts, intracytoplasmic lumina, and signet cells are noted. Lysosomal activities are reflected by entoses and programmed cell deaths forming cribriform carcinomas. In large tumors, degraded cells may align with others to facilitate formation of blood supply routes. Malignant cells would spread via ascites and through lymphatics.

  15. Caveolin-1 expression in ovarian carcinoma is MDR1 independent.

    PubMed

    Davidson, Ben; Goldberg, Iris; Givant-Horwitz, Vered; Nesland, Jahn M; Berner, Aasmund; Bryne, Magne; Risberg, Bjørn; Kopolovic, Juri; Kristensen, Gunnar B; Tropé, Claes G; van de Putte, Gregg; Reich, Reuven

    2002-02-01

    We studied the role of caveolin-1 in tumor progression and prognosis in serous ovarian carcinoma and the association between caveolin-1 and MDR1 expression. The study involved immunohistochemical analysis for caveolin-1 and P-glycoprotein (P-gp) expression in 75 effusions and 90 solid lesions from ovarian and primary peritoneal carcinoma; in situ hybridization for MDR1 messenger RNA (mRNA) expression in 62 effusions and all 90 tumors; and reverse transcription-polymerase chain reaction (RT-PCR) for caveolin-1 mRNA expression in 23 effusions. Immunohistochemical analysis localized caveolin-1 to the cell membrane in 43 effusions and 24 tumors. P-gp membrane expression was detected in 14 effusions and 11 tumors; MDR1 mRNA, in 20 effusions and 30 tumors. Caveolin-1 mRNA was expressed in 19 effusions. Caveolin-1 protein expression showed no association with that of P-gp protein or MDR1 mRNA. The expression of all markers was similar in carcinoma cells in pleural and peritoneal effusions. Caveolin-1 is a novel diagnostic marker for effusions; expression is moderately elevated in tumor cells in effusions, possibly owing to altered signal transduction and metabolism in cancer cells at this site. Expression seems MDR1 independent. PMID:11863219

  16. Cytokine signal transduction in P19 embryonal carcinoma cells: regulation of Stat3-mediated transactivation occurs independently of p21ras-Erk signaling.

    PubMed

    van Puijenbroek, A A; van der Saag, P T; Coffer, P J

    1999-09-15

    Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are members of a subfamily of related cytokines that share gp130 as common signal-transducing receptor component. CNTF has recently been demonstrated to induce increased survival and neuronal differentiation of P19 embryonal carcinoma (EC) cells; however, the molecular mechanisms underlying these effects are still elusive. Here we report that CNTF and LIF, but not interleukin-6, activated signal transducers and activators of transcription (STAT)-reporter constructs in P19 EC cells. Supershift analysis revealed that the STAT-element binding complex contained the transcription factor Stat3. Binding of Stat3 was inhibited by protein tyrosine kinase inhibitors, but not by the broad serine/threonine protein kinase inhibitor, H7. However, H7 inhibited CNTF-induced Stat3 transactivation. Using a dominant-negative p21ras construct and a specific inhibitor of mitogen-activated protein kinase kinase (MEK; PD098059) we demonstrated that CNTF-induced Stat3 transactivation was independent of the p21ras-mitogen-activated protein kinase (MAPK) pathway, while CNTF-induced MAPK activation was p21ras- and MEK-dependent. Taken together, our results demonstrate the activation of the p21ras-MAPK and STAT signal transduction pathways in response to CNTF and LIF in P19 EC cells and reveal that there is no modulating crosstalk between these pathways. Furthermore, our data suggest that CNTF- and LIF-induced Stat3 activation in P19 EC cells involves an H7-sensitive p21ras/MAPK- and Ca(2+)-independent kinase.

  17. Pycnogenol Induces Nuclear Translocation of Apoptosis-inducing Factor and Caspase-independent Apoptosis in MC-3 Human Mucoepidermoid Carcinoma Cell Line

    PubMed Central

    Yang, In-Hyoung; Shin, Ji-Ae; Cho, Sung-Dae

    2014-01-01

    Background: Pycnogenol is extracted from the pine bark of a tree known as Pinus pinaster that has variety biological effects. However, its anticancer activity has not yet been completely studied. The aim of this study is to investigate anticancer effect of pycnogenol in MC-3 human mucoepidermoid carcinoma (MEC) cell line. Methods: We describe the effect of anti-cancer of pycnogenol in MC-3 human oral MEC cells using trypan blue exclusion assay, 3-(4,5-dimethylthiazol-2-yl)-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) assay, Western blot, preparation of cytosolic and nuclear fractions, immunocytochemistry and reverse transcriptase polymerase chain reaction. Results: Pycnogenol significantly decreased cell viability and also induced caspase-independent apoptosis. We confirmed that pycnogenol induced the translocation of apoptosis-inducing factor into nucleus and regulated apoptosis. Also, Bak protein stability was partly enhanced by pycnogenol to elevate the expression level of Bak protein. Conclusions: Overall, pycnogenol may be a fascinating therapeutic drug candidate for the treatment of MEC. PMID:25574461

  18. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    SciTech Connect

    Huang, Eng-Yen; Chanchien, Chan-Chao; Lin, Hao; Wang, Chung-Chi; Wang, Chong-Jong; Huang, Chao-Cheng

    2013-12-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

  19. Tumor necrosis factor-α induces epithelial-mesenchymal transition of renal cell carcinoma cells via a nuclear factor kappa B-independent mechanism.

    PubMed

    Wu, Sheng-Tang; Sun, Guang-Huan; Hsu, Chih-Ying; Huang, Chang-Shuo; Wu, Yu-Hsin; Wang, Hsiao-Hsien; Sun, Kuang-Hui

    2011-09-01

    Chronic low dose of tumor necrosis factor-α (TNF-α) stimulation promotes tumorigenesis by facilitating tumor proliferation and metastasis. The plasma levels of TNF-α are increased in patients with renal cell carcinoma (RCC). Furthermore, high-grade clear cell RCC cell lines secrete more TNF-α than low-grade ones, and allow low-grade cell lines' gain of invasive ability. However, the molecular mechanism of TNF-α in mediating progression of RCC cells remains unclear. In the present study, TNF-α induced epithelial-mesenchymal transition (EMT) of RCC cells by repressing E-cadherin, promoting invasiveness and activating matrix metalloproteinase (MMP) 9 activity. RCC cells underwent promoted growth in vivo following stimulation with TNF-α. In addition, TNF-α induced phosphorylation of extracellular signal-regulated kinase, nuclear factor kappa B (NF-κB) and Akt in a time-dependent manner, and increased nuclear translocation and promoter activity of NF-κB. To investigate the role of NF-κB activation in TNF-α-induced EMT of RCC, we employed chemical inhibitors (NF-κB activation inhibitor and Bay 11-7082) and transfected dominant-negative (pCMV-IκBαM) and overexpressive (pFLAG-p65) vectors of NF-κB. While overexpression of NF-κB p65 alone could induce E-cadherin loss in RCC, EMT phenotypes and MMP9 expressions induced by TNF-α were not reversed by the inhibitors of NF-κB activation. These results suggest that the TNF-α signaling pathway is involved in the tumorigenesis of RCC. However, NF-κB activation is not crucial for invasion and EMT enhanced by TNF-α in RCC cells.

  20. Prognostic investigations of B7-H1 and B7-H4 expression levels as independent predictor markers of renal cell carcinoma.

    PubMed

    Safaei, Hamid Reza; Rostamzadeh, Ayoob; Rahmani, Omid; Mohammadi, Mohsen; Ghaderi, Omar; Yahaghi, Hamid; Ahmadi, Koroosh

    2016-06-01

    In order to evaluate the correlation of B7-H4 and B7-H1 with renal cell carcinoma (RCC), we analyzed B7-H1 and B7-H4 expressions and their clinical significance by immunohistochemical method. Our result indicated that B7-H4-positive staining was detected in 58.13 % of RCC tissues (25 tissues tumors), and there were 18 tissues of patients without detectable B7-H4. Furthermore, 21 cases (48.83 %) were B7-H1-positive. Positive tumor expressions of B7-H4 and B7-H1 were markedly related to advanced TNM stage (P = 0.001; P = 0.014), high grade (P = 0.001; P = 002), and larger tumor size (P = 0.002; P = 024) in RCC tissues than patients with B7-H4-negative and B7-H1-negative in RCC tissues. The patients with B7-H1 and B7-H4-positive expressions were found to be markedly correlated with the overall survival of the patients (P < 0.05) and tended to have an increased risk of death when compared with negative expression groups. Univariate analysis showed that B7-H4 and B7-H1 expressions, TNM stage, high grade, and tumor size were significantly related to the prognosis of RCC. Furthermore, multivariate analysis showed that B7-H4 and B7-H1 expressions decreased overall survival. The adjusted HR for B7-H1 was 2.83 (95 % CI 1.210-2.971; P = 0.031) and also was 2.918 (95 % CI 1.243-3.102; P = 0.006) for B7-H4 that showed these markers were independent prognostic factors in RCC patients. The expressions of B7-H1 and B7-H4 in RCC patients indicate that these markers may be as a predictor of tumor development and death risk. Further investigations can be helpful to confirm B7-H1 and B7-H4 roles as an independent predictor of clinical RCC outcome. PMID:26687644

  1. Fallacious Carcinoma- Spindle Cell Variant of Squamous Cell Carcinoma.

    PubMed

    Bavle, Radhika M; Govinda, Girish; Venkataramanaiah, Padmalatha Gundappanayakanahalli; Muniswamappa, Sudhakara; Venugopal, Reshma

    2016-07-01

    Spindle cell carcinoma is a unique, rare and peculiar biphasic tumour of head and neck which is not frequently observed in the oral cavity. This variant of squamous cell carcinoma although of monophasic epithelial origin, simulates a sarcoma and is an aggressive carcinoma with high frequency of recurrence and metastasis. A correct and timely diagnosis is of paramount importance. Most of the tumours require an Immunohistochemistry (IHC) panel for confirmation or diagnosis. We report a case of spindle cell carcinoma with varied histopathological morphology and clinical presentation in a middle aged female with a brief review of literature. PMID:27630965

  2. Fallacious Carcinoma- Spindle Cell Variant of Squamous Cell Carcinoma

    PubMed Central

    Bavle, Radhika M; Govinda, Girish; Muniswamappa, Sudhakara; Venugopal, Reshma

    2016-01-01

    Spindle cell carcinoma is a unique, rare and peculiar biphasic tumour of head and neck which is not frequently observed in the oral cavity. This variant of squamous cell carcinoma although of monophasic epithelial origin, simulates a sarcoma and is an aggressive carcinoma with high frequency of recurrence and metastasis. A correct and timely diagnosis is of paramount importance. Most of the tumours require an Immunohistochemistry (IHC) panel for confirmation or diagnosis. We report a case of spindle cell carcinoma with varied histopathological morphology and clinical presentation in a middle aged female with a brief review of literature.

  3. Fallacious Carcinoma- Spindle Cell Variant of Squamous Cell Carcinoma

    PubMed Central

    Bavle, Radhika M; Govinda, Girish; Muniswamappa, Sudhakara; Venugopal, Reshma

    2016-01-01

    Spindle cell carcinoma is a unique, rare and peculiar biphasic tumour of head and neck which is not frequently observed in the oral cavity. This variant of squamous cell carcinoma although of monophasic epithelial origin, simulates a sarcoma and is an aggressive carcinoma with high frequency of recurrence and metastasis. A correct and timely diagnosis is of paramount importance. Most of the tumours require an Immunohistochemistry (IHC) panel for confirmation or diagnosis. We report a case of spindle cell carcinoma with varied histopathological morphology and clinical presentation in a middle aged female with a brief review of literature. PMID:27630965

  4. Merkel cell carcinoma

    PubMed Central

    Koljonen, Virve

    2006-01-01

    Background Merkel cell carcinoma (MCC) is an unusual primary neuroendocrine carcinoma of the skin. MCC is a fatal disease, and patients have a poor chance of survival. Moreover, MCC lacks distinguishing clinical features, and thus by the time the diagnosis is made, the tumour usually have metastasized. MCC mainly affects sun-exposed areas of elderly persons. Half of the tumours are located in the head and neck region. Methods MCC was first described in 1972. Since then, most of the cases reported, have been in small series of patients. Most of the reports concern single cases or epidemiological studies. The present study reviews the world literature on MCC. The purpose of this article is to shed light on this unknown neuroendocrine carcinoma and provide the latest information on prognostic markers and treatment options. Results The epidemiological studies have revealed that large tumour size, male sex, truncal site, nodal/distant disease at presentation, and duration of disease before presentation, are poor prognostic factors. The recommended initial treatment is extensive local excision. Adjuvant radiation therapy has recently been shown to improve survival. Thus far, no chemotherapy protocol have achieved the same objective. Conclusion Although rare, the fatality of this malignancy makes is important to understand the etiology and pathophysiology. During the last few years, the research on MCC has produced prognostic markers, which can be translated into clinical patient care. PMID:16466578

  5. Clear cell odontogenic carcinoma.

    PubMed

    Iezzi, G; Rubini, C; Fioroni, M; Piattelli, A

    2002-02-01

    Clear cell tumours, in the head and neck region, are usually derived from salivary or odontogenic tissues, or may be metastatic. A few clear cells may be present in odontogenic cysts, while, odontogenic neoplasms composed predominantly of clear cells are quite rare. They include calcifying epithelial odontogenic tumours (CEOT), ameloblastoma and odontogenic carcinoma. Clear cell odontogenic tumour (CCOT) has been classified in the last WHO classification as a benign tumour, but it is now recognized as a more sinister lesion and current opinion is that CCOT should be designated as a carcinoma. These tumours are characterized by aggressive growth, recurrences, and metastatic disease. A recent review of the literature has yielded 30 cases of tumours with similar characteristics. These tumours have a peak incidence in the 5th-7th decades, with a female predilection. The anterior portions of the jaws, especially the mandible, are most frequently affected. The aggressive potential of these neoplasms is well documented by the extensive invasion of adjacent tissues, multiple recurrences and regional or distant metastases.

  6. Aqueous extract of Curcuma aromatica induces apoptosis and G2/M arrest in human colon carcinoma LS-174-T cells independent of p53.

    PubMed

    Hu, Bing; Shen, Ke-Ping; An, Hong-Mei; Wu, Yang; Du, Qin

    2011-02-01

    Curcuma aromatica is a common Chinese herb for treating diseases with blood stasis and has been regarded as an anticancer herb in modern clinical practice. However, the anticancer effects and related molecular mechanisms of Curcuma aromatica remain unclear. In the present study, human colon carcinoma LS-174-T cell line with wild-type p53 was used as a model cell to evaluate the anticancer effects of aqueous extract of Curcuma aromatica (AECA). AECA inhibits LS-174-T cell proliferation in a dose- and time-dependent manner and colony formation in a dose-dependent manner. AECA treatment induces apoptosis accompanied by caspase-8, -9, and -3 activation in LS-174-T cells. Moreover, blocking the activities of these caspases with a specific inhibitor significantly protected LS-174-T cells from AECA-induced apoptosis. AECA treatment also induces G2/M phase arrest in LS-174-T cells. Expression of p53 was unchanged after AECA treatment; specific silence of p53 did not influence AECA-induced apoptosis and G2/M phase arrest. Further, the expression of cyclin B1 and CDK1 was reduced by AECA. This study suggests that AECA might be effective as an antiproliferative herb for colon carcinoma, the antitumor activity of AECA may involve both extrinsic and intrinsic apoptosis, and AECA induces G2/M phase arrest via downregulation of cyclin B1 and CDK1 and without the participation of p53.

  7. Basal cell carcinoma

    PubMed Central

    2010-01-01

    Introduction Basal cell carcinoma (BCC) is the most common form of skin cancer, predominantly affecting the head and neck, and can be diagnosed clinically in most cases. Metastasis of BCC is rare, but localised tissue invasion and destruction can lead to morbidity. Incidence of BCC increases markedly after the age of 40 years, but incidence in younger people is rising, possibly as a result of increased sun exposure. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions on treatment response/recurrence (within 1 year of therapy) in people with basal cell carcinoma? What are the effects of interventions on long-term recurrence (a minimum of 2 years after treatment) in people with basal cell carcinoma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: cryotherapy/cryosurgery, curettage and cautery/electrodesiccation, fluorouracil, imiquimod 5% cream, photodynamic therapy, and surgery (conventional or Mohs' micrographic surgery). PMID:21718567

  8. Perianal Basal Cell Carcinoma

    PubMed Central

    Bulur, Isil; Boyuk, Emine; Saracoglu, Zeynep Nurhan; Arik, Deniz

    2015-01-01

    Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. Exposure to ultraviolet light is an important risk factor for BCC development and the disorder therefore develops commonly on body areas that are more exposed to sunlight, such as the face and neck. It is uncommon in the closed area of the body and quite rare in the perianal and genital regions. Herein, we report a 34-year-old patient with perianal BCC who had no additional risk factors. PMID:25848349

  9. Lobomycosis and squamous cell carcinoma*

    PubMed Central

    Nogueira, Lisiane; Rodrigues, Luciana; Rodrigues, Carlos Alberto Chirano; Santos, Mônica; Talhari, Sinésio; Talhari, Carolina

    2013-01-01

    The occurence of squamous cell carcinoma on long-lasting ulcers is classic. Malignant transformation may occur on burn scars and chronic ulcers of varying etiology, including infectious agents. Transformation of old lobomycosis lesion scars into squamous cell carcinoma has been rarely reported. Careful and long-term follow-up of such patients is important to avoid carcinomatous transformation. PMID:23739701

  10. Pre-existing Type 2 Diabetes Mellitus Is an Independent Risk Factor for Mortality and Progression in Patients With Renal Cell Carcinoma

    PubMed Central

    Vavallo, Antonio; Simone, Simona; Lucarelli, Giuseppe; Rutigliano, Monica; Galleggiante, Vanessa; Grandaliano, Giuseppe; Gesualdo, Loreto; Campagna, Marcello; Cariello, Marica; Ranieri, Elena; Pertosa, Giovanni; Lastilla, Gaetano; Selvaggi, Francesco Paolo; Ditonno, Pasquale; Battaglia, Michele

    2014-01-01

    Abstract Malignancies are one of the main causes of mortality in diabetic patients; however, to date, very limited data have been reported on the specific influence of type 2 diabetes mellitus (T2DM) on the survival of patients with renal cell carcinoma (RCC). In the present long-term retrospective study, we investigated whether T2DM may influence the overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in patients with surgically treated RCC. Medical records of 924 patients treated by radical or partial nephrectomy for sporadic, unilateral RCC were reviewed. Patients with type-1 DM and with T2 DM receiving insulin treatment were excluded. Survival estimates were calculated according to the Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate analyses were performed using the Cox regression model. Of the 924 RCC patients, 152 (16.5%) had T2DM. Mean follow-up was 68.5 months. Mean OS was 41.3 and 96.3 months in T2DM and non-T2DM patients, respectively (P < 0.0001). The estimated CSS rates at 1, 3, and 5 years in T2DM versus non-T2DM patients were 63.4% versus 76.7%, 30.4% versus 56.6%, and 16.3% versus 48.6%, respectively (P = 0.001). Mean PFS was significantly lower (31.5 vs 96.3 months; P < 0.0001) in the T2DM group. At multivariate analysis, T2DM was an independent adverse prognostic factor for OS (hazard ratio [HR] = 3.44; 95% confidence interval [CI]:2.40–4.92), CSS (HR = 6.39; 95% CI: 3.78–10.79), and PFS (HR = 4.71; 95% CI: 3.11–7.15). In conclusion, our findings suggest that patients with RCC and pre-existing T2DM have a shorter OS, increased risk of recurrence, and higher risk for kidney cancer mortality than those without diabetes. PMID:25501064

  11. Synchronous Renal Cell Carcinoma and Gastrointestinal Malignancies

    PubMed Central

    Dafashy, Tamer J.; Ghaffary, Cameron K.; Keyes, Kyle T.; Sonstein, Joseph

    2016-01-01

    While renal cell carcinoma is the most commonly diagnosed neoplasm of the kidney, its simultaneous diagnosis with a gastrointestinal malignancy is a rare, but well reported phenomenon. This discussion focuses on three independent cases in which each patient was diagnosed with renal cell carcinoma and a unique synchronous gastrointestinal malignancy. Case 1 explores the diagnosis and surgical intervention of a 66-year-old male patient synchronously diagnosed with clear cell renal cell carcinoma and a carcinoid tumor of the small bowel. Case 2 describes the diagnosis and surgical intervention of a 61-year-old male found to have clear cell renal cell carcinoma and a mucinous appendiceal neoplasm. Lastly, Case 3 focuses on the interventions and management of a 36-year-old female diagnosed with synchronous clear cell renal carcinoma and hereditary nonpolyposis colorectal cancer. This case series examines each distinct patient's presentation, discusses the diagnosis, and compares and contrasts the findings while discussing the literature on this topic. PMID:26904353

  12. Gastric reflux is an independent risk factor for laryngopharyngeal carcinoma

    PubMed Central

    Langevin, Scott M.; Michaud, Dominique S.; Marsit, Carmen J.; Nelson, Heather H.; Birnbaum, Ariel E.; Eliot, Melissa; Christensen, Brock C.; McClean, Michael D.; Kelsey, Karl T.

    2013-01-01

    Background Gastric reflux can reach into the upper airway, inducing cellular damage in the epithelial lining. This condition is believed to be a risk factor for development of laryngopharyngeal squamous cell carcinoma (LPSCC), although the literature is conflicting. Methods To better clarify this relationship, we assessed the association of self-reported heartburn history and medication use among 631 LPSCC patients and 1234 control subjects (frequency-matched on age, gender and town of residence) enrolled as part of a population-based case-control study of head and neck squamous cell carcinoma in the greater Boston area. Results After adjusting for age, gender, race, smoking, alcohol consumption, HPV16 seropositivity, education and body mass index, subjects reporting a history of frequent heartburn and who were neither a heavy smoker nor heavy drinker had a significantly elevated risk of LPSCC (OR = 1.78, 95% CI: 1.00–3.16). Among those with a history of heartburn, there was an inverse association between antacid use and LPSCC relative to those never taking heartburn medication (OR = 0.59, 95% CI: 0.38–0.93) that remained consistent when analyzed by smoking/drinking status, HPV16 status, or by primary tumor site. Conclusions Our data show that gastric reflux is an independent risk factor for squamous cancers of the pharynx and larynx. Further studies are needed to clarify the possible chemopreventive role of antacid use for patients with gastric reflux. Impact Elucidation of additional risk factors for head and neck cancer can allow for risk stratification and inform surveillance of high-risk patients. PMID:23703970

  13. Stages of Merkel Cell Carcinoma

    MedlinePlus

    ... other organs . Sun exposure and having a weak immune system can affect the risk of Merkel cell carcinoma. ... ultraviolet A (PUVA) therapy for psoriasis . Having an immune system weakened by disease, such as chronic lymphocytic leukemia ...

  14. Nevoid basal cell carcinoma syndrome

    MedlinePlus

    ... radiation. Exposure to radiation can lead to skin cancers. ... DG, Farndon PA. Nevoid basal cell carcinoma syndrome. 2002 Jun 20 ... al. eds. Cancer of the Skin. 2nd ed. Philadelphia, PA: Elsevier ...

  15. Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non-sarcomatoid renal carcinomas.

    PubMed

    Sircar, Kanishka; Yoo, Suk-Young; Majewski, Tadeusz; Wani, Khalida; Patel, Lalit R; Voicu, Horatiu; Torres-Garcia, Wandaliz; Verhaak, Roel G W; Tannir, Nizar; Karam, Jose A; Jonasch, Eric; Wood, Christopher G; Tamboli, Pheroze; Baggerly, Keith A; Aldape, Kenneth D; Czerniak, Bogdan

    2015-10-01

    Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma and compare them to non-sarcomatoid clear cell renal cell carcinoma. We examined the transcriptome of the epithelioid and sarcomatoid components of advanced stage sarcomatoid clear cell renal cell carcinoma (n=43) and non-sarcomatoid clear cell renal cell carcinoma (n=37) from independent discovery and validation cohorts using the cDNA microarray and RNA-seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays, from patients with sarcomatoid clear cell renal cell carcinoma (n=10) and advanced non-sarcomatoid clear cell renal cell carcinoma (n=155). The epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma had similar gene expression and DNA copy number signatures that were, however, distinct from those of high-grade, high-stage non-sarcomatoid clear cell renal cell carcinoma. Prognostic clear cell renal cell carcinoma gene expression profiles were shared by the biphasic components of sarcomatoid clear cell renal cell carcinoma and the sarcomatoid component showed a partial epithelial-to-mesenchymal transition signature. Our genome-scale microarray-based transcript data were validated in an independent set of sarcomatoid and non-sarcomatoid clear cell renal cell carcinomas using RNA-seq. Sarcomatoid clear cell renal cell carcinoma is molecularly distinct from non-sarcomatoid clear cell renal cell carcinoma, with its genetic programming largely shared by its biphasic morphological components. These data explain why a low percentage of sarcomatoid histology augurs a poor prognosis; suggest the

  16. Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1

    PubMed Central

    Sgaramella, N; Coates, P J; Strindlund, K; Loljung, L; Colella, G; Laurell, G; Rossiello, R; Muzio, L L; Loizou, C; Tartaro, G; Olofsson, K; Danielsson, K; Fåhraeus, R; Nylander, K

    2015-01-01

    Background: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. Methods: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. Results: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. Conclusion: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged ⩽40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair. PMID:26057450

  17. The spectrum of Merkel cell polyomavirus expression in Merkel cell carcinoma, in a variety of cutaneous neoplasms, and in neuroendocrine carcinomas from different anatomical sites.

    PubMed

    Ly, Thai Yen; Walsh, Noreen M; Pasternak, Sylvia

    2012-04-01

    earlier findings and implicate Merkel cell polyomavirus-independent pathogenesis in these cases. Overall, CM2B4 immunohistochemistry appears to be a specific method for Merkel cell polyomavirus detection and has the potential to play an important role in the diagnosis and classification of Merkel cell carcinoma in the future.

  18. General Information about Merkel Cell Carcinoma

    MedlinePlus

    ... Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  19. Potential targets for lung squamous cell carcinoma

    Cancer.gov

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  20. [Merkel cell carcinoma (trabecular carcinoma) of the skin].

    PubMed

    Zala, L; Armagni, C; Krebs, A

    1983-04-01

    The Merkel cell carcinoma was first designated some years ago by the descriptive term trabecular carcinoma. Both names refer to a skin tumor occurring in elderly patients. This is another example where ultrastructural differentiating criteria are necessary for a definite diagnosis i.e., identification of so-called neurosecretory-like granules by electron microscopy. We report clinical, histological, ultrastructural, and histogenetic aspects of such a disease in a woman suffering from a metastasizing Merkel cell carcinoma. PMID:6853165

  1. Merkel cell carcinoma and chronic arsenicism.

    PubMed

    Lien, H C; Tsai, T F; Lee, Y Y; Hsiao, C H

    1999-10-01

    Arsenic is a well-documented human carcinogen. Bowen's disease, squamous cell carcinoma, and basal cell carcinoma are the most common skin cancers found in patients exposed to arsenic over the long term. Merkel cell carcinoma has been documented in Taiwanese patients who resided in an endemic area of black foot disease, another condition found in patients with chronic arsenicism. We collected all cases of Merkel cell carcinoma diagnosed at two medical centers in Taiwan (N = 11) to find a possible association between chronic arsenicism and Merkel cell carcinoma. In our study 6 of the 11 patients were residents of the endemic areas for chronic arsenicism.

  2. Relaxin Enhances the Oncogenic Potential of Human Thyroid Carcinoma Cells

    PubMed Central

    Hombach-Klonisch, Sabine; Bialek, Joanna; Trojanowicz, Bogusz; Weber, Ekkehard; Holzhausen, Hans-Jürgen; Silvertown, Josh D.; Summerlee, Alastair J.; Dralle, Henning; Hoang-Vu, Cuong; Klonisch, Thomas

    2006-01-01

    The role of members of the insulin-like superfamily in human thyroid carcinoma is primarily unknown. Here we demonstrate the presence of RLN2 relaxin and relaxin receptor LGR7 in human papillary, follicular, and undifferentiated anaplastic thyroid carcinoma suggesting a specific involvement of relaxin-LGR7 signaling in thyroid carcinoma. Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells. Although RLN2 did not act as a mitogen, it acted as an autocrine/paracrine factor and significantly increased anchorage-independent growth and thyroid carcinoma cell motility and invasiveness through elastin matrices. Suppression of LGR7 expression by LGR7-siRNA abolished the RLN2-mediated accelerated tumor cell motility. The increased elastinolytic activity correlated with enhanced production and secretion of the lysosomal proteinases cathepsin-D (cath-D) and cath-L forms hereby identified as new RLN2 target molecules in human neoplastic thyrocytes. We found the intracellular distribution of procath-L specifically altered in RLN2 transfectants, providing first evidence for selective actions of relaxin on the powerful elastinolytic cath-L production, storage, and secretion in thyroid carcinoma cells. Thus, relaxin enhances the oncogenic potential and acts as novel endocrine modulator of invasiveness in human thyroid carcinoma cells. PMID:16877360

  3. Relaxin enhances the oncogenic potential of human thyroid carcinoma cells.

    PubMed

    Hombach-Klonisch, Sabine; Bialek, Joanna; Trojanowicz, Bogusz; Weber, Ekkehard; Holzhausen, Hans-Jürgen; Silvertown, Josh D; Summerlee, Alastair J; Dralle, Henning; Hoang-Vu, Cuong; Klonisch, Thomas

    2006-08-01

    The role of members of the insulin-like superfamily in human thyroid carcinoma is primarily unknown. Here we demonstrate the presence of RLN2 relaxin and relaxin receptor LGR7 in human papillary, follicular, and undifferentiated anaplastic thyroid carcinoma suggesting a specific involvement of relaxin-LGR7 signaling in thyroid carcinoma. Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells. Although RLN2 did not act as a mitogen, it acted as an autocrine/paracrine factor and significantly increased anchorage-independent growth and thyroid carcinoma cell motility and invasiveness through elastin matrices. Suppression of LGR7 expression by LGR7-siRNA abolished the RLN2-mediated accelerated tumor cell motility. The increased elastinolytic activity correlated with enhanced production and secretion of the lysosomal proteinases cathepsin-D (cath-D) and cath-L forms hereby identified as new RLN2 target molecules in human neoplastic thyrocytes. We found the intracellular distribution of procath-L specifically altered in RLN2 transfectants, providing first evidence for selective actions of relaxin on the powerful elastinolytic cath-L production, storage, and secretion in thyroid carcinoma cells. Thus, relaxin enhances the oncogenic potential and acts as novel endocrine modulator of invasiveness in human thyroid carcinoma cells.

  4. Loss of miR-200b promotes invasion via activating the Kindlin-2/integrin β1/AKT pathway in esophageal squamous cell carcinoma: An E-cadherin-independent mechanism.

    PubMed

    Zhang, Hai-Feng; Alshareef, Abdulraheem; Wu, Chengsheng; Li, Shang; Jiao, Ji-Wei; Cao, Hui-Hui; Lai, Raymond; Xu, Li-Yan; Li, En-Min

    2015-10-01

    Our previous studies have shown that loss of miR-200b enhances the invasiveness of esophageal squamous cell carcinoma (ESCC) cells. However, whether the miR-200-ZEB1/2-E-cadherin regulatory cascade, a master regulator of epithelial-to-mesenchymal transition (EMT), is involved in the regulation of ESCC invasion remains elusive. Here, we show that miR-200b represses ESCC cell invasion in vivo without altering the expression of E-cadherin and vimentin, two surrogate markers of EMT. However, an inverse correlation was observed between the expression levels of miR-200b and ZEB1/2 in both ESCC cell lines (n = 7, P < 0.05) and ESCC tumor samples (n = 88, P < 0.05). Methylation of E-cadherin gene was found to block the regulation of E-cadherin by the miR-200b-ZEB1/2 axis, indicating that an E-cadherin-independent mechanism can mediate the biological function of miR-200b in ESCC. We revealed that miR-200b suppresses the integrin β1-AKT pathway via targeting Kindlin-2 to mitigate ESCC cell invasiveness. In two independent cohorts of ESCC samples (n = 20 and n = 53, respectively), Kindlin-2 expression positively correlated with the activation status of both the integrin signaling pathway and the PI3K-AKT signaling pathway (both P < 0.01). These data highlight that suppression of the Kindlin-2-integrin β1-AKT regulatory axis is an alternative mechanism underlying the tumor suppressor function of miR-200b in ESCC.

  5. Human Adrenocortical Carcinoma Cell Lines

    PubMed Central

    Wang, Tao; Rainey, William E.

    2011-01-01

    Summary The human adrenal cortex secretes mineralocorticoids, glucocorticoids and adrenal androgens. These steroids are produced from unique cell types located within the three distinct zones of the adrenal cortex. Disruption of adrenal steroid production results in a variety of diseases that can lead to hypertension, metabolic syndrome, infertility and androgen excess. The adrenal cortex is also a common site for the development of adenomas, and rarely the site for the development of carcinomas. The adenomas can lead to diseases associated with adrenal steroid excess, while the carcinomas are particularly aggressive and have a poor prognosis. In vitro cell culture models provide an important tool to examine molecular and cellular mechanisms controlling both the normal and pathologic function of the adrenal cortex. Herein we discuss the human adrenocortical cell lines and their use as model systems for adrenal studies. PMID:21924324

  6. Renal cell carcinoma

    MedlinePlus

    Renal cancer; Kidney cancer; Hypernephroma; Adenocarcinoma of renal cells; Cancer - kidney ... ed. Philadelphia, PA: Elsevier; 2016:chap 57. National Cancer Institute: PDQ renal cell cancer treatment. Bethesda, MD: National Cancer Institute. ...

  7. Gastric Large Cell Neuroendocrine Carcinoma

    PubMed Central

    Rustagi, Tarun; Alekshun, Todd J.

    2010-01-01

    Case: A 63-year-old male presented with unintentional weight loss of 20 pounds over a 4-month duration. He reported loss of appetite, intermittent post-prandial nausea, bloating and early satiety. He also complained of dyspepsia and had been treated for reflux during the previous 2 years. He denied vomiting, dysphagia, odynophagia, abdominal pain, melena, hematochezia, or alterations in bowel habits. Additionally, he denied fevers, night sweats, cough, or dyspnea. He quit smoking 25 years ago, and denied alcohol use. His past medical history was significant for basal cell carcinoma treated with local curative therapy and he was without recurrence on surveillance. Pertinent family history included a paternal uncle with lung cancer at the age of 74. Physical examination was unremarkable except for occult heme-positive stools. Laboratory evaluation revealed elevated liver enzymes (ALT-112, AST-81, AlkPhos-364). CT scan of the chest, abdomen and pelvis showed diffuse heterogeneous liver with extensive nodularity, raising the concern for metastases. Serum tumor-markers: PSA, CEA, CA 19-9, and AFP were all within normal limits. Screening colonoscopy was normal, but esophagogastroduodenoscopy revealed a malignant-appearing ulcerative lesion involving the gastro-esophageal junction and gastric cardia. Pathology confirmed an invasive gastric large cell neuroendocrine carcinoma. Ultrasound-guided fine needle aspiration of a hepatic lesion revealed malignant cells with cytologic features consistent with large-cell type carcinoma and positive immunostaining for synaptophysin favoring neuroendocrine differentiation. A PET-CT demonstrated intense diffuse FDG uptake of the liver, suggesting diffuse hepatic parenchymal infiltration by tumor. There were multiple foci of intense osseous FDG uptake with corresponding osteolytic lesions seen on CT scan. The remaining intra-abdominal and intra-thoracic structures were unremarkable. The patient will receive palliative systemic therapy

  8. Renal cell carcinoma in childhood.

    PubMed

    Kabala, J E; Shield, J; Duncan, A

    1992-01-01

    The imaging features of renal cell carcinoma in 4 young patients (age 7 to 14 years) are described. A high proportion (75%) showed calcification on plain radiographs or computed tomography (CT). Both patients who underwent CT showed well defined high density tumours which were also echogenic on ultrasound examination. These findings are significantly different to those most commonly seen on studies of the tumour in adults.

  9. Caspase-independent cell deaths.

    PubMed

    Lockshin, Richard A; Zakeri, Zahra

    2002-12-01

    A very common and the best understood of the mechanisms of physiological cell death is apoptosis, resulting from the activation, through either of two primary pathways, of site-specific proteases called caspases. There are, however, many other routes to cell death, prominently including autophagy and proteasomal degradation of critical constituents of cells. These routes are frequently seen in experimental situations in which initiator or effector caspases are inhibited or blocked through genetic means, but they are also encountered during normal physiological and pathological processes. Most frequently, autophagic or proteasomal degradation is used to eliminate massive cytoplasm of very large cells, especially post-mitotic cells, and these pathways are prominent even though caspase genes, messages, and pro-enzymes are found in the cells. These forms of cell death are fully physiological and not simply a default pathway for a defective cell; and they are distinct from necrosis. We do not yet understand the extent to which the pathways are linked, what mechanisms trigger the caspase-independent deaths, and how the choices are made.

  10. Photodynamic therapy for basal cell carcinoma.

    PubMed

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

  11. Clear cell carcinoma of the lung.

    PubMed Central

    Edwards, C; Carlile, A

    1985-01-01

    Six tumours of the lung initially classified as clear cell carcinoma, were studied. Examination of further material by light and electron microscopy showed adenocarcinomatous differentiation in three cases and squamous differentiation in two. One case showed the features of a large cell anaplastic carcinoma. The clear appearance of the cytoplasm in paraffin sections was due to accumulations of glycogen that were partially removed during processing. It is concluded that clear cell carcinoma is not a single and separate entity. Images PMID:4031101

  12. Small cell carcinoma of epididymis: multimodal therapy.

    PubMed

    Lima, Guilherme C; Varkarakis, Ioannis M; Allaf, Mohamad E; Fine, Samson W; Kavoussi, Louis R

    2005-08-01

    Extrapulmonary small cell carcinoma is an infrequent tumor that can occur in various organs. Although a few sporadic reports about extrapulmonary small cell carcinoma have been published, much remains to be uncovered about the clinical features, optimal treatment, and natural history. We present a case of small cell carcinoma of the epididymis with retroperitoneal recurrence, an exceedingly rare tumor with behavior and treatment not well characterized. Multimodal therapy with chemotherapy and retroperitoneal lymph node dissection was necessary to manage this aggressive disease.

  13. Nevoid basal cell carcinoma syndrome.

    PubMed

    Karthiga, Kannan S; Sivapatha Sundharam, B; Manikandan, R

    2006-01-01

    Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS). NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  14. Anaplastic giant cell thyroid carcinoma.

    PubMed

    Wallin, G; Lundell, G; Tennvall, J

    2004-01-01

    Anaplastic (giant cell) thyroid carcinoma (ATC), is one of the most aggressive malignancies in humans with a median survival time after diagnosis of 3-6 months. Death from ATC was earlier seen because of local growth and suffocation. ATC is uncommon, accounting for less than 5 % of all thyroid carcinomas. The diagnosis can be established by means of multiple fine needle aspiration biopsies, which are neither harmful nor troublesome for the patient. The cytological diagnosis of this high-grade malignant tumour is usually not difficult for a well trained cytologist. The intention to treat patients with ATC is cure, although only few of them survive. The majority of the patients are older than 60 years and treatment must be influenced by their high age. We have by using a combined modality regimen succeeded in achieving local control in most patients. Every effort should be made to control the primary tumour and thereby improve the quality of remaining life and it is important for patients, relatives and the personnel to know that cure is not impossible. Different treatment combinations have been used since 30 years including radiotherapy, cytostatic drugs and surgery, when feasible. In our latest combined regimen, 22 patients were treated with hyper fractionated radiotherapy 1.6Gy x 2 to a total target dose of 46 Gy given preoperatively, 20 mg doxorubicin was administered intravenously once weekly and surgery was carried out 2-3 weeks after the radiotherapy. 17 of these 22 patients were operated upon and none of these 17 patients got a local recurrence. In the future we are awaiting the development of new therapeutic approaches to this aggressive type of carcinoma. Inhibitors of angiogenesis might be useful. Combretastatin has displayed cytotoxicity against ATC cell lines and has had a positive effect on ATC in a patient. Sodium iodide symporter (NIS) genetherapy is also being currently considered for dedifferentiated thyroid carcinomas with the ultimate aim of

  15. Small cell carcinoma of the bladder

    PubMed Central

    Calado, Bruno Nagel; Maron, Paulo Eduardo Goulart; Vedovato, Bruno César; Barrese, Tomas Zecchini; Fernandes, Roni de Carvalho; Perez, Marjo Deninson Cardenuto

    2015-01-01

    Small cell carcinoma of the urinary bladder is an extremely aggressive and rare tumor. Even though small cell carcinoma most commonly arises from the lungs there are several reports of small cell carcinoma in extrapulmonary sites. Due to its low frequency there is no well-established management for this disease. We report the case of a 61 year-old man with small cell carcinoma of the bladder who underwent radical cystectomy following neoadjuvant chemotherapy. We also reviewed the literature for the optimal treatment strategy. PMID:25517085

  16. 15-Deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} enhanced the anti-tumor activity of camptothecin against renal cell carcinoma independently of topoisomerase-II and PPAR{gamma} pathways

    SciTech Connect

    Yamamoto, Yasuhiro; Fujita, Megumi; Koma, Hiromi; Yamamori, Motohiro; Nakamura, Tsutomu; Okamura, Noboru; Yagami, Tatsurou

    2011-07-08

    Highlights: {yields} A topoisomerase-I inhibitor, camptothecin, exhibited synergistically toxicity with 15d-PGJ{sub 2}. {yields} The combination of 15d-PGJ{sub 2} and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. {yields} A PPAR{gamma} antagonist did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. {yields} The treatment of camptothecin combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. -- Abstract: Renal cell carcinoma (RCC) is chemoresistant cancer. Although several clinical trials were conducted to explore effective medications, the chemoresistance of RCC has not yet been conquered. An endogenous ligand for peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}), 15-deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} (15d-PGJ{sub 2}), induces apoptosis in RCC. Here, we examined synergistic effects of several carcinostatics on the anti-tumor activity of 15d-PGJ{sub 2} in Caki-2 cell line by MTT assay. A topoisomerase-I inhibitor, camptothecin (CPT), exhibited synergistically toxicity with 15d-PGJ{sub 2}, but neither 5-fluorouracil nor cisplatin did. The combination of 15d-PGJ{sub 2} and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. The synergistic effect of topoisomerase-I and II inhibitors was not also detected. A PPAR{gamma} antagonist, GW9662, did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. The treatment of CPT combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. These results suggest that 15d-PGJ{sub 2} exhibited the anti-tumor activity synergistically with CPT independent of topoisomerase-II and PPAR{gamma}.

  17. Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

    PubMed

    Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary.

  18. Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

    PubMed

    Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. PMID:27461832

  19. Epidermal growth factor-induced cyclooxygenase-2 expression in oral squamous cell carcinoma cell lines is mediated through extracellular signal-regulated kinase 1/2 and p38 but is Src and nuclear factor-kappa B independent.

    PubMed

    Husvik, Camilla; Bryne, Magne; Halstensen, Trond S

    2009-10-01

    The intracellular signalling cascade(s) mediating epidermal growth factor (EGF)-induced cyclooxygenase-2 (COX-2) expression is poorly defined in oral carcinomas. Investigation of two different oral squamous cell carcinoma (OSCC) cell lines with high EGF-induced COX-2 expression revealed, however, that this expression was dependent on two mitogen-activated protein kinase (MAPK) pathways [extracellular signal-regulated kinase 1/2 (ERK1/2) and p38] because combined inhibition of these pathways was needed to abolish EGF-induced COX-2 expression. Surprisingly, inhibition of phosphoinositide-3 kinase (PI3K) increased EGF-induced COX-2 expression in the basaloid OSCC cell line (C12), suggesting a PI3K-controlled, inhibitory COX-2-regulating pathway. Neither the transcription factor nuclear factor-kappaB (NF-kappaB), nor Src, was involved in EGF-induced COX-2 expression. The results suggest that EGF-induced COX-2 expression is regulated by several pathways, and emphasizes that individual tumors use different strategies for intracellular signalling. PMID:19758248

  20. FAK inhibition disrupts a β5 integrin signaling axis controlling anchorage-independent ovarian carcinoma growth

    PubMed Central

    Tancioni, Isabelle; Uryu, Sean; Sulzmaier, Florian J.; Shah, Nina R.; Lawson, Christine; Miller, Nichol L.G.; Jean, Christine; Chen, Xiao Lei; Ward, Kristy K.; Schlaepfer, David D.

    2014-01-01

    Ovarian cancer ascites fluid contains matrix proteins that can impact tumor growth via integrin receptor binding. In human ovarian tumor tissue arrays, we find that activation of the cytoplasmic focal adhesion (FAK) tyrosine kinase parallels increased tumor stage, β5 integrin, and osteopontin (OPN) matrix staining. Elevated OPN, β5 integrin, and FAK mRNA levels are associated with decreased serous ovarian cancer patient survival. FAK remains active within ovarian cancer cells grown as spheroids, and anchorage-independent growth analyses of seven ovarian carcinoma cell lines identified sensitive (HEY, OVCAR8) and resistant (SKOV3-IP, OVCAR10) cells to 0.1 μM FAK inhibitor (VS-4718, formerly PND-1186) treatment. VS-4718 promoted HEY and OVCAR8 G0/G1 cell cycle arrest followed by cell death whereas growth of SKOV3-IP and OVCAR10 cells were resistant to 1.0 μM VS-4718. In HEY cells, genetic or pharmacological FAK inhibition prevented tumor growth in mice with corresponding reductions in β5 integrin and OPN expression. β5 knockdown reduced HEY cell growth in soft agar, tumor growth in mice, and both FAK Y397 phosphorylation and OPN expression in spheroids. FAK inhibitor resistant (SKOV3-IP, OVCAR10) cells exhibited anchorage-independent Akt S473 phosphorylation and expression of membrane-targeted and active Akt in sensitive cells (HEY, OVCAR8) increased growth but did not create a FAK inhibitor resistant phenotype. These results link OPN, β5 integrin, and FAK in promoting ovarian tumor progression.β5 integrin expression may serve as a biomarker for serous ovarian carcinoma cells that possess active FAK signaling. PMID:24899686

  1. Renal cell carcinoma: Evolving and emerging subtypes

    PubMed Central

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-01-01

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  2. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma*

    PubMed Central

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado Filho, Carlos D'Apparecida Santos

    2016-01-01

    Background Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Methods Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). Results The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. Conclusion The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

  3. Biological and clinical significance of NAC1 expression in cervical carcinomas: a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas.

    PubMed

    Yeasmin, Shamima; Nakayama, Kentaro; Rahman, Mohammed Tanjimur; Rahman, Munmun; Ishikawa, Masako; Katagiri, Atsuko; Iida, Kouji; Nakayama, Naomi; Otuski, Yoshiro; Kobayashi, Hiroshi; Nakayama, Satoru; Miyazaki, Kohji

    2012-04-01

    This study examined the biological and clinical significance of NAC1 (nucleus accumbens associated 1) expression in both cervical squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas. Using immunohistochemistry, the frequency of positive NAC1 expression in adenocarcinomas/adenosquamous carcinomas (31.0%; 18/58) was significantly higher than that in squamous cell carcinomas (16.2%; 12/74) (P = .043). NAC1 gene amplification was identified by fluorescence in situ hybridization in 5 (7.2%) of 69 squamous cell carcinomas. NAC1 amplification was not identified in the adenocarcinomas (0%; 0/58). Positive NAC1 expression was significantly correlated with shorter overall survival in squamous cell carcinomas (P < .0001). A multivariate analysis showed that positive NAC1 expression in squamous cell carcinomas was an independent prognostic factor for overall survival after standard radiotherapy (P = .0003). In contrast to squamous cell carcinomas, positive NAC1 expression did not correlate with shorter overall survival in adenocarcinomas/adenosquamous carcinomas (P = .317). Profound growth inhibition, increased apoptosis, decreased cell proliferation, and decreased cell migration and invasion were observed in silencing RNA-treated cancer cells with NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1 overexpression stimulated proliferation, migration, and invasion in the cervical cancer cell lines TCS and Hela P3, which normally lack NAC1 expression. These findings indicate that NAC1 overexpression is critical to the growth and survival of cervical carcinomas irrespective of histologic type. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, cervical carcinoma patients with NAC1 expression may benefit from a targeted therapy irrespective of histologic type.

  4. No evidence of oncogenic KRAS mutations in squamous cell carcinomas of the anogenital tract and head and neck region independent of human papillomavirus and p16(INK4a) status.

    PubMed

    Prigge, Elena-Sophie; Urban, Katharina; Stiegler, Sandrine; Müller, Meike; Kloor, Matthias; Mai, Sabine; Ottstadt, Martine; Lohr, Frank; Wenz, Frederik; Wagner, Steffen; Wittekindt, Claus; Klussmann, Jens Peter; Hampl, Monika; von Knebel Doeberitz, Magnus; Reuschenbach, Miriam

    2014-11-01

    Carcinogenesis of squamous cell carcinomas (SCCs) in the anogenital tract and head and neck region is heterogeneous. A substantial proportion of SCC in the vulva, anus, and head and neck follows a human papillomavirus (HPV)-induced carcinogenic pathway. However, the molecular pathways of carcinogenesis in the HPV-independent lesions are not completely understood. We hypothesized that oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations might represent a carcinogenic mechanism in a proportion of those HPV-negative cancers. Considering the repeated observation of KRAS-associated p16(INK4a) overexpression in human tumors, it was assumed that KRAS mutations might be particularly present in the group of HPV-negative, p16(INK4a)-positive cancers. To test this hypothesis, we analyzed 66 anal, vulvar, and head and neck SCC with known immunohistochemical p16(INK4a) and HPV DNA status for KRAS mutations in exon 2 (codons 12, 13, and 15). We enriched the tumor collection with HPV DNA-negative, p16(INK4a)-positive cancers. A subset of 37 cancers was also analyzed for mutations in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene. None of the 66 tumors harbored mutations in KRAS exon 2, thus excluding KRAS mutations as a common event in SCC of the anogenital and head and neck region and as a cause of p16(INK4a) expression in these tumors. In addition, no BRAF mutations were detected in the 37 analyzed tumors. Further studies are required to determine the molecular events underlying HPV-negative anal, vulvar, and head and neck carcinogenesis. Considering HPV-independent p16(INK4a) overexpression in some of these tumors, particular focus should be placed on alternative upstream activators and potential downstream disruption of the p16(INK4a) pathway.

  5. Transitional cell bladder carcinoma with presentation mimicking ovarian carcinoma.

    PubMed

    Erickson, D R; Dabbs, D J; Olt, G J

    1996-05-01

    In the case described here, the patient's initial presentation suggested ovarian carcinoma. She had recurrent ascites, a pelvic mass, elevated CA-125, and extensive peritoneal carcinomatosis with transitional cell histology. The presence of hematuria prompted a cystoscopy, which revealed the true site of origin to be the urinary bladder rather than ovaries. This presentation is extremely rare for bladder cancer. Since transitional cell tumors from the bladder have a much worse prognosis than those of ovarian origin, it is important to identify the primary site correctly. Therefore, cystoscopy is essential for patients with hematuria, and should be considered in cases of apparent primary peritoneal carcinoma with transitional cell histology.

  6. Current Aspects on Oral Squamous Cell Carcinoma

    PubMed Central

    Markopoulos, Anastasios K

    2012-01-01

    Oral squamous cell carcinoma is the most common malignant epithelial neoplasm affecting the oral cavity. This article overviews the essential points of oral squamous cell carcinoma, highlighting its risk and genomic factors, the potential malignant disorders and the therapeutic approaches. It also emphasizes the importance of the early diagnosis. PMID:22930665

  7. Human papillomavirus in oesophageal squamous cell carcinoma.

    PubMed Central

    Loke, S L; Ma, L; Wong, M; Srivastava, G; Lo, I; Bird, C C

    1990-01-01

    Thirty seven cases of oesophageal squamous cell carcinoma were studied by applying DNA slot blot analysis and in situ hybridisation using type specific probes for HPV 6, 11, 16 and 18. Cases of condyloma accuminata, cervical carcinoma, and laryngeal papilloma were used as controls. Blocks including areas of invasive carcinoma, intraepithelial neoplasia, and normal epithelium were studied in each case. No HPV genome was detectable in any of the oesophageal cases. It is concluded that these types of HPV do not have an association with oesophageal squamous cell carcinoma. Images PMID:2175754

  8. Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma.

    PubMed

    Deshmukh, Mahesh; Shet, Tanuja; Bakshi, Ganesh; Desai, Sangeeta

    2011-01-01

    Tubulocystic renal cell carcinoma (TCRCC) is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC) and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.

  9. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    PubMed

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy. PMID:26971503

  10. Cisplatin, Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-11-02

    Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  11. [Acinar cell carcinoma of submaxillary gland].

    PubMed

    Comeche, C; Calabuig, C; Barona, R

    1997-01-01

    Although acine cell neoplasms have for a long time been regarded as benign tumors, they are presently considered to represent the carcinomas. These rare tumors mainly affect the parotid glands, and only exceptionally involve other salivary glands. Clinically, acic cell carcinoma present as isolated tumors simulating a pleomorphic adenoma. The diagnosis is histopathological, and complete surgical removal of the tumor is the treatment of choice, with cervical lymphatic voiding and/or postoperative radiotherapy in selected cases. A prolonged patient follow-up is required, for the tumor may recur many years after surgery. We report a case of acinic cell carcinoma in submaxillary gland.

  12. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

    PubMed

    Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

    2016-01-01

    Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events. PMID:26850723

  13. Quinacrine sensitizes hepatocellular carcinoma cells to TRAIL and chemotherapeutic agents.

    PubMed

    Wang, Wenge; Gallant, Jean-Nicolas; Katz, Sharyn I; Dolloff, Nathan G; Smith, Charles D; Abdulghani, Junaid; Allen, Joshua E; Dicker, David T; Hong, Bo; Navaraj, Arunasalam; El-Deiry, Wafik S

    2011-08-01

    Quinacrine has been widely explored in treatment of malaria, giardiasis, and rheumatic diseases. We find that quinacrine stabilizes p53 and induces p53-dependent and independent cell death. Treatment by quinacrine alone at concentrations of 10-20 mM for 1-2 d cannot kill hepatocellular carcinoma cells, such as HepG2, Hep3B, Huh7, which are also resistant to TRAIL. However, quinacrine renders these cells sensitive to treatment by TRAIL. Co-treatment of these cells with quinacrine and TRAIL induces overwhelming cell death within 3-4 h. Levels of DR5, a pro-apoptotic death receptor of TRAIL, are increased upon treatment with quinacrine, while levels of Mcl-1, an anti-apoptotic member of the Bcl-2 family, are decreased. While the synergistic effect of quinacrine with TRAIL appears to be in part independent of p53, knockdown of p53 in HepG2 cells by siRNA results in more cell death after treatment by quinacrine and TRAIL. The mechanism by which quinacrine sensitizes hepatocellular carcinoma cells to TRAIL and chemotherapies, and the potential for clinical application currently are being further explored. Lastly, quinacrine synergizes with chemotherapeutics, such as adriamycin, 5-FU, etoposide, CPT11, sorafenib, and gemcitabine, in killing hepatocellular carcinoma cells in vitro and the drug enhances the activity of sorafenib to delay tumor growth in vivo. PMID:21725212

  14. Basal Cell Carcinoma Developing from Trichoepithelioma: Review of Three Cases

    PubMed Central

    Satyanarayana, M. Ananta; Aryasomayajula, Sirish; Krishna, B.A. Rama

    2016-01-01

    Trichoepitheliomas (TE) are benign tumours but occasionally can undergo transformation to malignant neoplasms more commonly as Basal Cell Carcinoma (BCC). The correct diagnosis between these tumours is very important because basal cell carcinoma is locally aggressive neoplasm and requires total surgical excision with wide healthy margins while trichoepithelioma needs simple excision. We describe three patients who developed basal cell carcinoma with facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size, in all three patients, one patient with recurrent, hyper pigmented swelling with surface ulceration and in another patient there are multiple trichoepitheliomas, and other family members are also affected. The history, clinical features and histopathological findings were suggestive of the evolution of basal cell carcinoma directly from trichoepithelioma in our first two cases, but in the third case TE and BCC were separate lesions on face and we are uncertain about whether the BCC developed independently or by transformation from a trichoepithelioma. Based on our clinicopathological observations in the three patients and reports in the recent literature, BCC with follicular differentiation and trichoepithelioma are considered to be highly related. PMID:27134936

  15. Paraneoplastic Cough and Renal Cell Carcinoma

    PubMed Central

    Sullivan, Stephen

    2016-01-01

    A case of patient with intractable cough due to renal cell carcinoma is reported. The discussion reviews the literature regarding this unusual paraneoplastic manifestation of renal malignancy. PMID:27445553

  16. Treatment Options by Stage (Merkel Cell Carcinoma)

    MedlinePlus

    ... other organs . Sun exposure and having a weak immune system can affect the risk of Merkel cell carcinoma. ... ultraviolet A (PUVA) therapy for psoriasis . Having an immune system weakened by disease, such as chronic lymphocytic leukemia ...

  17. Treatment Option Overview (Merkel Cell Carcinoma)

    MedlinePlus

    ... other organs . Sun exposure and having a weak immune system can affect the risk of Merkel cell carcinoma. ... ultraviolet A (PUVA) therapy for psoriasis . Having an immune system weakened by disease, such as chronic lymphocytic leukemia ...

  18. Paraneoplastic Cough and Renal Cell Carcinoma.

    PubMed

    Sullivan, Stephen

    2016-01-01

    A case of patient with intractable cough due to renal cell carcinoma is reported. The discussion reviews the literature regarding this unusual paraneoplastic manifestation of renal malignancy. PMID:27445553

  19. Sunitinib benefits patients with renal cell carcinoma

    Cancer.gov

    Findings from clinical trial patients with metastatic renal cell carcinoma, a common kidney cancer, show they did not have accelerated tumor growth after treatment with sunitinib, in contrast to some study results in animals.

