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Sample records for cell carcinoma progression

  1. Cheilitis glandularis progressing to squamous cell carcinoma in and ...

    African Journals Online (AJOL)

    Cheilitis glandularis progressing to squamous cell carcinoma in and HIV-infected patient: Case Report. F M Butt, M L Chindia, F N Rana, A Ashani. Abstract. No Abstract. East African Medical Journal Vol. 84 (12) 2007 pp. 595-598. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT ...

  2. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

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    Chen Chang-Jie

    2010-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

  3. Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma

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    Alessandro Conti

    2013-01-01

    Full Text Available Vascular endothelial growth factor (VEGF plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF/Von Hippel-Lindau (VHL pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR, AKT, and phosphatidylinositol 3′-kinase (PI3K. Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents.

  4. Delineating genetic pathways of disease progression in head and neck squamous cell carcinoma

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    Worsham, MJ; Pals, G; Schouten, JP; van Spaendonk, RML; Concus, A; Carey, TE; Benninger, MS

    Objective: To identify altered gene targets that characterize disease progression in squamous cell carcinoma (SCC) of the head and neck (HNSCC). Genetic alterations in HNSCC cell lines reflect the tumor in vivo and can serve as valuable tools to study the development and progression of HNSCC.

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

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    2017-10-09

    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

  6. Role of hyaluronan synthase 2 to promote CD44-dependent oral cavity squamous cell carcinoma progression.

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    Wang, Steven J; Earle, Christine; Wong, Gabriel; Bourguignon, Lilly Y W

    2013-04-01

    CD44 is a transmembrane receptor found on many different benign and malignant cells. Hyaluronan (HA), a major component of the extracellular matrix, is the primary ligand for CD44 receptors. In cancer cells, HA interaction with CD44 promotes multiple signaling pathways that influence tumor cell progression behaviors in a variety of solid tumors. Increasing evidence indicates that HA and CD44 signaling play an important role in oral cavity squamous cell carcinoma progression. HA is primarily synthesized by hyaluronan synthases, and the current study investigated the role of hyaluronan synthase 2 (HAS 2) in oral cavity carcinoma progression behaviors. Analysis of HAS 2 mRNA and protein expression, HA production, and HAS 2-mediated tumor cell proliferation and migration behaviors with and without HAS 2 suppression were carried out on 2 established oral cavity cancer cell lines. Immunohistochemical analysis of HAS 2 and CD44 expression in oral cavity carcinoma tumor specimens was performed. HAS 2 was expressed in the 2 oral cancer cell lines, HSC-3 and SCC-4. Suppression of HAS 2 expression resulted in CD44-dependent decreased tumor cell migration, decreased tumor cell growth, and increased cisplatin sensitivity, suggesting the importance of tumor cell HA production to promote in vitro tumor progression behaviors in oral cancer cells. Increased HAS 2 expression in oral cavity carcinoma clinical specimens was associated with poor clinicopathologic characteristics and worse disease-free survival. HAS 2 may be a potential therapeutic target for the treatment of oral cavity cancer. Copyright © 2012 Wiley Periodicals, Inc.

  7. Progression of oral squamous cell carcinoma accompanied with reduced E-cadherin expression but not cadherin switch.

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    Takashi Hashimoto

    Full Text Available The cadherin switch from E-cadherin to N-cadherin is considered as a hallmark of the epithelial-mesenchymal transition and progression of carcinomas. Although it enhances aggressive behaviors of adenocarcinoma cells, the significance and role of cadherin switch in squamous cell carcinomas (SCCs are largely controversial. In the present study, we immunohistochemically examined expression of E-cadherin and N-cadherin in oral SCCs (n = 63 and its implications for the disease progression. The E-cadherin-positive carcinoma cells were rapidly decreased at the invasive front. The percentage of carcinoma cells stained E-cadherin at the cell membrane was reduced in parallel with tumor dedifferentiation (P<0.01 and enhanced invasion (P<0.01. In contrast, N-cadherin-positive cells were very limited and did not correlate with the clinicopathological parameters. Mouse tongue tumors xenotransplantated oral SCC cell lines expressing both cadherins in vitro reproduced the reduction of E-cadherin-positive carcinoma cells at the invasive front and the negligible expression of N-cadherin. These results demonstrate that the reduction of E-cadherin-mediated carcinoma cell-cell adhesion at the invasive front, but not the cadherin switch, is an important determinant for oral SCC progression, and suggest that the environments surrounding carcinoma cells largely affect the cadherin expression.

  8. MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression

    OpenAIRE

    Toll, Agust?; Salgado, Roc?o; Espinet, Blanca; D?az-Lagares, Angel; Hern?ndez-Ruiz, Eugenia; Andrades, Evelyn; Sandoval, Juan; Esteller, Manel; Pujol, Ram?n M; Hern?ndez-Mu?oz, Inmaculada

    2016-01-01

    Background Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and frequently progresses from an actinic keratosis (AK), a sun-induced keratinocyte intraepithelial neoplasia (KIN). Epigenetic mechanisms involved in the phenomenon of progression from AK to cSCC remain to be elicited. Methods Expression of microRNAs in sun-exposed skin, AK and cSCC was analysed by Agilent microarrays. DNA methylation of miR-204 promoter was determined by bisulphite treatment and pyros...

  9. MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression.

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    Marona, Paulina; Górka, Judyta; Mazurek, Zofia; Wilk, Waclaw; Rys, Janusz; Majka, Marcin; Jura, Jolanta; Miekus, Katarzyna

    2017-09-15

    Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity. MCPIP1 activity regulated secretion of VEGF, IL8, and CXCL12 leading to chemotaxis of microvascular endothelial cells, phosphorylation of VE-cadherin, and increased vascular permeability. Mechanistic investigations showed that MCPIP1 regulated ccRCC cell motility, lung metastasis, and mesenchymal phenotype by regulating key elements in the EMT signaling axis. Overall, our results illuminate how MCPIP1 serves as a key nodal point in coordinating tumor growth, angiogenesis, and metastatic spread in ccRCC. Cancer Res; 77(18); 4905-20. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Allicin inhibits human renal clear cell carcinoma progression via suppressing HIF pathway.

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    Song, Bin; Shu, Ying; Cui, Tianlei; Fu, Ping

    2015-01-01

    Hypoxia-inducible factor 1-alpha (HIF-1α) protects hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. Allicin is characterized by the anti-cancer characteristics. This study aims to explore whether allicin is involved in renal clear cell carcinoma progression through HIF-1α. A total of 40 RCC tissues and 39 normal renal tissues were collected H&E and immunohistochemistry were applied to study morphology changes. MTT assay and flow cytometry (FCM) were used to analyze cell viability and apoptosis. In vitro colony formation assay and wound healing assay were conducted to explore cell migration. The protein levels of Bcl-2, VEGF and HIF-1α were increased in RCC tissues. More importantly, treatment with allicin significantly decreased HIF-1α protein level, thereby reducing Bcl-2 and VEGF expression. In addition, allicin also obviously enhanced apoptotic cells. And colony formation capacity and cell migration rate were reduced in RCC-9863 cells treated with allicin. Further study revealed that overexpression of HIF-1α could partially repress allicin-induced downstream effects. To conclude, allicin inhibits human renal clear cell carcinoma progression partially by suppressing HIF pathway.

  11. Podoplanin expression in the development and progression of laryngeal squamous cell carcinomas

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    Fresno Manuel F

    2010-03-01

    Full Text Available Abstract Background Podoplanin expression is attracting interest as a marker for cancer diagnosis and prognosis. We therefore investigated the expression pattern and clinical significance of podoplanin during the development and progression of laryngeal carcinomas. Results Podoplanin expression was determined by immunohistochemistry in paraffin-embedded tissue specimens from 84 patients with laryngeal premalignancies and 53 patients with laryngeal squamous cell carcinomas. We found podoplanin expression extending from the basal to the suprabasal layer of the epithelium in 37 (44% of 84 dysplastic lesions, whereas normal epithelium showed negligible expression. Patients carrying podoplanin-positive lesions had a higher laryngeal cancer incidence than those with negative expression reaching borderline statistical significance (51% versus 30%, P = 0.071. Podoplanin expression in laryngeal carcinomas exhibited two distinct patterns. 20 (38% cases showed diffuse expression in most tumour cells and 33 (62% focal expression at the proliferating periphery of tumour nests. High podoplanin expression was inversely correlated with T classification (P = 0.033, disease stage (P = 0.006, and pathological grade (P = 0.04. There was a trend, although not significant, towards reduced disease-specific survival for patients with low podoplanin levels (P = 0.31 and diffuse expression pattern (P = 0.08. Conclusions Podoplanin expression increases in the early stages of laryngeal tumourigenesis and it seems to be associated with a higher laryngeal cancer risk. Podoplanin expression in laryngeal squamous cell carcinomas, however, diminishes during tumour progression. Taken together, these data support a role for podoplanin expression in the initiation but not in the progression of laryngeal cancers.

  12. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

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    Kucuk Omer

    2007-01-01

    Full Text Available Abstract Background We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC model established in our laboratory. Methods The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. Results In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Conclusion Our studies in both RCC and prostate tumor models demonstrate that the

  13. Safety and Efficacy of Nivolumab in Patients With Metastatic Renal Cell Carcinoma Treated Beyond Progression

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    George, Saby; Motzer, Robert J.; Hammers, Hans J.; Redman, Bruce G.; Kuzel, Timothy M.; Tykodi, Scott S.; Plimack, Elizabeth R.; Jiang, Joel; Waxman, Ian M.; Rini, Brian I.

    2017-01-01

    IMPORTANCE Response patterns with immunotherapy may differ from those of other treatments. This warrants further investigation because some patients may benefit from continued immunotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST)-defined first progression. OBJECTIVE To evaluate the safety and potential benefit of treatment with nivolumab, a programmed cell death 1 immune checkpoint inhibitor, beyond investigator-assessed first progression in patients with metastatic renal cell carcinoma (mRCC). DESIGN, SETTING, AND PARTICIPANTS Subgroup analysis of a blinded, randomized, multicenter, phase 2 dose-ranging trial initiated May 31, 2011, including patients with clear-cell mRCC previously treated with antiangiogenic therapy. Data cutoffs for this subgroup analysis were May 15, 2013, for progression-free survival and objective response rate and March 5, 2014, for overall survival and duration of response. In this analysis, patients treated beyond first progression received their last dose of nivolumab more than 6 weeks after RECIST-defined progression, and patients not treated beyond first progression discontinued nivolumab before or at RECIST-defined progression. INTERVENTIONS Nivolumab 0.3, 2, or 10 mg/kg intravenously every 3 weeks. MAIN OUTCOMES AND MEASURES Safety and efficacy of nivolumab treatment. RESULTS Of 168 patients (median [range] age, 61 [37–81] years; 72% male) randomized to nivolumab, 154 experienced progression (36 were treated beyond first progression, 26 were treated beyond first progression for ≤ 6 weeks, and 92 were not treated beyond first progression), 13 were treated and did not experience progression, and 1 was not treated. Prior to first progression, the RECIST-defined objective response rate was 14% (5 patients) and 16% (15 patients), and median progression-free survival was 4.2 (95% CI, 2.8–5.5) and 2.6 (95% CI, 1.5–3.9) months in patients treated and not treated beyond progression, respectively. Following initial

  14. The effect of medication nonadherence on progression-free survival among patients with renal cell carcinoma

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    Shafrin J

    2017-11-01

    Full Text Available Jason Shafrin,1 Jeffrey Sullivan,1 Jacquelyn W Chou,1 Michael N Neely,2 Justin F Doan,3 J Ross Maclean1 1Precision Health Economics, Los Angeles, CA, USA; 2Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, USA Objective: To examine how observed medication nonadherence to 2 second-line, oral anticancer medications (axitinib and everolimus affects progression-free survival (PFS among patients with renal cell carcinoma. Methods: We used an adherence–exposure–outcome model to simulate the impact of adherence on PFS. Using a pharmacokinetic/pharmacodynamic (PK/PD population model, we simulated drug exposure measured by area under the plasma concentration–time curve (AUC and minimum blood or trough concentration (Cmin under 2 scenarios: 1 optimal adherence and 2 real-world adherence. Real-world adherence was measured using the medication possession ratios as calculated from health insurance claims data. A population PK/PD model was simulated on individuals drawn from the Medical Expenditure Panel Survey (MEPS, a large survey broadly representative of the US population. Finally, we used previously published PK/PD models to estimate the effect of drug exposure (i.e., Cmin and AUC on PFS outcomes under optimal and real-world adherence scenarios. Results: Average adherence measured using medication possession ratios was 76%. After applying our simulation model to 2164 individuals in MEPS, drug exposure was significantly higher among adherent patients compared with nonadherent patients for axitinib (AUC: 249.5 vs. 159.8 ng×h/mL, P<0.001 and everolimus (AUC: 185.4 vs. 118.0 µg×h/L, P<0.001. Patient nonadherence in the real world decreased the expected PFS from an optimally adherent population by 29% for axitinib (8.4 months with optimal adherence vs. 6.0 months using real-world adherence, P<0.001 and by

  15. New candidate markers of head and neck squamous cell carcinoma progression

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    Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Kulbakin, D. E.; Choinzonov, E. L.

    2017-09-01

    The tumor progression in head and neck squamous cell carcinoma (HNSCC) is one of the main causes of high mortality of the patients with HNSCC. The tumor progression, particularly the metastasis, is characterized by the changes in the composition, functions and structure of different proteins. We have previously shown that serum of HNSCC patients contains the proteins which regulate various cellular processes—adenylyl cyclase associated protein 1 (CAP1), protein phosphatase 1 B (PPM1B), etc. The levels of CAP1 and PPM1B were determined using the enzyme immunoassay. The results of this study show that CAP1 and PPM1B take a part in the progression of HNSCC. The levels of CAP1 and PPM1B in the tumor and in morphologically normal tissue depended on the prevalence of the tumor process. The CAP1 and PPM1B levels were significantly higher in tumor tissue of the patients with regional metastasis. Our data allow assuming the potential possibility for predicting the outcome of the HNSCC measuring the level of tissue CAP1.

  16. MicroRNA-202 inhibits tumor progression by targeting LAMA1 in esophageal squamous cell carcinoma

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    Meng, Xiangrui, E-mail: xiangruimengzz@163.com [Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou 450000, Henan Province (China); Chen, Xiaoqi [Department of Digestion and Oncology, The First Affiliated Hospital of Henan Uninversity of TCM, 19 Renmin Road, Zhengzhou 450000, Henan Province (China); Lu, Peng [Department of Gastrointestinal Surgery, The People' s Hospital of Zhengzhou, 33 Huanghe Road, Zhengzhou 450000, Henan Province (China); Ma, Wang; Yue, Dongli; Song, Lijie; Fan, Qingxia [Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou 450000, Henan Province (China)

    2016-05-13

    Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies in the gastrointestinal tract. Emerging studies have indicated that microRNAs (miRNAs) are strongly implicated in the development and progression of ESCC. Here, we focused on the function and the underlying molecular mechanism of miR-202 in ESCC. The results showed that miR-202 was significantly down-regulated in ESCC tissues and cell lines. Overexpression of miR-202 in ECa-109 and KYSE-510 cells markedly suppressed cell proliferation and cell migration, and induced cell apoptosis. Furthermore, laminin α1 (LAMA1) expression was frequently positive in ESCC tissues and inversely correlated with miR-202 expression. Then we demonstrated that miR-202 targeted 3'-untranslated region (UTR) of LAMA1 and inhibited its protein expression. Additionally, LAMA1 overexpression rescued the proliferation inhibition and cell apoptosis elevation induced by miR-202. MiR-202 also inhibited the protein expression of p-FAK and p-Akt, which were all reversed by LAMA1 overexpression. Taken together, these findings suggest that miR-202 may function as a novel tumor suppressor in ESCC by repressing cell proliferation and migration, and its biological effects may attribute the inhibition of LAMA1-mediated FAK-PI3K-Akt signaling. - Highlights: • Expression of miR-202 was decreased in ESCC tissues and cell lines. • MiR-202 overexpression inhibited ESCC cell growth and induced apoptosis. • MiR-202 directly targeted LAMA1 in ESCC. • The LAMA1-FAK-PI3K signaling mediated the suppressive role of miR-202.

  17. Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.

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    Catanzaro, Daniele; Shackney, Stanley E; Schaffer, Alejandro A; Schwartz, Russell

    2016-01-01

    Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.

  18. Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.

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    Buda-Nowak, Anna; Kucharz, Jakub; Dumnicka, Paulina; Kuzniewski, Marek; Herman, Roman Maria; Zygulska, Aneta L; Kusnierz-Cabala, Beata

    2017-04-01

    Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly.

  19. Impact of Sulfatase-2 on cancer progression and prognosis in patients with renal cell carcinoma.

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    Kumagai, Shin; Ishibashi, Kei; Kataoka, Masao; Oguro, Toshiki; Kiko, Yuichirou; Yanagida, Tomohiko; Aikawa, Ken; Kojima, Yoshiyuki

    2016-11-01

    Heparan sulfate-specific endosulfatase-2 (SULF-2) can modulate the signaling of heparan sulfate proteoglycan-binding proteins. The involvement of SULF-2 in cancer growth varies by cancer type. The roles of SULF-2 expression in the progression and prognosis of renal cell carcinomas (RCC) have not yet been fully clarified. In the present study, the expression levels of SULF-2 mRNA and protein in 49 clinical RCC samples were determined by RT-PCR and immunostaining. The existence of RCC with higher SULF-2 expression and lower SULF-2 expression compared to the adjacent normal kidney tissues was suggested. High SULF-2 expression was correlated with an early clinical stage and less invasive pathological factors. Low SULF-2 expression was correlated with an advanced stage and higher invasive factors. Three-year cancer-specific survival (CSS) for high SULF-2 RCC and low SULF-2 RCC were 100% and 71.4%, respectively (log-rank P = 0.0019), with a significantly shorter CSS observed in low SULF-2 RCC patients. The influence of SULF-2 expression level on Wnt/VEGF/FGF signaling, cell viability and invasive properties was examined in three RCC cell lines, Caki-2, ACHN and 786-O, using a SULF-2 suppression model involving siRNA or a SULF-2 overexpression model involving a plasmid vector. High SULF-2 expression enhanced Wnt signaling and Wnt-induced cell viability, but not cell invasion. In contrast, low levels of SULF-2 expression significantly enhanced both cell invasion and viability through the activation of VEGF/FGF pathways. RCC with lower SULF-2 expression might have a higher potential for cell invasion and proliferation, leading to a poorer prognosis via the activation of VEGF and/or FGF signaling. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  20. Overexpression of WRAP53 is associated with development and progression of esophageal squamous cell carcinoma.

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    Xuguang Rao

    Full Text Available Esophageal squamous cell carcinoma (ESCC is a highly aggressive cancer whose underlying molecular mechanisms are poorly understood. The natural antisense transcript (NAT WRAP53 regulates p53 expression and WRAP53 protein is a component of telomerase. NATs play key roles in carcinogenesis, and although WRAP53 is known to increase cancer cell survival, its role in ESCC clinicopathology is unknown. The aim of this study was to investigate WRAP53 expression in ESCC and to correlate it with clinicopathological characteristics.WRAP53 mRNA and protein expression was measured by quantitative PCR (qRT-PCR and western blotting, respectively, in 4 ESSC cells lines and in 45 paired ESCC and non-neoplastic esophageal mucosa tissues. To correlate WRAP53 protein expression with clinicopathological characteristics, immunohistochemistry (IHC was performed on 134 ESCC and 85 non-neoplastic esophageal mucosa tissues.Expression of WRAP53 was detected in all ESCC cell lines and was upregulated in the ESCC tissues compared with the corresponding non-neoplastic tissues (P<0.01. More cells expressed WRAP53 protein in the ESCC tissues than in the non-neoplastic tissues (P<0.01. Overexpression of WRAP53 was significantly correlated with tumor infiltration depth (P = 0.000, clinical stage (P = 0.001, and lymph node metastasis (P = 0.025. Wrap53 expression was not correlated with age, gender, or tumor differentiation.This report indicates increased expression of WRAP53 in ESCC and that WRAP53 overexpression is correlated with tumor progression. WRAP53 may play a significant role in ESCC; accordingly, WRAP53 could be a useful biomarker for ESCC.

  1. EVALUATION OF STEROID HORMONES AND THEIR RECEPTORS IN DEVELOPMENT AND PROGRESSION OF RENAL CELL CARCINOMA

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    Nigel Bennett

    2014-06-01

    Full Text Available Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC, with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.

  2. Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma

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    van de Nieuwenhof, Hedwig P.; Bulten, Johan; Hollema, Harrie; Dommerholt, Rianne G.; Massuger, Leon F. A. G.; van der Zee, Ate G. J.; de Hullu, Joanne A.; van Kempen, Leon C. L. T.

    Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a

  3. Disturbed tryptophan metabolism correlating to progression and metastasis of esophageal squamous cell carcinoma.

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    Cheng, Jing; Jin, Hai; Hou, Xiaobei; Lv, Jie; Gao, Xianfu; Zheng, Guangyong

    2017-05-06

    Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies worldwide. Lymph node metastasis is the leading cause of death in ESCC patients. To identify early diagnostic and prognostic biomarkers of ESCC and elucidate underlying pathogenesis of the disease, a targeted metabolomics strategy based on liquid chromatography combined with tandem mass spectrometry was applied to explore tryptophan metabolism between ESCC patients, metastatic ESCC patients (mESCC), and healthy controls. Statistical analysis on metabolite expression abundance and compound concentration ratio was conducted to discriminate patients from healthy controls. The concentration ratio of kynurenine, 5-hydroxytryptophan, 5-hydroxyindole-3-acetic acid, 5-hydroxytryptamine to their precursor tryptophan were identified as potential biomarkers, presenting high diagnostic capacity for distinguishing ESCC and mESCC patients from healthy controls. Moreover, a prognostic prediction model was also built on these ratios to distinguish metastasis patients from non-metastasis patients successfully. The high performance of ESCC prediction models suggest that concentration ratios of compounds may be used as biomarkers for early diagnosis and prognosis of the disease. In addition, concentration ratios of compounds show a progressively increased trend from non-metastasis to metastasis patients compared with healthy controls, which is in accordance with process of malignant transformation of ESCC. This interested finding suggests that disturbed tryptophan metabolism is correlated to progression and metastasis of ESCC since concentration ratios of compounds reflect activity of enzymes involved in tryptophan metabolism. This study reveals the impact of tryptophan metabolism to tumorigenesis and metastasis of ESCC, which help biologists investigate mechanism of the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1

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    Tian, Zhijie [School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500 (China); Jiang, Hequn [The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041 (China); Liu, Ying; Huang, Yong [School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500 (China); Xiong, Xin [Laboratory Research Center, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016 (China); Wu, Hongwei, E-mail: hongweiwu2118@sina.com [The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041 (China); Dai, Xiaozhen, E-mail: xiaozhendai2012@163.com [School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500 (China); Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing 400044 (China); Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY (United States)

    2016-05-01

    MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as critical gene regulators by targeting mRNAs for translational repression or degradation. In this study, we showed that the expression level of miR-133b was decreased, while Sirt1 mRNA expression levels were increased in hepatocellular carcinoma (HCC) and cell lines, and we identified Sirt1 as a novel direct target of miR-133b. The over-expression of miR-133b suppressed Sirt1 expression. In addition, miR-133b over-expression resulted in attenuating HCC cell proliferation and invasion together with apoptosis increase in vitro. HepG2 cell transplantation revealed that up-regulation of miR-133b could inhibit HCC tumor genesis in vivo. Forced expression of Sirt1 partly rescued the effect of miR-133b in vitro. Furthermore, our study showed that miR-133b over-expression or Sirt1 down-regulation elevated E-cadherin expression, and repressed glypican-3 (GPC3) and the anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1) expression. The inhibition of GPC3 expression repressed Bcl-2, Bcl-xL, and Mcl-1 expression, and elevated E-cadherin expression. Moreover, the Sirt1 up-regulation resulted in increases in HCC cell proliferation and invasion together with decreases apoptosis, and increases in the cytosolic accumulation and nuclear translocation of the transcription factor β-catenin in vitro. But the effect of Sirt1 up-regulation was partly reversed by GPC3 down-regulation in vitro. Taken together, these findings provide insight into the role and mechanism of miR-133b in regulating HCC cell proliferation, invasion and apoptosis via the miR-133b/Sirt1/GPC3/Wnt β-catenin axis, and miR-133b may serve as a potential therapeutic target in HCC in the future. - Highlights: • Sirt1 is a direct target of miR-133b in HCC. • miR-133b over-expression suppresses HCC progression in vitro and in vivo. • Sirt1 restoration reverses the effect of miR-133b over-expression on HCC cells. • GPC3 down-regulation reverses

  5. A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

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    Kim, Su Jin [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); New Drug Development Center, Osong Medical Innovation Foundation, Cheongwon, Chungbuk (Korea, Republic of); Chang, Suhwan [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Yangsoon; Kim, Na Young; Hwang, Yeonsil; Min, Hye Jin; Yoo, Kyung-Sook; Park, Eun Hye; Kim, Seokho [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Chung, Young-Hwa [BK21-plus, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@dau.ac.kr [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Department of Biological Sciences, Dong-A University, Busan (Korea, Republic of)

    2014-11-07

    Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31{sup +} vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models.

  6. Progression of Intravesical Condyloma Acuminata to Locally Advanced Poorly Differentiated Squamous Cell Carcinoma

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    A. Khambati

    2016-07-01

    Full Text Available Condyloma acuminata (CA is a common sexually transmitted disease caused by Human Papilloma Virus (HPV infection. CA of the bladder, however, is an exceedingly rare lesion. We present a rare case of poorly differentiated locally invasive squamous cell carcinoma (SCC arising from recurrent CA of the bladder in an immunocompetent patient and discuss pathophysiology and management of this unusual condition.

  7. MUC13 overexpression in renal cell carcinoma plays a central role in tumor progression and drug resistance.

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    Sheng, Yonghua; Ng, Choa Ping; Lourie, Rohan; Shah, Esha T; He, Yaowu; Wong, Kuan Yau; Seim, Inge; Oancea, Iulia; Morais, Christudas; Jeffery, Penny L; Hooper, John; Gobe, Glenda C; McGuckin, Michael A

    2017-05-15

    Metastatic renal cell carcinoma is a largely incurable disease, and existing treatments targeting angiogenesis and tyrosine kinase receptors are only partially effective. Here we reveal that MUC13, a cell surface mucin glycoprotein, is aberrantly expressed by most renal cell carcinomas, with increasing expression positively correlating with tumor grade. Importantly, we demonstrated that high MUC13 expression was a statistically significant independent predictor of poor survival in two independent cohorts, particularly in stage 1 cancers. In cultured renal cell carcinoma cells MUC13 promoted proliferation and induced the cell cycle regulator, cyclin D1, and inhibited apoptosis by inducing the anti-apoptotic proteins, BCL-xL and survivin. Silencing of MUC13 expression inhibited migration and invasion, and sensitized renal cancer cells to killing by the multi-kinase inhibitors used clinically, sorafenib and sunitinib, and reversed acquired resistance to these drugs. Furthermore, we demonstrated that MUC13 promotion of renal cancer cell growth and survival is mediated by activation of nuclear factor κB, a transcription factor known to regulate the expression of genes that play key roles in the development and progression of cancer. These results show that MUC13 has potential as a prognostic marker for aggressive early stage renal cell cancer and is a plausible target to sensitize these tumors to therapy. © 2017 UICC.

  8. Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025.