  20. Renal Cell Carcinoma Metastasized to Pagetic Bone

    PubMed Central

    Ramirez, Ashley; Liu, Bo; Rop, Baiywo; Edison, Michelle; Valente, Michael

    2016-01-01

    Paget’s disease of the bone, historically known as osteitis deformans, is an uncommon disease typically affecting individuals of European descent. Patients with Paget’s disease of the bone are at increased risk for primary bone neoplasms, particularly osteosarcoma. Many cases of metastatic disease to pagetic bone have been reported. However, renal cell carcinoma metastasized to pagetic bone is extremely rare. A 94-year-old male presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen demonstrated a large mass in the right kidney compatible with renal cell carcinoma. The patient was also noted to have Paget’s disease of the pelvic bones and sacrum. Within the pagetic bone of the sacrum, there was an enhancing mass compatible with renal cell carcinoma. A subsequent biopsy of the renal lesion confirmed renal cell carcinoma. Paget’s disease of the bone places the patient at an increased risk for bone neoplasms. The most commonly reported sites for malignant transformation are the femur, pelvis, and humerus. In cases of malignant transformation, osteosarcoma is the most common diagnosis. Breast, lung, and prostate carcinomas are the most common to metastasize to pagetic bone. Renal cell carcinoma associated with Paget’s disease of the bone is very rare, with only one prior reported case. Malignancy in Paget's disease of the bone is uncommon with metastatic disease to pagetic bone being extremely rare. We report a patient diagnosed with concomitant renal cell carcinoma and metastatic disease within Paget’s disease of the sacrum. Further research is needed to assess the true incidence of renal cell carcinoma associated with pagetic bone.

  1. Renal Cell Carcinoma Metastasized to Pagetic Bone.

    PubMed

    Ramirez, Ashley; Liu, Bo; Rop, Baiywo; Edison, Michelle; Valente, Michael; Burt, Jeremy

    2016-01-01

    Paget's disease of the bone, historically known as osteitis deformans, is an uncommon disease typically affecting individuals of European descent. Patients with Paget's disease of the bone are at increased risk for primary bone neoplasms, particularly osteosarcoma. Many cases of metastatic disease to pagetic bone have been reported. However, renal cell carcinoma metastasized to pagetic bone is extremely rare. A 94-year-old male presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen demonstrated a large mass in the right kidney compatible with renal cell carcinoma. The patient was also noted to have Paget's disease of the pelvic bones and sacrum. Within the pagetic bone of the sacrum, there was an enhancing mass compatible with renal cell carcinoma. A subsequent biopsy of the renal lesion confirmed renal cell carcinoma. Paget's disease of the bone places the patient at an increased risk for bone neoplasms. The most commonly reported sites for malignant transformation are the femur, pelvis, and humerus. In cases of malignant transformation, osteosarcoma is the most common diagnosis. Breast, lung, and prostate carcinomas are the most common to metastasize to pagetic bone. Renal cell carcinoma associated with Paget's disease of the bone is very rare, with only one prior reported case. Malignancy in Paget's disease of the bone is uncommon with metastatic disease to pagetic bone being extremely rare. We report a patient diagnosed with concomitant renal cell carcinoma and metastatic disease within Paget's disease of the sacrum. Further research is needed to assess the true incidence of renal cell carcinoma associated with pagetic bone.

  2. Renal Cell Carcinoma Metastasized to Pagetic Bone.

    PubMed

    Ramirez, Ashley; Liu, Bo; Rop, Baiywo; Edison, Michelle; Valente, Michael; Burt, Jeremy

    2016-01-01

    Paget's disease of the bone, historically known as osteitis deformans, is an uncommon disease typically affecting individuals of European descent. Patients with Paget's disease of the bone are at increased risk for primary bone neoplasms, particularly osteosarcoma. Many cases of metastatic disease to pagetic bone have been reported. However, renal cell carcinoma metastasized to pagetic bone is extremely rare. A 94-year-old male presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen demonstrated a large mass in the right kidney compatible with renal cell carcinoma. The patient was also noted to have Paget's disease of the pelvic bones and sacrum. Within the pagetic bone of the sacrum, there was an enhancing mass compatible with renal cell carcinoma. A subsequent biopsy of the renal lesion confirmed renal cell carcinoma. Paget's disease of the bone places the patient at an increased risk for bone neoplasms. The most commonly reported sites for malignant transformation are the femur, pelvis, and humerus. In cases of malignant transformation, osteosarcoma is the most common diagnosis. Breast, lung, and prostate carcinomas are the most common to metastasize to pagetic bone. Renal cell carcinoma associated with Paget's disease of the bone is very rare, with only one prior reported case. Malignancy in Paget's disease of the bone is uncommon with metastatic disease to pagetic bone being extremely rare. We report a patient diagnosed with concomitant renal cell carcinoma and metastatic disease within Paget's disease of the sacrum. Further research is needed to assess the true incidence of renal cell carcinoma associated with pagetic bone. PMID:27660736

  3. Renal Cell Carcinoma Metastasized to Pagetic Bone

    PubMed Central

    Ramirez, Ashley; Liu, Bo; Rop, Baiywo; Edison, Michelle; Valente, Michael

    2016-01-01

    Paget’s disease of the bone, historically known as osteitis deformans, is an uncommon disease typically affecting individuals of European descent. Patients with Paget’s disease of the bone are at increased risk for primary bone neoplasms, particularly osteosarcoma. Many cases of metastatic disease to pagetic bone have been reported. However, renal cell carcinoma metastasized to pagetic bone is extremely rare. A 94-year-old male presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen demonstrated a large mass in the right kidney compatible with renal cell carcinoma. The patient was also noted to have Paget’s disease of the pelvic bones and sacrum. Within the pagetic bone of the sacrum, there was an enhancing mass compatible with renal cell carcinoma. A subsequent biopsy of the renal lesion confirmed renal cell carcinoma. Paget’s disease of the bone places the patient at an increased risk for bone neoplasms. The most commonly reported sites for malignant transformation are the femur, pelvis, and humerus. In cases of malignant transformation, osteosarcoma is the most common diagnosis. Breast, lung, and prostate carcinomas are the most common to metastasize to pagetic bone. Renal cell carcinoma associated with Paget’s disease of the bone is very rare, with only one prior reported case. Malignancy in Paget's disease of the bone is uncommon with metastatic disease to pagetic bone being extremely rare. We report a patient diagnosed with concomitant renal cell carcinoma and metastatic disease within Paget’s disease of the sacrum. Further research is needed to assess the true incidence of renal cell carcinoma associated with pagetic bone. PMID:27660736

  4. Everolimus in renal cell carcinoma.

    PubMed

    Wang, Y

    2010-08-01

    Everolimus (also known as RAD-001; Afinitor®) is an orally active inhibitor of the intracellular protein kinase mammalian target of rapamycin. The U.S. Food and Drug Administration and the European Medicines Agency recently approved everolimus for the treatment of advanced renal cell carcinoma (RCC) on the basis of the results of a randomized phase III clinical trial. In the trial, 10 mg daily everolimus was effective and well tolerated by patients with advanced RCC, whose disease had progressed while under the treatment with sunitinib and/or sorafenib. Everolimus treatment led to 36% of 6-month progression-free survival (PFS) rate and 31% of 3-month PFS rate. Most of the adverse events were mild to moderate (grade 1-2) in severity. The most frequent grade 3-4 adverse events were stomatitis, fatigue, pneumonitis and infections. Clinical trials on everolimus in combination with sunitinib, sorafenib, imatinib and vatalanib for the treatment of RCC are ongoing. PMID:20830316

  5. Metastatic renal cell carcinoma in the nasopharynx.

    PubMed

    Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

    2013-01-01

    Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment. PMID:23924557

  6. Primary esophageal small cell carcinoma with concomitant invasive squamous cell carcinoma or carcinoma in situ.

    PubMed

    Yamamoto, Junya; Ohshima, Koichi; Ikeda, Seiyou; Iwashita, Akinori; Kikuchi, Masahiro

    2003-11-01

    Esophageal small cell carcinoma (SmCC) is a rarer, more highly aggressive, and more rapidly growing neoplasm than esophageal squamous cell carcinoma (SqCC). SmCC and SqCC also differ in terms of chemotherapy of choice, response to therapy, and prognosis. Accordingly, it is important to differentiate the 2 carcinomas. We studied the histology and immunohistochemical profiles of 6 cases of esophageal SmCC to elucidate the correct diagnosis of this tumor. We performed immunohistochemical analysis antibodies against cytokeratins (CKAE1/AE3, CKCAM5.2, CK34betaE12, CK7, CK8, CK10/13, and CK19), epithelial membrane antigen (EMA), neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin-A, S-100 protein, carcinoembryonic antigen (CEA), E-cadherin, thyroid transcription factor-1 (TTF-1), and p53. In 3 of the 6 SmCCs, heterogeneous components of in situ or invasive SqCC were observed. SqCC was found in the mucosa adjacent to the main SmCC, and the boundary between SmCC and SqCC was distinct, with no transitional features. Staining for NCAM, NSE, and chromogranin-A was positive in SmCCs, but negative in SqCCs. Both SmCCs and SqCCs were positive for CKAE1/AE3, CKCAM5.2, CK8, and EMA, but only SqCCs were positive for CK34betaE12 and CK19. Moreover, SmCCs containing SqCC components were positive for CEA and E-cadherin, whereas SmCCs without SqCC were negative. Our study suggests that NCAM and NSE are useful markers in diagnosing esophageal SmCC, and CK34betaE12 and CK19 are useful for differentiating SqCC components from SmCC.

  7. Surgical management of Merkel cell carcinoma.

    PubMed Central

    Allen, P J; Zhang, Z F; Coit, D G

    1999-01-01

    OBJECTIVES: To characterize the natural history of Merkel cell carcinoma (MCC) and to analyze the influence of patient, tumor, and treatment-related variables on survival and recurrence. SUMMARY BACKGROUND DATA: Approximately 425 cases of MCC have been described in the literature. This study represents the largest experience reported. METHODS: A review was performed of patients who had been treated at Memorial Sloan-Kettering Cancer Center for MCC between 1969 and 1996. Follow-up data were available for 102 of the 109 (94%) patients identified. RESULTS: The overall 5-year disease-specific survival rate was 74%. The median follow-up was 35 months. For all patients, the only independent predictor of survival was the tumor stage at presentation. For patients with stage I disease, the tumor size at presentation was also an independent predictor of survival. Recurrence of disease occurred in 55 patients (55%), and the most common site of first recurrence was within the draining lymph nodes (n = 35). Elective lymph node dissection was the only parameter independently predictive of improved relapse-free survival. The overall disease-specific survival rate after recurrence was 62%. Predictors of improved disease-specific survival after recurrence included nodal as compared to local or distant recurrence, the ability to render the patient free of disease after recurrence, and a disease-free interval of >8 months. CONCLUSION: The prognosis for patients with MCC is favorable, and even after recurrence the majority of patients experience long-term survival. Incorporation of size into the staging system more accurately predicts survival in patients with stage I disease. Although elective lymph node dissection decreased the rate of recurrence, it was not associated with improved overall survival. PMID:9923806

  8. Merkel cell carcinoma with glandular differentiation admixed with sweat gland carcinoma and spindle cell carcinoma: histogenesis of merkel cell carcinoma from hair follicle stem cells.

    PubMed

    Koba, Shinichi; Nagase, Kotaro; Ikeda, Satoshi; Aoki, Shigehisa; Misago, Noriyuki; Narisawa, Yutaka

    2015-03-01

    We describe a unique case of Merkel cell carcinoma (MCC) with a heterogeneous differentiation exhibiting distinct triphasic phenotypic differentiation features: small cells typical of MCC, sweat gland carcinoma (sweat gland Ca.) with possible decapitation secretion, and spindle cell carcinoma (spindle cell Ca.). The patient was an 84-year-old Japanese woman. We evaluated the present case immunohistochemically with various antibodies. The histological features showed a gradual transition from MCC to sweat gland Ca. and spindle cell Ca. For clarifying the histogenesis, immunophenotypic analysis of the 3 different components of the carcinoma was performed using hair follicle stem cell markers (eg, CK15, CK19, and CD200) that have been identified as biomarkers of human bulge cells. The triphasic components immunohistochemically shared the characteristic feature of CK19 and CD200 expression. We posit that the MCC arose from hair follicle stem cells residing within the bulge area where Merkel cells are preferentially situated. Based on our findings, we recommend adding this rare neoplasm to the expanding morphological spectrum of MCC.

  9. Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2015-04-29

    Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx

  10. Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-11-04

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Major Salivary Gland Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  11. Identification of Prognostic Biomarkers for Progression of Invasive Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-06-30

    Carcinoma, Squamous Cell; Carcinoma, Squamous; Squamous Cell Carcinoma; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms

  12. [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how to treat?].

    PubMed

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

    Increasing exposure to UV radiation is considered the most important etiologic factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp and face, are the primary areas for developing non-melanoma skin cancers. Once a patient has presented with one tumor, additional lesions are common. The diagnosis is based on typical clinical picture and biopsy or excision for histopathological analysis. Various non-surgical treatment options have been established. Superficial basal cell carcinoma, superficial carcinoma in situ and all actinic keratoses are preferentially treated non-surgically. Most other basal cell and squamous cell carcinomas should be surgically removed. PMID:24724463

  13. Therapeutic challenges in renal cell carcinoma

    PubMed Central

    Penticuff, Justin C; Kyprianou, Natasha

    2015-01-01

    Renal cell carcinoma (RCC) is a malignancy that in advanced disease, is highly resistant to systemic therapies. Elucidation of the angiogenesis pathways and their intrinsic signaling interactions with the genetic and metabolic disturbances within renal cell carcinoma variants has ushered in the era of “targeted therapies”. Advanced surgical interventions and novel drugs targeting VEGF and mTOR, have improved patient survival and prolonged clinically stable-disease states. This review discusses the current understanding of diagnostic challenges and the mechanism-based clinical evidence on therapeutic management of advanced RCC. PMID:26309897

  14. Cytoreductive nephrectomy for metastatic renal cell carcinoma.

    PubMed

    Chery, Lisly J; Karam, Jose A; Wood, Christopher G

    2016-09-01

    The incidence of renal cell carcinoma is increasing, with up to one-third of patients presenting with metastatic disease. Combination therapy is used to prolong survival in patients with metastatic renal cell carcinoma, which carries a poor prognosis. Although two pivotal phase 3 trials have demonstrated the efficacy of immunotherapy after cytoreductive nephrectomy for metastatic disease, for now, targeted therapy has replaced immunotherapy as the preferred systemic treatment in these patients. Two ongoing phase 3 trials are evaluating the role of cytoreductive nephrectomy prior to targeted therapy. Proper patient selection is paramount in achieving successful outcomes. PMID:27673288

  15. Renal cell carcinoma with areas mimicking renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma.

    PubMed

    Petersson, Fredrik; Grossmann, Petr; Hora, Milan; Sperga, Maris; Montiel, Delia Perez; Martinek, Petr; Gutierrez, Maria Evelyn Cortes; Bulimbasic, Stela; Michal, Michal; Branzovsky, Jindrich; Hes, Ondrej

    2013-07-01

    We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for α-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for α-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.

  16. Altered gene expression in conjunctival squamous cell carcinoma.

    PubMed

    Mahale, Alka; Alkatan, Hind; Alwadani, Saeed; Othman, Maha; Suarez, Maria J; Price, Antoinette; Al-Hussain, Hailah; Jastaneiah, Sabah; Yu, Wayne; Maktabi, Azza; Deepak, Edward P; Eberhart, Charles G; Asnaghi, Laura

    2016-05-01

    Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progression of this disease are not well understood. We therefore compared the transcriptional profiles of eight snap-frozen conjunctival squamous cell carcinomas and one in situ lesion with normal conjunctival specimens in order to identify diagnostic markers or therapeutic targets. RNA was analyzed using oligonucleotide microarrays, and a wide range of transcripts with altered expression identified, including many dysregulated in carcinomas arising at other sites. Among the upregulated genes, we observed more than 30-fold induction of the matrix metalloproteinases, MMP-9 and MMP-11, as well as a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial microarray analysis. In addition, immunohistochemical analysis confirmed the overexpression of MMP-11 and S100A2, as well as reductions in clusterin, in several independent in situ carcinomas of conjunctiva. These data identify a number of alterations, including upregulation of MMP-9, MMP-11, and S100A2, as well as downregulation of clusterin, associated with epithelial tumorigenesis in the ocular surface. PMID:26916071

  17. Clear cell papillary renal cell carcinoma: a potential mimic of conventional clear cell renal carcinoma on core biopsy.

    PubMed

    Liddell, Heath; Mare, Anton; Heywood, Sean; Bennett, Genevieve; Chan, Hin Fan

    2015-01-01

    Clear cell papillary renal cell carcinoma (CCP-RCC) is a recently described, relatively uncommon variant of renal cell carcinoma (RCC) with a reported incidence of 4.1%. Thought to only arise in those with end stage renal disease, CCP-RCC is increasingly identified in those without renal impairment. CCP-RCCs have unique morphologic, genetic, and immunohistochemical features distinguishing them from both conventional clear cell renal cell carcinomas and papillary renal cell carcinomas. Immunohistochemically, these tumors are positive for CK7 and negative for CD10 and racemase. This is in contrast to conventional cell renal cell carcinomas (CK7 negative, CD10 positive) and papillary cell carcinomas (CK7, CD10, and racemase positive). These tumours appear to be indolent in nature, with no current documented cases of metastatic spread. We present the case of a 42-year-old female who presented with an incidental finding of a renal mass that on a core biopsy was reported as clear cell carcinoma, Fuhrman grade 1. She subsequently underwent a radical nephrectomy and further histological examination revealed the tumor to be a clear cell papillary renal cell carcinoma, Fuhrman grade 1. PMID:25709850

  18. Odontogenic squamous cell carcinoma with osseous metaplasia.

    PubMed

    Bennett, J H; Jones, J; Speight, P M

    1993-07-01

    Intra-osseous carcinomas of the jaw are rare tumours, thought to arise from residual elements of the odontogenic epithelium. We report an additional case which, unusually, was characterised by marked osseous metaplasia. We propose that the new bone formed around the tumour is the result of an epithelial-mesenchymal interaction between malignant odontogenic epithelium and osteogenic precursor cells in the surrounding stroma.

  19. Gingival Squamous Cell Carcinoma: a Case Report

    PubMed Central

    Cabral, Luiz Antonio Guimarães; de Carvalho, Luis Felipe das Chagas e Silva; Salgado, José Antônio Pereira; Brandão, Adriana Aigotti Haberbeck

    2010-01-01

    ABSTRACT Background Squamous cell carcinoma is a malignant epithelial neoplasm characterized by variable clinical manifestations. When located in the gingiva, this neoplasm may mimic common inflammatory lesions. The aim of this study was to report a case of atypical squamous cell carcinoma, in which the patient had no risk factors for the development of this neoplasm. Methods A 61 year old Caucasian female was seen with a 3 month history of a rapidly growing, painful nodule in the gingiva adjacent to tooth #11. Clinical examination revealed a proliferative lesion in the vestibular marginal gingiva of teeth #11 and #12, presenting with purulent exudation. Thus, in view of the clinical symptoms and differential diagnosis of an infectious granulomatous process and malignant neoplasm, an incisional biopsy was obtained from the lesion. Results The diagnosis of squamous cell carcinoma was made and fourteen days after incisional biopsy, healing was found to be unsatisfactory. The patient was referred for treatment consisting of surgical excision of the tumour. A removable partial denture was fabricated for rehabilitation, one month after surgery of the maxilla; the patient was submitted to dissection of the regional lymph nodes and radiotherapy for an additional 3 months. Three years after the end of treatment, the patient continues to be followed-up and does not show any sign of recurrence. Conclusions Gingival squamous cell carcinoma is a condition which chance of cure is higher when carcinomatous lesions are diagnosed and treated early. In this instance dentists play an important role in early detection of gingival squamous cell carcinoma. PMID:24421976

  20. A Case of Acantholytic Squamous Cell Carcinoma

    PubMed Central

    Lim, Ji Yeon; Do, Mi Ok; Kim, Seong Hyun; Hahm, Jeong Hee

    2008-01-01

    Acantholytic squamous cell carcinoma is a well-defined variant of squamous cell cancer in which significant portions of the neoplastic proliferation show a pseudoglandular or tubular microscopic pattern. It usually presents as a nodule with various colors, and it is accompanied by scaling, crusting, and ulceration on the sun-exposed areas of older aged individuals. Histologically, the tumor consists of a nodular, epidermal-derived proliferation that forms island-like structures. At least focally or sometimes extensively, the tumor cells shows a loss of cohesion within the central gland-like or tubular spaces. This tumor resembles the structure of eccrine neoplasms, but it is negative for dPAS, CEA and mucicarmine and it is only positive for EMA and cytokeratins. Herein we report a case of acantholytic squamous cell carcinoma that occurred on the face of an 82-year-old woman. PMID:27303210

  1. "Basal Cell Blanche": A Diagnostic Maneuver to Increase Early Detection of Basal Cell Carcinomas.

    PubMed

    Quach, Olivia Leigh; Barry, Megan; Roberts Cruse, Allison; Wilson, Barbara B

    2016-01-01

    Basal cell carcinomas represent one of the most common skin cancers and often present initially in the primary care setting. Subtle basal cell carcinomas may be difficult to detect, and early detection of these carcinomas remains important in limiting patient morbidity. In this article, we present a simple diagnostic maneuver, "basal cell blanche," to increase early detection of basal cell carcinomas. PMID:27170799

  2. Bilateral acrometastasis in a case renal cell carcinoma

    PubMed Central

    Vaishya, Raju; Vijay, Vipul; Vaish, Abhishek

    2014-01-01

    We present a unique case of bilateral skeletal metastasis below the knee in a patient with renal cell carcinoma. In this rarest of rare cases, bony metastases were the first presentation of a primary tumour. Incidentally, the primary tumour (renal cell carcinoma) involved the solitary kidney of the patient and the same patient also had coexisting carcinoma of the prostate. PMID:25368128

  3. MET Inhibition in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Xie, Zuoquan; Lee, Young H.; Boeke, Marta; Jilaveanu, Lucia B.; Liu, Zongzhi; Bottaro, Donald P.; Kluger, Harriet M.; Shuch, Brian

    2016-01-01

    Background: Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer. Small molecule VEGFR inhibitors are widely used but are not curative and various resistance mechanisms such as activation of the MET pathway have been described. Dual MET/VEGFR2 inhibitors have recently shown clinical benefit but limited preclinical data evaluates their effects in ccRCC. Methods: An interrogation of the Cancer Genome Atlas (TCGA) dataset was performed to evaluate oncogenic alterations in the MET/VEGFR2 pathway. We evaluated the in vitro effects of Cabozantinib, a dual MET/VEGFR2 inhibitor, using a panel of ccRCC cell lines. Drug effects of cell viability and proliferation, migration, cell scatter, anchorage independent growth, and downstream MET/VEGFR2 signaling pathways were assessed. Results: Twelve percent of TCGA cases had possible MET/HGF oncogenic alterations with co-occurrence noted (p<0.001). MET/HGF altered cases had worse overall survival (p=0.044). Cabozantinib was a potent inhibitor of MET and VEGFR2 in vitro in our cell line panel. PI3K, MAPK and mTOR pathways were also suppressed by cabozantinib, however the effects on cell viability in vitro were modest. At nanomolar concentrations of cabozantinib, HGF-stimulated migration, invasion, cellular scattering and soft agar colony formation were inhibited. Conclusions: We provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. While the MET pathway is implicated in VEGFR resistance, dual inhibitors may have direct anti-tumor effects in a patient subset with evidence of MET pathway involvement. Cabozantinib is a potent dual MET/VEGFR2 inhibitor, significantly inhibits cell migration and invasion in vitro and likely has anti-angiogenic effects similar to other VEGFR tyrosine kinase inhibitors. Future work involving in vivo models will be useful to better define mechanisms of potential anti-tumor activity. PMID:27390595

  4. Hsp90 Inhibitor AT13387 in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

    ClinicalTrials.gov

    2016-10-05

    Human Papillomavirus Infection; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  5. Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis.

    PubMed

    Kadota, Kyuichi; Nitadori, Jun-ichi; Rekhtman, Natasha; Jones, David R; Adusumilli, Prasad S; Travis, William D

    2015-09-01

    Currently, non-small cell lung carcinomas are primarily classified by light microscopy. However, recent studies have shown that poorly differentiated tumors are more accurately classified by immunohistochemistry. In this study, we investigated the use of immunohistochemical analysis in reclassifying lung carcinomas that were originally diagnosed as squamous cell carcinoma. Tumor slides and blocks were available for histologic evaluation, and tissue microarrays were constructed from 480 patients with resected lung carcinomas originally diagnosed as squamous cell carcinoma between 1999 and 2009. Immunohistochemical analyses for p40, p63, thyroid transcription factor-1 (TTF-1; clones SPT24 and 8G7G3/1), napsin A, chromogranin A, synaptophysin, and CD56 were performed. Staining intensity (weak, moderate, or strong) and distribution (focal or diffuse) were also recorded. Of all, 449 (93.5%) patients were confirmed as having squamous cell carcinomas; the cases were mostly diffusely positive for p40 and negative for TTF-1 (8G7G3/1). Twenty cases (4.2%) were reclassified as adenocarcinoma, as they were positive for TTF-1 (8G7G3/1 or SPT24) with either no or focal p40 expression, and all of them were poorly differentiated with squamoid morphology. In addition, 1 case was reclassified as adenosquamous carcinoma, 4 cases as large cell carcinoma, 4 cases as large cell neuroendocrine carcinoma, and 2 cases as small cell carcinoma. In poorly differentiated non-small cell lung carcinomas, an accurate distinction between squamous cell carcinoma and adenocarcinoma cannot be reliably determined by morphology alone and requires immunohistochemical analysis, even in resected specimens. Our findings suggest that TTF-1 8G7G3/1 may be better suited as the primary antibody in differentiating adenocarcinoma from squamous cell carcinoma.

  6. Genetic profile of clear cell odontogenic carcinoma.

    PubMed

    Carinci, Francesco; Volinia, Stefano; Rubini, Corrado; Fioroni, Massimiliano; Francioso, Francesca; Arcelli, Diego; Pezzetti, Furio; Piattelli, Adriano

    2003-05-01

    In the head and neck region, clear cell tumors are usually derived from salivary glands, odontogenic tissues, and metastasis. The World Health Organization has classified clear cell odontogenic tumor among benign tumors, but it is now recognized as a more sinister lesion, and current opinion is that it should be designated as a carcinoma. It is characterized by aggressive growth, recurrences, and metastasis. By using complementary DNA microarrays, several genes in clear cell odontogenic tumor were identified that are differentially regulated when compared with non-tumor tissue. In conclusion, the first genetic profiling of clear odontogenic carcinoma is reported. DNA microarrays can potentially help in identifying some genes whose products could be disease-specific targets for cancer therapy as well as a tool for better classifying odontogenic tumor.

  7. Renal cell carcinoma with intramyocardial metastases

    PubMed Central

    2014-01-01

    Background Cardiac metastases from renal cell carcinoma without vena caval involvement are extremely rare with a limited number of cases reported in the worldwide literature until now. Nevertheless, this rare location of metastasis may significantly influence patient treatment and prognosis. Cooperation between oncology, cardiology, and urology teams are indispensable in cases of patients suffering from intramyocardial tumors. For these individuals, treatment guidelines based on large-scale studies are unavailable and only case/case series analysis may provide clinicians with decision assistance. Case presentation In this paper, we report a case of a 50-year-old Caucasian male diagnosed with a 10.2 × 10.3 × 10.0 cm lower pole left renal mass in January 2002. He was subsequently treated with immunochemotherapy, tyrosine kinase inhibitors (TKIs), and mTOR inhibitors (mTORIs) - that is sunitinib, everolimus, and sorafenib. In March 2012, contrast-enhancing tumors in the left myocardium (∅22 mm) and in the interventricular septum (∅26 mm) were seen on CT. Cardiology testing was conducted and the patient was treated with pazopanib with a profound response. Overall survival since the clear cell renal cell carcinoma (ccRCC) diagnosis was 11 years 2 months and since diagnosis of multiple heart metastases was 1 year. Conclusions Cardiac metastases present a unique disease course in renal cell carcinoma. Cardiac metastases may remain asymptomatic, as in the case of this patient at the time of diagnosis. The most common cardiac presentation of renal cell carcinoma is hypertension, but other cardiac presentations include shortness of breath, cough, and arrhythmias. Targeted systemic therapy with tyrosine kinase inhibitors may be useful for this group of patients, but necrosis in the myocardium can result in tamponade and death. Regular cardiac magnetic resonance imaging scans are required for treatment monitoring. PMID:25193011

  8. Killer cell lines against Shope carcinoma cells in rabbits.

    PubMed

    Takahashi, M; Yamade, I; Seto, A

    1991-09-01

    Killer cell activity against Shope carcinoma cells was not detected in PBL nor in spleen cells from tumor-bearing B/J rabbits, but was induced by in vitro culture of these cells in the presence of IL-2 and X-irradiated carcinoma cells. HTLV-I-transformed killer cell lines were successfully obtained by the culturing of PBL from an HTLV-I-infected and tumor-bearing Chbb:HM rabbit. These killer cells included large cells with azurophilic granules in the cytoplasm and with a reniform nucleus, thus resembling large granular lymphocytes. The killer activity was similar against the Vx2K cell line from a random-bred rabbit and SCB cell lines from an B/J rabbit, suggesting the absence of MHC restriction. PMID:1655241

  9. Adipocyte Secreted Factors Enhance Aggressiveness of Prostate Carcinoma Cells

    PubMed Central

    Moreira, Ângela; Pereira, Sofia S.; Costa, Madalena; Morais, Tiago; Pinto, Ana; Fernandes, Rúben; Monteiro, Mariana P.

    2015-01-01

    Obesity has been associated with increased incidence and risk of mortality of prostate cancer. One of the proposed mechanisms underlying this risk association is the change in adipokines expression that could promote the development and progression of the prostate tumor cells. The main goal of this study was to evaluate the effect of preadipocyte and adipocyte secretome in the proliferation, migration and invasion of androgen independent prostate carcinoma cells (RM1) and to assess cell proliferation in the presence of the adiposity signals leptin and insulin. RM1 cells were co-cultured in with preadipocytes, adipocytes or cultured in their respective conditioned medium. Cell proliferation was assessed by flow cytometry and XTT viability test. Cell migration was evaluated using a wound healing injury assay of RM1 cells cultured with conditioned media. Cellular invasion of RM1 cells co-cultured with adipocytes and preadipocytes was assessed using matrigel membranes. Preadipocyte conditioned medium was associated with a small increase in RM1 proliferation, while adipocytes conditioned media significantly increased RM1 cell proliferation (p<0.01). Adipocytes also significantly increased the RM1 cells proliferation in co-culture (p <0.01). Cell migration was higher in RM1 cells cultured with preadipocyte and adipocyte conditioned medium. RM1 cell invasion was significantly increased after co-culture with preadipocytes and adipocytes (p <0.05). Insulin also increased significantly the cell proliferation in contrast to leptin, which showed no effect. In conclusion, prostate carcinoma cells seem to be influenced by factors secreted by adipocytes that are able to increase their ability to proliferate, migrate and invade. PMID:25928422

  10. Comprehensive Cytomorphologic Analysis of Pulmonary Adenoid Cystic Carcinoma: Comparison to Small Cell Carcinoma and Non-pulmonary Adenoid Cystic Carcinoma

    PubMed Central

    Kim, Seokhwi; Chu, Jinah; Kim, Hojoong; Han, Joungho

    2015-01-01

    Background: Cytologic diagnosis of pulmonary adenoid cystic carcinoma (AdCC) is frequently challenging and differential diagnosis with small cell carcinoma is often difficult. Methods: Eleven cytologically diagnosed cases of pulmonary AdCC were collected and reviewed according to fifteen cytomorphologic characteristics: small cell size, cellular uniformity, coarse chromatin, hyperchromasia, distinct nucleolus, frequent nuclear molding, granular cytoplasm, organoid cluster, sheet formation, irregular border of cluster, hyaline globule, hyaline basement membrane material, individual cell necrosis or apoptotic body, and necrotic background. Twenty cases of small cell carcinoma and fifteen cases of non-pulmonary AdCC were also reviewed for the comparison. Results: Statistically significant differences were identified between pulmonary AdCC and small cell carcinoma in fourteen of the fifteen cytomorphologic criteria (differences in sheet formation were not statistically significant). Cellular uniformity, distinct nucleolus, granular cytoplasm, distinct cell border, organoid cluster, hyaline globule, and hyaline basement membrane material were characteristic features of AdCC. Frequent nuclear molding, individual cell necrosis, and necrotic background were almost exclusively identified in small cell carcinoma. Although coarse chromatin and irregular cluster border were observed in both, they favored the diagnosis of small cell carcinoma. Hyaline globules were more frequently seen in non-pulmonary AdCC cases. Conclusions: Using the fifteen cytomorphologic criteria described by this study, pulmonary AdCC could be successfully distinguished from small cell carcinoma. Such a comprehensive approach to an individual case is recommended for the cytologic diagnosis of pulmonary AdCC. PMID:26477588

  11. Metastatic squamous cell carcinoma in a cat.

    PubMed

    Dhaliwal, Ravinder S; Kufuor-Mensah, Eric

    2007-02-01

    A 7-year-old, spayed female Persian cat was referred for evaluation of progressive paraplegia. The cat was thin, cachectic and paraplegic on presentation. The survey radiographs showed a left caudal pulmonary lesion and lytic skeletal lesions at the right iliac crest and left distal scapula. Due to a poor prognosis for complete recovery, the owner opted for euthanasia. Post-mortem examination revealed bilaterally small and irregular kidneys, lysis of the left iliac crest and left distal scapula and a dilated left ventricular lumen with a thin interventricular septum. Histologically, all the lesions were determined to be squamous cell carcinoma. It appears that the origin or the primary site of the malignancy in this case is pulmonary as cardiac and skeletal tissues are primarily mesenchymal in origin and are less likely to develop a primary epithelial malignancy. To the best of our knowledge, there is no description of cardiac or skeletal metastatic squamous cell carcinoma in a cat. PMID:16859943

  12. Laryngeal acinic cell carcinoma following thyroid irradiation

    SciTech Connect

    Reibel, J.F.; McLean, W.C.; Cantrell, R.W.

    1981-01-01

    Only three examples of acinic cell carcinoma of the larynx or trachea are found in the recent literature. A case of acinic cell carcinoma of the subglottic larynx and trachea was diagnosed and treated at the University of Virginia Medical Center. To our knowledge this is the first such case with a prior history of radiation to the neck. The patient is a 56-year-old woman who was irradiated for hyperthyroidism 46 years ago. When seen she also had parathyroid hyperplasia and multiple thyroid adenomas, conditions that frequently follow irradiation of the thyroid in children. These findings in this case support the concept that radiation may be responsible for inducing this tumor, which otherwise rarely occurs in this location. The use of electron microscopy was extremely useful in the diagnosis of this tumor. She was treated with total laryngectomy and right neck dissection and is now free of disease one year after surgery.

  13. SnapShot: Renal Cell Carcinoma.

    PubMed

    Ricketts, Christopher J; Crooks, Daniel R; Sourbier, Carole; Schmidt, Laura S; Srinivasan, Ramaprasad; Linehan, W Marston

    2016-04-11

    Renal cell carcinoma (RCC) is a heterogeneous disease made up of a number of different cancer types, with distinct histologies, clinical courses, therapeutic responses, and genetic drivers. Germline mutations in 14 genes have been associated with increased risk of RCC and can result in HIF pathway activation, chromatin dysregulation, and altered metabolism. Knowledge of these pathway alterations can inform the development of targeted therapeutic approaches. To view this SnapShot, open or download the PDF. PMID:27070709

  14. Nonconventional papillary thyroid carcinomas with pleomorphic tumor giant cells: a diagnostic pitfall with anaplastic carcinoma.

    PubMed

    Hommell-Fontaine, Juliette; Borda, Angela; Ragage, Florence; Berger, Nicole; Decaussin-Petrucci, Myriam

    2010-06-01

    The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different.

  15. Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas.

    PubMed

    Imamhasan, Abdukadir; Mitomi, Hiroyuki; Saito, Tsuyoshi; Hayashi, Takuo; Takahashi, Michiko; Kajiyama, Yoshiaki; Yao, Takashi

    2012-11-01

    Basaloid squamous cell carcinoma of the esophagus is a rare variant of squamous cell carcinoma. We reviewed 878 cases of esophageal squamous cell carcinoma and detected 22 cases (3%) of basaloid squamous cell carcinoma. These tumors and stage-matched paired conventional squamous cell carcinomas were investigated for clinicopathologic features and immunoreactivity of cytokeratin subtypes, p53, B-cell lymphoma 2 (bcl-2), β-catenin, and epidermal growth factor receptor. Molecular aberrations in p53, CTNNB1 (the gene encoding β-catenin), and epidermal growth factor receptor (EGFR) were also determined. Patients with basaloid squamous cell carcinomas demonstrated a 5-year survival rate of 42%, significantly worse than those with well-differentiated squamous cell carcinoma (P<.01). Histologically, solid nests with central necrosis and a cribriform pattern were identified in almost all (≥95%) cases, and ductal differentiation was less frequent (45%) but associated with significantly better survival (P<.05). Compared with conventional squamous cell carcinomas, the basaloid squamous cell carcinomas were less immunoreactive for cytokeratin 14, cytokeratin 903, and membranous β-catenin (P<.01-.001) but more reactive for bcl-2, nuclear β-catenin, epidermal growth factor receptor, and Ki-67 (P<.05-.001). Direct sequencing showed mutations of p53 (36%), EGFR (14%), but not CTNNB1; fluorescent in situ hybridization detected amplification of the epidermal growth factor receptor gene (22%). In basaloid squamous cell carcinomas, low-level expression of cytokeratin 14/cytokeratin 903 and mutations of p53 and EGFR had a significant influence on worse survival (P<.05-.001). We conclude that the esophageal basaloid squamous cell carcinoma, a neoplasm with particularly aggressive biologic behavior, should be differentiated from conventional squamous cell carcinomas. In this context, immunohistochemical assessment of several markers might provide a useful adjunct diagnostic tool

  16. Pulmonary manifestations of renal cell carcinoma.

    PubMed

    Agrawal, Abhinav; Sahni, Sonu; Iftikhar, Asma; Talwar, Arunabh

    2015-12-01

    Renal cell carcinoma (RCC) accounts for majority of all primary renal neoplasms. Classic manifestations of RCC include the triad of flank pain, hematuria and a palpable renal mass. Patients with RCC can develop various extra renal manifestations including involvements of the lungs, inferior vena cava, liver and the bones. The pulmonary manifestations of renal cell carcinoma include metastatic disease including endobronchial, pleural, parenchymal or lymph node metastasis, pleural effusion or hemothorax. Pulmonary embolism and tumor embolism is another common manifestation of renal cell carcinoma. RCC is a highly vascular tumor and can cause pulmonary arterio-venous fistulas leading to high output failure. Rarely, RCC can also present with paraneoplastic presentations including cough or bilateral diaphragm paralysis. Drugs used to treat RCC have been associated with drug related pneumonitis and form an important differential diagnosis in patients with RCC on therapy presenting with shortness of breath. In this review we discuss the various pulmonary manifestations of RCC. A high index of suspicion with these presentations can lead to an early diagnosis and assist in instituting an appropriate intervention. PMID:26525375

  17. Heparanase augments inflammatory chemokine production from colorectal carcinoma cell lines.

    PubMed

    Tsunekawa, Naoki; Higashi, Nobuaki; Kogane, Yusuke; Waki, Michihiko; Shida, Hiroaki; Nishimura, Yoshio; Adachi, Hayamitsu; Nakajima, Motowo; Irimura, Tatsuro

    2016-01-22

    To explore possible roles of heparanase in cancer-host crosstalk, we examined whether heparanase influences expression of inflammatory chemokines in colorectal cancer cells. Murine colorectal carcinoma cells incubated with heparanase upregulated MCP-1, KC, and RANTES genes and released MCP-1 and KC proteins. Heparanase-dependent production of IL-8 was detected in two human colorectal carcinoma cell lines. Addition of a heparanase inhibitor Heparastatin (SF4) did not influence MCP-1 production, while both latent and mature forms of heparanase augmented MCP-1 release, suggesting that heparanase catalytic activity was dispensable for MCP-1 production. In contrast, addition of heparin to the medium suppressed MCP-1 release in a dose-dependent manner. Similarly, targeted suppression of Ext1 by RNAi significantly suppressed cell surface expression of heparan sulfate and MCP-1 production in colon 26 cells. Taken together, it is concluded that colon 26 cells transduce the heparanase-mediated signal through heparan sulfate binding. We propose a novel function for heparanase independent of its endoglycosidase activity, namely as a stimulant for chemokine production. PMID:26713365

  18. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma

    PubMed Central

    Lopez, Jose Ignacio

    2016-01-01

    A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of this tumor subtype. This is the first reported case with multifocal presentation. PMID:27158455

  19. Obstructive jaundice in small cell lung carcinoma.

    PubMed

    Mokhtar Pour, Ali; Masir, Noraidah; Isa, Mohd Rose

    2015-08-01

    Small cell lung carcinoma (SCLC) commonly metastasizes to distant organs. However, metastasis to the pancreas is not a common event. Moreover, obstructive jaundice as a first clinical presentation of SCLC is extremely unusual. This case reports a 51-year-old male with SCLC, manifesting with obstructive jaundice as the initial clinical presentation. Endoscopic retrograde cholangiopancreatograghy (ERCP) and abdominal computed tomography (CT) scan showed a mass at the head of the pancreas. The patient underwent pancreatoduodenectomy (Whipple procedure). Histopathology revealed a chromogranin- A-positive poorly-differentiated neuroendocrine carcinoma of the pancreas. No imaging study of the lung was performed before surgery. A few months later, a follow-up CT revealed unilateral lung nodules with ipsilateral hilar nodes. A lung biopsy was done and histopathology reported a TTF- 1-positive, chromogranin A-positive, small cell carcinoma of the lung. On review, the pancreatic tumour was also TTF-1-positive. He was then treated with combination chemotherapy (cisplatin, etoposide). These findings highlight that presentation of a mass at the head of pancreas could be a manifestation of a metastatic tumour from elsewhere such as the lung, and thorough investigations should be performed before metastases can be ruled out. PMID:26277673

  20. Primary oat cell carcinoma of the larynx

    SciTech Connect

    Aguilar, E.A. III; Robbins, K.T.; Stephens, J.; Dimery, I.W.; Batsakis, J.G.

    1987-02-01

    The aggressiveness of small (oat) cell carcinoma of the larynx presents a therapeutic challenge to the oncologist. Since the first description of this type of carcinoma in 1972, 52 patients have been reported in the literature and a variety of treatment regimens have been used. The purpose of this study was to report two new cases and review all previous reports to determine the disease's biological behavior, clinical manifestations, and optimum treatment. Thirty-five percent of the tumors were transglottic, and 27% were supraglottic. Fifty-four percent of patients had regional metastases at initial presentation and 17.6% had distant metastases. The median survival was 10 months for all patients. Patients who were treated with chemotherapy with or without other modalities had the best 2-year survival rates (52.2%). Forty-one percent of patients had regional recurrence only, 12.5% had regional recurrence and distant metastases, and 2% developed distant metastases only. We conclude that patients with oat cell carcinoma of the larynx should be treated with combination chemotherapy and radiation therapy. Surgery is best reserved for persistent and recurrent disease at the primary site and neck.

  1. A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma

    ClinicalTrials.gov

    2016-09-15

    Carcinoma, Renal Cell; Kidney Diseases; Kidney Neoplasms; Urogenital Neoplasms; Urologic Diseases; Urologic Neoplasms; Neoplasms; Neoplasms by Histologic Type; Clear-cell Metastatic Renal Cell Carcinoma

  2. Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

    PubMed

    Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid.

  3. Photodynamic Therapy With HPPH in Treating Patients With Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2016-04-19

    Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity

  4. Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors

    PubMed Central

    Ruiz-Morales, José Manuel; Cano-García, Fernando

    2016-01-01

    Lung cancer is the principal cause of cancer-related death worldwide. The use of targeted therapies, especially tyrosine kinase inhibitors (TKIs), in specific groups of patients has dramatically improved the prognosis of this disease, although inevitably some patients will develop resistance to these drugs during active treatment. The most common cancer-associated acquired mutation is the epidermal growth factor receptor (EGFR) Thr790Met (T790M) mutation. During active treatment with targeted therapies, histopathological transformation to small-cell lung carcinoma (SCLC) can occur in 3–15% of patients with non-small-cell lung carcinoma (NSCLC) tumors. By definition, SCLC is a high-grade tumor with specific histological and genetic characteristics. In the majority of cases, a good-quality hematoxylin and eosin (H&E) stain is enough to establish a diagnosis. Immunohistochemistry (IHC) is used to confirm the diagnosis and exclude other neoplasia such as sarcomatoid carcinomas, large-cell carcinoma, basaloid squamous-cell carcinoma, chronic inflammation, malignant melanoma, metastatic carcinoma, sarcoma, and lymphoma. A loss of the tumor-suppressor protein retinoblastoma 1 (RB1) is found in 100% of human SCLC tumors; therefore, it has an essential role in tumorigenesis and tumor development. Other genetic pathways probably involved in the histopathological transformation include neurogenic locus notch homolog (NOTCH) and achaete-scute homolog 1 (ASCL1). Histological transformation to SCLC can be suspected in NSCLC patients who clinically deteriorate during active treatment. Biopsy of any new lesion in this clinical setting is highly recommended to rule out a SCLC transformation. New studies are trying to assess this histological transformation by noninvasive measures such as measuring the concentration of serum neuron-specific enolase. PMID:27652204

  5. Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors.

    PubMed

    Dorantes-Heredia, Rita; Ruiz-Morales, José Manuel; Cano-García, Fernando

    2016-08-01

    Lung cancer is the principal cause of cancer-related death worldwide. The use of targeted therapies, especially tyrosine kinase inhibitors (TKIs), in specific groups of patients has dramatically improved the prognosis of this disease, although inevitably some patients will develop resistance to these drugs during active treatment. The most common cancer-associated acquired mutation is the epidermal growth factor receptor (EGFR) Thr790Met (T790M) mutation. During active treatment with targeted therapies, histopathological transformation to small-cell lung carcinoma (SCLC) can occur in 3-15% of patients with non-small-cell lung carcinoma (NSCLC) tumors. By definition, SCLC is a high-grade tumor with specific histological and genetic characteristics. In the majority of cases, a good-quality hematoxylin and eosin (H&E) stain is enough to establish a diagnosis. Immunohistochemistry (IHC) is used to confirm the diagnosis and exclude other neoplasia such as sarcomatoid carcinomas, large-cell carcinoma, basaloid squamous-cell carcinoma, chronic inflammation, malignant melanoma, metastatic carcinoma, sarcoma, and lymphoma. A loss of the tumor-suppressor protein retinoblastoma 1 (RB1) is found in 100% of human SCLC tumors; therefore, it has an essential role in tumorigenesis and tumor development. Other genetic pathways probably involved in the histopathological transformation include neurogenic locus notch homolog (NOTCH) and achaete-scute homolog 1 (ASCL1). Histological transformation to SCLC can be suspected in NSCLC patients who clinically deteriorate during active treatment. Biopsy of any new lesion in this clinical setting is highly recommended to rule out a SCLC transformation. New studies are trying to assess this histological transformation by noninvasive measures such as measuring the concentration of serum neuron-specific enolase. PMID:27652204

  6. Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors.

    PubMed

    Dorantes-Heredia, Rita; Ruiz-Morales, José Manuel; Cano-García, Fernando

    2016-08-01

    Lung cancer is the principal cause of cancer-related death worldwide. The use of targeted therapies, especially tyrosine kinase inhibitors (TKIs), in specific groups of patients has dramatically improved the prognosis of this disease, although inevitably some patients will develop resistance to these drugs during active treatment. The most common cancer-associated acquired mutation is the epidermal growth factor receptor (EGFR) Thr790Met (T790M) mutation. During active treatment with targeted therapies, histopathological transformation to small-cell lung carcinoma (SCLC) can occur in 3-15% of patients with non-small-cell lung carcinoma (NSCLC) tumors. By definition, SCLC is a high-grade tumor with specific histological and genetic characteristics. In the majority of cases, a good-quality hematoxylin and eosin (H&E) stain is enough to establish a diagnosis. Immunohistochemistry (IHC) is used to confirm the diagnosis and exclude other neoplasia such as sarcomatoid carcinomas, large-cell carcinoma, basaloid squamous-cell carcinoma, chronic inflammation, malignant melanoma, metastatic carcinoma, sarcoma, and lymphoma. A loss of the tumor-suppressor protein retinoblastoma 1 (RB1) is found in 100% of human SCLC tumors; therefore, it has an essential role in tumorigenesis and tumor development. Other genetic pathways probably involved in the histopathological transformation include neurogenic locus notch homolog (NOTCH) and achaete-scute homolog 1 (ASCL1). Histological transformation to SCLC can be suspected in NSCLC patients who clinically deteriorate during active treatment. Biopsy of any new lesion in this clinical setting is highly recommended to rule out a SCLC transformation. New studies are trying to assess this histological transformation by noninvasive measures such as measuring the concentration of serum neuron-specific enolase.

  7. Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-10-18

    Cancer of Head and Neck; Head and Neck Cancer; Neoplasms, Head and Neck; Carcinoma, Squamous Cell of Head and Neck; Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma, Head and Neck

  8. Genetic landscape of esophageal squamous cell carcinoma.

    PubMed

    Gao, Yi-Bo; Chen, Zhao-Li; Li, Jia-Gen; Hu, Xue-Da; Shi, Xue-Jiao; Sun, Zeng-Miao; Zhang, Fan; Zhao, Zi-Ran; Li, Zi-Tong; Liu, Zi-Yuan; Zhao, Yu-Da; Sun, Jian; Zhou, Cheng-Cheng; Yao, Ran; Wang, Su-Ya; Wang, Pan; Sun, Nan; Zhang, Bai-Hua; Dong, Jing-Si; Yu, Yue; Luo, Mei; Feng, Xiao-Li; Shi, Su-Sheng; Zhou, Fang; Tan, Feng-Wei; Qiu, Bin; Li, Ning; Shao, Kang; Zhang, Li-Jian; Zhang, Lan-Jun; Xue, Qi; Gao, Shu-Geng; He, Jie

    2014-10-01

    Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications. PMID:25151357

  9. Combination therapy for metastatic renal cell carcinoma

    PubMed Central

    Buonerba, Carlo; Di Lorenzo, Giuseppe

    2016-01-01

    Current therapy for metastatic clear cell renal cell carcinoma (RCC) consists of the serial administration of single agents. Combinations of VEGF and mTOR inhibitors have been disappointing in previous randomized trials. However, the combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as FGF receptors, and everolimus demonstrated promising results in a randomized phase II trial. Moreover, the emergence of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors has spawned the investigation of combinations of these agents with VEGF inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors. These ongoing phase III trials in conjunction with the development of predictive biomarkers and agents inhibiting novel therapeutic targets may provide much needed advances in this still largely incurable disease. PMID:27047959

  10. Focus on Basal Cell Carcinoma

    PubMed Central

    Samarasinghe, Venura; Madan, Vishal; Lear, John T.

    2011-01-01

    Nonmelanoma skin cancers (NMSCs), which include basal and squamous cell cancers are the most common human cancers. BCCs have a relatively low metastatic rate and slow growth and are frequently underreported. Whilst there is a definite role of sunexposure in the pathogenesis of BCC, several additional complex genotypic, phenotypic and environmental factors are contributory. The high prevalence and the frequent occurrence of multiple primary BCC in affected individuals make them an important public health problem. This has led to a substantial increase in search for newer noninvasive treatments for BCC. Surgical excision with predetermined margins remains the mainstay treatment for most BCC. Of the newer non-invasive treatments only photodynamic therapy and topical imiquimod have become established in the treatment of certain BCC subtypes, while the search for other more effective and tissue salvaging therapies continues. This paper focuses on the pathogenesis and management of BCC. PMID:21152128

  11. Hürthle cell carcinoma: diagnostic and therapeutic implications

    PubMed Central

    Hanief, Mohamed R; Igali, Laszlo; Grama, Dimitrie

    2004-01-01

    Background Hürthle cell carcinoma is a variant of follicular cell carcinoma of thyroid. It may present as a low-grade tumour or as a more aggressive type. Prognosis depends upon the age of the patient, tumour size, extent of invasion and initial nodal or distant metastasis. Patient and methods The case of Hürthle cell carcinoma is reported in a 79-year-old man who presented with a rapidly increasing lump on the left side of his neck, having had a right hemithyroidectomy for colloid goitre 24-years-ago. Fine needle aspiration cytology confirmed the presence of Hürthle cells, raising the possibility of a Hürthle cell neoplasm. The patient underwent staging and surgery. Histology showed Hürthle cell carcinoma and the patient underwent adjuvant therapy. The literature on Hürthle cell neoplasms is reviewed. Conclusions Fine needle aspiration cytology may recognise Hürthle cell lesion but final diagnosis of carcinoma depends upon histological confirmation of vascular or capsular invasion. Staging and surgery in Hürthle cell carcinoma are similar to follicular carcinoma of thyroid with favourable outcome despite the controversy regarding the histological classification and adjuvant therapy. Elderly patients with Hürthle cell carcinoma need to be made aware of their poorer prognosis and should be offered more radical treatment. PMID:15306032

  12. Aggressive Metaplastic Carcinoma of the Breast with Osteoclastic Giant Cells.

    PubMed

    Khong, Kathleen; Zhang, Yanhong; Tomic, Mary; Lindfors, Karen; Aminololama-Shakeri, Shadi

    2015-09-01

    Metaplastic carcinoma of the breast is an uncommon type of malignancy that is aggressive but can mimic other benign breast neoplastic processes on imaging. We present a case of a young female patient who presented with a rapidly progressing metaplastic carcinoma with osteoclastic giant cells subtype. There have been only very rare published reports of this pathologic subtype of metaplastic carcinoma containing osteoclastic giant cells.

  13. Aggressive Metaplastic Carcinoma of the Breast with Osteoclastic Giant Cells

    PubMed Central

    Khong, Kathleen; Zhang, Yanhong; Tomic, Mary; Lindfors, Karen; Aminololama-Shakeri, Shadi

    2015-01-01

    Metaplastic carcinoma of the breast is an uncommon type of malignancy that is aggressive but can mimic other benign breast neoplastic processes on imaging. We present a case of a young female patient who presented with a rapidly progressing metaplastic carcinoma with osteoclastic giant cells subtype. There have been only very rare published reports of this pathologic subtype of metaplastic carcinoma containing osteoclastic giant cells. PMID:26629304

  14. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

    Atwood, Scott X.; Whitson, Ramon J.; Oro, Anthony E.

    2014-01-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists. PMID:24985127

  15. Epidemiology and Staging of Renal Cell Carcinoma

    PubMed Central

    Ridge, Carole A.; Pua, Bradley B.; Madoff, David C.

    2014-01-01

    Incidence and mortality trends attributed to kidney cancer exhibit marked regional variability, likely related to demographic, environmental, and genetic factors. Efforts to identify reversible factors, which lead to the development of renal cell carcinoma (RCC), have led not only to a greater understanding of the etiology of RCC but also the genetic and histologic characteristics of renal tumors. This article describes this evolution by discussing contemporary RCC incidence and mortality data, the risk factors for development of RCC, the histologic features, and anatomic and integrated staging systems that guide treatment. PMID:24596434

  16. Tubulocystic Renal Cell Carcinoma: A Great Imitator

    PubMed Central

    Banerjee, Indraneel; Yadav, Sher Singh; Tomar, Vinay; Yadav, Suresh; Talreja, Shyam

    2016-01-01

    Tubulocystic renal cell carcinoma (TCRC) is a rare renal tumor. Patients are usually asymptomatic; it is usually detected incidentally, during imaging studies for Bosniak type III and type IV renal cysts. These tumors rarely metastasize. The role of targeted therapy in such rare tumors is still controversial. We report a case of TCRC initially presented as a Bosniak type II renal cyst and was discovered ultimately to be a metastatic disease. This type of presentation might broaden our understanding of this rare disease. PMID:27601972

  17. Cutaneous tuberculosis and squamous-cell carcinoma.

    PubMed

    Ljubenovic, Milanka S; Ljubenovic, Dragisa B; Binic, Ivana I; Jankovic, Aleksandar S; Jancic, Snezana A

    2011-01-01

    The incidence of all forms of cutaneous tuberculosis, including lupus vulgaris (the most common form) decreased progressively in developed countries during the twentieth century, this change being attributed to improved living standards and specific therapy. Despite the decrease in cutaneous tuberculosis, some cases are still found and correct diagnosis and management are fundamental, both for the patients and for public health. Long lasting, misdiagnosed or untreated cutaneous tuberculosis may lead to different forms of cancer. This case report involves a 74-year old male farmer with lupus vulgaris on his face. During anti-tuberculosis treatment he developed a tumor on his forehead, which was histologically confirmed as a squamous cell carcinoma.

  18. Basal cell carcinomas: attack of the hedgehog.

    PubMed

    Epstein, Ervin H

    2008-10-01

    Basal cell carcinomas (BCCs) were essentially a molecular 'black box' until some 12 years ago, when identification of a genetic flaw in a rare subset of patients who have a great propensity to develop BCCs pointed to aberrant Hedgehog signalling as the pivotal defect leading to formation of these tumours. This discovery has facilitated a remarkable increase in our understanding of BCC carcinogenesis and has highlighted the carcinogenic role of this developmental pathway when aberrantly activated in adulthood. Importantly, a phase 1 first-in-human trial of a Hedgehog inhibitor has shown real progress in halting and even reversing the growth of these tumours.

  19. Contemporary Treatment of Metastatic Renal Cell Carcinoma.

    PubMed

    Stukalin, Igor; Alimohamed, Nimira; Heng, Daniel Y C

    2016-04-15

    The introduction of targeted therapy has revolutionized the treatment of patients with metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Over the past few years, research exploring novel targeted agents has blossomed, leading to the approval of various targeted therapies. Furthermore, results from the CheckMate025 and the METEOR trials have brought about two additional novel options: the programmed cell death 1 (PD-1) checkpoint inhibitor nivolumab and the MET/VEGFR/AXL inhibitor cabozantinib, respectively. With the variety of therapeutic agents available for treatment of mRCC, research examining appropriate sequencing and combinations of the drugs is ongoing. This review discusses the role of prognostic criteria, such as those from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. It also covers the current standard of treatment for mRCC with targeted therapy in first-, second-, and third-line setting. Additionally, the novel mechanism of action of nivolumab and cabozantinib, therapeutic sequencing and ongoing clinical trials are discussed. PMID:27471582

  20. Contemporary Treatment of Metastatic Renal Cell Carcinoma

    PubMed Central

    Stukalin, Igor; Alimohamed, Nimira; Heng, Daniel Y.C.

    2016-01-01

    The introduction of targeted therapy has revolutionized the treatment of patients with metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Over the past few years, research exploring novel targeted agents has blossomed, leading to the approval of various targeted therapies. Furthermore, results from the CheckMate025 and the METEOR trials have brought about two additional novel options: the programmed cell death 1 (PD-1) checkpoint inhibitor nivolumab and the MET/VEGFR/AXL inhibitor cabozantinib, respectively. With the variety of therapeutic agents available for treatment of mRCC, research examining appropriate sequencing and combinations of the drugs is ongoing. This review discusses the role of prognostic criteria, such as those from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. It also covers the current standard of treatment for mRCC with targeted therapy in first-, second-, and third-line setting. Additionally, the novel mechanism of action of nivolumab and cabozantinib, therapeutic sequencing and ongoing clinical trials are discussed. PMID:27471582

  1. Lysyl oxidase-like 2 as a new poor prognosis marker of squamous cell carcinomas.

    PubMed

    Peinado, Héctor; Moreno-Bueno, Gema; Hardisson, David; Pérez-Gómez, Eduardo; Santos, Vanesa; Mendiola, Marta; de Diego, Juan Ignacio; Nistal, Manuel; Quintanilla, Miguel; Portillo, Francisco; Cano, Amparo

    2008-06-15

    Lysyl oxidase-like 2 (Loxl2) interacts with and stabilizes Snai1 transcription factor, promoting epithelial-mesenchymal transition. Either Loxl2 or Snai1 knock-down blocks tumor growth and induces differentiation, but the specific role of each factor in tumor progression is still unknown. Comparison of the gene expression profiles of the squamous cell carcinoma cell line HaCa4 after knocking-down Loxl2 or Snai1 revealed that a subset of epidermal differentiation genes was specifically up-regulated in Loxl2-silenced cells. In agreement, although both Loxl2- and Snai1-knockdown cells showed reduced in vivo invasion, only Loxl2-silenced cells exhibited a skin-like epidermal differentiation program. In addition, we show that expression of Loxl2 and Snai1 correlates with malignant progression in a two-stage mouse skin carcinogenesis model. Furthermore, we found that increased expression of both LOXL2 and SNAI1 correlates with local recurrence in a cohort of 256 human laryngeal squamous cell carcinomas. We describe for the first time that high levels of LOXL2 are associated with decreased overall and disease-free survival in laryngeal squamous cell carcinomas, lung squamous cell carcinoma, and lymph node-negative (N(0)) breast adenocarcinomas. Altogether, our results show that LOXL2 can be used as a new poor prognosis indicator in human squamous cell carcinomas promoting malignant transformation by both SNAI1-dependent and SNAI1-independent pathways.

  2. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

    PubMed Central

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis.

  3. Acute cholecystitis or metastatic renal cell carcinoma? a diagnostic dilemma.

    PubMed

    Finkelstein, L H; Coffman, L M

    1996-05-01

    Renal cell carcinoma is known to metastasize to many different organ systems. Lung and bone are clearly the most common sites of metastasis, but the symptoms at presentation may simulate those of other diseases of the organ system involved. The patient with metastatic renal cell carcinoma described here had symptoms of acute cholecystitis.

  4. Multiple basal cell carcinomas arising in port-wine haemangiomas.

    PubMed

    Magaña-García, M; Magaña-Lozano, M

    1988-09-01

    We report the case of a 49-year-old man, who had had two port-wine stains from birth, in which many basal cell carcinomas developed during his forties. The appearance of multiple basal cell carcinomas in port-wine stains has not been reported previously to our knowledge and may represent a new syndrome.

  5. Immunity to squamous carcinoma in mice immunized with dendritic cells transfected with genomic DNA from squamous carcinoma cells.

    PubMed

    O-Sullivan, InSug; Ng, Lauren K; Martinez, Don M; Kim, Tae S; Chopra, Amla; Cohen, Edward P

    2005-10-01

    Immunotherapy of squamous cell carcinoma (SCC) at an early stage of the disease increases the likelihood of success. We report a new vaccination strategy designed to prepare SCC vaccines from microgram amounts of tumor tissue, enabling the treatment of patients with minimal residual disease. The vaccine was prepared by transfer of sheared genomic DNA-fragments (25 kb) from KLN205 cells, an SCC cell line of DBA/2 mouse origin, into syngeneic bone marrow-derived mature dendritic cells (DCs). More than 90% of the transfected DCs took up DNA from the neoplasm and transferred genes were expressed as protein. The DCs expressed CD11c, CD11b, and the costimulatory molecules CD40, CD80 and CD86, characteristic of mature DCs. Syngeneic DBA/2J mice, highly susceptible to the growth of KLN205 cells, were injected intravenously (i.v.) with the transfected DCs, followed by a subcutaneous (s.c.) injection of the tumor cells. The strong immunogenic properties of the transfected cells were indicated by the finding that the survival of the tumor-bearing mice was prolonged (P<.001), relative to that of mice in various control groups. Enzyme-linked immuno spot (ELISPOT IFN-gamma) assays revealed the activation of cell-mediated immunity directed toward the SCC in mice immunized with the transfected DCs. Two independent in vitro cytotoxicity assays indicated the presence of robust cell-mediated immunity directed toward the SCC in mice immunized with the transfected cells.

  6. Hyalinizing clear cell carcinoma of the oral cavity and of the parotid gland.

    PubMed

    Rinaldo, A; McLaren, K M; Boccato, P; Maran, A G

    1999-01-01

    Hyalinizing clear cell carcinoma (HCCC) is a rare, recently described tumor of salivary gland origin. Differential diagnosis includes benign lesions as clear cell change in a pleomorphic adenoma or in oncocytoma and malignant tumors - i.e. epithelial-myoepithelial carcinoma, polymorphous low-grade adenocarcinoma, mucoepidermoid carcinoma, clear cell acinic carcinoma, clear cell squamous carcinoma, clear cell malignant melanoma, clear cell odontogenic carcinoma, clear cell rhabdomyosarcoma, sebaceous carcinoma and metastasis of renal carcinoma. A favorable prognosis after wide local excision has been evidenced. Three new cases of HCCC (2 in the oral cavity and 1 in the parotid gland) are presented.

  7. Small cell carcinoma of the prostate

    PubMed Central

    Nadal, Rosa; Schweizer, Michael; Kryvenko, Oleksandr N.; Epstein, Jonathan I.; Eisenberger, Mario A.

    2015-01-01

    Pure small-cell carcinoma (SCC) of the prostate is a rare entity and one of the most aggressive malignancies of the prostate. Histologically, prostatic SCCs of the prostate are part of a spectrum of anaplastic tumours of the prostate and are similar to SCCs of the lungs. In most cases, SCC of the prostate is associated with conventional prostatic adenocarcinoma. Both components of these mixed tumours frequently share molecular alterations such as ERG gene rearrangements or AURKA and MYCN amplifications, suggesting a common clonal origin. The clinical behaviour of small-cell prostate carcinomas is characterized by extensive local disease, visceral disease, and low PSA levels despite large metastatic burden. Commonly, the emergence of the SCC occurs in patients with high-grade adenocarcinoma who are often treated with androgen deprivation treatment (ADT). However, SCCs do not usually benefit from ADT. A biopsy of accessible lesions is strongly recommended to identify those with SCC pathological features, as management is undoubtedly affected by this finding. Chemotherapy is the standard approach for treating patients with either localized or advanced prostatic SCC. Despite the emergence of more-aggressive treatment modalities, the prognosis of men with prostatic SCC remains dismal. PMID:24535589

  8. Squamous cell carcinoma of the extremities

    SciTech Connect

    Lifeso, R.M.; Bull, C.A.

    1985-06-15

    Between January 1976 and January 1983, 37 cases of squamous cell carcinoma of the extremities have been treated at the King Faisal Specialist Hospital and Research Centre by the authors. Each case has arisen in an area of preexisting scar or sinus. Twenty-nine cases were treated by definitive amputation, with 2 local recurrences and 12 nodal metastases. Seven cases had local excision, with three local recurrences and two nodal metastases. Recurrence rate was highest in Grade II and Grade III lesions, and 11 of 15 cases with Grade II disease had metastases to the regional lymph nodes an average of 5 months after surgery. With Grade I disease patients, 4 of 15 had nodal metastases an average of 5 months after surgery. Prophylactic regional nodal irradiation or node dissection was performed in seven cases. None of these cases have shown nodal metastases at an average of 24 months following definitive surgery and radiation. Routine prophylactic regional node irradiation is recommended in all cases of peripheral squamous cell carcinoma.

  9. A Case of Hereditary Leiomyomatosis and Renal Cell Carcinoma

    PubMed Central

    Mehrtens, Sarah; Veitch, David; Kulakov, Elizabeth; Perrett, Conal M.

    2016-01-01

    A 49-year-old lady presented with multiple recurring painful lesions over her thighs, arms, and back. Past medical history included a left sided nephrectomy for renal cell carcinoma and a hysterectomy for multiple uterine fibroids (leiomyomas). Histopathological examination revealed changes consistent with pilar leiomyomas. Gene mutation analysis confirmed a diagnosis of hereditary leiomyomatosis and renal cell carcinoma. Hereditary leiomyomatosis and renal cell carcinoma is an uncommon autosomal dominant condition characterised by the concurrent presentation of cutaneous and uterine leiomyomas. Renal cell carcinoma associated with this condition is more aggressive and a significant cause of mortality. Due to this association with potentially fatal renal cell carcinoma we felt that it was important to highlight this case with an update on pathophysiology and management. PMID:27144040

  10. HLA expression in hepatocellular carcinoma cell lines.

    PubMed

    Wadee, A A; Paterson, A; Coplan, K A; Reddy, S G

    1994-08-01

    The present study undertook to investigate the biological significance of human leucocyte antigen expression in hepatocellular carcinoma and to elucidate the role of potential modulating agents on human leucocyte antigen expression. These studies used several hepatic tumour-derived cell lines as in vitro model systems. The cell lines included PLC/PRF/5 (Alexander cell line), Hep3B, HepG2, TONG PHC, HA22T/VGH, HA59T/VGH and Mahlavu. The cell lines K562 and Raji were used as negative and positive controls, respectively. K562, a B lymphoid-derived cell line, was shown to express negligible amounts of human leucocyte antigens, while Raji, an erythromyeloid-derived cell line, expressed both class I and class II human leucocyte antigens as well as their respective invariant chains, beta 2-microglobulin and Ii. Using an ELISA, experiments performed on these cell lines confirmed the natural expression of class I and class II antigens by the HA22T/VGH and HA59T/VGH cell lines, whereas PLC/PRF/5 displayed class II surface antigens only. The effects of modulating agents such as interferon-gamma sodium butyrate and clofazimine on human leucocyte antigen expression were investigated using the HA22T/VGH, HA59T/VGH and TONG PHC cell lines. These agents increased class II and class II human leucocyte antigen expression on HA22T/VGH and TONG PHC cells, but had no effect on the HA59T/VGH cell line. The results suggest a potential use for these agents as modulators of human leucocyte antigen expression by human heptocellular cell lines.

  11. Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma.

    PubMed

    Fadare, Oluwole; Liang, Sharon X

    2012-12-01

    Hepatocyte nuclear factor 1-beta (HNF1β) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1β protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4+ scale) by the intensity of staining (0 to 3+ scale) for each case. HNF1β expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1β expression, including 11 (73%) of 15, 9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1β expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1β, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear

  12. Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

    PubMed Central

    Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

    2016-01-01

    Bruton’s tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer. PMID:27508020

  13. A case of endocrine cell carcinoma combined with squamous cell carcinoma of the esophagus resected by endoscopic submucosal dissection.

    PubMed

    Watanabe, Ko; Hikichi, Takuto; Sato, Masaki; Nakamura, Jun; Takagi, Tadayuki; Suzuki, Rei; Sugimoto, Mitsuru; Waragai, Yuichi; Kikuchi, Hitomi; Konno, Naoki; Watanabe, Hiroshi; Obara, Katsutoshi; Ohira, Hiromasa

    2014-01-01

    A 55-year-old man with esophageal carcinoma received endoscopic submucosal dissection (ESD) in en-bloc resection. Histopathological examination revealed an admixture of squamous cell carcinoma (SCC) and endocrine cell carcinoma (ECC) with invasion of the deep submucosa. Immunohistochemically, CD 56 and chromogranin A were positive for ECC. Small-cell, medium-cell, and large-cell type ECC were partly surrounded with SCC and partly formed the duct, presenting various patterns. After ESD, he received chemotherapy including CPT-11 plus Cisplatin. He is alive and in good condition today, 55 months after ESD, with no evidence of recurrence.

  14. Lung Metastasis of Renal Cell Carcinoma: ACase Report of Pulmonary Sarcomatoid Carcinoma.

    PubMed

    Fan, Tao; Song, Ying-Jie

    2016-06-01

    Pulmonary sarcomatoid carcinoma (PSC) is a rare malignant cancer composed of sarcoma and sarcoma-like elements with spindle or giant cell features. We report the case of a 60-year-old male with past medical history of right renal cell carcinoma 2 years earlier. Apulmonary nodule was detected in the left upper lobe, 23 months after nephrectomy. Systemic positron emission tomography-computerized tomography (PET-CT) revealed one high metabolic mass shadow in the left upper lobe. Chest CTscan with contrast revealed a left upper lobe mass (2.9 x 2.5 cm). The case was suspected to be a lung metastasis of renal cell carcinoma. After surgery, the pathology revealed PSC-giant cell carcinoma. The tumor's pathology and treatment methods are discussed. PMID:27376226

  15. Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery

    ClinicalTrials.gov

    2016-10-04

    Head and Neck Squamous Cell Carcinoma; Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Laryngeal Verrucous Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oral Cavity Verrucous Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma

  16. Squamous cell carcinoma in a capybara (Hydrochoerus hydrochaeris).

    PubMed

    Hamano, Takahisa; Terasawa, Fumio; Tachikawa, Yoshiharu; Murai, Atsuko; Mori, Takashi; El-Dakhly, Khaled; Sakai, Hiroki; Yanai, Tokuma

    2014-09-01

    A 4-year and 2-month-old male capybara (Hydrochoerus hydrochaeris) was diagnosed with squamous cell carcinoma on the buttocks after chronic recurrent dermatosis. The capybara was euthanized, examined by computed tomography and necropsied; the tumor was examined histologically. Computed tomography showed a dense soft tissue mass with indistinct borders at the buttocks. Histological examination of the tumor revealed islands of invasive squamous epithelial tumor cells with a severe desmoplastic reaction. Based on the pathological findings, the mass was diagnosed as a squamous cell carcinoma. This is the first study to report squamous cell carcinoma in a capybara.

  17. Squamous Cell Carcinoma in a Capybara (Hydrochoerus hydrochaeris)

    PubMed Central

    HAMANO, Takahisa; TERASAWA, Fumio; TACHIKAWA, Yoshiharu; MURAI, Atsuko; MORI, Takashi; EL-DAKHLY, Khaled; SAKAI, Hiroki; YANAI, Tokuma

    2014-01-01

    ABSTRACT A 4-year and 2-month-old male capybara (Hydrochoerus hydrochaeris) was diagnosed with squamous cell carcinoma on the buttocks after chronic recurrent dermatosis. The capybara was euthanized, examined by computed tomography and necropsied; the tumor was examined histologically. Computed tomography showed a dense soft tissue mass with indistinct borders at the buttocks. Histological examination of the tumor revealed islands of invasive squamous epithelial tumor cells with a severe desmoplastic reaction. Based on the pathological findings, the mass was diagnosed as a squamous cell carcinoma. This is the first study to report squamous cell carcinoma in a capybara. PMID:24909968

  18. Transformation of Merkel cell carcinoma to ganglioneuroblastoma in intracranial metastasis.

    PubMed

    Lach, Boleslaw; Joshi, Sangeeta S; Murty, Naresh; Huq, Nasimul

    2014-09-01

    Merkel cell carcinoma is an aggressive neuroendocrine tumor occasionally demonstrating aberrant differentiation to other epithelial and nonepithelial cell lines. We describe a case of Merkel cell carcinoma displaying unique patterns of differentiation in the primary focus and brain metastasis. The skin primary was almost uniformly small cell carcinoma positive for epithelial and neuroendocrine markers, with a few glial fibrillary acidic protein- and cytokeratin 20-positive cells. The neoplasm contained giant cells immunoreactive for neurofilament and negative for epithelial markers. The neck lymph node metastasis was a typical neuroendocrine Merkel cell carcinoma positive for cytokeratin 20. A solitary dural intracranial metastasis displayed features of aggressive ganglioneuroblastoma, expressing many neuronal antigens with no evidence of glial or epithelial differentiation. After total gross resection, the tumor recurred within 3 months, and the patient developed skeletal metastases and died 6 months after craniotomy. PMID:24996688

  19. Next Generation Sequencing of Cytokeratin 20-Negative Merkel Cell Carcinoma Reveals Ultraviolet Signature Mutations and Recurrent TP53 and RB1 Inactivation

    PubMed Central

    Harms, Paul W.; Collie, Angela M. B.; Hovelson, Daniel H.; Cani, Andi K.; Verhaegen, Monique E.; Patel, Rajiv M.; Fullen, Douglas R.; Omata, Kei; Dlugosz, Andrzej A.; Tomlins, Scott A.; Billings, Steven D.

    2016-01-01

    Merkel cell carcinoma is a rare but highly aggressive cutaneous neuroendocrine carcinoma. Cytokeratin-20 (CK20) is expressed in approximately 95% of Merkel cell carcinomas and is useful for distinction from morphologically similar entities including metastatic small cell lung carcinoma. Lack of CK20 expression may make diagnosis of Merkel cell carcinoma more challenging, and has unknown biological significance. Approximately 80% of CK20-positive Merkel cell carcinomas are associated with the oncogenic Merkel cell polyomavirus. Merkel cell carcinomas lacking Merkel cell polyomavirus display distinct genetic changes from Merkel cell polyomavirus-positive Merkel cell carcinoma, including RB1 inactivating mutations. Unlike CK20-positive Merkel cell carcinoma, the majority of CK20-negative Merkel cell carcinomas are Merkel cell polyomavirus-negative, suggesting CK20-negative Merkel cell carcinomas predominantly arise through virus-independent pathway(s) and may harbor additional genetic differences from conventional Merkel cell carcinoma. Hence, we analyzed 15 CK20-negative Merkel cell carcinoma tumors (ten Merkel cell polyomavirus-negative, four Merkel cell polyomavirus-positive, and one undetermined) using the Ion Ampliseq Comprehensive Cancer Panel, which assesses copy number alterations and mutations in 409 cancer-relevant genes. Twelve tumors displayed prioritized high-level chromosomal gains or losses (average 1.9 per tumor). Non-synonymous high confidence somatic mutations were detected in 14 tumors (average 11.9 per tumor). Assessing all somatic coding mutations, an ultraviolet-signature mutational profile was present, and more prevalent in Merkel cell polyomavirus-negative tumors. Recurrent deleterious tumor suppressor mutations affected TP53 (9/15, 60%), RB1 (3/15, 20%), and BAP1 (2/15, 13%). Oncogenic activating mutations included PIK3CA (3/15, 20%), AKT1 (1/15, 7%)) and EZH2 (1/15, 7%). In conclusion, CK20-negative Merkel cell carcinoma display overlapping

  20. Bile duct invasion can be an independent prognostic factor in early stage hepatocellular carcinoma

    PubMed Central

    Jang, Ye-Rang; Kim, Hyeyoung; Lee, Jeong-Moo; Yi, Nam-Joon; Suh, Kyung-Suk

    2015-01-01

    Backgrounds/Aims In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. Methods We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. Results Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. Conclusions Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2). PMID:26693236

  1. Treatment of squamous carcinoma in mice with a vaccine enriched for cells that induce immunity to squamous carcinoma--a new vaccination strategy.

    PubMed

    Chopra, Amla; Kim, Tae Sung; O-Sullivan, InSug; Martinez, Don; Cohen, Edward P

    2006-07-15

    We report a new vaccination strategy for squamous cell carcinoma (SCC). The vaccine was prepared by transfer of unfractionated DNA-fragments (25 kb) from squamous carcinoma cells (KLN205, DBA/2 origin (H-2(d))) into LM mouse fibroblasts (C3H/He origin; H-2(k)), a highly immunogenic cell line. To enhance their nonspecific immunogenic properties, the fibroblasts were modified before DNA transfer to secrete IL-2 and to express additional allogeneic MHC class I determinants. As the transferred DNA integrates into the genome of the recipient cells, and is replicated as the cells divide, sufficient DNA to prepare the vaccine could be obtained from as few as 10(7) squamous carcinoma cells (4 mm tumor). Since only a small proportion of the transfected cell-population was expected to have incorporated genes specifying antigens associated with the squamous carcinoma cells (TAA), we devised a novel approach to enrich the vaccine for cells that induce immunity to the SCC. Aliquots of the transfected population were divided into 10 small pools (initial inoculums = 1 x 10(3)). We reasoned that if the starting inoculums were sufficiently small, then the distribution of highly immunogenic and weakly immunogenic cells in each pool would not be the same. Cells from individual pools were allowed to increase in number. A portion of the expanded cell populations were maintained frozen/viable for later recovery. The remaining portions were used to immunize naïve DBA/2 mice. Pools containing greater numbers of immunogenic cells were identified by 2 independent assays. Frozen aliquots of cells from the pool that stimulated immunity to the squamous carcinoma to the greatest extent were recovered and subdivided for additional rounds of immune selection. Enhanced immunity to squamous carcinoma mediated by CD8+ T cells was induced in tumor-bearing mice treated solely by immunization with the enriched cell-population.

  2. Chromogranin positive cells in colorectal carcinoma and transitional mucosa.

    PubMed Central

    Mori, M; Mimori, K; Kamakura, T; Adachi, Y; Ikeda, Y; Sugimachi, K

    1995-01-01

    AIMS--Immunostaining of chromogranin identifies gastrointestinal mucosal endocrine cells. The detailed distribution and significance of chromogranin positive cells in colorectal carcinomas and in transitional mucosa remain unclear. The aim of this study was to clarify these aspects. METHODS--The distribution of chromogranin positive cells was studied by immunohistochemical methods in normal epithelium remote from carcinoma, in transitional mucosa, and in carcinomas of the colorectum. In selected cases northern or western blot analyses were performed. RESULTS--Chromogranin positive cells were seen in the lower third of the normal crypts and less frequently in transitional mucosa. Thirty five per cent (n = 38) of colorectal carcinomas showed immunohistochemically positive carcinoma cells in the tumour tissue. Northern and western blot analyses showed similar results. There was no difference in clinicopathological factors, including prognosis, between chromogranin positive cases of colorectal carcinoma (n = 38) and chromogranin negative cases (n = 70). CONCLUSIONS--Neuroendocrine cell differentiation is controlled in transitional mucosa and the presence of chromogranin positive cells in carcinoma tissue does not influence the patient's prognosis. Images PMID:7560204

  3. The dermatoscopic universe of basal cell carcinoma

    PubMed Central

    Lallas, Aimilios; Apalla, Zoe; Argenziano, Giuseppe; Longo, Caterina; Moscarella, Elvira; Specchio, Francesca; Raucci, Margaritha; Zalaudek, Iris

    2014-01-01

    Following the first descriptions of the dermatoscopic pattern of basal cell carcinoma (BCC) that go back to the very early years of dermatoscopy, the list of dermatoscopic criteria associated with BCC has been several times updated and renewed. Up to date, dermatoscopy has been shown to enhance BCC detection, by facilitating its discrimination from other skin tumors and inflammatory skin diseases. Furthermore, upcoming evidence suggests that the method is also useful for the management of the tumor, since it provides valuable information about the histopathologic subtype, the presence of clinically undetectable pigmentation, the expansion of the tumor beyond clinically visible margins and the response to non-ablative treatments. In the current article, we provide a summary of the traditional and latest knowledge on the value of dermatoscopy for the diagnosis and management of BCC. PMID:25126452

  4. Renal cell carcinoma: links and risks

    PubMed Central

    Kabaria, Reena; Klaassen, Zachary; Terris, Martha K

    2016-01-01

    This review provides an overview of the incidence of renal cell carcinoma (RCC) and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses). The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. PMID:27022296

  5. Lupus vulgaris with squamous cell carcinoma.

    PubMed

    Motswaledi, Mojakgomo Hendrick; Doman, Chantal

    2007-12-01

    Tuberculosis is still a significant problem in developing countries. Cutaneous forms of tuberculosis account for approximately 10% of all cases of extrapulmonary tuberculosis. Cutaneous tuberculosis may be because of true infection with Mycobacterium tuberculosis or because of tuberculids. Tuberculids are immunological reactions to haematogenously spread antigenic components of M. tuberculosis. True cutaneous tuberculosis may be because of inoculation or haematogenous spread of M. tuberculosis to the skin. Lupus vulgaris is the commonest form of true cutaneous tuberculosis. Other forms of true cutaneous tuberculosis are tuberculous chancre, tuberculosis verrucosa cutis, scrofuloderma, periorificial tuberculosis and miliary tuberculosis of the skin. Lupus vulgaris is usually chronic and progressive. It occurs in patients with moderate to high immunity against M. tuberculosis as evidenced by strongly positive tuberculin test. Long-standing cases of lupus vulgaris may be complicated by squamous cell carcinoma (SCC). We describe a patient who had undiagnosed lupus vulgaris for 35 years until she developed SCC on the lesion of lupus vulgaris.

  6. Metabolic alterations in renal cell carcinoma.

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Brunelli, Matteo; Piva, Francesco; Modena, Alessandra; Bimbatti, Davide; Fantinel, Emanuela; Santini, Daniele; Cheng, Liang; Cascinu, Stefano; Montironi, Rodolfo; Tortora, Giampaolo

    2015-11-01

    Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies.

  7. Small Cell Carcinoma of the Gall Bladder.

    PubMed

    Haid, Max; Gahju, Badri; Schulz, Craig; Sterner, David; Falconer, Steven

    2016-04-01

    Small cell carcinoma of the gall bladder (SCCGB) is a rare condition, with only 53 prior cases reported in the world literature when our case was first diagnosed. Our patient was found to have limited stage disease and was treated with sequential laparoscopic cholecystectomy, etoposide/carboplatin chemotherapy followed by consolidating loco-regional radiation therapy. She is alive and well without evidence of disease more than 132 months since diagnosis. We describe here our experience in the diagnosis, staging workup, treatment, and surveillance of a case of SCCGB and review the published literature. Treated aggressively with currently available methods, patients with limited stage SCCGB can have an excellent prognosis. The authors' intent is to provide a reasonable plan of treatment for other physicians facing such an unusual patient. PMID:27197345

  8. Duodenal bleeding from metastatic renal cell carcinoma.

    PubMed

    Rustagi, Tarun; Rangasamy, Priya; Versland, Mark

    2011-04-20

    Massive upper gastrointestinal bleeding due to malignancy is relatively uncommon and the duodenum is the least frequently involved site. Duodenal metastasis is rare in renal cell carcinoma (RCC) and early detection, especially in case of a solitary mass, helps in planning further therapy. We report a case of intractable upper gastrointestinal bleeding from metastatic RCC to the duodenum. The patient presented with melena and anemia, 13 years after nephrectomy for RCC. On esophagogastroduodenoscopy, a submucosal mass was noted in the duodenum, biopsies of which revealed metastatic RCC. In conclusion, metastasis from RCC should be considered in nephrectomized patients presenting with gastrointestinal symptoms and a complete evaluation, especially endoscopic examination followed by biopsy, is suggested.

  9. Renal cell carcinoma: links and risks.

    PubMed

    Kabaria, Reena; Klaassen, Zachary; Terris, Martha K

    2016-01-01

    This review provides an overview of the incidence of renal cell carcinoma (RCC) and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses). The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. PMID:27022296

  10. Duodenal Bleeding from Metastatic Renal Cell Carcinoma

    PubMed Central

    Rustagi, Tarun; Rangasamy, Priya; Versland, Mark

    2011-01-01

    Massive upper gastrointestinal bleeding due to malignancy is relatively uncommon and the duodenum is the least frequently involved site. Duodenal metastasis is rare in renal cell carcinoma (RCC) and early detection, especially in case of a solitary mass, helps in planning further therapy. We report a case of intractable upper gastrointestinal bleeding from metastatic RCC to the duodenum. The patient presented with melena and anemia, 13 years after nephrectomy for RCC. On esophagogastroduodenoscopy, a submucosal mass was noted in the duodenum, biopsies of which revealed metastatic RCC. In conclusion, metastasis from RCC should be considered in nephrectomized patients presenting with gastrointestinal symptoms and a complete evaluation, especially endoscopic examination followed by biopsy, is suggested. PMID:21577373

  11. Sequential scintigraphic staging of small cell carcinoma

    SciTech Connect

    Bitran, J.D.; Bekerman, C.; Pinsky, S.

    1981-04-15

    Thirty patients with small cell carcinoma (SCC) of the lung were sequentially staged following a history and physical exam with liver, bran, bone, and gallium-67 citrate scans. Scintigraphic evaluation disclosed 7 of 30 patients (23%) with advanced disease, stage IIIM1. When Gallium-67 scans were used as the sole criteria for staging, they proved to be accurate and identified six of the seven patients with occult metastatic disease. Gallium-67 scans proved to be accurate in detecting thoracic and extrathoracic metastases in the 30 patients with SCC, especially within the liver and lymph node-bearing area. The diagnostic accuracy of gallium-67 fell in regions such as bone or brain. Despite the limitations of gallium-67 scanning, the authors conclude that these scans are useful in staging patients with SCC and should be the initial scans used in staging such patients.

  12. Retinoic acid receptor alpha mediates growth inhibition by retinoids in human colon carcinoma HT29 cells.

    PubMed

    Nicke, B; Kaiser, A; Wiedenmann, B; Riecken, E O; Rosewicz, S

    1999-08-11

    Although retinoids have been suggested to inhibit chemically induced colon carcinogenesis, the molecular mechanisms underlying retinoid-mediated growth regulation in colon carcinoma cells are unknown. Therefore, we investigated the biological effects of retinoids on growth in HT29 colon carcinoma cells. All-trans retinoic acid (ATRA) treatment of HT29 cells resulted in a profound inhibition of anchorage-independent growth without biochemical or morphological evidence for induction of differentiation. Treatment with the selective RARalpha agonist Ro 40-6055 completely mimicked the effects of ATRA on growth and transactivation of a betaRAREx2-luciferase reporter construct, while RARbeta- and gamma-specific analogues were ineffective. Furthermore, ATRA-regulated growth and transactivation could be completely blocked by a RARalpha-selective receptor antagonist. Thus, ATRA potently inhibits anchorage-independent growth in HT29 cells and this effect is mainly if not exclusively mediated by the retinoic acid receptor alpha.

  13. Odontogenic ghost cell carcinoma with pulmonary metastasis

    PubMed Central

    Sukumaran, Renu; Somanathan, Thara; Kattoor, Jayasree

    2015-01-01

    Odontogenic ghost cell carcinoma (OGCC) is an exceptionally rare malignant odontogenic epithelial tumor. It is characterized by ameloblastic-like islands of epithelial cells with aberrant keratinization in the form of ghost cells with varying amounts of dysplastic dentin. Malignant histological characteristics include infiltration, cellular pleomorphism, numerous mitosis and necrosis. Its biological behavior varies from slow-growing locally invasive lesions to rapidly growing highly aggressive tumors. OGCC metastasizing to distant sites is extremely rare. Only three cases of metastasis have been reported in literature. We are reporting the case of a 54-year-old male patient who presented with tender swelling in the malar region. Histopathological examination revealed OGCC and he received postoperative radiotherapy. Two years later, he presented with a lung mass. Biopsy from the lung lesion showed the same morphology as that of maxillary tumor with scattered ghost cells. This case points to the aggressive behavior of OGCC and its metastatic potential. It also highlights the need for long-term follow-up of these patients. PMID:26980967

  14. Sciatica leading to the discovery of a renal cell carcinoma

    PubMed Central

    Amine Lakmichi, Mohamed; Jarir, Redouane; Kabour, Jamal; Dahami, Zakaria; Said Moudouni, Mohamed; Sarf, Ismail

    2011-01-01

    Metastatic renal cell cancer is not exceptional in kidney cancer (30% of patients with kidneyl cancer). Its prognosis is particularly severe. However, sciatic neuralgia (sciatica) remains an exceptional revealing clinical sign of this disease. The authors report the case of a patient admitted with right sciatica as chief complain, leading to the discovery of a renal cell carcinoma. Although uncommon, renal cell carcinoma spine metastasis should be included in the differential diagnosis of back pain and sciatica. PMID:22355428

  15. Sciatica leading to the discovery of a renal cell carcinoma.

    PubMed

    Lakmichi, Mohamed Amine; Jarir, Redouane; Kabour, Jamal; Dahami, Zakaria; Said Moudouni, Mohamed; Sarf, Ismail

    2011-01-01

    Metastatic renal cell cancer is not exceptional in kidney cancer (30% of patients with kidneyl cancer). Its prognosis is particularly severe. However, sciatic neuralgia (sciatica) remains an exceptional revealing clinical sign of this disease. The authors report the case of a patient admitted with right sciatica as chief complain, leading to the discovery of a renal cell carcinoma. Although uncommon, renal cell carcinoma spine metastasis should be included in the differential diagnosis of back pain and sciatica.

  16. MANDIBULAR SQUAMOUS CELL CARCINOMA IN A BOBCAT (LYNX RUFUS).

    PubMed

    Sladakovic, Izidora; Burnum, Anne; Blas-Machado, Uriel; Kelly, Lisa S; Garner, Bridget C; Holmes, Shannon P; Divers, Stephen J

    2016-03-01

    A 23-yr-old female spayed bobcat (Lynx rufus) presented with a 1-wk history of hypersalivation. On examination, the right mandible was markedly thickened, the right mandibular dental arcade was missing, and the oral mucosa over the right mandible was ulcerated and thickened. Skull radiographs and fine needle aspirate cytology were supportive of squamous cell carcinoma. The bobcat was euthanized as a result of its poor prognosis. Necropsy confirmed a diagnosis of oral squamous cell carcinoma of the mandible. To the authors' knowledge, this is the first report of oral squamous cell carcinoma in a bobcat.

  17. MANDIBULAR SQUAMOUS CELL CARCINOMA IN A BOBCAT (LYNX RUFUS).

    PubMed

    Sladakovic, Izidora; Burnum, Anne; Blas-Machado, Uriel; Kelly, Lisa S; Garner, Bridget C; Holmes, Shannon P; Divers, Stephen J

    2016-03-01

    A 23-yr-old female spayed bobcat (Lynx rufus) presented with a 1-wk history of hypersalivation. On examination, the right mandible was markedly thickened, the right mandibular dental arcade was missing, and the oral mucosa over the right mandible was ulcerated and thickened. Skull radiographs and fine needle aspirate cytology were supportive of squamous cell carcinoma. The bobcat was euthanized as a result of its poor prognosis. Necropsy confirmed a diagnosis of oral squamous cell carcinoma of the mandible. To the authors' knowledge, this is the first report of oral squamous cell carcinoma in a bobcat. PMID:27010306

  18. Clear cell papillary renal cell carcinoma: a review.

    PubMed

    Kuroda, Naoto; Ohe, Chisato; Kawakami, Fumi; Mikami, Shuji; Furuya, Mitsuko; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Zhou, Ming; Petersson, Fredrik; López, José I; Hes, Ondrej; Michal, Michal; Amin, Mahul B

    2014-01-01

    The disease concept of clear cell (tubulo) papillary renal cell carcinoma (CCP-RCC) as a distinct subtype of renal cell carcinoma has been recently established. First described in the setting of end stage renal disease, this tumor type is more frequently recognized and encountered in a sporadic setting. In this article, we provide an overview of the recent understanding of this tumor. Macroscopically, tumors are well circumscribed with well-developed tumor capsule. Histologically, the tumor cells are cuboidal to low columnar cell with clear cytoplasm and papillary and tubulo-papillary configuration. Immunohistochemically, tumor cells generally show diffuse expression for cytokeratin 7, CA9 (cup-shaped pattern), HIF-1, GLUT-1 and high molecular weight cytokeratin, but negative for AMACR, RCC Ma and TFE3. CD10 is negative or focally positive in most tumors. Genetically, this tumor has no characteristics of clear cell RCC or papillary RCC. Prognostically, patients with CCP-RCC behave in an indolent fashion in all previously reported cases. In conclusion, although this tumor has been integrated into recent International Society of Urologic Pathology Classification of renal neoplasia, both aspects of disease concept and clinical behavior are yet to be fully elucidated. Further publications of large cohorts of patients will truly help understand the biologic potential and the molecular underpinnings of this tumor type. PMID:25550767

  19. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids

    PubMed Central

    Batchelder, Cynthia A.; Martinez, Michele L.; Duru, Nadire; Meyers, Frederick J.; Tarantal, Alice F.

    2015-01-01

    Renal cell carcinomas arise from the nephron but are heterogeneous in disease biology, clinical behavior, prognosis, and response to systemic therapy. Development of patient-specific in vitro models that efficiently and faithfully reproduce the in vivo phenotype may provide a means to develop personalized therapies for this diverse carcinoma. Studies to maintain and model tumor phenotypes in vitro were conducted with emerging three-dimensional culture techniques and natural scaffolding materials. Human renal cell carcinomas were individually characterized by histology, immunohistochemistry, and quantitative PCR to establish the characteristics of each tumor. Isolated cells were cultured on renal extracellular matrix and compared to a novel polysaccharide scaffold to assess cell-scaffold interactions, development of organoids, and maintenance of gene expression signatures over time in culture. Renal cell carcinomas cultured on renal extracellular matrix repopulated tubules or vessel lumens in renal pyramids and medullary rays, but cells were not observed in glomeruli or outer cortical regions of the scaffold. In the polysaccharide scaffold, renal cell carcinomas formed aggregates that were loosely attached to the scaffold or free-floating within the matrix. Molecular analysis of cell-scaffold constructs including immunohistochemistry and quantitative PCR demonstrated that individual tumor phenotypes could be sustained for up to 21 days in culture on both scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures. The use of three-dimensional scaffolds to engineer a personalized in vitro renal cell carcinoma model provides opportunities to advance understanding of this disease. PMID:26317980

  20. Detection of squamous carcinoma cells using gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Dai, Wei-Yun; Lee, Sze-tsen; Hsu, Yih-Chih

    2015-03-01

    The goal of this study is to use gold nanoparticle as a diagnostic agent to detect human squamous carcinoma cells. Gold nanoparticles were synthesized and the gold nanoparticle size was 34.3 ± 6.2 nm. Based on the over-expression of epidermal growth factor receptor (EGFR) biomarkers in squamous carcinoma cells, we hypothesized that EGFR could be a feasible biomarker with a target moiety for detection. We further modified polyclonal antibodies of EGFR on the surface of gold nanoparticles. We found selected squamous carcinoma cells can be selectively detected using EGFR antibody-modified gold nanoparticles via receptor-mediated endocytosis. Cell death was also examined to determine the survival status of squamous carcinoma cells with respect to gold nanoparticle treatment and EGFR polyclonal antibody modification.

  1. Serum Gamma-Glutamyl-Transferase Independently Predicts Outcome After Transarterial Chemoembolization of Hepatocellular Carcinoma: External Validation

    SciTech Connect

    Guiu, Boris Deschamps, Frederic; Boulin, Mathieu; Boige, Valerie; Malka, David; Ducreux, Michel; Hillon, Patrick; Baere, Thierry de

    2012-10-15

    Purpose: An Asian study showed that gamma glutamyl transpeptidase (GGT) can predict survival after transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). This study was designed to validate in a European population this biomarker as an independent predictor of outcome after TACE of HCC and to determine a threshold value for clinical use. Methods: In 88 consecutive patients treated by TACE for HCC, the optimal threshold for GGT serum level was determined by a ROC analysis. Endpoints were time-to-treatment failure (TTTF) and overall survival (OS). All multivariate models were internally validated using bootstrapping (90 replications). Results: Median follow-up lasted 373 days, and median overall survival was 748 days. The optimal threshold for GGT was 165 U/L (sensitivity: 89.3%; specificity: 56.7%; area under the ROC curve: 0.7515). Median TTTF was shorter when GGT was {>=}165 U/L (281 days vs. 850 days; P < 0.001). GGT {>=}165 U/L (hazard ratio (HR) = 2.06; P = 0.02), WHO PS of 2 (HR = 5.4; P = 0.002), and tumor size (HR = 1.12; P = 0.014) were independently associated with shorter TTTF. Median OS was shorter when GGT was {>=}165 U/L (508 days vs. not reached; P < 0.001). GGT {>=} 165 U/L (HR = 3.05; P = 0.029), WHO PS of 2 (HR = 12.95; P < 0.001), alfa-fetoprotein (HR = 2.9; P = 0.01), and tumor size (HR = 1.096; P = 0.013) were independently associated with shorter OS. The results were confirmed by bootstrapping. Conclusions: Our results provide in a European population the external validation of GGT as an independent predictor of outcome after TACE of HCC. A serum level of GGT {>=} 165 U/L is independently associated with both shorter TTTF and OS.

  2. Metabolic signatures of renal cell carcinoma.

    PubMed

    Lim, Hwee Ying; Yip, Yin Mun; Chiong, Edmund; Tiong, Ho Yee; Halliwell, Barry; Esuvaranathan, Kesavan; Wong, Kim Ping

    2015-05-15

    Clear cell renal cell carcinoma (ccRCC) is characterized by the constitutive up-regulation of the hypoxia inducible factor-1. One of its target enzymes, pyruvate dehydrogenase (PDH) kinase 1 (PDHK1) showed increased protein expression in tumor as compared to patient-matched normal tissues. PDHK1 phosphorylated and inhibited PDH whose enzymatic activity was severely diminished, depriving the TCA cycle of acetylCoA. We and others have shown a decrease in the protein expressions of all respiratory complexes alluding to a compromise in oxidative phosphorylation (OXPHOS). On the contrary, we found that key parameters of OXPHOS, namely ATP biosynthesis and membrane potential were consistently measurable in mitochondria isolated from ccRCC tumor tissues. Interestingly, an endogenous mitochondrial membrane potential (MMP) was evident when ADP was added to mitochondria isolated from ccRCC but not in normal tissues. In addition, the MMP elicited in the presence of ADP by respiratory substrates namely malate/glutamate, succinate, α-ketoglutarate and isocitrate was invariably higher in ccRCC. Two additional hallmarks of ccRCC include a loss of uncoupling protein (UCP)-2 and an increase in UCP-3. Based on our data, we proposed that inhibition of UCP3 by ADP could contribute to the endogenous MMP observed in ccRCC and other cancer cells. PMID:25839656

  3. Bone Metastasis from Renal Cell Carcinoma.

    PubMed

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The "vicious cycle" hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

  4. Bone Metastasis from Renal Cell Carcinoma

    PubMed Central

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The “vicious cycle” hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

  5. Basal Cell Carcinoma. Part 1: Basal Cell Carcinoma Has Come of Age.

    PubMed

    Deng, Min; Marsch, Amanda F; Petronic-Rosic, Vesna

    2015-01-01

    Almost 2 centuries after its recognition, basal cell carcinoma (BCC) remains the most common cancer worldwide, with a 30% overall lifetime risk in the United States and an incidence that continues to increase annually. The increasing incidence of BCC is multifactorial and likely correlates to multiple risk factors, including exposure to both ionizing and UV radiation. Despite its relatively indolent growth, what was once referred to as a rodent ulcer or basal cell epithelioma is now identified as a full-fledged malignancy. The authors describe the societal burden of this disease and characterize its malignant potential, emphasizing associated clinical and histopathologic prognostic features. PMID:26380507

  6. Sorafenib Tosylate, Cisplatin, and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2016-07-27

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  7. Squamous cell carcinoma of the nasal vestibule.

    PubMed

    Horsmans, J D; Godballe, C; Jørgensen, K E; Bastholt, L; Løntoft, E

    1999-09-01

    From 1978 to 1992, 66 patients (32 women and 34 men) were treated for carcinoma of the nasal vestibule at Odense University Hospital. The treatment was radiotherapy (41 patients), surgery (13 patients) or a combination of the two modalities (12 patients). Twenty-one patients (32%) developed recurrence. Of these, 17 (81%) were diagnosed within the first two years of follow up. The recurrence rate was found to be correlated to the anatomic site of the tumour-origin; septal site of origin meant higher risk of recurrence. Five-year disease specific and crude survival of all patients were 87.0% and 58.5%, respectively. Several variables (sex, age, anatomic site of origin, Wang-classification, tumour volume and regional lymphnode metastases at time of diagnosis) were evaluated as possible prognostic indicators. In univariate analysis, regional lymph node metastases at the time of diagnosis and anatomic site of origin of the tumour showed a significant influence on survival. In multivariate analysis, septal origin of primary tumour was a significant, independent predictive factor of recurrence and the presence of lymph node metastases at the time of diagnosis showed to be a highly significant prognosticator of both disease specific and crude survival (p < 0.0001). We conclude that patients with primary lymph node metastases and septal location of primary tumour need intensive primary treatment and close follow up. PMID:10567990

  8. Carcinoma in basal cell adenoma of the parotid gland.

    PubMed

    Nagao, T; Sugano, I; Ishida, Y; Matsuzaki, O; Konno, A; Kondo, Y; Nagao, K

    1997-01-01

    Malignant transformation of basal cell adenoma (BCA) of the parotid gland is rarely reported, and when occurred, may principally become manifest as a malignant basaloid tumor, i.e. basal cell adenocarcinoma or adenoid cystic carcinoma. We describe herein three cases of non-basaloid carcinoma arising in BCA. The incidence of this malignant tumor was 0.2% of all parotid gland tumors and 4.3% of BCAs in our series. One case was salivary duct carcinoma showing histologic evidence of transition between malignant and benign elements. The remaining two cases were well-encapsulated parotid gland tumors, which were composed of BCA and scattered foci of malignant transformation. Malignant components were adenocarcinoma, not otherwise specified (NOS), and sometimes intermixed with neoplastic myoepithelial cells included BCA cells. These two cases were regarded to be intracapsular carcinoma in BCA. BCA components showed solid, tubular and trabecular arrangements. The patients' prognosis was quite variable among these three cases; the first case died of disease after 27 months, whereas the latter two cases are alive and well for 4 and 10 years after surgery. Ki-67 labeling index indicated that cell proliferative activity was at least five times higher in carcinomas than BCAs. Non-basaloid carcinomas such as salivary duct carcinoma or adenocarcinoma, NOS, do develop in BCAs as in the case of a pleomorphic adenoma with malignant transformation, though the incidence may be extremely rare.

  9. Spindle cell carcinoma of the esophagus: A multicenter analysis in comparison with typical squamous cell carcinoma.

    PubMed

    Zhang, Baihua; Xiao, Qin; Yang, Desong; Li, Xu; Hu, Jun; Wang, Yonggang; Wang, Wenxiang

    2016-09-01

    This study conducted a retrospective multicenter analysis to investigate the clinicopathological features, optimal therapeutic strategy, and prognosis of spindle cell carcinoma (SpCC) of the esophagus.A total of 71 patients with esophageal SpCC from 3 large cancer centers in China were systematically analyzed. All patients received curative resection, 13 patients received adjuvant radiotherapy and 15 patients received adjuvant combination chemotherapy. Additionally, a total of 1852 patients with typical esophageal SCC (SCC) were selected as controls in this study.SpCC mostly presented as a polypoid appearance (66.2%), and the surrounding mucosa showed high-grade hyperplasia or superficial SCC in 31 cases (43.7%). Two patients even had extensive carcinoma in situ that spread to the resection margins. Patients in the SpCC group were more likely to present with stage I lesions compared with those in the typical SCC group (33.8% vs 8.0%, P < 0.001). Although the percentage of T1/2 lesions was higher in the SpCC group than in the typical SCC group (67.6% vs 29.7%, P < 0.001), both groups had similar rates of locoregional lymphatic metastases (45.1% vs 48.4%, P = 0.578). The median survival time and 5-year overall survival of the SpCC group was 43 months and 44.8%, respectively, higher than 37.5 months and 38.3%, respectively, for the typical SCC group (P = 0.044). In univariate analysis, the macroscopical type and pathological T, N, and TNM stages had a statistically significant impact on the prognosis of SpCC after curative resection. However, only the TNM stage (hazard ratio, 2.708; 95% confidence interval, 1.786-4.105, P < 0.001) was identified as an independent prognostic factor in multivariate analysis. The 5-year OS of SpCC in stages I (79.8%) and II (39.7%) were significantly longer than that of stages III/IV (16.2%) (P < 0.001 and P = 0.012). As those SpCC cases that received chemoradiotherapy were in more advanced stages, their

  10. Expression of membrane glycoproteins in normal keratinocytes and squamous carcinoma cell lines

    SciTech Connect

    Rayter, Z. ); McIlhinney, R. ); Gusterson, B. )

    1989-08-01

    Con A acceptor glycoproteins were analyzed by 2D-PAGE and {sup 125}I-Con A overlay in three squamous carcinoma cell lines and compared with those in the simian virus (SV40)-transformed keratinocyte cell line SVK-14 and in normal keratinocytes. The majority of the glycoproteins identified by this technique were expressed at similar levels in all of the cells examined, independent of the culture conditions used. A cell surface glycoprotein gp34 was increased in the tumor cells compared with normal keratinocytes and expression varied with the culture density. Another glycoprotein, gp21, was found to be increased in expression in normal keratinocytes and stratified hyperconfluent cultures of squamous carcinoma cell lines. This paper describes the potential of this technique to identify membrane glycoproteins which may be expressed as a function of proliferation or differentiation.

  11. Uterine Clear Cell Carcinoma of Postmenopausal Woman: A Case Report.

    PubMed

    Chung, Soo-Ho; Park, Jung-Woo

    2016-08-01

    Endometrial cancer is the most common gynecologic malignancy in developed countries. Clear cell carcinoma typically occurs in the ovaries, and very rarely occurs in the endometrium; it accounts for less than 3% of all endometrial cancers. It is presumed that clear cell carcinomas are of Müllerian duct origin, and an association with exposure to diethylstilbestrol (DES) or other nonsteroidal follicle stimulating hormones has been described. We report a case of a postmenopausal woman who presented with vaginal bleeding without a specific medical history. Under the impression of an endometrial mass, we performed a laparoscopic operation. Pathologic results showed clear cell carcinoma of the endometrium. Depth of invasion was 0.2 cm out of a 0.5 cm total thickness, and the rectal shelf mass was clear cell carcinoma. We report the case with a brief review of the relevant literature. PMID:27617248

  12. Uterine Clear Cell Carcinoma of Postmenopausal Woman: A Case Report

    PubMed Central

    Chung, Soo-Ho

    2016-01-01

    Endometrial cancer is the most common gynecologic malignancy in developed countries. Clear cell carcinoma typically occurs in the ovaries, and very rarely occurs in the endometrium; it accounts for less than 3% of all endometrial cancers. It is presumed that clear cell carcinomas are of Müllerian duct origin, and an association with exposure to diethylstilbestrol (DES) or other nonsteroidal follicle stimulating hormones has been described. We report a case of a postmenopausal woman who presented with vaginal bleeding without a specific medical history. Under the impression of an endometrial mass, we performed a laparoscopic operation. Pathologic results showed clear cell carcinoma of the endometrium. Depth of invasion was 0.2 cm out of a 0.5 cm total thickness, and the rectal shelf mass was clear cell carcinoma. We report the case with a brief review of the relevant literature.

  13. Uterine Clear Cell Carcinoma of Postmenopausal Woman: A Case Report

    PubMed Central

    Chung, Soo-Ho

    2016-01-01

    Endometrial cancer is the most common gynecologic malignancy in developed countries. Clear cell carcinoma typically occurs in the ovaries, and very rarely occurs in the endometrium; it accounts for less than 3% of all endometrial cancers. It is presumed that clear cell carcinomas are of Müllerian duct origin, and an association with exposure to diethylstilbestrol (DES) or other nonsteroidal follicle stimulating hormones has been described. We report a case of a postmenopausal woman who presented with vaginal bleeding without a specific medical history. Under the impression of an endometrial mass, we performed a laparoscopic operation. Pathologic results showed clear cell carcinoma of the endometrium. Depth of invasion was 0.2 cm out of a 0.5 cm total thickness, and the rectal shelf mass was clear cell carcinoma. We report the case with a brief review of the relevant literature. PMID:27617248

  14. Multi-Target Approach to Metastatic Adrenal Cell Carcinoma.

    PubMed

    Wahab, Norasyikin A; Zainudin, Suehazlyn; AbAziz, Aini; Mustafa, Norlaila; Sukor, Norlela; Kamaruddin, Nor Azmi

    2016-09-01

    Adrenal cell carcinoma is a rare tumor and more than 70% of patients present with advanced stages. Adrenal cell carcinoma is an aggressive tumor with a poor prognosis. Surgical intervention is the gold standard treatment and mitotane is the only drug approved for the treatment of adrenal cell carcinoma. Until recently in 2012, the etoposide, doxorubicin, cisplatin plus mitotane are approved as first-line therapy based on response rate and progression-free survival. This case illustrates a case of advanced adrenal cell carcinoma in a young girl who presented with huge adrenal mass with inferior vena cava thrombosis and pulmonary embolism. Multi-approach of therapy was used to control the tumor size and metastasis. Therefore, it may prolong her survival rate for up to 5 years and 4 months. PMID:27631184

  15. Recent advances in the management of renal cell carcinoma

    PubMed Central

    Molina, Ana M.; Nanus, David M.

    2016-01-01

    Therapeutic options for patients with metastatic renal cell carcinoma have significantly improved over the past few years with the recent approval of two new agents resulting in prolonged progression-free and overall survival. PMID:27019698

  16. Nevoid basal cell carcinoma syndrome (Gorlin syndrome).

    PubMed

    Lo Muzio, Lorenzo

    2008-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5-10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  17. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    PubMed Central

    Lo Muzio, Lorenzo

    2008-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  18. Heparanase expression and glycosaminoglycans profile in renal cell carcinoma.

    PubMed

    Batista, Lucas Teixeira E Aguiar; Matos, Leandro Luongo; Machado, Leopoldo Ruiz; Suarez, Eloah Rabello; Theodoro, Thérèse Rachell; Martins, João Roberto Maciel; Nader, Helena Bonciani; Pompeo, Antonio Carlos Lima; Pinhal, Maria Aparecida da Silva

    2012-11-01

    A better understanding of the molecular mechanisms of renal cell carcinogenesis could contribute to a decrease in the mortality rate of this disease. The aim of this study was to evaluate the glycosaminoglycans profile and heparanase expression in renal cell carcinoma. The study included 24 patients submitted to nephrectomy with confirmed pathological diagnosis of renal cell carcinoma. The majority of the samples (87.5%) were classified in the initial stage of renal cell carcinoma (clinical stages I and II). Heparanase messenger ribonucleic acid expression was evaluated by quantitative real-time reverse transcription polymerase chain reaction, and sulfated glycosaminoglycans were identified and quantified by agarose gel electrophoresis of renal cell carcinoma samples or non-neoplastic tissues obtained from the same patients (control group). The sulfated glycosaminoglycans and hyaluronic acid were analyzed in urine samples of the patients before and after surgery. The data showed a significant statistical increase in chondroitin sulfate, and a decrease in heparan sulfate and dermatan sulfate present in neoplastic tissues compared with non-neoplastic tissues. Higher heparanase messenger ribonucleic acid expression in the neoplastic tissues was also shown, compared with the non-neoplastic tissues. The urine glycosaminoglycans profile showed no significant difference between renal cell carcinoma and control samples. Extracellular matrix changes observed in the present study clarify that heparanase is possibly involved with heparan sulfate turnover, and that heparanase and the glycosaminoglycans can modulate initial events of renal cell carcinoma development.

  19. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-10-28

    Head and Neck Squamous Cell Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  20. Delayed recurrence of renal cell carcinoma presenting as a haemorrhoid

    PubMed Central

    Davies, James R.L.; Smith, Gavin; Cornaby, Andrew J.; Thomas, Teresa; Lamparelli, Michael J.

    2015-01-01

    Metastatic non-colorectal cancer of the anal canal is a rare entity. To date, only four cases have been described in the literature. We present a 76-year-old man who was referred with an unusual perianal lesion. He had a history of renal cell carcinoma 7 years previously. Histologically, the lesion revealed clear cell carcinoma in keeping with metastasis. To our knowledge, this is only the second time a renal carcinoma metastasis to the anal canal has been identified. PMID:25818654

  1. Digital necrosis with squamous cell carcinoma of the tonsil

    PubMed Central

    Warrier, Vinod; Ahmad, Ali; Alshatti, Yaqoub; Jafar, Ali

    2016-01-01

    Background Digital necrosis is a rare phenomenon of paraneoplastic syndrome associated with squamous cell carcinoma of the tonsil. Since 1965, more than 70 cases have been reported worldwide in the literature. Case report A 54-year-old male smoker presented with Raynaud’s phenomenon, proceeding to frank gangrene of the fingers. Working up the case finally pointed toward carcinoma of the tonsil as the underlying cause – a rare paraneoplastic manifestation. Conclusion No definite etiology has been found to be the cause of Raynaud’s phenomenon in this case of the squamous cell carcinoma of the tonsil. A brief discussion of the literature is also presented. PMID:27390535

  2. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2016-10-12

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  3. Wnt Signaling in Renal Cell Carcinoma

    PubMed Central

    Xu, Qi; Krause, Mirja; Samoylenko, Anatoly; Vainio, Seppo

    2016-01-01

    Renal cell carcinoma (RCC) accounts for 90% of all kidney cancers. Due to poor diagnosis, high resistance to the systemic therapies and the fact that most RCC cases occur sporadically, current research switched its focus on studying the molecular mechanisms underlying RCC. The aim is the discovery of new effective and less toxic anti-cancer drugs and novel diagnostic markers. Besides the PI3K/Akt/mTOR, HGF/Met and VHL/hypoxia cellular signaling pathways, the involvement of the Wnt/β-catenin pathway in RCC is commonly studied. Wnt signaling and its targeted genes are known to actively participate in different biological processes during embryonic development and renal cancer. Recently, studies have shown that targeting this pathway by alternating/inhibiting its intracellular signal transduction can reduce cancer cells viability and inhibit their growth. The targets and drugs identified show promising potential to serve as novel RCC therapeutics and prognostic markers. This review aims to summarize the current status quo regarding recent research on RCC focusing on the involvement of the Wnt/β-catenin pathway and how its understanding could facilitate the identification of potential therapeutic targets, new drugs and diagnostic biomarkers. PMID:27322325

  4. Pulmonary Large-Cell Neuroendocrine Carcinoma

    PubMed Central

    Fasano, Morena; Della Corte, Carminia Maria; Papaccio, Federica; Ciardiello, Fortunato

    2015-01-01

    Lung neuroendocrine tumors are a heterogeneous subtype of pulmonary cancers representing approximately 20% of all lung cancers, including small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). The frequency appears to be approximately 3% for LCNEC. Diagnosis of LCNEC requires attention to neuroendocrine features by light microscopy and confirmation by immunohistochemical staining for neuroendocrine markers. Both SCLC and pulmonary LCNEC are high-grade and poor-prognosis tumors, with higher incidence in males and smokers and peripheral localization. LCNEC is very rare, and the precise diagnosis on small specimens is very difficult, so we have still too few data to define a standard of treatment for pulmonary LCNECs. Data of literature, most based on retrospective analysis, indicated a poor 5-year overall survival, with a high incidence of recurrence after surgery, even in stage I disease. Primary surgery should be the first option in all operable patients because there is no validate therapeutic approach for LCNEC due to lack of clinical trials in this setting. Neoadjuvant platinum-based regimens remain only an option for potentially resectable tumors. In advanced stages, SCLC-like chemotherapy seems the best option of treatment, with a good response rate but a poor overall survival (from 8 to 16 months in different case series). New agents are under clinical investigation to improve LCNEC patients’ outcome. We reviewed all data on treatment options feasible for pulmonary LCNEC, both for localized and extensive disease. PMID:26039012

  5. Mutational Analysis of Merkel Cell Carcinoma

    PubMed Central

    Erstad, Derek J.; Cusack, James C.