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    Escudier, Bernard; Motzer, Robert J; Sharma, Padmanee; Wagstaff, John; Plimack, Elizabeth R; Hammers, Hans J; Donskov, Frede; Gurney, Howard; Sosman, Jeffrey A; Zalewski, Pawel G; Harmenberg, Ulrika; McDermott, David F; Choueiri, Toni K; Richardet, Martin; Tomita, Yoshihiko; Ravaud, Alain; Doan, Justin; Zhao, Huanyu; Hardy, Helene; George, Saby

    2017-09-01

    Response patterns to nivolumab differ from those seen with other approved targeted therapies. To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond (Response Evaluation Criteria In Solid Tumors) RECIST progression. This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study. Patients continuing to tolerate therapy and exhibiting investigator-assessed clinical benefit were eligible to be treated beyond RECIST progression (TBP) and received therapy for ≥4 wk after first progression; patients not treated beyond RECIST progression (NTBP) received 0 wk to Nivolumab 3mg/kg intravenously every 2 wk. Of 406 nivolumab-treated patients, 316 (78%) progressed by RECIST criteria. Of those who progressed, 48% were TBP, 52% were NTBP. Before being TBP, objective response rate (95% confidence interval) was 20% (14-28) and 14% (9-21) in patients TBP and NTBP, respectively. Differences in clinical characteristics assessed at first progression between patients TBP versus NTBP included better Karnofsky performance status, less deterioration in Karnofsky performance status, shorter time to response, lower incidence of new bone lesions, and improved quality of life. Postprogression, 13% of all patients TBP (20/153) had ≥30% tumor burden reduction including patients with preprogression and postprogression tumor measurements (n=142) and complete/partial response (28%, 8/29), stable disease (6%, 3/47), and progressive disease (14%, 9/66) as their best response before being TBP. Incidence of treatment-related adverse events in patients TBP was lower after (59%) versus before (71%) progression. Limitations included potential bias from the nonrandomized nature of the analysis. A subset of patients with advanced renal cell carcinoma and RECIST progression experienced tumor reduction postprogression with nivolumab, and had an acceptable safety profile. Clinical judgment

  9. Expression of YY1 correlates with progression and metastasis in esophageal squamous cell carcinomas

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    Luo J

    2014-09-01

    Full Text Available Judong Luo,1,* Xin Jiang,1,* LiLi Cao,2,* Kejun Dai,1 Shuyu Zhang,3,4 Xin Ge,3,4 Xifa Zhou,1 Xujing Lu1 1Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, People's Republic of China; 2Department of Molecular Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan; 3School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, 4Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X, Soochow University, Suzhou, People's Republic of China  *These authors contributed equally to this work Objective: Esophageal squamous cell carcinoma (ESCC is one of the deadliest cancers worldwide. Yin Yang 1 (YY1 is a ubiquitous and multifunctional zinc-finger transcription factor that plays important biological functions in cell homeostasis and tumorigenesis. The purpose of this study was to investigate the expression of YY1 in different ESCC tissues and the potential relationship with clinicopathological features. Methods: One hundred and four ESCC tissues were collected in this study. The protein levels of YY1 were measured by immunohistochemistry. TE-1 cell invasion in vitro was assessed using the Transwell assay. Results: There were no obvious differences between expression levels in patients over age 64 and those younger than 64, and no noticeable distinction was observed between males and females. However, the YY1 protein level was significantly higher in ESCC tissues with lymph node metastasis than those without lymph node metastasis (P=0.042. Furthermore, the expression of the YY1 protein was stronger in stage III–IV patients than in stage I–II patients (P=0.002, but the protein levels between different histological grades (well, moderate, or poor showed no statistical significance. Similarly, there was no

  10. Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

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    Quiroga-Garza Gabriela

    2012-02-01

    Full Text Available Abstract Seven percent of renal cell carcinoma (RCC cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC and a tubulocystic renal carcinoma (TCRC in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR and distal tubule cell (CK19 markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2 of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3 showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1790525735655283

  11. Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression.

    Science.gov (United States)

    Quiroga-Garza, Gabriela; Piña-Oviedo, Sergio; Cuevas-Ocampo, Karime; Goldfarb, Richard; Schwartz, Mary R; Ayala, Alberto G; Monzon, Federico A

    2012-02-27

    Seven percent of renal cell carcinoma (RCC) cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC) and a tubulocystic renal carcinoma (TCRC) in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR) and distal tubule cell (CK19) markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2) of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3) showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1790525735655283.

  12. Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma

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    Xue Yi-Jun

    2012-09-01

    Full Text Available Abstract Background Fork head box M1 (FoxM1 is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC. Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models. Methods Real-time quantitative PCR, western blot and immunohistochemistry were used to explore FoxM1 expression in ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was knocked down by small interfering RNA (siRNA in Caki-1 and 786-O cells; proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis were assayed. Results FoxM1 expression was up-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that FoxM1 expression was significantly correlated with primary tumor stage (P P = 0.01, distant metastasis (P = 0.01, TNM stage (P P = 0.003. The Kaplan–Meier survival curves revealed that high FoxM1 expression was associated with poor prognosis in ccRCC patients (P P = 0.008. Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix metalloproteinase-2 (MMP-2, MMP-9 and vascular endothelial growth factor (VEGF, resulting in the inhibition of migration, invasion, and angiogenesis. Conclusions These results suggest that FoxM1 expression is likely to play important roles in ccRCC development and progression, and that FoxM1 is a prognostic biomarker and a

  13. A Comprehensive Study of Progressive Cytogenetic Alterations in Clear Cell Renal Cell Carcinoma and a New Model for ccRCC Tumorigenesis and Progression

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    Zhongfa Zhang

    2010-01-01

    Full Text Available We present a comprehensive study of cytogenetic alterations that occur during the progression of clear cell renal cell carcinoma (ccRCC. We used high-density high-throughput Affymetrix 100 K SNP arrays to obtain the whole genome SNP copy number information from 71 pretreatment tissue samples with RCC tumors; of those, 42 samples were of human ccRCC subtype. We analyzed patterns of cytogenetic loss and gain from different RCC subtypes and in particular, different stages and grades of ccRCC tumors, using a novel algorithm that we have designed. Based on patterns of cytogenetic alterations in chromosomal regions with frequent losses and gains, we inferred the involvement of candidate genes from these regions in ccRCC tumorigenesis and development. We then proposed a new model of ccRCC tumorigenesis and progression. Our study serves as a comprehensive overview of cytogenetic alterations in a collection of 572 ccRCC tumors from diversified studies and should facilitate the search for specific genes associated with the disease.

  14. Cancer Stem Cells Accountability in Progression of Head and Neck Squamous Cell Carcinoma: The Most Recent Trends!

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    Samapika Routray

    2014-01-01

    Full Text Available Cancer stem cells (CSCs play a major role in local recurrence and metastatic spread in head and neck squamous cell carcinomas (HNSCC. Evidence suggests that cancer stem cells are resistant to conventional therapy. So the emerging concepts of the role of cancer stem cells in the pathobiology of HNSCC should be understood carefully to be able to create new paradigms in treatment plans.

  15. Microencapsulation of engineered cells to deliver sustained high circulating levels of interleukin-6 to study hepatocellular carcinoma progression.

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    Moran, Diarmuid M; Koniaris, Leonidas G; Jablonski, Elizabeth M; Cahill, Paul A; Halberstadt, Craig R; McKillop, Iain H

    2006-01-01

    Interlukin-6 (IL-6) is a pleitropic cytokine that plays a central role in normal and abnormal hepatic function and response. The aims of the current study were to determine the viability of using cell encapsulation technology to introduce a genetically modified xenogeneic (CHO) cell population to elevate circulating levels of rhIL-6 in a rat model and determine the effects of sustained high rhIL-6 levels on hepatocellular carcinoma (HCC) progression in vivo. An alginate matrix was combined with transfected CHO cells, selected for their ability to synthesize rhIL-6, and used to generate uniform alginate-cell beads. Once encapsulated transfected cells continued to undergo replication, formed colonies within the bead, and synthesized/released large quantities of rhIL-6 into culture medium in vitro. Intraperitoneal implantation of beads into rats resulted in significantly increased circulating and intrahepatic levels of rhIL-6 up to 4 days postimplantation. Prolonged implantation led to the escape of CHO cells from the bead, resulting in a host response and CHO cell death within the bead. Subsequently CHO-IL-6 encapsulated cells were implanted into rats previously inoculated intrahepatically with the H4IIE HCC cell line. These studies demonstrated the maintenance of high circulating/intrahepatic rhIL-6 levels in this model. Despite significantly increased rhIL-6, this technique did not significantly alter the rate of net tumor progression. However, Stat3 activity was significantly increased in both normal liver and HCC tissue resected from animals implanted with CHO-IL-6 cells. Collectively these data demonstrate the short-term viability of using cell encapsulation technology to generate high levels of active circulating and intrahepatic cytokines and raise the possibility of modifying specific signal transduction cascades identified to be important during tumor progression.

  16. Basal Cell Carcinoma: From the Molecular Understanding of the Pathogenesis to Targeted Therapy of Progressive Disease

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    Daniela Göppner

    2011-01-01

    Full Text Available Due to intensified research over the past decade, the Hedgehog (HH pathway has been identified as a pivotal defect implicated in roughly 25% of all cancers. As one of the most frequent cancer worldwide, the development of Basal cell carcinoma (BCC due to activation of the HH pathway has been convincingly demonstrated. Thus the discovery of this central tumor-promoting signalling pathway has not only revolutionized the understanding of BCC carcinogenesis but has also enabled the development of a completely novel therapeutic approach. Targeting just a few of several potential mutations, HH inhibitors such as GDC-0449 achieved already the first promising results in metastatic or locally advanced BCC. This paper summarizes the current understanding of BCC carcinogenesis and describes the current “mechanism-based” therapeutic strategies.

  17. Targeting TPX2 Suppresses the Tumorigenesis of Hepatocellular Carcinoma Cells Resulting in Arrested Mitotic Phase Progression and Increased Genomic Instability.

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    Hsu, Chao-Wen; Chen, Yu-Chia; Su, Hsing-Hao; Huang, Guan-Jin; Shu, Chih-Wen; Wu, Tony Tong-Lin; Pan, Hung-Wei

    2017-01-01

    Hepatocellular carcinoma (HCC) remains one of the most difficult cancers to treat, with chemotherapies being relatively ineffective. Therefore, a better knowledge of molecular hepatocarcinogenesis will provide opportunities for designing targeted therapies. TPX2 (targeting protein for Xklp2) is overexpressed as a consequence of oncogenic alterations and is likely to alter the proper regulation of chromosome segregation in cancer cells. Disrupting the machinery which is responsible for mitosis and chromosome instability in cancer cells can be one of the most successful strategies for cancer therapy. Therefore, we consider the targeting TPX2 could provide novel therapeutic strategies for cancer. In this study, increased TPX2 protein expression was present in 16 (42%) of 38 primary HCCs and was associated with advanced stage, distant metastatic HCCs and poor prognosis. Knockdown of TPX2 inhibited cancer cell growth and downregulation of cyclin A, cyclin E and CDK2 proteins. However, over-expressed EGFP-TPX2 protein enhanced the in vitro tumor spheroid formation and rescued the TPX2 depleted cell growth. Targeting TPX2 caused a rising impaired chromosomal instability resulting in multinuclearity, cell cycle progression arrest, apotosis, senescence and an increased polyploidy in cells. An image-cytometry analysis revealed cell cycle progression arrest after TPX2 inhibition. A correlation was observed between the downregulation of the protein levels of genes related to chromosomal segregation and spindle assembly checkpoint (securin, seprase, Aurora A, Aurora B, Cyclin B1, Cyclin B2, MPS1, BUB1, BUB3, MAD1 and MAD2) and increased cell ploidy, indicating mitotic progression failure and the loss of the balance of genomic instability. In vitro tumor spheroid assay and in vivo xenografts mouse model showed a therapeutic opportunity. Our findings indicate that targeting TPX2 lead to suppress tumorigenicity in liver cancer cells, suggesting that TPX2 is a potential target for

  18. Linc-ROR promotes esophageal squamous cell carcinoma progression through the derepression of SOX9.

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    Wang, Lianghai; Yu, Xiaodan; Zhang, Zhiyu; Pang, Lijuan; Xu, Jiang; Jiang, Jinfang; Liang, Weihua; Chai, Yuhang; Hou, Jun; Li, Feng

    2017-12-13

    Novel therapies tailored to the molecular composition of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. We investigated the regulatory network of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) and sex-determining region Y-box 9 (SOX9), and their therapeutic relevance in ESCC. Linc-ROR and SOX9 expression were examined in ESCC specimens, cell lines, and cultured tumorspheres. We investigated the effects of linc-ROR on SOX9 expression and malignant phenotypes by CCK8, colony formation, Transwell, and sphere-forming assay. The linc-ROR/SOX9 interaction mediated by multiple microRNAs (miRNAs) was confirmed by bioinformatic analysis, luciferase assay, and RNA-binding protein immunoprecipitation, transient overexpression or antagonizing endogenous candidate miRNAs. The effect of linc-ROR depletion on tumor growth was assessed by xenograft assay. A positive correlation between linc-ROR and SOX9 expression was found in clinical ESCC specimens (r = 0.562, P = 0.036), cell lines, and tumorspheres. Silencing of linc-ROR significantly inhibited cell proliferation, motility, chemoresistance, and self-renewal capacity. Mechanistically, linc-ROR modulating the derepression of SOX9 by directly sponging multiple miRNAs including miR-15b, miR-33a, miR-129, miR-145, and miR-206. Antagonizing these miRNAs counteracted with linc-ROR silencing, whereas the repression of SOX9 abrogated malignant phenotypes induced by the cocktail of miRNA inhibitors. Moreover, linc-ROR disruption was sufficient to attenuate tumor growth and cancer stem cell marker expression in vivo. Our results demonstrate that the linc-ROR-miRNA-SOX9 regulatory network may represent a novel therapeutic target for ESCC.

  19. WNT1-inducible signaling pathway protein-1 contributes to tumor progression and treatment failure in oral squamous cell carcinoma.

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    Jung, Eun Kyung; Kim, Sun-Ae; Yoon, Tae Mi; Lee, Kyung-Hwa; Kim, Hee Kyung; Lee, Dong Hoon; Lee, Joon Kyoo; Chung, Ik-Joo; Joo, Young-Eun; Lim, Sang Chul

    2017-08-01

    WNT1-inducible-signaling pathway protein-1 (WISP-1) belongs to the family of cysteine rich 61/connective tissue growth factor/nephroblastoma overexpressed matricellular proteins, which are involved in various biological processes, including cell adhesion, proliferation, differentiation, angiogenesis and carcinogenesis. In the present study, the expression of WISP-1 was investigated, and its association with clinicopathological factors and prognosis in patients with oral squamous cell carcinoma (OSCC) was evaluated. Additionally, the role of WISP-1 in invasion and apoptosis of human OSCC cells was evaluated. Immunoreactivity of WISP-1 was increased in OSCC tissue compared with adjacent normal tissue samples. High expression of WISP-1 protein was observed in 24/84 (28.57%) OSCC specimens. Additionally, high WISP-1 expression was significantly associated with treatment failure (P=0.042). The 5-year overall survival rate was 33% in patients with high WISP1 expression, and 66% in patients with low WISP-1 expression. WISP-1 expression in the human OSCC SCC-1483 cell line was observed. Furthermore, WISP-1 knockdown using small interfering (si)RNA significantly reduced cell invasion and induced apoptosis compared with control siRNA-transfected cells. These findings suggested that WISP-1 is associated with tumor progression and poor prognosis by increasing tumor cell invasion and inhibiting cell apoptosis in human OSCC.

  20. Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

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    Soares Fernando A

    2011-04-01

    Full Text Available Abstract Background Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+ and recurrent head and neck squamous cell carcinoma (HNSCC may increase our understanding of the complex biology of this disease. Methods Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative or tumor recurrence (recurrent or non-recurrent tumor after treatment (surgery with neck dissection followed by radiotherapy. Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results The most frequent alterations were the repression of modules in negative lymph node (N0 and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway

  1. Suppression of mitochondrial respiration with auraptene inhibits the progression of renal cell carcinoma: involvement of HIF-1α degradation.

    Science.gov (United States)

    Jang, Yunseon; Han, Jeongsu; Kim, Soo Jeong; Kim, Jungim; Lee, Min Joung; Jeong, Soyeon; Ryu, Min Jeong; Seo, Kang-Sik; Choi, Song-Yi; Shong, Minho; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-11-10

    Renal cell carcinoma (RCC) progression resulting from the uncontrolled migration and enhanced angiogenesis is an obstacle to effective therapeutic intervention. Tumor metabolism has distinctive feature called Warburg effect, which enhances the aerobic glycolysis rapidly supplying the energy for migration of tumor. To manipulate this metabolic change characteristic of aggressive tumors, we utilized the citrus extract, auraptene, known as a mitochondrial inhibitor, testing its anticancer effects against the RCC4 cell line. We found that auraptene impaired RCC4 cell motility through reduction of mitochondrial respiration and glycolytic pathway-related genes. It also strongly disrupted VEGF-induced angiogenesis in vitro and in vivo. Hypoxia-inducible factor 1a (HIF-1a), a key regulator of cancer metabolism, migration and angiogenesis that is stably expressed in RCCs by virtue of a genetic mutation in the von Hippel-Lindau (VHL) tumor-suppressor protein, was impeded by auraptene, which blocked HIF-1a translation initiation without causing cytotoxicity. We suggest that blockade HIF-1a and reforming energy metabolism with auraptene is an effective approach for suspension RCC progression.

  2. ARTD1 regulates cyclin E expression and consequently cell-cycle re-entry and G1/S progression in T24 bladder carcinoma cells

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    Léger, Karolin; Hopp, Ann-Katrin; Fey, Monika; Hottiger, Michael O.

    2016-01-01

    ABSTRACT ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli. In synchronized cells, ARTD1 knockdown, but not inhibition of its enzymatic activity, caused specific down-regulation of cyclin E during cell cycle re-entry and G1/S progression through alterations of the chromatin composition and histone acetylation, but not of other E2F-1 target genes. Although Cdk2 formed a functional complex with the residual cyclin E, p27Kip1 protein levels increased in G1 upon ARTD1 knockdown most likely due to inappropriate cyclin E-Cdk2-induced phosphorylation-dependent degradation, leading to decelerated G1/S progression. These results provide evidence that ARTD1 regulates cell cycle re-entry and G1/S progression via cyclin E expression and p27Kip1 stability independently of its enzymatic activity, uncovering a novel cell cycle regulatory mechanism. PMID:27295004

  3. ARTD1 regulates cyclin E expression and consequently cell-cycle re-entry and G1/S progression in T24 bladder carcinoma cells.

    Science.gov (United States)

    Léger, Karolin; Hopp, Ann-Katrin; Fey, Monika; Hottiger, Michael O

    2016-08-02

    ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli. In synchronized cells, ARTD1 knockdown, but not inhibition of its enzymatic activity, caused specific down-regulation of cyclin E during cell cycle re-entry and G1/S progression through alterations of the chromatin composition and histone acetylation, but not of other E2F-1 target genes. Although Cdk2 formed a functional complex with the residual cyclin E, p27(Kip 1) protein levels increased in G1 upon ARTD1 knockdown most likely due to inappropriate cyclin E-Cdk2-induced phosphorylation-dependent degradation, leading to decelerated G1/S progression. These results provide evidence that ARTD1 regulates cell cycle re-entry and G1/S progression via cyclin E expression and p27(Kip 1) stability independently of its enzymatic activity, uncovering a novel cell cycle regulatory mechanism.

  4. Increased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis.

    Science.gov (United States)

    Harms, Kelly L; Chubb, Heather; Zhao, Lili; Fullen, Douglas R; Bichakjian, Christopher K; Johnson, Timothy M; Carskadon, Shannon; Palanisamy, Nallasivam; Harms, Paul W

    2017-09-01

    Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P=.005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Immunotherapy with concurrent subcutaneous GM-CSF, low-dose IL-2 and IFN-alpha in patients with progressive metastatic renal cell carcinoma

    NARCIS (Netherlands)

    Verra, N.; Jansen, R.; Groenewegen, G.; Mallo, H.; Kersten, M. J.; Bex, A.; Vyth-Dreese, F. A.; Sein, J.; van de Kasteele, W.; Nooijen, W. J.; de Waal, M.; Horenblas, S.; de Gast, G. C.

    2003-01-01

    The purpose of the study was to determine toxicity, efficacy and immunologic effects of concurrent subcutaneous injections of low-dose interleukin-2 (LD-IL-2), granulocyte-monocyte colony-stimulating factor (GM-CSF) and interferon-alpha 2b (IFNalpha) in progressive metastatic renal cell carcinoma.

  6. Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1

    Directory of Open Access Journals (Sweden)

    Junichiro Miyazaki

    2017-04-01

    Full Text Available Renal cell carcinoma (RCC is the most lethal urological malignancy with high risk of recurrence; thus, new prognostic biomarkers are needed. In this study, a new RCC antigen, PTPL1 associated RhoGAP1 (PARG1, was identified by using serological identification of recombinant cDNA expression cloning with sera from RCC patients. PARG1 protein was found to be differentially expressed in RCC cells among patients. High PARG1 expression is significantly correlated with various clinicopathological factors relating to cancer cell proliferation and invasion, including G3 percentage (P = .0046, Ki-67 score (p expression is also correlated with high recurrence of N0M0 patients (P = .0084 and poor prognosis in RCC patients (P = .0345. Multivariate analysis has revealed that high PARG1 expression is an independent factor for recurrence (P = .0149 of N0M0 RCC patients. In in vitro studies, depletion of PARG1by siRNA in human RCC cell lines inhibited their proliferation through inducing G1 cell cycle arrest via upregulation of p53 and subsequent p21Cip1/Waf1, which are mediated by increased RhoA-ROCK activities. Similarly, PARG1 depletion cells inhibited invasion ability via increasing RhoA-ROCK activities in the RCC cell lines. Conversely, overexpression of PARG1 on human embryonic kidney cell line HEK293T promotes its cell proliferation and invasion. These results indicate that PARG1 plays crucial roles in progression of human RCC in increasing cell proliferation and invasion ability via inhibition of the RhoA-ROCK axis, and PARG1 is a poor prognostic marker, particularly for high recurrence of N0M0 RCC patients.

  7. S100A8/A9 (calprotectin negatively regulates G2/M cell cycle progression and growth of squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Ali Khammanivong

    Full Text Available Malignant transformation results in abnormal cell cycle regulation and uncontrolled growth in head and neck squamous cell carcinoma (HNSCC and other cancers. S100A8/A9 (calprotectin is a calcium-binding heterodimeric protein complex implicated in cell cycle regulation, but the specific mechanism and role in cell cycle control and carcinoma growth are not well understood. In HNSCC, S100A8/A9 is downregulated at both mRNA and protein levels. We now report that downregulation of S100A8/A9 correlates strongly with a loss of cell cycle control and increased growth of carcinoma cells. To show its role in carcinogenesis in an in vitro model, S100A8/A9 was stably expressed in an S100A8/A9-negative human carcinoma cell line (KB cells, HeLa-like. S100A8/A9 expression increases PP2A phosphatase activity and p-Chk1 (Ser345 phosphorylation, which appears to signal inhibitory phosphorylation of mitotic p-Cdc25C (Ser216 and p-Cdc2 (Thr14/Tyr15 to inactivate the G2/M Cdc2/cyclin B1 complex. Cyclin B1 expression then downregulates and the cell cycle arrests at the G2/M checkpoint, reducing cell division. As expected, S100A8/A9-expressing cells show both decreased anchorage-dependent and -independent growth and mitotic progression. Using shRNA, silencing of S100A8/A9 expression in the TR146 human HNSCC cell line increases growth and survival and reduces Cdc2 inhibitory phosphorylation at Thr14/Tyr15. The level of S100A8/A9 endogenous expression correlates strongly with the reduced p-Cdc2 (Thr14/Tyr14 level in HNSCC cell lines, SCC-58, OSCC-3 and UMSCC-17B. S100A8/A9-mediated control of the G2/M cell cycle checkpoint is, therefore, a likely suppressive mechanism in human squamous cell carcinomas and may suggest new therapeutic approaches.

  8. S100A8/A9 (Calprotectin) Negatively Regulates G2/M Cell Cycle Progression and Growth of Squamous Cell Carcinoma

    Science.gov (United States)

    Khammanivong, Ali; Wang, Chengxing; Sorenson, Brent S.; Ross, Karen F.; Herzberg, Mark C.

    2013-01-01

    Malignant transformation results in abnormal cell cycle regulation and uncontrolled growth in head and neck squamous cell carcinoma (HNSCC) and other cancers. S100A8/A9 (calprotectin) is a calcium-binding heterodimeric protein complex implicated in cell cycle regulation, but the specific mechanism and role in cell cycle control and carcinoma growth are not well understood. In HNSCC, S100A8/A9 is downregulated at both mRNA and protein levels. We now report that downregulation of S100A8/A9 correlates strongly with a loss of cell cycle control and increased growth of carcinoma cells. To show its role in carcinogenesis in an in vitro model, S100A8/A9 was stably expressed in an S100A8/A9-negative human carcinoma cell line (KB cells, HeLa-like). S100A8/A9 expression increases PP2A phosphatase activity and p-Chk1 (Ser345) phosphorylation, which appears to signal inhibitory phosphorylation of mitotic p-Cdc25C (Ser216) and p-Cdc2 (Thr14/Tyr15) to inactivate the G2/M Cdc2/cyclin B1 complex. Cyclin B1 expression then downregulates and the cell cycle arrests at the G2/M checkpoint, reducing cell division. As expected, S100A8/A9-expressing cells show both decreased anchorage-dependent and -independent growth and mitotic progression. Using shRNA, silencing of S100A8/A9 expression in the TR146 human HNSCC cell line increases growth and survival and reduces Cdc2 inhibitory phosphorylation at Thr14/Tyr15. The level of S100A8/A9 endogenous expression correlates strongly with the reduced p-Cdc2 (Thr14/Tyr14) level in HNSCC cell lines, SCC-58, OSCC-3 and UMSCC-17B. S100A8/A9-mediated control of the G2/M cell cycle checkpoint is, therefore, a likely suppressive mechanism in human squamous cell carcinomas and may suggest new therapeutic approaches. PMID:23874958

  9. Basal Cell Carcinoma

    Science.gov (United States)

    ... think Sebaceous carcinoma Skin cancer in people of color Skin reactions from targeted cancer therapy Squamous cell carcinoma What is Mohs surgery? Why see a board-certified dermatologist? Other conditions Diseases: A-Z index Skin, hair, and nail ...

  10. Squamous Cell Carcinoma

    Science.gov (United States)

    ... think Sebaceous carcinoma Skin cancer in people of color Skin reactions from targeted cancer therapy Squamous cell carcinoma What is Mohs surgery? Why see a board-certified dermatologist? Other conditions Diseases: A-Z index Skin, hair, and nail ...

  11. Identification of SLAMF3 (CD229) as an Inhibitor of Hepatocellular Carcinoma Cell Proliferation and Tumour Progression

    Science.gov (United States)

    Cartier, Flora; Amrathlal, Rabbind Singh; Ossart, Christèle; Ouled-Haddou, Hakim; Ghamlouch, Hussein; Galmiche, Antoine; Chatelain, Denis; Lamotte, Luciane; Debuysscher, Véronique; Fuentes, Vincent; Nguyen-Khac, Eric; Regimbeau, Jean-Marc; Marolleau, Jean-Pierre; Latour, Sylvain; Bouhlal, Hicham

    2013-01-01

    Although hepatocellular carcinoma (HCC) is one of the most common malignancies and constitutes the third leading cause of cancer-related deaths, the underlying molecular mechanisms are not fully understood. In the present study, we demonstrate for the first time that hepatocytes express signalling lymphocytic activation molecule family member 3 (SLAMF3/CD229) but not other SLAMF members. We provide evidence to show that SLAMF3 is involved in the control of hepatocyte proliferation and in hepatocellular carcinogenesis. SLAMF3 expression is significantly lower in primary human HCC samples and HCC cell lines than in human healthy primary hepatocytes. In HCC cell lines, the restoration of high levels of SLAMF3 expression inhibited cell proliferation and migration and enhanced apoptosis. Furthermore, SLAMF3 expression was associated with inhibition of HCC xenograft progression in the nude mouse model. The restoration of SLAMF3 expression levels also decreased the phosphorylation of MAPK ERK1/2, JNK and mTOR. In samples from resected HCC patients, SLAMF3 expression levels were significantly lower in tumorous tissues than in peritumoral tissues. Our results identify SLAMF3 as a specific marker of normal hepatocytes and provide evidence for its potential role in the control of proliferation of HCC cells. PMID:24376606

  12. Identification of SLAMF3 (CD229 as an inhibitor of hepatocellular carcinoma cell proliferation and tumour progression.

    Directory of Open Access Journals (Sweden)

    Ingrid Marcq

    Full Text Available Although hepatocellular carcinoma (HCC is one of the most common malignancies and constitutes the third leading cause of cancer-related deaths, the underlying molecular mechanisms are not fully understood. In the present study, we demonstrate for the first time that hepatocytes express signalling lymphocytic activation molecule family member 3 (SLAMF3/CD229 but not other SLAMF members. We provide evidence to show that SLAMF3 is involved in the control of hepatocyte proliferation and in hepatocellular carcinogenesis. SLAMF3 expression is significantly lower in primary human HCC samples and HCC cell lines than in human healthy primary hepatocytes. In HCC cell lines, the restoration of high levels of SLAMF3 expression inhibited cell proliferation and migration and enhanced apoptosis. Furthermore, SLAMF3 expression was associated with inhibition of HCC xenograft progression in the nude mouse model. The restoration of SLAMF3 expression levels also decreased the phosphorylation of MAPK ERK1/2, JNK and mTOR. In samples from resected HCC patients, SLAMF3 expression levels were significantly lower in tumorous tissues than in peritumoral tissues. Our results identify SLAMF3 as a specific marker of normal hepatocytes and provide evidence for its potential role in the control of proliferation of HCC cells.

  13. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

    OpenAIRE

    de Faria, J

    1985-01-01

    The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

  14. Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model

    Science.gov (United States)

    Mazzilli, Sarah A.; Hershberger, Pamela A.; Reid, Mary E.; Bogner, Paul N.; Atwood, Kristopher; Trump, Donald L.; Johnson, Candace S.