    2014-01-01

    Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy that is associated with a poor prognosis. The pathogenesis of MCC is not well understood, and despite a recent plethora of mutational analyses, we have yet to find a set of signature mutations implicated in the majority of cases. Mutations, including TP53, Retinoblastoma and PIK3CA, have been documented in subsets of patients. Other mechanisms are also likely at play, including infection with the Merkel cell polyomavirus in a subset of patients, dysregulated immune surveillance, epigenetic alterations, aberrant protein expression, posttranslational modifications and microRNAs. In this review, we summarize what is known about MCC genetic mutations and chromosomal abnormalities, and their clinical significance. We also examine aberrant protein function and microRNA expression, and discuss the therapeutic and prognostic implications of these findings. Multiple clinical trials designed to selectively target overexpressed oncogenes in MCC are currently underway, though most are still in early phases. As we accumulate more molecular data on MCC, we will be better able to understand its pathogenic mechanisms, develop libraries of targeted therapies, and define molecular prognostic signatures to enhance our clinicopathologic knowledge. PMID:25329450

  6. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma.

    PubMed

    Torres, T; Fernandes, I; Costa, V; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  7. BASAL CELL CARCINOMA OF THE NOSE—Treatment with Chemosurgery

    PubMed Central

    Beirne, Gilbert A.; Beirne, Clinton G.

    1956-01-01

    Basal cell carcinomas of the nose probably originate from embryologic cell rests left between cartilages and bones in the fusion and migration of the nasal precursors. Some carcinomas have been found to invade to the mucosal surface between subcutaneous structures or around the alar margins. Recurrences are particularly likely to develop deep extensions due to overlying scar tissue. In many cases, chemosurgical removal has disclosed unsuspected deep and lateral extensions. It is the treatment method of choice for many such lesions. PMID:13276824

  8. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    PubMed Central

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  9. Genomic Heterogeneity of Translocation Renal Cell Carcinoma

    PubMed Central

    Couturier, Jérôme; Molinié, Vincent; Escudier, Bernard; Camparo, Philippe; Su, Xiaoping; Yao, Hui; Tamboli, Pheroze; Lopez-Terrada, Dolores; Picken, Maria; Garcia, Marileila; Multani, Asha S.; Pathak, Sen; Wood, Christopher G.; Tannir, Nizar M.

    2013-01-01

    Purpose Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity. Experimental design Cytogenomic analysis was performed with 250K single-nucleotide polymorphism microarrays on 16 tumor specimens and 4 cell lines. LINE-1 methylation, a surrogate marker of DNA methylation, was performed on 27 cases using pyrosequencing. Results tRCC showed cytogenomic heterogeneity, with 31.2% and 18.7% of cases presenting similarities with clear-cell and papillary RCC profiles, respectively. The most common alteration was a 17q gain in 7 tumors (44%), followed by a 9p loss in 6 cases (37%). Less frequent were losses of 3p and 17p in 5 cases (31%) each. Patients with 17q gain were older (P = 0.0006), displayed more genetic alterations (P < 0.003) and had a worse outcome (P = 0.002) than patients without it. Analysis comparing gene-expression profiling of a subset of tumors bearing 17q gain and those without suggest large scale dosage effects and TP53 haploinsufficiency without any somatic TP53 mutation identified. Cell-line based cytogenetic studies revealed that 17q gain can be related to isochromosome 17 and/or to multiple translocations occurring around 17q breakpoints. Finally, LINE-1 methylation was lower in tRCC tumors from adults compared to tumors from young patients (71.1% vs. 76.7%, P = 0.02). Conclusions Our results reveal genomic heterogeneity of tRCC with similarities to other renal tumor subtypes and raise important questions about the role of TFEB/TFE3 translocations and other chromosomal imbalances in tRCC biology. PMID:23817689

  10. [Basal cell carcinoma. Molecular genetics and unusual clinical features].

    PubMed

    Reifenberger, J

    2007-05-01

    Basal cell carcinoma is the most common human cancer. Its incidence is steadily increasing. The development of basal cell carcinoma is linked to genetic factors, including the individual skin phototype, as well as the cumulative exposure to UVB. The vast majority of basal cell carcinomas are sporadic tumors, while familial cases associated with certain hereditary syndromes are less common. At the molecular level, basal cell carcinomas are characterized by aberrant activation of sonic hedgehog signaling, usually due to mutations either in the ptch or smoh genes. In addition, about half of the cases carry mutations in the tp53 tumor suppressor gene, which are often UVB-associated C-->T transition mutations. Clinically, basal cell carcinomas may show a high degree of phenotypical variability. In particular, tumors occurring in atypical locations, showing an unusual clinical appearance, or imitating other skin diseases may cause diagnostic problems. This review article summarizes the current state of the art concerning the etiology, predisposition and molecular genetics of basal cell carcinoma. In addition, examples of unusual clinical manifestations are illustrated. PMID:17440702

  11. Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-08

    Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

  12. Clear Cell Renal Cell Carcinoma With Borderline Features of Clear Cell Papillary Renal Cell Carcinoma: Combined Morphologic, Immunohistochemical, and Cytogenetic Analysis.

    PubMed

    Williamson, Sean R; Gupta, Nilesh S; Eble, John N; Rogers, Craig G; Michalowski, Susan; Zhang, Shaobo; Wang, Mingsheng; Grignon, David J; Cheng, Liang

    2015-11-01

    Clear cell papillary renal cell carcinoma is increasingly recognized as a distinct tumor with unique morphology, immunohistochemistry, and cytogenetics. Histopathology often mimics clear cell renal cell carcinoma; however, metastasis has not been reported, emphasizing the clinical value of recognizing these likely nonaggressive tumors. We studied tumors with borderline morphology of clear cell papillary renal cell carcinoma, utilizing immunohistochemistry and fluorescence in situ hybridization or karyotyping. Tumors from 22 patients (ages 33 to 82 y) were analyzed. Clear cell papillary renal cell carcinoma-like morphology varied from 10% to 90% of the tumor (median 25%). Sources of resemblance included: branched glands (95%), nuclear alignment (68%), small papillary tufts (32%), focal branching papillae (27%), and prominent papillary structures (9%). Carbonic anhydrase IX uniformly revealed diffuse positivity. Staining for cytokeratin 7 (CK7) was focal (64%) or negative (18%) in most tumors (82%); however, >50% labeling was present in 4 (18%). Reactivity for both CD10 and α-methyl-acyl-CoA-racemase (AMACR) was usually present (median 80% and 60% of cells). Seven tumors showed reactivity for high-molecular weight keratin (32%). Chromosome 3p loss was confirmed in 15 tumors (68%), including 4/7 with labeling for high-molecular weight keratin or >50% reactivity for CK7. A discordant immunohistochemical pattern typically correlates with loss of material from chromosome 3p in tumors with incomplete morphology of clear cell papillary renal cell carcinoma, supporting classification as clear cell renal cell carcinoma. Diffuse labeling for CK7 can uncommonly be observed in clear cell renal cell carcinomas confirmed to have chromosome 3p loss, although these do not exhibit the expected staining pattern of clear cell papillary renal cell carcinoma, including positivity for CD10 and AMACR. PMID:26457355

  13. Thioredoxin reductase: A novel, independent prognostic marker in patients with hepatocellular carcinoma

    PubMed Central

    Li, Chunyan; Peng, Yan; Mao, Binglang; Qian, Kun

    2015-01-01

    Here we found that hepatocellular carcinoma (HCC) patients with recurrence outcome and nonsurvivors had significantly increased thioredoxin reductase (TrxR) serum levels on reoperation (P < 0.0001 and P < 0.0001). Multivariate regression analysis adjusted for common risk factors showed that TrxR was an independent predictor of recurrence (hazard ratios [HR] = 4.19; 95% confidence intervals [CI]: 3.21–7.08) and overall survival (HR = 5.56; 95% CI: 3.42–10.21). The area under the receiver operating characteristic curve of TrxR was 0.837 (95% CI, 0.794–0.881) for recurrence outcome and 0.901 (95% CI, 0.869–0.933) for mortality, which was superior to high-sensitivity-C-reactive protein and a-fetoprotein (P < 0.001). The preoperative serum TrxR level is an independent and significant indicator predictive of poor prognosis and early recurrence in patients with HCC, which offering reliable information for predicting survival. PMID:25970775

  14. (1)H NMR metabolomics analysis of renal cell carcinoma cells: Effect of VHL inactivation on metabolism.

    PubMed

    Cuperlovic-Culf, Miroslava; Cormier, Kevin; Touaibia, Mohamed; Reyjal, Julie; Robichaud, Sarah; Belbraouet, Mehdi; Turcotte, Sandra

    2016-05-15

    Von Hippel-Lindau (VHL) is an onco-suppressor involved in oxygen and energy-dependent promotion of protein ubiquitination and proteosomal degradation. Loss of function mutations of VHL (VHL-cells) result in organ specific cancers with the best studied example in renal cell carcinomas. VHL has a well-established role in deactivation of hypoxia-inducible factor (HIF-1) and in regulation of PI3K/AKT/mTOR activity. Cell culture metabolomics analysis was utilized to determined effect of VHL and HIF-1α or HIF-2α on metabolism of renal cell carcinomas (RCC). RCC cells were stably transfected with VHL or shRNA designed to silence HIF-1α or HIF-2α genes. Obtained metabolic data was analysed qualitatively, searching for overall effects on metabolism as well as quantitatively, using methods developed in our group in order to determine specific metabolic changes. Analysis of the effect of VHL and HIF silencing on cellular metabolic footprints and fingerprints provided information about the metabolic pathways affected by VHL through HIF function as well as independently of HIF. Through correlation network analysis as well as statistical analysis of significant metabolic changes we have determined effects of VHL and HIF on energy production, amino acid metabolism, choline metabolism as well as cell regulation and signaling. VHL was shown to influence cellular metabolism through its effect on HIF proteins as well as by affecting activity of other factors.

  15. Selective toxicity of rhodamine 123 in carcinoma cells in vitro.

    PubMed

    Lampidis, T J; Bernal, S D; Summerhayes, I C; Chen, L B

    1983-02-01

    The study of mitochondria in situ has recently been facilitated through the use of rhodamine 123, a mitochondrial-specific fluorescent dye. It has been found to be nontoxic when applied for short periods to a variety of cell types and has thus become an invaluable tool for examining mitochondrial morphology and function in the intact living cell. In this report, however, we demonstrate that with continuous exposure, rhodamine 123 selectively kills carcinoma as compared to normal epithelial cells grown in vitro. At doses of rhodamine 123 which were toxic to carcinoma cells, the conversion of mitochondrial-specific to cytoplasmic-nonspecific localization of the drug was observed prior to cell death. At 10 microgram/ml, greater than 50% cell death occurred within 7 days in all nine of the carcinoma cell types and lines of different origin studied, while six of six normal epithelial cell types and lines remained unaffected. Cotreating carcinoma cells with 2-deoxyglucose and rhodamine 123 enhanced the inhibition of growth by rhodamine 123 alone in clonogenic survival assays. The observation of the selective toxicity of rhodamine 123 appears to be unique in view of the absence of selective toxicity reported in vitro for the various antitumor agents currently in clinical use. Preliminary results with rhodamine 123 in animal tumor systems indicate antitumor activity for carcinomas.

  16. Alveolar-cell carcinoma: a problem in sputum cytodiagnosis.

    PubMed Central

    Spriggs, A I; Cole, M; Dunnill, M S

    1982-01-01

    Cytology and histology are correlated in a series of 22 cases chosen to illustrate the differential diagnosis between clusters of benign bronchial or bronchiolar cells seen in sputum, and those of alveolar cell carcinoma or adenocarcinoma with alveolar spread. Alveolar-cell carcinoma is characterised by clusters of small epithelial cells in spherical or irregular formations, none showing enough polarity to distinguish a smooth or palisaded surface. The appearances are most distinctive if vacuolation is absent. The diagnosis cannot, however, be confidently made in all cases from morphological features of cells in sputum. Images PMID:6294147

  17. Renal cell carcinoma in tuberous sclerosis complex.

    PubMed

    Yang, Ping; Cornejo, Kristine M; Sadow, Peter M; Cheng, Liang; Wang, Mingsheng; Xiao, Yu; Jiang, Zhong; Oliva, Esther; Jozwiak, Sergiusz; Nussbaum, Robert L; Feldman, Adam S; Paul, Elahna; Thiele, Elizabeth A; Yu, Jane J; Henske, Elizabeth P; Kwiatkowski, David J; Young, Robert H; Wu, Chin-Lee

    2014-07-01

    Renal cell carcinoma (RCC) occurs in 2% to 4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathologic, and molecular features, enabling separation of these 46 tumors into 3 groups. The largest subset of tumors (n=24) had a distinct morphologic, immunologic, and molecular profile, including prominent papillary architecture and uniformly deficient succinate dehydrogenase subunit B (SDHB) expression prompting the novel term "TSC-associated papillary RCC (PRCC)." The second group (n=15) were morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT), whereas the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated PRCCs had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCCs showed strong, diffuse labeling for carbonic anhydrase IX (100%), CK7 (94%), vimentin (88%), and CD10 (83%) and were uniformly negative for SDHB, TFE3, and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes, which may help to expand the morphologic spectrum of TSC-associated RCC. PMID:24832166

  18. A Rare Constellation of Hürthle Cell Thyroid Carcinoma and Parathyroid Carcinoma.

    PubMed

    Zakerkish, Mehrnoosh; Rajaei, Elham; Dargahi, Mehrdad; Bahadoram, Mohammad

    2015-12-01

    Separate occurrence of thyroid and parathyroid carcinoma in patients is extremely rare, and to the best of our knowledge, only 7 patients with documented parathyroid and papillary thyroid carcinomas have been described formerly in published reports. We report a patient with an extremely unusual clinical presentation of Hürthle cell carcinoma in thyroid and parathyroid carcinoma. The patient displayed a rare presentation of life-threatening hypercalcaemia after total para-thyroidectomy and failed to respond to standard therapy. Our review of available literature yielded insufficient evidence in managing such. When a patient with thyroid cancer is diagnosed, checking for serum calcium is advised. This is considered a useful method for detecting possible incidental parathyroid lesion and screening the probable concealed parathyroid pathology.

  19. Anabolic androgens affect the competitive interactions in cell migration and adhesion between normal mouse urothelial cells and urothelial carcinoma cells.

    PubMed

    Huang, Chi-Ping; Hsieh, Teng-Fu; Chen, Chi-Cheng; Hung, Xiao-Fan; Yu, Ai-Lin; Chang, Chawnshang; Shyr, Chih-Rong

    2014-09-26

    The urothelium is constantly rebuilt by normal urothelial cells to regenerate damaged tissues caused by stimuli in urine. However, the urothelial carcinoma cells expand the territory by aberrant growth of tumor cells, which migrate and occupy the damaged tissues to spread outside and disrupt the normal cells and organized tissues and form a tumor. Therefore, the interaction between normal urothelial cells and urothelial carcinoma cells affect the initiation and progression of urothelial tumors if normal urothelial cells fail to migrate and adhere to the damages sites to regenerate the tissues. Here, comparing normal murine urothelial cells with murine urothelial carcinoma cells (MBT-2), we found that normal cells had less migration ability than carcinoma cells. And in our co-culture system we found that carcinoma cells had propensity migrating toward normal urothelial cells and carcinoma cells had more advantages to adhere than normal cells. To reverse this condition, we used anabolic androgen, dihyrotestosterone (DHT) to treat normal cells and found that DHT treatment increased the migration ability of normal urothelial cells toward carcinoma cells and the adhesion capacity in competition with carcinoma cells. This study provides the base of a novel therapeutic approach by using anabolic hormone-enforced normal urothelial cells to regenerate the damage urothelium and defend against the occupancy of carcinoma cells to thwart cancer development and recurrence.

  20. Carcinomas of ovary and lung with clear cell features: can immunohistochemistry help in differential diagnosis?

    PubMed

    Howell, Nicole R; Zheng, Wenxin; Cheng, Liang; Tornos, Carmen; Kane, Philip; Pearl, Michael; Chalas, Eva; Liang, Sharon X

    2007-04-01

    Metastatic lung carcinomas with clear cell morphology can be confused with primary ovarian clear cell carcinomas. We performed immunohistochemical stains in 14 cases of non-small cell lung carcinomas with clear cell features and 14 cases of ovarian clear cell carcinomas using a panel of markers, including thyroid transcription factor 1 (TTF-1), carcinoembryonic antigen (CEA), Wilms tumor gene 1, octamer-binding transcription factor 4 (OCT-4), cancer antigen 125 (CA-125), estrogen receptor, and progesterone receptor. Among non-small cell lung carcinomas with clear cell features, 87.5% of adenocarcinomas (or 50% overall frequency in lung carcinomas) were positive for TTF-1, whereas none of the ovarian clear cell carcinomas were positive (P = 0.002). All 14 ovarian clear cell carcinomas stained for CA-125 as compared with 1 non-small cell lung carcinoma (P < 0.001). On the other hand, 85% of non-small cell lung carcinomas stained for CEA, whereas none of the ovarian clear cell carcinomas did (P < 0.001). Interestingly, 4 ovarian clear cell carcinomas (28%) showed positive staining for the germ cell marker OCT-4. Either lung or ovarian carcinomas stained for Wilms tumor gene 1, estrogen receptor, or progesterone receptor very infrequently; and the difference between the 2 groups was not statistically significant. Our results suggest that an immunohistochemical panel consisting of TTF-1, CEA, CA-125, and OCT-4 is helpful in distinguishing most pulmonary and ovarian carcinomas with clear cell features.

  1. A Case of Gastric Cancer with Neuroendocrine Carcinoma, Signet Ring Cell Carcinoma Components, and Intramural Metastases

    PubMed Central

    Aoyagi, Keishiro; Kizaki, Junya; Isobe, Taro; Akagi, Yoshito

    2016-01-01

    Patient: Male, 67 Final Diagnosis: Gastric cancer with neuroendocrine carcinoma Symptoms: — Medication: — Clinical Procedure: Total gastrectomy • splenectomy with D2 lymph node dissection Specialty: Surgery Objective: Rare co-existance of disease or pathology Background: Many neuroendocrine carcinomas exhibit medullary infiltration and expanded proliferation. Differentiated tubular adenocarcinoma is frequently seen in the superficial region in many neuroendocrine carcinoma cases. However, the present case showed non-medullary infiltration and signet ring cell carcinoma in the superficial region, with intramural metastases distributed throughout the whole of the stomach. Case Report: A 67-year-old man was referred to our institution for treatment of gastric cancer. Type IIc-like advanced gastric cancer was detected in the greater curvature of the middle body of the stomach. The patient underwent total gastrectomy, splenectomy with D2 lymph node dissection, and Roux-en-Y reconstruction with curative resection. The tumor was diagnosed as a large-cell endocrine carcinoma of the stomach. A solid growth of signet ring cells was seen in the mucosa and submucosa. Intramural metastases were observed in many other depressed lesions. Large-cell carcinoma invaded the submucosa, mainly in the intramural metastatic site. Metastasis to one lesser curvature lymph node was also seen on histological examination. The final diagnosis was a gastric cancer of type 0–IIc (T4a) [M] (with intramural metastases) at T4aN1H0P0M0 Stage IIIA. This patient has remained alive without recurrence for 72 months after surgery. Conclusions: We recommend close preoperative examination of neuroendocrine carcinoma, taking intramural metastases into consideration. PMID:27102318

  2. Predictive markers in advanced renal cell carcinoma.

    PubMed

    Michaelson, M Dror; Stadler, Walter M

    2013-08-01

    Predictive markers of response to therapy are increasingly important in advanced renal cell carcinoma (RCC) due to the proliferation of treatment options in recent years. Different types of potential predictive markers may include clinical, toxicity-based, serum, tissue, and radiologic biomarkers. Clinical factors are commonly used in overall prognostic models of RCC but have limited utility in predicting response to therapy. Correlation between development of particular toxicities and response to therapy has been noted, such as the correlation between hypertension and response to angiogenesis-targeted therapy. Serum and tissue biomarkers will be covered in detail elsewhere, but factors such as serum lactate dehydrogenase (LDH) and circulating cytokines show promise in this regard. Finally, baseline or early treatment radiology studies may have predictive ability for longer term efficacy, with most studies to date focusing on functional imaging modalities such as positron emission tomography (PET) scans, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), and DCE ultrasound (US). The ultimate goal of developing predictive biomarkers is to enable rational and personalized treatment strategies for patients with advanced RCC. PMID:23972709

  3. New basal cell carcinoma susceptibility loci

    PubMed Central

    Stacey, Simon N.; Helgason, Hannes; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A.; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G.; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M.; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T.; Halldorsson, Bjarni V.; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I.; Gudbjartsson, Daniel F.; Olafsson, Jon H.; Stefansson, Kari

    2015-01-01

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10−12), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10−9), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10−12) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10−16). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained. PMID:25855136

  4. Small cell carcinoma of the urinary bladder.

    PubMed

    Pant-Purohit, Mukta; Lopez-Beltran, Antonio; Montironi, Rodolfo; MacLennan, Gregory T; Cheng, Liang

    2010-02-01

    Small cell carcinoma of the urinary bladder (SCCUB) is a rare and aggressive cancer of the bladder. SCCUB is part of neuroendocrine family of tumors that affect several organ systems including respiratory, gastrointestinal and male and female genitourinary tract. SCCUB affect males predominantly with common risk factors include smoking, bladder calculi, bladder manipulation, and chronic cystitis. Prognosis of SCCUB remains poor due to high metastatic potential and lack of symptoms in earlier stages of the disease. Pathogenesis of the disease is linked to loss of genetic material, hypermethylation of tumor suppressors and at times amplification of the chromosomal regions carrying oncogenes. Majority of cases are treated with local resection of the tumor with neoadjuvant or adjuvant platinum-based chemotherapy regimen. Radiation therapy is used as alternative to radical cystectomy or as palliative measure. This article provides epidemiology, molecular pathogenesis, histochemistry, and current management options for SCCUB. Furthermore we reviewed all recent studies involving advancement in targeted molecular therapy for neuroendocrine tumors. PMID:20017108

  5. Molecular Classification of Oral Squamous Cell Carcinoma

    PubMed Central

    Bavle, Radhika Manoj; Konda, Paremala; Muniswamappa, Sudhakara; Makarla, Soumya

    2016-01-01

    Oral Squamous Cell Carcinoma (OSCC) is the commonest tumour in the oro-facial region with increasing incidence in the recent years. The disease is challenging as it still depicts a high morbidity and mortality rate. Clinico-pathological data, tumour site, pathologic site tumor, lymphnode, metastasis (TNM) staging, histological grade, invasion, perineural invasion and metastasis have been evaluated to a great depth in relation to OSCC. Co-morbidity factors like use of tobacco, alcohol consumption and various other factors including genetic predisposition have been looked at for finding a suitable treatment protocol. The crux of the matter in understanding the complexity of oral cancer lies in the biological heterogeneity of the tumour. Similar heterogeneity is seen in clinical presentation, histopathology and molecular changes at the cellular level. In spite of the disease being diagnosed, a prediction of the same related to behaviour has remained elusive. Hence, it is time to look beyond at the genetic and epigenetic events leading to molecular and cytogenetic changes that elucidate the pathogenesis and help in design and implementation of targeted drug therapy. A molecular classification of OSCC needs to be put in place much before a clinician can design the treatment protocol of the same and predict the prognosis. PMID:27790599

  6. Perfusion computed tomography in renal cell carcinoma

    PubMed Central

    Das, Chandan J; Thingujam, Usha; Panda, Ananya; Sharma, Sanjay; Gupta, Arun Kumar

    2015-01-01

    Various imaging modalities are available for the diagnosis, staging and response evaluation of patients with renal cell carcinoma (RCC). While contrast enhanced computed tomography (CT) is used as the standard of imaging for size, morphological evaluation and response assessment in RCC, a new functional imaging technique like perfusion CT (pCT), goes down to the molecular level and provides new perspectives in imaging of RCC. pCT depicts regional tumor perfusion and vascular permeability which are indirect parameters of tumor angiogenesis and thereby provides vital information regarding tumor microenvironment. Also response evaluation using pCT may predate the size criteria used in Response Evaluation Criteria in Solid Tumors, as changes in the perfusion occurs earlier following tissue kinase inhibitors before any actual change in size. This may potentially help in predicting prognosis, better selection of therapy and more accurate and better response evaluation in patients with RCC. This article describes the techniques and role of pCT in staging and response assessment in patients with RCCs. PMID:26217456

  7. Temporal bone squamous cell carcinoma - Penang experience.

    PubMed

    Ng, S Y; Pua, K C; Zahirrudin, Z

    2015-12-01

    Temporal bone squamous cell carcinoma (TBSCC) is rare and poses difficulties in diagnosing, staging and management. We describe a case series with six patients who were diagnosed TBSCC, from January 2009 to June 2014, with median age of 62 years old. All patients presented with blood-stain discharge and external auditory canal mass, showing that these findings should highly alert the diagnosis of TBSCC. Three patients staged T3 and another three with T4 disease. High-resolution CT (HRCT) temporal findings were noted to be different from intraoperative findings and therefore we conclude that MRI should be done to look for middle ear involvement or other soft tissue invasion for more accurate staging. Lateral temporal bone resection (LTBR) and parotidectomy was done for four patients with or without neck dissection. Patients with positive margin, perineural invasion or parotid and glenoid involvement carry poorer prognosis and postoperative radiotherapy may improve the survival rate. One patient had successful tumor resection via piecemeal removal approach in contrast with the recommended en bloc resection shows that with negative margin achieved, piecemeal removal approach can be a good option for patients with T2-3 disease. In general, T4 tumor has dismal outcome regardless of surgery or radiotherapy given.

  8. Squamous cell carcinoma of the bladder.

    PubMed

    Johnson, D E; Schoenwald, M B; Ayala, A G; Miller, L S

    1976-05-01

    Clinical and morphological features of 90 cases of squamous cell carcinoma of the bladder have been reviewed. The lesions were solitary in 90 per cent of the patients, developed without a history of vesical malignant disease in 82 per cent and were invasive at the time of diagnosis in all cases. Ureteral obstruction was demonstrated in 42 per cent of the group. The over-all survival rate at 5 years was only 10.6 per cent. There were 17 patients who received no therapy, all of whom were dead before 2 years. Unassisted supervoltage radiation therapy for patients with stages B2 and C lesions yielded a 5-year survival rate only 17.7 per cent. However, preoperative radiotherapy followed by simple total cystectomy and urinary diversion in a small number of patients with stages B2 and C lesions resulted in a 5-year survival rate in excess of 34 per cent. We are encouraged by this finding and believe that combination therapy warrants further clinical trial.

  9. Novel investigational drugs for basal cell carcinoma

    PubMed Central

    Tang, Jean Y; Epstein, Ervin H

    2011-01-01

    Importance of the field In the United States, the annual incidence of basal cell carcinoma (BCC) is close to 1 million. Ultraviolet radiation exposure is the main risk factor; however, the availability of ever more potent sunscreens and education have not prevented the rise in BCC incidence. Therefore, concerted effects to identify novel preventive and therapeutic strategies are necessary. Areas covered in this review This article summarizes our current understanding of the etiology and molecular mechanisms of BCC tumorigenesis and discusses the preclinical and clinical studies to identify agents with anti-BCC efficacy. What the reader will gain The discovery that hyperactive Hh pathway signaling causes several cancers, including BCC, has spawned the development of many pharmacologic inhibitors of Hh signaling. Early clinical testing of the most advanced, GDC-0449, demonstrated impressive efficacy in patients with advanced BCC. Other promising anti-BCC chemopreventive strategies include drugs that are already FDA-approved for treating other diseases. Take home message Preclinical and clinical trials with pre-existing FDA-approved drugs suggest novel uses for BCC chemoprevention and treatment. Also, new chemical entities that inhibit the Hh pathway show promise, and in combination with other drugs may provide a nonsurgical cure for this most common cancer. PMID:20662553

  10. Molecular profiling of head and neck squamous cell carcinoma

    PubMed Central

    Gatalica, Zoran; Knezetic, Joseph; Reddy, Sandeep; Nathan, Cherie‐Ann; Javadi, Nader; Teknos, Theodoros

    2015-01-01

    Abstract Background Head and neck squamous cell carcinoma (HNSCC) exhibits high rates of recurrence, and with few approved targeted agents, novel treatments are needed. We analyzed a molecular profiling database for the distribution of biomarkers predictive of chemotherapies and targeted agents. Methods Seven hundred thirty‐five patients with advanced HNSCC (88 with known human papillomavirus [HPV] status), were profiled using multiple platforms (gene sequencing, gene copy number, and protein expression). Results Among the entire patient population studied, epidermal growth factor receptor (EGFR) was the protein most often overexpressed (90%), TP53 gene most often mutated (41%), and phosphatidylinositol 3‐kinase (PIK3CA) most often amplified (40%; n = 5). With the exception of TP53 mutation, other biomarker frequencies were not significantly different among HPV‐positive or HPV‐negative patients. PIK3CA mutations and phosphatase and tensin homolog (PTEN) loss are frequent events, independent of HPV status. The immune response‐modulating programmed cell death 1 (PD1) and programmed cell death ligand 1 (PDL1) axis was active across sites, stages, and HPV status. Conclusion Molecular profiling utilizing multiple platforms provides a range of therapy options beyond standard of care. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1625–E1638, 2016 PMID:26614708

  11. Chemically induced bidirectional differentiation of embryonal carcinoma cells in vitro.

    PubMed Central

    Speers, W. C.; Birdwell, C. R.; Dixon, F. J.

    1979-01-01

    N,N-dimethylacetamide, hexamethylene bisacetamide, and Polybrene induced rapid and extensive differentiation in vitro in an otherwise slowly differentiating subline of embryonal carcinoma cells. The type of differentiated cell induced was dependent on the spatial organization of the stem cells during drug treatment. In monalayer culture "epithelial" cells were produced exclusively. However, treatment of aggregated suspension cultures yielded predominantly "fibroblast-like" cells. The undifferentiated embryonal carcinoma cells and the two differentiated cell types were morphologically distinct when examined by light microscopy, scanning electron microscopy, and transmission electron microscopy; and they had differences in cell surface antigens. Both differential cell types produced large amounts of fibronectin, whereas the embryonal carcinoma cells produced only minimal amounts. This system provides a convenient way to induce relatively synchronous differentiation of embryonal carcinoma cells into specific differentiated cell types. Images Figure 5 Figure 6 Figure 1 Figure 2 Figure 3 Figure 4 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:507191

  12. Radiosensitization of Oropharyngeal Squamous Cell Carcinoma Cells by Human Papillomavirus 16 Oncoprotein E6*I

    SciTech Connect

    Pang, Ervinna; Delic, Naomi C.; Hong, Angela; Zhang Mei; Rose, Barbara R.; Lyons, J. Guy

    2011-03-01

    Purpose: Patients with oropharyngeal squamous cell carcinoma (OSCC) whose disease is associated with high-risk human papillomavirus (HPV) infection have a significantly better outcome than those with HPV-negative disease, but the reasons for the better outcome are not known. We postulated that they might relate to an ability of HPV proteins to confer a better response to radiotherapy, a commonly used treatment for OSCC. Methods and Materials: We stably expressed the specific splicing-derived isoforms, E6*I and E6*II, or the entire E6 open reading frame (E6total), which gives rise to both full length and E6*I isoforms, in OSCC cell lines. Radiation resistance was measured in clonogenicity assays, p53 activity was measured using transfected reporter genes, and flow cytometry was used to analyze cell cycle and apoptosis. Results: E6*I and E6total sensitized the OSCC cells to irradiation, E6*I giving the greatest degree of radiosensitization (approximately eightfold lower surviving cell fraction at 10 Gy), whereas E6*II had no effect. In contrast to radiosensitivity, E6*I was a weaker inhibitor than E6total of tumor suppressor p53 transactivator activity in the same cells. Flow cytometric analyses showed that irradiated E6*I expressing cells had a much higher G2M:G1 ratio than control cells, indicating that, after G2, cells were diverted from the cell cycle to programmed cell death. Conclusion: This study supports a role for E6*I in the enhanced responsiveness of HPV-positive oropharyngeal carcinomas to p53-independent radiation-induced death.

  13. Small cell carcinoma of the anus in the setting of prior squamous dysplasia and carcinoma in situ

    PubMed Central

    Edgar, Mark A.; Hawk, Natalyn N.; Sullivan, Patrick S.; Stapleford, Liza J.

    2013-01-01

    Small cell carcinoma of the anus is a rare tumor that has been infrequently described in the literature. In contrast to squamous cell carcinoma, which is known to be associated with high-risk subtypes of human papillomavirus (HPV), the etiology of small cell carcinoma of the anal canal is not established. We present a case of a patient with small cell carcinoma of the anal canal in the setting of prior squamous dysplasia and carcinoma in situ. In conjunction with recently published data demonstrating the presence of HPV in tumor specimens from patients with small cell carcinoma of the anal canal, our patient’s clinical course suggests a possible link between HPV and this rare malignancy. PMID:23730521

  14. Computational Modelling of Metastasis Development in Renal Cell Carcinoma

    PubMed Central

    Baratchart, Etienne; Benzekry, Sébastien; Bikfalvi, Andreas; Colin, Thierry; Cooley, Lindsay S.; Pineau, Raphäel; Ribot, Emeline J; Saut, Olivier; Souleyreau, Wilfried

    2015-01-01

    The biology of the metastatic colonization process remains a poorly understood phenomenon. To improve our knowledge of its dynamics, we conducted a modelling study based on multi-modal data from an orthotopic murine experimental system of metastatic renal cell carcinoma. The standard theory of metastatic colonization usually assumes that secondary tumours, once established at a distant site, grow independently from each other and from the primary tumour. Using a mathematical model that translates this assumption into equations, we challenged this theory against our data that included: 1) dynamics of primary tumour cells in the kidney and metastatic cells in the lungs, retrieved by green fluorescent protein tracking, and 2) magnetic resonance images (MRI) informing on the number and size of macroscopic lesions. Critically, when calibrated on the growth of the primary tumour and total metastatic burden, the predicted theoretical size distributions were not in agreement with the MRI observations. Moreover, tumour expansion only based on proliferation was not able to explain the volume increase of the metastatic lesions. These findings strongly suggested rejection of the standard theory, demonstrating that the time development of the size distribution of metastases could not be explained by independent growth of metastatic foci. This led us to investigate the effect of spatial interactions between merging metastatic tumours on the dynamics of the global metastatic burden. We derived a mathematical model of spatial tumour growth, confronted it with experimental data of single metastatic tumour growth, and used it to provide insights on the dynamics of multiple tumours growing in close vicinity. Together, our results have implications for theories of the metastatic process and suggest that global dynamics of metastasis development is dependent on spatial interactions between metastatic lesions. PMID:26599078

  15. Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas.

    PubMed

    Roa, Juan C; Tapia, Oscar; Cakir, Asli; Basturk, Olca; Dursun, Nevra; Akdemir, Deniz; Saka, Burcu; Losada, Hector; Bagci, Pelin; Adsay, N Volkan

    2011-08-01

    The information in the literature on squamous cell and adenosquamous carcinomas of the gallbladder is highly limited. In this study, 606 resected invasive gallbladder carcinoma cases were analyzed. Squamous differentiation was identified in 41 cases (7%). Those without any identifiable glandular-type invasive component were classified as pure squamous cell carcinomas (8 cases) and those with the squamous component constituting 25-99% of the tumors were classified as adenosquamous carcinomas (26 cases) and included into the analysis. The remaining 7 that had <25% squamous component were classified as adenocarcinoma with focal squamous change and excluded. The clinicopathological characteristics of adenosquamous carcinoma/squamous cell carcinomas were documented and contrasted with that of ordinary gallbladder adenocarcinomas. The average patient age was 65 years (range 26-81); female/male ratio, 3.8. In only 13%, there was a preoperative clinical suspicion of malignancy. Grossly, 58% presented as thickening and hardening of the wall and 6% were polypoid. In 12%, mucosa adjacent to the tumor revealed squamous metaplasia. All pure squamous cell carcinomas had prominent keratinization. Giant cells and tumor-infiltrating eosinophils were observed in 29 and 51% of the squamous cell carcinomas/adenosquamous carcinomas versus 10% (P=0.02) and 6% (P=0.001) in gallbladder adenocarcinomas, respectively. All but three cases had 'advanced' (pT2 and above) carcinomas. Follow-up was available in 31 patients: 25 died of disease (median=5 months, range 0-20), and 6 were alive (median=64 months, range 5-112.5). The survival of patients with squamous cell carcinomas/adenosquamous carcinomas was significantly worse than that of gallbladder adenocarcinomas (P=0.003), and this adverse prognosis persisted when compared with stage-matched advanced gallbladder adenocarcinoma cases (median=11.4 months, P=0.01). In conclusion, squamous differentiation was noted in 7% of gallbladder

  16. Retinopathy secondary to radiation therapy for squamous cell carcinoma

    SciTech Connect

    Groomer, A.E.; Gutwein, D.E. )

    1989-09-01

    This report discusses a case of radiotherapy-induced retinopathy following treatment of squamous cell carcinoma. Treatment of the carcinoma with external beam radiotherapy to the supraorbital region and base of the skull was followed by the onset of retinopathy. The sensory retina, as well as other central nervous system tissues, is highly resistant to radiation damage; however, the retinal vasculature is extremely sensitive to radiation damage, producing a retinopathy that is characteristic of other vascular occlusive diseases. Management is discussed.

  17. Intratumoral PV701 in Treating Patients With Advanced or Recurrent Unresectable Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-23

    Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

  18. A subset of prostatic basal cell carcinomas harbor the MYB rearrangement of adenoid cystic carcinoma.

    PubMed

    Bishop, Justin A; Yonescu, Raluca; Epstein, Jonathan I; Westra, William H

    2015-08-01

    Adenoid cystic carcinoma (ACC) is a basaloid tumor consisting of myoepithelial and ductal cells typically arranged in a cribriform pattern. Adenoid cystic carcinoma is generally regarded as a form of salivary gland carcinoma, but it can arise from sites unassociated with salivary tissue. A rare form of prostate carcinoma exhibits ACC-like features; it is no longer regarded as a true ACC but rather as prostatic basal cell carcinoma (PBCC) and within the spectrum of basaloid prostatic proliferations. True ACCs often harbor MYB translocations resulting in the MYB-NFIB fusion protein. MYB analysis could clarify the true nature of prostatic carcinomas that exhibit ACC features and thus help refine the classification of prostatic basaloid proliferations. Twelve PBCCs were identified from the pathology consultation files of Johns Hopkins Hospital. The histopathologic features were reviewed, and break-apart fluorescence in situ hybridization for MYB was performed. All 12 cases exhibited prominent basaloid histology. Four were purely solid, 7 exhibited a cribriform pattern reminiscent of salivary ACC, and 1 had a mixed pattern. The MYB rearrangement was detected in 2 (29%) of 7 ACC-like carcinomas but in none (0%) of the 5 PBCCs with a prominent solid pattern. True ACCs can arise in the prostate as is evidenced by the presence of the characteristic MYB rearrangement. When dealing with malignant basaloid proliferations in the prostate, recommendations to consolidate ACCs with other tumor types may need to be reassessed, particularly in light of the rapidly advancing field of biologic therapy where the identification of tumor-specific genetic alterations presents novel therapeutic targets.

  19. Gravity-Independent Orientation of Honeycomb Cells

    NASA Astrophysics Data System (ADS)

    Pratt, S. C.

    Honey bees have long been assumed to build their comb with the cells in either of two preferred orientations with respect to gravity ("vertical" or "horizontal"). I show here that these typical cell orientations in fact derive from substrate orientation and a simple building rule, rather than the influence of gravity itself. When bees were induced to build comb on substrates at four different orientations with respect to gravity, they always made cells with one vertex pointing directly toward the substrate. This produced horizontal and vertical cells on vertical and horizontal substrates, respectively, but yielded intermediate orientations on oblique substrates. The apparent preference for vertical and horizontal cells may simply reflect substrate orientation in the rectilinear hives from which cell measurements have been taken.

  20. Merkel Cell Carcinoma of Unknown Primary Origin

    PubMed Central

    Deneve, Jeremiah L.; Messina, Jane L.; Marzban, Suroosh S.; Gonzalez, Ricardo J.; Walls, Brooke M.; Fisher, Kate J.; Ann Chen, Y.; Wayne Cruse, C.; Sondak, Vernon K.; Zager, Jonathan S.

    2015-01-01

    Background Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes. Methods After institutional review board approval, our institutional database spanning the years 1998–2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed. Results From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months. Conclusions Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients. PMID:22271206

  1. Chemoprevention of esophageal squamous cell carcinoma

    SciTech Connect

    Stoner, Gary D. Wang Lishu; Chen Tong

    2007-11-01

    Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.

  2. p63 immunohistochemistry differentiates salivary gland oncocytoma and oncocytic carcinoma from metastatic renal cell carcinoma.

    PubMed

    McHugh, Jonathan B; Hoschar, Aaron P; Dvorakova, Mari; Parwani, Anil V; Barnes, E Leon; Seethala, Raja R

    2007-12-01

    Metastatic renal cell carcinoma (RCC) can pose diagnostic challenges in the head and neck often resembling benign and malignant oncocytic lesions. Immunohistochemical panels have been reported to help with this differential but are not entirely specific or sensitive. We have noticed that p63 routinely stains salivary gland oncocytomas but not metastatic RCC. Nineteen oncocytomas, 9 cases of oncocytosis, 9 oncocytic carcinomas and 16 head and neck metastatic RCC were studied. Morphologic features evaluated were cytoplasmic character (clear versus oncocytic), Fuhrman nuclear grade, mitotic rate, growth pattern, presence of lumens/blood lakes and stromal characteristics. Tumors were stained with antibodies to p63, renal cell carcinoma marker (RCCm), CD10, and vimentin. Eight benign oncocytic tumors (29%) had clear cell features while 6 metastatic RCC (37%) had oncocytic features. Median Fuhrman nuclear grade was 2 in oncocytoma and oncocytosis and 3 both oncocytic carcinoma and metastatic RCC. Mitotic rates were only significantly different between benign oncocytic tumors and metastatic RCC. All oncocytomas had lumina compared to half of metastatic RCC, all of which also demonstrated blood lakes. Seven benign oncocytic tumors (25%) and 5 oncocytic carcinomas (56%) had RCC-like vascular stroma. All primary salivary gland tumors were positive for p63, predominately in basal cell-type distribution. None of the metastatic RCC was positive. RCCm was entirely specific but lacked sensitivity for metastatic RCC while CD10 and vimentin showed variable sensitivity and specificity. While clinical history and morphology usually are adequate, demonstration of p63 staining can definitively exclude metastatic RCC from the differential diagnosis of similar appearing tumors in salivary glands, namely oncocytoma and oncocytic carcinoma, with 100% specificity and sensitivity. While RCCm, CD10, and vimentin performed adequately, they were significantly less reliable than p63 with both

  3. [Usefulness of the present renal cell carcinoma classifications].

    PubMed

    Algaba, F; Arce, Y; Trias, I; Santaularia, J M; Antonio Rosales, A

    2006-04-01

    The purpose of classifying neoplasias is to recognize groups with similar progress and prognosis and, if possible, receiving the same treatment. This is why those classifications are systematically being submitted to review and improvement through the new technologies. Differentiation of various entities in renal cancer has been comparatively fast, as the new genetic and molecular discoveries have confirmed the morphologic criteria of the different cell types, thus making it possible to open new therapeutic pathways. Using the current WHO classification we recognize subtypes with excellent prognosis (Multilocular cystic renal carcinoma, Type I renal papillary carcinoma, Tubular and fusocellular mucinous carcinoma), other very aggressive ones (Bellini's collecting duct carcinoma, Medullary carcinoma), and also that the sarcomatoid transformation, even in small areas, impacts the prognosis negatively. Childhood-characteristic renal carcinomas associated with chromosome translocations have been recognized (genetic fusion TFE3 or TFEB), as well as the family forms of renal carcinoma. Regarding the UICC (International Union Against Cancer) classification, there are a series of aspects under argument (size, venous invasion, microvascular invasion, invasion of the adipous tissue of the renal sinus) that shall be discussed too, since it is possible that some modifications of the TNM might occur in the near future.

  4. Comparative transcriptional profiling of human Merkel cells and Merkel cell carcinoma.

    PubMed

    Mouchet, Nicolas; Coquart, Nolwenn; Lebonvallet, Nicolas; Le Gall-Ianotto, Christelle; Mogha, Ariane; Fautrel, Alain; Boulais, Nicholas; Dréno, Brigitte; Martin, Ludovic; Hu, Weiguo; Galibert, Marie-Dominique; Misery, Laurent

    2014-12-01

    Merkel cell carcinoma is believed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly understood events. Transcriptional profiling using cDNA microarrays was performed on cells from MCPy-negative and MCPy-positive Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and some downregulated genes. The extensive list of genes that were identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy.

  5. Transcriptional attenuation in colon carcinoma cells in response to butyrate.

    PubMed

    Daroqui, Maria C; Augenlicht, Leonard H

    2010-10-01

    The short-chain fatty acid sodium butyrate (NaB), produced in the colonic lumen, induces cell cycle arrest, differentiation, and/or apoptosis in colorectal carcinoma cells in vitro, establishing a potential role for NaB in colon cancer prevention. We have previously shown that butyrate decreases cyclin D1 and c-myc expression, each essential for intestinal tumor development, by transcriptional attenuation. Here, we determined that butyrate-induced transcriptional attenuation of the cyclin D1 and c-myc genes in SW837 human colorectal adenocarcinoma cells occurs at ∼100 nucleotides downstream of the transcription start site, with a similar positioning in Caco-2 cells. A concomitant decrease in RNA polymerase II occupancy at the 5' end of each gene was observed. Because transcriptional regulation is associated with chromatin remodeling, we investigated by chromatin immunoprecipitation whether the histone deacetylase inhibitory activity of butyrate altered chromatin structure at the attenuated loci. Although the distributions of histone H3 trimethylated on K4 and K36 along the cyclin D1 and c-myc genes were consistent with current models, butyrate induced only modest decreases in these modifications, with a similar effect on acetylated H3 and a modest increase in histone H3 trimethylated on K27. Finally, transcriptome analysis using novel microarrays showed that butyrate-induced attenuation is widespread throughout the genome, likely independent of transcriptional initiation. We identified 42 loci potentially paused by butyrate and showed that the transcription patterns are gene specific. The biological functions of these loci encompass a number of effects of butyrate on the physiology of intestinal epithelial cells.

  6. A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer

    ClinicalTrials.gov

    2014-04-21

    HER2 + Breast Cancer, HER2 + Gastric Cancer, Squamous Cell Carcinoma of Head and Neck, Esophageal Squamous Cell Carcinoma; HER2 + Breast Cancer; HER2 + Gastric Cancer; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma

  7. [Merkel cell carcinoma experience in a reference medical center.

    PubMed

    Roesch-Dietlen, Federico; Devezé-Bocardi, Raúl; Ruiz-Juárez, Isabel; Grube-Pagola, Peter; Romero-Sierra, Graciela; Remes-Troche, José María; Silva-Cañetas, Carmen Sofía; Lozoya-López Escalera, Hilda

    2013-01-01

    Background: Merkel cell carcinoma is a rare tumor that occurs on areas exposed to ultraviolet light. It is usually asymptomatic and it is diagnosed late often. The treatment is surgical, associated with adjuvant radiotherapy. The objective was to present the experience in the management of Merkel cell carcinoma in a reference medical center. Methods: all patients with Merkel cell carcinoma treated at the Instituto de Investigaciones Médico-Biológicas of the Universidad Veracruzana during the period 2008 to 2011 were studied. Sex, age, evolution time, tumor localization, size, metastases and treatment were analyzed. Results: of 3217 patients treated, three cases were Merkel cell carcinoma (0.09 %), their age was 52.1 ± 14.17, male predominance of 66.67 %; the evolution time was of 29.66 ± 35.36 months; the tumour localization was on inguinal region, anterior chest and left arm; the noodle size was of 6.0 ± 5.19 cm; two patients had lymph node metastases. In two cases, resection and lymphadenectomy were performed. They all received radiation therapy and chemotherapy in one case. Histologically the medium variant predominated; immunohistochemistry was positive in the three cases. One patient died ten months after the study was done. Conclusions: our experience is similar with others authors, Merkel cell carcinoma is a rare tumor, usually diagnosed late, and it has poor survival.

  8. Squamous Cell Carcinoma in Combination with a Symbrachydactyly: Initial Management and Long-Term Followup

    PubMed Central

    Sanchez, Tomas; Walder, Daniel; Esenwein, Philipp

    2014-01-01

    A 68-year-old female patient presented with a rapidly growing, exulcerating tumor of the left hand in the area of a congenital symbrachydactyly at the digiti II and III. A biopsy of the tumor showed a squamous cell carcinoma. Further workup showed two suspicious axillar enhancements with no evidence of bony infiltration and no further metastasis. An amputation of the second and third ray of the left hand at the metacarpal level and additionally an axillar revision and lymph node dissection were performed and confirmed the suspicion of a squamous cell carcinoma, fortunately without affection of any lymph nodes. After 9 years the patient showed an excellent function of the left hand. Symbrachydactyly malformations and squamous cell carcinoma of the hand are both rare conditions. We could not find a reference that shows a common genetic condition to both and so far this is the first description of a squamous cell carcinoma in the region of a symbrachydactyly. It remains unclear whether our case is a coincidence of two rare independent diseases or there is a pathogenetic link between the malformation and the tumor on a genetic level. PMID:25024859

  9. Retroperitoneal cystic metastasis from a small clear cell renal carcinoma.

    PubMed

    Ishii, N; Yonese, J; Tsukamoto, T; Maezawa, T; Ishikawa, Y; Fukui, I

    2001-11-01

    A 39-year-old housewife was referred to our hospital for the treatment of a small renal tumor. A 25 x 35 mm cystic mass that had been detected by computerized tomography scan just caudal to the renal hilus proved to be a metastasis from the renal carcinoma of clear cell type. The pathogenesis may have been due to tumor cells obstructing a lymphatic vessel draining the kidney. Cystic metastasis from renal cell carcinoma is very rare and this appears to be the second published case in the world.

  10. Expression of stromelysin 3 in basal cell carcinomas.

    PubMed

    Cribier, B; Noacco, G; Peltre, B; Grosshans, E

    2001-01-01

    Stromelysin 3 is a member of the metalloproteinase family, which is expressed in various remodelling processes. The prognosis of breast cancers and squamous cell carcinomas is correlated to the level of expression of this protein. The purpose of the present work was to evaluate the expression of stromelysin 3 in the major types of basal cell carcinomas. We selected cases of primary tumours that were fully excised, without previous biopsy: 40 Pinkus tumors, 40 superficial, 40 nodular, 38 morpheiform basal cell carcinomas and 10 cases showing deep subcutaneous or muscular invasion. Immunohistochemistry was carried out using monoclonal anti-ST3 antibodies (MC Rio, IGBMC Strasbourg), and evaluated on a semi-quantitative scale from 0 to 3. Positively stained cells were restricted to the periphery of the epithelial cells, which, by contrast, never expressed stromelysin 3. The global rate of expression was 27% in Pinkus tumors, 65% in superficial, 72.5% in nodular, 87% in morpheiform and 100% in deeply invasive carcinomas. The rates of tumours showing the highest number of positively stained cells (class 2 or 3) were respectively 7.5%, 20%, 45%, 63% and 100%. This systematic study of stromelysin3 expression in basal cell carcinomas confirms that it is a marker of poor prognosis, because the rate of positive tumours was much higher in aggressive carcinomas. Moreover, the majority of tumours showing an intense expression (i.e. the highest number of positively stained cells in their stroma) were of the morpheiform and deeply invasive types, which are of poor prognosis. Altogether, the studies performed on cutaneous tumours are consistent with the theory of stromelysin 3 playing an active role in tumour progression.

  11. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC): a rapid autopsy report of metastatic renal cell carcinoma.

    PubMed

    Udager, Aaron M; Alva, Ajjai; Chen, Ying-Bei; Siddiqui, Javed; Lagstein, Amir; Tickoo, Satish K; Reuter, Victor E; Chinnaiyian, Arul M; Mehra, Rohit

    2014-04-01

    Rapid ("warm") autopsies of patients with advanced metastatic cancer provide invaluable insight into the natural history, pathobiology, and morphology of advanced and treatment-resistant tumors. Here, we report a rapid autopsy case of a hereditary leiomyomatosis and renal cell carcinoma (HLRCC) patient with advanced metastatic renal cell carcinoma (RCC)-the first such case described for either a primary renal tumor or HLRCC-related cancer. Mutations in the fumarate hydratase (FH) gene underlie HLRCC, a rare syndrome involving cutaneous and uterine leiomyomata and aggressive kidney tumors. Loss of heterozygosity at the wild-type FH gene locus results in profound cellular metabolic derangement, "pseudohypoxic" upregulation of hypoxia-inducible factor 1α (HIF-1α)-dependent transcription, and aberrant protein succination; these molecular changes drive oncogenesis of kidney tumors in HLRCC patients. The current index patient had a high-grade RCC with classic morphologic features of HLRCC, including large nuclei with prominent eosinophilic nucleoli and perinucleolar clearing. In addition, this patient's RCC demonstrated extensive sarcomatoid and rhabdoid features-morphologies not previously well described in HLRCC-associated kidney tumors. Here, we report the extent of metastatic dissemination and supplement this unique tumor morphology with mitochondrial enzyme histochemistry and extended immunohistochemical analysis. Tumor cells strongly expressed PAX8, vimentin, CD10, and the HIF target GLUT1 and showed increased nuclear p53 accumulation; the expression of other RCC markers was negative. We also detail microscopic tubular epithelial changes in the grossly uninvolved ipsilateral renal parenchyma and demonstrate sporadic, aberrant upregulation of the HIF targets GLUT1 and CAIX in dysplastic peritumoral tubules. PMID:24625422

  12. Basal cell epithelioma (carcinoma) in children and teenagers

    SciTech Connect

    Rahbari, H.; Mehregan, A.H.

    1982-01-15

    Among over 390,000 routine dermatopathologic specimens there were 85 cases diagnosed as basal cell epithelioma (carcinoma) (BCE) in persons 19 years old or younger. This number was refined to 40 cases de novo BCE in children and teenagers. Basal cell epithelioma unrelated to other conditions is rare in the young and it should be differentiated from similar fibroepithelial growths.

  13. Cytologic diagnosis of acinic-cell carcinoma of salivary glands.

    PubMed

    Nagel, H; Laskawi, R; Büter, J J; Schröder, M; Chilla, R; Droese, M

    1997-05-01

    The cytologic findings in fine-needle aspiration (FNA) biopsies obtained from 40 primary and 18 recurrent acinic-cell carcinomas (ACC) were retrospectively analyzed. Cytomorphologically, ACC is characterized by acinar differentiated tumor cells. In addition to these diagnostic clue cells, other types of neoplastic cells including vacuolated cells, cells resembling oncocytes, and nonspecific glandular cells are encountered. A pronounced lymphocytic reaction is a hallmark in 10% of ACC aspirates. Both the variety of tumor cell differentiation and the pronounced lymphocytic reaction observed in ACC aspirates may result in confusion with other salivary gland lesions. The differential diagnosis of ACC encompasses adenocarcinoma, mucoepidermoid carcinoma, pleomorphic adenoma, Warthin tumor, sebaceous lymphadenoma, benign lymphoepithelial lesion, sialoadenosis, sialadenitis caused by radiotherapy, and lymphadenitis. Primary ACCs were correctly diagnosed in 68%; additionally, ACC was suspected or included in the differential diagnosis in 15%. Increased familiarity with the spectrum of cytomorphologic findings and the potential diagnostic pitfalls in ACC will improve the cytodiagnosis of this neoplasm.

  14. Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-07-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  15. New therapeutic options for actinic keratosis and basal cell carcinoma.

    PubMed

    Sligh, James E

    2014-06-01

    Actinic keratosis (AK) is a common premalignant skin lesion that is frequently treated by cryosurgery. Basal cell carcinoma is the most common malignancy of man, and early-stage lesions are usually cured via surgery. Advanced basal cell carcinoma may require more extensive surgery resulting in deformity, and many advanced lesions cannot be treated surgically. Several recent developments have improved therapeutic options for both conditions. Cryosurgery is still a mainstay of treatment for AK, but the introduction of effective topical agents, imiquimod cream and ingenol mebutate, has provided alternatives to cryosurgery. For advanced basal cell carcinoma, the small-molecule inhibitor vismodegib has proven to be an effective therapy for lesions that are not amenable to surgery and has demonstrated ability to achieve dramatic improvement in advanced, potentially disfiguring cancer. PMID:25268601

  16. Case report: microcystic transitional cell carcinoma of the urinary bladder.

    PubMed

    Radopoulos, Demetrios; Kalyvas, Konstantinos; Kotakidou, Rodi; Panagiotopoulou, Konstantina; Katsikas, Vasilios; Papathanasiou, Michalis

    2005-01-01

    We report a rare case of microcystic transitional cell carcinoma involving the urinary bladder, in a 38-year-old man, and we add our experience in the treatment of this neoplasm. The tumor was muscle invasive, and a radical cystectomy was performed. The patient received no postoperative chemotherapy or radiotherapy, and he has not signs of local recurrence or distal metastasis after 3 years of intense follow up. Even though the number of cases documented so far, is insufficient to draw safe conclusions regarding the optimal treatment of the microcystic variant of transitional cell carcinoma. Our case indicates that even in cases of microcystic transitional cell carcinoma with infiltrative nature, aggressive therapy is associated with good control of the disease locally and distally.