    2015-01-01

    The chemopreventive actions of vitamin D were examined in the N-nitroso-tris-chloroethylurea (NTCU) mouse model, a progressive model of lung squamous cell carcinoma (SCC). SWR/J mice were fed a deficient diet (D) containing no vitamin D3, a sufficient diet (S) containing 2000 IU/kg vitamin D3, or the same diets in combination with the active metabolite of vitamin D, calcitriol (C) (80 μg/kg, weekly). The percentage (%) of the mucosal surface of large airways occupied by dysplastic lesions was determined in mice after treatment with a total dose of 15 or 25 μmol NTCU (N). After treatment with 15 μmol NTCU, the % of the surface of large airways containing high-grade dysplastic (HGD) lesions were vitamin D-deficient +NTCU (DN), 22.7 % (p<0.05 compared to vitamin D-sufficient +NTCU (SN)); DN + C, 12.3%; SN, 8.7%; and SN + C, 6.6%. The extent of HGD increased with NTCU dose in the DN group. Proliferation, assessed by Ki-67 labeling, increased upon NTCU treatment. The highest Ki-67 labeling index was seen in the DN group. As compared to SN mice, DN mice exhibited a 3-fold increase (p <0.005) in circulating white blood cells (WBC), a 20% (p <0.05) increase in IL-6 levels, and a 4 -fold (p <0.005) increase in WBC in bronchial lavages. Thus, vitamin D repletion reduces the progression of premalignant lesions, proliferation, and inflammation, and may thereby suppress development of lung SCC. Further investigations of the chemopreventive effects of vitamin D in lung SCC are warranted. PMID:26276745

  15. Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma

    Science.gov (United States)

    Fakhry, Carole; Zhang, Qiang; Nguyen-Tan, Phuc Felix; Rosenthal, David; El-Naggar, Adel; Garden, Adam S.; Soulieres, Denis; Trotti, Andy; Avizonis, Vilija; Ridge, John Andrew; Harris, Jonathan; Le, Quynh-Thu; Gillison, Maura

    2014-01-01

    Purpose Risk of cancer progression is reduced for patients with human papillomavirus (HPV) –positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced. Patients and Methods Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol. Results A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment. Conclusion Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC. PMID:24958820

  16. Controversies in renal cell carcinoma: treatment choice after progression on vascular endothelial growth factor-targeted therapy.

    Science.gov (United States)

    Calvo, Emiliano; Grünwald, Viktor; Bellmunt, Joaquim

    2014-05-01

    The mammalian target of rapamycin inhibitor (mTORI) everolimus and the tyrosine kinase inhibitor (TKI) axitinib are the only two post-first-line treatment options for metastatic renal cell carcinoma (mRCC) licensed at present. Extrapolation of robust phase III studies suggests that median progression-free survival (PFS) is similar between agents. This presents a dilemma for the physician planning treatment for their patients with mRCC: should they be treated with a TKI-mTORI or a TKI-TKI sequence? The lack of direct comparison between axitinib and everolimus leaves the clinician without clear guidance on the optimal choice in second-line therapy. In phase III studies, both post first-line everolimus and axitinib have been shown to delay disease progression; however, cumulative toxicity with sequential use of TKIs may result in more treatment interruptions or dose reductions or increased likelihood of adverse events. While everolimus exerts a tolerability advantage, axitinib is associated with higher response rate and a similar PFS benefit. Proven superiority cannot be used to guide treatment sequence selection in mRCC. Instead, therapeutic planning requires us to take a long-term view of our patient's treatment that includes quality of life and a balance between symptom control, adverse event management and avoidance of unnecessary drug interruptions or dose reductions. In the absence of curative therapies, sustaining a patient's quality of life is a major goal throughout the course of treatment and choosing a second-line agent that is able to adequately achieve this by limiting adverse events should be a priority. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Liao Yi-Ji

    2009-12-01

    Full Text Available Abstract Background Trimethylation of lysine 27 on histone H3 (H3K27me3 by enhancer of zeste homolog 2 (EZH2 is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed and correlates with poor prognosis in many cancers. However, the clinical implication of H3K27me3 in human malignancies has not been well established. We wished to ascertain whether a correlation exists between the expression of H3K27me3 and clinical outcome in a group of patients with esophageal squamous cell carcinoma (ESCC treated with definitive chemoradiotherapy (CRT. Methods The method of immunohistochemistry (IHC was utilized to examine the protein expression of H3K27me3 in 98 pretreatment biopsy specimens of ESCC and in 30 samples of normal esophageal mucosa. The clinical/prognostic significance of H3K27me3 expression was statistically analyzed. Results The expression frequency and expression levels of H3K27me3 were significantly higher in ESCCs than in normal tissues. There was a positive correlation between H3K27me3 expression and WHO grade (P = 0.016, tumor size (P = 0.019, T status (P = 0.024, locoregional progression (P = 0.009 and EZH2 expression (P = 0.036. High H3K27me3 expression was associated with poor locoregional progression-free survival (LPFS (P = 0.010 in ESCC. Further analysis demonstrated that H3K27me3 could stratify patient outcome in T2-3 (P = 0.048, N0 (P = 0.005 and M0 (P = 0.018 stages as well as in CRT effective group (P = 0.022. Conclusions Our data suggests that H3K27me3 expression examined by IHC might be useful for stratifying LPFS for different subsets of ESCC patients treated with definitive CRT.

  18. Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025

    DEFF Research Database (Denmark)

    Escudier, Bernard; Motzer, Robert J; Sharma, Padmanee

    2017-01-01

    BACKGROUND: Response patterns to nivolumab differ from those seen with other approved targeted therapies. OBJECTIVE: To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond (Response Evaluation Criteria In Solid Tumors) RE...

  19. Chromophobe Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Jyotsna Vijaykumar Wader

    2013-04-01

    Full Text Available Renal cell carcinoma is the most common neoplasm of the kidney comprised of different histological variants. Chromophobe renal cell carcinoma (ChRCC is a rare subtype of renal cell carcinoma (RCC mainly diagnosed in the sixth decade of life. It is important to identify this entity because it has significantly better prognosis than the clear cell (conventional and papillary renal cell carcinomas. The chromophobe renal cell carcinoma should be differentiated from oncocytoma and clear cell carcinoma. We report a case of a 70 year-old male who presented with a six month history of hematuria, left sided flank pain and a palpable non-tender lump in the left lumbar region. On radiology, the possibility of a left renal neoplasm was raised. A left radical nephrectomy was done and histopathological diagnosis of Type 2 (mixed chromophobe renal cell carcinoma was given. We present this case owing to its relative rarity of incidence, difficulties encountered and differential diagnoses to be considered during diagnosis as the prognosis and management protocols differ with different variants.

  20. Nuclear expression of hypoxia-inducible factor-1alpha in clear cell renal cell carcinoma is involved in tumor progression.

    Science.gov (United States)

    Di Cristofano, Claudio; Minervini, Andrea; Menicagli, Michele; Salinitri, Giuseppe; Bertacca, Gloria; Pefanis, Gerasimos; Masieri, Lorenzo; Lessi, Francesca; Collecchi, Paola; Minervini, Riccardo; Carini, Marco; Bevilacqua, Generoso; Cavazzana, Andrea

    2007-12-01

    The most frequent genomic abnormality in clear cell renal cell carcinoma (cc-RCC) is inactivation of Von Hippel-Lindau gene (VHL). pVHL19 is a ligase promoting proteosomal degradation of hypoxia-inducible factor-1alpha (HIF-1alpha); pVHL30 is associated with microtubules. VHL exert its oncogenetic action both directly and through HIF-1alpha activation. TNM classification is unable to define a correct prognostic evaluation of intracapsular cc-RCC. The nucleo-cytoplasmic trafficking in VHL/HIF-1alpha pathway could be relevant in understanding the molecular pathogenesis of renal carcinogenesis. This study analyzes VHL/HIF-1alpha proteins in a large series of intracapsular cc-RCCs, correlating their expression and cellular localization with prognosis. Two anti-pVHL (clones Ig32 and Ig33) and 1 anti-HIF-1alpha were used on tissue microarrays from 136 intracapsular cc-RCCs (mean follow-up: 74 mo). Clone 32 recognizes both pVHLs, whereas clone 33 only pVHL30. Results were matched with clinicopathologic variables and tumor-specific survival (TSS). A strong cytoplasmic positivity was found for all antibodies in the largest part of cases, associated to a strong nuclear localization in the case of HIF-1alpha. All pVHL-negative cases were associated with high HIF-1alpha expression. pVHL negativity and HIF-1alpha nuclear positivity significantly correlated with shorter TSS. In multivariate analysis both pVHL negativity and HIF-1alpha nuclear expression were independent predictors of TSS. The localization of the proteins well matches with their role and with the supposed tumor molecular pathways. The correlation with prognosis of VHL/HIF-1alpha alterations confirms the relevance of their molecular pathway and of the cellular trafficking of their products in the pathogenesis of renal cancer.

  1. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  2. Research Progress of Immunotherapy in Nasopharyngeal Carcinoma

    Directory of Open Access Journals (Sweden)

    Jian-nan SHAO

    2017-09-01

    Full Text Available Nasopharyngeal carcinoma (NPC is the most common head and neck cancer in Southeast Asia and Southern China, for which simple radiotherapy or concurrent radiochemotherapy is a main treatment means, with good therapeutic effects. However, although local control rate and survival rate for NPC are improved, distant metastasis is still a main cause of treatment failure. In recent years, immunotherapy has become a focus in the field of cancer research and comprehensive treatment for cancer, and has obtained certain therapeutic effects in several tumors so far, such as melanin and lymphoma. Due to its advantages of high effcacy, good specifcity and less side effects, immunotherapy has become a new promising alternative treatment for patients with NPC. This review was mainly focused on research progress of immunotherapy in NPC, specifically including adoptive immune cell therapy, tumor vaccine, checkpoint inhibitor, and immune gene therapy.

  3. Nevoid basal cell carcinoma syndrome

    Science.gov (United States)

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic ... syndrome is known as PTCH ("patched"). The gene is passed down ...

  4. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  5. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

    Science.gov (United States)

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

    2016-01-01

    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. 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). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). 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. 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.

  6. The association between renal sinus fat area and the progression-free survival in Chinese non-metastatic clear-cell renal cell carcinoma patients

    Science.gov (United States)

    Huang, Haichao; Chen, Shi; Yu, Wei; Ye, Zirong; Li, Wei; Xing, Jinchun; Wu, Xiurong

    2017-01-01

    In this retrospective study, we evaluated the association between renal sinus fat area (RSFA) and survival in 268 Chinese non-metastatic clear-cell renal cell carcinoma (ccRCC) patients. Patients with high RSFA exhibited better progression-free survival than those with low RSFA in both univariable (HR: 0.240; 95% CI: 0.119–0.482; p < 0.001) and multivariable (HR: 0.432; 95% CI: 0.369–2.749; p = 0.027) analyses. A propensity-score matched (PSM) analysis using Kaplan-Meier curves confirmed our findings (log-rank test; p = 0.028). Based on the multivariable analysis, we constructed a prognostic nomogram with 4 factors, namely, RSFA, Fuhrman grade, AJCC stage and sarcomatoid component. The c-index values for the Leibovich scoring system and the nomogram were 0.762 (95%CI, 0.688–0.835) and 0.823 (95%CI, 0.759–0.888), respectively. These findings demonstrate that high RSFA is associated with better progression-free survival in non-metastatic ccRCC. PMID:29029447

  7. [Sarcomatoid renal cell carcinoma].

    Science.gov (United States)

    Arnoux, V; Lechevallier, E; Pamela, A; Long, J-A; Rambeaud, J-J

    2013-06-01

    The objective was to perform a systematic review of literature concerning epidemiology, clinical and biological data, prognosis and therapy of sarcomatoid renal cell carcinomas. Data on sarcomatoid renal cell carcinomas have been sought by querying the server Medline with MeSH terms following or combination of them: "renal carcinoma", "renal cell carcinoma," "renal cancer", "sarcomatoid" "sarcomatoid transformation" and "sarcomatoid differentiation." The articles obtained were selected according to their methodology, the language in English or French, the relevance and the date of publication. Twenty papers were selected. According to the literature, a sarcomatoid contingent can be observed in all subtypes of renal cell carcinomas, with a frequency of 1 to 15% of cases. The median age at diagnosis was 60 years with a majority of symptomatic patients (90%), mainly with abdominal pain and hematuria. These tumors were often found in patients with locally advanced or metastatic (45-77%). The imaging was not specific for the diagnosis and biopsy had a low sensitivity for identifying a sarcomatoid contingent. The treatment was based on a combination of maximal surgical resection whenever possible and systemic therapy for metastastic disease. Pathological data often showed large tumors, Furhman 4 grades, combined biphasic carcinomatous contingent (clear cell carcinoma in most cases) and sarcomatoid. Genetically, there was no specific abnormality but a complex association of chromosomal additions and deletions. The prognosis was pejorative with a specific median survival of 5 to 19 months without any impact of the sarcomatoid contingent rate. Sarcomatoid renal cell carcinoma is a form not to ignore despite its rarity. Mainly symptomatic and discovered at an advanced stage, it has a poor prognosis, requiring multidisciplinary management quickly and correctly. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. Gingival squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Amit Walvekar

    2017-01-01

    Full Text Available Oral squamous cell carcinoma (OSCC is the most common epithelial malignancy affecting the oral cavity. The most common sites for the development are lateral surface of tongue and floor of mouth; the least common sites are soft palate, gingiva, and buccal mucosa. Gingival squamous cell carcinoma can mimic a multitude of oral lesions and enlargements, especially those of inflammatory origin. In addition, predisposing and presenting factors are different from those of other OSCCs. Careful examination as well as routine biopsy are crucial for accurate diagnosis.

  9. Type 1 plasminogen activator inhibitor (PAI-1 in clear cell renal cell carcinoma (CCRCC and its impact on angiogenesis, progression and patient survival after radical nephrectomy

    Directory of Open Access Journals (Sweden)

    Seidal Tomas

    2010-12-01

    Full Text Available Abstract Background To examine the expression of type 1 plasminogen inhibitor (PAI-1 in clear cell renal cell carcinoma (CCRCC, and its possible association with microvessel density (MVD, the expression of thrombospondin-1 (TSP-1, nuclear grade, tumour stage, continuously coded tumour size (CCTS and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy. Methods A total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43% died of RCC, while 47 patients (29% died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%. Results Nine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046 and directly with advanced stage (p = 0.008, high NG (3+4 (p = 0.002, tumour size (p = 0.011, microvessel density (p = 0.049 and disease progression (p = 0.002. In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS (p Conclusions PAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.

  10. Intraosseous acinic cell carcinoma

    African Journals Online (AJOL)

    2011-12-17

    Dec 17, 2011 ... provisional diagnosis of benign odontogenic tumor was given. Intraosseous acinic cell carcinoma. V Hiremath, N Mishra1, SG Patil2. Departments of Oral Pathology and 1Oral Medicine and Radiology, Mansarovar Dental College, Bhopal, 2 Department Of. Oral and Maxillofacial Surgery, H.K.E' S.N. Dental ...

  11. Ovarian Carcinoma Stem Cells

    Science.gov (United States)

    2009-05-01

    b- myb , is also highly expressed in both FNAR cells (3.33-fold) and human 1 ovarian carcinoma [37]. 2 High levels of interleukin-6 (IL-6), a...AW916991 3.56 Thioredoxin AW140607 3.07 Stathmin BF281472 3.23 b- myb RGIAC37 3.33 Gene Expression Profiling of FNAR Cells 8 9 10 25 1 2 3 4

  12. Inhibition of CIP2A attenuates tumor progression by inducing cell cycle arrest and promoting cellular senescence in hepatocellular carcinoma.

    Science.gov (United States)

    Yang, Xue; Qu, Kai; Tao, Jie; Yin, Guozhi; Han, Shaoshan; Liu, Qingguang; Sun, Hao

    2018-01-08

    CIP2A is a recent identified oncogene that inhibits protein phosphatase 2A (PP2A) and stabilizes c-Myc in cancer cells. To investigate the potential oncogenic role and prognostic value of CIP2A, we comprehensively analyzed the CIP2A expression levels in pan-cancer and observed high expression level of CIP2A in majority cancer types, including hepatocellular carcinoma (HCC). Based on a validation cohort including 60 HCC and 20 non-tumorous tissue samples, we further confirmed the high mRNA and protein expression levels of CIP2A in HCC, and found high CIP2A mRNA expression level was associated with unfavorable overall and recurrence-free survival in patients with HCC. Mechanistic investigations revealed that inhibition of CIP2A significantly attenuated cellular proliferation in vitro and tumourigenicity in vivo. Bioinformatic analysis suggested that CIP2A might be involved in regulating cell cycle. Our experimental data further confirmed CIP2A knockdown induced cell cycle arrest at G1 phase. We found accumulated cellular senescence in HCC cells with CIP2A knockdown, companying expression changes of senescence associated proteins (p21, CDK2, CDK4, cyclin D1, MCM7 and FoxM1). Mechanistically, CIP2A knockdown repressed FoxM1 expression and induced FoxM1 dephosphorylation. Moreover, inhibition of PP2A by phosphatase inhibitor rescued the repression of FoxM1. Taken together, our results showed that CIP2A was highly expressed in HCC. Inhibition of CIP2A induced cell cycle arrest and promoted cellular senescence via repressing FoxM1 transcriptional activity, suggesting a potential anti-cancer target for patients with HCC. Copyright © 2017. Published by Elsevier Inc.

  13. MUC1, a new hypoxia inducible factor target gene, is an actor in clear renal cell carcinoma tumor progression.

    Science.gov (United States)

    Aubert, Sébastien; Fauquette, Valérie; Hémon, Brigitte; Lepoivre, Réjane; Briez, Nicolas; Bernard, David; Van Seuningen, Isabelle; Leroy, Xavier; Perrais, Michaël

    2009-07-15

    The hypoxia inducible factor (HIF) signaling pathway is known as the main renal carcinogenetic pathway. MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in clear renal cell carcinomas (cRCC) with correlation to two major prognostic factors: tumor-node-metastasis stage and nuclear Fürhman grade. We questioned whether there is a direct link between the HIF pathway and MUC1 overexpression in renal tumors. Interestingly, we observed concomitant increase of HIF-1alpha and MUC1 in metastatic cRCC group versus nonmetastatic cRCC group. Using different renal cell models and small interfering RNA assays targeting either HIF-1alpha or YC-1, a HIF-1 pharmacologic inhibitor, we showed induction of MUC1 expression under hypoxia by a HIF-dependent mechanism. Chromatin immunoprecipitation assay showed a direct binding of HIF-1alpha at the MUC1 promoter. In addition, combined site-directed mutagenesis and gel shift assay allowed the identification of two functional putative hypoxia responsive elements at -1488/-1485 and at -1510/-1507 in the promoter. Using a rat kidney model of ischemia/reperfusion, we confirmed in vivo that clamping renal pedicle for 1 hour followed by 2 hours of reperfusion induced increased MUC1 expression. Furthermore, MUC1 knockdown induced significant reduction of invasive and migration properties of renal cancer cells under hypoxia. Altogether, these results show that MUC1 is directly regulated by HIF-1alpha and affects the invasive and migration properties of renal cancer cells. Thus, MUC1 could serve as a potential therapeutic target in cRCC.

  14. Actinic keratosis associated with squamous and basal cell carcinomas: an evaluation of neoplastic progression by a standardized AgNOR analysis

    Directory of Open Access Journals (Sweden)

    G Giuffrè

    2009-08-01

    Full Text Available In an attempt to investigate the neoplastic progression in different stages of actinic keratosis (AK, a standardized AgNOR analysis was performed in 94 cases of AK, 35 of which were associated with squamous cell carcinoma (SCC or basal cell carcinoma (BCC, and in 31 cases of SCC and 22 cases of BCC. The cases were subdivided into low- and high- AgNOR-expressing (AgNOR status AK by using the mean area of AgNORs per cell (NORA value (3.996 ?m2 as the cut-off. In AK samples, a progressive increase of the mean NORA value from Stage I to Stage IV was encountered. In addition, a significantly higher mean NORA value was found in the AK cases associated with SCC, in comparison to those without SCC; by contrast, no significant differences in the mean NORA value were noted between AK cases with or without BCC. A highly significant association between a high AgNOR quantity and the coexistence of SCC was encountered in AK; no association was appreciable between the AgNOR quantity and the co-occurrence of BCC. Moreover, when the co-existence of SCC in AK was considered as the reference point, the AK cases associated with SCC mostly (95.5% presented a high AgNOR quantity (high sensitivity, but only 57.6% of cases without SCC displayed a low AgNOR quantity (low specificity. Additionally, our data document that the standardised AgNOR analysis represents a strong negative predictor for the association between SCC and AK. Indeed, a low AgNOR quantity mostly is associated with AK cases without SCC.

  15. IncRNA H19 promotes tongue squamous cell carcinoma progression through β-catenin/GSK3β/EMT signaling via association with EZH2.

    Science.gov (United States)

    Zhang, Da-Ming; Lin, Zhao-Yu; Yang, Zhao-Hui; Wang, You-Yuan; Wan, Di; Zhong, Jiang-Long; Zhuang, Pei-Lin; Huang, Zhi-Quan; Zhou, Bin; Chen, Wei-Liang

    2017-01-01

    H19 is involved in tumor metastasis and associated with tumor progression. Enhancer of zest homolog 2 (EZH2) is overexpressed in multiple cancer types and correlates with tumor proliferation, epithelial-mesenchymal transition, and poor prognosis. However, the interaction between H19 and EZH2 to promote tongue squamous cell carcinoma (TSCC) progression remains largely uncharacterized. Insitu hybridization and quantitative reverse-transcription PCR (qRT-PCR) were performed to measure H19 expression in primary TSCC and adjacent normal tissues and cell lines. EZH2 expression was determined by immunohistochemistry in matched primary TSCC and adjacent normal tissues. The correlation between H19 and EZH2 expression and clinicopathological characteristics were analyzed. The roles of H19 in cell proliferation, apoptosis, and invasion were analyzed using a H19-targeted lentivirus. Western blot and qRT-PCR were carried out to detect downstream signal pathway changes. Expression levels of downstream signaling proteins in primary TSCC tissues and adjacent normal tissues were analyzed by immunohistochemistry. H19 and EZH2 were upregulated in TSCC tissues compared to matched normal tissues, and significantly correlated with WHO grade, lymph node metastasis, and poor prognosis. H19 silencing attenuated cell proliferation, apoptosis, and invasion in vitro. H19 knockdown inhibited the activation of β-catenin/GSK-3β/cyclin D1/c-myc, upregulated E-cadherin and zonula occludens-1 (ZO-1), and inhibited N-cadherin, vimentin, Snail1, Twist1, and ZEB1. Silencing H19 expression also inhibited tumor progression and lung metastasis in an animal model. Our findings indicate that H19 promotes TSCC progression through association with EZH2, and affects downstream β-Catenin/GSK3β/EMT signaling, suggesting that H19 inhibition might be a potential target for the treatment of TSCC.

  16. Relation of erythrocyte indices and serum iron level with clinical and histological progression of oral squamous cell carcinoma in Central India.

    Science.gov (United States)

    Anees Ahmed, Riyaz Ahmed; Ganvir, Sindhu M; Hazarey, Vinay K

    2014-02-01

    This study aims to evaluate the relation of erythrocyte indices and serum iron level with clinical and histopathological progression of oral squamous cell carcinoma (OSCC). Eighty newly diagnosed OSCC patients recruited for the study were divided according to tumor size int three groups. Erythrocyte indices (e.g., hemoglobin [Hb], red blood cell [RBC] count, packed cell volume [PCV]) and serum iron level (S.Fe) were evaluated with normal reference values, control subject, primary tumor size and histopathological grading. Correlation of Hb to S.Fe was also analyzed. We found that 56.36, 61.81, and 83.63% of males and 76, 32, and 88% of female patients were anemic in terms of Hb%, RBC count and PCV respectively, whereas the remainding indices and S.Fe were within normal range (P  0.05). Moderate to weak correlation was observed between Hb and S.Fe (P < 0.05). Tumor-induced hemolysis appeared to be responsible for anemia in OSCC and its severity increased with the progression of tumor. Moderate to weak correlation exists between Hb and S.Fe probably owing to the dual requirement of iron for bone marrow and the tumor. © 2012 Wiley Publishing Asia Pty Ltd.

  17. Serpin peptidase inhibitor clade A member 1 (SerpinA1) is a novel biomarker for progression of cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Farshchian, Mehdi; Kivisaari, Atte; Ala-Aho, Risto; Riihilä, Pilvi; Kallajoki, Markku; Grénman, Reidar; Peltonen, Juha; Pihlajaniemi, Taina; Heljasvaara, Ritva; Kähäri, Veli-Matti

    2011-09-01

    The incidence of keratinocyte-derived nonmelanoma skin cancers is increasing worldwide because of cumulative recreational exposure to sunlight. At present, no specific molecular markers are available for assessing the progression of premalignant actinic keratoses to invasive cutaneous squamous cell carcinoma (SCC). We examined the role of the Serpin family in skin SCCs. Expression profiling of cutaneous SCC cell lines (n = 8) revealed up-regulation of SerpinA1 compared with normal epidermal keratinocytes (n = 5). Analysis with quantitative RT-PCR showed that the mean level of SerpinA1 mRNA was markedly up-regulated in cutaneous SCC cell lines (n = 8) compared with in normal keratinocytes. SerpinA1 production by SCC cells was dependent on p38 mitogen-activated protein kinase activity and was up-regulated by epidermal growth factor, tumor necrosis factor-α, interferon-γ, and IL-1β. Immunostaining of tissue arrays with 148 human tissue samples revealed tumor cell-associated expression of SerpinA1 in 19 of 36 actinic keratoses, 22 of 29 Bowen's disease samples, 67 of 71 sporadic SCCs, and all 12 recessive dystrophic epidermolysis bullosa-associated SCCs examined. Moreover, tumor cell-associated SerpinA1 staining was detected in all chemically induced mouse skin SCCs studied (n = 17). Overexpression of SerpinA1 mRNA was also detected by quantitative RT-PCR in chemically induced mouse skin SCCs (n = 14) compared with control tissues (n = 14). These data identify SerpinA1 as a novel tumor cell-associated biomarker for progression of cutaneous SCCs. Copyright © 2011. Published by Elsevier Inc.

  18. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1)

    DEFF Research Database (Denmark)

    Machiels, Jean-Pascal H; Haddad, Robert I; Fayette, Jérôme

    2015-01-01

    BACKGROUND: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setti...

  19. Mechanistic attributes of S100A7 (psoriasin) in resistance of anoikis resulting tumor progression in squamous cell carcinoma of the oral cavity.

    Science.gov (United States)

    Dey, Kaushik Kumar; Sarkar, Siddik; Pal, Ipsita; Das, Subhasis; Dey, Goutam; Bharti, Rashmi; Banik, Payel; Roy, Joygopal; Maity, Sukumar; Kulavi, Indranil; Mandal, Mahitosh

    2015-01-01

    Squamous cell carcinoma of the oral cavity (SCCOC) is the dominant origin of cancer associated mortality. Previous findings by our study reported that acquisition of anoikis resistance has a significant role in tumor progression of oral cavity. Several genes were over-expressed in anoikis-resistant cells under detached conditions which we confirmed earlier by microarray. Normal oral squamous epithelia grow adherent to a basement membrane, and when detached from the extracellular matrix, undergoes programmed cell death. The acquisition of anoikis-resistance is crucial phenomena in oral tumor advancement. In the current study, we have identified S100A7 expression as contributing factor for anoikis resistance and tumorigenicity in human oral cancer cells. Further, we have explored that elevated S100A7 expression in anoikis-sensitive oral keratinocytes and cancer cells reshape them more resistant to anoikis and apoptosis inducers via activation of cellular intrinsic and extrinsic avenue. A subset of human cancer cell lines TU167, JMAR, JMARC39, JMARC42 and MDA-MB-468 were utilized for the generation of resistant stable cell lines. Further, immunohistochemistry, western blot and immunoprecipitation, assays of apoptosis, soft agar assay, orthotopic animal model and signaling elucidation were performed to establish our hypothesis. S100A7 gene is found to be responsible for anoikis resistance and tumorigenicity in human oral cancer cells. We have observed up-regulation of S100A7 in anoikis resistant cell lines, orthotropic model and patients samples with head and neck cancer. It is also noticed that secretion of S100A7 protein in conditioned medium by anoikis resistant head & neck cancer cell and in saliva of head and neck cancer patients. Up-regulation of S100A7 expression has triggered enhanced tumorigenicity and anchorage-independent growth of cancer cells through Akt phosphorylation leading to development of aniokis resistance in head and neck cancer cells. These data

  20. Rapid tumor progression in a patient with HPV type 16 associated anal squamous cell carcinoma suffering from long-standing Crohn's disease: A case report

    Directory of Open Access Journals (Sweden)

    Fischer AK

    2016-10-01

    Full Text Available Background and aim: Squamous cell carcinoma (SCC is the most common cancer of the anal region, typically associated with high-risk (hr HPV infection. Furthermore, there is evidence that Crohn's disease predisposes to adenocarcinoma in patients with perianal disease. Materials and methods: A 57-year old patient presenting with long history of Crohn's disease since the age of mid-twenties, went through several surgeries including ileocolectomy and anal fistula resection, combined with immunosuppressive therapy additionally periodically since 2008. One year before death (in 2015 a painful fistula was diagnosed with extensive high grade anal intraepithelial neoplasia (AIN-HG and evidence of invasive growth as non-keratinizing SCC. Tissue samples from several previous and current resection specimens were re-evaluated and extensively investigated for Crohn´s type inflammation, dysplasia and HPV both by immunohistochemistry (p16/Ki67 and molecular subtyping of HPV. Results: AIN-HG and invasive anal squamous cell carcinoma turned out to be strongly positive for p16/Ki67 staining and molecular analysis disclosed a HPV-16 subtype. In contrast, HPV-analysis was negative in all available previous tissue samples including one anal fistula resected five years before (in 2009 which was lined by non-keratinized squamous epithelium without any evidence of dysplasia. Thus, the patient was diagnosed as Crohn's disease with hr-HPV infection that rapidly (< 5ys progressed to AIN-HG and anal SCC. Finally, osseous metastases occurred and the patient died shortly after. Conclusions: This case of a patient diagnosed with SCC of the anal canal in combination with Crohn's disease as well as HPV Type 16 infection, points to the pathomechanism leading to dysplasia and finally cancer. We assume that immunosuppressive therapy in Crohn's disease may predispose to both persistent HPV infection and HPV related invasive anal carcinoma. The accelerated progression of HPV

  1. Merkel cell carcinoma

    Directory of Open Access Journals (Sweden)

    Koljonen Virve

    2006-02-01

    Full Text Available Abstract 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.