  17. Unusual renal tumour: multilocular cystic renal cell carcinoma.

    PubMed

    Palmeiro, Marta Morna; Niza, João Luz; Loureiro, Ana Luisa; Conceição e Silva, João Paulo

    2016-01-01

    Multilocular cystic renal cell carcinoma (MCRCC) is a rare presentation of renal cell carcinoma. Most patients are asymptomatic and frequently MCRCCs are detected incidentally. MCRCCs have good prognosis because of their low malignant potential. We report a case of a 39-year-old woman who presented with mild right flank pain and normal laboratory data. On imaging examinations, a Bosniak III cystic lesion was detected in the lower third of the right kidney. She underwent right partial nephrectomy and histopathology showed a multilocular cystic renal cell carcinoma Fuhrman grade 1. In this article, we also present a review of the literature on MCRCC, highlight the correlation of the pathological and imaging characteristics of these low aggressive renal lesions, and underscore the importance of their recognition to prevent unnecessary radical surgery. PMID:26957035

  18. Small cell carcinoma of the cervix: a case report.

    PubMed

    Korcum, Aylin Fidan; Aksu, Gamze; Bozcuk, Hakan; Pestereli, Elif; Simsek, Tayup

    2008-04-01

    Small cell carcinoma of the uterine cervix accounts for 1-3% of all cervix cancers. It is an aggressive disease with a poor prognosis. To date, no effective treatment protocol has been determined. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. Recent data suggests that survival in patients with early staged small cell carcinoma of the cervix is better with surgery combined with chemo-radiotherapy. Here, we presented two patients with stage IB1 small cell carcinoma of the uterine cervix. For both patients, definitive surgery was performed with pelvic and para-aortic lymphadenectomy. Subsequently, they were treated with pelvic external radiotherapy and high-dose-rate intracavitary brachytherapy with concurrent cisplatin based chemotherapy. They were alive with no evidence of disease at 91 and 65 months, respectively.

  19. Late recurrence of acinic cell carcinoma of the parotid gland.

    PubMed

    Miki, H; Masuda, E; Ohata, S; Komaki, K; Hirokawa, M; Uehara, H; Asano, H; Monden, Y

    1999-08-01

    Acinic cell carcinoma of the salivary glands is a rare cancer representing a low grade malignancy. The recurrence of a tumor is sometimes encountered, usually within 5 years of initial operation. We describe an unusual recurrence after a long interval following primary surgery. In 1987, a 60-year-old woman underwent excision of a mass in the superficial lobe of the right parotid gland under the preoperative diagnosis of a benign tumor. A histologic diagnosis of acinic cell carcinoma was made by examining sections from the resected mass. The patient noted several small nodules in the right parotid region in 1995, but she did not visit our clinic until 1998 when tenderness developed. A locally recurrent tumor and cervical lymph nodes containing metastases were resected and postoperative radiotherapy was given 11 years after the first operation. At least 10 years of follow-up may be necessary for patients with acinic cell carcinoma because of slow-tumor growth.

  20. Clear cell papillary renal cell carcinoma: a clinicopathological study emphasizing ultrastructural features and cytogenetic heterogeneity.

    PubMed

    Shi, Shan-Shan; Shen, Qin; Xia, Qiu-Yuan; Tu, Pin; Shi, Qun-Li; Zhou, Xiao-Jun; Rao, Qiu

    2013-01-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized renal neoplasm, which was initially described in end-stage renal disease (ESRD), but some cases have been reported in otherwise normal kidneys. We report a series of 11 CCPRCC (age range, 33-72 years; male-to-female ratio, 8:3). Follow-up was available for 8 patients. No patients developed local recurrence, distant or lymph-node metastasis, or cancer death. Histologically, all tumors exhibit morphologic features typical of CCPRCC including a mixture of cystic and papillary components, covered by small to medium-sized cuboidal cells with abundant clear cytoplasm. All 11 cases exhibited moderate to strong positivity for CK7, CA9, Vim, and HIF-1α, coupled with negative reactions for CD10, P504S, and RCC. We did not find any VHL gene mutations in all 11 cases. Losses of chromosomes 3 (monoploid chromosome 3) was detected in 3 cases. Ultrastructurally, the tumor cells composed of numerous glycogens with scanty cell organelles, reminiscent of clear cell renal cell carcinoma (CCRCC). In conclusion, the coexpression of CA9 and HIF-1α in the absence of VHL gene abnormalities in CCPRCC suggests activation of the HIF pathway by mechanisms independent of VHL gene mutation. Losses of chromosomes 3 (monosomies chromosome 3) was detected in 3 cases suggesting that at least some of these lesions have demonstrated abnormalities of chromosomes 3. Ultrastructurally, CCPRCC composed of numerous glycogens with scanty cell organelles, reminiscent of CCRCC suggesting the close pathogenesis relationship of CCPRCC with CCRCC. PMID:24294381

  1. Diosgenin induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma cells.

    PubMed

    Li, Yongjian; Wang, Xiaorong; Cheng, Silu; Du, Juan; Deng, Zhengting; Zhang, Yani; Liu, Qun; Gao, Jingdong; Cheng, Binbin; Ling, Changquan

    2015-02-01

    Diosgenin is a major compound of Dioscoreaceae plants such as yam, which is used as a drug in Traditional Chinese Medicine, and a common vegetable worldwide. The anticancer effect of diosgenin has been reported in various tumor cells, including leukemia, gastric, colorectal, and breast cancer. However, the activity of diosgenin on hepatocellular carcinoma (HCC) and the underlying mechanism have not been completely investigated. Therefore, we investigated the efficacy and associated mechanisms of diosgenin in HCC cells. Flow cytometric analysis was performed to determine the presence of cell cycle arrest and apopotic cells. Diosgenin significantly inhibited the growth of Bel-7402, SMMC-7721 and HepG2 HCC cells in a concentration-dependent manner. Diosgenin treatment for 24 h induced G2/M cell cycle arrest and apoptosis of hepatoma cells. Diosgenin inhibited Akt phosphorylation and upregulated p21 and p27 expression, but did not alter the expression of p53, suggesting diosgenin-induced upregulation of p21 and p57 is p53-independent in HCC cells. Diosgenin induced HCC cell apoptosis by activating caspase cascades -3, -8 and -9. However, diosgenin did not affect Bcl-2 and Bax levels. In conclusion, results of the present study suggest that diosgenin may be an active anti-HCC agent obtained from natural plants and provide new insights in understanding the mechanisms of diosgenin. PMID:25434486

  2. Malignant Pericardial Tamponade in a Case of Signet Cell Gastric Carcinoma.

    PubMed

    Nambiar, Rakul; Prabhakaran, Sunil Prasobh; Pillai, Padmakumar Rajasekharan; Dalus, D

    2015-10-01

    We report a case of gastric signet cell carcinoma, presenting as cardiac tamponade, in a young male patient. The diagnosis of gastric signet cell carcinoma was confirmed by immunohistochemistry of the lymph node specimen in our patient. PMID:27608703

  3. Clear cell papillary renal cell carcinoma is the fourth most common histologic type of renal cell carcinoma in 290 consecutive nephrectomies for renal cell carcinoma.

    PubMed

    Zhou, Haijun; Zheng, Shaojiang; Truong, Luan D; Ro, Jae Y; Ayala, Alberto G; Shen, Steven S

    2014-01-01

    Clear cell papillary renal cell carcinoma (CCP-RCC) has recently been recognized as a distinct subtype of renal cell carcinoma (RCC) due to its unique morphologic, immunohistochemical, and genetic features and indolent clinical behavior. However, the incidence of this tumor in a nephrectomy series for renal mass has not been fully investigated. Twelve cases of CCP-RCC were identified from a total of 290 consecutive partial (n = 137) or radical nephrectomies (n = 153) for RCC from 2010 to 2012 in our hospital. In this series, CCP-RCC was the fourth most common (4.1%) kidney tumor following clear cell (conventional) (70%), papillary (16.6%), and chromophobe (5.9%) RCCs. The average age of the CCP-RCC patients was 58.2 years (range, 18-81 years), with an equal sex distribution. Four cases (33.3%) were associated with end-stage renal disease. Of the 12 CCP-RCCs, 9 presented as solitary tumors; 2 coexisted with clear cell RCC; and 1 with papillary RCC. The average size of tumors was 2.5 cm (range, 0.8-6.0 cm). All tumors were pT1 (10 pT1a and 2 pT1b). Two cases were initially misclassified as clear cell RCC. Strong positive cytokeratin 7 stain and negative stains with α-methylacyl-CoA racemase and RCC marker differentiate CCP-RCC from low-grade clear cell RCC with similar histologic features. We conclude that CCP-RCC is a common renal neoplastic entity, representing the fourth most common (4.1%) RCC. It can be easily misclassified due to its overlapping features with low-grade clear cell RCC. In equivocal cases, immunohistochemical stains with a small panel of markers (cytokeratin 7, α-methylacyl-CoA racemase, RCC marker, or CD10) are warranted in making the correct histologic classification. PMID:24182559

  4. Citrus consumption and risk of basal cell carcinoma and squamous cell carcinoma of the skin.

    PubMed

    Wu, Shaowei; Cho, Eunyoung; Feskanich, Diane; Li, Wen-Qing; Sun, Qi; Han, Jiali; Qureshi, Abrar A

    2015-10-01

    Animal experiments have demonstrated the photocarcinogenic properties of furocoumarins, a group of naturally occurring chemicals that are rich in citrus products. We conducted a prospective study for citrus consumption and risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on data from 41530 men in the Health Professionals Follow-up Study (1986-2010) and 63759 women in the Nurses' Health Study (1984-2010) who were free of cancers at baseline. Over 24-26 years of follow-up, we documented 20840 incident BCCs and 3544 incident SCCs. Compared to those who consumed citrus products less than twice per week, the pooled multivariable-adjusted hazard ratios were 1.03 [95% confidence interval (95% CI): 0.99-1.08] for BCC and 1.14 (95% CI: 1.00-1.30) for SCC for those who consumed two to four times per week, 1.06 (95% CI: 1.01-1.11) for BCC and 1.15 (95% CI: 1.02-1.28) for SCC for five to six times per week, 1.11 (95% CI: 1.06-1.16) for BCC and 1.22 (95% CI: 1.08-1.37) for SCC for once to 1.4 times per day and 1.16 (95% CI: 1.09-1.23) for BCC and 1.21 (95% Cl: 1.06-1.38) for SCC for 1.5 times per day or more (P trend = 0.001 for BCC and 0.04 for SCC). In contrast, consumption of non-citrus fruit and juice appeared to be inversely associated with risk of BCC and SCC. Our findings support positive associations between citrus consumption and risk of cutaneous BCC and SCC in two cohorts of men and women, and call for further investigations to better understand the potential photocarcinogenesis associated with dietary intakes. PMID:26224304

  5. Citrus consumption and risk of basal cell carcinoma and squamous cell carcinoma of the skin.

    PubMed

    Wu, Shaowei; Cho, Eunyoung; Feskanich, Diane; Li, Wen-Qing; Sun, Qi; Han, Jiali; Qureshi, Abrar A

    2015-10-01

    Animal experiments have demonstrated the photocarcinogenic properties of furocoumarins, a group of naturally occurring chemicals that are rich in citrus products. We conducted a prospective study for citrus consumption and risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on data from 41530 men in the Health Professionals Follow-up Study (1986-2010) and 63759 women in the Nurses' Health Study (1984-2010) who were free of cancers at baseline. Over 24-26 years of follow-up, we documented 20840 incident BCCs and 3544 incident SCCs. Compared to those who consumed citrus products less than twice per week, the pooled multivariable-adjusted hazard ratios were 1.03 [95% confidence interval (95% CI): 0.99-1.08] for BCC and 1.14 (95% CI: 1.00-1.30) for SCC for those who consumed two to four times per week, 1.06 (95% CI: 1.01-1.11) for BCC and 1.15 (95% CI: 1.02-1.28) for SCC for five to six times per week, 1.11 (95% CI: 1.06-1.16) for BCC and 1.22 (95% CI: 1.08-1.37) for SCC for once to 1.4 times per day and 1.16 (95% CI: 1.09-1.23) for BCC and 1.21 (95% Cl: 1.06-1.38) for SCC for 1.5 times per day or more (P trend = 0.001 for BCC and 0.04 for SCC). In contrast, consumption of non-citrus fruit and juice appeared to be inversely associated with risk of BCC and SCC. Our findings support positive associations between citrus consumption and risk of cutaneous BCC and SCC in two cohorts of men and women, and call for further investigations to better understand the potential photocarcinogenesis associated with dietary intakes.

  6. Increased expression of metastasis-associated in colon cancer-1 in renal cell carcinoma is associated with poor prognosis.

    PubMed

    Jin, Zhong; Xu, Naijin; Guo, Kai; Xu, Peng; Li, Pengju; Zhang, Yiming; Li, Xiezhao; Zheng, Shaobo; Liu, Chunxiao; Xu, Abai; Huang, Peng

    2015-01-01

    Metastasis-associated in colon cancer-1 (MACC1) expression in tumor specimens is an independent prognostic indicator of metastasis, which has recently gained considerable attention in cancer research, due to its overexpression in several types of carcinoma. However, MACC1 expression patterns and its possible role in renal cell carcinoma remain unknown. This study aimed to investigate MACC1 expression in renal cell carcinoma via immunohistochemical analysis and determine the relationship between MACC1 expression and cancer prognosis. Positive MACC1 expression was found to significantly correlate with distant metastasis and TNM stage (P < 0.05). A Kaplan-Meier survival analysis revealed that patients with higher MACC1 expression had a significantly lower disease-free rate (P < 0.05). These results indicate that MACC1 expression is significantly associated with prognosis in patients with renal cell carcinoma. To the best of our knowledge, this is the first study on the significance of MACC1 as a prognostic marker in renal cell carcinoma. MACC1 expression may be a useful target for the development of new therapeutic approaches, including molecular targeted therapeutic agents, for renal cell carcinoma.

  7. Overexpression of CD39 in hepatocellular carcinoma is an independent indicator of poor outcome after radical resection

    PubMed Central

    Cai, Xiao-Yan; Ni, Xiao-Chun; Yi, Yong; He, Hong-Wei; Wang, Jia-Xing; Fu, Yi-Peng; Sun, Jian; Zhou, Jian; Cheng, Yun-Feng; Jin, Jian-Jun; Fan, Jia; Qiu, Shuang-Jian

    2016-01-01

    Abstract Nucleoside triphosphate diphosphohydrolase-1 (ENTPD1/CD39) is the rate-limiting enzyme in a cascade leading to the generation of immunosuppressive adenosine and plays an important role in tumor progression. This study aimed to evaluate the expression of CD39 and CD39+Foxp3+ regulatory T cells (Tregs) and to determine their prognostic role in patients with hepatocellular carcinoma (HCC) after radical resection. Immunohistochemistry (IHC) and double IHC were used to analyze CD39 expression or the expression of CD39 and Foxp3 in a cohort of 324 HCC patients who underwent curative resection. The quantification of CD39 expression levels was determined using a computerized image analysis system and was evaluated by mean optical density (MOD), which corresponded to the positive staining intensity of CD39. The number of positive Foxp3 cells and both CD39 and Foxp3 positive cells in each 1-mm-diameter cylinder were counted under high-power magnification (×400). The “minimum P value” approach was used to obtain the optimal cutoff value for the best separation between groups of patients in relation to time to recurrence (TTR) or overall survival (OS). The expression of CD39 in HCC cell lines with stepwise metastatic potential and in human umbilical vein endothelial cells was determined by reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence. The SPSS 17.0 statistical package was used for statistics. CD39 was principally expressed on vascular endothelial cells, macrophagocytes, Tregs, and tumor cells in HCC. Compared with paired peritumoral tissues, tumoral tissues had a significantly higher expression level of CD39 (P < 0.0001). Overexpression of tumoral CD39 was related to increased tumor recurrence and shortened overall survival. Furthermore, the expression level of peritumoral CD39 showed a prognostic role in TTR and OS. Double IHC showed that tumoral tissues had significantly higher Foxp3+Tregs and CD39+Foxp3+Tregs

  8. Basal cell carcinoma masquerading as a hallux valgus

    PubMed Central

    Hallock, Geoffrey G; Bulatao, Imelda S

    2007-01-01

    The incidence of primary skin cancers of the foot is exceedingly low; conversely, problems associated with a hallux valgus are common. A nonhealing ulcer overlying a hallux valgus managed conservatively with ointments and orthotic adjustments, and even with skin grafts, did not resolve over a period of 10 years. Ultimately, a shave biopsy revealed that the lesion was a basal cell carcinoma. Wide local excision and another skin graft resulted in tumour eradication and, finally, healing. Basal cell carcinoma associated with a hallux valgus has not been previously reported, and this reinforces the concept that malignant degeneration as the cause of any chronic ulceration should not be overlooked. PMID:19554132

  9. Relationship of Angiogenesis and Oral Squamous Cell Carcinoma.

    PubMed

    Marla, V; Hegde, V; Shrestha, A

    2015-01-01

    Angiogenesis is an important aspect of a variety of physiological and pathological processes; and depends on the alteration of the balance between pro-angiogenic and anti-angiogenic factors. The role of angiogenesis in the progression and metastasis of neoplasm is a well established phenomenon. With regards to oral squamous cell carcinoma, it is a field of ongoing research and requires validation for it being used as a mode of anti-cancer therapy. This review focuses on the concept of angiogenesis, the factors associated with it, the relationship of angiogenesis with oral epithelial dysplasia and oral squamous cell carcinoma; the methods of studying angiogenesis and anti angiogenic therapy. PMID:26643840

  10. Anal squamous cell carcinoma: An evolution in disease and management

    PubMed Central

    Osborne, Marc C; Maykel, Justin; Johnson, Eric K; Steele, Scott R

    2014-01-01

    Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus. PMID:25278699

  11. Unexpected Anal Squamous Cells Carcinoma after Open Hemorrhoidectomy

    PubMed Central

    Luca, Navarra; Valentina, Abruzzese; Federico, Sista; Renato, Pietroletti

    2015-01-01

    We report a case of unexpected anal squamous cells carcinoma found in hemorrhoidectomy specimen. The patient had a 3-year history of prolapsing hemorrhoids. A prolapsing hemorrhoid was present at eleven o'clock in lithotomy. Milligan-Morgan was performed and gross examination of the specimen was unremarkable. Histopathologic evaluation showed noninvasive squamous cells carcinoma. The present case report evidences the opportunity of routine histopathologic analysis of hemorrhoidal specimens particularly in case of long-standing prolapse. Questions arise in the option of those techniques where no specimens are collected or tissue is excised far from deceased area. PMID:25922781

  12. Unexpected anal squamous cells carcinoma after open hemorrhoidectomy.

    PubMed

    Luca, Navarra; Valentina, Abruzzese; Federico, Sista; Renato, Pietroletti

    2015-01-01

    We report a case of unexpected anal squamous cells carcinoma found in hemorrhoidectomy specimen. The patient had a 3-year history of prolapsing hemorrhoids. A prolapsing hemorrhoid was present at eleven o'clock in lithotomy. Milligan-Morgan was performed and gross examination of the specimen was unremarkable. Histopathologic evaluation showed noninvasive squamous cells carcinoma. The present case report evidences the opportunity of routine histopathologic analysis of hemorrhoidal specimens particularly in case of long-standing prolapse. Questions arise in the option of those techniques where no specimens are collected or tissue is excised far from deceased area.

  13. Metastatic Renal Cell Carcinoma to the Oral Cavity.

    PubMed

    Guimarães, Douglas Magno; Pontes, Flavia Sirotheau Correa; Miyahara, Ligia Akiko Ninokata; Guerreiro, Marcella Yasmin Reis; de Almeida, Maria Clara Lopes; Pontes, Helder Antonio Rebelo; Pinto, Decio Dos Santos

    2016-09-01

    Metastases to the oral cavity are extremely rare events, representing less than 1% of all malignant oral tumors. Renal cell carcinoma constitutes about 3% of solid tumors in adults, and it is the most frequent kidney neoplasm, representing about 90% of kidney malignancies. Due to the silent growth of this neoplasm, most patients have no symptoms and the diagnosis is belated, usually after metastases. The present study reports an additional patient of metastatic renal cell carcinoma to the oral cavity regarding the clinical and pathologic features. PMID:27607131

  14. Cerebral metastases from Merkel cell carcinoma: long-term survival

    PubMed Central

    Honeybul, S.

    2016-01-01

    Merkel cell carcinoma is a rare primary cutaneous neuroendocrine tumour that is locally aggressive. In most cases the primary treatment is local surgical excision; however, there is a high incidence recurrence both local and distant. Cerebral metastases from Merkel cell carcinoma are extremely uncommon with only 12 cases published in the literature. This case is particularly unusual in that, not only was no established primary lesion identified, but also the patient has survived for 10 years following initial diagnosis and for 9 years following excision of a single brain metastasis. PMID:27765804

  15. Synchronous sebaceous lymphadenoma with squamous cell carcinoma - case report.

    PubMed

    Shukla, Mridula; Panicker, Sathibai

    2003-12-24

    BACKGROUND: Sebaceous lymphadenoma is a rare benign salivary gland tumour of uncertain histogenesis. So is synchronous occurrence of two benign or malignant neoplasms. CASE-REPORT: 68-year-old female presented with right side parotid swelling associated with pain and gradual increase is size. Fine needle aspiration cytology of parotid swelling was suggestive of pleomorphic adenoma. Total conservative parotidectomy was performed and histopathology of the specimen revealed sebaceous lymphadenoma with squamous cell carcinoma. CONCLUSIONS: Sebaceous lymphadenoma and squamous cell carcinoma are two rare benign and malignant neoplasms arising in parotid gland. Synchronous occurrence of these two entities has not been reported.

  16. Acinic cell carcinoma of the parotid gland in children.

    PubMed

    Levine, S B; Potsic, W P

    1986-09-01

    Acinic cell carcinoma is an infrequent malignancy of salivary gland tissue in adults that is very rare in children. Review of the English literature reveals only 25 reported cases of this neoplasm in pediatric populations. This is a case report of the youngest known child to undergo parotidectomy and facial nerve dissection for an acinic cell carcinoma. The unusual clinical and surgical findings might suggest the need for changes in approach to treatment of a tumor that has been previously described as relatively benign.

  17. Renal cell carcinoma arising in ipsilateral duplex system.

    PubMed

    Mohan, Harsh; Kundu, Reetu; Dalal, Usha

    2014-09-01

    Congenital anomalies of the kidney and urinary tract are common and include a wide anatomic spectrum. Duplex systems are one of the more common renal anomalies, with the majority being asymptomatic. Little is known about the molecular pathogenesis of these anomalies; however, certain causative genes have been implicated. The finding of renal cell carcinoma arising in a kidney with the duplication of pelvicalyceal system and ureters, as in the present case, is uncommon. The association between a duplex system and renal cell carcinoma may be more than a coincidence, requiring a deeper insight and further elucidation. PMID:26328175

  18. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    SciTech Connect

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang Zhang, Yi

    2013-11-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  19. Presence of Porphyromonas gingivalis in gingival squamous cell carcinoma

    PubMed Central

    Katz, Joseph; Onate, Mairelys D; Pauley, Kaleb M; Bhattacharyya, Indraneel; Cha, Seunghee

    2011-01-01

    Periodontal disease has been recently linked to a variety of systemic conditions such as diabetes, cardiovascular disease, preterm delivery, and oral cancer. The most common bacteria associated with periodontal disease, Porphyromonas gingivalis (P. gingivalis) has not yet been studied in the malignant gingival tissues. The objective of this study was to investigate the presence of P. gingivalis in specimens from squamous cell carcinoma patients. We have performed immunohistochemical staining to investigate the presence of P. gingivalis and Streptococcus gordonii (S. gordonii), a non invasive oral bacteria, in paraffin embedded samples of gingival squamous cell carcinoma (n=10) and normal gingiva (n=5). Staining for P. gingivalis revealed the presence of the bacteria in normal gingival tissues and gingival carcinoma, with higher levels (more than 33%, P<0.05) detected in the carcinoma samples. The staining intensity was also significantly enhanced in the malignant tissue by 2 folds (P<0.023) compared to specimens stained for the non-invasive S. gordonii. P. gingivalis is abundantly present in malignant oral epithelium suggesting a potential association of the bacteria with gingival squamous cell carcinoma. PMID:22010579

  20. Carcinoma ex pleomorphic adenoma of the buccal region is composed of salivary duct carcinoma and squamous cell carcinoma components.

    PubMed

    Nakamori, K; Ohuchi, T; Hasegawa, T; Hiratsuka, H

    2009-10-01

    A 73-year-old female presented with an asymptomatic mass in the left buccal region that she had first noticed 4 years earlier. The tumor, which was located in the buccal space, was clinically diagnosed as a salivary gland tumor and treated by excision. Histopathological examination revealed a capsule of connective tissue consisting of three different histopathological neoplastic areas in a large, fibrous, hyalinizing stromal background. The neoplastic lesion contained two malignant and one benign element, with histological characteristics consistent with squamous cell carcinoma (SCC), salivary duct carcinoma (SDC) and pleomorphic adenoma (PA). The SCC nests showed no continuity with the buccal mucosa. Both the SCC and SDC nests were surrounded by non-atypical myoepithelial cells, suggesting that both components may have developed from transformation of metaplastic luminal epithelial cells of PA. The tumor was diagnosed as a non-invasive carcinoma (SCC and SDC) ex pleomorphic adenoma (Ca-ex-PA). There was no evidence of recurrence 16 months after operation.

  1. [A case of spindle cell carcinoma of the breast].

    PubMed

    Oshida, Sayuri; Hayashi, Keiko; Habiro, Takeyoshi; Nemoto, Kazuhiko; Sengoku, Norihiko; Watanabe, Masahiko

    2014-11-01

    The patient was a 53-year-old woman in whom ultrasonography of the breast revealed a lobular mass, 14 mm in diameter, in the right AB region. Spindle cells were obtained on fine-needle aspiration biopsy, but it was not possible to diagnose whether the tumor was benign or malignant. Contrast-enhanced magnetic resonance imaging showed a mass with a cystic component that was darkly stained in the early phase. Needle biopsy showed a dense proliferation of atypical spindle cells with no distinct epithelial-like arrangement. The differential diagnosis included mesenchymal malignant tumors such as fibrosarcoma, some phyllodes tumors, and epithelial tumors with sarcomatoid differentiation. Immunostaining revealed that the tumor was cytokeratin (AE1/AE3)-negative, partially CAM 5.2-positive, p63-positive, S100-negative, SMA-positive, partially vimentin-positive, with a Ki-67 index of 80% and negativity for ER, PgR, and HER2. Spindle-cell carcinoma was thus diagnosed. A partial right mastectomy with sentinel lymph-node biopsy was performed. Immunostaining of the resected specimen confirmed spindle cell carcinoma. The General Rules for Clinical and Pathological Recording of Breast Cancer classify spindle cell carcinoma as a special type of invasive cancer with a sarcomatoid structure, consisting of spindle-shaped cancer cells. This type of carcinoma is extremely rare, accounting for less than 1% of all breast cancers. PMID:25731380

  2. The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary carcinoma cells.

    PubMed

    Hou, Lin; Xu, Bing; Mohankumar, Kumarasamypet M; Goffin, Vincent; Perry, Jo K; Lobie, Peter E; Liu, Dong-Xu

    2012-12-01

    The HOX genes are a highly conserved subgroup of homeodomain-containing transcription factors that are crucial to normal development. Forced expression of HOXA1 results in oncogenic transformation of immortalized human mammary cells with aggressive tumour formation in vivo. Microarray analysis identified that the prolactin receptor (PRLR) was significantly upregulated by forced expression of HOXA1 in mammary carcinoma cells. To determine prolactin (PRL) involvement in HOXA1‑induced oncogenicity in mammary carcinoma cells (MCF-7), we examined the effect of human prolactin (hPRL)-initiated PRLR signal transduction on changes in cellular behaviour mediated by HOXA1. Forced expression of HOXA1 in MCF-7 cells increased PRLR mRNA and protein expression. Forced expression of HOXA1 also enhanced hPRL-stimulated phosphorylation of both STAT5A/B and p44/42 MAPK, and increased subsequent transcriptional activity of STAT5A and STAT5B, and Elk-1 and Sap1a, respectively. Moreover, forced expression of HOXA1 in MCF-7 cells enhanced the hPRL‑stimulated increase in total cell number as a consequence of enhanced cell proliferation and cell survival, and also enhanced hPRL-stimulated anchorage-independent growth in soft agar. Increased anchorage-independent growth was attenuated by the PRLR antagonist ∆1-9-G129R‑hPRL. In conclusion, we have demonstrated that HOXA1 increases expression of the cell surface receptor PRLR and enhances PRLR-mediated signal transduction. Thus, the PRLR is one mediator of HOXA1‑stimulated oncogenicity in mammary carcinoma cells. PMID:23064471

  3. GRID INDEPENDENT FUEL CELL OPERATED SMART HOME

    SciTech Connect

    Dr. Mohammad S. Alam

    2003-12-07

    A fuel cell power plant, which utilizes a smart energy management and control (SEMaC) system, supplying the power need of laboratory based ''home'' has been purchased and installed. The ''home'' consists of two rooms, each approximately 250 sq. ft. Every appliance and power outlet is under the control of a host computer, running the SEMaC software package. It is possible to override the computer, in the event that an appliance or power outage is required. Detailed analysis and simulation of the fuel cell operated smart home has been performed. Two journal papers has been accepted for publication and another journal paper is under review. Three theses have been completed and three additional theses are in progress.

  4. Rapid induction of senescence in human cervical carcinoma cells

    NASA Astrophysics Data System (ADS)

    Goodwin, Edward C.; Yang, Eva; Lee, Chan-Jae; Lee, Han-Woong; Dimaio, Daniel; Hwang, Eun-Seong

    2000-09-01

    Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.

  5. UOK 268 Cell Line for Hereditary Leiomyomatosis and Renal Cell Carcinoma | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Urologic Oncology Branch seeks parties to co-develop the UOK 262 immortalized cell line as research tool to study aggressive hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated recurring kidney cancer.

  6. Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma

    SciTech Connect

    Nakamura, Tomoyuki; Sato, Yuko; Watanabe, Daisuke; Ito, Hideki; Shimonohara, Nozomi; Tsuji, Takahiro; Nakajima, Noriko; Suzuki, Yoshio; Matsuo, Koma; Nakagawa, Hidemi; Sata, Tetsutaro; Katano, Harutaka

    2010-03-15

    To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal in any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.

  7. Ten human carcinoma cell lines derived from squamous carcinomas of the head and neck.

    PubMed Central

    Easty, D. M.; Easty, G. C.; Carter, R. L.; Monaghan, P.; Butler, L. J.

    1981-01-01

    Ten cell lines of human squamous carcinomas of the tongue and larynx have been established from surgical specimens removed from 36 unselected patients, in order to provide systems for investigating the invasive and tissue-destructive capacity of squamous carcinomas of the head and neck. The morphology, ultrastructure and growth characteristics of the 10 lines are described. Detailed cytogenetic analysis of the first 4 lines indicates that each is karyotypically unique, with no evidence of cross-contamination. Nine of the 10 cell lines secrete immunoreactive beta human chorionic gonadotrophin (beta-hCG) in the culture medium. No correlation was demonstrated between the ability of the cell lines to secrete plasminogen activator and their capacity to grow in soft agar or as xenografts in immune-deficient mice. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:7195729

  8. Metastatic metaplastic breast carcinoma mimicking pulmonary squamous cell carcinoma on fine-needle aspiration.

    PubMed

    Nguyen, Doreen N; Kawamoto, Satomi; Cimino-Mathews, Ashley; Illei, Peter B; Rosenthal, Dorothy L; VandenBussche, Christopher J

    2015-10-01

    Metaplastic squamous cell carcinoma (SCC) of the breast is a rare type of breast cancer. Metastases to the lung, which can be a major site of second primary tumor development among breast cancer patients, are difficult to distinguish from primary SCC of the lung and present a unique challenge for pathologists. There are few available discriminating immunohistochemical markers as squamous differentiation typically leads to loss of expression of characteristic primary epithelial cell markers of both breast and lung origin. GATA protein binding 3 (GATA-3) is a useful marker of breast origin in metastatic ductal and lobular carcinomas including poorly differentiated triple-negative carcinomas and some metaplastic carcinomas. Here, we present a case of metastatic SCC presenting as a solitary lung mass with regional lymph node metastases and a single satellite lesion in a patient with a history of metaplastic SCC of the breast. In addition to the routine markers of squamous differentiation, the metastases were also positive for estrogen receptor (ER) and GATA-3 on cytologic material obtained by transbronchial FNA. This suggests that immunoreactivity for ER and GATA-3 may support a diagnosis of metastatic SCC in the context of a prior metaplastic SCC of the breast.

  9. Head and neck squamous cell carcinoma: new translational therapies.

    PubMed

    Prince, Anthony; Aguirre-Ghizo, Julio; Genden, Eric; Posner, Marshall; Sikora, Andrew

    2010-01-01

    Head and neck squamous cell carcinoma includes cancers of the mouth, throat, larynx, and lymph nodes of the neck. Although early disease is amenable to single-modality treatment with surgery or radiation, patients with advanced disease have a dramatically worse prognosis, despite potentially morbid/toxic treatment regimens involving surgery, radiation, chemotherapy, or all 3 modalities. The present review seeks to provide an overview of current understanding and treatment of head and neck squamous cell carcinoma for the nonspecialist clinician or basic/translational researcher, followed by an overview of major translational approaches to the treatment of head and neck squamous cell carcinoma. Translational research topics addressed include targeted molecular therapy, immunotherapy, minimally invasive robotic surgery, and ablation of dormant/residual tumor cells. Despite the many potentially promising avenues of head and neck squamous cell carcinoma research, only 2 new treatment approaches (antiepidermal growth factor receptor therapy and robotic surgery) have been approved by the US Food and Drug Administration in the past 30 years. Focused research programs involving integrated teams of clinicians, basic scientists, and translational clinician-researchers have the potential to accelerate discovery and change treatment paradigms for patients with head and neck cancer. PMID:21105129

  10. Acinic cell carcinoma on the lower lip resembling a mucocele.

    PubMed

    Cho, J H; Yoon, S Y; Bae, E Y; Lee, C N; Lee, J D; Cho, S H

    2005-09-01

    A 64-year-old woman presented with a 2-week history of an asymptomatic mass involving the lower lip. Histopathological examination showed a well-circumscribed tumour composed of many lobules separated by thin, fibrous connective tissue. Individual lobules were composed of round or polyhedral tumour cells, which had a characteristic finely granular and vacuolated cytoplasm and eccentric hyperchromatic nuclei. Positive staining was observed with Periodic acid-Shiff, and immunohistochemistry for cytokeratin, alpha-1 antitrypsin, and S-100 protein resulting in a final diagnosis of acinic cell carcinoma. Acinic cell carcinoma represents a well-established, although uncommon, entity in the classification of neoplasms of salivary gland origin. The parotid salivary gland is the most frequent site of acinic cell carcinoma, whereas the lip is a particularly unusual site. The unusual presentation of this tumour may lead to confusion with a mucocele. Given these findings, we suggest that acinic cell carcinoma should be considered in the differential diagnosis of any mucocele-like mass on the lower lip. PMID:16045674

  11. Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells

    PubMed Central

    Rombo, Roman; Weiher, Hans; Schmidt-Wolf, Ingo G.H.

    2016-01-01

    We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK) assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer. PMID:27141211

  12. Alternate Fuel Cell Membranes for Energy Independence

    SciTech Connect

    Storey, Robson, F.; Mauritz, Kenneth, A.; Patton, Derek, L.; Savin, Daniel, A.

    2012-12-18

    The overall objective of this project was the development and evaluation of novel hydrocarbon fuel cell (FC) membranes that possess high temperature performance and long term chemical/mechanical durability in proton exchange membrane (PEM) fuel cells (FC). The major research theme was synthesis of aromatic hydrocarbon polymers of the poly(arylene ether sulfone) (PAES) type containing sulfonic acid groups tethered to the backbone via perfluorinated alkylene linkages and in some cases also directly attached to the phenylene groups along the backbone. Other research themes were the use of nitrogen-based heterocyclics instead of acid groups for proton conduction, which provides high temperature, low relative humidity membranes with high mechanical/thermal/chemical stability and pendant moieties that exhibit high proton conductivities in the absence of water, and synthesis of block copolymers consisting of a proton conducting block coupled to poly(perfluorinated propylene oxide) (PFPO) blocks. Accomplishments of the project were as follows: 1) establishment of a vertically integrated program of synthesis, characterization, and evaluation of FC membranes, 2) establishment of benchmark membrane performance data based on Nafion for comparison to experimental membrane performance, 3) development of a new perfluoroalkyl sulfonate monomer, N,N-diisopropylethylammonium 2,2-bis(p-hydroxyphenyl) pentafluoropropanesulfonate (HPPS), 4) synthesis of random and block copolymer membranes from HPPS, 5) synthesis of block copolymer membranes containing high-acid-concentration hydrophilic blocks consisting of HPPS and 3,3'-disulfonate-4,4'-dichlorodiphenylsulfone (sDCDPS), 6) development of synthetic routes to aromatic polymer backbones containing pendent 1H-1,2,3-triazole moieties, 7) development of coupling strategies to create phase-separated block copolymers between hydrophilic sulfonated prepolymers and commodity polymers such as PFPO, 8) establishment of basic performance

  13. Do Clear Cell Papillary Renal Cell Carcinomas Have Malignant Potential?

    PubMed

    Diolombi, Mairo L; Cheng, Liang; Argani, Pedram; Epstein, Jonathan I

    2015-12-01

    There have been no recurrences or metastases of clear cell papillary renal cell carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language literature. We identified all our cases of CCPRCC (1990 to 2013), reviewing all cases that preceded the formal designation of the entity. Immunohistochemical stains were performed on 32 cases during their initial workup. In addition, stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one with atypical follow-up and the other with a more compact morphology, although not performed initially. An extended panel with AMACR, CD10, and renal cell carcinoma (RCC) was added to the case with atypical follow-up. Fluorescence in situ hybridization for chromosomes 3p, 7, and 17 was performed on the latter case and on another clinically presumed metastatic tumor. In classic cases, immunohistochemical staining was not performed. Fifty-eight patients (31 women; 27 men) with follow-up data were included in our study; 39 cases were from our consult service. The patients' ages ranged from 36 to 83 years. Thirty-five patients had cystic or partially cystic lesions; 6 tumors were multifocal, 3 of which were bilateral. The majority (53 patients; 91.4%) presented with stage pT1 disease (size range, 0.2 to 8 cm), 2 patients presented with pT2 disease (8.5 and 10.3 cm), 1 patient presented with pT3 disease (6.5 cm sarcomatoid RCC focally extending out of the kidney), and pathologic stage was unavailable in 2 cases. Treatment consisted of 29 partial nephrectomies, 26 radical nephrectomies, 2 cryoablations, and 1 cyst ablation. The resection margins were negative in all but one case, with this case disease free after a 26-month period. Two patients had intraoperative tumor disruption and were disease free at 9 and 34 months. Five patients had synchronous ipsilateral renal cell carcinomas (non-CCPRCC). Mean follow-up time was 21 months (range, 1 to 175 mo), with all but 3 patients having no evidence of

  14. Evaluation and staging of squamous cell carcinoma of the oral cavity and oropharynx: limitations despite technological breakthroughs.

    PubMed

    Zafereo, Mark E

    2013-08-01

    Squamous cell carcinoma of the oral cavity (SCCOC) and squamous cell carcinoma of the oropharynx (SCCOP) represent two distinct disease entities. SCCOC continues to be related to tobacco risk factors, and the current anatomic staging system provides useful prognostic value. Most patients with SCCOP in Western countries now have HPV-associated tumors, and tumor HPV status is considered the most important prognostic factor. Smoking status is emerging as an important prognostic factor for HPV-driven SCCOP, independent of tumor HPV status. Sentinel lymph node biopsy and FDG-PET/CT imaging are diagnostic staging tools useful in select patients with SCCOC and SCCOP.

  15. Photosensitizer Adhered to Cell Culture Microplates Induces Phototoxicity in Carcinoma Cells

    PubMed Central

    Ziegler, Verena; Kiesslich, Tobias; Krammer, Barbara; Plaetzer, Kristjan

    2013-01-01

    In vitro experiments in plastic receptacles are the basis of characterization of new photosensitizers (PSs) for the photodynamic therapy. We recently reported that lipophilic PSs adhere to cell culture microplates in a kinetic-like manner (Engelhardt et al., 2011). In the current study, we examined the interaction and phototoxic effects of the microplate-adhered PS in cancer cells. Therefore, we preloaded microplates with hypericin, Foscan, PVP-hypericin, or aluminum (III) phthalocyanine tetrasulfonate chloride (AlPCS4) for 24 hours and measured the PS distribution after addition of A431 human carcinoma cells: following another 24 hours up to 68% of hypericin were detected in the cell fraction. The hydrophilic PVP-hypericin and AlPCS4 also diffused into the cells, but the quantities of PS adherence were considerably lower. Microplate-adhered Foscan appeared not to be redistributed. In contrast to the hydrophilic PSs, the cellular phototoxicity of microplate-adhered lipophilic PS was high, independent of whether the PS (i) was pre-loaded onto microplates or (ii) added simultaneously with the cells or (iii) one day after cell seeding. Based on these results, we suggest testing lipophilic PS dyes for their adherence to microplates. Furthermore, the ability of plastic materials to (reversibly) store PSs might represent a new approach for the PS delivery or the development of antimicrobial coatings. PMID:23509741

  16. Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death.

    PubMed

    Sun, Hengwen; Yang, Shana; Li, Jianhua; Zhang, Yajie; Gao, Dongsheng; Zhao, Shenting

    2016-03-25

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. PMID:26920061

  17. Nuclear fractal dimension as a prognostic factor in oral squamous cell carcinoma.

    PubMed

    Goutzanis, L; Papadogeorgakis, N; Pavlopoulos, P M; Katti, K; Petsinis, V; Plochoras, I; Pantelidaki, C; Kavantzas, N; Patsouris, E; Alexandridis, C

    2008-04-01

    Strong theoretical reasons exist for using fractal geometry in measurements of natural objects, including most objects studied in pathology. Indeed, fractal dimension provides a more precise and theoretically more appropriate approximation of their structure properties and especially their shape complexity. The aim of our study was to evaluate the nuclear fractal dimension (FD) in tissue specimens from patients with oral cavity carcinomas in order to assess its potential value as prognostic factor. Relationships between FD and other factors including clinicopathologic characteristics were also investigated. Histological sections from 48 oral squamous cell carcinomas as well as from 17 non-malignant mucosa specimens were stained with Hematoxylin-Eosin for pathological examination and with Feulgen for nuclear complexity evaluation. The sections were evaluated by image analysis using fractal analysis software to quantify nuclear FD by the box-counting method. Carcinomas presented higher mean values of FD compared to normal mucosa. Well differentiated neoplasms had lower FD values than poorly differentiated ones. FD was significantly correlated with the nuclear size. Patients with FD lower than the median value of the sample had statistically significant higher survival rates. Within the sample of patients studied, FD was proved to be an independent prognostic factor of survival in oral cancer patients. In addition this study provides evidence that there are several statistically significant correlations between FD and other morphometric characteristics or clinicopathologic factors in oral squamous cell carcinomas. PMID:17692559

  18. Preclinical validation of talaporfin sodium-mediated photodynamic therapy for esophageal squamous cell carcinoma.

    PubMed

    Ohashi, Shinya; Kikuchi, Osamu; Tsurumaki, Mihoko; Nakai, Yukie; Kasai, Hiroi; Horimatsu, Takahiro; Miyamoto, Shin'ichi; Shimizu, Akira; Chiba, Tsutomu; Muto, Manabu

    2014-01-01

    Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC. PMID:25090101

  19. BIRC2 amplification in squamous cell carcinomas of the uterine cervix.

    PubMed

    Choschzick, M; Tabibzada, A M; Gieseking, F; Woelber, L; Jaenicke, F; Sauter, G; Simon, R

    2012-08-01

    Oncogene amplification is a key step in cell transformation towards malignancy. Chromosomal aberrations involving the long arm of chromosome 11, including amplifications at 11q13 and 11q22, have been previously reported in cervical cancer. While the role of the CCND1 gene as the driver gene for 11q13 amplification is well established in different tumor types, the significance of the 11q22 amplicon is less clear. The 11q22 amplicon corresponds to several putative target genes including the apoptose inhibitor BIRC2, recently detected as amplified in cervical cancer cell lines. To better understand the distribution and frequency of 11q amplification sites in uterine cervical carcinomas, we analyzed BIRC2 and CCND1 copy number changes using fluorescence in situ hybridization in a tissue microarray containing 238 cervical cancers. High-level amplification of BIRC2 was found in 12.9 % of tumors. Amplification of BIRC2 in cervical carcinomas was homogeneous as shown in corresponding whole tissue sections of amplified tumors at the tissue microarray. BIRC2 amplification was significantly more frequent than CCND1 amplification (2.1 %) in our cohort (p < 0.01), and amplification of both genes were independent from each other. BIRC2 amplification was associated with younger-patient age (p < 0.05) and squamous cell differentiation (p = 0.025) of cervix carcinomas. However, BIRC2 copy number changes were not related to tumor stage, grading and nodal status of cervical cancers. In conclusion, BIRC2 is amplified in a subset of squamous cell carcinoma of the uterine cervix. Further studies are necessary to evaluate possible prognostic effects of BIRC2 copy number gains in cervical carcinomas.

  20. Independence.

    ERIC Educational Resources Information Center

    Stephenson, Margaret E.

    2000-01-01

    Discusses the four planes of development and the periods of creation and crystallization within each plane. Identifies the type of independence that should be achieved by the end of the first two planes of development. Maintains that it is through individual work on the environment that one achieves independence. (KB)

  1. Chromophobe renal cell carcinoma with sarcomatoid transformation in a dog.

    PubMed

    Kobayashi, Naohito; Suzuki, Kazuhiko; Murakami, Hironobu; Kagawa, Eriko; Aoki, Itirou; Nagashima, Yoji

    2010-11-01

    A 12-year-old spayed female Siberian husky dog presented with hematuria and weight loss. An abdominal ultrasonographic examination revealed a left renal tumor measuring 8 cm in diameter, and a nephrectomy was performed. The resected kidney contained a cavitated tumor with a white solid region. Histologically, this tumor was composed of large polygonal cells with abundant and cloudy cytoplasm and focal sarcomatoid change. The neoplastic epithelial cells were reactive with colloidal iron staining; Dolichos biflorus agglutinin, peanut agglutinin, and Ulex europaeus agglutinin I lectins; and cluster of differentiation 10 and c-KIT antigens but not for periodic acid-Schiff or vimentin stain. Neoplastic sarcomatoid cells stained positive for vimentin. Because these histopathologic features are identical to those of human chromophobe renal cell carcinoma, the present case was diagnosed as canine chromophobe renal cell carcinoma.

  2. Circulating Tumor Cell Composition in Renal Cell Carcinoma

    PubMed Central

    Bublitz, Kira; Lazaridis, Lazaros; Goergens, André; Giebel, Bernd; Schuler, Martin; Hoffmann, Andreas-Claudius

    2016-01-01

    Purpose Due to their minimal-invasive yet potentially current character circulating tumor cells (CTC) might be useful as a “liquid biopsy” in solid tumors. However, successful application in metastatic renal cell carcinoma (mRCC) has been very limited so far. High plasticity and heterogeneity of CTC morphology challenges currently available enrichment and detection techniques with EpCAM as the usual surface marker being underrepresented in mRCC. We recently described a method that enables us to identify and characterize non-hematopoietic cells in the peripheral blood stream with varying characteristics and define CTC subgroups that distinctly associate to clinical parameters. With this pilot study we wanted to scrutinize feasibility of this approach and its potential usage in clinical studies. Experimental Design Peripheral blood was drawn from 14 consecutive mRCC patients at the West German Cancer Center and CTC profiles were analyzed by Multi-Parameter Immunofluorescence Microscopy (MPIM). Additionally angiogenesis-related genes were measured by quantitative RT-PCR analysis. Results We detected CTC with epithelial, mesenchymal, stem cell-like or mixed-cell characteristics at different time-points during anti-angiogenic therapy. The presence and quantity of N-cadherin-positive or CD133-positive CTC was associated with inferior PFS. There was an inverse correlation between high expression of HIF1A, VEGFA, VEGFR and FGFR and the presence of N-cadherin-positive and CD133-positive CTC. Conclusions Patients with mRCC exhibit distinct CTC profiles that may implicate differences in therapeutic outcome. Prospective evaluation of phenotypic and genetic CTC profiling as prognostic and predictive biomarker in mRCC is warranted. PMID:27101285

  3. Male pelvic squamous cell carcinoma of unknown primary origin.

    PubMed

    Chiec, Lauren; Verma, Sadhna; Kendler, Ady; Abdel Karim, Nagla

    2014-01-01

    Pelvic squamous cell carcinoma of unknown primary origin has been described in several case reports of female patients. However, there have been no published reports describing male patients with pelvic squamous cell cancer of unknown primary origin. Our case describes a 52-year-old man who presented with right buttock pain, rectal urgency, and constipation. His physical examination demonstrated tenderness to palpation around his gluteal folds. Computed tomography scan of his abdomen and pelvis demonstrated a large mass in his retroperitoneum. The mass was determined to be squamous cell carcinoma of unknown primary origin. Additionally, the patient had small nodules in his right lower lung lobe and right hepatic lobe. The patient was treated with concomitant chemoradiation, including cisplatin and intensity-modulated radiation therapy, followed by carboplatin and paclitaxel. The patient achieved partial remission, in which he remained one year after his presentation. Our case is consistent with the literature which suggests that squamous cell carcinoma of unknown primary origin occurring outside of the head and neck region may have a more favorable prognosis than other carcinomas of unknown primary origin. Further studies are necessary to determine the most appropriate work-up, diagnosis, and optimal treatment strategies. PMID:25478265

  4. Tracheal Resection With Carinal Reconstruction for Squamous Cell Carcinoma.

    PubMed

    Lancaster, Timothy S; Krantz, Seth B; Patterson, G Alexander

    2016-07-01

    Surgical resection is the treatment of choice for primary malignancies of the trachea. We present here the rare case of a lifelong nonsmoker with primary squamous cell carcinoma of the trachea, requiring tracheal resection and anterior carinal reconstruction. Patient preparation, surgical technique, and considerations to avoid airway anastomotic complications are discussed.

  5. Giant gingival pseudoepitheliomatous hyperplasia in lung squamous cell carcinoma.

    PubMed

    Xiang, Guolin; Long, Xing; Han, Qianchao; Tian, Lihua

    2012-07-01

    We here describe a case of giant primary gingival pseudoepitheliomatous hyperplasia in a 53-year-old Chinese male patient with lung squamous cell carcinoma (SCC). The pathogenesis of the lesion and the deferential diagnosis from invasive SCC are also discussed. To our knowledge, such a hugeous primary pseudoepitheliomatous hyperplasia of the gingiva accompanied with lung SCC is unusual.

  6. Fetal rhabdomyoma and nevoid basal cell carcinoma syndrome.

    PubMed

    DiSanto, S; Abt, A B; Boal, D K; Krummel, T M

    1992-01-01

    A 6-year-old white female presented with a fetal rhabdomyoma of the posterior mediastinum and retroperitoneum. Radiologic evaluation and family history revealed features of the nevoid basal cell carcinoma syndrome (NBS). Literature review disclosed two other children with NBS and fetal rhabdomyoma, which should be regarded as one of the soft tissue tumors associated with NBS.

  7. Human papillomavirus type 16 DNA in periungual squamous cell carcinomas

    SciTech Connect

    Moy, R.L.; Eliezri, Y.D.; Bennett, R.G. ); Nuovo, G.J.; Siverstein, S. Columbia Univ., New York, NY ); Zitelli, J.A. )

    1989-05-12

    Ten squamous cell carcinomas (in situ or invasive) of the fingernail region were analyzed for the presence of DNA sequences homologous to human papilloma-virus (HPV) by dot blot hybridization. In most patients, the lesions were verrucae of long-term duration that were refractory to conventional treatment methods. Eight of the lesions contained HPV DNA sequences, and in six of these the sequences were related to HPV 16 as deduced from low-stringency nucleic acid hybridization followed by low- and high-stringency washes. Furthermore, the restriction endonuclease digestion pattern of DNA isolated from four of these lesions was diagnostic of episomal HPV 16. The high-frequency association of HPV 16 with periungual squamous cell carcinoma is similar to that reported for HPV 16 with squamous cell carcinomas on mucous membranes at other sites, notably the genital tract. The findings suggest that HPV 16 may play an important role in the development of squamous cell carcinomas of the finger, most notably those lesions that are chronic and located in the periungual area.

  8. Prostate specific antigen gene expression in androgen insensitive prostate carcinoma subculture cell line.

    PubMed

    Tsui, Ke-Hung; Feng, Tsui-Hsia; Chung, Li-Chuan; Chao, Chun-Hsiang; Chang, Phei-Lang; Juang, Horng-Heng

    2008-01-01

    A novel prostate cancer cell line (PC-J) was isolated from an androgen independent non-prostate specific antigen (non-PSA) producing carcinoma cell line. The homologous correlation between PC-J and PC-3 was determined by short tandem repeat analysis. The PSA promoter activity was detected by transient expression assay in the PC-J and LNCaP cells but not in androgen insensitive PC-3 cells. When the PC-J cells were cotransfected with androgen receptor, androgen receptor coactivators and PSA reporter vector cells, the reporter assays indicated that nuclear receptor coactivator 4 (NCOA4) but not androgen receptor activator 24 (ARA24) increased the sensitivity and maximum stimulation of dihydrotestosterone (DHT)-inducing PSA promoter activity. The RT-PCR assays revealed that the expression of several tumor markers, including interleukin-6, prostate stem cell antigen (PSCA), prostate epithelium-specific Ets transcription factor (PDEF) and matriptase, was lower in the PC-J cells than in the PC-3 cells. This cell model elucidated the regulation of PSA expression and enabled comparison of the gene profile at different stages of metastasis in prostatic carcinoma.

  9. Bortezomib With or Without Irinotecan in Treating Patients With Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2014-05-07

    Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  10. Comprehensive molecular characterization of clear cell renal cell carcinoma.

    PubMed

    2013-07-01

    Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.

  11. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

    PubMed Central

    2013-01-01

    Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (e.g. VHL) and the maintenance of chromatin states (e.g. PBRM1). We surveyed more than 400 tumors using different genomic platforms and identified 19 significantly mutated genes. The PI3K/Akt pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodeling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving down-regulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, up-regulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 and GRB10. Remodeling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumor stage and severity and offers new views on the opportunities for disease treatment. PMID:23792563

  12. Enterovesical Fistula Secondary to Squamous Cell Carcinoma of the Bladder.

    PubMed

    Sellers, William; Fiorelli, Robert

    2015-11-01

    Enterovesical fistulas are a well-known complication of inflammatory and malignant bowel disease. Bladder carcinoma, however, is an extremely rare etiology. We describe a case of squamous cell carcinoma of the bladder with an enterovesical fistula. This rare phenomenon has never been previously reported in western literature. We review the diagnosis, work up and treatment of enterovesical fistulas. Unfortunately, the prognosis for these highly invasive tumors is very poor and the treatment is often palliative. The high morbidity and mortality makes management of these patients exceptionally challenging.

  13. Isolated adrenal masses in nonsmall-cell bronchogenic carcinoma

    SciTech Connect

    Oliver, T.W. Jr.; Bernardino, M.E.; Miller, J.I.; Mansour, K.; Greene, D.; Davis, W.A.

    1984-10-01

    Computed tomography has become an important diagnostic modality in the preoperative staging of patients with bronchogenic carcinoma. The adrenal glands represent one of the most frequent sites of metastasis. Therefore, an isolated adrenal mass discovered on preoperative thoracoabdominal CT poses a diagnostic problem. Three hundred thirty patients with histologically proved nonsmall-cell bronchogenic carcinoma were evaluated. Thirty-two had adrenal masses without further evidence of disease in the abdomen, Eight of these 32 masses were metastases, 17 were proved adenomas, and 7 did not undergo biopsy. Thus an isolated adrenal mass is more likely benign than metastatic, and biopsy is advocated prior to withholding potentially curative surgery.

  14. Citrus consumption and risk of basal cell carcinoma and squamous cell carcinoma of the skin

    PubMed Central

    Wu, Shaowei; Cho, Eunyoung; Feskanich, Diane; Li, Wen-Qing; Sun, Qi; Han, Jiali; Qureshi, Abrar A.

    2015-01-01

    Animal experiments have demonstrated the photocarcinogenic properties of furocoumarins, a group of naturally occurring chemicals that are rich in citrus products. We conducted a prospective study for citrus consumption and risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on data from 41530 men in the Health Professionals Follow-up Study (1986–2010) and 63759 women in the Nurses’ Health Study (1984–2010) who were free of cancers at baseline. Over 24–26 years of follow-up, we documented 20840 incident BCCs and 3544 incident SCCs. Compared to those who consumed citrus products less than twice per week, the pooled multivariable-adjusted hazard ratios were 1.03 [95% confidence interval (95% CI): 0.99–1.08] for BCC and 1.14 (95% CI: 1.00–1.30) for SCC for those who consumed two to four times per week, 1.06 (95% CI: 1.01–1.11) for BCC and 1.15 (95% CI: 1.02–1.28) for SCC for five to six times per week, 1.11 (95% CI: 1.06–1.16) for BCC and 1.22 (95% CI: 1.08–1.37) for SCC for once to 1.4 times per day and 1.16 (95% CI: 1.09–1.23) for BCC and 1.21 (95% Cl: 1.06–1.38) for SCC for 1.5 times per day or more (P trend = 0.001 for BCC and 0.04 for SCC). In contrast, consumption of non-citrus fruit and juice appeared to be inversely associated with risk of BCC and SCC. Our findings support positive associations between citrus consumption and risk of cutaneous BCC and SCC in two cohorts of men and women, and call for further investigations to better understand the potential photocarcinogenesis associated with dietary intakes. PMID:26224304

  15. Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

    SciTech Connect

    Felthaus, O.; Ettl, T.; Gosau, M.; Driemel, O.; Brockhoff, G.; Reck, A.; Zeitler, K.; Hautmann, M.; Reichert, T.E.; Schmalz, G.; Morsczeck, C.

    2011-04-01

    Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simple method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.

  16. Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression

    PubMed Central

    Bhatia, Kishor; Goedert, James J.; Modali, Rama; Preiss, Liliana; Ayers, Leona W.

    2010-01-01

    Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), a clinically and pathologically heterogeneous malignancy of dermal neuroendocrine cells. To investigate this heterogeneity, we developed a tissue microarray (TMA) to characterize immunohistochemical staining of candidate tumor cell proteins and a quantitative PCR assay to detect MCPyV and measure viral loads. MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of these had less than 1 viral copy per 300 cells. Viral abundance of 0.06–1.2viral copies/cell was directly related to presence of retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl transferase (TdT) by immunohistochemical staining (P≤0.003). Higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis, and longer survival (P≤0.08). These data suggest that MCC may arise through different oncogenic pathways, including ones independent of pRb and MCPyV. PMID:19551862

  17. miR-411 regulated ITCH expression and promoted cell proliferation in human hepatocellular carcinoma cells.

    PubMed

    Xia, Kunkun; Zhang, Yi; Cao, Shengli; Wu, Yang; Guo, Wenzhi; Yuan, Weitang; Zhang, Shuijun

    2015-03-01

    Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third most common cause of cancer mortality in the world. In this study, we report that miR-411 expression is markedly upregulated in HCC cells and HCC tissues compared with normal control tissues and cells. Previous studies have shown that miR-411 plays a crucial role in a variety of biological processes in various human cancer cells. However, the specific function of miR-411 in HCC remains unclear. Ectopic expression of miR-411 promoted the proliferation and anchorage-independent growth of HCC cells, whereas inhibition of miR-411 reduced this effect. Bioinformatics analysis further revealed ITCH, a putative tumor suppressor as a potential target of miR-411. Data from luciferase reporter assays showed that miR-411 directly binds to the 3'-untranslated region (3'-UTR) of ITCH mRNA and repressed expression at both transcriptional and translational levels. In functional assays, miR-411 promoted HCC cell proliferation, which could be suppressed by miR-411-in. Taken together, our data provide convincing evidence that miR-411 functions as an onco-miRNA, which was associated with cell proliferation of HCC, and its oncogenic effect is mediated chiefly through direct suppression of ITCH expression.

  18. Dectin-1 predicts adverse postoperative prognosis of patients with clear cell renal cell carcinoma

    PubMed Central

    Xia, Yu; Liu, Li; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

    2016-01-01

    Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P < 0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients’ survival together with other clinical parameters (P < 0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients’ RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P < 0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments. PMID:27600310

  19. Dectin-1 predicts adverse postoperative prognosis of patients with clear cell renal cell carcinoma.

    PubMed

    Xia, Yu; Liu, Li; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

    2016-01-01

    Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P < 0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients' survival together with other clinical parameters (P < 0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients' RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P < 0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments. PMID:27600310

  20. Podoplanin associates with adverse postoperative prognosis of patients with clear cell renal cell carcinoma.

    PubMed

    Xia, Yu; Liu, Li; Xiong, Ying; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xu, Jiejie; Guo, Jianming

    2016-09-01

    Podoplanin, a transmembrane sialomucin-like glycoprotein, was recently shown to be involved in tumor progression and metastasis, and its potential role in facilitating platelet-based tumor embolization and promigratory phenotype of cancer cells was also demonstrated. In this study, we assessed the clinical significance of tumoral podoplanin expression in 295 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays and analyzing the staining intensity. Univariate analysis suggested an adverse prognostic effect of high tumoral podoplanin expression on patients' overall survival (OS) and recurrence-free survival (RFS) (P < 0.001 for both). In the multivariate analysis, high tumoral podoplanin expression (using staining intensity as either a continuous or dichotomous variable) was still an independent adverse prognostic factor for patient survival (OS, P < 0.001, RFS, P < 0.001 for continuous; OS, P < 0.001, RFS, P = 0.002 for dichotomous). Moreover, stratified analysis identified a higher prognostic power in the intermediate/high risk patient groups. After utilizing those parameters in the validated multivariate analysis, two nomograms were constructed to predict ccRCC patients' OS and RFS (c-index 0.815 and 0.805, respectively), and performed better than existing integrated models (P < 0.001 for all comparisons). In conclusion, high tumoral podoplanin expression could independently predict an adverse clinical outcome for ccRCC patients, and it might be useful in future for clinical decision-making and therapeutic developments. PMID:27389969

  1. Squamous cell carcinoma and pilonidal cyst disease.

    PubMed

    Esposito, Francesco; Lauro, Mario; Tirone, Lucio Pasquale; Festa, Rosa Maria; Peluso, Gaia; Mazzoni, Giada; Scognamiglio, Marco; Grimaldi, Simona; Fresini, Antonio

    2015-02-20

    Il carcinoma a cellule squamose insorgente su malattia del seno pilonidale è una patologia abbastanza rara che sopraggiunge in presenza di malattia con decorso decennale. È caratterizzato da una crescita lenta ma da un’elevata invasività locale. Gli autori riportano il caso di un paziente di 63 anni con storia pluridecennale di malattia del seno pilonidale con ascessualizzazioni ricorrenti trattato chirurgicamente con resezione ampia e ricostruzione mediante uso di lembi. A distanza di 30 mesi non sono state osservate complicanze o recidive locali.

  2. Spindle cell carcinoma of the mandible: Clinicopathological and immunohistochemical characteristics.

    PubMed

    Al-Bayaty, Haytham; Balkaran, Ramaa L

    2016-01-01

    Spindle cell carcinoma, a rare variant of squamous cell carcinoma, has propensity to occur in the upper aero digestive tract, including the oral mucosa. In this oral pathology communication, we report the occurrence of this neoplasm in the left mandible as a large fleshy growth with destruction of bone in a 73-year-old Afro-Trinidadian female. The distinction of this tumor from other malignant spindle cell mesenchymal tumors is important. Selective sampling of this specimen for possible transitional areas of squamous and spindle cell appearance, immunohistochemical staining for cytokeratin, vimentin, and S-100 protein are helpful in establishing the diagnosis. According to the patient's insistence, debulking of the tumor was performed under general anesthesia. Eight months later the patient succumbed to the disease.

  3. Collision Tumor With Renal Cell Carcinoma and Plasmacytoma: Further Evidence of a Renal Cell and Plasma Cell Neoplasm Relationship?

    PubMed Central

    Berquist, Sean W.; Hassan, Abd-elrahman Said; Miakicheva, Olga; Dufour, Catherine; Hamilton, Zachary; Shabaik, Ahmed; Derweesh, Ithaar H.

    2016-01-01

    Renal solitary extramedullary plasmacytomas belong to a group of plasma cell neoplasms, which generally have been associated with renal cell carcinoma. We present a case report of a patient with collision tumor histology of extramedullary plasmacytoma and clear cell renal cell carcinoma, the first in the known literature. Standard work-up for a plasma cell neoplasm was conducted and the mass was resected. The patient remains disease-free at 28 months post-surgery. The report calls into question pre-surgical renal mass biopsy protocol and suggests a relationship between renal cell carcinoma and plasma cell neoplasms. PMID:27175345

  4. Dissemination of Walker 256 carcinoma cells to rat skeletal muscle

    SciTech Connect

    Ueoka, H.; Hayashi, K.; Namba, T.; Grob, D.

    1986-03-05

    After injection of 10/sup 6/ Walker 256 carcinoma cells labelled with /sup 125/I-5-iodo-2'-deoxyuridine into the tail vein, peak concentration in skeletal muscle was 46 cells/g at 60 minutes, which was lower than 169202, 1665, 555, 198 and 133 cells/g, respectively, at 30 or 60 minutes in lung, liver, spleen, kidney and heart. Because skeletal muscle constitutes 37.4% of body weight, the total number of tumor cells was 2323 cells, which was much greater than in spleen, kidney and heart with 238, 271, and 85 cells, respectively, and only less than in lung and liver, at 222857 and 11700 cells, respectively. The total number in skeletal muscle became greater than in liver at 4 hours and than in lung at 24 hours. Ten minutes after injection of 7.5 x 10/sup 6/ Walker 256 carcinoma cells into the abdominal aorta of rats, a mean of 31 colony-forming cells were recovered from the gastrocnemius, while 106 cells were recovered from the lung after injection into the tail vein. These results indicate that a large number of viable tumor cells can be arrested in skeletal muscle through circulation. The rare remote metastasis of malignancies into skeletal muscle despite constantly circulating tumor cells does not appear to be due to poor dissemination of tumor cells into muscle but due to unhospitable environment of skeletal muscle.

  5. Gastric metastasis of renal cell carcinoma 20 years after radical nephrectomy

    PubMed Central

    Akay, Ebru; Kala, Mehtap; Karaman, Hatice

    2016-01-01

    Renal cell carcinomas account for 2–3% of malignant neoplasms in adults. The lung, soft tissues and bone represent the most frequent sites of distant metastasis in renal cell carcinoma. Gastric metastasis is rare. Our case was a 72-year-old man with complaints of fatigue and loss of appetite. In history, he had unergone radical nephrectomy due to renal cell carcinoma in 1993. A polypoid lesion was observed in upper gastrointestinal endoscopy. Histopathology of gastric biopsy specimen was reported as renal cell carcinoma. In English literature, there are 50 cases diagnosed as gastric metastasis from renal cell carcinoma. To date, there are only 4 cases with extremely late gastric metastasis of renal cell carcinoma. Herein, we present a rare case which underwent radical nephrectomy due to renal cell carcinoma and found to have gastric metastasis at 20. year of his follow-up. PMID:27274897

  6. Review of paraneoplastic syndromes associated with oropharyngeal squamous cell carcinoma

    PubMed Central

    Mathew, Deepu George; Rooban, T; Janani, V; Joshua, E; Rao, UK; Ranganathan, K

    2010-01-01

    Malignancies are usually preceded by the presence of various paraneoplastic syndromes (PNS), which could be the indirect and/or remote effects of the metabolites produced by neoplastic cells. PNS manifested by oropharyngeal squamous cell carcinomas, which is the most common head and neck malignancy, are highlighted in this review. Knowledge of the clinical spectrum of these syndromes will equip the oral physician for early diagnosis and management of these hidden malignancies, especially of the pharyngeal region. PMID:21731261

  7. Merkel Cell Carcinoma: When Does Size Matter for Radiotherapy?

    PubMed Central

    Roach, Michelle; Lee, Mark T

    2015-01-01

    Merkel cell carcinoma is a very aggressive, rare cancer of the skin. It has a high propensity for local, regional, and distant recurrence and has recently been associated with a viral etiology from the recently diagnosed Merkel Cell Polyoma Virus. The optimal management remains controversial. We discuss the case of a man with a 26 cm axillary lymph node metastasis of unknown primary treated with radiotherapy. PMID:26858924

  8. Spindle cell carcinoma of the tongue combined with double primary cancer of the thyroid gland: a case report

    PubMed Central

    2016-01-01

    Spindle cell carcinoma (SpCC) is referred to as a variant of oral squamous cell carcinoma. It is also known as "sarcomatoid squamous cell carcinoma" because it consists of normal squamous carcinoma cells with spindle-shaped cells that appear similar to a sarcoma. The term, "second primary tumor" (SPT) or "double primary tumor", is proposed for a second tumor that develops independently from the first. SPTs can present as either synchronous or metachronous lesions. Synchronous SPTs are defined as tumors occurring simultaneously or within 6 months after the first tumor. The patient in this case, whose primary tumor was in the tongue, was diagnosed with SpCC with metastases to both neck lymph nodes. This case also exhibited a second primary cancer as a synchronous lesion in the thyroid gland, which is uncommon. All carcinomas, both in the tongue and thyroid gland, were removed surgically, and especially in the tongue, an anterolateral thigh free flap was performed successfully to replace the defect.

  9. Spindle cell carcinoma of the tongue combined with double primary cancer of the thyroid gland: a case report.

    PubMed

    Kim, Tae-Hwan; Kim, Chul-Hwan

    2016-08-01

    Spindle cell carcinoma (SpCC) is referred to as a variant of oral squamous cell carcinoma. It is also known as "sarcomatoid squamous cell carcinoma" because it consists of normal squamous carcinoma cells with spindle-shaped cells that appear similar to a sarcoma. The term, "second primary tumor" (SPT) or "double primary tumor", is proposed for a second tumor that develops independently from the first. SPTs can present as either synchronous or metachronous lesions. Synchronous SPTs are defined as tumors occurring simultaneously or within 6 months after the first tumor. The patient in this case, whose primary tumor was in the tongue, was diagnosed with SpCC with metastases to both neck lymph nodes. This case also exhibited a second primary cancer as a synchronous lesion in the thyroid gland, which is uncommon. All carcinomas, both in the tongue and thyroid gland, were removed surgically, and especially in the tongue, an anterolateral thigh free flap was performed successfully to replace the defect. PMID:27595090

  10. Spindle cell carcinoma of the tongue combined with double primary cancer of the thyroid gland: a case report

    PubMed Central

    2016-01-01

    Spindle cell carcinoma (SpCC) is referred to as a variant of oral squamous cell carcinoma. It is also known as "sarcomatoid squamous cell carcinoma" because it consists of normal squamous carcinoma cells with spindle-shaped cells that appear similar to a sarcoma. The term, "second primary tumor" (SPT) or "double primary tumor", is proposed for a second tumor that develops independently from the first. SPTs can present as either synchronous or metachronous lesions. Synchronous SPTs are defined as tumors occurring simultaneously or within 6 months after the first tumor. The patient in this case, whose primary tumor was in the tongue, was diagnosed with SpCC with metastases to both neck lymph nodes. This case also exhibited a second primary cancer as a synchronous lesion in the thyroid gland, which is uncommon. All carcinomas, both in the tongue and thyroid gland, were removed surgically, and especially in the tongue, an anterolateral thigh free flap was performed successfully to replace the defect. PMID:27595090

  11. Clear cell papillary renal cell carcinoma-like tumors in patients with von Hippel-Lindau disease are unrelated to sporadic clear cell papillary renal cell carcinoma.

    PubMed

    Williamson, Sean R; Zhang, Shaobo; Eble, John N; Grignon, David J; Martignoni, Guido; Brunelli, Matteo; Wang, Mingsheng; Gobbo, Stefano; Baldridge, Lee Ann; Cheng, Liang

    2013-08-01

    Clear cell papillary renal cell carcinoma (CCPRCC) shares morphologic overlap with clear cell renal cell carcinoma, although it lacks chromosome 3p and VHL gene abnormalities. Rare cases have been reported in von Hippel-Lindau (VHL) patients (germline mutation of the VHL gene), the significance of which is uncertain. We analyzed morphologic, immunohistochemical, and molecular features in 14 CCPRCC-like tumors and 13 clear cell renal cell carcinomas from 12 patients with VHL disease. Gross appearance of CCPRCC-like tumors ranged from yellow-orange to tan, red-brown, or extensively cystic. Histologic features included: small papillary tufts (79%), branched tubules (71%), branched papillae (64%), flattened peripheral cysts (64%), and apically aligned nuclei (43%). Almost all CCPRCC-like tumors (82%) lacked the characteristic immunoprofile of sporadic CCPRCC (CK7, CAIX, CD10, AMACR), often showing diffuse CD10 labeling (64%), negative or focal CK7 reactivity (55%), or both (18%). Three tumors (27%) showed strong AMACR staining. Chromosome 3p deletion was often present (82%), similar to that observed in clear cell renal cell carcinomas (80%); no CCPRCC-like tumor had chromosome 7 or 17 abnormalities. In summary, tumors that histologically resemble CCPRCC sometimes occur in patients with VHL disease but usually lack the characteristic immunohistochemical and molecular profile, suggesting that they do not share the same pathogenesis. PMID:23648463

  12. Diagnosis and treatment in primary bladder small cell carcinoma: Literature review.

    PubMed

    Celik, Orcun; Ekin, Gokhan; Ipekci, Tumay; Budak, Salih; Ilbey, Yusuf Ozlem

    2016-03-01

    Small cell bladder carcinoma is a rare and frequently fatal disease. It can be distinguished from classical urothelial carcinoma microscopically and immunohistochemically. Small cell bladder carcinoma has histologically similar properties with other small cell carcinomas in other organs. It has a worse prognosis when compared to urothelial bladder cancer. Multimodal treatments are recommended although there is no widely accepted consensus regarding to the treatment algorithm because of its rarity. In this review, clinical properties and diagnosis of small cell bladder carcinoma, its histopathological and immunohistochemical properties and treatment modalities are examined. PMID:27072176

  13. Acanthosis Nigricans associated with clear-cell renal cell carcinoma

    PubMed Central

    Narvaez, Margarita Rosa Aveiga; Reis, Paola Vasconcellos Soares; Gomes, Augusto Cesar Marins; Paraskevopoulos, Daniela Kallíope de Sá; Santana, Frederico; Fugita, Oscar Eduardo Hidetoshi

    2016-01-01

    Acanthosis nigricans (AN), an entity recognized since the 19th century, is a dermatopathy associated with insulin-resistant conditions, endocrinopathies, drugs, chromosome abnormalities and neoplasia. The latter, also known as malignant AN, is mostly related to abdominal neoplasms. Malignant AN occurs frequently among elderly patients. In these cases, the onset is subtle, and spreading involves the flexural regions of the body, particularly the axillae, palms, soles, and mucosa. Gastric adenocarcinoma is the most frequent associated neoplasia, but many others have been reported. Renal cell carcinoma (RCC), although already reported, is rarely associated with malignant AN. The authors report the case of a woman who was being treated for depression but presented a long-standing and marked weight loss, followed by darkening of the neck and the axillary regions. Physical examination disclosed a tumoral mass in the left flank and symmetrical, pigmented, velvety, verrucous plaques on both axillae, which is classical for AN. The diagnostic work-up disclosed a huge renal mass, which was resected and further diagnosed as a RCC. The post-operative period was uneventful and the skin alteration was evanescent at the first follow-up consultation. The authors call attention to the association of AN with RCC. PMID:27284539

  14. Acanthosis Nigricans associated with clear-cell renal cell carcinoma.

    PubMed

    Ferraz de Campos, Fernando Peixoto; Narvaez, Margarita Rosa Aveiga; Reis, Paola Vasconcellos Soares; Gomes, Augusto Cesar Marins; Paraskevopoulos, Daniela Kallíope de Sá; Santana, Frederico; Fugita, Oscar Eduardo Hidetoshi

    2016-01-01

    Acanthosis nigricans (AN), an entity recognized since the 19th century, is a dermatopathy associated with insulin-resistant conditions, endocrinopathies, drugs, chromosome abnormalities and neoplasia. The latter, also known as malignant AN, is mostly related to abdominal neoplasms. Malignant AN occurs frequently among elderly patients. In these cases, the onset is subtle, and spreading involves the flexural regions of the body, particularly the axillae, palms, soles, and mucosa. Gastric adenocarcinoma is the most frequent associated neoplasia, but many others have been reported. Renal cell carcinoma (RCC), although already reported, is rarely associated with malignant AN. The authors report the case of a woman who was being treated for depression but presented a long-standing and marked weight loss, followed by darkening of the neck and the axillary regions. Physical examination disclosed a tumoral mass in the left flank and symmetrical, pigmented, velvety, verrucous plaques on both axillae, which is classical for AN. The diagnostic work-up disclosed a huge renal mass, which was resected and further diagnosed as a RCC. The post-operative period was uneventful and the skin alteration was evanescent at the first follow-up consultation. The authors call attention to the association of AN with RCC. PMID:27284539

  15. Detection and Characterization of Carcinoma Cells in the Blood

    NASA Astrophysics Data System (ADS)

    Racila, Emilian; Euhus, David; Weiss, Arthur J.; Rao, Chandra; McConnell, John; Terstappen, Leon W. M. M.; Uhr, Jonathan W.

    1998-04-01

    A highly sensitive assay combining immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis has been developed to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 ml) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls was examined by flow cytometry for the presence of circulating epithelial cells defined as nucleic acid+, CD45-, and cytokeratin+. Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with cancer including 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytospin preparations were made after immunomagnetic enrichment and were analyzed. Epithelial cells from patients with breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast, no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consistent with that of neoplastic cells. Of 8 patients with breast cancer followed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemotherapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.

  16. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    PubMed Central

    Martinez, Victor D.; Becker-Santos, Daiana D.; Vucic, Emily A.; Lam, Stephen; Lam, Wan L.

    2011-01-01

    Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epigenomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans. PMID:22175027

  17. Conjunctival squamous cell carcinoma in a reindeer (Rangifer tarandus tarandus).

    PubMed

    Gonzalez-Alonso-Alegre, Elisa M; Rodriguez-Alvaro, Alfonso; Martinez-Nevado, Eva; Martinez-de-Merlo, Elena M; Sanchez-Maldonado, Belen

    2013-07-01

    An 8-year-old female adult reindeer (Rangifer tarandus tarandus) was referred to the Veterinary Hospital of Madrid for evaluation of a conjunctival mass on the left eye which had been present for about 2 months. A surgical excision was performed and biopsy material submitted for light microscopic evaluation which confirmed the diagnosis of conjuctival squamous cell carcinoma. Nuclear p53 immunolabeling was found in 52% of the neoplastic cells. Follow-up examination at 12 months postsurgery did not reveal recurrence of this neoplasm. Conjunctival squamous cell carcinoma has not been reported previously in reindeer and seems to have similar characteristics to the one existing in bovine species.

  18. Radiosensitization of human bronchogenic carcinoma cells by interferon beta

    SciTech Connect

    Gould, M.N.; Kakria, R.C.; Olson, S.; Borden, E.C.

    1984-01-01

    The effects of interferons on the radiosensitivity of in vitro human bronchogenic carcinoma cells was investigated. Human fibroblast-derived interferon (IFN-beta) was found to sensitize cells to gamma irradiation while either HuIFN-alpha or mouse IFN-alpha/beta did not. The observed radiosensitization was supra-additive and resulted in a decrease in the shoulder width of the radiation dose-cell survival curve but did not affect the slope. The degree of radiosensitization of the various IFNs tested paralleled the antiproliferative effects of these IFNs on this cell line.

  19. Trichoepithelioma and Basal Cell Carcinoma with Squamous Differentiation: Is it Causal or Coincidental?

    PubMed Central

    Agarwal, Palak; Agarwal, Charu; Bhardwaj, Minakshi; Ahuja, Arvind; Rani, Seema

    2015-01-01

    Trichoepitheliomas (TEs) are benign cutaneous tumors that occur either as solitary non-familial or multiple familial. We report a case of multiple familial trichoepithelioma (MFT) in a 55-year-old female patient and her son who came with complaints of single ulcerated mass involving the left nasolabial fold and cheek. She had multiple papules and nodules all over the face and neck since 25 years. Histopathological examination of an ulcerated lesion revealed features of basal cell carcinoma (BCC) with squamous differentiation, which was confirmed by immunohistochemistry. A skin biopsy obtained from the papule on neck showed features of TE. However, whether BCC developed independently or by transformation from TE was uncertain. Her 36-year-old son presented with similar lesions on the face and a skin biopsy showed features of TE. Though malignant transformation of TE is quite rare, awareness of the potential for evolution of carcinoma in patients with MFT is important for management of these patients. PMID:26288412

  20. Oral squamous cell carcinoma in a pigtailed macaque (Macaca nemestrina).

    PubMed

    Stockinger, Diane E; Fong, Derek L; Vogel, Keith W; Durning, W McIntyre; Torrence, Anne E; Rose, Timothy M; Staheli, Jeannette P; Baldessari, Audrey; Murnane, Robert D; Hukkannen, Renee R

    2014-06-01

    An adult, gravid, female pigtailed macaque (Macaca nemestrina) presented for facial swelling centered on the left mandible that was approximately 5 cm wide. Differential diagnoses included infectious, inflammatory, and neoplastic origins. Definitive antemortem diagnosis was not possible, and the macaque's condition worsened despite supportive care. Necropsy findings included a mandibular mass that was locally invasive and expansile, encompassing approximately 80% of the left mandibular bone. The mass replaced portions of the soft palate, hard palate, sinuses, ear canal, and the caudal-rostral calvarium and masseter muscle. Histologically, the mass was a neoplasm that was poorly circumscribed, unencapsulated, and infiltrative invading regional bone and soft tissue. The mass consisted of polygonal squamous epithelial cells with intercellular bridging that breached the epithelial basement membrane and formed invasive nests, cords, and trabeculae. The mitotic rate averaged 3 per 400× field of view, with occasional bizarre mitotic figures. Epithelial cells often exhibited dyskeratosis, and the nests often contained compact lamellated keratin (keratin pearls). The neoplasm was positive via immunohistochemistry for pancytokeratin, variably positive for S100, and negative for vimentin, smooth muscle actin, and desmin. The gross, histologic, and immunohistochemical findings were consistent with an aggressive oral squamous cell carcinoma. The neoplasm was negative via PCR for papilloma virus. In general, neoplasia in macaques is rare. Although squamous cell carcinomas are one of the most common oral neoplasia in many species, to our knowledge this case represents the first reported oral squamous cell carcinoma in a pigtailed macaque.

  1. Using Molecular Biology to Develop Drugs for Renal Cell Carcinoma

    PubMed Central

    Cowey, C. Lance; Rathmell, W. Kimryn

    2010-01-01

    Background Renal cell carcinoma is a disease marked by a unique biology which has governed it’s long history of poor response to conventional cancer treatments. The discovery of the signaling pathway activated as a result of inappropriate constitutive activation of the hypoxia inducible factors (HIF), transcription factors physiologically and transiently stabilized in response to low oxygen, has provided a primary opportunity to devise treatment strategies to target this oncogenic pathway. Objective A review of the molecular pathogenesis of renal cell cancer as well as molecularly targeted therapies, both those currently available and those in development, will be provided. In addition, trials involving combination or sequential targeted therapy are discussed. Methods A detailed review of the literature describing the molecular biology of renal cell cancer and novel therapies was performed and summarized. Results/Conclusion Therapeutics targeting angiogenesis have provided the first class of agents which provide clinical benefit in a large majority of patients and heralded renal cell carcinoma as a solid tumor paradigm for the development of novel therapeutics. Multiple strategies targeting this pathway and now other identified pathways in renal cell carcinoma provide numerous potential opportunities to make major improvements in treating this historically devastating cancer. PMID:20648240

  2. [Epidermoid carcinoma of the urethra and glans penis: two independent tumors?].

    PubMed

    Pascual Regueiro, D; García de Jalón Martínez, A; Trívez Boned, M A; Gil Martínez, P; Azúa Romeo, J; Rioja Sanz, L A

    2004-01-01

    A 64 years-old man is treated in our hospital presenting a big tumor in glans penis. During the surgical act, another neoplasm is detected in the urethra. The microscopic study showed a concomintant epidermoid carcinoma of glans penis and urethra with non-affected tissue between both tumors. PMID:15666524

  3. Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma.

    PubMed

    van Kempen, Pauline M W; Noorlag, Rob; Braunius, Weibel W; Moelans, Cathy B; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; van Es, Robert J J; Willems, Stefan M

    2015-10-01

    Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I-II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC. PMID:26194878

  4. HIF1-Alpha Expression Predicts Survival of Patients with Squamous Cell Carcinoma of the Oral Cavity

    PubMed Central

    dos Santos, Marcelo; Mercante, Ana Maria da Cunha; Louro, Iúri Drumond; Gonçalves, Antônio José; de Carvalho, Marcos Brasilino; da Silva, Eloiza Helena Tajara; da Silva, Adriana Madeira Álvares

    2012-01-01

    Background Oral squamous cell carcinoma is an important cause of death and morbidity wordwide and effective prognostic markers are still to be discovered. HIF1α protein is associated with hypoxia response and neovascularization, essential conditions for solid tumors survival. The relationship between HIF1α expression, tumor progression and treatment response in head and neck cancer is still poorly understood. Patients and Methods In this study, we investigated HIF1α expression by immunohistochemistry in tissue microarrays and its relationship with clinical findings, histopathological results and survival of 66 patients with squamous cell carcinoma of the lower mouth. Results Our results demonstrated that high HIF1α expression is associated with local disease-free survival, independently from the choice of treatment. Furthermore, high expression of HIF1α in patients treated with postoperative radiotherapy was associated with survival, therefore being a novel prognostic marker in squamous cell carcinoma of the mouth. Additionally, our results showed that MVD was associated with HIF1α expression and local disease relapse. Conclusion These findings suggest that HIF1α expression can be used as a prognostic marker and predictor of postoperative radiotherapy response, helping the oncologist choose the best treatment for each patient. PMID:23028863

  5. Identification of HRAS as cancer-promoting gene in gastric carcinoma cell aggressiveness

    PubMed Central

    Wu, Xiao Yu; Liu, Wen Tao; Wu, Zhen Feng; Chen, Che; Liu, Jia Yun; Wu, Guan Nan; Yao, Xue Quan; Liu, Fu Kun; Li, Gang

    2016-01-01

    Gastric carcinoma is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that HRAS is markedly up-regulated in gastric carcinoma. Prognostic analysis indicated that HRAS expression might be a prognostic indicator for the survival of patients with gastric carcinoma. Ectopic expression of HRAS in gastric carcinoma cells accelerated proliferation, migration, invasion, angiogenesis, and clone formation ability of gastric carcinoma cells in vitro. Furthermore, HRAS over-expressing significantly promoted the tumorigenicity of gastric carcinoma cells in vivo whereas silencing endogenous HRAS caused opposite outcomes. Moreover, we demonstrated that HRAS enhanced gastric carcinoma aggressiveness by activating VEGFA/PI3K/AKT pathway and Raf-1 signaling. Together, our results provide new evidence that HRAS overexpression promotes the progression of gastric carcinoma and might represent a novel therapeutic target for its treatment. PMID:27725900

  6. A case of renal cell carcinoma metastasizing to invasive ductal breast carcinoma.

    PubMed

    Chen, Tai-Di; Lee, Li-Yu

    2014-02-01

    Tumor-to-tumor metastasis is an uncommon but well-documented phenomenon. We present a case of a clear cell renal cell carcinoma (RCC) metastasizing to an invasive ductal carcinoma (IDC) of the breast. A 74-year-old woman with a past history of clear cell RCC status after radical nephrectomy underwent right modified radical mastectomy for an enlarging breast mass 3 years after nephrectomy. Histological examination revealed a small focus with distinct morphological features similar to clear cell RCC encased in the otherwise typical IDC. Immunohistochemical studies showed that this focus was positive for CD10 and vimentin, in contrast to the surrounding IDC, which was negative for both markers and positive for Her2/neu. Based on the histological and immunohistochemical features, the patient was diagnosed with metastasis of clear cell RCC to the breast IDC. To the best of our knowledge, this is the first reported case of a breast neoplasm as the recipient tumor in tumor-to-tumor metastasis. PMID:24530247

  7. Melatonin antiproliferative effects require active mitochondrial function in embryonal carcinoma cells

    PubMed Central

    Loureiro, Rute; Magalhães-Novais, Silvia; Mesquita, Katia A.; Baldeiras, Ines; Sousa, Isabel S.; Tavares, Ludgero C.; Barbosa, Ines A.; Oliveira, Paulo J.; Vega-Naredo, Ignacio

    2015-01-01

    Although melatonin oncostatic and cytotoxic effects have been described in different types of cancer cells, the specific mechanisms leading to its antitumoral effects and their metabolic context specificity are still not completely understood. Here, we evaluated the effects of melatonin in P19 embryonal carcinoma stem cells (CSCs) and in their differentiated counterparts, cultured in either high glucose medium or in a galactose (glucose-free) medium which leads to glycolytic suppression and increased mitochondrial metabolism. We found that highly glycolytic P19 CSCs were less susceptible to melatonin antitumoral effects while cell populations relying on oxidative metabolism for ATP production were more affected. The observed antiproliferative action of melatonin was associated with an arrest at S-phase, decreased oxygen consumption, down-regulation of BCL-2 expression and an increase in oxidative stress culminating with caspase-3-independent cell death. Interestingly, the combined treatment of melatonin and dichloroacetate had a synergistic effect in cells grown in the galactose medium and resulted in an inhibitory effect in the highly resistant P19 CSCs. Melatonin appears to exert its antiproliferative activity in P19 carcinoma cells through a mitochondrially-mediated action which in turn allows the amplification of the effects of dichloroacetate, even in cells with a more glycolytic phenotype. PMID:26025920

  8. Non-autocrine, constitutive activation of Met in human anaplastic thyroid carcinoma cells in culture

    PubMed Central

    Bergström, J D; Hermansson, A; Ståhl, T Diaz de; Heldin, N-E

    1999-01-01

    Activation of Met by its ligand HGF has been shown to elicit both mitogenic and motogenic responses in thyrocytes in vitro. In the present study we have investigated the expression of Met in human anaplastic thyroid carcinoma cells in culture. There was a variation in expression level and size of Met in the different cell lines; high Met expression was found in four cell lines, compared to non-neoplastic human thyrocytes. Treatment with glucoproteinase F showed that the size differences observed were due to variances in the degree of glycosylation. Interestingly, in cell lines with high expression of Met, the receptor proteins were found to be constitutively tyrosine phosphorylated. None of these cell lines expressed HGF mRNA, and addition of suramin did not affect the level of tyrosine phosphorylation of Met in unstimulated cells, suggesting the absence of autocrine stimulatory pathways. Furthermore, we did not observe MET gene amplification, activating mutations or phosphatase defects. The tyrosine phosphorylated receptors appeared functionally active since the receptors associated with the adaptor molecule Shc. In summary, we have found ligand-independent constitutively activated Met in four out of six anaplastic thyroid carcinoma cell lines. © 1999 Cancer Research Campaign PMID:10360640

  9. Raman spectroscopic study of keratin 8 knockdown oral squamous cell carcinoma derived cells

    NASA Astrophysics Data System (ADS)

    Singh, S. P.; Alam, Hunain; Dmello, Crismita; Vaidya, Milind M.; Krishna, C. Murali

    2012-03-01

    Keratins are one of most widely used markers for oral cancers. Keratin 8 and 18 are expressed in simple epithelia and perform both mechanical and regulatory functions. Their expression are not seen in normal oral tissues but are often expressed in oral squamous cell carcinoma. Aberrant expression of keratins 8 and 18 is most common change in human oral cancer. Optical-spectroscopic methods are sensitive to biochemical changes and being projected as novel diagnostic tools for cancer diagnosis. Aim of this study was to evaluate potentials of Raman spectroscopy in detecting minor changes associated with differential level of keratin expression in tongue-cancer-derived AW13516 cells. Knockdown clones for K8 were generated and synchronized by growing under serum-free conditions. Cell pellets of three independent experiments in duplicate were used for recording Raman spectra with fiberoptic-probe coupled HE-785 Raman-instrument. A total of 123 and 96 spectra from knockdown clones and vector controls respectively in 1200-1800 cm-1 region were successfully utilized for classification using LDA. Two separate clusters with classification-efficiency of ~95% were obtained. Leave-one-out cross-validation yielded ~63% efficiency. Findings of the study demonstrate the potentials of Raman spectroscopy in detecting even subtle changes such as variations in keratin expression levels. Future studies towards identifying Raman signals from keratin in oral cells can help in precise cancer diagnosis.

  10. Reduced expression of Slit2 in renal cell carcinoma.

    PubMed

    Ma, Wei-Jie; Zhou, Yu; Lu, Dan; Dong, Dong; Tian, Xiao-Jun; Wen, Jie-Xi; Zhang, Jun

    2014-01-01

    Slit2, initially identified as an important axon guidance molecule in the nervous system, was suggested to be involved in multiple cellular processes. Recently, Slit2 was reported to function as a potential tumor suppressor in diverse tumors. In this study, we systematically analyzed the expression level of Slit2 in renal cell carcinoma. Compared to paired adjacent non-malignant tissues, both Slit2 mRNA and protein expression were significantly down-regulated in renal cell carcinoma (RCC). Methylation-specific PCR showed that Slit2 promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation dramatically induced Slit2 expression in cancer cell lines with weak expression of Slit2. Besides, bisulfite genomic sequencing confirmed that dense methylation existed in Slit2 promoter. Furthermore, in paired RCC samples, Slit2 methylation was observed in 8 out of 38 patients (21.1 %), which was well correlated with the down-regulation of Slit2 in RCC. Therefore, Slit2 may also be a potential tumor suppressor in RCC, which is down-regulated in RCC partially due to promoter methylation.

  11. Possible prognostic value of BORIS transcript variants ratio in laryngeal squamous cell carcinomas - a pilot study.

    PubMed

    Novak Kujundžić, Renata; Grbeša, Ivana; Ivkić, Mirko; Krušlin, Božo; Konjevoda, Paško; Gall Trošelj, Koraljka

    2014-07-01

    BORIS is a paralog of a highly conserved, multi-functional chromatin factor CTCF. Unlike CTCF, which has been shown to possess tumor-suppressive properties, BORIS belongs to the "cancer/testis antigen" family normally expressed only in germ cells and aberrantly activated in a variety of tumors. The consequences of BORIS expression, relative abundance of its isoforms, and its role in carcinogenesis have not been completely elucidated. It activates transcription of hTERT and MYC, genes relevant for laryngeal carcinoma progression. In this study, BORIS expression has been analyzed at the transcriptional level by RT-PCR and protein level by semi-quantitative immunohistochemistry in 32 laryngeal squamous cell carcinomas and adjacent non-tumorous tissue. BORIS was detected in 44 % (14/32) laryngeal squamous cell carcinoma samples, while it was detected only in one normal, tumor-adjacent tissue sample. Tree based survival analysis, using the recursive partitioning algorithm mvpart, extracted the ratio of relative abundance of BORIS transcript variants containing exon 7 (BORIS 7+) and those lacking exon 7 (BORIS 7-) as an independent prognostic factor associated with disease relapse during a 5-year follow-up period. Patients having BORIS 7+/BORIS 7- ratio ≥1 had a higher rate of disease relapse than patients with BORIS 7+/BORIS 7- ratio <1. Hazard ratio for that group, based on Cox Proportional Hazard Regression, was 3.53. This is the first study analyzing expression of BORIS protein and transcript variants in laryngeal squamous cell carcinoma relative to its possible prognostic value for recurrence and overall survival. PMID:24563233

  12. Evidence for aldosterone-dependent growth of renal cell carcinoma

    PubMed Central

    King, Sharon; Bray, Susan; Galbraith, Sarah; Christie, Lesley; Fleming, Stewart

    2014-01-01

    The aim if this study was to investigate the hypothesis that K-RAS 4A is upregulated in a mineralocorticoid-dependent manner in renal cell carcinoma and that this supports the proliferation and survival of some renal cancers. Expression of the K-RAS in renal tumour tissues and cell lines was examined by real-time PCR and Western blot and mineralocorticoid receptor, and its gatekeeper enzyme 11β-hydroxysteroid dehydrogenase-2 was examined by immunocytochemistry on a tissue microarray of 27 cases of renal cell carcinoma. Renal cancer cells lines 04A018 (RCC4 plus VHL) and 04A019 (RCC4 plus vector alone) were examined for the expression of K-RAS4A and for the effect on K-RAS expression of spironolactone blockade of the mineralocorticoid receptor. K-RAS4A was suppressed by siRNA, and the effect on cell survival, proliferation and activation of the Akt and Raf signalling pathways was investigated in vitro. K-RAS4A was expressed in RCC tissue and in the renal cancer cell lines but K-RAS was downregulated by spironolactone and upregulated by aldosterone. Spironolactone treatment and K-RAS suppression both led to a reduction in cell number in vitro. Both Akt and Raf pathways showed activation which was dependent on K-RAS expression. K-RAS expression in renal cell carcinoma is at least partially induced by aldosterone. Aldosterone supports the survival and proliferation of RCC cells by upregulation of K-RAS acting through the Akt and Raf pathways. PMID:24802662

  13. Cutaneous Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Gurudutt, Vivek V.; Genden, Eric M.

    2011-01-01

    Cutaneous squamous cell carcinoma of the head and neck is an epidemic that reaches all parts of the world. Making the diagnosis relies on the acumen of the clinician and pathologist. Various pathologic subtypes exist and differ in histology and prognosis. High-risk tumors need aggressive treatment and vigilant surveillance to monitor for recurrence. Large tumors, deep tissue invasion, perineural involvement, recurrence, location in high-risk areas, and immunosuppression are implicated in worsening prognosis. Surgery is the mainstay of treatment with adjuvant radiation therapy as needed for aggressive tumors; however, other modalities are potentially useful for low-risk lesions. The use of Mohs surgery has become increasingly useful and has shown high success rates. Involvement of parotid and neck lymph nodes significantly affects outcomes and the physician should be comfortable with management of this complex disease. This paper examines the diagnosis, pathology, clinical course, and treatment options for cutaneous squamous cell carcinoma of the head and neck. PMID:21461387

  14. Cutaneous squamous cell carcinoma of the head and neck.

    PubMed

    Gurudutt, Vivek V; Genden, Eric M

    2011-01-01

    Cutaneous squamous cell carcinoma of the head and neck is an epidemic that reaches all parts of the world. Making the diagnosis relies on the acumen of the clinician and pathologist. Various pathologic subtypes exist and differ in histology and prognosis. High-risk tumors need aggressive treatment and vigilant surveillance to monitor for recurrence. Large tumors, deep tissue invasion, perineural involvement, recurrence, location in high-risk areas, and immunosuppression are implicated in worsening prognosis. Surgery is the mainstay of treatment with adjuvant radiation therapy as needed for aggressive tumors; however, other modalities are potentially useful for low-risk lesions. The use of Mohs surgery has become increasingly useful and has shown high success rates. Involvement of parotid and neck lymph nodes significantly affects outcomes and the physician should be comfortable with management of this complex disease. This paper examines the diagnosis, pathology, clinical course, and treatment options for cutaneous squamous cell carcinoma of the head and neck. PMID:21461387

  15. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome)

    PubMed Central

    Kiran, N. K.; Tilak Raj, T. N.; Mukunda, K. S.; Rajashekar Reddy, V.

    2012-01-01

    The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient. PMID:23633824

  16. Giant Cornu Cutaneum Superimposed on Basal Cell Carcinoma.

    PubMed

    Agirgol, S; Mansur, A T; Bozkurt, K; Azakli, H N; Babacan, A; Dikmen, A

    2015-09-01

    Cornu cutaneum (CC) is a clinical term that describes the horn-like keratotic lesions extending vertically from the skin. Benign, premalignant or malignant lesions may be present at the base of CC. Seborrhoeic keratosis and squamous cell carcinoma (SCC) are the most commonly reported benign and malignant forms, respectively. Basal cell carcinoma (BCC) at the base is rare. Here, we report on an 85-year old female patient having multiple CC lesions, one being giant on her face and two of the lesions diagnosed with BCC at the base. This case is of significance due to the presence of giant and multiple CC and detection of BCC at the base of more than one lesion. This present case indicates the need for the treatment of possible malignant lesions underlying CC in the elderly by total surgical excision.

  17. Giant Cornu Cutaneum Superimposed on Basal Cell Carcinoma

    PubMed Central

    Agirgol, S; Mansur, AT; Bozkurt, K; Azakli, HN; Babacan, A; Dikmen, A

    2015-01-01

    ABSTRACT Cornu cutaneum (CC) is a clinical term that describes the horn-like keratotic lesions extending vertically from the skin. Benign, premalignant or malignant lesions may be present at the base of CC. Seborrhoeic keratosis and squamous cell carcinoma (SCC) are the most commonly reported benign and malignant forms, respectively. Basal cell carcinoma (BCC) at the base is rare. Here, we report on an 85-year old female patient having multiple CC lesions, one being giant on her face and two of the lesions diagnosed with BCC at the base. This case is of significance due to the presence of giant and multiple CC and detection of BCC at the base of more than one lesion. This present case indicates the need for the treatment of possible malignant lesions underlying CC in the elderly by total surgical excision. PMID:26624603

  18. Penis keratoacanthoma transforming into squamous cell carcinoma: a rare case

    PubMed Central

    Deng, Fei; Liu, Xuemei; Zhou, Yihong; Liu, Jianye; Tang, Yuxin; Tang, Jin; Yao, Kun; Xia, Bing; Dai, Yingbo

    2015-01-01

    Keratoacanthoma is variously regarded as a benign epithelial tumor, characterized by a rapid-growing and solitary flesh-colored nodule with a central keratin plug on the sun-exposed skin. Under certain circumstances, it can transform into squamous cell carcinoma. In this paper, we present a case of a 50-year-old man with a 2.5 × 3 × 2.2 cm mass on his penis stub-end. The patient was treat with a partial penectomy after further expert discussions and histopathology the lesion demonstrated penis keratoacanthoma. He received a partial penectomy again and the pathological result revealed squamous cell carcinoma this time. This case indicates that undergoing a partial penectomy on initial diagnosis of a penile tumor secondary to penile keratoacanthoma should be considered because of its high malignant potency. To our best knowledge, this is the first study to describe the malignant conversion of penis keratoacanthoma. PMID:26885065

  19. Magnetic Resonance Imaging as a Biomarker for Renal Cell Carcinoma

    PubMed Central

    Wu, Yan; Kwon, Young Suk; Labib, Mina; Foran, David J.; Singer, Eric A.

    2015-01-01

    As the most common neoplasm arising from the kidney, renal cell carcinoma (RCC) continues to have a significant impact on global health. Conventional cross-sectional imaging has always served an important role in the staging of RCC. However, with recent advances in imaging techniques and postprocessing analysis, magnetic resonance imaging (MRI) now has the capability to function as a diagnostic, therapeutic, and prognostic biomarker for RCC. For this narrative literature review, a PubMed search was conducted to collect the most relevant and impactful studies from our perspectives as urologic oncologists, radiologists, and computational imaging specialists. We seek to cover advanced MR imaging and image analysis techniques that may improve the management of patients with small renal mass or metastatic renal cell carcinoma. PMID:26609190

  20. A rare case of large cell neuroendocrine carcinoma

    PubMed Central

    Lin, Diwei; Tan, Amanda Jia Hui; De Sousa, Agnelo Francis; Singh-Rai, Rajinder

    2014-01-01

    We present a very rare case of de novo large cell neuroendocrine carcinoma (LCNEC) of the prostate in an 84-year-old man on a background of high grade, superficially invasive transitional cell carcinoma of the bladder. Pure LCNEC of the prostate is extremely rare. Most LCNEC of the prostate are thought to originate by clonal progression under the selection pressure of therapy and refractory to long-term hormonal treatment for adenocarcinoma of the prostate. De novo LCNEC is only described in case reports and is thought to develop via direct malignant transformation. Limited data in the English literature makes it difficult to accurately predict the prognosis of LCNEC of the prostate. However, current evidence suggesting that increasing neuroendocrine differentiation in prostate adenocarcinoma is associated with a higher stage, high-grade disease and a worse prognosis. PMID:25331150

  1. Personalized targeted therapy for esophageal squamous cell carcinoma

    PubMed Central

    Kang, Xiaozheng; Chen, Keneng; Li, Yicheng; Li, Jianying; D'Amico, Thomas A; Chen, Xiaoxin

    2015-01-01

    Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial. PMID:26167067

  2. Carcinoma ex-pleomorphic adenoma of the parotid gland consisting of high-grade salivary duct carcinoma and keratinizing squamous cell carcinoma.

    PubMed

    Magaki, Shino D; Bhuta, Sunita; Abemayor, Elliot; Nabili, Vishad; Sepahdari, Ali R; Lai, Chi K

    2015-09-01

    Carcinoma ex-pleomorphic adenoma (CXPA) is a rare salivary gland malignancy that presents diagnostic difficulties partly because of its wide range of histologic presentations. We report a case of a 77-year-old man, who presented with a 6-year history of a parotid mass that had undergone rapid growth within weeks. Magnetic resonance imaging revealed an infiltrative mass in the parotid gland, and the fine-needle aspiration (FNA) biopsy result was highly suspicious for carcinoma. Subsequent excision of the tumor demonstrated a poorly differentiated epithelial neoplasm consisting of keratinizing squamous cell carcinoma (SCC) and adenocarcinoma with regions of both ductal carcinoma in situ and invasive salivary duct carcinoma (SDC). Only focal areas exhibited a benign pleomorphic adenoma component. To our knowledge, this is the first case of a CXPA that consists of both a high-grade SDC and a keratinizing SCC in the parotid gland.

  3. Solitary thyroid metastasis from clear-cell renal carcinoma.

    PubMed Central

    Madore, P.; Lan, S.

    1975-01-01

    A 58-year-old woman underwent nephrectomy because of clear-cell renal carcinoma. Seven years later a solitary thyroid metastasis was detected. She is alive and well 17 months after thyroidectomy. The rarity of this manifestation is well known but its explanation is not clear. The long metastasis-free interval, a characteristic shared by other hormonally dependent neoplasms, has been explained in part by the concept of "dormant cells", which do not undergo division. The stimulus that provokes these cells into division is at present not known. Images FIG. 1 FIG. 2 PMID:1122443

  4. Tubulocystic renal cell carcinoma: Report of a rare case.

    PubMed

    Kakkar, Aanchal; Sharma, Mehar C; Uppal, Manpreet; Chumber, Sunil

    2015-01-01

    Cystic neoplasms of the kidney are rare, and present a unique diagnostic challenge. We report the case of an elderly male who presented with a large cystic neoplasm, which was a diagnostic dilemma clinically and radiologically. Histopathological examination showed a tumour composed of variably sized tubules lined by atypical cells having large round nuclei with prominent nucleoli. Hobnailing was seen at places. Tumour cells were immunopositive for pancytokeratin, vimentin, CD10, CK19 and AMACR, confirming a diagnosis of tubulocystic renal cell carcinoma (TC-RCC). PMID:26425234

  5. A case of urothelial carcinoma, lipid cell variant.

    PubMed

    Kojima, Yui; Takasawa, Akira; Murata, Masaki; Akagashi, Keigo; Inoue, Tomomi; Hara, Mamie; Tokunaga, Yuichi; Minase, Takashi; Hasegawa, Tadashi; Sawada, Norimasa

    2013-03-01

    The lipid cell variant of urothelial carcinoma is a rare variant of urinary bladder cancer, comprised of lipoblast-like cells. In this report, we describe a case of the lipid cell variant of aggressive urothelial carcinoma. A 78-year-old man was admitted to the hospital because of gross hematuria. On cystoscopy, an ulcerative lesion, non-papillary architecture, was observed in the lateral wall of the bladder. Transurethral resection was performed. Histopathological findings of the bladder tumor indicated neoplastic cells forming irregular solid nests and sheets. Lipoblast-like neoplastic cells that had eccentric nuclei and cytoplasmic vacuoles were observed, not only in the resected specimen, but also in urine samples. On mucin histochemistry, the tumor cell cytoplasm contained no neutral or acidic mucus. The lipoblast-like cells were positive for cytokeratins (AE1/AE3, CK7) and adipophilin, known as a protein associated with neutral lipid synthesis. In general, it is difficult to prove the existence of intracytoplasmic lipid in formalin-fixed paraffin-embedded materials. This is the first report in which the presence of lipid in vacuoles of the lipid cell variant has been verified by immunohistochemistry.

  6. Primary small cell undifferentiated (neuroendocrine) carcinoma of the maxillary sinus.

    PubMed

    Yadav, Santosh Kumar; Shetty, Premalatha

    2014-01-01

    Primary small cell neuroendocrine carcinoma (SNEC) of the paranasal sinuses is an extremely rare and distinctive tumor with aggressive clinical behavior. Moreover, SNECs originating in the head and neck region have been reported to be highly aggressive and to have a poor prognosis. This report describes a patient with a maxillary sinus SNEC who was successfully treated with neoadjuvant chemotherapy and concurrent chemoradiotherapy. PMID:24639904

  7. Solitary Spinal Epidural Metastasis from Prostatic Small Cell Carcinoma

    PubMed Central

    Maeng, Young Hee

    2016-01-01

    Solitary, spinal epidural metastasis (SEM) that is not related to vertebral metastasis is very rare. And solitary SEM from prostatic cancer is rarely found in previously published reports. However, it is clinically significant due to the possibility of neurologic dysfunction, and it can be assessed by MRI. In this report, we show a case of solitary SEM arising from prostatic small cell carcinoma detected by MRI. PMID:27413569

  8. Gallbladder small cell carcinoma: a case report and literature review.

    PubMed

    Adachi, Toshiyuki; Haraguchi, Masashi; Irie, Junji; Yoshimoto, Tomoko; Uehara, Ryohei; Ito, Shinichiro; Tokai, Hirotaka; Noda, Kazumasa; Tada, Nobuhiro; Hirabaru, Masataka; Inoue, Keiji; Minami, Shigeki; Eguchi, Susumu

    2016-12-01

    Gallbladder small cell carcinoma (SCC) comprises only 0.5 % of all gallbladder cancer and consists of aggressive tumors with poor survival outcomes against current treatments. These tumors are most common in elderly females, particularly those with cholecystolithiasis. We report the case of a 79-year-old woman with gallbladder small cell carcinoma. The patient had intermittent right upper quadrant abdominal pain and was admitted to our hospital due to suspected acute cholecystitis. She regularly received medical treatment for diabetes, hypertension, and dyslipidemia. On initial laboratory evaluation, the levels of aspartate aminotransferase (AST), total bilirubin, and C-reactive protein (CRP) were markedly elevated. She underwent computed tomography (CT) for screening. CT images showed a thick-walled gallbladder containing multiple stones and multiple 3-cm-sized round nodular lesions, which were suggestive of metastatic lymph nodes. After percutaneous transhepatic gallbladder drainage was performed, endoscopic ultrasound-guided fine needle aspiration of enlarged lymph nodes resulted in a diagnosis of small cell carcinoma or adenocarcinoma. However, we could not identify the primary lesion before the surgery because of no decisive factors. We performed cholecystectomy because there was a possibility of cholecystitis recurrence risk and also partial liver resection because we suspected tumor invasion. The final pathological diagnosis was neuroendocrine carcinoma of the gallbladder, small cell type. The tumor stage was IVb, T3aN1M1. The patient died 13 weeks after the surgery. In the present paper, we review the current available English-language literature of gallbladder SCC.

  9. Gonadal vein tumor thrombosis due to renal cell carcinoma.

    PubMed

    Haghighatkhah, Hamidreza; Karimi, Mohammad Ali; Taheri, Morteza Sanei

    2015-01-01

    Renal cell carcinoma (RCC) had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC.

  10. Alveolar cell carcinoma: diagnostic pitfalls in evaluating the chest roentgenogram

    SciTech Connect

    Shin, M.S.; Bailey, W.C.

    1985-02-01

    A report is given of two patients with initial symptoms of congestive heart failure who had an extensive work-up that failed to reveal any signs of pulmonary malignancy. Subsequent biopsy by fiberoptic bronchoscopy confirmed alveolar cell carcinoma in both cases, suggesting that bronchoscopy with biopsy should be considered in patients with congestive heart failure if pulmonary edema does not resolve with appropriate therapy. 11 references, 2 figures.

  11. Angiomyolipoma with epithelial cysts: mimic of renal cell carcinoma.

    PubMed

    Rosenkrantz, Andrew B; Hecht, Elizabeth M; Taneja, Samir S; Melamed, Jonathan

    2010-01-01

    Angiomyolipoma with epithelial cysts (AMLEC) is a rare variant of angiomyolipoma with minimal fat that contains epithelial-lined cysts and may mimic a cystic renal cell carcinoma. While 17 cases have been described in the pathology literature since this entity was first described in 2006, the radiologic appearance was not demonstrated in any of these cases. We report the CT and MRI appearance of AMLEC found incidentally in a patient with lupus nephritis.

  12. New York esophageal squamous cell carcinoma-1 and cancer immunotherapy.

    PubMed

    Esfandiary, Ali; Ghafouri-Fard, Soudeh

    2015-01-01

    New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

  13. Thermal Protection during Percutaneous Thermal Ablation of Renal Cell Carcinoma

    PubMed Central

    Kam, Anthony W.; Littrup, Peter J.; Walther, McClellan M.; Hvizda, Julia; Wood, Bradford J.

    2008-01-01

    Thermal injury to collateral structures is a known complication of thermal ablation of tumors. The authors present the use of CO2 dissection and inserted balloons to protect the bowel during percutaneous radiofrequency (RF) ablation and cryotherapy of primary and locally recurrent renal cell carcinoma. These techniques offer the potential to increase the number of tumors that can be treated with RF ablation or cryotherapy from a percutaneous approach. PMID:15231890

  14. Effects of orexin A on glucose metabolism in human hepatocellular carcinoma in vitro via PI3K/Akt/mTOR-dependent and -independent mechanism.

    PubMed

    Liu, Yuanyuan; Zhao, Yuyan; Guo, Lei

    2016-01-15

    Orexins are hypothalamic neuropeptides that regulate food intake, energy homeostasis, reward system and sleep/wakefulness states. The purpose of this study was to investigate the effects of orexin A on glucose metabolism in human hepatocellular carcinoma cell line, Hep3B, and determine the possible mechanisms. Hep3B cells were incubated with different concentrations of orexin A (10(-9)-10(-7) M) in vitro in the presence or absence of the orexin receptor 1 (OX1R) inhibitor (SB334867), Akt inhibitor (PF-04691502) and mammalian target of rapamycin (mTOR) inhibitor (temsirolimus). Subsequently, OX1R protein expression, glucose transporter 1 (GLUT1) expression, glucose uptake, the mRNA expression of lactate dehydrogenase (LDHA), pyruvate dehydrogenase kinase 1 (PDK1) and pyruvate dehydrogenase B (PDHB), lactate generation and mitochondrial pyruvate dehydrogenase (PDH) enzyme activity were measured. The activity of phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling was also determined. OX1R was expressed in hepatoma tissues and Hep3B cells. Stimulation of the Hep3B cells with orexin A resulted in a dose-dependent increase of GLUT1 expression and glucose uptake, which was associated with the activation of PI3K/Akt/mTOR pathway. Further, orexin A increased PDHB expression and PDH enzyme activity, decreased LDHA, PDK1 mRNA levels and lactate generation independent of PI3K/Akt/mTOR pathway. Our results demonstrated that orexin A directed the cellular metabolism towards mitochondrial glucose oxidation rather than glycolysis. These findings provide functional evidence of the metabolic actions of orexin A in hepatocellular carcinoma cells.

  15. Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

    PubMed Central

    Huang, Han Hsiang; Kuo, Shyh Ming; Wu, Yi-Jhen; Su, Jui-Hsin

    2016-01-01

    The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC50) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma

  16. Prevalence and clinical features of human papillomavirus in head and neck squamous cell carcinoma in Okinawa, southern Japan.

    PubMed

    Deng, Zeyi; Hasegawa, Masahiro; Matayoshi, Sen; Kiyuna, Asanori; Yamashita, Yukashi; Maeda, Hiroyuki; Suzuki, Mikio

    2011-11-01

    Previous studies from Okinawa, a subtropical island in southern Japan, demonstrated a higher prevalence of human papillomavirus (HPV) in oral carcinoma and a higher incidence of oral and pharyngeal carcinoma than those for mainland Japan. The present study aims to investigate epidemiologic and clinical features of HPV in head and neck squamous cell carcinoma (HNSCC) in Okinawa. A total of 150 DNA samples from 150 Okinawan patients with head and neck squamous cell carcinoma (HNSCC) were screened for HPV sequences by PCR using three consensus primer sets, and HPV types were determined by direct sequencing. The samples were consisted of 46 cases from the hypopharynx, 44 from the oropharynx, 16 from the larynx, 25 from the oral cavity, 10 from the maxillary sinus, and 9 from the nasopharynx. HPV DNA was detected in 45 (30.0%) HNSCCs, and HPV-16 was identified in 86.7% of positive specimens. The highest prevalence of the HPV sequence was found in oropharyngeal carcinomas (50.0%), especially in tonsillar cancer (63.6%). Multivariate analysis showed that oropharyngeal carcinoma (P = 0.002; OR = 5.34; 95% CI = 1.83-15.58), oral cavity carcinoma (P = 0.012; OR = 4.94; 95% CI = 1.43-17.10), and histological poor differentiation (P = 0.011; OR = 4.25; 95% CI = 1.39-13.04) each independently increased the prevalence of HPV infection. The present study reveals that patients with HNSCC, e.g., oropharyngeal and oral cavity carcinomas, in Okinawa have relatively high HPV-16 positive rates and low HPV-18 positive rates comparing with mainland Japan.