  2. Molecular characterization and clinical implications of spindle cells in nasopharyngeal carcinoma: a novel molecule-morphology model of tumor progression proposed.

    Directory of Open Access Journals (Sweden)

    Weiren Luo

    Full Text Available Up to now, the precise molecular and morphological changes underlying the invasive and metastatic properties of nasopharyngeal carcinoma (NPC remain largely unresolved. We speculate that neoplastic spindle cells, which are prominently found in the invasive tumor front and the surrounding stroma, might be responsible for the aggressive patterns. Expression profiling of various biomarkers relevant to cancer stem cells (CSCs and epithelial-mesenchymal transition (EMT was performed by tissue microarray-based immunohistochemistry in NPC samples. The expression of EBER and LMP1 was detected by in situ hybridization and immunohistochemistry, respectively. We found that overexpression of CSCs-related markers (ALDH1, Nanog and ABCG2 and up-regulation of EMT markers (Fibronectin, MMP-2, Periostin, SPARC, Snail and Slug, together with E- to N-cadherin switching, occurred preferentially in tumors containing a large proportion of spindle-shaped malignant cells. Furthermore, CSCs-like properties were highly present in spindle cells compared with non-spindle cells of tumors, and correlated strongly with EMT features. In addition, EBV-related factors EBER and LMP1 were highly expressed and correlated strongly with CSCs and EMT characteristics in neoplastic spindle cells. Importantly, high proportion of spindle cells (≥20% correlated significantly with various aggressive aspects including lymph node metastasis (P = 0.031 and local recurrence (P = 0.014. Patients with high proportion of spindle cells had poor survival (P = 0.004, though it was not an independent value. In conclusion, we demonstrate that spindle cells could be valuable morphological indicators of tumor progression and unfavorable prognosis of NPC. An integrated molecule-morphology model of NPC firstly constructed may shed significant light on the metastatic cascade and clinical relevance of patients.

  3. Paxillin promotes tumor progression and predicts survival and relapse in oral cavity squamous cell carcinoma by microRNA-218 targeting.

    Science.gov (United States)

    Wu, De-Wei; Chuang, Chun-Yi; Lin, Wea-Long; Sung, Wen-Wei; Cheng, Ya-Wen; Lee, Huei

    2014-08-01

    High-risk human papillomavirus (HPV) 16-infected oral cavity squamous cell carcinoma (OCSCC) differs significantly from non-HPV-infected OCSCC. However, the molecular pathogenesis of HPV-infected OCSCC remains unclear. Paxillin (PXN) has been reported to promote lung tumor progression by miR-218 targeting. In addition, expression of miR-218 has been shown to be reduced by HPV16 E6 in cervical cancer. We thus asked whether PXN can promote tumor progression by E6-reduced miR-218 in OCSCC, especially in HPV-infected OCSCC. Mechanistic studies demonstrated that PXN expression increased markedly upon E6-mediated reductions in miR-218, resulting in increased colony formation and invasion capabilities in HPV-infected OCSCC cells. Among tumor specimens, HPV16/18 infection was negatively associated with miR-218 expression and positively associated with PXN expression. Kaplan-Meier and Cox regression models demonstrated that patients with low-miR-218 tumors or high-PXN tumors exhibited shorter overall survival (OS) and relapse-free survival (RFS) than those with high-miR-218 tumors or low-PXN tumors. Interestingly, HPV-infected patients with low-miR-218, high-PXN tumors and both combinations exhibited the worst OS and RFS compared with patients in their counterparts. These observations in patients were consistent with the findings from the cell model. Therefore, we suggest that PXN might be targeted to suppress tumor progression and consequently to improve outcomes in OCSCC, especially in HPV-infected OCSCC. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Penis squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Leonor Hernández Piñero

    2015-09-01

    Full Text Available Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagnosed belatedly. Partial amputation of the penis was considered to be performed, but there was no consent on behalf of his family. The patient’s general condition was getting worse until he died.

  5. Perianal Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Isil Bulur

    2015-02-01

    Full Text Available 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.

  6. Perianal Basal Cell Carcinoma

    Science.gov (United States)

    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

  7. Lobomycosis and squamous cell carcinoma*

    Science.gov (United States)

    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

  8. Red Dot Basal Cell Carcinoma

    Science.gov (United States)

    2017-01-01

    Red dot basal cell carcinoma, a distinctive morphologic variant of basal cell carcinoma that presents as a small red macule (dot) or papule, is described on a woman’s thigh. A high index of suspicion is necessary to consider the diagnosis since the tumor mimics a telangiectasia or an angioma. PMID:28670359

  9. Analysis of the Fibrinogen and Neutrophil-Lymphocyte Ratio in Esophageal Squamous Cell Carcinoma: A Promising Blood Marker of Tumor Progression and Prognosis.

    Science.gov (United States)

    Arigami, Takaaki; Okumura, Hiroshi; Matsumoto, Masataka; Uchikado, Yasuto; Uenosono, Yoshikazu; Kita, Yoshiaki; Owaki, Tetsuhiro; Mori, Shinichiro; Kurahara, Hiroshi; Kijima, Yuko; Ishigami, Sumiya; Natsugoe, Shoji

    2015-10-01

    Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies in gastrointestinal tract cancers and even patients with early ESCC have a high metastatic potential. Difficulties are associated with clinically predicting tumor progression and prognosis based on conventional tumor markers determined from preoperative blood examinations. The aim of the present study was to measure plasma fibrinogen levels and the neutrophil-lymphocyte ratio (NLR) in blood and compare the clinical impacts of their combined values (fibrinogen and neutrophil-lymphocyte ratio score-F-NLR score) and the modified Glasgow Prognostic Score (mGPS) in patients with ESCC.We classified 238 patients with ESCC based on cut-off values for hyperfibrinogenemia (>400 mg/dL) and high NLR (>3.0) as F-NLR scores of 2 (both of these hematological abnormalities), 1 (one of these abnormalities), or 0 (neither abnormality). We also categorized patients based on cut-off values for high C-reactive protein (CRP) (>0.5 mg/dL) and hypoalbuminemia (analysis identified the depth of tumor invasion, lymph node metastasis, and F-NLR score as independent prognostic factors (P = 0.002, P = 0.007, and P = 0.037, respectively).The results of the present study showed that the F-NLR score is a promising blood predictor for tumor progression and outcomes in patients with ESCC.

  10. Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis.

    Science.gov (United States)

    Yan, Xin-Long; Jia, Ya-Li; Chen, Lin; Zeng, Quan; Zhou, Jun-Nian; Fu, Chun-Jiang; Chen, Hai-Xu; Yuan, Hong-Feng; Li, Zhi-Wei; Shi, Lei; Xu, Ying-Chen; Wang, Jing-Xue; Zhang, Xiao-Mei; He, Li-Juan; Zhai, Chao; Yue, Wen; Pei, Xue-Tao

    2013-06-01

    Cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)-155 in HCC cells was significantly up-regulated by coculture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the down-regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. S100A4 secreted from LC-MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013). Copyright © 2013 American Association for the Study of Liver Diseases.

  11. Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jonathan A Ewald

    Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

  12. Renal cell carcinoma with melanin pigment

    Science.gov (United States)

    Shetty, Jayaprakash; Chandrika; Laxman, Prabhu

    2010-01-01

    The incidence of renal cell carcinoma has been steadily increasing. There are several morphological types of renal cell carcinoma. Recognizing histologic patterns of renal cell carcinoma is important for correct diagnosis and subsequent medical care for the patient. Melanotic tumors in the kidney are very rare. Here, we present an unusual case of renal cell carcinoma with melanin pigment. PMID:20877613

  13. [Breast carcinoma metastasis into a renal cell carcinoma].

    Science.gov (United States)

    Perrin, Christophe; Talarmin, Marie; Fontaine, Aurélie; Kerbrat, Pierre; Audrain, Odile; Rioux-Leclercq, Nathalie; Chiforeanu, Dan Cristian

    2011-10-01

    We report the case of a patient carrying a right breast carcinoma whose imaging exams showed lung and bone metastasic release, and incidentally synchronous right renal tumor. Histologic examination of the renal tumor found a mammary carcinoma metastasis into a clear renal cell carcinoma. This is the second case report of breast cancer with metastasis in a resected renal clear cell carcinoma. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  14. Synchronous thyroid carcinoma and squamous cell carcinoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Seo [Chonnam National Univ. School of Dentistry, Kwangju (Korea, Republic of)

    2006-12-15

    Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (SCC) is unusual. This report presents a synchronous thyroid carcinoma and squamous cell carcinoma in the anterior palate region of a 41-year-old man. The clinical, radiologic, and histologic features are described. At 10-month follow-up after operation, no evidence of recurrence ana metastasis was present.

  15. Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    De Velasco, Guillermo; Xie, Wanling; Donskov, Frede

    2017-01-01

    BACKGROUND: A significant subgroup of metastatic renal cell carcinoma (mRCC) patients discontinue vascular endothelial growth factor-targeted therapies (VEGF-TT) because of toxicity. Whether clinical outcomes differ in patients who receive second-line (2L) targeted therapy on the basis of reason ...

  16. Lysyl oxidase-like 2 represses Notch1 expression in the skin to promote squamous cell carcinoma progression

    Science.gov (United States)

    Martin, Alberto; Salvador, Fernando; Moreno-Bueno, Gema; Floristán, Alfredo; Ruiz-Herguido, Cristina; Cuevas, Eva P; Morales, Saleta; Santos, Vanesa; Csiszar, Katalin; Dubus, Pierre; Haigh, Jody J; Bigas, Anna; Portillo, Francisco; Cano, Amparo

    2015-01-01

    Lysyl oxidase-like 2 (LOXL2) is involved in a wide range of physiological and pathological processes, including fibrosis and tumor progression, implicating intracellular and extracellular functions. To explore the specific in vivo role of LOXL2 in physiological and tumor contexts, we generated conditional gain- and loss-of-function mouse models. Germ-line deletion of Loxl2 promotes lethality in half of newborn mice mainly associated to congenital heart defects, while Loxl2 overexpression triggers male sterility due to epididymal dysfunction caused by epithelial disorganization, fibrosis and acute inflammation. Remarkably, when challenged to chemical skin carcinogenesis, Loxl2-overexpressing mice increased tumor burden and malignant progression, while Loxl2-deficient mice exhibit the opposite phenotypes. Loxl2 levels in premalignant tumors negatively correlate with expression of epidermal differentiation markers and components of the Notch1 pathway. We show that LOXL2 is a direct repressor of NOTCH1. Additionally, we identify an exclusive expression pattern between LOXL2 and members of the canonical NOTCH1 pathway in human HNSCC. Our data identify for the first time novel LOXL2 roles in tissue homeostasis and support it as a target for SCC therapy. PMID:25759215

  17. Interpreting overall survival results when progression-free survival benefits exist in today's oncology landscape: a metastatic renal cell carcinoma case study

    Directory of Open Access Journals (Sweden)

    Tang Y

    2014-09-01

    Full Text Available Yiyun Tang,1 Paul Bycott,1 Örjan Åkerborg,2 Linus Jönsson,2 Sylvie Negrier,3 Connie Chen4 1Pfizer Global Research and Development, La Jolla, CA, USA; 2OptumInsight, Stockholm, Sweden; 3Medical Oncology Department, University of Lyon, Lyon, France; 4Pfizer Global Outcomes Research, New York, NY, USA Background: The debate surrounding the acceptance of progression-free survival (PFS as an intermediate endpoint to overall survival (OS has grown in recent years, due to the challenges in demonstrating an OS benefit within clinical trials today. PFS is generally a good predictor of OS for cases where survival post-progression (SPP is short, and less so when SPP is long. SPP depends on multiple factors, including residual effect from experimental treatment and effect from crossover or other subsequent therapies, posing unique challenges into the translation of PFS benefit into OS. Methods: The objective of this analysis was to conduct simulations investigating how increasing SPP impacts PFS translation to OS, utilizing data from the AXIS (axitinib versus sorafenib in advanced metastatic renal cell carcinoma trial. The underlying assumption was a treatment benefit in PFS (the PFS distribution parameters were chosen to be equal to median PFS in the AXIS trial but no treatment effect on SPP, implying that PFS improvement is directly reflected in OS improvement. Results: The probability of a statistically significant difference between arms for OS decreased from 54.7% to 6.1% when median SPP was increased from one to 20 months. The probability of the hazard ratio of OS being ≥0.9 was similarly increased from 24.3% to 72.6%, even though the hazard ratio for PFS was 0.69. Conclusion: The present study shows that when simulated SPP is added to trial PFS data, the existing PFS benefit is diluted. Knowing that the AXIS treatment arms are well balanced with respect to post-trial treatments, we conclude that the PFS to OS benefit translation is primarily

  18. Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Lildballe, Dorte Launholt; Nguyen, Khoa Tran; Poulsen, Steen Seier

    2011-01-01

    No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker....

  19. Simultaneous Laryngeal Squamous Cell Carcinoma and Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Bighan Khademi

    2011-04-01

    Full Text Available The association of squamous cell carcinoma of the larynx with thyroid papillary carcinoma is an unusual finding. From 2004 to 2011, approximately 250 patients underwent laryngectomies due to squamous cell carcinoma of the larynx at the Otolaryngology Department of Khalili Hospital, affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. In three patients, synchronous occurrence of squamous cell carcinoma and thyroid papillary carcinoma was found. Histopathologic study of the lymph nodes revealed metastatic papillary thyroid carcinoma in one case. We report three cases of thyroid papillary carcinoma incidentally found on histological examinations of resected thyroid lobes, as a procedure required for treatment of head and neck squamous cell carcinoma. In comparison, laryngeal squamous cell carcinoma needs more aggressive treatment than well-differentiated thyroid carcinoma. The prevalence of thyroid papillary carcinoma, as an incidental finding in our study was 0.01%. Therefore, preoperative evaluation of the thyroid gland by ultrasonography and fine needle aspiration biopsy of suspicious lesions is recommended in patients who are candidates for open laryngectomy.

  20. Nevoid Basal Cell Carcinoma Syndrome

    Directory of Open Access Journals (Sweden)

    F Handa

    1985-01-01

    Full Text Available A 65 years old male developed nevoid basal cell carcinoma syndrome, manifesting as multiple basal cell epitheliomas, marked mutilation of the face and characteristic pitting on the palms and soles. Calcification of the falx cerebri and scoliosis of the lumbar spine were also seen.

  1. The role of mast cells in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Swetha Gudiseva

    2017-03-01

    Full Text Available The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment. The current paper reviewed research papers on mast cells in oral squamous cell carcinoma through the PubMed database from 1980 to the present date. The present paper is an attempt to summarise the research reports on the role of mast cells in oral squamous cell carcinoma. Further to this note, this paper also outlines the role of mast cells in normal physiological processes and tumour biology.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    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

  4. Cardiac Metastasis in Renal Cell Carcinoma

    African Journals Online (AJOL)

    abp

    2015-10-21

    Oct 21, 2015 ... following: pleural mesothelioma (48.4%), melanoma (27.8%), lung adenocarcinoma (21%), undifferentiated carcinomas (19.5%), lung squamous cell carcinoma (18.2%) and breast carcinoma (15.5%). High rates of heart metastatisation have also been observed in patients affected by ovarian carcinoma ...

  5. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda Plovmand

    2016-01-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  6. Research progress in c-Met and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    WANG Changqing

    2015-06-01

    Full Text Available c-Met plays a pivotal role in the development and progression of hepatocellular carcinoma (HCC, which can lead to proliferation, survival, cytoskeleton reorganization, separation and diffusion, and angiogenesis of tumor cells. Moreover, c-Met is an important prognostic factor for HCC. In HCC, c-Met acts as an activator of a series of signaling pathways, including PI3K/AKT/mTOR, ERK/MAPK, and Rac-Pak. In recent years, it has been reported that small-molecule kinase inhibitors can abolish phosphorylation at the intracellular carboxyl terminal of c-Met, and then inhibit the recruitment of signal convertors and downstream signaling pathways, which finally achieve anti-tumor activities. Based on the carcinogenic activity of c-Met in HCC, this paper points out that selective inhibitors of c-Met hold promise for targeted therapies for HCC.

  7. Basal cell carcinoma-treatment with cryosurgery

    Directory of Open Access Journals (Sweden)

    Kaur S

    2003-03-01

    Full Text Available Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  8. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  9. Retroperitoneal Cystic Metastases from Renal Cell Carcinoma

    OpenAIRE

    Rastogi Rajul

    2008-01-01

    Many malignant tumors produce retroperitoneal nodal metastases. However, cystic nodal retroperitoneal metastases are uncommon. Renal cell carcinoma is one of the very few carcinomas that can infrequently produce cystic nodal retroperitoneal metastases. Hence, This is a case of retroperitoneal cystic nodal metastases secondary to renal cell carcinoma, which has been rarely reported in the medical literature

  10. Keratinising Squamous cell carcinoma- A rarity

    Directory of Open Access Journals (Sweden)

    Akheel Mohammad

    2016-01-01

    Full Text Available Keratocystic odontogenic tumor (KCOT is still a dilemma in the field of medical science because of its biological behavior and transformation of this benign odontogenic tumor to a carcinomatous type, which is called as odontogenic carcinoma. We are presenting here a case of squamous cell carcinoma occurring in recurrent KCOT of temporal region. The rarity of this article is the location of the lesion which is rarest at temporal region. Malignant transformation of these KCOT′s has been reported only in 15 cases in literature, the majority occurring in jaws but no case reported for lesion of temporal region. The pathogenesis of the tumor, the biologic progression, overall clinical, and histopathological features of this rare malignancy, and its management is reported and discussed.

  11. Lactobacillus decelerates cervical epithelial cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Katarina Vielfort

    Full Text Available We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells.

  12. Fructose-1,6-bisphosphatase opposes renal carcinoma progression.

    Science.gov (United States)

    Li, Bo; Qiu, Bo; Lee, David S M; Walton, Zandra E; Ochocki, Joshua D; Mathew, Lijoy K; Mancuso, Anthony; Gade, Terence P F; Keith, Brian; Nissim, Itzhak; Simon, M Celeste

    2014-09-11

    Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is characterized by elevated glycogen levels and fat deposition. These consistent metabolic alterations are associated with normoxic stabilization of hypoxia-inducible factors (HIFs) secondary to von Hippel-Lindau (VHL) mutations that occur in over 90% of ccRCC tumours. However, kidney-specific VHL deletion in mice fails to elicit ccRCC-specific metabolic phenotypes and tumour formation, suggesting that additional mechanisms are essential. Recent large-scale sequencing analyses revealed the loss of several chromatin remodelling enzymes in a subset of ccRCC (these included polybromo-1, SET domain containing 2 and BRCA1-associated protein-1, among others), indicating that epigenetic perturbations are probably important contributors to the natural history of this disease. Here we used an integrative approach comprising pan-metabolomic profiling and metabolic gene set analysis and determined that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) is uniformly depleted in over six hundred ccRCC tumours examined. Notably, the human FBP1 locus resides on chromosome 9q22, the loss of which is associated with poor prognosis for ccRCC patients. Our data further indicate that FBP1 inhibits ccRCC progression through two distinct mechanisms. First, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cell of origin, thereby inhibiting a potential Warburg effect. Second, in pVHL (the protein encoded by the VHL gene)-deficient ccRCC cells, FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. This unique dual function of the FBP1 protein explains its ubiquitous loss in ccRCC, distinguishing FBP1 from previously identified tumour suppressors that are not consistently mutated in all tumours.

  13. The predictive value of p53, p27(kip1), and alpha-catenin for progression in superficial bladder carcinoma.

    NARCIS (Netherlands)

    Schrier, B.P.; Vriesema, J.L.J.; Witjes, J.A.; Kiemeney, L.A.L.M.; Schalken, J.A.

    2006-01-01

    OBJECTIVE: The aim of the study was to confirm the predictive value of cell cycle regulatory proteins, p53 and p27(kip1), and the cell adhesion complex protein alpha-catenin, for progression in patients with superficial bladder carcinoma. METHODS: Forty-one patients with progression after primary

  14. Small cell glioblastoma or small cell carcinoma

    DEFF Research Database (Denmark)

    Hilbrandt, Christine; Sathyadas, Sathya; Dahlrot, Rikke H

    2013-01-01

    was admitted to the hospital with left-sided loss of motor function. A MRI revealed a 6 cm tumor in the right temporoparietal area. The histology was consistent with both glioblastoma multiforme (GBM) and small cell lung carcinoma (SCLC) but IHC was suggestive of a SCLC metastasis. PET-CT revealed...

  15. Nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Kannan Karthiga

    2006-01-01

    Full Text Available 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.

  16. Photodynamic therapy for basal cell carcinoma.

    Science.gov (United States)

    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.

  17. Knocking-down of CREPT prohibits the progression of oral squamous cell carcinoma and suppresses cyclin D1 and c-Myc expression.

    Directory of Open Access Journals (Sweden)

    Juntao Ma

    Full Text Available As a regulator essential for many cell cycle-related proteins, the robust expression of Cell cycle-Related and Expression-elevated Protein in Tumor (CREPT implicates a poor diagnosis of endoderm and mesoderm-derived tumors. Whether CREPT plays the same role in the tumorigenesis derived from ectodermal tissues remains elusive.To explore the role of CREPT in ectoderm-derived tumors, cells from 7oral squamous cell carcinoma (OSCC lines and 84clinical OSCC samples were exploited in this study. Quantitative PCR, Western blot assay and immunohistochemistry were applied in the evaluation of CREPT, cyclin D1 and c-Myc expression. Knocking-down of CREPT was performed by lentivirus delivering specific shRNA of CREPT. The effects of CREPT on OSCC were examined by cell proliferation, colony formation, apoptosis, cell migration and xenograft implantation experiments.Compared with human normal oral keratinocytes, OSCC cell lines showed a significantly elevated expression of CREPT in both mRNA and protein levels. Consistently, samples from OSCC patients also exhibited a noticeably stronger CREPT expression than the noncancerous samples. In contrast, knocking down of CREPT in OSCC cell lines significantly reduced proliferation, colony formation and migration as well as the expression of cyclin D1 and c-Myc, but promoted apoptosis. Statistical analysis also suggested that CREPT expression was significantly correlated with the T and N classification of OSCC. Furthermore, CAL27 mouse xenograft model confirmed that down-regulation of CREPT prohibited cyclin D1 and c-Myc expression, through which decreased the in vivo tumor growth, but increased the survival ratio of hosts.In OSCC cell lines, up-regulated CREPT expression enhanced cell proliferation, migration and cell cycle as well as promoted cyclin D1 and c-Myc expression as it did in endoderm and mesoderm-origin tumors. Our study strongly suggests that CREPT could be used as a marker for the OSCC prognosis and

  18. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    National Research Council Canada - National Science Library

    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...

  19. Targeted Therapy for Renal Cell Carcinoma.

    Science.gov (United States)

    Joshi, R; Rawal, S

    2015-01-01

    Our study aims to evaluate the use of targeted therapy in metastatic renal cell carcinoma Methods: This is a prospective study done over three years from December 2010 to December, 2013.Out of Forty seven patients of metastatic renal cell carcinoma 8(neo-adjuvant cases) were excluded and 39 were included in this study. All patients received Tyrosine kinase inhibitor, sunitinib therapy (50 mg OD, 4/2 scheme). All 39 patients underwent radical nephrectomy prior to sunitinib therapy. Patients were followed up every cycle for their clinical symptoms following sunitinib therapy and every 3 months with chest X-ray, ultra-sonography and bone scan. CT scan was done if needed. A RECIST criterion was used to evaluate the complete, partial and no tumor response. The median survival was 28.5 months (CI 9.253-47.7) and progression free survival (PFS) was 9.16 months(CI 6.08-12.23).According to RECIST, stable disease was found in 6 patients till date and a complete response in two patients. Clear cell histology was found in 30(76.9%) patients, papillary variety in 6(15.39%) patients, chromophobe type was seen in one patient and rest had mixed sarcomatoid papillary and rhabdoid clear cell variety. Twenty four patients (61.5%) had multiple metastases. Most frequent metastasis was seen in lungs in 14 patients (36%) and bone in 12 patients (31%).Metastases were also seen in draining lymph nodes, adrenals, omentum,skin, liver, and brain. In our cohort, use of sunitinib showed similar outcome to previously published articles. Our study supports the use of sunitinib in metastatic renal cell carcinoma.

  20. Sustained systemic response paralleled with ovarian metastasis progression by sunitinib in metastatic renal cell carcinoma: Is this an anti-angiogenic potentiation of cancer?

    Directory of Open Access Journals (Sweden)

    Uttam K Mete

    2015-01-01

    Full Text Available Metastatic renal cell cancer is associated with poor prognosis and survival and is resistant to conventional chemotherapy. Therapeutic targeting of molecular pathways for tumor angiogenesis and other specific activation mechanisms offers improved tumor response and prolonged survival. A 48-year-old, female patient presented with large right renal mass with features suggesting of renal cell cancer without metastasis on contrast enhanced computed tomography (CT. Right radical nephrectomy was done. After 9 months of surgery, she got metastasis in lung, liver and ovary. The patient received sunitinib via an expanded access program. After eight 6-week cycles of sunitinib, a reassessment CT scan confirmed an excellent partial response with the almost complete disappearance (90% of liver and lung metastasis but the adnexal mass had increased in size (>10 times and the possibility was thought of second malignancy. Excision of the mass performed. Histopathology of the mass depicted metastatic renal cell cancer. There is possibility of a ′site-specific anti-angiogenic potentiation mechanism′ of malignancy in relation to sunitinib based upon the preclinical studies, in reference to the index case. Regression of one site with concurrent progression is possible. The exact mechanism of site-specific response, especially organ specific progression by vascular endothelial growth factor inhibitors in metastatic renal cell cancer warrants further study.

  1. Immunohistochemical distinction of ocular sebaceous carcinoma from basal cell and squamous cell carcinoma.

    Science.gov (United States)

    Sinard, J H

    1999-06-01

    Diagnosis of sebaceous carcinoma of the periorbital region is often delayed. Clinically, this lesion can mimic several inflammatory disorders. Histopathologically, it can mimic either squamous cell or basal cell carcinoma. To identify an immunohistochemical approach to assist in the diagnosis of periorbital sebaceous carcinoma. The immunohistochemical profiles of several cases of periorbital sebaceous, basal cell, and squamous cell carcinoma were examined. Although at least focal epithelial membrane antigen (EMA) staining can effectively distinguish sebaceous carcinoma (10 of 11 were positive) from basal cell carcinoma (1 of 16 were positive), most squamous cell carcinomas examined were also focally EMA positive (11 of 14). However, Cam 5.2 reactivity was seen in most sebaceous carcinomas (8 of 11) but no squamous cell carcinomas (0 of 14). In addition, at least focal BRST-1 reactivity was also seen in most sebaceous carcinomas (7 of 11) but no basal cell carcinomas (0 of 16). Periorbital sebaceous, basal cell, and squamous cell carcinomas have different immunohistochemical staining profiles; a panel of commonly available antibodies, including anti-EMA, BRST-1, and Cam 5.2, may help distinguish these diseases from each other when that distinction cannot be clearly made by light microscopy alone.