  17. Independent controls for neocortical neuron production and histogenetic cell death

    NASA Technical Reports Server (NTRS)

    Verney, C.; Takahashi, T.; Bhide, P. G.; Nowakowski, R. S.; Caviness, V. S. Jr

    2000-01-01

    We estimated the proportion of cells eliminated by histogenetic cell death during the first 2 postnatal weeks in areas 1, 3 and 40 of the mouse parietal neocortex. For each layer and for the subcortical white matter in each neocortical area, the number of dying cells per mm(2) was calculated and the proportionate cell death for each day of the 2-week interval was estimated. The data show that cell death proceeds essentially uniformly across the neocortical areas and layers and that it does not follow either the spatiotemporal gradient of cell cycle progression in the pseudostratified ventricular epithelium of the cerebral wall, the source of neocortical neurons, or the 'inside-out' neocortical neuronogenetic sequence. Therefore, we infer that the control mechanisms of neocortical histogenetic cell death are independent of mechanisms controlling neuronogenesis or neuronal migration but may be associated with the ingrowth, expansion and a system-wide matching of neuronal connectivity. Copyright 2000 S. Karger AG, Basel.

  18. RENAL CELL CARCINOMA METASTASIS TO THE SINONASAL CAVITY: CASE REPORT.

    PubMed

    Kovačić, Marijan; Krvavica, Ana; Rudić, Milan

    2015-06-01

    Renal cell carcinoma accounts for 3% of all adult malignant tumors. Common sites of metastases are lungs, bone, liver, brain and adrenal glands. Metastatic disease to the head and neck ranges from 15% to 30%. The 5-year survival rate after nephrectomy is 60%-75%, but with multiorgan metastases the 5-year survival rate is significantly lower, 0-7%. A case is presented of a female patient diagnosed with renal cell carcinoma metastases to the paranasal sinuses, diagnosed and treated at the Department of ENT and Head and Neck Surgery, Zadar General Hospital, Zadar, Croatia. The tumor was surgically removed. Unfortunately, the patient died one year after the procedure due to multiorgan failure. Although metastases of renal cell carcinoma to the head and neck are very rare, it should be first suspected when investigating a metastatic tumor in this region. Surgical excision offers the best hope for long term survival. In case of unresectable tumor, other treatment options should be considered such as radiotherapy, immunotherapy and chemotherapy.

  19. Human skin cells support thymus-independent T cell development.

    PubMed

    Clark, Rachael A; Yamanaka, Kei-ichi; Bai, Mei; Dowgiert, Rebecca; Kupper, Thomas S

    2005-11-01

    Thymic tissue has previously been considered a requirement for the generation of a functional and diverse population of human T cells. We report that fibroblasts and keratinocytes from human skin arrayed on a synthetic 3-dimensional matrix support the development of functional human T cells from hematopoietic precursor cells in the absence of thymic tissue. Newly generated T cells contained T cell receptor excision circles, possessed a diverse T cell repertoire, and were functionally mature and tolerant to self MHC, indicating successful completion of positive and negative selection. Skin cell cultures expressed the AIRE, Foxn1, and Hoxa3 transcription factors and a panel of autoantigens. Skin and bone marrow biopsies can thus be used to generate de novo functional and diverse T cell populations for potential therapeutic use in immunosuppressed patients. PMID:16224538

  20. Human skin cells support thymus-independent T cell development

    PubMed Central

    Clark, Rachael A.; Yamanaka, Kei-ichi; Bai, Mei; Dowgiert, Rebecca; Kupper, Thomas S.

    2005-01-01

    Thymic tissue has previously been considered a requirement for the generation of a functional and diverse population of human T cells. We report that fibroblasts and keratinocytes from human skin arrayed on a synthetic 3-dimensional matrix support the development of functional human T cells from hematopoietic precursor cells in the absence of thymic tissue. Newly generated T cells contained T cell receptor excision circles, possessed a diverse T cell repertoire, and were functionally mature and tolerant to self MHC, indicating successful completion of positive and negative selection. Skin cell cultures expressed the AIRE, Foxn1, and Hoxa3 transcription factors and a panel of autoantigens. Skin and bone marrow biopsies can thus be used to generate de novo functional and diverse T cell populations for potential therapeutic use in immunosuppressed patients. PMID:16224538

  1. Improving gene transfer in human renal carcinoma cells: Utilization of adenovirus vectors containing chimeric type 5 and type 35 fiber proteins

    PubMed Central

    ACHARYA, BISHNU; TERAO, SHUJI; SUZUKI, TORU; NAOE, MICHIO; HAMADA, KATSUYUKI; MIZUGUCHI, HIROYUKI; GOTOH, AKINOBU

    2010-01-01

    The transduction efficacy of adenovirus serotype 5 (Ad5) vector in human renal carcinoma cells is generally low due to the down-regulated expression of Coxsackie and adenovirus receptor (CAR) in target cells. By contrast, the infectivity of adenovirus serotype 35 vectors depends on the binding rate to CD46 receptor, independent of CAR. In this study, we examined whether an adenovirus vector containing chimeric type 5 and type 35 fiber proteins (Ad5/F35) increases transduction efficiency compared to Ad5 vector in human renal carcinoma cells in vitro. The expression of CAR was much lower in the human renal carcinoma cells than in control HEK293 cells. By contrast, the expression of CD46 was similar and perhaps at a higher level in the human renal carcinoma cells than in the HEK293 cells. The transduction efficacy of Ad5/F35 vector was dramatically higher compared to that of Ad5 in human renal carcinoma cells, and was correlated to the expression of CD46. Thus, Ad5/35 vector may be useful for the development of novel gene therapy approaches to renal cell carcinoma. PMID:22993573

  2. Improving gene transfer in human renal carcinoma cells: Utilization of adenovirus vectors containing chimeric type 5 and type 35 fiber proteins.

    PubMed

    Acharya, Bishnu; Terao, Shuji; Suzuki, Toru; Naoe, Michio; Hamada, Katsuyuki; Mizuguchi, Hiroyuki; Gotoh, Akinobu

    2010-05-01

    The transduction efficacy of adenovirus serotype 5 (Ad5) vector in human renal carcinoma cells is generally low due to the down-regulated expression of Coxsackie and adenovirus receptor (CAR) in target cells. By contrast, the infectivity of adenovirus serotype 35 vectors depends on the binding rate to CD46 receptor, independent of CAR. In this study, we examined whether an adenovirus vector containing chimeric type 5 and type 35 fiber proteins (Ad5/F35) increases transduction efficiency compared to Ad5 vector in human renal carcinoma cells in vitro. The expression of CAR was much lower in the human renal carcinoma cells than in control HEK293 cells. By contrast, the expression of CD46 was similar and perhaps at a higher level in the human renal carcinoma cells than in the HEK293 cells. The transduction efficacy of Ad5/F35 vector was dramatically higher compared to that of Ad5 in human renal carcinoma cells, and was correlated to the expression of CD46. Thus, Ad5/35 vector may be useful for the development of novel gene therapy approaches to renal cell carcinoma.

  3. Renal-cell carcinomas in end-stage kidneys: a clinicopathological study with emphasis on clear-cell papillary renal-cell carcinoma and acquired cystic kidney disease-associated carcinoma.

    PubMed

    Bhatnagar, Ramneesh; Alexiev, Borislav A

    2012-02-01

    Clear-cell papillary renal-cell carcinoma (CCPC) and acquired cystic kidney disease-associated carcinoma (ACDAC) are neoplasms with distinct morphological characteristics that behave less aggressively than conventional renal-cell carcinomas. End-stage kidney specimens from 61 patients (47 males and 14 females) with 109 renal-cell carcinomas were selected. Papillary renal-cell carcinoma was the most common malignancy (61/109, 56%), followed by CCPC (20/109, 18%). The CCPC showed a papillary or tubular/solid architecture, clear cytoplasm, low nuclear grade, and a distinct immunohistochemical profile (RCC-, vimentin+, CK7+, p504S-). ACDAC displayed a variety of architectural patterns, eosinophilic cytoplasm, high nuclear grade, intratumoral calcium oxalate deposits, and an immunohistochemical profile similar to type 2 papillary renal-cell carcinoma (RCC+, vimentin+, CK7-/+, p504S+). Less than 5% (3/69) of pathologically staged renal-cell carcinomas in end-stage kidneys presented with lymphogenous and/or hematogenous metastases.

  4. Signet ring cell carcinoma of the eyelid - the monocle tumour.

    PubMed

    Mortensen, Anouck Leuba; Heegaard, Steffen; Clemmensen, Ole; Prause, Jan Ulrik

    2008-04-01

    We report the clinical and histopathological characteristics of two cases of signet ring cell carcinoma of the eye lids, and discuss the histogenesis of this neoplasm. Two 72-year-old Caucasian males both presented with slowly growing tumours of the eyelids. The tumours were excised and specimens were examined using light- and transmission electron microscopic techniques. Clinically, the tumours infiltrated both eyelids on one side of the face with swelling and periocular inflammation, creating a monocle-like appearance. Extensive clinical work-up excluded periocular metastases. Histopathologically, the tumours were composed of rather bland cells with mainly histiocytoid morphology. A minor proportion had a signet ring cell appearance. The cytoplasmic inclusions giving the signet ring morphology were PAS- and colloidal iron positive. The tumour cells reacted with antibodies against cytokeratins, carcinoembryonic antigen, epithelial membrane antigen, gross cystic disease fluid protein-15 and lysozyme. Transmission electron microscopy demonstrated tumour cells containing intracytoplasmic vacuoles lined by microvilli. The tumour cells aggregated in duct-like clusters. A diagnosis of primary signet ring cell carcinoma was made in both cases. Histopathological, immunohistological and ultrastructural findings indicated that the tumours were of sweat gland origin.

  5. Retinoic acid-induced neural differentiation of embryonal carcinoma cells.

    PubMed Central

    Jones-Villeneuve, E M; Rudnicki, M A; Harris, J F; McBurney, M W

    1983-01-01

    We have previously shown that the P19 line of embryonal carcinoma cells develops into neurons, astroglia, and fibroblasts after aggregation and exposure to retinoic acid. The neurons were initially identified by their morphology and by the presence of neurofilaments within their cytoplasm. We have more fully documented the neuronal nature of these cells by showing that their cell surfaces display tetanus toxin receptors, a neuronal cell marker, and that choline acetyl-transferase and acetyl cholinesterase activities appear coordinately in neuron-containing cultures. Several days before the appearance of neurons, there is a marked decrease in the amount of an embryonal carcinoma surface antigen, and at the same time there is a substantial decrease in the volumes of individual cells. Various retinoids were able to induce the development of neurons in cultures of aggregated P19 cells, but it did not appear that polyamine metabolism was involved in the effect. We have isolated a mutant clone which does not differentiate in the presence of any of the drugs which are normally effective in inducing differentiation of P19 cells. This mutant and others may help to elucidate the chain of events triggered by retinoic acid and other differentiation-inducing drugs. Images PMID:6656766

  6. Myoepithelial Cell Differentiation Markers in Ductal Carcinoma in Situ Progression

    PubMed Central

    Russell, Tanya D.; Jindal, Sonali; Agunbiade, Samiat; Gao, Dexiang; Troxell, Megan; Borges, Virginia F.; Schedin, Pepper

    2016-01-01

    We describe a preclinical model that investigates progression of early-stage ductal carcinoma in situ (DCIS) and report that compromised myoepithelial cell differentiation occurs before transition to invasive disease. Human breast cancer MCF10DCIS.com cells were delivered into the mouse mammary teat by intraductal injection in the absence of surgical manipulations and accompanying wound-healing confounders. DCIS-like lesions developed throughout the mammary ducts with full representation of human DCIS histologic patterns. Tumor cells were incorporated into the normal mammary epithelium, developed ductal intraepithelial neoplasia and DCIS, and progressed to invasive carcinoma, suggesting the model provides a rigorous approach to study early stages of breast cancer progression. Mammary glands were evaluated for myoepithelium integrity with immunohistochemical assays. Progressive loss of the myoepithelial cell differentiation markers p63, calponin, and α-smooth muscle actin was observed in the mouse myoepithelium surrounding DCIS-involved ducts. p63 loss was an early indicator, calponin loss intermediate, and α-smooth muscle actin a later indicator of compromised myoepithelium. Loss of myoepithelial calponin was specifically associated with gain of the basal marker p63 in adjacent tumor cells. In single time point biopsies obtained from 16 women diagnosed with pure DCIS, a similar loss in myoepithelial cell markers was observed. These results suggest that further research is warranted into the role of myoepithelial cell p63 and calponin expression on DCIS progression to invasive disease. PMID:26343330

  7. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  8. The price of independence: cell separation in fission yeast.

    PubMed

    Martín-García, Rebeca; Santos, Beatriz

    2016-04-01

    The ultimate goal of cell division is to give rise to two viable independent daughter cells. A tight spatial and temporal regulation between chromosome segregation and cytokinesis ensures the viability of the daughter cells. Schizosaccharomyces pombe, commonly known as fission yeast, has become a leading model organism for studying essential and conserved mechanisms of the eukaryotic cell division process. Like many other eukaryotic cells it divides by binary fission and the cleavage furrow undergoes ingression due to the contraction of an actomyosin ring. In contrast to mammalian cells, yeasts as cell-walled organisms, also need to form a division septum made of cell wall material to complete the process of cytokinesis. The division septum is deposited behind the constricting ring and it will constitute the new ends of the daughter cells. Cell separation also involves cell wall degradation and this process should be precisely regulated to avoid cell lysis. In this review, we will give a brief overview of the whole cytokinesis process in fission yeast, from the positioning and assembly of the contractile ring to the final step of cell separation, and the problems generated when these processes are not precise. PMID:26931605

  9. Establishment of an ASPL-TFE3 renal cell carcinoma cell line (S-TFE).

    PubMed

    Hirobe, Megumi; Masumori, Naoya; Tanaka, Toshiaki; Kitamura, Hiroshi; Tsukamoto, Taiji

    2013-06-01

    Xp11 translocation renal cell carcinoma is a rare disease diagnosed in children and adolescents in the advanced stage with an aggressive clinical course. Various gene fusions including the transcription factor E3 (TFE3) gene located on chromosome X cause the tumor. We established an Xp11 translocation renal cell carcinoma cell line from a renal tumor in a 18-y-old Japanese female and named it "S-TFE." The cell line and its xenograft demonstrated definite gene fusion including TFE3. They showed strong nuclear staining for TFE3 in immunohistochemistry, TFE3 gene rearrangement in dual-color, break-apart FISH analysis and ASPL-TFE3 type 1 fusion transcripts detected by RT-PCR and direct DNA sequencing. Although many renal cell carcinoma cell lines have been established and investigated, only a few cell lines are recognized as Xp11.2 translocation carcinoma. S-TFE will be useful to examine the characteristics and drug susceptibility of Xp11 translocation renal cell carcinoma. PMID:23760492

  10. Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary neuroendocrine carcinomas.

    PubMed

    Masai, Kyohei; Tsuta, Koji; Kawago, Mitsumasa; Tatsumori, Takahiro; Kinno, Tomoaki; Taniyama, Tomoko; Yoshida, Akihiko; Asamura, Hisao; Tsuda, Hitoshi

    2013-07-01

    Recent clinical trials have revealed that accurate histologic typing of non-small cell lung cancer is essential. Until now, squamous cell carcinoma (SQC) and adenocarcinoma (ADC) markers have not been thoroughly analyzed for pulmonary neuroendocrine carcinomas (NECs). We analyzed the expression of 8 markers [p63, cytokeratin (CK) 5/6, SOX2, CK7, desmocollin 3, thyroid transcription factor-1 (8G7G3/1 and SPT24), and napsin A] in 224 NECs. SOX2 (76.2%) had the greatest expression for NECs. CK5/6 (1.4%), desmocollin 3 (0.5%), and napsin A (0%) were expressed less or not at all in NECs. Although our investigated markers have been reported useful for differentiating between SQC and ADC, some of them were also present in a portion of pulmonary NECs. In our study, CK5/6 and desmocollin 3 were highly specific markers for SQC, and napsin A was highly specific for ADC. These markers are recommended for diagnosis of poorly differentiated non-small cell lung cancer.

  11. Smac mimetic sensitizes renal cell carcinoma cells to interferon-α-induced apoptosis.

    PubMed

    Reiter, Michael; Eckhardt, Ines; Haferkamp, Axel; Fulda, Simone

    2016-05-28

    The prognosis of metastatic or relapsed renal cell carcinoma (RCC) is still very poor, highlighting the need for new treatment strategies. Here, we identify a cooperative antitumor activity of interferon-α (IFNα) together with the Smac mimetic BV6 that antagonizes antiapoptotic IAP proteins. BV6 and IFNα act together to reduce cell viability and to induce apoptosis in various RCC cell lines. Molecular studies revealed that BV6/IFNα co-treatment triggers apoptosis independently of autocrine/paracrine Tumor Necrosis Factor (TNF)α signaling, since the TNFα-blocking antibody Enbrel fails to rescue cell death. Importantly, knockdown of Receptor-Interacting Protein (RIP)1 significantly decreases BV6/IFNα-mediated apoptosis, whereas the RIP1 kinase inhibitor necrostatin-1 (Nec-1) provides no protection. This demonstrates that RIP1 protein is critically required for BV6/IFNα-induced apoptosis, while RIP1 kinase activity is dispensable, pointing to a scaffold function of RIP1. Consistently, BV6 and IFNα cooperate to trigger the interaction of RIP1, Fas-Associated Death Domain protein (FADD) and caspase-8 to form a cytosolic cell death complex that drives caspase activation. Addition of the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) significantly protects RCC cells against BV6/IFNα-induced apoptosis, demonstrating that caspase activity is required for apoptosis. In conclusion, the combination approach of IFNα and BV6 represents a promising strategy for cooperative induction of apoptosis in RCC cells, which warrants further investigation. PMID:26912071

  12. Trefoil factor 3 as a novel biomarker to distinguish between adenocarcinoma and squamous cell carcinoma.

    PubMed

    Wang, Xiao-Nan; Wang, Shu-Jing; Pandey, Vijay; Chen, Ping; Li, Qing; Wu, Zheng-Sheng; Wu, Qiang; Lobie, Peter E

    2015-05-01

    In carcinoma, such as of the lung, the histological subtype is important to select an appropriate therapeutic strategy for patients. However, carcinomas with poor differentiation cannot always be distinguished on the basis of morphology alone nor on clinical findings. Hence, delineation of poorly differentiated adenocarcinoma and squamous cell carcinoma, the 2 most common epithelial-origin carcinomas, is pivotal for selection of optimum therapy. Herein, we explored the potential utility of trefoil factor 3 (TFF3) as a biomarker for primary lung adenocarcinoma and extrapulmonary adenocarcinomas derived from different organs. We observed that 90.9% of lung adenocarcinomas were TFF3-positive, whereas no expression of TFF3 was observed in squamous cell carcinomas. The subtype of lung carcinoma was confirmed by four established biomarkers, cytokeratin 7 and thyroid transcription factor 1 for adenocarcinoma and P63 and cytokeratin 5/6 for squamous cell carcinoma. Furthermore, expression of TFF3 mRNA was observed by quantitative PCR in all of 11 human lung adenocarcinoma cell lines and highly correlated with markers of the adenocarcinomatous lineage. In contrast, little or no expression of TFF3 was observed in 4 lung squamous cell carcinoma cell lines. By use of forced expression, or siRNA-mediated depletion of TFF3, we determined that TFF3 appeared to maintain rather than promote glandular differentiation of lung carcinoma cells. In addition, TFF3 expression was also determined in adenocarcinomas from colorectum, stomach, cervix, esophagus, and larynx. Among all these extrapulmonary carcinomas, 93.7% of adenocarcinomas exhibited TFF3 positivity, whereas only 2.9% of squamous cell carcinomas were TFF3-positive. Totally, 92.9% of both pulmonary and extrapulmonary adenocarcinomas exhibited TFF3 positivity, whereas only 1.5% of squamous cell carcinomas were TFF3-positive. In conclusion, TFF3 is preferentially expressed in adenocarcinoma and may function as an additional

  13. Trefoil Factor 3 as a Novel Biomarker to Distinguish Between Adenocarcinoma and Squamous Cell Carcinoma

    PubMed Central

    Wang, Xiao-Nan; Wang, Shu-Jing; Pandey, Vijay; Chen, Ping; Li, Qing; Wu, Zheng-Sheng; Wu, Qiang; Lobie, Peter E.

    2015-01-01

    Abstract In carcinoma, such as of the lung, the histological subtype is important to select an appropriate therapeutic strategy for patients. However, carcinomas with poor differentiation cannot always be distinguished on the basis of morphology alone nor on clinical findings. Hence, delineation of poorly differentiated adenocarcinoma and squamous cell carcinoma, the 2 most common epithelial-origin carcinomas, is pivotal for selection of optimum therapy. Herein, we explored the potential utility of trefoil factor 3 (TFF3) as a biomarker for primary lung adenocarcinoma and extrapulmonary adenocarcinomas derived from different organs. We observed that 90.9% of lung adenocarcinomas were TFF3-positive, whereas no expression of TFF3 was observed in squamous cell carcinomas. The subtype of lung carcinoma was confirmed by four established biomarkers, cytokeratin 7 and thyroid transcription factor 1 for adenocarcinoma and P63 and cytokeratin 5/6 for squamous cell carcinoma. Furthermore, expression of TFF3 mRNA was observed by quantitative PCR in all of 11 human lung adenocarcinoma cell lines and highly correlated with markers of the adenocarcinomatous lineage. In contrast, little or no expression of TFF3 was observed in 4 lung squamous cell carcinoma cell lines. By use of forced expression, or siRNA-mediated depletion of TFF3, we determined that TFF3 appeared to maintain rather than promote glandular differentiation of lung carcinoma cells. In addition, TFF3 expression was also determined in adenocarcinomas from colorectum, stomach, cervix, esophagus, and larynx. Among all these extrapulmonary carcinomas, 93.7% of adenocarcinomas exhibited TFF3 positivity, whereas only 2.9% of squamous cell carcinomas were TFF3-positive. Totally, 92.9% of both pulmonary and extrapulmonary adenocarcinomas exhibited TFF3 positivity, whereas only 1.5% of squamous cell carcinomas were TFF3-positive. In conclusion, TFF3 is preferentially expressed in adenocarcinoma and may function as an

  14. Overexpression of Transient Receptor Protein Cation Channel Subfamily A Member 1, Confers an Independent Prognostic Indicator in Nasopharyngeal Carcinoma

    PubMed Central

    Wu, You-Ting; Yen, Shao-Lun; Li, Chien-Feng; Chan, Ti-Chun; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Shiue, Yow-Ling

    2016-01-01

    Background: Detection of oncogenes provides chances to understand tumor development and progression. Transient receptor protein cation channel subfamily A, member 1 (TRPA1) transcript was significantly upregulated in nasopharyngeal carcinoma (NPC) with a stepwise upregulation from low- to high-stage NPCs from a preliminary data analysis in the Gene Expression Omnibus database. The TRPA1 gene is a member of the TRP channel family, encoding integral membrane proteins that functions as cation channels. Loss of calcium homeostasis takes place in cancer cells. Methods: Immunostaining of TRPA1 was analyzed on 124 biopsies from NPC patients retrospectively. The H-score method was used to evaluate the immunoexpression of TRPA1. The correlations between H-score of TRPA1 protein level and clinicopathological factors, as well as the significances of TRPA1 protein level for disease-specific, distal-metastasis-free and local recurrence-free survivals were assessed. Results: These patients were characterized to be no initial metastasis and medicated with the traditional procedure. The TRPA1 score was found to be associated with clinicopathological parameters and patient survivals. Along with the guideline of 7th edition of the American Joint Committee on Cancer, we found that TRPA1 upregulation (50%) was associated with advanced primary tumor (P = 0.009) and overall clinical stage (P = 0.019). In univariate log-rank testing, primary tumor, nodal status, stage and TRPA1 protein level significantly contributed to worse disease-specific survival, distal metastasis-free survival and local recurrence-free survival. In multivariate analysis, high TRPA1 protein level and tumor stage emerged as independent prognostic indicators for inferior disease-specific survival (P = 0.014; P = 0.003), distal metastasis-free survival (P = 0.004; P = 0.034) and recurrence-free survival (P = 0.017; P = 0.015). Conclusions: The upregulation of TRPA1 protein level is frequently correlated to unfavorable

  15. Fangchinoline induces autophagic cell death via p53/sestrin2/AMPK signalling in human hepatocellular carcinoma cells

    PubMed Central

    Wang, Ning; Pan, Weidong; Zhu, Meifen; Zhang, Maosheng; Hao, Xiaojian; Liang, Guangyi; Feng, Yibin

    2011-01-01

    BACKGROUND AND PURPOSE Fangchinoline is a novel anti-tumour agent with little known of its cellular and molecular mechanisms of action. Here we have investigated the mode of cell death induced by fangchinoline and its underlying mechanism in two human hepatocellular carcinoma cell lines, HepG2 and PLC/PRF/5. EXPERIMENTAL APPROACH Apoptosis and autophagy were monitored in fangchinoline-treated HepG2 and PLC/PRF/5 cells by histological methods. The signal transduction pathways involved in activation of autophagy were examined, using immunoblotting, real-time PCR and siRNA techniques. KEY RESULTS Fangchinoline did not induce apoptosis in HepG2 and PLC/PRF/5 cells but triggered, dose-dependently, autophagy, an alternative mode of cell death which may contribute to fangchinoline's anti-tumour action. Nuclear translocation of p53 was involved in induction of autophagy by fangchinoline, followed by selective transactivation of the autophagy-related gene sestrin2 and initiation of the autophagic process. Signalling by the AMP-activated protein kinase was also involved as a downstream target of sestrin2 and induced mTOR-independent autophagic cell death in both cell lines. siRNA for Atg 5 or pharmacological block of p53 abolished fangchinoline-induced autophagy and inhibition of autophagy switched cell death to apoptosis in these cells, suggesting that cell death is irreversible once autophagy is induced by fangchinoline. CONCLUSIONS AND IMPLICATIONS Fangchinoline is a highly specific agent inducing autophagic cell death in hepatocellular carcinoma cells with a novel mechanism, which elucidates the potential of fangchinoline to potentiate programmed cell death in cancer cells. PMID:21418191

  16. HIF-1α Promotes A Hypoxia-Independent Cell Migration.

    PubMed

    Li, Liyuan; Madu, Chikezie O; Lu, Andrew; Lu, Yi

    2010-01-01

    Hypoxia-inducible factor-1α (HIF-1α) is known as a transactivator for VEGF gene promoter. It can be induced by hypoxia. However, no study has been done so far to dissect HIF-1α-mediated effects from hypoxia or VEGF-mediated effects. By using a HIF-1α knockout (HIF-1α KO) cell system in mouse embryonic fibroblast (MEF) cells, this study analyzes cell migration and HIF-1α, hypoxia and VEGF activation. A hypoxia-mediated HIF-1α induction and VEGF transactivation were observed: both HIF-1α WT lines had significantly increased VEGF transactivation, as an indicator for HIF-1α induction, in hypoxia compared to normoxia; in contrast, HIF-1α KO line had no increased VEGF transactivation under hypoxia. HIF-1α promotes cell migration: HIF-1α-KO cells had a significantly reduced migration compared to that of the HIF-1α WT cells under both normoxia and hypoxia. The significantly reduced cell migration in HIF-1α KO cells can be partially rescued by the restoration of WT HIF-1α expression mediated by adenoviral-mediated gene transfer. Interestingly, hypoxia has no effect on cell migration: the cells had a similar cell migration rate under hypoxic and normoxic conditions for both HIF-1α WT and HIF-1α KO lines, respectively. Collectively, these data suggest that HIF-1α plays a role in MEF cell migration that is independent from hypoxia-mediated effects.

  17. HIF-1α Promotes A Hypoxia-Independent Cell Migration

    PubMed Central

    Li, Liyuan; Madu, Chikezie O.; Lu, Andrew; Lu, Yi

    2010-01-01

    Hypoxia-inducible factor-1α (HIF-1α) is known as a transactivator for VEGF gene promoter. It can be induced by hypoxia. However, no study has been done so far to dissect HIF-1α-mediated effects from hypoxia or VEGF-mediated effects. By using a HIF-1α knockout (HIF-1α KO) cell system in mouse embryonic fibroblast (MEF) cells, this study analyzes cell migration and HIF-1α, hypoxia and VEGF activation. A hypoxia-mediated HIF-1α induction and VEGF transactivation were observed: both HIF-1α WT lines had significantly increased VEGF transactivation, as an indicator for HIF-1α induction, in hypoxia compared to normoxia; in contrast, HIF-1α KO line had no increased VEGF transactivation under hypoxia. HIF-1α promotes cell migration: HIF-1α-KO cells had a significantly reduced migration compared to that of the HIF-1α WT cells under both normoxia and hypoxia. The significantly reduced cell migration in HIF-1α KO cells can be partially rescued by the restoration of WT HIF-1α expression mediated by adenoviral-mediated gene transfer. Interestingly, hypoxia has no effect on cell migration: the cells had a similar cell migration rate under hypoxic and normoxic conditions for both HIF-1α WT and HIF-1α KO lines, respectively. Collectively, these data suggest that HIF-1α plays a role in MEF cell migration that is independent from hypoxia-mediated effects. PMID:20882121

  18. Endonucleases induced TRAIL-insensitive apoptosis in ovarian carcinoma cells

    SciTech Connect

    Geel, Tessa M.; Meiss, Gregor; Gun, Bernardina T. van der; Kroesen, Bart Jan; Leij, Lou F. de; Zaremba, Mindaugas; Silanskas, Arunas; Kokkinidis, Michael; Ruiters, Marcel H.; McLaughlin, Pamela M.; Rots, Marianne G.

    2009-09-10

    TRAIL induced apoptosis of tumor cells is currently entering phase II clinical settings, despite the fact that not all tumor types are sensitive to TRAIL. TRAIL resistance in ovarian carcinomas can be caused by a blockade upstream of the caspase 3 signaling cascade. We explored the ability of restriction endonucleases to directly digest DNA in vivo, thereby circumventing the caspase cascade. For this purpose, we delivered enzymatically active endonucleases via the cationic amphiphilic lipid SAINT-18{sup Registered-Sign }:DOPE to both TRAIL-sensitive and insensitive ovarian carcinoma cells (OVCAR and SKOV-3, respectively). Functional nuclear localization after delivery of various endonucleases (BfiI, PvuII and NucA) was indicated by confocal microscopy and genomic cleavage analysis. For PvuII, analysis of mitochondrial damage demonstrated extensive apoptosis both in SKOV-3 and OVCAR. This study clearly demonstrates that cellular delivery of restriction endonucleases holds promise to serve as a novel therapeutic tool for the treatment of resistant ovarian carcinomas.

  19. Review of terminology of precursors of vulvar squamous cell carcinoma.

    PubMed

    Scurry, James; Wilkinson, Edward J

    2006-07-01

    The popular term for vulvar squamous cell carcinoma in situ/dysplasia is vulvar intraepithelial neoplasia (VIN). VIN is a histological diagnosis based on loss of squamous epithelial maturation associated with enlarged, hyperchromatic, pleomorphic nuclei and increased, usually atypical mitoses. There are two types of VIN: the usual (not otherwise specified) type, also known as warty-basaloid, and the differentiated type. There are 3 grading systems for warty-basaloid VIN: the traditional 3-grade system of VIN 1-3, a low-grade/high grade Bethesda-like system and the International Society for the Study of Vulvovaginal Disease's proposal for only 1 grade. The ISSVD system eliminates VIN 1 and combines VIN 2 and 3 on the grounds that VIN 1 has not been shown to be a reproducible diagnosis and VIN 2 and 3 are not reliably separated. The evidence supports the ISSVD proposal. Warty basaloid VIN may be sub-typed into warty and basaloid VIN. Sub-typing has clinical relevance but its reproducibility is not proven. Warty-basaloid VIN may regress. Differentiated VIN has been typically diagnosed co-incident with squamous cell carcinoma. With increased frequency of performance of biopsy of hyperplastic lesions, differentiated VIN should be diagnosed more commonly before squamous carcinoma occurs.

  20. [Renal cell carcinoma producing erythrocytosis due to inappropriate production of erythropoietin].

    PubMed

    Villanueva-Gimeno, M M; Vicario-Bermúdez, J M; Fonseca-López, Ch; Caballero-Castro, J P; Zabala-López, S I; Sánchez-Elipe, M A; González-Gómez, N

    2013-01-01

    Erythrocytosis, or polycythaemia, is an increase, in absolute terms, of the erythrocyte mass. The most common solid tumour related to this phenomenon is renal cell carcinoma, which can produce erythrocytosis by increasing erythropoietin production. About 30% of symptomatic renal cell carcinomas are diagnosed due to the appearance of a paraneoplastic syndrome. Polycythaemia is one of these. Surgery, (radical or partial nephrectomy), is the treatment of choice in renal cell carcinoma and helps to keep the erythrocytosis situation under control. PMID:23834980

  1. Summary of the first annual Genitourinary Medical Oncology Conference Renal Cell Carcinoma Forum

    PubMed Central

    Wood, Lori A; Escudier, Bernard; Reaume, Neil

    2007-01-01

    The first annual Canadian Genitourinary Medical Oncology Conference was held in June 2006 before the Canadian Urology Association Annual Meeting. This article summarizes 3 presentations that took place as part of the Renal Cell Carcinoma Forum: “Treatment of Metastatic Renal Cell Carcinoma: 2006 and Beyond” was presented by Dr. Bernard Escudier; “Practical Experience with Targeted Therapy,” by Dr. Lori Wood; and “Sarcomatoid Renal Cell Carcinoma,” by Dr. Neil Reaume. PMID:18542786

  2. Epidemiologic aspects of renal cell carcinoma.

    PubMed

    McLaughlin, Joseph K; Lipworth, Loren; Tarone, Robert E

    2006-10-01

    Renal cell cancer accounts for 2% of all new cancer cases worldwide. Incidence rates have been rising steadily around the world. In the United States, the rates have been rapidly increasing among black Americans, whose incidence rate has now surpassed that of white Americans. Cigarette smoking and obesity are the most consistently established causal risk factors, accounting for more than 20% and 30% of renal cell cancers, respectively. Hypertension, rather than antihypertensive drugs, appears to influence renal cell cancer development, although the mechanism is unknown. Analgesics have not been convincingly linked with renal cell cancer risk. In general, there appears to be a protective effect of fruit and vegetable consumption, although no particular component of diet has been clearly implicated. There are sporadic and inconsistent reports of occupations or occupational exposures being associated with this cancer. Epidemiologic studies are needed to identify reasons for the increasing incidence of renal cell cancer, with particular focus on why the incidence rate for black Americans has risen to significantly surpass that of white Americans.

  3. Bronchorrhoea in a case of alveolar cell carcinoma.

    PubMed Central

    Spiro, S G; Lopez-Vidriero M-T; Charman, J; Das, I; Reid, L

    1975-01-01

    In a case of bronchorrhoea associated with alveolar cell carcinoma thf rheological and chemical features of the sputum indicated that it was bronchial fluid and not saliva and part bronchial secretion, partly serum transudate. The viscosity and chemical constituents were similar to those found in bronchorrhoea when associated with chronic bronchitis, asthma, or bronchiectasis. The surfactant studies suggested an alveolar origin for most of thf fluid, while the failure of fluid restriction, corticosteroids, atropine, or cytotoxic drugs to influence the sputum volume and properties indicated that the cells responsible are "autonomous". Images PMID:164485

  4. Basal cell carcinoma — molecular biology and potential new therapies

    PubMed Central

    Kasper, Maria; Jaks, Viljar; Hohl, Daniel; Toftgård, Rune

    2012-01-01

    Basal cell carcinoma (BCC) of the skin, the most common malignancy in individuals of mixed European descent, is increasing in incidence due to an aging population and sun exposure habits. The realization that aberrant activation of Hedgehog signaling is a pathognomonic feature of BCC development has opened the way for exciting progress toward understanding BCC biology and translation of this knowledge to the clinic. Genetic mouse models closely mimicking human BCCs have provided answers about the tumor cell of origin, and inhibition of Hedgehog signaling is emerging as a potentially useful targeted therapy for patients with advanced or multiple BCCs that have hitherto lacked effective treatment. PMID:22293184

  5. Labeling index in squamous cell carcinoma of the larynx

    SciTech Connect

    Balzi, M.; Ninu, B.M.; Becciolini, A.; Scubla, E.; Boanini, P.; Gallina, E.; Gallo, O.; Fini-Storchi, O.; Bondi, R. )

    1991-07-01

    Two cell kinetic parameters, the 3H-thymidine labeling index (TLI) and the mitotic index (MI), were studied in vitro on fragments of squamous cell carcinoma tissue of the larynx. They were evaluated to identify those elements able to characterize the growth of these solid tumors. The values of these parameters were analyzed as a function of the clinical stage and the involvement of the regional lymph nodes. Results showed a statistically significant increase in the TLI from stage T1 to T3. No statistically significant differences in the TLI values were observed between the patients with positive and negative lymph nodes.

  6. Na+-independent phosphate transport in Caco2BBE cells

    PubMed Central

    Candeal, Eduardo; Caldas, Yupanqui A.; Guillén, Natalia; Levi, Moshe

    2014-01-01

    Pi transport in epithelia has both Na+-dependent and Na+-independent components, but so far only Na+-dependent transporters have been characterized in detail and molecularly identified. Consequently, in the present study, we initiated the characterization and analysis of intestinal Na+-independent Pi transport using an in vitro model, Caco2BBE cells. Only Na+-independent Pi uptake was observed in these cells, and Pi uptake was dramatically increased when cells were incubated in high-Pi DMEM (4 mM) from 1 day to several days. No response to low-Pi medium was observed. The increased Pi transport was mainly caused by Vmax changes, and it was prevented by actinomycin D and cycloheximide. Pi transport in cells grown in 1 mM Pi (basal DMEM) decreased at pH > 7.5, and it was inhibited with proton ionophores. Pi transport in cells incubated with 4 mM Pi increased with alkaline pH, suggesting a preference for divalent phosphate. Pi uptake in cells in 1 mM Pi was completely inhibited only by Pi and partially inhibited by phosphonoformate, oxalate, DIDS, SITS, SO42−, HCO3−, and arsenate. This inhibition pattern suggests that more than one Pi transporter is active in cells maintained with 1 mM Pi. Phosphate transport from cells maintained at 4 mM Pi was only partially inhibited by phosphonoformate, oxalate, and arsenate. Attempts to identify the responsible transporters showed that multifunctional anion exchangers of the Slc26 family as well as members of Slc17, Slc20, and Slc37 and the Pi exporter xenotropic and polytropic retrovirus receptor 1 are not involved. PMID:25298422

  7. Na+-independent phosphate transport in Caco2BBE cells.

    PubMed

    Candeal, Eduardo; Caldas, Yupanqui A; Guillén, Natalia; Levi, Moshe; Sorribas, Víctor

    2014-12-15

    Pi transport in epithelia has both Na(+)-dependent and Na(+)-independent components, but so far only Na(+)-dependent transporters have been characterized in detail and molecularly identified. Consequently, in the present study, we initiated the characterization and analysis of intestinal Na(+)-independent Pi transport using an in vitro model, Caco2BBE cells. Only Na(+)-independent Pi uptake was observed in these cells, and Pi uptake was dramatically increased when cells were incubated in high-Pi DMEM (4 mM) from 1 day to several days. No response to low-Pi medium was observed. The increased Pi transport was mainly caused by Vmax changes, and it was prevented by actinomycin D and cycloheximide. Pi transport in cells grown in 1 mM Pi (basal DMEM) decreased at pH > 7.5, and it was inhibited with proton ionophores. Pi transport in cells incubated with 4 mM Pi increased with alkaline pH, suggesting a preference for divalent phosphate. Pi uptake in cells in 1 mM Pi was completely inhibited only by Pi and partially inhibited by phosphonoformate, oxalate, DIDS, SITS, SO4 (2-), HCO3 (-), and arsenate. This inhibition pattern suggests that more than one Pi transporter is active in cells maintained with 1 mM Pi. Phosphate transport from cells maintained at 4 mM Pi was only partially inhibited by phosphonoformate, oxalate, and arsenate. Attempts to identify the responsible transporters showed that multifunctional anion exchangers of the Slc26 family as well as members of Slc17, Slc20, and Slc37 and the Pi exporter xenotropic and polytropic retrovirus receptor 1 are not involved.

  8. Gorlin's syndrome, or nevoid basal cell carcinoma syndrome.

    PubMed Central

    Fitzpatrick, P. J.; Thompson, G. A.

    1982-01-01

    Gorlin's syndrome is a condition inherited in an autosomal dominant fashion. It involves many organs, but principally affects the skin, skeleton, and endocrine and nervous systems. The most common features are multiple nervi and basal cell carcinomas of the skin, benign jaw cysts, dyskeratotic pits in the palms and soles, rib and vertebral abnormalities, brachymetacarpalism, and calcification of the falx cerebri. In 14 patients, 4 of whom belonged to one family, the age at the time of diagnosis ranged from 11 to 63 years. Ten patients are alive, but five are severely disfigured by carcinomas. Two patients died of complications resulting from uncontrolled tumours, and two died of other cancers. New skin tumours constantly develop; small ones can be excised, but large ones require extensive surgery with or without radiotherapy. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 FIG. 9 FIG. 10 FIG. 11 PMID:7116263

  9. KRAS Mutations in Canine and Feline Pancreatic Acinar Cell Carcinoma.

    PubMed

    Crozier, C; Wood, G A; Foster, R A; Stasi, S; Liu, J H W; Bartlett, J M S; Coomber, B L; Sabine, V S

    2016-07-01

    Companion animals may serve as valuable models for studying human cancers. Although KRAS is the most commonly mutated gene in human ductal pancreatic cancers (57%), with mutations frequently occurring at codons 12, 13 and 61, human pancreatic acinar cell carcinomas (ACCs) lack activating KRAS mutations. In the present study, 32 pancreatic ACC samples obtained from 14 dogs and 18 cats, including seven metastases, were analyzed for six common activating KRAS mutations located in codons 12 (n = 5) and 13 (n = 1) using Sequenom MassARRAY. No KRAS mutations were found, suggesting that, similar to human pancreatic ACC, KRAS mutations do not play a critical role in feline or canine pancreatic ACC. Due to the similarity of the clinical disease in dogs and cats to that of man, this study confirms that companion animals offer potential as a suitable model for investigating this rare subtype of pancreatic carcinoma.

  10. Protein Profiling of Bladder Urothelial Cell Carcinoma

    PubMed Central

    Hu, Jinghai; Ye, Fei; Cui, Miao; Lee, Peng; Wei, Chengguo; Hao, Yuanyuan; Wang, Xiaoqing; Wang, Yanbo; Lu, Zhihua; Galsky, Matthew; McBride, Russell; Wang, Li; Wang, Dongwen; Cordon-Cardo, Carlos; Wang, Chunxi; Zhang, David Y.

    2016-01-01

    This study aimed to detect protein changes that can assist to understand the underlying biology of bladder cancer. The data showed forty five proteins were found to be differentially expressed comparing tumors vs non-tumor tissues, of which EGFR and cdc2p34 were correlated with muscle invasion and histological grade. Ten proteins (ß-catenin, HSP70, autotaxin, Notch4, PSTPIP1, DPYD, ODC, cyclinB1, calretinin and EPO) were able to classify muscle invasive BCa (MIBC) into 2 distinct groups, with group 2 associated with poorer survival. Finally, 3 proteins (P2X7, cdc25B and TFIIH p89) were independent factors for favorable overall survival. PMID:27626805

  11. Protein Profiling of Bladder Urothelial Cell Carcinoma.

    PubMed

    Hu, Jinghai; Ye, Fei; Cui, Miao; Lee, Peng; Wei, Chengguo; Hao, Yuanyuan; Wang, Xiaoqing; Wang, Yanbo; Lu, Zhihua; Galsky, Matthew; McBride, Russell; Wang, Li; Wang, Dongwen; Cordon-Cardo, Carlos; Wang, Chunxi; Zhang, David Y

    2016-01-01

    This study aimed to detect protein changes that can assist to understand the underlying biology of bladder cancer. The data showed forty five proteins were found to be differentially expressed comparing tumors vs non-tumor tissues, of which EGFR and cdc2p34 were correlated with muscle invasion and histological grade. Ten proteins (ß-catenin, HSP70, autotaxin, Notch4, PSTPIP1, DPYD, ODC, cyclinB1, calretinin and EPO) were able to classify muscle invasive BCa (MIBC) into 2 distinct groups, with group 2 associated with poorer survival. Finally, 3 proteins (P2X7, cdc25B and TFIIH p89) were independent factors for favorable overall survival. PMID:27626805

  12. Merkel cell carcinoma with an unusual immunohistochemical profile.

    PubMed

    Pilloni, L; Manieli, C; Senes, G; Ribuffo, D; Faa, G

    2009-12-29

    The clinical and morphological picture of Merkel cell carcinoma (MCC) may be rather challenging; therefore, the immunohistochemical profile plays a relevant role in confirming the microscopic diagnosis. A panel of antibodies including cytokeratins 20, 7 and epithelial membrane antigen, and neuron-specific enolase is used in confirming the morphological diagnosis of MCC. The majority of MCCs express CK20 and are CK7-negative. Herein, we present a case of primary cutaneous neuroendocrine carcinoma with an atypical immunohistochemical pattern. A 83-years old woman presented with a painless plaque, red to violaceous in colour, located in the leg. The skin tumor was excided, formalin-fixed and paraffinembedded. Tissue sections were immunostained with a panel of antibodies routinely utilized in complex primary skin tumors for evidencing epithelial and neuroendocrine differentiation of tumor cells. The neuroendocrine differentiation of tumor cells was evidenced by their immunoreactivity for synaptophysin, chromograninA and neuron-specific enolase. Tumor cells also showed diffuse cytoplasmic staining for CK7. No immunoreactivity was detected for CK20 and thyroid transcription factor-1. Our data, together with previous rare reports of CK20-/CK7+ MCCs, lay stress on the importance of routinely utilizing a panel of antibodies in the differential diagnosis of complex primary carcinomas of the skin and may have important implications in expanding the differential diagnosis of skin tumors. In particular, caution should be taken in excluding the diagnosis of MCC only on the basis of the absence of reactivity of tumor cells for CK20, favouring the wrong diagnosis of less aggressive skin tumors. PMID:22073365

  13. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    PubMed Central

    Chiappini, Franck

    2012-01-01

    Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC) reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1) there are few markers specific to the HCC (tumor cells versus nontumor cells) and (2) they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC. PMID:22690340

  14. Catecholaminergic neurons result from intracerebral implantation of embryonal carcinoma cells.

    PubMed Central

    Wojcik, B E; Nothias, F; Lazar, M; Jouin, H; Nicolas, J F; Peschanski, M

    1993-01-01

    A replication-defective retrovirus was used to introduce the marker gene nlsLacZ into the murine embryonal carcinoma (EC) cell line PCC7-S-aza-R-1009. Undifferentiated EC cells were implanted into the central nervous system of adult rats. One month later, the grafted cells continued to express the nlsLacZ gene. Immunohistochemical analysis demonstrated the presence of EC-derived neurons. These neurons were capable of expressing tyrosine hydroxylase and extended neurites into the host parenchyma. EC-derived glial cells could not be detected. There was no evidence of tumorigenicity. These results demonstrate the utility of EC cells for introduction of exogenous gene products into the central nervous system in experimental models of gene therapy. Images PMID:8094557

  15. TERT promoter mutations in renal cell carcinomas and upper tract urothelial carcinomas.

    PubMed

    Wang, Kun; Liu, Tiantian; Liu, Li; Liu, Jikai; Liu, Cheng; Wang, Chang; Ge, Nan; Ren, Hongbo; Yan, Keqiang; Hu, Sanyuan; Björkholm, Magnus; Fan, Yidong; Xu, Dawei

    2014-04-15

    TERT promoter mutations are identified in many malignancies including bladder cancer (BC) and upper tract urothelial carcinoma (UTUC). In contrast, no mutations were found in renal cell carcinoma (RCC) as reported in a recent study. Because the mutant TERT promoter in urine DNA was recently tested as a marker for BC, it is important to ascertain whether these mutations are truly absent in RCCs. Here we determined TERT promoter mutations in 109 patients with RCC and 14 patients with UTUC. The mutations were found in 9/96 (9.3%) clear cell RCC (ccRCC) tumors and 1/8 (13%) chromophobe RCC tumors. Among ccRCC patients, the mutation was correlated with the advanced stages and metastasis, and higher TERT expression. Among UTUCs, the mutation was detected in tumors from 3/5 (60%) patients with renal pelvic cancer and 1/9 (11%) patients with ureter cancer. The mutation was also detected in 1 of 4 urine samples from patients with mutation+ UTUC. Collectively, TERT promoter mutations do occur in RCCs and are associated with aggressive disease. The mutation is more frequent in renal pelvic cancer. Thus, the mutant TERT promoter found in urine may come from not only BC, but also RCC or UTUC. PMID:24742867

  16. TERT promoter mutations in renal cell carcinomas and upper tract urothelial carcinomas

    PubMed Central

    Liu, Jikai; Liu, Cheng; Wang, Chang; Ge, Nan; Ren, Hongbo; Yan, Keqiang; Hu, Sanyuan; Björkholm, Magnus; Fan, Yidong; Xu, Dawei

    2014-01-01

    TERT promoter mutations are identified in many malignancies including bladder cancer (BC) and upper tract urothelial carcinoma (UTUC). In contrast, no mutations were found in renal cell carcinoma (RCC) as reported in a recent study. Because the mutant TERT promoter in urine DNA was recently tested as a marker for BC, it is important to ascertain whether these mutations are truly absent in RCCs. Here we determined TERT promoter mutations in 109 patients with RCC and 14 patients with UTUC. The mutations were found in 9/96 (9.3%) clear cell RCC (ccRCC) tumors and 1/8 (13%) chromophobe RCC tumors. Among ccRCC patients, the mutation was correlated with the advanced stages and metastasis, and higher TERT expression. Among UTUCs, the mutation was detected in tumors from 3/5 (60%) patients with renal pelvic cancer and 1/9 (11%) patients with ureter cancer. The mutation was also detected in 1 of 4 urine samples from patients with mutation+ UTUC. Collectively, TERT promoter mutations do occur in RCCs and are associated with aggressive disease. The mutation is more frequent in renal pelvic cancer. Thus, the mutant TERT promoter found in urine may come from not only BC, but also RCC or UTUC. PMID:24742867

  17. Basal cell carcinoma and breast carcinoma following repeated fluoroscopic examinations of the chest

    SciTech Connect

    Myskowski, P.L.; Gumpertz, E.; Safai, B.

    1985-03-01

    A 69-year-old white Italian woman was first seen at Memorial Sloan-Kettering Cancer Center in 1981 concerning several skin growths on her back. The patient had had several basal cell carcinomas surgically removed from her back during the preceding 5 years. There was no history of arsenic ingestion or prolonged sun exposure and her family history was negative for skin cancer. The patient had developed pulmonary tuberculosis in 1938 and was treated with pneumothorax therapy. She had had more than 50 fluoroscopic examinations of the chest following this therapy, as well as multiple diagnostic x-ray films since that time. On the back, clustered in the interscapular region, were multiple scars and nine erythematous nodules with pearly borders, telangiectasia, and translucent surfaces. Within several nodules there were areas of light and dark brown pigmentation. Biopsy of all lesions revealed basal cell carcinoma, some of which were pigmented, without evidence of chronic radiodermatitis. All lesions were treated with curettage and electrodesiccation three times with good cosmetic results.

  18. Multiple nephron-sparing procedures in solitary kidney with recurrent, metachronous, nonfamilial renal cell carcinoma.

    PubMed

    Nosnik, Israel P; Mouraviev, Vladimir; Nelson, Rendon; Polascik, Thomas J

    2006-12-01

    Patients with metachronous bilateral renal cell carcinoma pose a significant challenge given the high mortality of renal cell carcinoma and the poor quality of life should dialysis become necessary. In addition, patients may be subject to morbidity due to potential multiple treatments of the multifocal renal tumors. We present the case of a 71-year-old woman with multifocal, bilateral clear cell carcinoma who maintained a minimal change in serum creatinine after undergoing unilateral radical nephrectomy, subsequent percutaneous radiofrequency ablation, percutaneous cryoablation, laparoscopic cryoablation, and open partial nephrectomy for recurrent renal cell carcinoma in a solitary kidney.

  19. Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma.

    PubMed

    Brunelli, Matteo; Gobbo, Stefano; Cossu-Rocca, Paolo; Cheng, Liang; Hes, Ondrej; Delahunt, Brett; Pea, Maurizio; Bonetti, Franco; Mina, Maria M; Ficarra, Vincenzo; Chilosi, Marco; Eble, John N; Menestrina, Fabio; Martignoni, Guido

    2007-03-01

    The hallmark of chromophobe renal cell carcinoma is multiple chromosomal losses from among chromosomes 1, 2, 6, 10 and 17. Chromophobe renal cell carcinoma with distant metastases or sarcomatoid transformation are uncommon and little is known about their chromosomal abnormalities. We collected six sarcomatoid chromophobe renal cell carcinomas and three primary chromophobe renal cell carcinomas with distant metastases. A cytogenetic analysis by fluorescent in situ hybridization on paraffin-embedded tissue was performed using centromeric probes for chromosomes 1, 2, 6, 10 and 17. We found more than one signal in four of six (66%) sarcomatoid chromophobe renal cell carcinomas, in both sarcomatoid and adjacent epithelial components. Both primary chromophobe renal cell carcinomas and matched metastases showed single signals for all chromosomes studied in two cases and no abnormalities in the remaining case. We concluded that: (1) both epithelial and sarcomatoid components of sarcomatoid chromophobe renal cell carcinoma show different genetic abnormalities from those characteristic of chromophobe renal cell carcinoma; (2) sarcomatoid chromophobe renal cell carcinomas frequently have multiple gains (polysomy) of chromosomes 1, 2, 6, 10 and 17; (3) distant metastases show the same genetic patterns, usually chromosomal losses (monosomy), found in the primary tumors.

  20. Taxol and discodermolide represent a synergistic drug combination in human carcinoma cell lines.

    PubMed

    Martello, L A; McDaid, H M; Regl, D L; Yang, C P; Meng, D; Pettus, T R; Kaufman, M D; Arimoto, H; Danishefsky, S J; Smith, A B; Horwitz, S B

    2000-05-01

    Recently, three natural products have been identified, the epothilones, eleutherobin, and discodermolide, whose mechanism of action is similar to that of Taxol in that they stabilize microtubules and block cells in the mitotic phase of the cell cycle. In this report, we have compared and contrasted the effects of these new agents in Taxol-sensitive and -resistant cell lines. We also have taken advantage of a human lung carcinoma cell line, A549-T12, that was isolated as a Taxol-resistant cell line and found to require low concentrations of Taxol (2-6 nM) for normal cell division. This study then examined the ability of these new compounds to substitute for Taxol in sustaining the growth of A549-T12 cells. Immunofluorescence and flow cytometry have both indicated that the epothilones and eleutherobin, but not discodermolide, can substitute for Taxol in this Taxol-dependent cell line. In A549-T12 cells, the presence of Taxol significantly amplified the cytotoxicity of discodermolide, and this phenomenon was not observed in combinations of Taxol with either the epothilones or eleutherobin. Median effect analysis using the combination index method revealed a schedule-independent synergistic interaction between Taxol and discodermolide in four human carcinoma cell lines, an effect that was not observed between Taxol and epothilone B. Flow cytometry revealed that concurrent exposure of A549 cells to Taxol and discodermolide at doses that do not induce mitotic arrest caused an increase in the hypodiploid population, thereby indicating that a possible mechanism for the observed synergy is the potentiation of apoptosis. Our results suggest that Taxol and discodermolide may constitute a promising chemotherapeutic combination.

  1. DETECTION OF HUMAN PAPILLOMA VIRUS IN HEAD AND NECK SQUAMOUS CELL CARCINOMAS: A LITERATURE REVIEW.

    PubMed

    Jelihovschi, I; Bidescu, Aida Corina; Tucaliuc, Simona Elena; Iancu, Luminiţa Smaranda

    2015-01-01

    Human papilloma viruses (HPV) are the most common sexually transmitted viruses. There is mounting evidence that incriminates HPV as a risk factor for malignant transformation of oropharyngeal epithelium. In 2011 the International Research Agency of Cancer and National Cancer Institute (USA) declared HPV-16 as an independent risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Leaders in the field of HPV research admit that this subtype of head and neck cancer is a sexually transmitted entity and its global incidence is on the rise. In the 1980s, clinicians observed a new group of patients with head and neck squamous cell carcinoma (HNSCC) independent of tobacco smoking or alcohol use. The new HNSCC patient is a middle-aged man, non-smoker, non-drinker with higher social status and the suspected risk factors for HNSCC being related to sexual practices (oral sex, multiple sexual partners, unprotected sex and drug use). Routine HPV testing of HNSCC patients is seriously considered as HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical and pathologic entity that has a markedly better prognosis than HPV-negative oropharyngeal cancers. The current treatment protocols for OPSCC include radiation, chemotherapy and surgery alone or in combination, involving high toxicity levels. Future therapeutic concepts for OPSCC may be personalized in relation to HPV-status to avoid unnecessary toxicity. The current review summarizes the contemporary trends in the diagnosis of HPV-related head and neck cancers, presenting the advantages and disadvantages of the main methods.

  2. SU-E-P-18: Intensity-Modulated Radiation Therapy for Cervical Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Bai, W; Qiao, X; Zhou, Z; Song, Y; Zhang, R; Zhen, C

    2015-06-15

    Purpose: To retrospectively analyze the outcomes and prognostic factors of cervical esophageal squamous cell carcinoma (SCC) treated with intensity modulated radiation therapy (IMRT). Methods: Thirty-seven patients with cervical esophageal SCC treated with IMRT were analyzed retrospectively. They received 54–66 Gy in 27–32 fractions. Nineteen patients received concurrent (n=12) or sequential (n=7) platinum-based two drugs chemoradiotherapy. Overall survival (OS), local control rates (LCR) and prognostic factors were evaluated. Acute toxicities and patterns of first failures were observed. Results: The median follow-up was 46 months for alive patients. The l-, 3-, 4- and 5-year OS of the all patients were 83.8%, 59.1%, 47.5% and 32.6% respectively. The median survival time was 46 months. The l-, 3-,4- and 5-year LCR were 82.9%, 63.0%, 54.5% and 54.5%, respectively. Univariate and Multivariate analysis all showed that size of GTV was an independent prognostic factor (p=0.033, p=0.039). There were no patients with Grade 3 acute radiation esophagitis and Grade 2–4 acute pneumonitis. The local failure accounted for 70.0% of all treatment-related failures. Conclusion: IMRT is safe and effective in the treatment of cervical esophageal squamous cell carcinoma. Size of GTV is an independent prognostic factor. Local failure still remains the main reason of treatment failures. The authors declare no conflicts of interest in preparing this article.