  2. Hürthle cell carcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Ahmadi S

    2016-11-01

    Full Text Available Sara Ahmadi,1 Michael Stang,2 Xiaoyin “Sara” Jiang,3 Julie Ann Sosa2,4,5 1Division of Endocrinology, Department of Medicine, 2Section of Endocrine Surgery, Department of Surgery, 3Department of Pathology, Duke University Medical Center, 4Duke Cancer Institute, 5Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA Abstract: Hürthle cell carcinoma (HCC can present either as a minimally invasive or as a widely invasive tumor. HCC generally has a more aggressive clinical behavior compared with the other differentiated thyroid cancers, and it is associated with a higher rate of distant metastases. Minimally invasive HCC demonstrates much less aggressive behavior; lesions <4 cm can be treated with thyroid lobectomy alone, and without radioactive iodine (RAI. HCC has been observed to be less iodine-avid compared with other differentiated thyroid cancers; however, recent data have demonstrated improved survival with RAI use in patients with HCC >2 cm and those with nodal and distant metastases. Patients with localized iodine-resistant disease who are not candidates for a wait-and-watch approach can be treated with localized therapies. Systemic therapy is reserved for patients with progressive, widely metastatic HCC. Keywords: thyroid cancer, thyroid nodule, follicular cell carcinoma, Hurthle cell lesion, minimally invasive HCC

  3. Hybrid clear cell odontogenic carcinoma and ameloblastic ...

    African Journals Online (AJOL)

    Clear cell odontogenic carcinoma (CCOC) which was previously designated clear cell odontogenic tumor also exhibits an aggressive biologic behavior and a tendency to metastasize to distant locations. Both lesions are rare. We report an odontogenic carcinoma with a dual histomorphologic feature of CCOC and AC ...

  4. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)

    2012-01-01

    textabstractThere are many different cutaneous malignancies, but malignant melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent approximately 98% of all skin cancers.In literature, these three skin cancers are often divided into melanoma and nonmelanoma skin cancers

  5. Hybrid clear cell odontogenic carcinoma and ameloblastic ...

    African Journals Online (AJOL)

    Ameloblastic carcinoma (AC) produces extensive local destruction, perforation of the cortical plate, extension into surrounding soft tissues, numerous recurrent lesions, and metastasis, usually to cervical lymph nodes. Clear cell odontogenic carcinoma (CCOC) which was previously designated clear cell odontogenic tumor ...

  6. Current Aspects on Oral Squamous Cell Carcinoma

    OpenAIRE

    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.

  7. Surgical treatment of basal cell carcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Gualdi, G; Monari, P; Apalla, Z; Lallas, A

    2015-08-01

    Non melanoma skin cancers (NMSC) are the most common human neoplasms, encompassing basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but also cutaneous lymphomas, adnexal tumors, merckel cell carcinoma and other rare tumors. The incidence of BCC and SCC varies significantly among different populations, and the overall incidence of both tumors has increased over the last decades. Although generally associated with a favorable prognosis, recent evidence suggests that the mortality rates of SCC might have been underestimated up-to-date.1 According to Medicare data, NMSC is the fifth most expensive cancer for health care systems. This increased economic burden is not associated with the cost of treating an individual patient, but with the large number of affected patients and the recurrence rates.2 Therefore, the adequate management of the primary tumor with a complete excision becomes a priority not only for the patient but also for the public health systems. Multiple treatment modalities are currently usedin clinicalpractice for the treatment of NMSC. While surgical excision (SE) remains the gold standard of care, non-surgical techniques have gained appreciation due to lower morbidity and better cosmetic results. The optimal management of treatment includes a complete tumor clearance, preservation of the normal tissue function, and the best possible cosmetic outcome.3 Surgery with a predefined excision margin is the treatment of choice for most NMSCs, with Mohs micrographic surgery being recommended for tumors considered to be at a higher recurrence risk or those developing on cosmetically sensitive areas.4, 5 Therefore, the surgical approach of a NMSC consists with three different and equally important steps. First the preoperative clinical assessment of the tumor margins, which can be facilitated by the use of dermoscopy. Second, the definition of the surgical margins depending on the tumor subtype and its biological behavior. Finally, the surgical

  8. Expression of ANO1/DOG1 is associated with shorter survival and progression of breast carcinomas.

    Science.gov (United States)

    Bae, Jun Sang; Park, Jeong Yeol; Park, See-Hyoung; Ha, Sang Hoon; An, Ae Ri; Noh, Sang Jae; Kwon, Keun Sang; Jung, Sung Hoo; Park, Ho Sung; Kang, Myoung Jae; Jang, Kyu Yun

    2018-01-02

    The expression of ANO1 is considered to have diagnostic specificity for gastrointestinal stromal tumors. However, its function as a calcium-activated chloride channel suggests that the expression of ANO1 is not restricted to gastrointestinal stromal tumors. Recently, it has been reported that ANO1 has roles in the progression of human malignant tumors. However, the role of ANO1 in breast carcinoma has been controversial. Therefore, we investigated the expression of ANO1 in 139 breast carcinoma patients and the role of ANO1 in vitro . The immunohistochemical expression of ANO1 was significantly associated with the expression of β-catenin, cyclin D1, MMP9, snail, and E-cadherin. Especially, ANO1 expression was an independent indicator of poor prognosis of shorter overall survival and relapse-free survival of breast carcinoma patients by multivariate analysis. In MCF7 and MDA-MB-231 breast carcinoma cells, inhibition of ANO1 with T16Ainh-A01 or siRNA for ANO1 significantly suppressed the proliferation of cells. Knock-down of ANO1 with siRNA induced G0/G1 cell cycle arrest and significantly inhibited the invasiveness of breast carcinoma cells. Knock-down of ANO1 decreased the expression of β-catenin, cyclin D1, MMP9, snail, and N-cadherin, and increased the expression of E-cadherin. In conclusion, this study demonstrates that ANO1 expression is an indicator of poor prognosis of breast carcinoma patients and suggests that ANO1 might be a therapeutic target for breast carcinoma patients with ANO1-positive tumors and poor prognosis.

  9. Metastatic Basal Cell Carcinoma: A Biological Continuum of Basal Cell Carcinoma?

    Directory of Open Access Journals (Sweden)

    Karaninder S. Mehta

    2012-01-01

    Full Text Available Basal cell carcinoma (BCC accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide surgical excision of a pathologically diagnosed basal cell carcinoma. The recurrence was diagnosed as infiltrative BCC and found metastasizing to skin, soft tissue and muscles, and pretracheal and axillary lymph nodes. Three cycles of chemotherapy comprising intravenous cisplatin (50 mg and 5-florouracil (5-FU, 750 mg on 2 consecutive days and repeated at every 21 days were effective. As it remains unclear whether metastatic BCC is itself a separate subset of basal cell carcinoma, we feel that early BCC localized at any site perhaps constitutes a biological continuum that may ultimately manifest with metastasis in some individuals and should be evaluated as such. Long-standing BCC is itself potentially at risk of recurrence/dissemination; it is imperative to diagnose and appropriately treat all BCC lesions at the earliest.

  10. Pancreatic-carcinoma-cell-derived pro-angiogenic factors can induce endothelial-cell differentiation of a subset of circulating CD34+ progenitors

    National Research Council Canada - National Science Library

    Vizio, Barbara; Biasi, Fiorella; Scirelli, Tiziana; Novarino, Anna; Prati, Adriana; Ciuffreda, Libero; Montrucchio, Giuseppe; Poli, Giuseppe; Bellone, Graziella

    2013-01-01

    .... Recent studies suggest that circulating endothelial progenitor cells are recruited into the angiogenic vascular system of several cancers, including pancreatic carcinoma, and that they correlate with clinical progress...

  11. Clinicopathological analysis of basal cell carcinoma of the anal region and its distinction from basaloid squamous cell carcinoma.

    Science.gov (United States)

    Patil, Deepa T; Goldblum, John R; Billings, Steven D

    2013-10-01

    Basal cell carcinoma of the anal region is rare and morphologically difficult to distinguish from basaloid squamous cell carcinoma, particularly on biopsies. This distinction has therapeutic and prognostic implications. We reviewed morphological features of 9 basal cell carcinomas and 15 basaloid squamous cell carcinomas from the anal region diagnosed during 1993-2011 and determined the utility of Ber-EP4, BCL2, TP63, CK5/6, CDKN2A, and SOX2 as diagnostic tools. Immunostains were scored in a semi-quantitative manner (1+-1-10%, 2+-11-50%, 3+->50%). All basal cell carcinomas were located in the perianal region, while all basaloid squamous cell carcinomas originated in the anal canal/anorectum. Nodular subtype of basal cell carcinoma was the most common subtype. Retraction artifact was the only significant distinguishing histological feature of basal cell carcinoma compared with basaloid squamous cell carcinoma (88% vs 26%; P=0.04). Atypical mitoses were more common in basaloid squamous cell carcinomas (71% vs 11%; P=0.05). An in situ component was only present in basaloid squamous cell carcinomas, and was noted in 6/15 cases. Basal cell carcinomas had 2-3+ Ber-EP4 (basal cell carcinoma 100% vs basaloid squamous cell carcinoma 40%; Pbasal cell carcinomas 100% vs basaloid squamous cell carcinoma 33%; Pcarcinomas (basal cell carcinoma 0% vs basaloid squamous cell carcinoma 93%; Pbasal cell carcinoma from basaloid squamous cell carcinoma. An in situ component, when present, supports the diagnosis of basaloid squamous cell carcinoma. Immunostains are extremely helpful as diffuse Ber-EP4 and BCL2 expression is a feature of basal cell carcinoma and basaloid squamous cell carcinoma is typified by diffuse CDKN2A and SOX2 expression.

  12. Case Report: Scleral Metastasis of Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Mahmodlou, Rahim; Asadi Amoli, Fahimeh; Abbasi, Ata; Seyed Mokhtari, Seyed Arman; Pourasghary, Sajjad

    2018-01-05

    In this report, a case of ocular scleral metastasis was reported in a patient with a past history of esophageal squamous cell carcinoma. The patient was a 58-year-old male who was admitted to Urmia Imam Khomeini Hospital, Urmia, Iran, 8 years ago with progressive dysphasia. Seven years after initial diagnosis and treatment of esophageal cancer, the patient had no signs or symptoms of the disease. But 2 months ago, he was referred to the hospital due to ocular swelling, redness and watering. Pathologic examination of the excised lesion at Farabi Hospital reported metastasis of squamous cell carcinoma to the connective tissue of the sclera.

  13. Respiratory squamous cell carcinomas in vibroacoustic disease.

    Science.gov (United States)

    Reis Ferreira, José; Mendes, Carla P; Alves-Pereira, Mariana; Castelo Branco, Nuno A A

    2006-01-01

    In 1987, the autopsy of a vibroacoustic disease (VAD) patient disclosed two tumours: a renal cell carcinoma and a malignant glioma in the brain. Since 1987, malignancy in VAD patients has been under close surveillance. To date, in a universe of 945 individuals, there are 46 cases of malignancies, of which 11 are multiple. Of the 11 cases of respiratory tract tumours, all were squamous cell carcinomas (SqCC). This report focuses on the morphological features of these tumours. Tumour fragments were collected (endoscopic biopsy or surgery) from 11 male VAD patients (ave. age: 58+/-9 years, 3 non-smokers): 2 in glottis and 9 in the lung. In the 3 non-smokers, 2 had lung tumours and 1 had a glottis tumour. All were employed as or retired aircraft technicians, military or commercial pilots. Fragments were fixed either for light and electron microscopy. Immunohistochemistry studies used chromagranine and synaptophysine staining. All lung tumours were located in the upper right lobe bronchi and were histologically poorly differentiated SqCC (Figs. 1, 2). The search with neuroendocrine markers was negative. The average age of tumour onset in helicopter pilots was below 50 years old while for the other professional groups it was above 50. Nine patients are deceased. The 2 surviving patients are heavy smokers (> 2 packs/day). Smoking habits had no influence on tumour outcome and progression. Epidemiological studies indicate that squamous cell carcinomas account for approximately 40% of all lung tumours in men. It seems to be highly relevant that all VAD patient respiratory tract tumours are squamous cell carcinomas. It is not surprising that helicopter pilots are the ones who are affected the earliest because previous studies have shown that helicopter pilots exhibited the highest values for the frequency of sister chromatid exchanges. Generally, epidemiological tumor studies do not take histological tumor type into account, but given the results herein, it would seem of the

  14. Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

    DEFF Research Database (Denmark)

    Almstrup, K; Hoei-Hansen, C E; Nielsen, J E

    2005-01-01

    The carcinoma in situ (CIS) cell is the common precursor of nearly all testicular germ cell tumours (TGCT). In a previous study, we examined the gene expression profile of CIS cells and found many features common to embryonic stem cells indicating that initiation of neoplastic transformation...... into CIS occurs early during foetal life. Progression into an overt tumour, however, typically first happens after puberty, where CIS cells transform into either a seminoma (SEM) or a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of CIS cells to that of testicular SEM...... and a sample containing a mixture of N-SEM components, and analyse the data together with the previously published data on CIS. Genes showing expression in the SEM or N-SEM were selected, in order to identify gene expression markers associated with the progression of CIS cells. The identified markers were...

  15. Lobomycosis and squamous cell carcinoma Lobomicose e carcinoma espinocelular

    Directory of Open Access Journals (Sweden)

    Lisiane Nogueira

    2013-04-01

    Full Text Available 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.A ocorrência de carcinoma espinocelular sobre lesões cutâneas de longa evolução é clássica em cicatrizes de queimadura e úlceras crônicas de etiologia variada, inclusive infecciosa. Na literatura, são raros os casos de pacientes com lobomicose de longa evolução que desenvolveram CEC. O seguimento cuidadoso desses pacientes é importante, pois, nas áreas de traumas, ulcerações e cicatrizes crônicas pode ocorrer degeneração carcinomatosa.

  16. Lupus vulgaris with squamous cell carcinoma.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  18. Focus on Merkel cell carcinoma: diagnosis and staging

    Energy Technology Data Exchange (ETDEWEB)

    Grandhaye, Marion; Teixeira, Pedro Gondim; Blum, Alain [Imagerie Guilloz CHU de Nancy Hopital Central, Nancy (France); Henrot, Philippe [Service de Radiologie Institut de Cancerologie de Lorraine, Vandoeuvre les Nancy (France); Morel, Olivier [Medecine Nucleaire CHU Nancy Hopital Brabois, Vancoeuvre les Nancy (France); Sirveaux, Francois [Service de Chirurgie Centre chirurgical Emile Galle, Nancy (France); Verhaeghe, Jean-Luc [Service de Chirurgie Institut de Cancerologie de Lorraine, Vandoeuvre les Nancy (France)

    2015-06-01

    Merkel cell carcinoma is a rare lymphophilic skin tumor of neuroendocrine origin with the potential for rapid progression. Small, localized lesions are diagnosed and treated clinically, but advanced tumors often undergo imaging evaluation. Due to its rarity, radiologists are unaware of evocative imaging features and usually do not consider Merkel cell carcinoma in the differential diagnosis of soft tissue tumors. Appropriate staging is important to determine appropriate treatment and has an impact on patient prognosis. Multimodality imaging is usually needed, and there is no consensus on the optimal imaging strategy. The purpose of this article is to review various aspects of Merkel cell carcinoma imaging and look in detail at how optimal multimodality staging should be carried out. (orig.)

  19. Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma.

    Science.gov (United States)

    Pontisso, P; Calabrese, F; Benvegnù, L; Lise, M; Belluco, C; Ruvoletto, M G; Marino, M; Valente, M; Nitti, D; Gatta, A; Fassina, G

    2004-02-23

    Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are still unclear and new tools for diagnostic and therapeutic purposes are ongoing. We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer. Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs of different aetiology and in 20 normal livers. Proliferative activity was assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver tissue was available for SCCA cDNA amplification and sequencing. Squamous cell carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in none of the 20 controls. In the majority of the cases, the positive signal was found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable SCCA (scoreSCCA score >or=2 (mean+/-s.d.: 2%+/-2.4 vs 7.5%+/-10.3, PSCCA1 variant (G(351) to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion, SCCA variants are overexpressed in HCC, independently of tumour aetiology. A novel SCCA1 variant has been identified in one third of liver tumours.

  20. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  1. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie

    2014-01-01

    SUMMARY: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local...... control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  2. A Case Report of Spindle Cell (Sarcomatoid Carcinoma of the Larynx

    Directory of Open Access Journals (Sweden)

    Harry Boamah

    2012-01-01

    Full Text Available Spindle cell carcinoma (SpCC or sarcomatoid carcinoma is a highly malignant variant of squamous cell carcinoma which comprises 2% to 3% of all laryngeal cancers. It is considered to be a biphasic tumor that is composed of a squamous cell carcinoma (in situ or invasive and spindle cell carcinoma with sarcomatous appearance. Most spindle cell tumors are polypoid and pedunculated; they are often detected at an early stage, removed by polypectomy during diagnosis, and tend to have a very good prognosis. We present a case of spindle cell carcinoma in a 67-year-old Caucasian male who presented with progressive hoarseness of his voice, dysphagia, odynophagia and a 20-pound weight loss. The patient underwent direct laryngoscopy with excision of the malignant mass and received radiation therapy. His symptoms gradually improved, and he regained good control of his voice.

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

    Science.gov (United States)

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

    2016-02-05

    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.

  4. Multiple skin cancers in a single patient: Multiple pigmented Bowen′s disease, giant basal cell carcinoma, squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ravi Saini

    2015-01-01

    Full Text Available Basal cell carcinoma (BCC and squamous cell carcinoma are the most common type of nonmelanoma skin cancers (NMSCs. Bowen′s disease (BD, a premalignant condition, has a marginal potential (3-5% to progress to invasive carcinoma. We report here a rarest of a rare case of multiple pigmented BD with overlying squamous cell cancer along with a giant neglected BCC on the scalp of a 76-year-old man. The occurrence of multiple BD and NMSC in a single patient compelled us to explore the following hypothesis: (1 The multiple precancerous and cancerous lesions can be due to common etiopathogenesis. Chronic ultraviolet exposure, immunosupresssion, human papillomavirus infection, dietary factors, and environmental factors including arsenic exposure were probed in to. (2 There is evolution of precancerous lesions into a different type of cancers in different time frame. (3 The new cancerous lesions are subsequent cancers that developed after neglected untreated primary cancer.

  5. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Choueiri, Toni K; Escudier, Bernard; Powles, Thomas

    2015-01-01

    to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. METHODS: We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily......BACKGROUND: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance...... received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus. CONCLUSIONS: Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell...

  6. Molecular basis of basal cell carcinoma*

    Science.gov (United States)

    Montagna, Erik; Lopes, Otávio Sérgio

    2017-01-01

    Basal cell carcinoma is the most common cancer, presenting low mortality but high morbidity, and it has as risk factor exposure to sunlight, especially UVB spectrum. The most important constitutional risk factors for basal cell carcinoma development are clear phototypes (I and II, Fitzpatrick classification), family history of basal cell carcinoma (30-60%), freckles in childhood, eyes and light hair. The environmental risk factor better established is exposure to ultraviolet radiation. However, different solar exposure scenarios probably are independent risk factors for certain clinical and histological types, topographies and prognosis of this tumor, and focus of controversy among researchers. Studies confirm that changes in cellular genes Hedgehog signaling pathway are associated with the development of basal cell carcinoma. The cellular Hedgehog signaling pathway is activated in organogenesis, but is altered in various types of tumors. PMID:28954101

  7. Molecular basis of basal cell carcinoma.

    Science.gov (United States)

    Montagna, Erik; Lopes, Otávio Sérgio

    2017-01-01

    Basal cell carcinoma is the most common cancer, presenting low mortality but high morbidity, and it has as risk factor exposure to sunlight, especially UVB spectrum. The most important constitutional risk factors for basal cell carcinoma development are clear phototypes (I and II, Fitzpatrick classification), family history of basal cell carcinoma (30-60%), freckles in childhood, eyes and light hair. The environmental risk factor better established is exposure to ultraviolet radiation. However, different solar exposure scenarios probably are independent risk factors for certain clinical and histological types, topographies and prognosis of this tumor, and focus of controversy among researchers. Studies confirm that changes in cellular genes Hedgehog signaling pathway are associated with the development of basal cell carcinoma. The cellular Hedgehog signaling pathway is activated in organogenesis, but is altered in various types of tumors.

  8. Sunitinib benefits patients with renal cell carcinoma

    Science.gov (United States)

    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.

  9. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Bilir

    2014-01-01

    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  10. Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Todenhöfer Tilman

    2012-03-01

    Full Text Available Abstract Background Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma. Case presentation A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable. Conclusions Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.

  11. Cardiac metastasis from a renal cell carcinoma

    Science.gov (United States)

    Alghamdi, Abdulaziz; Tam, James

    2006-01-01

    A 59-year-old man developed an episode of syncope while he was driving. This resulted in a motor vehicle accident, and the patient sustained an open fracture of the left femur. Biopsy of the left femur fracture showed a metastastic renal cell carcinoma, and echocardiography revealed a right ventricular mass without contiguous vena caval or right atrial involvement. This is one of the few reported cases of renal cell carcinoma associated with syncope as an initial symptom. PMID:17151773

  12. Significance of myofibroblasts in oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Thode, Christenze; Jørgensen, Trine G.; Dabelsteen, Erik

    2011-01-01

    It is now recognized that the tumor microenvironment makes significant contribution to tumor progression. Activated fibroblast endothelial cells, inflammatory cells, and various extra cellular matrix components are parts of this microenvironment. Most of the activated fibroblasts are a......-smooth muscle actin-positive myofibroblast that often represent the majority of tumor stromal cells. Their production of growth factors chemokines and extracellular matrix facilitates tumor growth. Myofibroblast have been demonstrated in close to 50% of oral squamous cell carcinomas. In this review, we...... highlight the histological distribution of myofibroblast in oral squamous cell and the myofibroblast relation to tumor growth on prognosis....

  13. Oncolytic vaccinia therapy of squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Yong A

    2009-07-01

    Full Text Available Abstract Background Novel therapies are necessary to improve outcomes for patients with squamous cell carcinomas (SCC of the head and neck. Historically, vaccinia virus was administered widely to humans as a vaccine and led to the eradication of smallpox. We examined the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68 as an oncolytic agent against a panel of six human head and neck SCC cell lines. Results All six cell lines supported viral transgene expression (β-galactosidase, green fluorescent protein, and luciferase as early as 6 hours after viral exposure. Efficient transgene expression and viral replication (>150-fold titer increase over 72 hrs were observed in four of the cell lines. At a multiplicity of infection (MOI of 1, GLV-1h68 was highly cytotoxic to the four cell lines, resulting in ≥ 90% cytotoxicity over 6 days, and the remaining two cell lines exhibited >45% cytotoxicity. Even at a very low MOI of 0.01, three cell lines still demonstrated >60% cell death over 6 days. A single injection of GLV-1h68 (5 × 106 pfu intratumorally into MSKQLL2 xenografts in mice exhibited localized intratumoral luciferase activity peaking at days 2–4, with gradual resolution over 10 days and no evidence of spread to normal organs. Treated animals exhibited near-complete tumor regression over a 24-day period without any observed toxicity, while control animals demonstrated rapid tumor progression. Conclusion These results demonstrate significant oncolytic efficacy by an attenuated vaccinia virus for infecting and lysing head and neck SCC both in vitro and in vivo, and support its continued investigation in future clinical trials.

  14. Monoclonal antibody Ber-EP4 reliably discriminates between microcystic adnexal carcinoma and basal cell carcinoma.

    Science.gov (United States)

    Krahl, Dieter; Sellheyer, Klaus

    2007-10-01

    Sclerosing cutaneous neoplasms often represent a diagnostic challenge. The monoclonal antibody Ber-EP4 recognizes two glycopolypeptides found in most human epithelial cells. It is diagnostically highly reliable in the differentiation between basal cell carcinoma and cutaneous squamous cell carcinoma. In this study, we report its application in the differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and basal cell carcinoma. Biopsy samples from 28 sclerosing and infiltrating basal cell carcinomas, 13 microcystic adnexal carcinomas and 16 desmoplastic trichoepitheliomas were examined after immunohistochemical staining with Ber-EP4. Ber-EP4 did not label any of the microcystic adnexal carcinomas, whereas all 28 basal cell carcinomas were Ber-EP4 positive. Twenty-seven of the 28 showed moderate or strong staining intensity, with the majority being strong. Only one basal cell carcinoma was weakly positive. Twelve of the 16 desmoplastic trichoepitheliomas were immunoreactive with Ber-EP4 and the staining was more variable than those of basal cell carcinomas. Ber-EP4 reliably differentiates microcystic adnexal carcinoma from basal cell carcinoma to the same extent as it distinguishes the latter tumor from squamous cell carcinoma. While it stains the majority of desmoplastic trichoepitheliomas, these tumors still have to be considered in the differential diagnosis with microcystic adnexal carcinoma, when Ber-EP4 is applied.

  15. Staging of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Lisse, Ullrich G.; Meindl, Thomas; Coppenrath, Eva; Degenhart, Christoph; Graser, Anno; Scherr, Michael; Reiser, Maximilian F. [Ludwig Maximilians University, Munich (Germany). Department of Clinical Radiology; Mueller-Lisse, Ulrike L. [University of Munich (Germany). Department of Urology

    2007-09-15

    As in other malignant tumors, prognosis in renal cell carcinoma (RCC) depends on tumor extent and metastasis at the time of primary diagnosis. Staging systems formalize the way in which the extent of RCC is being described and classified. Primary staging of RCC aims at evaluating surgical options. Since surgical excision, which is the mainstay of therapy in non-metastatic RCC, and, recently, minimally invasive ablation methods have evolved significantly over the last decades, staging systems continue to evolve along the way. The 40-year-old Robson classification has been replaced with the TNM classification of RCC, because the latter adapts more easily to changing patterns of diagnosis and therapy. Modern cross-sectional imaging methods, such as multidetector-row computed tomography (MDCT), and magnetic resonance imaging (MRI), perform highly in T-staging of local tumor extent and M-staging of distant metastasis. However, both MDCT and MRI perform poorly in N-staging of lymphadenopathy. At present, 18-F-desoxy-glucose positron emission tomography (FDG-PET) appears to be unreliable in the detection of RCC and its metastasis. This overview of current radiological and surgical literature attempts to describe how modern staging systems for RCC are organized, and which radiological and surgical developments currently influence the way in which primary staging and prognosis of RCC depend on one another. (orig.)

  16. Development of squamous cell carcinoma into basal cell carcinoma under treatment with Vismodegib.

    Science.gov (United States)

    Saintes, C; Saint-Jean, M; Brocard, A; Peuvrel, L; Renaut, J J; Khammari, A; Quéreux, G; Dréno, B

    2015-05-01

    Basal cell carcinoma (BCC) is the most common cancer in humans. Vismodegib, a Hedgehog pathway inhibitor, has proved its effectiveness in treating non-resectable advanced BCC. However, its action on squamous cell carcinoma (SCC) is unknown. We present three SCC cases developed into BCC in vismodegib-treated patients. We have described three cases of patients developing SCC during treatment by vismodegib for BCC. Patient 1 was treated with vismodegib for five facial BCC. Due to the progression of one of the lesions at month 3 (M3), a biopsy was performed and showed SCC. Patient 2 was treated with vismodegib for a large facial BCC. A biopsy was performed at M2 on a BCC area not responding to treatment and showed SCC. Patient 3 was treated with vismodegib for a BCC on the nose. Due to vismodegib ineffectiveness, a biopsy was performed and showed SCC. Two similar cases have been described in the literature. This could be due to the appearance of the squamous contingent of a metatypical BCC or to the squamous differentiation of stem cells through inhibition of the hedgehog pathway. In practice, any dissociated response of a BCC to vismodegib should be biopsied. © 2014 European Academy of Dermatology and Venereology.

  17. High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma

    National Research Council Canada - National Science Library

    Dhabhar, Firdaus S; Saul, Alison N; Holmes, Tyson H; Daugherty, Christine; Neri, Eric; Tillie, Jean M; Kusewitt, Donna; Oberyszyn, Tatiana M

    2012-01-01

    .... We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive...

  18. Expressão imuno-histoquímica das metaloproteinases 2 e 9 não está associada à progressão do carcinoma de células escamosas de esôfago Metalloproteinases 2 and 9 immunohistochemistry expression is not associated to esophageal squamous cell carcinoma progression

    Directory of Open Access Journals (Sweden)

    Izabella Paz Danezi Felin

    2009-08-01

    Full Text Available INTRODUÇÃO: O carcinoma de células escamosas do esôfago está entre os tipos mais agressivos de câncer e de pior prognóstico. As metaloproteinases de matriz (MMPs, especialmente as MMP-2 e MMP-9, vêm sendo utilizadas para avaliação prognóstica do câncer, associadas a invasão, tamanho e crescimento tumoral. OBJETIVO: O presente estudo visa investigar as expressões imuno-histoquímicas de MMP-2 e MMP-9, avaliando se existe correlação entre sua expressão e o estadiamento tumoral, invasão vascular, invasão local (pT e diferenciação tumoral no carcinoma de células escamosas de esôfago. MATERIAL E MÉTODO: Foi realizado um estudo retrospectivo utilizando 31 blocos de parafina contendo tumores de carcinoma escamoso esofágico, obtidas por esofagectomias realizadas entre 1998 e 2003, no Hospital Universitário de Santa Maria (HUSM. Os cortes histológicos foram submetidos à reação imuno-histoquímica, com sistema de amplificação por polímero não-biotinilado Novolink para detecção de MMP-2 e MMP-9. RESULTADOS: A avaliação da MMP-2 apresentou positividade fraca em apenas cinco casos, não demonstrando correlação com as variáveis estudadas. Também não foram observadas associações significativas entre as variáveis do estudo e o grau de expressão imuno-histoquímica da MMP-9. CONCLUSÃO: A expressão imuno-histoquímica das MMP-2 e MMP-9 não parece ser influenciada pelos parâmetros investigados. Nesse sentido, estudos adicionais são necessários para melhor compreensão de sua associação aos fatores prognósticos do carcinoma de células escamosas de esôfago.INTRODUCTION: Esophageal squamous cell carcinoma is an aggressive malignant neoplasia with poor prognosis. The expression of matrix metalloproteinases (MMPs, mainly 2 and 9, has been used for the prognostic evaluation of cancer in association with tumor invasion, size and tumoral growth analysis. OBJECTIVE: The aim of the present study was to investigate

  19. Immunosuppressive Environment in Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Nielsen, Patricia S; Gjerdrum, Lise M R

    2016-01-01

    Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed...

  20. Metastatic giant basal cell carcinoma: a case report.

    Science.gov (United States)

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  1. BASALOID SQUAMOUS CELL CARCINOMA OF THE LARYNX: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Mileta Golubović

    2013-03-01

    Full Text Available Basaloid squamous cell carcinoma is a highly aggressive tumor. The aim of this study was to present a case of a 60 year-old man having progressive hoarseness that lasted for six months. Indirect laryngoscopy and histopathologic examination detected an exophytic growth that involved the left false vocal fold. The patient underwent a left-sided, vertical partial hemilaryngectomy. Patient had no signs of tumor recurrence or metastases eighteen months later.

  2. Role of everolimus in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Saby George

    2009-08-01

    Full Text Available Saby George1, Ronald M Bukowski21University of Texas Health Sciences Center, MC-8221, Division of Hematology and Oncology, San Antonio, Texas, USA; 2CCF Lerner College of Medicine Division of Hematology and Oncology, Cleveland, Ohio, USAAbstract: The therapeutic options in metastatic renal cell carcinoma have been recently expanded by the discovery of the VHL gene, the mutation of which is associated with development of clear cell carcinoma, and overexpression of the angiogenesis pathway, resulting in a very vascular tumor. This breakthrough in science led to the development of a variety of small molecules inhibiting the VEGF-dependent angiogenic pathway, such as sunitinib and sorafenib. These agents prolong overall and progression-free survival, respectively. The result was the development of robust front-line therapies which ultimately fail and are associated with disease progression. In this setting, there existed an unmet need for developing second-line therapies for patients with refractory metastatic renal cell carcinoma (MRCC. Everolimus (RAD 001 is an oral inhibitor of the mammalian target of rapamycin (mTOR pathway. The double-blind, randomized, placebo-controlled phase III trial of everolimus (RECORD-1 conducted in MRCC patients after progression on sunitinib or sorafenib, or both, demonstrated a progression-free survival benefit favoring the study drug (4.9 months vs 1.9 months, HR 0.33, 95% CI 0.25 to 0.43, P ≤ 0 0.001. Everolimus thus established itself as a standard of care in the second-line setting for patients with MRCC who have failed treatment with VEGF receptor inhibitors.Keywords: mTOR inhibitor, mammalian target of rapamycin inhibitor, signal transduction inhibitor, renal cell carcinoma, targeted therapy

  3. Regulation of glycolysis in head and neck squamous cell carcinoma

    OpenAIRE

    Kumar, Dhruv

    2017-01-01

    Glycolysis is highly upregulated in head and neck squamous cell carcinoma (HNSCC). HNSCC glycolysis is an important contributor to disease progression and decreases sensitivity to radiation or chemotherapy. Despite therapeutic advances, the survival rates for HNSCC patients remain low. Understanding glycolysis regulation in HNSCC will facilitate the development of effective therapeutic strategies for this disease. In this review, we will evaluate the regulation of altered HNSCC glycolysis and...

  4. New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy

    Directory of Open Access Journals (Sweden)

    Kevin Zarrabi

    2017-02-01

    Full Text Available Abstract Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.

  5. Investigating the biochemical progression of liver disease through fibrosis, cirrhosis, dysplasia, and hepatocellular carcinoma using Fourier transform infrared spectroscopic imaging

    Science.gov (United States)

    Sreedhar, Hari; Pant, Mamta; Ronquillo, Nemencio R.; Davidson, Bennett; Nguyen, Peter; Chennuri, Rohini; Choi, Jacqueline; Herrera, Joaquin A.; Hinojosa, Ana C.; Jin, Ming; Kajdacsy-Balla, Andre; Guzman, Grace; Walsh, Michael J.

    2014-03-01

    Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma. HCC ranks the fourth most prevalent malignant tumor and the third leading cause of cancer related death in the world. Hepatocellular carcinoma develops in the context of chronic liver disease and its evolution is characterized by progression through intermediate stages to advanced disease and possibly even death. The primary sequence of hepatocarcinogenesis includes the development of cirrhosis, followed by dysplasia, and hepatocellular carcinoma.1 We addressed the utility of Fourier Transform Infrared (FT-IR) spectroscopic imaging, both as a diagnostic tool of the different stages of the disease and to gain insight into the biochemical process associated with disease progression. Tissue microarrays were obtained from the University of Illinois at Chicago tissue bank consisting of liver explants from 12 transplant patients. Tissue core biopsies were obtained from each explant targeting regions of normal, liver cell dysplasia including large cell change and small cell change, and hepatocellular carcinoma. We obtained FT-IR images of these tissues using a modified FT-IR system with high definition capabilities. Firstly, a supervised spectral classifier was built to discriminate between normal and cancerous hepatocytes. Secondly, an expanded classifier was built to discriminate small cell and large cell changes in liver disease. With the emerging advances in FT-IR instrumentation and computation there is a strong drive to develop this technology as a powerful adjunct to current histopathology approaches to improve disease diagnosis and prognosis.

  6. Urothelial Carcinoma Stem Cells: Current Concepts, Controversies, and Methods.

    Science.gov (United States)

    Hatina, Jiri; Parmar, Hamendra Singh; Kripnerova, Michaela; Hepburn, Anastasia; Heer, Rakesh

    2018-01-01

    Cancer stem cells are defined as a self-renewing and self-protecting subpopulation of cancer cells able to differentiate into morphologically and functionally diverse cancer cells with a limited lifespan. To purify cancer stem cells, two basic approaches can be applied, the marker-based approach employing various more of less-specific cell surface marker molecules and a marker-free approach largely based on various self-protection mechanisms. Within the context of urothelial carcinoma, both methods could find use. The cell surface markers have been mainly derived from the urothelial basal cell, a probable cell of origin of muscle-invasive urothelial carcinoma, with CD14, CD44, CD90, and 67LR representing successful examples of this strategy. The marker-free approaches involve side population sorting, for which a detailed protocol is provided, as well as the Aldefluor assay, which rely on a specific overexpression of efflux pumps or the detoxification enzyme aldehyde dehydrogenase, respectively, in stem cells. These assays have been applied to both non-muscle-invasive and muscle-invasive bladder cancer samples and cell lines. Urothelial carcinoma stem cells feature a pronounced heterogeneity as to their molecular stemness mechanisms. Several aspects of urothelial cancer stem cell biology could enter translational development rather soon, e.g., a specific CD44(+)-derived gene expression signature able to identify non-muscle-invasive bladder cancer patients with a high risk of progression, or deciphering a mechanism responsible for repopulating activity of urothelial carcinoma stem cells within the context of therapeutic resistance.

  7. Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Cheng-Yuan Wang

    2010-02-01

    Full Text Available Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1 to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.

  8. Cabozantinib versus everolimus, nivolumab, axitinib, sorafenib and best supportive care: A network meta-analysis of progression-free survival and overall survival in second line treatment of advanced renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Billy Amzal

    Full Text Available Relative effect of therapies indicated for the treatment of advanced renal cell carcinoma (aRCC after failure of first line treatment is currently not known. The objective of the present study is to evaluate progression-free survival (PFS and overall survival (OS of cabozantinib compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI treatment.Systematic literature search identified 5 studies for inclusion in this analysis. The assessment of the proportional hazard (PH assumption between the survival curves for different treatment arms in the identified studies showed that survival curves in two of the studies did not fulfil the PH assumption, making comparisons of constant hazard ratios (HRs inappropriate. Consequently, a parametric survival network meta-analysis model was implemented with five families of functions being jointly fitted in a Bayesian framework to PFS, then OS, data on all treatments. The comparison relied on data digitized from the Kaplan-Meier curves of published studies, except for cabozantinib and its comparator everolimus where patient level data were available. This analysis applied a Bayesian fixed-effects network meta-analysis model to compare PFS and OS of cabozantinib versus its comparators. The log-normal fixed-effects model displayed the best fit of data for both PFS and OS, and showed that patients on cabozantinib had a higher probability of longer PFS and OS than patients exposed to comparators. The survival advantage of cabozantinib increased over time for OS. For PFS the survival advantage reached its maximum at the end of the first year's treatment and then decreased over time to zero.With all five families of distributions, cabozantinib was superior to all its comparators with a higher probability of longer PFS and OS during the analyzed 3 years, except with the Gompertz model, where nivolumab was

  9. Renal Cell Carcinoma Metastatic to Thyroid Gland, Presenting Like Anaplastic Carcinoma of Thyroid

    Directory of Open Access Journals (Sweden)

    Khalid Riaz

    2013-01-01

    Full Text Available Background. Renal cell carcinoma (RCC has unpredictable and diverse behavior. The classic triad of hematuria, loin pain, and abdominal mass is uncommon. At time of diagnosis, 25%–30% of patients are found to have metastases. Bones, lungs, liver, and brain are the frequent sites of metastases. RCC with metastasis to the head and neck region and thyroid gland is the rarest manifestation and anaplastic carcinoma behaving metastatic thyroid mass is an extremely rare presentation of RCC. Case Presentation. A 56-year-old Saudi man with past history of right radical nephrectomy 5 years back presented with 3 months history of rapid increasing neck mass with dysphagia, presenting like anaplastic thyroid carcinoma. Tru-cut biopsy turned out to be metastatic renal cell carcinoma. Patient was treated with radiation therapy 30 Gy in 10 fractions to mass. Patient died 4 months after the discovery of anaplastic thyroid looking metastasis. Conclusion. Rapidly progressing thyroid metastases secondary to RCC are rare and found often unresectable which are not amenable to surgery. Palliative radiotherapy can be considered for such patients.

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

    Science.gov (United States)

    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

  11. Epidemiologia do carcinoma basocelular Epidemiology of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Valquiria Pessoa Chinem

    2011-04-01

    Full Text Available O carcinoma basocelular é a neoplasia maligna mais comum em humanos e sua incidência vem aumentando nas últimas décadas. Sua grande frequência gera significativo ônus ao sistema de saúde, configurando problema de saúde pública. Apesar das baixas taxas de mortalidade e de rara ocorrência de metástases, o tumor pode apresentar comportamento invasivo local e recidivas após o tratamento, provocando importante morbidade. Exposição à radiação ultravioleta representa o principal fator de risco ambiental associado a sua gênese. Entretanto, descrevem-se outros elementos de risco: fotótipos claros, idade avançada, história familiar de carcinomas de pele, olhos e cabelos claros, sardas na infância e imunossupressão, além de aspectos comportamentais, como exercício profissional exposto ao sol, atividade rural e queimaduras solares na juventude. Entre 30% e 75% dos casos esporádicos estão associados à mutação do gene patched hedgehog, mas outras alterações genéticas são ainda descritas. A neoplasia é comumente encontrada concomitantemente com lesões cutâneas relacionadas à exposição solar crônica, tais como: queratoses actínicas, lentigos solares e telangiectasias faciais. A prevenção do carcinoma basocelular se baseia no conhecimento de fatores de risco, no diagnóstico e tratamento precoces e na adoção de medidas específicas, principalmente, nas populações susceptíveis. Os autores apresentam uma revisão da epidemiologia do carcinoma basocelular.Basal cell carcinoma is the most common malignant neoplasm in humans and its incidence has increased over the last decades. Its high frequency significantly burdens the health system, making the disease a public health issue. Despite the low mortality rates and the rare occurrence of metastases, the tumor may be locally invasive and relapse after treatment, causing significant morbidity. Exposure to ultraviolet radiation is the main environmental risk factor

  12. Axitinib in sequential therapy in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Agata Kuchar

    2015-05-01

    Full Text Available Efficacy of new molecularly targeted drugs in the treatment of renal cell carcinoma (RCC, confirmed in clinical studies in relation to survival and prolongation of time to progression, has became a big chance for patients with metastatic renal cell cancer. Axitinib is a potent and selective receptor tyrosine kinase for vascular endothelial growth factor (VEGFR-1, -2, -3, platelet-derived growth factor  (PDGRF- and c-KIT. This is a case report of a 57-year old female patient with a history of left nephrectomy due to clear cell renal cell carcinoma. The patient had received three prior systemic treatments (interferon – sorafenib – everolimus. After consecutive progression the patient was qualified to 4th line therapy – axitinib at a dose of 5 mg twice daily. Partial response to treatment was achieved. After 6 months therapy was stopped due to the disease progression. The total time to progression was 37.5 months. The total survival time from the disease diagnosis was 45 months. Based on literature date and own experience we showed that sequential treatment RCC is associated with improved survival. In summary, axitinib may be an effective drug after failure of tyrosine-kinase inhibitor (TKI therapy in previous lines of therapy.

  13. Squamous cell carcinoma in the submandibular space

    Energy Technology Data Exchange (ETDEWEB)

    An, Byung Mo; Lee, Sam Sun; Heo, Min Suk; Choi, Hyun Bae; Choi, Soon Chul [Seoul National Univ. College of Dentistry, Seoul (Korea, Republic of)

    2001-06-15

    A 66-year-old man visited author's institute complaining of the swelling on the submandibular gland area. Clinically, the exophytic mass penetrated the skin of the submandibular area. On MRI, the lesion occupied the left submandibular space and extended downward, protruding exterior to the subcutaneous fat layer, but the center of the lesion was located on the side of the skin and the growth exterior to the skin was prominent. Demarcation of the lesion and the submandibular gland was unclear. Histopathologically the epithelial nests and keratin production were seen, then the biopsy result was squamous cell carcinoma. The stroma of lesion showed a myxoid characteristic and some ducts showed metaplasia of the ductal cells, which suggested the gland-origin carcinoma. However, lots of keratin production and carcinomatous change of cells continuous to the normal epithelium of the skin, the skin-origin carcinoma invading into the submandibular gland area could not be excluded.

  14. SKLB70326, a novel small-molecule inhibitor of cell-cycle progression, induces G{sub 0}/G{sub 1} phase arrest and apoptosis in human hepatic carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yuanyuan; He, Haiyun [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Peng, Feng [Department of Thoracic Oncology of the Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Liu, Jiyan; Dai, Xiaoyun; Lin, Hongjun; Xu, Youzhi; Zhou, Tian; Mao, Yongqiu; Xie, Gang; Yang, Shengyong; Yu, Luoting; Yang, Li [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Zhao, Yinglan, E-mail: alancenxb@sina.com [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer SKLB70326 is a novel compound and has activity of anti-HCC. Black-Right-Pointing-Pointer SKLB70326 induces cell cycle arrest and apoptosis in HepG2 cells. Black-Right-Pointing-Pointer SKLB70326 induces G{sub 0}/G{sub 1} phase arrest via inhibiting the activity of CDK2, CDK4 and CDK6. Black-Right-Pointing-Pointer SKLB70326 induces apoptosis through the intrinsic pathway. -- Abstract: We previously reported the potential of a novel small molecule 3-amino-6-(3-methoxyphenyl)thieno[2.3-b]pyridine-2-carboxamide (SKLB70326) as an anticancer agent. In the present study, we investigated the anticancer effects and possible mechanisms of SKLB70326 in vitro. We found that SKLB70326 treatment significantly inhibited human hepatic carcinoma cell proliferation in vitro, and the HepG2 cell line was the most sensitive to its treatment. The inhibition of cell proliferation correlated with G{sub 0}/G{sub 1} phase arrest, which was followed by apoptotic cell death. The SKLB70326-mediated cell-cycle arrest was associated with the downregulation of cyclin-dependent kinase (CDK) 2, CDK4 and CDK6 but not cyclin D1 or cyclin E. The phosphorylation of the retinoblastoma protein (Rb) was also observed. SKLB70326 treatment induced apoptotic cell death via the activation of PARP, caspase-3, caspase-9 and Bax as well as the downregulation of Bcl-2. The expression levels of p53 and p21 were also induced by SKLB70326 treatment. Moreover, SKLB70326 treatment was well tolerated. In conclusion, SKLB70326, a novel cell-cycle inhibitor, notably inhibits HepG2 cell proliferation through the induction of G{sub 0}/G{sub 1} phase arrest and subsequent apoptosis. Its potential as a candidate anticancer agent warrants further investigation.

  15. Metastatic giant basal cell carcinoma: a case report | Khadija | Pan ...

    African Journals Online (AJOL)

    ... characterised by a slow growing behavior, metastasis are extremely rare, and it ... develops to a giant basal cell carcinoma,resulting ofpatient's negligence. ... cell carcinoma metastaticin lung occurringin a 79 years old male patient, with a ...

  16. Emerging therapeutics in refractory renal cell carcinoma.

    Science.gov (United States)

    Koshkin, Vadim S; Rini, Brian I

    2016-06-01

    Metastatic renal cell carcinoma (mRCC) has seen the introduction of numerous new treatments over the past decade. However, the efficacy of these therapies has plateaued, and new treatment options are needed for the majority of patients with mRCC whose disease inevitably progresses through one or more standard therapies ('refractory' mRCC). Recently approved agents in this space have shown great promise. This article reviews the evidence behind current management strategies for mRCC. After reviewing clinical trials that established current first-line therapies and agents used in the refractory setting, we address new ideas for the treatment of refractory disease including combination therapies and novel targeted agents. In particular, we focus on targeted immunotherapy in refractory mRCC. We conclude by considering future directions in combination treatments utilizing these novel agents. Numerous approaches have produced tangible benefits for the treatment of patients with mRCC. These include development of next generation VEGFR/TKIs, targeted immunotherapy agents, and the development of combined regimens. In particular, immunotherapy agents targeting the PD1/PD-L1 pathway have shown great promise with a robust survival advantage seen in patients treated with nivolumab. A tolerable side effect profile of immunotherapy agents makes them amenable for use in combination therapies and ongoing trials are addressing this question.

  17. Rising incidence of Merkel cell carcinoma

    DEFF Research Database (Denmark)

    Lyhne, Dorte; Lock-Andersen, Jørgen; Dahlstrøm, Karin

    2011-01-01

    Abstract Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark, and to investi......Abstract Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark...

  18. Squamous Cell Carcinoma of the Distal Common Bile Duct

    OpenAIRE

    Jain A; Juneja M; Naik S; Sharma S; Kapoor S; Sewkani A; Varshney S

    2005-01-01

    CONTEXT: Squamous cell carcinoma of the biliary tree is rare. Although few cases of squamous cell carcinoma of the intrahepatic bile-duct and gallbladder have been reported, until today, only four cases of squamous cell carcinoma of the extrahepatic bile duct have been reported in the literature. CASE REPORT: We present a case of squamous cell carcinoma of the distal common bile duct presenting with obstructive jaundice in a 60-year-old male which was successfully managed by a Whipple's pancr...

  19. Hybrid verrucous-squamous cell carcinoma of the ovary with synchronous squamous cell carcinoma of the endometrium.

    Science.gov (United States)

    Fancher, Tiffany T; Hamzi, Munir H; Macaron, Shady H; Magno, Winston B; Dudrick, Stanley J; Palesty, J Alexander

    2008-01-01

    Verrucous carcinoma, a variant of well-differentiated squamous cell carcinoma, is usually described in the literature as arising in the oral cavity, skin, and larynx. The reports on verrucous carcinoma arising in the genital tract, usually originating in the vagina, vulva, or uterine cervix, are few. Verrucous carcinoma arising in the ovary has not been previously reported. In this article, a unique hybrid carcinoma, a large aggressive verrucous carcinoma in combination with squamous carcinoma of the left ovary and synchronously occurring with a squamous cell carcinoma in the endometrium, is presented. This unique case of a hybrid carcinoma includes the first-known case of this type of carcinoma involving the ovary. The negative cervical evaluation findings, together with the histologic patterns of the tumors in the uterus and the ovary, support the conclusion that these 2 carcinomas are synchronous, one arising in the left ovary and the other arising in the uterus.

  20. Histologic Mimics of Basal Cell Carcinoma.

    Science.gov (United States)

    Stanoszek, Lauren M; Wang, Grace Y; Harms, Paul W

    2017-11-01

    - Basal cell carcinoma (BCC) is the most common human malignant neoplasm and is a frequently encountered diagnosis in dermatopathology. Although BCC may be locally destructive, it rarely metastasizes. Many diagnostic entities display morphologic and immunophenotypic overlap with BCC, including nonneoplastic processes, such as follicular induction over dermatofibroma; benign follicular tumors, such as trichoblastoma, trichoepithelioma, or basaloid follicular hamartoma; and malignant tumors, such as sebaceous carcinoma or Merkel cell carcinoma. Thus, misdiagnosis has significant potential to result in overtreatment or undertreatment. - To review key features distinguishing BCC from histologic mimics, including current evidence regarding immunohistochemical markers useful for that distinction. - Review of pertinent literature on BCC immunohistochemistry and differential diagnosis. - In most cases, BCC can be reliably diagnosed by histopathologic features. Immunohistochemistry may provide useful ancillary data in certain cases. Awareness of potential mimics is critical to avoid misdiagnosis and resulting inappropriate management.

  1. Advanced Squamous Cell Carcinoma of Cornea in a Child with ...

    African Journals Online (AJOL)

    tumors such as squamous cell carcinomas, (SCCs) basal cell carcinoma, malignant melanoma, fibrosarcoma, etc.,. The pathogenesis in a majority of these cases involve. Advanced Squamous Cell Carcinoma of. Cornea in a Child with Xeroderma Pigmentosa. Misra Somen, Bhandari Akshay Jawahirlal, Neeta Misra, Dipti ...

  2. Small Cell Carcinoma of the Ovary: Report of a Case with Unusual and Aggressive Presentation

    Directory of Open Access Journals (Sweden)

    Fatemeh Sadat Najib

    2017-07-01

    Full Text Available Small cell carcinoma of the ovary is an aggressive malignant tumor with no standard treatment. Despite surgery, chemotherapy and radiation, this tumor has a poor prognosis with rapid progression. The authors report a case of small cell carcinoma of the ovary in a 37-year-old woman who presented twice with an acute abdomen and unstable hemodynamics which led to two urgent laparatomies. The patient died two months after her diagnosis of small cell carcinoma of the ovary and one course of chemotherapy.

  3. Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2014-06-01

    Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

  4. Optical coherence tomography of basal cell carcinoma

    DEFF Research Database (Denmark)

    Yücel, D.; Themstrup, L.; Manfredi, Maddalena

    2016-01-01

    Background: Basal cell carcinoma (BCC) is the most prevalent malignancy in Caucasians. Optical coherence tomography (OCT) is a non-invasive optical imaging technology using the principle of interferometry. OCT has shown a great potential in diagnosing, monitoring, and follow-up of BCC. So far most...

  5. The epidemiology of renal cell carcinoma

    NARCIS (Netherlands)

    Ljungberg, B.; Campbell, S.C.; Cho, H.Y.; Jacqmin, D.; Lee, J.E.; Weikert, S.; Kiemeney, L.A.L.M.

    2011-01-01

    CONTEXT: Kidney cancer is among the 10 most frequently occurring cancers in Western communities. Globally, about 270 000 cases of kidney cancer are diagnosed yearly and 116 000 people die from the disease. Approximately 90% of all kidney cancers are renal cell carcinomas (RCC). OBJECTIVE: The causes

  6. Pathological Fracture Complicating Squamous Cell Carcinoma: A ...

    African Journals Online (AJOL)

    Josephine Nakato

    Burrows and Lyall2 reported malignant transformation of a venous ulcer. Kubler5 gives a rare report of malignant transformation of chronic changes in the skin that lead to squamous cell carcinoma. The cause of this ulcer was not known in this case due to the fact that the patient presented late by which time the ulcer had ...

  7. Merkel cell carcinoma masquerading as a chalazion.

    Science.gov (United States)

    Rawlings, Nigel G; Brownstein, Seymour; Jordan, David R

    2007-06-01

    A 62-year-old woman presented with a large rapidly growing violaceous mass initially diagnosed as a chalazion. Histopathologic examination disclosed Merkel cell carcinoma (MCC). Radiotherapy was not tolerated. Despite chemotherapy, she succumbed to widespread metastases 13 months later. MCC must be included in the differential diagnosis of solitary eyelid nodules, requiring early and aggressive treatment.

  8. Utilizing pre-therapy clinical schema and initial CT changes to predict progression-free survival in patients with metastatic renal cell carcinoma on VEGF-targeted therapy: a preliminary analysis.

    Science.gov (United States)

    Smith, Andrew D; Shah, Shetal N; Rini, Brian I; Lieber, Michael L; Remer, Erick M

    2013-10-01

    Because of varying treatment effectiveness with vascular endothelial growth factor (VEGF)-targeted therapy in patients with metastatic renal cell carcinoma (RCC), the association of prognostic pre-therapy clinical schema, initial post-therapy computed tomography (CT) findings, and combination thereof in predicting progression-free survival (PFS) was investigated. A predictive biomarker that combines clinical risk factors and CT imaging features associated with initial response to therapy would be useful in stratifying patients into risk groups to guide therapy, in designing and interpreting results of clinical trials, in planning risk-directed therapy, and in patient counseling. Early identification of poor responders using an imaging biomarker may reduce drug-related toxicity and cost and allow for a therapeutic intervention before disease burden significantly advances. For this institutional review board-approved HIPAA-compliant retrospective study, baseline data for 82 patients with metastatic RCC treated with sunitinib or sorafenib was obtained for risk stratification by Memorial Sloan Kettering Cancer Center (MSKCC) criteria and criteria by Heng et al. (J Clin Oncol 2009;27:5794-9), (described here as "VEGF prognostic factors criteria"). The initial post-therapy CT was evaluated by Response Assessment Criteria in Solid Tumors (RECIST), Choi criteria, and Morphology, Attenuation, Size, and Structure (MASS) criteria. Kaplan-Meier estimates of PFS (the reference standard) for each patient group and overall accuracy of each method and combined criteria were calculated. The MSKCC model, VEGF prognostic factors criteria, RECIST, MASS criteria, MSKCC + MASS criteria, and VEGF prognostic factors + MASS criteria each demonstrated significant differences in PFS among patient groups (P therapy clinical risk factors and CT imaging response by MASS criteria more effectively predicted PFS in patients with metastatic RCC on VEGF-targeted therapy than any single method

  9. The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Shuo Chen

    2013-12-01

    Full Text Available Background: Ras homolog gene family member A (RhoA is involved in Wnt-5a–induced migration of gastric and breast cancer cells. We investigated the roles of RhoA and Wnt-5a in ovarian carcinoma. Methods: RhoA and Wnt-5a mRNA and protein expression in normal fallopian tube epithelium, benign tumors, primary ovarian carcinomas, and metastatic omentum were quantified. RhoA or Wnt-5a was knocked down in OVCAR3 ovarian carcinoma cells using siRNAs and cell phenotype and expression of relevant molecules were assayed. Results: RhoA and Wnt-5a mRNA and protein expression were found to be significantly higher in metastatic omentum than in ovarian carcinomas, benign tumors, and normal fallopian tube epithelium (p < 0.05, and positively associated with differentiation and FIGO staging (stage I/II vs. stage III/IV in ovarian carcinoma (p < 0.05. RhoA and Wnt-5a expression were positively correlated in ovarian carcinoma (p = 0.001, R2 = 0.1669. RhoA or Wnt-5a knockdown downregulated RhoA and Wnt-5a expression; reduced cell proliferation; promoted G1 arrest and apoptosis; suppressed lamellipodia formation, cell migration, and invasion; and reduced PI3K, Akt, p70S6k, Bcl-xL, survivin, and VEGF mRNA or protein expression. Conclusions: This is the first demonstration that RhoA and Wnt-5a are associated with ovarian carcinogenesis and apoptosis inhibition; there might be positive correlation between RhoA and Wnt-5a expression. RhoA is a potential tumorigenesis, differentiation, and progression biomarker in ovarian carcinoma.

  10. Squamous cell carcinoma of the conjunctiva

    Directory of Open Access Journals (Sweden)

    Stephen Gichuhi

    2017-02-01

    Full Text Available Squamous cell carcinoma of the conjunctiva is the end-stage of a spectrum of disease referred to as ocular surface squamous neoplasia (OSSN. OSSN is a malignant disease of the eyes that can lead to loss of vision and, in severe cases, death. The main risk factors for both are exposure to solar ultraviolet radiation outdoors, HIV/AIDS, human papilloma virus and allergic conjunctivitis. The limbal epithelial cells appear to be the progenitors of this disease.

  11. Intraosseous carcinoma of the jaws: A clinicopathologic review. Part III: Primary intraosseous squamous cell carcinoma

    NARCIS (Netherlands)

    Woolgar, J.A.; Triantafyllou, A.; Ferlito, A.; Devaney, K.O.; Lewis Jr., J.S.; Rinaldo, A.; Slootweg, P.J.; Barnes, L.