  3. Xp11 translocation renal cell carcinoma morphologically mimicking clear cell-papillary renal cell carcinoma in an adult patient: report of a case expanding the morphologic spectrum of Xp11 translocation renal cell carcinomas.

    PubMed

    Parihar, Asmita; Tickoo, Satish K; Kumar, Sunil; Arora, Vinod Kumar

    2015-05-01

    Xp11 translocation renal cell carcinoma (RCC) is a relatively rare tumor mainly affecting children and adolescents. It shows significant morphological overlap with the 2 most common adult renal tumors, which are the clear cell (conventional) RCC and papillary RCC. We describe case of a young adult female who presented with right flank pain and abdominal mass. Radiological investigations showed features suggestive of renal cell carcinoma in the right kidney. Histopathological findings while suggestive of Xp11 carcinoma, showed significant overlap with the recently described entity clear cell papillary RCC. TFE3 immunohistochemistry confirmed the tumor to be Xp11 translocation RCC. The patient had an aggressive course with lymph node metastasis. In this report, we discuss differential diagnosis and the diagnostic challenges of Xp11 translocation RCC in adults.

  4. Photodynamic therapy-induced programmed cell death in carcinoma cell lines

    NASA Astrophysics Data System (ADS)

    He, Xiao-Yan; Sikes, Robert A.; Thomsen, Sharon L.; Chung, L.; Jacques, Steven L.

    1993-06-01

    The mode of cell death following photodynamic therapy (PDT) was investigated from the perspective of programmed cell death (apoptosis). Human prostate carcinoma cells (PC3), human non-small cell lung carcinoma (H322a), and rat mammary carcinoma (MTF7) were treated by PDT following sensitization with dihematoporphyrin ether (DHE). The response of these carcinoma cell lines to PDT was variable. An examination of extracted cellular DNA by gel electrophoresis showed the characteristic DNA ladder pattern indicative of internucleosomal cleavage of DNA during apoptosis. MTF7 and PC3 responded to PDT by inducing apoptosis while H322a had no apoptotic response. The magnitude of the response and the PDT dosage required to induce the effect were different in PC3 and MTF7. MTF7 cells responded with rapid apoptosis at the dose of light and drug that yielded 50% cell death (LD50). In contrast, PC3 showed only marginal apoptosis at the LD50 but had a marked response at the LD85. Furthermore, the onset of apoptosis followed slower kinetics in PC3 (2 hr - 4 hr) than in MTF7 (< 1 hr). H322a cells were killed by PDT but failed to exhibit any apoptotic response. This study indicates that apoptosis may occur during PDT induced cell death, but this pathway is not universal for all cancer cell lines.

  5. The Use of P63 Immunohistochemistry for the Identification of Squamous Cell Carcinoma of the Lung

    PubMed Central

    Conde, Esther; Angulo, Bárbara; Redondo, Pilar; Toldos, Oscar; García-García, Elena; Suárez-Gauthier, Ana; Rubio-Viqueira, Belén; Marrón, Carmen; García-Luján, Ricardo; Sánchez-Céspedes, Montse; López-Encuentra, Angel; Paz-Ares, Luis; López-Ríos, Fernando

    2010-01-01

    Introduction While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of “carcinoma NOS (not otherwise specified)” in a prospective series of small tumor samples. Methods With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC. Results The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs. Conclusions P63 IHC is useful for the identification of lung SCCs. PMID:20808915

  6. B cells mediate chronic allograft rejection independently of antibody production.

    PubMed

    Zeng, Qiang; Ng, Yue-Harn; Singh, Tripti; Jiang, Ke; Sheriff, Khaleefathullah A; Ippolito, Renee; Zahalka, Salwa; Li, Qi; Randhawa, Parmjeet; Hoffman, Rosemary A; Ramaswami, Balathiripurasundari; Lund, Frances E; Chalasani, Geetha

    2014-03-01

    Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture.

  7. Accuracy of classifying poorly differentiated non-small cell lung carcinoma biopsies with commonly used lung carcinoma markers.

    PubMed

    Zachara-Szczakowski, Susanna; Verdun, Tyler; Churg, Andrew

    2015-05-01

    Immunohistochemical (IHC) staining is an important adjunct to the classification of non-small cell lung carcinoma (NSCLC). Several studies have used tissue microarrays derived from resection specimens to evaluate the accuracy of IHC staining for classifying NSCLC, but few have used actual biopsies of poorly differentiated carcinomas, and the question of how often biopsy IHC in such tumors leads to the correct classification has received little attention. We identified 40 cases of NSCLC that, on biopsy, could not be subclassified by morphology and that had subsequent resection specimens. TTF-1, napsin, p63/p40, and CK5 or a subset thereof were used for IHC classification. Of the 40 cases classified by IHC on biopsy, 33 (82%) had no change in diagnosis after resection. Of the remaining 7 cases, 3 were classified as NSCLC--not otherwise specified on biopsy and subclassified as either adenocarcinoma or squamous cell carcinoma (SCC) on the surgical specimen. One adenocarcinoma biopsy was reclassified as pleomorphic carcinoma. Two SCCs were changed to adenosquamous carcinoma, and 1 SCC was changed to large cell lung carcinoma. Only 1 antibody pair (2%) was discordant between biopsy, and almost all reclassifications were done based on morphologic features rather than change in IHC pattern. We conclude that IHC staining allows accurate subclassification of poorly differentiated NSCLCs on small lung biopsies in most cases, but there is still a substantial "miss" rate (here, 18%). Surgical resection specimens allow further subclassification, mainly due to architectural features not present in the biopsies.

  8. Heparin treatment increases thioredoxin interacting protein expression in hepatocellular carcinoma cells.

    PubMed

    Gunes, Aysim; Iscan, Evin; Topel, Hande; Avci, Sanem Tercan; Gumustekin, Mukaddes; Erdal, Esra; Atabey, Nese

    2015-08-01

    Heparins play an important role in cell growth, differentiation, migration and invasion. However, the molecular mechanisms of heparin mediated cellular behaviors are not well defined. To determine the effect of heparin on gene expression, we performed a cDNA microarray in a hepatocellular carcinoma cell line and found that heparin regulates transcription of genes involved in glucose metabolism. In this study, we showed a new role of heparin in the regulation of thioredoxin interacting protein, which is a major regulator of glucose metabolism, in hepatocellular carcinoma cell lines. We determined the importance of a unique carbohydrate response element located on its promoter for the heparin-induced activation of thioredoxin-interacting protein and the modulatory role of heparin on nuclear accumulation of carbohydrate response element associated proteins. We showed the importance of heparin mediated histone modifications and down-regulation of Enhancer of zeste 2 polycomb repressive complex 2 expression for heparin mediated overexpression of thioredoxin-interacting protein. When we tested biological significance of these data; we observed that cells overexpressing thioredoxin-interacting protein are less adhesive and proliferative, however they have a higher migration and invasion ability. Interestingly, heparin treatment increased thioredoxin-interacting protein expression in liver of diabetic rats. In conclusion, our results show that heparin activates thioredoxin-interacting protein expression in liver and hepatocellular carcinoma cells and provide the first evidences of regulatory roles of heparin on carbohydrate response element associated factors. This study will contribute future understanding of the effect of heparin on glucose metabolism and glucose independent overexpression of thioredoxin-interacting protein during hepatocarcinogenesis.

  9. Anoikis Mediators in Oral Squamous Cell Carcinoma

    PubMed Central

    Bunek, Julius; Kamarajan, Pachiyappan; Kapila, Yvonne L.

    2010-01-01

    Anoikis—apoptotic cell death triggered by loss of extracellular matrix (ECM) contacts— is dysregulated in many chronic debilitating and fatal diseases. Mechanisms rendering tumor cells resistant to anoikis, although not completely understood, possess significant therapeutic promise. In death receptor-mediated anoikis mechanisms, FAK and RIP dissociate, leading to association of RIP with Fas, formation of the death-inducing signaling complex (DISC), activation of caspase-3, and propagation of anoikis. In contrast, anoikis resistance is accomplished through constitutive activation of survival pathways that include integrin-dependent activation of focal adhesion kinase (FAK) and extracellular-signal-regulated kinase (ERK). In addition, FAK and receptor-interacting protein (RIP) association confers anoikis resistance by inhibiting the association of RIP with Fas and formation of the death signaling complex, which allows cells to escape anoikis. Up-regulation of CD44 also contributes to survival signals and promotes anoikis resistance. This review will focus on the roles of death receptors, pro-survival pathways, and the molecular players involved in anoikis escalation and resistance in OSCC. PMID:21114588

  10. A Phase Ib/II Study of BYL719 and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-06-30

    Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (RM HNSCC) Patients Who Are Resistant or Ineligible/Intolerant to Platinum-based Chemotherapy.; Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma

  11. NDRG2 suppresses the proliferation of clear cell renal cell carcinoma cell A-498

    PubMed Central

    2010-01-01

    Background Recently, the anti-tumor activity of N-myc downstream-regulated gene 2 (NDRG2) was shown decreased expression in clear cell renal cell carcinoma (CCRCC), but the role of the down-expression of NDRG2 has not been described. Methods The NDRG2 recombinant adenovirus plasmid was constructed. The proliferation rate and NDRG2 expression of cell infected with recombinant plasmid were mesured by MTT, Flow cytometry analysis and western blot. Results The CCRCC cell A-498 re-expressed NDRG2 when infected by NDRG2 recombinant adenovirus and significantly decreased the proliferation rate. Fluorescence activated cell sorter analysis showed that 25.00% of cells expressed NDRG2 were in S-phase compared to 40.67% of control cells, whereas 62.08% of cells expressed NDRG2 were in G1-phase compared to 54.39% of control cells (P < 0.05). In addition, there were much more apoptotic cells in NDRG2-expressing cells than in the controls (P < 0.05). Moreover, upregulation of NDRG2 protein was associated with a reduction in cyclin D1, cyclin E, whereas cyclinD2, cyclinD3 and cdk2 were not affected examined by western blot. Furthermore, we found that p53 could upregulate NDRG2 expression in A-498 cell. Conclusions We found that NDRG2 can inhibit the proliferation of the renal carcinoma cells and induce arrest at G1 phase. p53 can up-regulate the expression of NDRG2. Our results showed that NDRG2 may function as a tumor suppressor in CCRCC. PMID:20673333

  12. ADAM12 induces estrogen-independence in breast cancer cells.

    PubMed

    Roy, Roopali; Moses, Marsha A

    2012-02-01

    Antiestrogen therapy has been used successfully to prolong disease-free and overall survival of ER positive breast cancer patients. However, 50% of patients with ER+ tumors fail to respond to such therapy or eventually acquire resistance to endocrine therapy, resulting in tumor progression and mortality. It is imperative, therefore, to understand the mechanisms that lead to hormone refractory breast cancer in order to develop therapeutics that can modulate the resistance to antiestrogen therapy. The protease, ADAM12, can be detected in the urine of breast cancer patients and its levels correlate with disease status, stage, and cancer risk. Within the context of this study, the authors have investigated the role of the two distinct isoforms of ADAM12 in breast tumor cell proliferation and as potential mediators of endocrine resistance. Using stable clones of ADAM12-overexpressing MCF-7 cells, the authors analyzed proliferation rates of these ER+ breast tumor cells both in estrogen-depleted medium and in the presence of the antiestrogens, tamoxifen, and ICI 182,780. Acquired estrogen resistance in these cells was analyzed using phospho-RTK analysis. Upregulation and phosphorylation of proteins were detected via immunoprecipitation and immunoblotting. EGFR and MAPK inhibitors were used to explore the mechanism of acquired estrogen resistance in breast tumor cells. It was observed that overexpression of the two isoforms, transmembrane ADAM12-L, and secreted ADAM12-S, in breast tumor cells promoted estrogen-independent proliferation. In ADAM12-L-expressing cells, estrogen-independence was a direct result of increased EGFR expression and MAPK activation, whereas, the mechanism in ADAM12-S-expressing cells may be enhanced IGF-1R signaling. The importance of the EGFR signaling pathway in the estrogen-independent growth of ADAM12-L expressing cells was highlighted by the effect of EGFR inhibitors AG1478 and PD15035 or MAPK inhibitor U0126, each of which abolished the

  13. Src inhibits midline axon crossing independent of Frazzled/Deleted in Colorectal Carcinoma (DCC) receptor tyrosine phosphorylation.

    PubMed

    O'Donnell, Michael P; Bashaw, Greg J

    2013-01-01

    The phylogenetically conserved Netrin family of chemoattractants signal outgrowth and attractive turning of commissural axons through the Deleted in Colorectal Carcinoma (DCC) family of receptors. Src family kinases are thought to be major signaling effectors of Netrin/DCC. In vertebrates, Src and the closely related Fyn kinases phosphorylate DCC and form a receptor-bound signaling complex leading to activation of downstream effectors. Here we show that, in the Drosophila embryonic CNS, Src kinases are dispensable for midline attraction of commissural axons. Consistent with this observation, tyrosine phosphorylation of the Netrin receptor DCC or its Drosophila ortholog, Frazzled, is not necessary for attraction to Netrin. Moreover, we uncover an unexpected function of Src kinases: inhibition of midline axon crossing through a novel mechanism. We propose that distinct signaling outputs must exist for midline axon crossing independent of Src kinases in commissural neurons.

  14. Osteoactivin Promotes Migration of Oral Squamous Cell Carcinomas.

    PubMed

    Arosarena, Oneida A; Dela Cadena, Raul A; Denny, Michael F; Bryant, Evan; Barr, Eric W; Thorpe, Ryan; Safadi, Fayez F

    2016-08-01

    Nearly 50% of patients with oral squamous cell carcinoma (OSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell adhesion, migration, and invasion. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies. The aims were to determine how integrin interactions modulate OA-induced OSCC cell migration; and to investigate OA effects on cell survival and proliferation. We confirmed OA mRNA and protein overexpression in OSCC cell lines. We assessed OA's interactions with integrins using adhesion inhibition assays, fluorescent immunocytochemistry and co-immunoprecipitation. We investigated OA-mediated activation of mitogen-activated protein kinases (MAPKs) and cell survival. Integrin inhibition effects on OA-mediated cell migration were determined. We assessed effects of OA knock-down on cell migration and proliferation. OA is overexpressed in OSCC cell lines, and serves as a migration-promoting adhesion molecule. OA co-localized with integrin subunits, and co-immunoprecipitated with the subunits. Integrin blocking antibodies, especially those directed against the β1 subunit, inhibited cell adhesion (P = 0.03 for SCC15 cells). Adhesion to OA activated MAPKs in UMSCC14a cells and OA treatment promoted survival of SCC15 cells. Integrin-neutralizing antibodies enhanced cell migration with OA in the extracellular matrix. OA knock-down resulted in decreased proliferation of SCC15 and SCC25 cells, but did not inhibit cell migration. OA in the extracellular matrix promotes OSCC cell adhesion and migration, and may be a novel target in the prevention of HNSCC spread. J. Cell. Physiol. 231: 1761-1770, 2016. © 2015 Wiley Periodicals, Inc. PMID:26636434

  15. Osteoactivin Promotes Migration of Oral Squamous Cell Carcinomas.

    PubMed

    Arosarena, Oneida A; Dela Cadena, Raul A; Denny, Michael F; Bryant, Evan; Barr, Eric W; Thorpe, Ryan; Safadi, Fayez F

    2016-08-01

    Nearly 50% of patients with oral squamous cell carcinoma (OSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell adhesion, migration, and invasion. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies. The aims were to determine how integrin interactions modulate OA-induced OSCC cell migration; and to investigate OA effects on cell survival and proliferation. We confirmed OA mRNA and protein overexpression in OSCC cell lines. We assessed OA's interactions with integrins using adhesion inhibition assays, fluorescent immunocytochemistry and co-immunoprecipitation. We investigated OA-mediated activation of mitogen-activated protein kinases (MAPKs) and cell survival. Integrin inhibition effects on OA-mediated cell migration were determined. We assessed effects of OA knock-down on cell migration and proliferation. OA is overexpressed in OSCC cell lines, and serves as a migration-promoting adhesion molecule. OA co-localized with integrin subunits, and co-immunoprecipitated with the subunits. Integrin blocking antibodies, especially those directed against the β1 subunit, inhibited cell adhesion (P = 0.03 for SCC15 cells). Adhesion to OA activated MAPKs in UMSCC14a cells and OA treatment promoted survival of SCC15 cells. Integrin-neutralizing antibodies enhanced cell migration with OA in the extracellular matrix. OA knock-down resulted in decreased proliferation of SCC15 and SCC25 cells, but did not inhibit cell migration. OA in the extracellular matrix promotes OSCC cell adhesion and migration, and may be a novel target in the prevention of HNSCC spread. J. Cell. Physiol. 231: 1761-1770, 2016. © 2015 Wiley Periodicals, Inc.

  16. Photodynamic therapy in the treatment of basal cell carcinoma

    PubMed Central

    Matei, C; Tampa, M; Poteca, T; Panea-Paunica, G; Georgescu, SR; Ion, RM; Popescu, SM; Giurcaneanu, C

    2013-01-01

    Photodynamic therapy (PDT) is a medical procedure based on the activation of the molecules of various exogenous or endogenous chemical substances called photosensitizers by a light source emitting radiation of an adequate wavelength, usually situated in the visible spectrum; photosensitizers are chemical compounds bearing the capacity to selectively concentrate in the neoplastic cells. The energy captured by the molecules of these substances pervaded in the tumor cells is subsequently discharged in the surrounding tissue, triggering certain photodynamic reactions that result in the destruction of the tumor. The procedure is applicable in numerous medical fields. Skin basal cell carcinoma (BCC), the most frequent type of cancer of the human species, is a cutaneous tumor that responds very well to this innovative treatment method. By reviewing numerous recent studies in the field, this article aims to present the role and the indications of photodynamic therapy in the management of basal cell carcinoma, as well as the most important results achieved so far by this therapy in the field of dermato-oncology. PMID:23599819

  17. Basal Cell Carcinoma of the Umbilicus: A Comprehensive Literature Review

    PubMed Central

    Cohen, Philip R

    2016-01-01

    Basal cell carcinoma (BCC) typically occurs in sun-exposed sites. Only 16 individuals with umbilical BCC have been described in the literature, and the characteristics of patients with umbilical BCC are summarized. PubMed was used to search the following terms: abdomen, basal cell carcinoma, basal cell nevus syndrome, and umbilicus. Papers with these terms and references cited within these papers were reviewed. BCC of the umbilicus has been reported in five men and 11 women; one man had two tumors. Two patients had basal cell nevus syndrome (BCNS). Other risk factors for BCC were absent. The tumor most commonly demonstrated nodular histology (64%, 9/14); superficial and fibroepithelioma of Pinkus variants were noted in three and two patients, respectively. The tumor was pigmented in eight individuals. Treatment was conventional surgical excision (87%, 13/15) or Mohs micrographic surgery (13%, 2/15); either adjuvant laser ablation or radiotherapy was performed in two patients. The prognosis after treatment was excellent with no recurrence or metastasis (100%, 16/16). In conclusion, BCC of the umbilicus is rare. It usually presents as a tumor with a non-aggressive histologic subtype in an individual with no risk factors for this malignancy. There has been no recurrence or metastasis following excision of the cancer. PMID:27738570

  18. Collision of Ductal Carcinoma In Situ of Anogenital Mammary-like Glands and Vulvar Sarcomatoid Squamous Cell Carcinoma.

    PubMed

    Tran, Tien A N; Deavers, Michael T; Carlson, J Andrew; Malpica, Anais

    2015-09-01

    A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.

  19. Clinicopathological Characteristics and Survival Outcomes of Primary Signet Ring Cell Carcinoma in the Stomach: Retrospective Analysis of Single Center Database

    PubMed Central

    Liu, Xiaowen; Cai, Hong; Sheng, Weiqi; Yu, Lin; Long, Ziwen; Shi, Yingqiang; Wang, Yanong

    2015-01-01

    Purpose To investigate the clinicopathological features and prognosis of signet ring cell carcinoma of the stomach (SRC). Methods A total of 1464 gastric cancer patients who underwent curative gastrectomy from 2000 to 2008 at a single center were evaluated. Signet ring cell carcinoma (SRC) was defined as the presence of at least 50% signet ring cells in the pathologic specimen. The clinicopathological parameters and prognosis of SRC were analyzed by comparing with non-signet ring cell carcinoma (NSRC). Results Of 1464 patients, 138 patients (9.4%) were classified as SRC. There were significant differences in gender, age, tumor location, TNM stage, p21 expression, and p53 expression between SRC and NSRC. The 5-year survival rates of SRC and NSRC were 36.2% and 49.5%, respectively. The prognosis of SRC was poorer than that of NSRC (P <0.001). Multivariate analysis showed that SRC histology was an independent factor for poor prognosis (P <0.001). Conclusion Patients with SRC tend to present with a more advanced stage and poorer prognosis than patients with other types of gastric carcinoma. PMID:26642199

  20. SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

    PubMed

    Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

    2016-10-01

    Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory.

  1. SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

    PubMed

    Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

    2016-10-01

    Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory. PMID:27327192

  2. Clear cell carcinoma of the female genital tract (not everything is as clear as it seems).

    PubMed

    Offman, Saul L; Longacre, Teri A

    2012-09-01

    Clear cell carcinoma has a storied history in the female genital tract. From the initial designation of ovarian clear cell adenocarcinoma as "mesonephroma" to the linkage between vaginal clear cell carcinoma and diethylstilbestrol exposure in utero, gynecologic tract clear cell tumors have puzzled investigators, posed therapeutic dilemmas for oncologists, and otherwise presented major differential diagnostic challenges for pathologists. One of the most common errors in gynecologic pathology is misdiagnosis of clear cell carcinoma, on both frozen section and permanent section. Given the poor response to platinum-based chemotherapy for advanced-stage disease and increased risk of thromboembolism, accurate diagnosis of clear cell carcinoma is important in the female genital tract. This review (1) presents the clinical and pathologic features of female genital tract clear cell carcinomas; (2) highlights recent molecular developments; (3) identifies areas of potential diagnostic confusion; and (4) presents solutions for these diagnostic problems where they exist.

  3. Pathway Signature and Cellular Differentiation in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Tun, Han W.; Marlow, Laura A.; von Roemeling, Christina A.; Cooper, Simon J.; Kreinest, Pamela; Wu, Kevin; Luxon, Bruce A.; Sinha, Mala; Anastasiadis, Panos Z.; Copland, John A.

    2010-01-01

    Background Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer. The purpose of this study is to define a biological pathway signature and a cellular differentiation program in ccRCC. Methodology We performed gene expression profiling of early-stage ccRCC and patient-matched normal renal tissue using Affymetrix HG-U133a and HG-U133b GeneChips combined with a comprehensive bioinformatic analyses, including pathway analysis. The results were validated by real time PCR and IHC on two independent sample sets. Cellular differentiation experiments were performed on ccRCC cell lines and their matched normal renal epithelial cells, in differentiation media, to determine their mesenchymal differentiation potential. Principal Findings We identified a unique pathway signature with three major biological alterations—loss of normal renal function, down-regulated metabolism, and immune activation–which revealed an adipogenic gene expression signature linked to the hallmark lipid-laden clear cell morphology of ccRCC. Culturing normal renal and ccRCC cells in differentiation media showed that only ccRCC cells were induced to undergo adipogenic and, surprisingly, osteogenic differentiation. A gene expression signature consistent with epithelial mesenchymal transition (EMT) was identified for ccRCC. We revealed significant down-regulation of four developmental transcription factors (GATA3, TFCP2L1, TFAP2B, DMRT2) that are important for normal renal development. Conclusions ccRCC is characterized by a lack of epithelial differentiation, mesenchymal/adipogenic transdifferentiation, and pluripotent mesenchymal stem cell-like differentiation capacity in vitro. We suggest that down-regulation of developmental transcription factors may mediate the aberrant differentiation in ccRCC. We propose a model in which normal renal epithelial cells undergo dedifferentiation, EMT, and adipogenic transdifferentiation, resulting in ccRCC. Because ccRCC cells grown in adipogenic

  4. Unresectable basaloid squamous cell carcinoma of the trachea treated with concurrent chemoradiotherapy: a case report with review of literature.

    PubMed

    Joshi, Nikhil P; Haresh, Kunhi Parambath; Das, Prasenjit; Kumar, Rajender; Prabhakar, Ramachandran; Sharma, Daya Nand; Heera, Puthiyeduthu; Julka, Pramod Kumar; Rath, Goura Kishor

    2010-01-01

    Basaloid squamous cell carcinoma is an uncommon variant of squamous cell carcinoma of the trachea. We describe the case of an unresectable basaloid squamous cell carcinoma of the trachea treated with concurrent chemoradiotherapy up to a dose of 60 Gy in 33 fractions with weekly paclitaxel and carboplatin. The pathological recognition of basaloid squamous cell carcinoma and its distinction from adenoid cystic carcinoma of the trachea is important for its management. Combining systemic chemotherapy with locoregional radiation is a logical approach to treatment, especially for the basaloid squamous cell carcinoma of the trachea, given its tendency to metastasize early after definitive therapy. PMID:21119264

  5. Gene profiling analysis for patients with oral verrucous carcinoma and oral squamous cell carcinoma

    PubMed Central

    Wang, Yue-Hong; Tian, Xin; Liu, Ou-Sheng; Fang, Xiao-Dan; Quan, Hong-Zhi; Xie, Shang; Gao, Shan; Tang, Zhan-Gui

    2014-01-01

    Oral verrucous carcinoma (OVC) is one malignant tumor which was carved out from the oral squamous cell carcinoma (OSCC). However, the clinical and pathological features as well as the treatment strategies of OVC are different from OSCC. Here, global transcript abundance of tumor tissues from five patients with primary OVC and six patients with primary OSCC including their matched adjacently normal oral mucosa were profiled using the Affymetrix HGU133 Plus 2.0. Ingenuity Systems IPA software was used to analyse the gene function and biological pathways. There were 109 differentially expressed genes (more than 2-fold) between OVC and the adjacently normal tissue, among them 66 were up-regulated and 43 were down-regulated; 1172 differentially expressed genes (more than 2-fold) between OSCC and the adjacently normal tissue, among them 608 were up-regulated and 564 were down-regulated. There were 39 common differentially expressed genes in OVC and OSCC compared with their matched normal oral mucosa, among them 22 up-regulated and 17 down-regulated, and 8 of them different between OVC and OSCC. In addition, the gene expression profile was further validated by quantitative real-time PCR (Q-RT-PCR) analysis for four of those 39 selected genes. PMID:25126189

  6. Biphenotypic human papillomavirus-associated head and neck squamous cell carcinoma: a report of two cases.

    PubMed

    Pitiyage, Gayani; Lei, Mary; Guererro Urbano, Teresa; Odell, Edward; Thavaraj, Selvam

    2015-07-11

    Human papillomavirus-associated oropharyngeal squamous cell carcinoma is now recognised as a subtype of head and neck cancer with distinct clinical, molecular and histological characteristics. The majority of these carcinomas are of non-keratinising squamous type but there is a growing number of histomorphologic variants of this disease. Here we describe the clinical, histomorphologic and immunophenotypic features of two cases of human papillomavirus-associated oropharyngeal squamous cell carcinoma demonstrating a clearly delineated biphasic differentiated and undifferentiated phenotype.

  7. Human Papillomavirus–Related Squamous Cell Carcinoma of the Oropharynx

    PubMed Central

    Chernock, Rebecca D.; Zhang, Qin; El-Mofty, Samir K.; Thorstad, Wade L.; Lewis, James S.

    2013-01-01

    Objectives To evaluate the frequency of human papillomavirus–related oropharyngeal squamous cell carcinoma in African Americans and whites and to examine patient outcomes in these 2 groups. Design Retrospective study. Setting One tertiary care, university medical center. Patients Information on patients with stage III/IV oropharyngeal squamous cell carcinoma diagnosed between 1998 and 2007, and with primary surgical samples available for review, were selected from a radiotherapy database. One patient was Native American and was excluded from analysis; data on 174 patients were analyzed. Results One hundred forty-eight patients (85.1%) were white and 26 (14.9%) were African American. Human papillomavirus in situ hybridization–positive and p16-positive tumors were much more common in whites (63.5% and 83.1% of tumors, respectively) than in African Americans (11.5% and 34.6% of tumors, respectively) (P<.001). African Americans were also more likely to have received definitive (nonsurgical) rather than postoperative radiation therapy (P=.001) and had a higher frequency of T3/T4–stage tumors (P=.03) compared with whites. Disease-free survival was significantly shorter for African Americans (P=.02). In multivariate analysis, viral status (P=.006), T stage (P=.02), and treatment type (P=.002), but not race (P=.98), were significant factors contributing to disease-free survival. Conclusions In high-stage oropharyngeal squamous cell carcinoma, the proportion of human papillomavirus–related tumors is much higher in whites than in African Americans. African Americans also appear to develop higher T-stage tumors and are more likely to receive definitive therapy. The shorter disease-free survival observed in African Americans may be due to viral status, treatment type, and higher T stage, but does not appear to be due to race. PMID:21339403

  8. GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo.

    PubMed

    Chimento, Adele; Sirianni, Rosa; Casaburi, Ivan; Zolea, Fabiana; Rizza, Pietro; Avena, Paola; Malivindi, Rocco; De Luca, Arianna; Campana, Carmela; Martire, Emilia; Domanico, Francesco; Fallo, Francesco; Carpinelli, Giulia; Cerquetti, Lidia; Amendola, Donatella; Stigliano, Antonio; Pezzi, Vincenzo

    2015-08-01

    We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC.

  9. GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo

    PubMed Central

    Zolea, Fabiana; Rizza, Pietro; Avena, Paola; Malivindi, Rocco; De Luca, Arianna; Campana, Carmela; Martire, Emilia; Domanico, Francesco; Fallo, Francesco; Carpinelli, Giulia; Cerquetti, Lidia; Amendola, Donatella; Stigliano, Antonio; Pezzi, Vincenzo

    2015-01-01

    We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC. PMID:26131713

  10. GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo.

    PubMed

    Chimento, Adele; Sirianni, Rosa; Casaburi, Ivan; Zolea, Fabiana; Rizza, Pietro; Avena, Paola; Malivindi, Rocco; De Luca, Arianna; Campana, Carmela; Martire, Emilia; Domanico, Francesco; Fallo, Francesco; Carpinelli, Giulia; Cerquetti, Lidia; Amendola, Donatella; Stigliano, Antonio; Pezzi, Vincenzo

    2015-08-01

    We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC. PMID:26131713

  11. Properties of lewis lung carcinoma cells surviving curcumin toxicity.

    PubMed

    Yan, Dejun; Geusz, Michael E; Jamasbi, Roudabeh J

    2012-01-01

    The anti-inflammatory agent curcumin can selectively eliminate malignant rather than normal cells. The present study examined the effects of curcumin on the Lewis lung carcinoma (LLC) cell line and characterized a subpopulation surviving curcumin treatments. Cell density was measured after curcumin was applied at concentrations between 10 and 60 μM for 30 hours. Because of the high cell loss at 60 μM, this dose was chosen to select for surviving cells that were then used to establish a new cell line. The resulting line had approximately 20% slower growth than the original LLC cell line and based on ELISA contained less of two markers, NF-κB and ALDH1A, used to identify more aggressive cancer cells. We also injected cells from the original and surviving lines subcutaneously into syngeneic C57BL/6 mice and monitored tumor development over three weeks and found that the curcumin surviving-line remained tumorigenic. Because curcumin has been reported to kill cancer cells more effectively when administered with light, we examined this as a possible way of enhancing the efficacy of curcumin against LLC cells. When LLC cells were exposed to curcumin and light from a fluorescent lamp source, cell loss caused by 20 μM curcumin was enhanced by about 50%, supporting a therapeutic use of curcumin in combination with white light. This study is the first to characterize a curcumin-surviving subpopulation among lung cancer cells. It shows that curcumin at a high concentration either selects for an intrinsically less aggressive cell subpopulation or generates these cells. The findings further support a role for curcumin as an adjunct to traditional chemical or radiation therapy of lung and other cancers.

  12. Selective transgene expression for detection and elimination of contaminating carcinoma cells in hematopoietic stem cell sources.

    PubMed Central

    Chen, L; Pulsipher, M; Chen, D; Sieff, C; Elias, A; Fine, H A; Kufe, D W

    1996-01-01

    Tumor contamination of bone marrow (BM) and peripheral blood (PB) may affect the outcome of patients receiving high dose chemotherapy with autologous transplantation of hematopoietic stem cell products. In this report, we demonstrate that replication defective adenoviral vectors containing the cytomegalovirus (CMV) or DF3/MUC1 carcinoma-selective promoter can be used to selectively transduce contaminating carcinoma cells. Adenoviral-mediated reporter gene expression in breast cancer cells was five orders of magnitude higher than that found in BM, PB, and CD34+ cells. Our results demonstrate that CD34+ cells have low to undetectable levels of integrins responsible for adenoviral internalization. We show that adenoviral-mediated transduction of a reporter gene can detect one breast cancer cell in 5 x 10(5) BM or PB cells with a vector containing the DF3/MUC1 promoter. We also show that transduction of the HSV-tk gene for selective killing by ganciclovir can be exploited for purging cancer cells from hematopoietic stem cell populations. The selective expression of TK followed by ganciclovir treatment resulted in the elimination of 6-logs of contaminating cancer cells. By contrast, there was little effect on CFU-GM and BFU-E formulation or on long term culture initiating cells. These results indicate that adenoviral vectors with a tumor-selective promoter provide a highly efficient and effective approach for the detection and purging of carcinoma cells in hematopoietic stem cell preparations. PMID:8958216

  13. Pneumopericardium as a non-small-cell lung carcinoma complication

    PubMed Central

    Kubisa, Anna; Dec, Paweł; Szewczak-Głodek, Małgorzata; Kochanowski, Leszek; Kubisa, Bartosz; Feledyk, Grzegorz; Czarnecka, Michalina; Wójcik, Janusz; Grodzki, Tomasz

    2016-01-01

    Below we present a case of a young man with symptoms of progressive weakness, fever, cough, rapid decrease in body weight and the presence of a tumor in the left axillary region. The chest radiography and echocardiography revealed gas bubbles in the pericardium. The more detailed diagnostics and computed tomography of the chest showed an infiltration of the left lung cavity and a fistula among the bronchus, pleural and pericardial cavities. Further diagnostics demonstrated that the pneumopericardium (diagnosed by means of chest radiograph and echocardiography) was a complication of a primary non-small-cell lung carcinoma.

  14. Natural Compounds: DNA Methyltransferase Inhibitors in Oral Squamous Cell Carcinoma.

    PubMed

    Jha, Meenakshi; Aggarwal, Ruchi; Jha, Abhimanyu Kumar; Shrivastava, Anju

    2015-10-01

    Oral squamous cell carcinoma (OSCC) is a multistep process which is modulated by several endogenous and environmental factors. Epigenetic changes have been found to be equally responsible for OSCC as genetic changes. A plethora of genes showing hypermethylation have been discovered in OSCC. Since these changes are reversible, a lot of emphasis is on using the natural compounds for their ability to cause demethylation which could lead to reactivation of the inactivated tumor suppressor genes. This review encompasses the promoter hypermethylation of tumor suppressor genes in OSCC and its possible reversal using natural compounds. In addition, new compounds which could be screened for their demethylating ability have also been proposed. PMID:26210787

  15. Magnetic resonance imaging of pancreatic metastases from renal cell carcinoma.

    PubMed

    Sikka, Amrita; Adam, Sharon Z; Wood, Cecil; Hoff, Frederick; Harmath, Carla B; Miller, Frank H

    2015-01-01

    Pancreatic metastases are rare but are thought to be most commonly from renal cell carcinoma (RCC). These metastases can present many years after the initial tumor is resected, and accordingly, these patients require prolonged imaging follow-up. Although the computed tomographic findings of these metastases have been extensively reviewed in the literature, little has been written about the magnetic resonance imaging appearance of these metastases. Pancreatic metastases from RCC are typically T1 hypointense and T2 hyperintense. After intravenous administration of gadolinium, they are typically hypervascular and less commonly hypovascular. Chemical shift and diffusion-weighted imaging can aid in the diagnosis of these metastases.

  16. Papilloma and squamous cell carcinoma in koi carp (Cyprinus carpio).

    PubMed

    Wildgoose, W H

    1992-02-22

    Over a period of two years four ornamental koi carp (Cyprinus carpio) of one variety in a mixed population of 16 were affected with papillomas of the head and body. In one fish there was a transition of these tumours into a squamous cell carcinoma in the region of the head and posterior gill space, with deep invasion of the underlying bone. One of the fish recovered completely after the sloughing of the papillomas. In view of the progressive nature of the lesions, the condition was presumed to be due to an infectious agent, but transmission electron microscopy failed to reveal any virus particles. PMID:1566540

  17. Simultaneous Esophageal Squamous Cell Carcinoma and Adenocarcinoma: A Case Report

    PubMed Central

    Maleki, Iradj; Shekarriz, Ramin; Nosrati, Anahita; Orang, Elahe

    2015-01-01

    Esophageal squamous cell carcinoma is a rather common cancer in northern Iran. Incidence of adenocarcinoma of esophagus has an increasing trend in Iran. Co-existence of both cancers in one patient is very rare. We report a middle age woman from northern Iran with a typical presentation of esophageal cancer, who was found to have a dual esophageal cancer. The disease was found in the advanced stage with pulmonary metastasis at the presentation. Palliative chemo-radiotherapy induced partial clinical response PMID:26609356

  18. Simultaneous Esophageal Squamous Cell Carcinoma and Adenocarcinoma: A Case Report.

    PubMed

    Maleki, Iradj; Shekarriz, Ramin; Nosrati, Anahita; Orang, Elahe

    2015-10-01

    Esophageal squamous cell carcinoma is a rather common cancer in northern Iran. Incidence of adenocarcinoma of esophagus has an increasing trend in Iran. Co-existence of both cancers in one patient is very rare. We report a middle age woman from northern Iran with a typical presentation of esophageal cancer, who was found to have a dual esophageal cancer. The disease was found in the advanced stage with pulmonary metastasis at the presentation. Palliative chemo-radiotherapy induced partial clinical response. PMID:26609356

  19. [Giant cells undifferentiated parotid carcinoma. Report of two cases].

    PubMed

    Pino Rivero, V; González Palomino, A; Trinidad Ruiz, G; Pardo Romero, G; Montero García, C; Mogollón Cano-Cortés, T; Pando Pinto, J M; Blasco Huelva, A

    2005-01-01

    Tumours of the salivary glands represent a 5% of all head and neck neoplasms. Their origin is the parotid gland in about 80% of the cases. Most of them are benign. We are reporting two cases of patients diagnosed, by our ENT Department, as undifferentiated giant cells parotid carcinoma with cervical metastasis. They were operated by total parotidectomy and radical neck disection and later recieved treatment with radiotherapy. After two years-follow-up both patients are standing alive. The tumoral size is the most important pronostic factor in this histological type.

  20. KLN205--a murine lung carcinoma cell line.

    PubMed

    Kaneko, T; LePage, G A; Shnitka, T K

    1980-10-01

    KLN205 cells, a cloned cell line established from the Nettesheim lung carcinoma, grow in various synthetic media such as MEM, Fisher's or Roswell Park Memorial Institute Medium (RPMI) with the addition of 5 to 20% fetal bovine serum (FBS), calf-serum (CS) or horse serum (HS). They grow optimally in minimum Eagle's medium plus nonessential amino acids (NEAA) plus 5 to 10% FBS or HS. The cells are transplantable to DBA/2, BDF1, AKD2F1, and BALB/c, but not to C3H/He or ICR mice. The growth curves, plating efficiency, ultrastructural characteristics, modal number of chromosomes and transplantability to mice of various strains are almost the same for early and late passage of cells passaged in vitro. These parameters for 16th and 36th passages were: doubling time, 31 and 33 hr; plating efficiency, 12.4 +/- 1.2 and 14.6 +/- 2.6%; modal number of chromosomes, 73 and 76; lung colony formation in DBA/2, 50 and 45.9/mouse; and subcutaneous tumor diameter 24.5 and 27.4 mm, respectively. Only the numbers of lung colonies formed in BDF1 mice were different: 24.4/mouse with 16th passage cells, and 10.2/mouse with 36th passage cells. The results suggest that KLN205 is a relatively stable cultured cell line through 36 passages. As was expected, immunosuppression by higher concentrations of triaminolone acetonide (TA) enhanced lung colony formation in BDF1 mice. On the other hand, a low concentration of TA inhibited lung colony formation in DBA/2 mice, which was unexpected. These results suggest that KLN205 offers a model for investigations on metastases to lungs as well as chemotherapy for lung carcinoma.

  1. p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma

    PubMed Central

    Sánchez-Prieto, Ricardo; Saada, Sofiane; Naves, Thomas; Guillaudeau, Angélique; Perraud, Aurélie; Sindou, Philippe; Lacroix, Aurélie; Descazeaud, Aurélien; Lalloué, Fabrice; Jauberteau, Marie-Odile

    2016-01-01

    p75NTR, a member of TNF receptor family, is the low affinity receptor common to several mature neurotrophins and the high affinity receptor for pro-neurotrophins. Brain-Derived Neurotrophic Factor (BDNF), a member of neurotrophin family has been described to play an important role in development and progression of several cancers, through its binding to a high affinity tyrosine kinase receptor B (TrkB) and/or p75NTR. However, the functions of these two receptors in renal cell carcinoma (RCC) have never been investigated. An overexpression of p75NTR, pro-BDNF, and to a lesser extent for TrkB and sortilin, was detected by immunohistochemistry in a cohort of 83 clear cell RCC tumors. p75NTR, mainly expressed in tumor tissues, was significantly associated with higher Fuhrman grade in multivariate analysis. In two derived-RCC lines, 786-O and ACHN cells, we demonstrated that pro-BDNF induced cell survival and migration, through p75NTR as provided by p75NTR RNA silencing or blocking anti-p75NTR antibody. This mechanism is independent of TrkB activation as demonstrated by k252a, a tyrosine kinase inhibitor for Trk neurotrophin receptors. Taken together, these data highlight for the first time an important role for p75NTR in renal cancer and indicate a putative novel target therapy in RCC. PMID:27120782

  2. Targeted treatments in advanced renal cell carcinoma: focus on axitinib

    PubMed Central

    Verzoni, Elena; Grassi, Paolo; Testa, Isabella; Iacovelli, Roberto; Biondani, Pamela; Garanzini, Enrico; De Braud, Filippo; Procopio, Giuseppe

    2014-01-01

    Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials. PMID:24715765

  3. Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas.

    PubMed

    Pryor, Jennifer G; Simon, Rochelle A; Bourne, Patricia A; Spaulding, Betsy O; Scott, Glynis A; Xu, Haodong

    2009-02-01

    Merkel cell carcinoma is an uncommon and aggressive primary cutaneous neuroendocrine carcinoma with a high rate of recurrence and metastasis. Optimal management is controversial; consequently, it is imperative to identify the signaling pathways involved in the pathogenesis of Merkel cell carcinoma so that effective therapeutic targeting agents can be developed. We previously reported that K homology domain-containing protein overexpressed in cancer is expressed in high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. The K homology domain-containing protein overexpressed in cancer (KOC), also known as L523S and IMP-3, is an insulin-like growth factor II messenger RNA-binding protein that promotes tumor cell proliferation by enhancing insulin-like growth factor II protein expression. Expression of KOC in Merkel cell carcinoma has not been investigated. We studied 20 Merkel cell carcinomas by immunohistochemistry using a monoclonal antibody against L523S/KOC. Of 20 Merkel cell carcinomas, 18 (90%) overexpressed KOC, with 11 (55%) overexpressing KOC in greater than 90% of tumor cells, 3 (15%) overexpressing KOC in 50% to 90% of tumor cells, 3 (15%) overexpressing KOC in 10% to 50% of tumor cells, and 1 (5%) overexpressing KOC in less than 10% of tumor cells. The immunostaining intensity was variable, with moderate to strong staining in 14 cases and weak staining in the remaining 4. Extent of expression of K homology domain-containing protein overexpressed in cancer predicted metastasis (P = .04) and was weakly correlated with increased tumor size (P = .08). In conclusion, Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer with an expression pattern similar to high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. We propose K homology domain-containing protein overexpressed in cancer as a potential target molecule for the treatment of high

  4. T-regulatory cells are relatively deficient in squamous carcinomas undergoing regression in mice immunized with a squamous carcinoma vaccine enriched for immunotherapeutic cells.

    PubMed

    Chopra, A; O-Sullivan, I; Carr, J; Kim, T S; Cohen, E P

    2007-06-01

    In a prior report (Int J Cancer 2006; 119: 339-348), we described a new vaccination strategy for squamous cell carcinoma (SCC). The vaccine was prepared by transfer of unfractionated DNA-fragments (25 kb) from KLN205 cells, a squamous carcinoma cell line (DBA/2 origin; H-2(d)) into LM cells, a highly immunogenic mouse fibroblast cell line (C3H/He origin; (H-2(k))). As only a small proportion of the transfected cell population was expected to have incorporated DNA segments that included genes specifying antigens associated with the squamous carcinoma cells, we devised a novel strategy to enrich the vaccine for immunotherapeutic cells. Enhanced immunity to squamous carcinoma was induced in tumor-bearing mice treated solely by immunization with the enriched vaccine, which translated into prolonged survival without toxicity. Here, we describe the characteristics of the cell populations infiltrating established squamous carcinomas undergoing regression in mice immunized with vaccines enriched for immunotherapeutic cells. The results indicated that CD8+ T cells were predominant and that T-regulatory cells (FoxP3+, CD4/CD25+, CD4/CD62L(high), CD4/CTLA-4e) were relatively deficient in the regressing tumors. Inflammatory infiltrates were not detected in various organs and tissues of mice immunized with the DNA-based vaccine.

  5. Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells.

    PubMed

    Daker, Maelinda; Bhuvanendran, Saatheeyavaane; Ahmad, Munirah; Takada, Kenzo; Khoo, Alan Soo-Beng

    2013-03-01

    Nasopharyngeal carcinoma (NPC) is a unique tumour of epithelial origin with a distinct geographical distribution, closely associated with the Epstein‑Barr virus (EBV). EBV‑encoded RNAs (EBERs) are small non‑polyadenylated RNAs that are abundantly expressed in latent EBV‑infected NPC cells. To study the role of EBERs in NPC, we established stable expression of EBERs in HK1, an EBV‑negative NPC cell line. Cells expressing EBERs consistently exhibited an increased growth rate. However, EBERs did not confer resistance towards cisplatin‑induced apoptosis or promote migration or invasion ability in the cells tested. Using microarray gene expression profiling, we identified potential candidate genes that were deregulated in NPC cells expressing EBERs. Gene Ontology analysis of the data set revealed that EBERs upregulate the cellular lipid metabolic process. Upregulation of low‑density lipoprotein receptor (LDLR) and fatty acid synthase (FASN) was observed in EBER‑expressing cells. NPC cells exhibited LDL‑dependent cell proliferation. In addition, a polyphenolic flavonoid compound, quercetin, known to inhibit FASN, was found to inhibit proliferation of NPC cells.

  6. Fine-needle aspiration cytology of metastatic transitional cell carcinoma.

    PubMed

    Dey, Pranab; Amir, Thasneem; Jogai, Sanjay; Al Jussar, Aisha

    2005-04-01

    In this article we described the fine-needle aspiration cytology (FNAC) of five cases of metastatic transitional cell carcinoma (TCC). There were four cases of metastatic lymph nodes and one case of metastatic skin lesion. All of the TCC cases were primarily in the urinary bladder and were high grade on histopathology (grade 3). Three cases showed bladder muscle involvement and two cases showed superficial TCC at the time of primary diagnosis. FNAC smears showed abundant cellularity. The cells were present in discrete and small syncytial clusters. Nuclear position of the cell was central to eccentric. Many cells showed prominent nucleoli. Cercariform cells (CCs) were noted in four cases. These cells are malignant cells with a nucleated globular body and a unipolar nontapering cytoplasmic process. Two cases showed intranuclear inclusions. Prominent cytoplasmic vacuoles were noted in three cases. In addition, cell cannibalism and attempted pearl formations were noted in two cases.In conclusion, clinical history along with the certain cytological features such as the presence of CCs, cells with eccentric nuclei, and intranuclear inclusions are helpful to diagnose metastatic TCC on FNAC material. PMID:15754372

  7. Multiple metastatic renal cell carcinoma isolated to pancreas.

    PubMed

    Comunoğlu, Cem; Altaca, Gülüm; Demiralay, Ebru; Moray, Gökhan

    2012-06-01

    Renal cell carcinoma (RCC) metastases to the pancreas are reported to be rare. Isolated multiple pancreatic metastases are even rarer. We report a 68-year-old asymptomatic male patient who presented with multiple metastatic nodular lesions in the pancreas demonstrated by computerized tomography 3.5 years after radical nephrectomy performed for clear cell RCC. Spleen-preserving total pancreatectomy was performed. Gross examination revealed five well-demarcated tumoral nodules in the head, body and tail of the pancreas. Histopathological examination revealed clusters of epithelial clear cells, immunohistochemically positive for CD10 and vimentin, and negative for CK19 and chromogranin, supporting a diagnosis of metastatic RCC. The patient has remained well at 29 months post-resection, in agreement with recent experience that radical resection for multiple isolated metastatic nodular lesions can achieve improved survival and better quality of life.

  8. Acinar cell carcinoma of exocrine pancreas in two horses.

    PubMed

    de Brot, S; Junge, H; Hilbe, M

    2014-05-01

    Two horses were presented with non-specific clinical signs of several weeks' duration and were humanely destroyed due to a poor prognosis. At necropsy examination, both horses had multiple small, white nodules replacing pancreatic tissue and involving the serosal surface of the abdominal cavity, the liver and the lung. Microscopically, neoplastic cells were organized in acini and contained abundant (case 1) or sparse (horse 2) intracytoplasmic zymogen granules. Immunohistochemically, both tumours expressed amylase and pan-cytokeratin, but not insulin or neuron-specific enolase. In case 2, a low percentage of neoplastic cells expressed glucagon and synaptophysin. The presence of zymogen granules was confirmed in both cases by electron microscopy and occasional fibrillary or glucagon granules were observed in cases 1 and 2, respectively. A diagnosis of pancreatic acinar cell carcinoma was established in both horses.

  9. Merkel Cell Carcinoma: A Virus-Induced Human Cancer

    PubMed Central

    Chang, Yuan; Moore, Patrick S.

    2013-01-01

    Merkel cell polyomavirus (MCV) is the first polyomavirus directly linked to human cancer, and its recent discovery helps to explain many of the enigmatic features of Merkel cell carcinoma (MCC). MCV is clonally integrated into MCC tumor cells, which then require continued MCV oncoprotein expression to survive. The integrated viral genomes have a tumor-specific pattern of tumor antigen gene mutation that incapacitates viral DNA replication. This human cancer virus provides a new model in which a common, mostly harmless member of the human viral flora can initiate cancer if it acquires a precise set of mutations in a host with specific susceptibility factors, such as age and immune suppression. Identification of this tumor virus has led to new opportunities for early diagnosis and targeted treatment of MCC. PMID:21942528

  10. Immunohistochemical Evaluation of Mast Cells in Leukoplakia and Oral Squamous Cell Carcinoma

    PubMed Central

    Narasimhan, Malathi

    2016-01-01

    Introduction More than 90% of oral cancers are squamous cell carcinomas with oral leukoplakia being the most common potentially malignant disorder. Among the cell types in the stroma, mast cells play an important role in tumourigenesis through various mechanisms. Aim The present study was aimed at comparing the mast cell count among normal oral mucosa, leukoplakia and Oral squamous cell carcinoma (OSSC) and to evaluate the possible role of mast cells in carcinogenesis. Materials and Methods Mast cell count was assessed immunohistochemically using anti-mast cell tryptase amongst 20 cases of leukoplakia and OSSC each and 10 normal gingival samples. Overall comparison was done using Kruskal Wallis test and intergroup comparison was done using Mann-Whitney U test. Results The results of the present study showed an increase in mast cell count from normal oral mucosa (Mean: 7.73) to leukoplakia (Mean: 15.11) to squamous cell carcinoma (Mean: 22.73). Comparison of mean number of mast cells amongst three groups (p-value: 0.001) and intergroup comparisons showed statistical significance. Conclusion Mast cells favour malignant transformation and can be used as indicators of disease progression. PMID:27656549

  11. Dihydroartemisinin (DHA) induces ferroptosis and causes cell cycle arrest in head and neck carcinoma cells.

    PubMed

    Lin, Renyu; Zhang, Ziheng; Chen, Lingfeng; Zhou, Yunfang; Zou, Peng; Feng, Chen; Wang, Li; Liang, Guang

    2016-10-10

    Head and neck cancer is the sixth most common cancer worldwide. Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, exhibits a wide range of biological roles including a highly efficient and specific anti-tumor activity. Here, we aimed to examine the effect of DHA on head and neck carcinoma cells and elucidate the potential mechanisms. We used five head and neck carcinoma cell lines and two non-tumorigenic normal epithelial cell lines to achieve our goals. Cells were exposed to DHA and subjected to cellular activity assays including viability, cell cycle analysis, cell death, and angiogenic phenotype. Our results show that DHA causes cell cycle arrest which is mediated through Forkhead box protein M1 (FOXM1). We also demonstrate that DHA induces ferroptosis and apoptosis in head and neck carcinoma cells. Lastly, our results show that DHA alters the angiogenic phenotype of cancer cells by reducing the expression of angiogenic factors and the ability of cancer cells to support endothelial cell tubule formation. Our study suggests that DHA specifically causes head and neck cancer cell death through contribution from both ferroptosis and apoptosis. DHA may represent an effective strategy in head and neck cancer treatment.

  12. A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells.

    PubMed

    Yim, Dongsool; Singh, Rana P; Agarwal, Chapla; Lee, Sookyeon; Chi, Hyungjoon; Agarwal, Rajesh

    2005-02-01

    We isolated a coumarin compound decursin (C(19)H(20)O(5); molecular weight 328) from Korean angelica (Angelica gigas) root and characterized it by spectroscopy. Here, for the first time, we observed that decursin (25-100 micromol/L) treatment for 24 to 96 hours strongly inhibits growth and induces death in human prostate carcinoma DU145, PC-3, and LNCaP cells. Furthermore, we observed that decursinol [where (CH(3))(2)-C=CH-COO- side chain of decursin is substituted with -OH] has much lower effects compared with decursin, suggesting a possible structure-activity relationship. Decursin-induced growth inhibition was associated with a strong G(1) arrest (P < 0.001) in DU145 and LNCaP cells, and G(1), S as well as G(2)-M arrests depending upon doses and treatment times in PC-3 cells. Comparatively, decursin was nontoxic to human prostate epithelial PWR-1E cells and showed only moderate growth inhibition and G(1) arrest. Consistent with G(1) arrest in DU145 cells, decursin strongly increased protein levels of Cip1/p21 but showed a moderate increase in Kip1/p27 with a decrease in cyclin-dependent kinases (CDK); CDK2, CDK4, CDK6, and cyclin D1, and inhibited CDK2, CDK4, CDK6, cyclin D1, and cyclin E kinase activity, and increased binding of CDK inhibitor (CDKI) with CDK. Decursin-caused cell death was associated with an increase in apoptosis (P < 0.05-0.001) and cleaved caspase-9, caspase-3, and poly(ADP-ribose) polymerase; however, pretreatment with all-caspases inhibitor (z-VAD-fmk) only partially reversed decursin-induced apoptosis, suggesting the involvement of both caspase-dependent and caspase-independent pathways. These findings suggest the novel anticancer efficacy of decursin mediated via induction of cell cycle arrest and apoptosis selectively in human prostate carcinoma cells.

  13. Independent stem cell lineages regulate adipose organogenesis and adipose homeostasis

    PubMed Central

    Jiang, Yuwei; Berry, Daniel C.; Tang, Wei; Graff, Jonathan M.

    2014-01-01

    Summary Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA)-mural cell fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments, Developmental and Adult. These two compartments are sequentially required for organ formation and maintenance. Although both Developmental and Adult progenitors are specified during the developmental period and express PPARγ, they have distinct micro-anatomical, functional, morphogenetic and molecular profiles. Further, the two compartments derive from different lineages, while adult adipose progenitors fate map from an SMA+ mural lineage, Developmental progenitors do not. Remarkably, the Adult progenitor compartment appears to be specified earlier than the Developmental cells, and then enters the already developmentally formed adipose depots. Thus, two distinct cell compartments control adipose organ development and organ homeostasis, which may provide discrete therapeutic target for childhood and adult obesity. PMID:25437556

  14. Effects of HPV-16 infection on hypopharyngeal squamous cell carcinoma and FaDu cells.

    PubMed

    Lu, Wuhao; Feng, Long; Li, Ping; Wang, Yuanyuan; Du, Yuwen; Chen, Xiaonan; Wu, Shujun; Zhao, Guoqiang; Lou, Weihua

    2016-01-01

    Hypopharyngeal squamous cell carcinoma is a common type of malignant tumor among head and neck squamous cell carcinomas (HNSCCs). Heavy smoking and/or drinking is associated with the development of HNSCC. However, HNSCC also occurs in individuals that do not drink or smoke, possibly due to infection with the human papilloma virus (HPV). HPV-16 has been shown to be closely associated with the occurrence of several types of cancers. However, its role in hypopharyngeal squamous cell carcinoma remains unclear. In the present study, we investigated the effects of HPV-16 on hypopharyngeal squamous cell carcinoma and FaDu cells. Lentiviral vectors were used to establish FaDu cells that expressed the E6 and E7 proteins of HPV-16. We used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays and western blotting to detect and determine the levels of expression for E6-E7 mRNAs and proteins. Cell Counting Kit-8 (CCK-8) assays, enzyme-linked immunosorbent assays (ELISA), Transwell assays, and flow cytometry were used to assess the effects of HPV-16 E6-E7 on the proliferation, invasion, metastasis and apoptosis of FaDu cells. Expression of microRNAs was analyzed by qRT-PCR. We found that the expression levels of HPV-16 E6-E7 were increased in FaDu cells transfected with the lentiviral vector compared with that observed in the control cells. In addition, the rates of apoptosis were decreased in the transfected cells, while proliferation was increased. The average numbers of cells penetrating the Matrigel were significantly higher than those for the controls. We detected miR-363 and miR-15a, and their expression levels were significantly increased in the HPV-16-positive patients and in FaDu cells expressing HPV-16 E6-E7. We found that HPV-16 E6-E7 appeared to inhibit apoptosis, and to increase cell proliferation, invasion and metastasis. Furthermore, miR-363 and miR-15a were overexpressed in the hypopharyngeal squamous cell carcinoma samples infected with

  15. Altered glutathione metabolism in oxaliplatin resistant ovarian carcinoma cells.