    2013-01-01

    This is the third part of a review of the clinicopathologic features of intraosseous carcinoma of the jaws (IOCJ). In parts 1 and 2, we discussed metastatic and salivary-type and odontogenic carcinomas, respectively. This part deals with primary intraosseous squamous cell carcinoma. Again, based on

  12. HER2-Positive Metaplastic Spindle Cell Carcinoma Associated with Synchronous Bilateral Apocrine Carcinoma of the Breast

    Directory of Open Access Journals (Sweden)

    Katsumi Kito

    2014-01-01

    Full Text Available Apocrine carcinoma, which is strictly defined as over 90% of tumor cells showing apocrine differentiation, is a rare variant of breast cancer. Here we report an uncommon case in which apocrine carcinomas developed concurrently in both breasts; in addition, a sarcomatoid spindle cell lesion was coincident in the right breast. Both apocrine carcinomas were immunohistochemically negative for estrogen receptor (ER and progesterone receptor (PgR, but diffusely positive for androgen receptor (AR, GCDFP-15, and HER2. The presence of intraductal components in bilateral carcinomas and the absence of lymph node metastasis suggested that they were more likely to be individual primary lesions rather than metastatic disease. The spindle cell lesion showed a relatively well-circumscribed nodule contiguous with the apocrine carcinoma. HER2 oncoprotein overexpression was observed not only in the apocrine carcinoma, but also in the spindle cell lesion. Since the spindle cell component was intimately admixed with apocrine carcinoma and had focal cytokeratin expression, we diagnosed it as metaplastic spindle cell carcinoma, which was originated from the apocrine carcinoma. To our knowledge, this is the first case report of a patient with synchronous bilateral apocrine carcinomas coinciding with metaplastic carcinoma.

  13. AHNAK enables mammary carcinoma cells to produce extracellular vesicles that increase neighboring fibroblast cell motility.

    Science.gov (United States)

    Silva, Thaiomara A; Smuczek, Basílio; Valadão, Iuri C; Dzik, Luciana M; Iglesia, Rebeca P; Cruz, Mário C; Zelanis, André; de Siqueira, Adriane S; Serrano, Solange M T; Goldberg, Gary S; Jaeger, Ruy G; Freitas, Vanessa M

    2016-08-02

    Extracellular vesicles play important roles in tumor development. Many components of these structures, including microvesicles and exosomes, have been defined. However, mechanisms by which extracellular vesicles affect tumor progression are not fully understood. Here, we investigated vesicular communication between mammary carcinoma cells and neighboring nontransformed mammary fibroblasts. Nonbiased proteomic analysis found that over 1% of the entire proteome is represented in these vesicles, with the neuroblast differentiation associated protein AHNAK and annexin A2 being the most abundant. In particular, AHNAK was found to be the most prominent component of these vesicles based on peptide number, and appeared necessary for their formation. In addition, we report here that carcinoma cells produce vesicles that promote the migration of recipient fibroblasts. These data suggest that AHNAK enables mammary carcinoma cells to produce and release extracellular vesicles that cause disruption of the stroma by surrounding fibroblasts. This paradigm reveals fundamental mechanisms by which vesicular communication between carcinoma cells and stromal cells can promote cancer progression in the tumor microenvironment.

  14. Clinical Significance of Langerhans Cells in Squamous Cell Carcinoma of the Larynx

    Directory of Open Access Journals (Sweden)

    Francisco Esteban

    2012-01-01

    Full Text Available Langerhans cells (LCs may be involved in the immunosurveillance against tumors as antigen-presenting cells. Our objective has been to determine the relevance of LC in progression of larynx squamous cell carcinomas and their relationship with different subpopulations of tumor-infiltrating cells. LCs were investigated by immunohistochemical methods using anti-CD1 antibody. LCs were detected in most of the primary tumors studied (44 out of 50 and also in metastases (6 out of 10 and recurrences (2 out of 3, but we did not find any statistical association between number of LCs and clinical-pathological parameters or survival. However, the number of LCs was increased in patients with evident infiltration of lymphocytes, mainly cytotoxic T cells. We can conclude that although LCs did not show clinical utility as prognostic marker, they may play a role in releasing an active immune response in larynx carcinomas, according to their ability to present antigens to sensitized T cells.

  15. Cytologic and histopathologic diagnosis in bronchopulmonary squamous cell carcinoma.

    Science.gov (United States)

    Drăgan, Ana Maria; Roşca, Elena; Muţiu, Gabriela

    2011-01-01

    The classification of squamous cell carcinomas, based on cellular differentiation features, includes the poorly differentiated epidermoid carcinomas and well-differentiated epidermoid carcinomas. The histogenetic cytologic data clarify conventional cytodiagnosis of poorly differentiated epidermoid carcinomas and poorly differentiated adenocarcinoma, and also eliminate other categories such as large cell carcinoma and small cell anaplastic carcinoma. We conducted a study for evaluating the degree of differentiation of pulmonary squamous cell carcinoma in 620 patients - 551 men (88.8%) and 69 women (11.1%) who had lung cancer confirmed by cytologic, histologic and bronchoscopic examination. The cytologic examination was performed on slides with samples obtained by bronchial brushing and prints of bronchial biopsy stained with the Giemsa method. Histopathologic examination was performed on samples obtained by bronchial biopsy and stained with Hematoxylin-Eosin. At cytologic examination we found: poorly differentiated epidermiod carcinomas in 66 cases (33.8%), moderately differentiated epidermoid carcinomas in 22 cases (11.2%) and well differentiated epidermoid carcinomas in 107 cases (54.8%). Histological examination revealed: poorly differentiated epidermoid carcinomas in 133 cases (45.7%), moderately differentiated epidermoid carcinomas in 32 cases (10.9%), and well differentiated epidermoid carcinomas in 126 cases (43.2%). Our results suggested the importance of the association between cytologic and histopatologic examinations in the diagnosis of lung cancer.

  16. Electroporation Enhances Bleomycin Efficacy in Cats with Periocular Carcinoma and Advanced Squamous Cell Carcinoma of the Head.

    Science.gov (United States)

    Spugnini, E P; Pizzuto, M; Filipponi, M; Romani, L; Vincenzi, B; Menicagli, F; Lanza, A; De Girolamo, R; Lomonaco, R; Fanciulli, M; Spriano, G; Baldi, A

    2015-01-01

    Advanced carcinoma of the head represents a substantial health problem in cats for local control and overall survival. Evaluate the capability of electrochemotherapy (ECT) to improve bleomycin efficacy in cats with periocular carcinoma and advanced carcinoma of the head. Twenty-one cats with periocular carcinoma (17 squamous cell carcinoma [SCC] and 4 anaplastic carcinoma) and 26 cats with advanced SCC of the head. Nonrandomized prospective controlled study. Periocular carcinoma cohorts: 12 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT under anesthesia; 9 cats were treated with bleomycin alone. Advanced head SCC cohorts: 14 cats were treated with bleomycin (15 mg/m(2) i.v.) coupled with ECT administered under sedation; 12 control cats were treated with bleomycin alone. ECT treatments (2-8) were performed every other week until complete remission (CR) or tumor progression occurred. Toxicities were minimal and mostly treated symptomatically. Overall response rate in the ECT treated animals was 89% (21 Complete Response [CR] and 2 Partial Response [PR]) whereas controls had response rate of 33% (4 CR and 3 PR). Median time to progression in ECT group was 30.5 months, whereas in controls it was 3.9 months (P < .0001). Median time to progression for ECT cohorts was 24.2 months for periocular cohort and 20.6 in advanced head SCC cohort, respectively. Electrochemotherapy is well tolerated for advanced SCC of the head in cats; its use may be considered among loco-regional strategies for cancer therapy in sensitive body regions such as periocular region. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  17. Wound Myiasis in a Patient with Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Mohammad Namazi

    2009-01-01

    Full Text Available A 60-year-old, otherwise healthy, male farmer presented to our Dermatology Department with a large ulcer on his lower right leg. The lesion had started as a small papule 6 months before, which became eroded and transformed into a rather rapidly progressive ulcer. On careful inspection, numerous larvae were found moving within the wound. The larvae were analyzed and found to be Lucilia sericata (the green bottle blowfly. The lesion was diagnosed histopathologically as squamous cell carcinoma. The myiasis was treated by submerging the wound in a dilute permanganate potassium solution.

  18. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Lijie [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Dong, Pingping [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Liu, Longzi; Gao, Qiang; Duan, Meng [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Zhang, Si; Chen, She [Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Xue, Ruyi, E-mail: xue.ruyi@zs-hospital.sh.cn [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Wang, Xiaoying, E-mail: xiaoyingwang@fudan.edu.cn [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China)

    2016-04-29

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.

  19. New agents in renal cell carcinoma.

    Science.gov (United States)

    Dabney, Raetasha; Devine, Ryan; Sein, Nancy; George, Benjamin

    2014-09-01

    Prior to 2005, the treatment options for metastatic renal cell carcinoma (mRCC) were limited. There has been a proliferation of agents since the introduction of sorafenib, sunitinib, and becavicumab for clinical use in advanced renal cell carcinoma. Recently, four new agents have been approved by the US Food and Drug Administration (FDA) for use in mRCC. These agents come from two unique targeted pathways for RCC, tyrosine kinase inhibitors (TKIs) of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors. This review examines the investigational evolution, phases of development, adverse event profiles, and future directions of pazopanib, axitinib, everolimus, and temsirolimus as well as new novel agents being explored in clinical trials for these targeted pathways.

  20. Hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity in oral squamous cell carcinoma derived cells.

    Science.gov (United States)

    Chaudhari, Pratik Rajeev; Charles, Silvania Emlit; D'Souza, Zinia Charlotte; Vaidya, Milind Murlidhar

    2017-11-15

    BPAG1e and Plectin are hemidesmosomal linker proteins which anchor intermediate filament proteins to the cell surface through β4 integrin. Recent reports indicate that these proteins play a role in various cellular processes apart from their known anchoring function. However, the available literature is inconsistent. Further, the previous study from our laboratory suggested that Keratin8/18 pair promotes cell motility and tumor progression by deregulating β4 integrin signaling in oral squamous cell carcinoma (OSCC) derived cells. Based on these findings, we hypothesized that linker proteins may have a role in neoplastic progression of OSCC. Downregulation of hemidesmosomal linker proteins in OSCC derived cells resulted in reduced cell migration accompanied by alterations in actin organization. Further, decreased MMP9 activity led to reduced cell invasion in linker proteins knockdown cells. Moreover, loss of these proteins resulted in reduced tumorigenic potential. SWATH analysis demonstrated upregulation of N-Myc downstream regulated gene 1 (NDRG1) in linker proteins downregulated cells as compared to vector control cells. Further, the defects in phenotype upon linker proteins ablation were rescued upon loss of NDRG1 in linker proteins knockdown background. These data together indicate that hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity possibly through NDRG1 in OSCC derived cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Radiation-induced basal cell carcinoma

    OpenAIRE

    Zargari, Omid

    2015-01-01

    Background: The treatment of tinea capitis using radiotherapy was introduced at the beginning of the twentieth century. A variety of cancers including basal cell carcinoma (BCC) are seen years after this treatment. Objective: We sought to determine the clinical characteristics of BCCs among irradiated patients. Methods: The clinical records of all patients with BCC in a clinic in north of Iran were reviewed. Results: Of the 58 cases of BCC, 29 had positive history for radiotherapy in their ch...

  2. Squamous cell carcinoma in situ after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kambara, Takeshi; Nishiyama, Takafumi; Yamada, Rie; Nagatani, Tetsuo; Nakajima, Hiroshi [Yokohama City Univ. (Japan). School of Medicine; Sugiyama, Asami

    1997-12-31

    We report two cases with Squamous Cell Carcinoma (SCC) in situ caused by irradiation to hand eczemas, resistant to any topical therapies. Both of our cases clinically show palmer sclerosis and flexor restriction of the fingers, compatible to chronic radiation dermatitis. Although SCC arising in chronic radiation dermatitis is usually developed ten to twenty years after irradiation, in our cases SCC were found more than forty years after irradiation. (author)

  3. Basal cell carcinoma of the perineum.

    Science.gov (United States)

    Levin, Adriane Ann; Dabade, Tushar; Dandekar, Monisha; Rogers, Gary; Rosmarin, David

    2014-08-17

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. Most BCCs are found on areas of UV-damaged skin, The study of BCCs of sun-protected regions, however, suggests a more complex pathogenesis. We present a case of BCC of the perineum in a man with no previous history of skin cancer. This is the first report of BCC in this region and one of a small body of cases arising on or near the genital and perianal regions.

  4. Papillocystic Variant of Acinar Cell Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Jasim Radhi

    2010-01-01

    Full Text Available Acinar cell pancreatic carcinoma is a rare solid malignant neoplasm. Recent review of the literature showed occasional cases with papillary or papillocystic growth patterns, ranging from 2 to 5 cm in diameter. We report a large 10 cm pancreatic tumor with papillocystic pathology features involving the pancreatic head. The growth pattern of these tumors could be mistaken for intraductal papillary mucinous tumors or other pancreatic cystic neoplasms.

  5. RPA1 expression in esophageal carcinoma and its influence on radiosensitivity of esophageal carcinoma TE-1 cells.

    Science.gov (United States)

    Zhang, D J; Xiang, J; Wang, X; Wang, J; Xiao, J C; Xu, W; Xu, H; Xin, Y; Zhang, L Z; Pei, D S; Zheng, J N; Gu, Y M

    2015-12-01

    To determinate the RPA1 expression in esophageal carcinoma and the paired tumor-adjacent tissue, and to explore the influence of RPA1 on radiosensitivity of esophageal carcinoma TE-1 cells. Firstly, the RPA1 expression of 40 cases esophageal carcinoma and their adjacent tissues were detected by immunohistochemistry. Secondly, The esophageal carcinoma cell subline-radiation resistance model (TE-1R) was constructed by radiation-induction, the RPA1 expression and proliferation activity of TE-1 and TE-1R cells were detected by Western blot and MTT assay respectively. After radiation, the expression of RPA1 and cell apoptosis were detected by Western blot and FACS respectively. Cell clone formation and survival rate were detected by clonogenic assay. Thirdly, Inhibiting RPA1 expression by siRNA in TE-1 cells, the expression of RPA1 was detected by RT-PCR and Western blot, Cell proliferation inhibition ratio and cell apoptosis after radiation were detected by MTT assay and FACS respectively. The RPA1 expression in esophageal carcinoma was significantly higher than that in the tumor-adjacent tissues, which was associated with tumor invasion and lymph node metastasis. The RPA1 expression in TE-1R cells was higher than that in TE-1 cells, while the proliferation activity of TE-1R cells was lower than that of TE-1 cells, and the apoptosis rate of TE-1R cells after radiation was less than that of TE-1 cells. In addtion, the clone formation and survival rate of TE-1R cells were higher than that of TE-1 cells. Moreover, inhibiting RPA1 expression by siRNA-RPA1 could promoted proliferation inhibition ratio and apoptosis rate of TE-1 cells after radiation. The over-expression of RPA1 in esophageal carcinoma was related with progression and metastasis. Moreover, radiation induced the excessive expression RPA1 in TE-1 cells, and the radiosensitivity of TE-1R cells was less than that of TE-1 cells. Furthermore, inhibiting RPA1 expression could increase radiosensitivity of TE-1 cells

  6. SIADH Induced by Pharyngeal Squamous Cell Carcinoma: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Hafiz Muhammad Sharjeel Arshad

    2016-01-01

    Full Text Available Background. The Syndrome of Inappropriate Antidiuretic Hormone (SIADH is considered to be the most common cause of euvolemic hyponatremia. The most common malignancy associated with SIADH is small cell lung cancer. We present a rare case of a patient with SIADH secondary to well differentiated squamous cell carcinoma of the naso-oropharynx. Case. A 46-year-old Caucasian woman presented to emergency department with four-week history of progressive dysphagia. On examination, she was found to have a pharyngeal mass. CT scan and MRI of neck confirmed a mass highly suspicious of carcinoma. Patient’s serum sodium level decreased to 118 mEq/L and other labs including serum and urine osmolality confirmed SIADH. She was started on fluid restriction and oral sodium tablets which gradually improved her serum sodium levels. Biopsy confirmed diagnosis of squamous cell carcinoma of pharynx. Conclusion. SIADH can be caused by squamous cell carcinoma. Appropriate management includes fluid restriction.

  7. CT features of nonfunctioning islet cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Eelkema, E.A.; Stephens, D.H.; Ward, E.M.; Sheedy, P.F. II

    1984-11-01

    To determine the computed tomographic (CT) characteristics of nonfunctioning islet cell carcinoma of the pancreas, the CT scans of 27 patients with that disease were reviewed. The pancreatic tumor was identified as a mass in 26 patients (96%) Of the 25 tumors evaluated with contrast enhancement, 20 became partially diffusely hyperdense relative to nearby normal pancreatic tissue. Hepatic metastases were identified in 15 patients (56%), regional lymphadenopathy in 10 (37%), atrophy of the gland proximal to the tumor in six (22%), dilatation of the biliary ducts in five (19%), and dilatation of the pancreatic duct in four (15%). The CT appearances of the nonfunctioning islet cell tumors were compared with those of 100 ordinary (ductal) pancreatic adenocarcinomas. Although the two types of tumors were sometimes indistinguishable, features found to be more characteristic of islet cell carcinoma included a pancreatic mass of unusually large size, calcification within the tumor, and contrast enhancement of either the primary tumor or hepatic metastases. Involvement of the celiac axis or proximal superior mesenteric artery was limited to ductal carcinoma.

  8. Intradural squamous cell carcinoma in the sacrum

    Directory of Open Access Journals (Sweden)

    Fujisawa Kozo

    2009-02-01

    Full Text Available Abstract Background Leptomeningeal carcinomatosis occurs in patients with cancer at the rate of approximately 5%; it develops particularly in patients with breast cancer, lung cancer, melanoma, leukemia, or malignant lymphoma. We describe a rare case of leptomeningeal carcinomatosis in which spinal intradural squamous cell carcinoma with no lesions in the cerebral meninges and leptomeninx, was the primary lesion. Methods A 64-year-old man complained of sacral pain. Although the patient was treated with analgesics, epidural block and nerve root block, sacral pain persisted. Since acute urinary retention occurred, he was operated on. The patient was diagnosed as having an intradural squamous cell carcinoma of unknown origin. Results Since the patient presented with a slightly decreased level of consciousness 2 months after surgery, he was subjected to MRI scanning of the brain and spinal cord, which revealed disseminated lesions in the medulla oblongata. The patient died of pneumonia and sepsis caused by methicillin-resistant Staphylococcus aureus 5 months after surgery. Conclusion We report the first case of a patient with intradural squamous cell carcinoma with unknown origin that developed independently in the sacrum.

  9. Low Concentration of Caffeine Inhibits the Progression of the Hepatocellular Carcinoma via Akt Signaling Pathway.

    Science.gov (United States)

    Dong, Shuying; Kong, Jian; Kong, Jinge; Shen, Qiang; Kong, Fandong; Sun, Wenbing; Zheng, Lemin

    2015-01-01

    Accumulating evidences have reported that caffeine has anticancer effects at high blood concentrations. However, whether caffeine has anticancer effects on human hepatocellular carcinoma (HCC) cells at low concentration, especially at physiologically applicable concentration (cell lines HepG2 and Huh7 were used. The cells were incubated with varying concentrations of caffeine (0, 50, 100, 200, 400 or 600 μM). MTT assay was used to investigate the proliferation ability in vitro. Migration and invasion abilities were determined by wound healing assay and transwell assay. The molecular changes were detected by western blot. An ectopic nude mice model which the mice were gavaged with caffeine was used to reveal the anticancer effects of caffeine on HepG2 cells in vivo. Results showed that caffeine could inhibit the proliferation, migration and invasion significantly at physiologically applicable concentration in vitro. Also the associated molecular changes of cancer progression were observed. In animal experiment, the mice gavaged with caffeine also performanced reduced tumor burden in vivo. Moreover, the interrelated protein expression was also observed in vivo which was coincident with the results in vitro. All in all, this observation indicated that caffeine may suppress the progression of HCC through Akt signaling pathway. This makes caffeine a potential candidate for treating HCC which will be a safer and more effective treatment by giving for a long time at physiologically applicable concentration.

  10. The Role of Myoepithelial Maspin in Breast Carcinoma Progression, Diagnosis and Screening

    National Research Council Canada - National Science Library

    Barsky, Sanford

    2002-01-01

    In glandular organs a precancerous stale precedes invasive carcinoma. in the breast this state is recognized as DGIS and consists of an epithelial cell proliferation confined by myoepithelial cells...

  11. Diagnosis and treatment of Basal cell and squamous cell carcinoma.

    Science.gov (United States)

    Firnhaber, Jonathon M

    2012-07-15

    Family physicians are regularly faced with identifying, treating, and counseling patients with skin cancers. Nonmelanoma skin cancer, which encompasses basal cell and squamous cell carcinoma, is the most common cancer in the United States. Ultraviolet B exposure is a significant factor in the development of basal cell and squamous cell carcinoma. The use of tanning beds is associated with a 1.5-fold increase in the risk of basal cell carcinoma and a 2.5-fold increase in the risk of squamous cell carcinoma. Routine screening for skin cancer is controversial. The U.S. Preventive Services Task Force cites insufficient evidence to recommend for or against routine whole-body skin examination to screen for skin cancer. Basal cell carcinoma most commonly appears as a pearly white, dome-shaped papule with prominent telangiectatic surface vessels. Squamous cell carcinoma most commonly appears as a firm, smooth, or hyperkeratotic papule or plaque, often with central ulceration. Initial tissue sampling for diagnosis involves a shave technique if the lesion is raised, or a 2- to 4-mm punch biopsy of the most abnormal-appearing area of skin. Mohs micrographic surgery has the lowest recurrence rate among treatments, but is best considered for large, high-risk tumors. Smaller, lower-risk tumors may be treated with surgical excision, electrodesiccation and curettage, or cryotherapy. Topical imiquimod and fluorouracil are also potential, but less supported, treatments. Although there are no clear guidelines for follow-up after an index nonmelanoma skin cancer, monitoring for recurrence is prudent because the risk of subsequent skin cancer is 35 percent at three years and 50 percent at five years.

  12. Merkel Cell Carcinoma Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Merkel cell carcinoma is a rare disease in which cancer cells form in Merkel cells in the skin and starts most often in areas of skin exposed to the sun. Find out about risk factors, symptoms, tests to diagnose, prognosis, staging, and treatment for Merkel cell carcinoma.

  13. Mutational Status of FGFR3 in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    P. Motahhary

    2012-01-01

    Full Text Available Objective: Head and neck squamous cell carcinoma, including oral squamous cell carcinoma (OSCC is the sixth most common cancer in the human population.Despite significant efforts committed in treatment of OSCC the overall survival rate of OSCC has not improved significantly. Activating mutations in the fibroblast growth factor receptor 3 (FGFR3 genes are responsible for some humancancers, including bladder and cervical carcinoma. Despite a high frequency in some benign skin disorders, FGFR3 mutations have not been reported in cutaneous malignancies. Therefore, FGFR3 gene may play a role in epithelial biology and mutations of FGFR3 gene may contribute to the development of OSCC.Materials and Methods: In this cross-sectional study, DNA was extracted and purified from snap frozen tissue biopsy sections of 20 OSCC cases. Exons 7 and 15 were amplified by polymerase chain reaction (PCR and sequenced in both directions.Results: In three cases silent mutations were identified in exon 7 (882 T to Cwhich may be introduced as Single Nucleotide Polymorphism (SNP and no mutation was identified in exon 15.Conclusion: FGFR3 gene mutation in exon 7 and 15 has no significant role in the development and progression of OSCC. Analyzing other exons or considering other advanced gene mutation assessment techniques may clarify the role of this receptor mutation in OSCC pathogenesis.

  14. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, Annika; Trepiakas, Redas; Wenandy, Lynn

    2008-01-01

    Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...... with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype...

  15. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma - A clinical, phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, A.; Trepiakas, R.; Wenandy, L.

    2008-01-01

    Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...... with a DC- based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype...

  16. Dynamic protein interaction modules in human hepatocellular carcinoma progression.

    Science.gov (United States)

    Yu, Hui; Lin, Chen-Ching; Li, Yuan-Yuan; Zhao, Zhongming

    2013-01-01

    Gene expression profiles have been frequently integrated with the human protein interactome to uncover functional modules under specific conditions like disease state. Beyond traditional differential expression analysis, differential co-expression analysis has emerged as a robust approach to reveal condition-specific network modules, with successful applications in a few human disease studies. Hepatocellular carcinoma (HCC), which is often interrelated with the Hepatitis C virus, typically develops through multiple stages. A comprehensive investigation of HCC progression-specific differential co-expression modules may advance our understanding of HCC's pathophysiological mechanisms. Compared with differentially expressed genes, differentially co-expressed genes were found more likely enriched with Hepatitis C virus binding proteins and cancer-mutated genes, and they were clustered more densely in the human reference protein interaction network. These observations indicated that a differential co-expression approach could outperform the standard differential expression network analysis in searching for disease-related modules. We then proposed a differential co-expression network approach to uncover network modules involved in HCC development. Specifically, we discovered subnetworks that enriched differentially co-expressed gene pairs in each HCC transition stage, and further resolved modules with coherent co-expression change patterns over all HCC developmental stages. Our identified network modules were enriched with HCC-related genes and implicated in cancer-related biological functions. In particular, APC and YWHAZ were highlighted as two most remarkable genes in the network modules, and their dynamic interaction partnership was resolved in HCC development. We demonstrated that integration of differential co-expression with the protein interactome could outperform the traditional differential expression approach in discovering network modules of human diseases

  17. Xp11 Translocation Renal Cell Carcinoma: Unusual Variant Masquerading as Upper Tract Urothelial Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Arash Akhavein

    2014-05-01

    Full Text Available Xp11 translocation renal cell carcinoma (TRCC is a rare subtype of renal cell carcinoma characterized by chromosomal translocations involving the TFE3 gene located at the Xp11.2 locus. Initial cases were more common in children, but cases in older adults have begun to accrue and suggest a relatively more aggressive course. We report a case of Xp11 TRCC in a 63-year-old female patient with initial presentation mimicking upper urinary tract urothelial cell carcinoma, with biopsy proving TRCC. She underwent a radical nephrectomy and paracaval lymph node dissection and is followed up with the intent to initiate vascular endothelial growth factor–targeted therapy in case of recurrence.

  18. Nivolumab, Carboplatin, and Paclitaxel in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma That Can Be Removed by Surgery

    Science.gov (United States)

    2017-11-20

    Name Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; 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 IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Laryngeal Squamous Cell Carcinoma; Stage IV Oral Cavity Squamous Cell Carcinoma; Stage IV 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; Stage IVC Hypopharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Oral Cavity Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  19. Squamous cell carcinoma of the anal canal.

    LENUS (Irish Health Repository)

    Martin, F T

    2012-01-31

    Squamous cell carcinoma ofthe anal canal represents 1.5% of all malignancies affectingthe gastrointestinal tract. Over the past 20 years dramatic changes have been seen in both the epidemiological distribution of the disease and in the therapeutic modalities utilised to manage it. CLINICAL MANAGEMENT: Historically abdominoperineal resection had been the treatment of choice with local resection reserved for early stage disease. Work by Nigro et al. has revolutionised how we currently manage carcinoma of the anal canal, demonstrating combined modality chemoradiotherapy as an appropriate alternative to surgical resection with the benefit of preserving sphincter function. Surgery is then reserved for recurrent disease with salvage abdominoperineal resection. This article reviews current literature and highlights the changing therapeutic modalities with selected clinical cases

  20. Long Noncoding RNAs Act as Novel Biomarkers for Hepatocellular Carcinoma: Progress and Prospects

    Directory of Open Access Journals (Sweden)

    Han Bao

    2017-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common cancers worldwide and confers a poor prognosis. Novel diagnostic or prognostic biomarkers and effective therapeutic targets for HCCs are urgently needed. Currently, dozens of long noncoding RNAs (lncRNAs have been identified as playing critical roles in cancer development and progression. Advanced studies have shown that several well-known lncRNAs are dysregulated in HCC tissue as compared to adjacent noncancerous tissue. Furthermore, highly stable cell-free circulating nucleic acids (cfCNAs, including lncRNAs, aberrantly expressed in the plasma of HCC patients, have been detected. In this review, we focus on the most extensively investigated lncRNAs in HCC and discuss the potential of HCC-related lncRNAs as novel biomarkers for early diagnosis and prognosis.

  1. Transitional cell carcinoma express vitamin D receptors

    DEFF Research Database (Denmark)

    Hermann, G G; Andersen, C B

    1997-01-01

    Recently, vitamin D analogues have shown antineoplastic effect in several diseases. Vitamin D analogues exert its effect by interacting with the vitamin D receptor (VDR). Studies of VDR in transitional cell carcinoma (TCC) have not been reported. The purpose of the present study was therefore...... to examine whether human bladder tumor cells express VDR. Tumor biopsies were obtained from 26 patients with TCC. Expression of VDR was examined by immunohistochemical experiments. All tumors expressed VDR. Biopsies from advanced disease contained more VDR positive cells than low stage disease (p ....05). Similarly, also tumor grade appeared to be related to the number of cells expressing the receptor. Normal urothlium also expressed VDR but only with low intensity. Our study shows that TCC cells possess the VDR receptor which may make them capable to respond to stimulation with vitamin D, but functional...

  2. Spindle cell carcinoma of the nasal cavity

    Directory of Open Access Journals (Sweden)

    Mark D DeLacure

    2013-02-01

    Full Text Available Spindle cell carcinoma (SpCC is a unique variant of squamous cell carcinoma (SCC. SpCC confined to the nasal cavity is extremely rare, with only one case having been previously reported. We present a case report of nasal cavity SpCC and review the literature on this rare entity. A 29-year-old male presented with intermittent epistaxis from the left nasal cavity. On physical examination, the patient had an ulcerated mass in the left nasal vestibule and a biopsy showed a proliferation of spindle and epitheliod cells. The patient underwent wide local excision of the mass via a lateral alotomy approach and reconstruction with a composite conchal bowl skin and cartilage graft. Histologically, the mass had dyplastic squamous epithelium and spindle-shaped cells admixed with epitheliod cells. Immunohistochemistry was only positive for pancytokeratin AE1/AE3 and vimentin. Six months after surgery, the patient continues to have no evidence of disease. On literature review, only one previous case of SpCC confined to the nasal cavity was identified. We present a rare case of nasal cavity SpCC. No definite treatment protocol exists for this unique entity, but we believe that this tumor should primarily be treated with aggressive, wide local excision. Adjuvant radiation and/or chemotherapy have also been used anecdotally.

  3. Clinical variants, stages, and management of basal cell carcinoma

    Science.gov (United States)

    Dourmishev, Lyubomir A.; Rusinova, Darena; Botev, Ivan

    2013-01-01

    Basal cell carcinoma (BCC) is the most common paraneoplastic disease among human neoplasms. The tumor affects mainly photoexposed areas, most often in the head and seldom appears on genitalia and perigenital region. BCC progresses slowly and metastases are found in less than 0.5% of the cases; however, a considerable local destruction and mutilation could be observed when treatment is neglected or inadequate. Different variants as nodular, cystic, micronodular, superficial, pigment BCC are described in literature and the differential diagnosis in some cases could be difficult. The staging of BCC is made according to Tumor, Node, Metastasis (TNM) classification and is essential for performing the adequate treatment. Numerous therapeutic methods established for treatment of BCC, having their advantages or disadvantages, do not absolutely dissolve the risk of relapses. The early diagnostics based on the good knowledge and timely organized and adequate treatment is a precondition for better prognosis. Despite the slow progress and numerous therapeutic methods, the basal cell carcinoma should not be underestimated. PMID:23439912

  4. Clinical variants, stages, and management of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lyubomir A Dourmishev

    2013-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common paraneoplastic disease among human neoplasms. The tumor affects mainly photoexposed areas, most often in the head and seldom appears on genitalia and perigenital region. BCC progresses slowly and metastases are found in less than 0.5% of the cases; however, a considerable local destruction and mutilation could be observed when treatment is neglected or inadequate. Different variants as nodular, cystic, micronodular, superficial, pigment BCC are described in literature and the differential diagnosis in some cases could be difficult. The staging of BCC is made according to Tumor, Node, Metastasis (TNM classification and is essential for performing the adequate treatment. Numerous therapeutic methods established for treatment of BCC, having their advantages or disadvantages, do not absolutely dissolve the risk of relapses. The early diagnostics based on the good knowledge and timely organized and adequate treatment is a precondition for better prognosis. Despite the slow progress and numerous therapeutic methods, the basal cell carcinoma should not be underestimated.

  5. Pigmented basal cell carcinoma mimicking a superficial spreading melanoma.

    Science.gov (United States)

    Hasbún Acuña, Paula; Cullen Aravena, Roberto; Maturana Donaire, César; Ares Mora, Raúl; Porras Kusmanic, Ninoska

    2016-12-20

    Basal cell carcinoma is the most common form of skin cancer, especially in elderly people. Pigmented basal cell carcinoma is a rare subtype and has been described in the literature as a nodular and hyperpigmented lesion; rarely, it can appear as an extensive pigmented plate, which may be clinically indistinguishable from superficial spreading melanoma and Bowen disease. Dermatoscopy has a high sensitivity in the diagnosis of basal cell carcinoma. When Menzies criteria are used; however, the final diagnosis is made by histopathology. The objective of the present report is to analyze the case of a patient with pigmented basal cell carcinoma simulating a superficial spreading melanoma.

  6. [A Case Report of Splenic Metastasis of Renal Cell Carcinoma].

    Science.gov (United States)

    Yamaguchi, Shunsuke; Haba, Tomomi; Kawaguchi, Makoto; Koike, Hiroshi

    2017-09-01

    A 64-year-old female patient underwent radical left nephrectomy in 2005 after being diagnosed with renal cell carcinoma. The pathological diagnosis was pT2b pN0 M0 clear cell carcinoma. Three years postoperatively, metastatic recurrence in the para-aortic lymph node was noted, and the patient underwent retroperitoneal lymph node dissection in 2008. The pathological diagnosis was renal cell carcinoma (a combination of clear cell carcinoma and type 2 papillary cell carcinoma). Five years later, she exhibited splenic metastasis on computed tomography, but no other distant metastases were observed. She underwent splenectomy in 2013, and the pathological diagnosis was splenic metastasis of renal cell carcinoma (type 2 papillary cell carcinoma). Three months after the splenectomy, she developed multiple bone metastases but refused to undergo treatment with molecularly targeted drugs ; hence, she was transferred to palliative care services. Fourteen months after the splenectomy, she died of cancer. Most metastatic splenic tumors occur as part of multiple organ metastases in the terminal stage of renal cell carcinoma. If splenic metastasis of renal cell carcinoma is observed, further imaging studies should be performed, and splenectomy should only be considered if a definitive diagnosis of sporadic splenic metastasis is made.

  7. Carcinoma basocelular em localizações incomuns Basal cell carcinoma in unusual locations

    Directory of Open Access Journals (Sweden)

    Ane Beatriz Mautari Niwa

    2006-10-01

    Full Text Available Os autores apresentam cinco pacientes que desenvolveram carcinomas basocelulares em locais incomuns de ocorrência desse tumor. O objetivo é relatar a raridade topográfica da neoplasia cutânea e discutir o conceito de localização incomum para o carcinoma basocelular.The authors present five patients who develop basal cell carcinomas in sites this tumor rarely occurs. The aim is to report the rare location of this frequent cutaneous malignancy and to briefly discuss the concept of unusual location of basal cell carcinoma.

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

    Science.gov (United States)

    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

  9. Progressive encephalomyelitis with rigidity: a paraneoplastic presentation of oat cell carcinoma of the lung. Case report Encefalomielite progressiva com rigidez: uma apresentação paraneoplásica de carcinoma de pequenas células de pulmão. Relato de caso

    Directory of Open Access Journals (Sweden)

    Mariana Spitz

    2004-06-01

    Full Text Available Progressive encephalomyelitis with rigidity and myoclonus (PEWR is a rare neurological disorder, characterised by muscular rigidity, painful spasms, myoclonus, and evidence of brain stem and spinal cord involvement. A 73-year-old white man was admitted with a 10-day history of painful muscle spasms and continuous muscle rigidity on his left lower limb. He had involuntary spasms on his legs and developed encephalopathy with cranial nerves signs and long tract spinal cord symptomatology. Brain CT scan and spinal MRI were normal. The CSF showed lymphocytic pleocytosis and no other abnormalities. EMG showed involuntary muscle activity with 2-6 seconds of duration, interval of 30-50 ms and a frequency of 2/second in the left lower limb. Anti-GAD antibodies were detected in the blood. We detected radiological signs of lung cancer during the follow-up, which proved to be an oat cell carcinoma. The patient died two weeks after the diagnosis of the cancer.A encefalomielite progressiva com rigidez e mioclonia (PEWR é doença neurológica rara, caracterizada por rigidez muscular, espasmos dolorosos, mioclonia e evidência de envolvimento de tronco cerebral e medula espinhal. Um paciente branco de 73 anos foi admitido com história de 10 dias de espasmos musculares dolorosos e rigidez muscular contínua no membro inferior esquerdo. Apresentava espasmos involuntários em membros inferiores e evoluiu com encefalopatia associada a sinais de nervos cranianos e sintomatologia de trato longo de medula espinhal. A tomografia computadorizada de crânio e a ressonância magnética de coluna foram normais. O LCR evidenciou pleocitose linfocítica, sem outras alterações. A EMG mostrou atividade muscular involuntária, de duração de 2-6 segundos, intervalo de 30-50 ms e uma freqüência de 2/segundo no membro inferior esquerdo. Foram detectados anticorpos anti-GAD no sangue. Na evolução, foram observados sinais radiográficos de neoplasia pulmonar, sendo

  10. EXPRESSION PROFILES AND METHYLATION GENES IN CLEAR CELL RENAL CARCINOMA

    Directory of Open Access Journals (Sweden)

    E. A. Braga

    2016-01-01

    Full Text Available Renal cancer (RC is a common malignancy of the genitourinary system. Clear cell renal cell carcinoma is the most common histological type of RC. In most cases diagnosis and prognosis of clear cell renal cell carcinoma are based on the results of instrumental tests, while search for novel molecular RC markers and their characterization remain relevant. Molecular genetic abnormalities accompanied with changes in gene expression underly the RC carcinogenesis; however, diagnostic panels of the expression markers of RC are still not widely used. This review represents the results of recent research in the area of gene expression markers of RC aimed to elaborate prognostic test systems. Application of the NotI-microarray methodology allowed for identification of many novel genes associated with RC pathogenesis. The relationship of alterations of expression level and methylation of chromosome 3 genes with RC progression and metastasis has been shown. Based on this data, a  diagnostic marker system for RC have been proposed with identification of expression and methylation profiles and novel markers, that is an urgent problem in modern urologic oncology.

  11. Focus on Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Venura Samarasinghe

    2011-01-01

    Full Text Available 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.

  12. ROLE OF THE MORPHOMETRIC PARAMETERS OF INTRATUMORAL MICROVESSELS AND THE PROLIFERATIVE ACTIVITY OF TUMOR CELLS IN RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. A. Gorban

    2014-08-01

    Full Text Available Tumor cell proliferation and angiogenesis are essential factors for tumor growth, progression, and metastasis.Objective: to assess the relationship between the values of proliferative activity and the morphometric parameters of intratumoral microvessels in metastatic and localized carcinomas of the kidney.Materials and methods. Surgical specimens taken from 54 patients (32 men and 22 women aged 26 to 69 years (mean age 55 ± 1.5 years with the verified diagnosis of clear-cell renal cell carcinoma (RCC were studied.Conclusion. Proliferative activity and angioarchitectonics are an important biological characteristic of a tumor of unequal clinical value in RCC. Metastatic carcinoma has a higher proliferative activity and a low tumor vascularization than those of localized carcinoma.

  13. Chemotherapy for pulmonary large cell neuroendocrine carcinomas : Does the regimen matter?

    NARCIS (Netherlands)

    Derks, Jules L.; van Suylen, Robert Jan; Thunnissen, Erik; den Bakker, Michael A.; Groen, Harry J.; Smit, Egbert F.; Damhuis, Ronald A.; van den Broek, Esther C.; Speel, Ernst-Jan M.; Dingemans, Anne-Marie C.

    Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC. The Netherlands Cancer

  14. MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration.

    Science.gov (United States)

    Zhu, Jie; Cui, Liang; Xu, Axiang; Yin, Xiaotao; Li, Fanglong; Gao, Jiangping

    2017-03-07

    Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells. Western blot and real-time qPCR (quantitative Polymerase Chain Reaction) was performed to examine the protein and mRNA levels of MEIS1. Cell proliferation, survival, in vitro migration and invasion were tested by MTT, colony formation, soft-agar, transwell (in vitro invasion/migration) assays, and tumor in vivo growthwas measured on nude mice model. In addition, flow-cytometry analysis was used to detect cell cycle arrest or non-apoptotic cell death of ccRCC cells induced by MEIS1. MEIS1 exhibits a decreased expression in ccRCC cell lines than that in non-tumor cell lines. MEIS1 overexpression inhibits ccRCC cells proliferation and induces G1/S arrest concomitant with marked reduction of G1/S transition regulators, Cyclin D1 and Cyclin A. Moreover, MEIS1-1 overexpression also induces non-apoptotic cell death of ccRCC cells via decreasing the levels of pro-survival regulators Survivin and BCL-2. Transwell migration assay (TMA) shows that MEIS1 attenuates in vitro invasion and migration of ccRCC cells with down-regulated epithelial-mesenchymal transition (EMT) process. Further, in nude mice model, MEIS1 inhibits the in vivo growth of Caki-1 cells. By investigating the role of MEIS1 in ccRCC cells' survival, proliferation, anchorage-independent growth, cell cycle progress, apoptosis and metastasis, in the present work, we propose that MEIS1 may play an important role in clear cell renal cell carcinoma (cc

  15. Carcinoma espinocelular de reto: relato de caso Squamous cell carcinoma of the rectum: a case report

    OpenAIRE

    Juliana Magalhães Lopes; Juliana Barreto Salem; Flávia Balsamo; Hernán Augusto Centurión Sobral; Letícia Sarmanho; Galdino José Sitonio Formiga

    2010-01-01

    O Carcinoma Espinocelular de Reto é entidade extremamente rara e seu comportamento biológico permanece desconhecido. O tratamento pode variar entre radio e quimioterapia isoladamente ou complementar ao tratamento cirúrgico. Relatamos caso de carcinoma espinocelular de reto superior, tratado com radio e quimioterapia, com regressão total da lesão.Squamous cell carcinoma of the rectum is a extremely rare neoplasm and its biological behavior remains unknown. Treatment varies from surgery with an...

  16. Over-expression of BAG-1 in head and neck squamous cell carcinomas (HNSCC) is associated with cisplatin-resistance

    OpenAIRE

    Liu, Shutong; Ren, Bo; Gao, Hang; Liao, Suchan; Zhai, Ying-Xian; Li, Shirong; Su, Xue-Jin; Jin, Ping; Stroncek, David; Xu, Zhixiang; Zeng, Qinghua; Li, Yulin

    2017-01-01

    Background In order to improve therapy for head and neck squamous cell carcinoma (HNSCC), biomarkers associated with local and/or distant tumor relapses and cancer drug resistance are urgently needed. This study identified a potential biomarker, Bcl-2 associated athanogene-1 (BAG-1), that is implicated in HNSCC insensitive to cisplatin and tumor progression. Methods Primary and advanced (relapsed from parental) University of Michigan squamous cell carcinoma cell lines were tested for sensitiv...

  17. [Descriptive study on basal cell eyelid carcinoma].

    Science.gov (United States)

    Pfeiffer, M J; Pfeiffer, N; Valor, C

    2015-09-01

    To describe a series of cases of basal cell carcinomas of the eyelid. A descriptive and retrospective study was conducted by reviewing the medical outcome, histopathological history, and photographic images of 200 patients with basal cell eyelid carcinomas. All were treated in the Herzog Carl Theodor Eye Hospital in Munich, Germany, between 2000 and 2013. In the present study, it was found that females are more affected than males. The mean age of presentation of the tumor occurred at the age of 70 years. In 50% of the cases the tumor was found on the lower lid, especially medially from the center of the lid. The lid margin was involved in 47% of all tumors. The mean diameter was 9.2mm. The recurrence rate after surgery with histologically clear resection margins was 5%. There was a significant relationship between tumor diameter and age. As tumors where located farther away from medial and closer to the lid margin, they became larger. There is a predominance of women affected by this tumor. This may be related to the fact that the sample was taken from those attending an oculoplastic surgery clinic, where there are generally more women than men attending. The formation of basal cell carcinomas increases with age. The infrequent involvement of the upper lid could be explained by the protection of the the eyebrow. The frequent involvement of the lower lid may be due to the light reflection (total reflection) by the cornea on the lower lid margin. Also chemical and physical effects of the tears may be more harmful on the lower lid. Patients tend to ask for medical help when they are females, younger, when the tumor is closer to the medial canthus or when the tumor is away from the lid margin. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Nonsurgical Treatment Options for Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Mary H. Lien

    2011-01-01

    Full Text Available Basal cell carcinoma (BCC remains the most common form of nonmelanoma skin cancer (NMSC in Caucasians, with perhaps as many as 2 million new cases expected to occur in the United States in 2010. Many treatment options, including surgical interventions and nonsurgical alternatives, have been utilized to treat BCC. In this paper, two non-surgical options, imiquimod therapy and photodynamic therapy (PDT, will be discussed. Both modalities have demonstrated acceptable disease control rates, cosmetically superior outcomes, and short-term cost-effectiveness. Further studies evaluating long-term cure rates and long-term cost effectiveness of imiquimod therapy and PDT are needed.

  19. Epidemiology and staging of renal cell carcinoma.

    Science.gov (United States)

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

    2014-03-01

    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.

  20. Primary Squamous Cell Carcinoma of the Stomach

    Directory of Open Access Journals (Sweden)

    Juan Antonio González-Sánchez

    2017-01-01

    Full Text Available Squamous cell carcinoma (SCC of the stomach is a rare entity. There are several theories regarding the development of this tumor, but its pathogenesis remains obscure. Fewer than 100 cases of primary SCC of the stomach have been published in the literature. Due to advanced stage at the time of diagnosis in most of these cases, the prognosis is generally poor. In the case presented here, endoscopy revealed a vegetative tumor in the stomach described as SCC by biopsy. Following curative surgery, adjuvant chemotherapy was administered; however, the patient died 3 years and 4 months after surgery after recurrence was diagnosed.

  1. Primary Squamous Cell Carcinoma of the Stomach.

    Science.gov (United States)

    González-Sánchez, Juan Antonio; Vitón, Rebeca; Collantes, Elena; Rodríguez-Montes, José Antonio

    2017-01-01

    Squamous cell carcinoma (SCC) of the stomach is a rare entity. There are several theories regarding the development of this tumor, but its pathogenesis remains obscure. Fewer than 100 cases of primary SCC of the stomach have been published in the literature. Due to advanced stage at the time of diagnosis in most of these cases, the prognosis is generally poor. In the case presented here, endoscopy revealed a vegetative tumor in the stomach described as SCC by biopsy. Following curative surgery, adjuvant chemotherapy was administered; however, the patient died 3 years and 4 months after surgery after recurrence was diagnosed.

  2. Fanconi anemia and vaginal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Jesus Paula Carvalho

    2012-01-01

    Full Text Available Fanconi Anemia (FA is an autosomal recessive disease characterized by chromosome instability, cellular hypersensitivity to DNA cross-linking agents, and increased predisposition to malignancies. We describe here a 28 year-old female with FA and vaginal squamous cell carcinoma treated by radiation therapy alone. The patient developed arm phlebitis, pulmonary fungal infection, and severe rectal bleeding, followed by hypocalcaemia, hypokalemia, vaginal bacterial and fungal infection, with subsequent leg and arm phlebitis, perineal abscess, and sepsis. The patient died 12 weeks later.

  3. Unilateral Renal Cell Carcinoma in a Dog

    Directory of Open Access Journals (Sweden)

    J. Y. Chung

    2014-01-01

    Full Text Available A 4-year-old, neutered male, American Cocker Spaniel weighing 8.3 kg was presented with a 1-month history of weight-loss, anorexia, intermittent vomiting and bloody-diarrhea. Abnormal blood tests results, a large mass on the kidney field in radiographic views and ultrasonography were presented. Nephroureterectomy was tried, but a large mass in the kidney and metastasis to the spleen caused to decline the surgery and treatment. The dog was euthanized, and necropsy and histological review revealed the renal cell carcinoma.

  4. Overview of Hurthle cell carcinoma of thyroid

    Directory of Open Access Journals (Sweden)

    Martin A Korzeniowski

    2017-07-01

    Full Text Available The clinical behaviour of Hurthle cell carcinoma (HCC of the thyroid is variable and there are many controversies in the literature. Here, we summarize an up-to-date review of the literature on genetics, diagnosis (ultrasound scan, fine needle aspiration, frozen section, etc., and management. At presentation, treatment decision should be made by a multidisciplinary board. Recurrent HCCs are seldom curable despite salvage treatments, which include radioactive iodine ablation, radiofrequency ablation, ethanol ablation, external radiotherapy, and systemic therapy. Further research is needed to develop more efficacious systemic treatments. Currently, lenvatinib, sunitinib, and sorafenib are available. The completed and ongoing clinical trials for HCC are summarized

  5. Squamous Cell Carcinoma of Mammary Gland in Domestic Cat

    OpenAIRE

    Filgueira,Kilder Dantas; Reche Junior,Archivaldo

    2012-01-01

    Background: In the feline species, 80% to 93% of neoplasias in the mammary gland are malignant, being the majority carcinomas. Among them, there is the mammary squamous cell carcinoma, which amounts to a very rare neoplasm in the domestic cat, with considerable potential for malignancy. This study aimed to report a case of squamous cell mammary carcinoma in the feline species. Case: A female cat, mixed breed, ten years old, presented history of skin lesion. The cat had been spayed two years b...

  6. Large cell neuroendocrine carcinoma of the ampulla of Vater.

    LENUS (Irish Health Repository)

    Beggs, Rachel E

    2012-09-01

    Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution.

  7. Percutaneous Cryoablation for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Tsitskari Maria

    2015-06-01

    Full Text Available Renal cell carcinoma (RCC is the most common type of kidney cancer in adults. Nephron sparing resection (partial nephrectomy has been the “gold standard” for the treatment of resectable disease. With the widespread use of cross sectional imaging techniques, more cases of renal cell cancers are detected at an early stage, i.e. stage 1A or 1B.  This has provided an impetus for expanding the nephron sparing options and especially, percutaneous ablative techniques.  Percutaneous ablation for RCC is now performed as a standard therapeutic nephron-sparing option in patients who are poor candidates for resection or when there is a need to preserve renal function due to comorbid conditions, multiple renal cell carcinomas, and/or heritable renal cancer syndromes. During the last few years, percutaneous cryoablation has been gaining acceptance as a curative treatment option for small renal cancers. Clinical studies to date indicate that cryoablation is a safe and effective therapeutic method with acceptable short and long term outcomes and with a low risk, in the appropriate setting.  In addition it seems to offer some advantages over radio frequency ablation (RFA and other thermal ablation techniques for renal masses.

  8. Cryospray ablation (CSA in the palliative treatment of squamous cell carcinoma of the esophagus

    Directory of Open Access Journals (Sweden)

    Johnston Mark H

    2007-03-01

    Full Text Available Abstract Background Esophageal carcinoma is the ninth most prevalent cancer worldwide with squamous cell carcinoma (SCCA and adenocarcinoma accounting for the vast majority of new cases (13,900 in 2003. Cure rates in the U.S. are less than 10%, similar to lung cancer. More than 50% of patients with esophageal carcinoma present with unresectable or metastatic disease, are not surgical candidates, or display disease progression despite the addition of neoadjuvant chemoradiotherapy to surgery. Need for improved palliation exits. Case presentation This case describes a 73-year-old African American male who presented with recurrent squamous cell carcinoma (SCCA of the esophagus who has a achieved complete remission for 24 months via endoscopic cryospray ablation. Conclusion Endoscopic cryo spray ablation warrants further investigation as a palliative treatment modality for esophageal cancer. This is the first reported case in the medical literature.

  9. C4.4A as a biomarker in pulmonary adenocarcinoma and squamous cell carcinoma

    DEFF Research Database (Denmark)

    Jacobsen, Benedikte; Kriegbaum, Mette Camilla; Santoni-Rugiu, Eric

    2014-01-01

    The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uPAR family of membrane proteins, qualifies as such a potential...... informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression...... to invasive carcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A...

  10. Proteomic identification of keratin alterations with enhanced proliferation of oral carcinoma cells by loss of mucosa-associated lymphoid tissue 1 expression.

    Science.gov (United States)

    Kawamoto, Yukihiro; Ohyama, Yoshito; Chiba, Tadashige; Yagishita, Hisao; Sakashita, Hideaki; Imai, Kazushi

    2013-09-01

    Progression of oral carcinomas associates with aberrant activation and inactivation of molecules that work in established or unknown pathways. Although mucosa‑associated lymphoid tissue 1 (MALT1) expressed in normal oral epithelium is inactivated in the aggressive subset of carcinomas with worse prognosis, phenotypic changes of carcinoma cells upon the loss of expression is unknown. We performed a proteomic analysis to identify MALT1‑regulated proteins in oral carcinoma cells. Four different keratins were included in the ten most abundantly changed proteins. K8/18 were upregulated in MALT1 stably‑expressing carcinoma cells and K5/14 in MALT1‑marginal control cells. K8/18 upregulation and K5/14 downregulation were MALT1 dose‑dependent and observed in a series of oral carcinoma cells. MALT1 suppressed cell proliferation (0.52-fold, Poral carcinomas into the advanced state.

  11. Oral Squamous Cell Carcinoma Mutational Profile in Taiwanese Population | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Oral squamous cell carcinoma (OSCC) is a major oral cancer subtype that is the fourth most common cancer affecting Taiwanese men. Despite known risk behaviors such as cigarette smoking, alcohol drinking, and betel nut chewing often indulged by Taiwanese men, the genetic contribution to the incidence or progression of OSCC has yet been elucidated in the Taiwanese population.

  12. Squamous cell carcinoma of the middle ear arising from CSOM: A case report

    Directory of Open Access Journals (Sweden)

    S R Davanageri

    2014-01-01

    Full Text Available Squamous cell carcinoma occurring in a background of chronic suppurative otitis media (CSOM is a rare complication. It runs an aggressive course. Hence early identification is significant to prevent disease progression and to improve the survival rate. Subjecting granulation tissue from middle ear for histopathologic examination is of importance to rule out associated malignant change.

  13. Cell death induction by the BH3 mimetic GX15-070 in thyroid carcinoma cells.

    Science.gov (United States)

    Broecker-Preuss, Martina; Viehof, Jan; Jastrow, Holger; Becher-Boveleth, Nina; Fuhrer, Dagmar; Mann, Klaus

    2015-07-22

    The evasion of cell death is one of the hallmarks of cancer, contributing to both tumor progression and resistance to therapy. Dedifferentiated and anaplastic thyroid carcinomas that do not take up radioiodine are resistant to conventional anticancer treatments and patients with these tumors are difficult to treat. BH3 mimetics are a new class of drugs that target anti-apoptotic proteins of the BCL-2 family and promote cell death. The purpose of this study was to analyze the molecular effects of the BH3 mimetic GX15-070 on thyroid carcinoma cell lines and to characterize cell death induced by GX15-070. A total of 17 cell lines derived from follicular, papillary, and anaplastic thyroid carcinomas were treated with GX15-070. Cell viability was measured with MTT assay while cell cycle phase distribution and subG1 peaks were determined after propidium iodide staining. We assessed cell death via the caspase 3/7 activity, caspase cleavage products, lactate dehydrogenase (LDH) liberation assays, and a LC3 analysis by western blot. Ultrastructural changes were analysed by electron microscopy of GX15-070-treated cells. After GX15-070 treatment, the number of viable cells was decreased in all cell lines examined, with IC50 values ranging from 48nM to 3.25 μM. We observed biochemical markers of autophagic cell death and necrosis like LC3 conversion and LDH release after the GX15-070 treatment. Electron microscopy revealed several common characteristic ultrastructural changes like swelling of mitochondria, dilatation of rough endoplasmic reticulum, membrane blebbing and formation of vacuoles. GX15-070 treatment induced DNA fragmentation detected by subG1-peak induction and an arrest in G1 phase of the cell cycle. Caspase activation after GX15-070 incubation was detected but had no effect on viability of cells. With these experiments we demonstrated the efficacy of the BH3 mimetic drug GX15-070 acting against dedifferentiated thyroid carcinoma cells of various histological

  14. Evaluation of Bone Cancer Pain Induced by Different Doses of Walker 256 Mammary Gland Carcinoma Cells.

    Science.gov (United States)

    Dong, Changsheng; Wu, RuiXin; Wu, Jing; Guo, Jing; Wang, Fangyuan; Fu, Yanli; Wang, Qing; Xu, Ling; Wang, Juyong

    2016-01-01

    Cancer pain is a complex medical syndrome. Understanding its underlying mechanisms relies on the use of animal models which can mimic the human condition. A crucial component of this model is the quantity of tumor cells; however, the exact relationship between the doses of tumor cells on bone cancer pain is yet unknown. We explored the relationship of different doses of Walker 256 carcinoma cells using a bone cancer pain model in rats, and evaluated its success and stability. Experimental animal study using a comparative design. Experimental Animal Center and Tumor Institute of Traditional Chinese Medicine. We constructed the bone cancer pain model by implanting Walker 256 carcinoma cells into the right tibia of Sprague-Dawley (SD) rats (150 - 170 g). Spontaneous pain, mechanical threshold, and paw withdrawal latency (PWL) were measured and x-ray, bone mineral density (BMD), histological, interleukin-1 beta (IL-1beta) mRNA, carboxyterminal telopeptide of type I collagen (ICTP), and bone alkaline phosphatase (BAP) were analyzed for bone pain model evaluation. The results showed that: (1) the 3 doses (3×105, 3.5×105, 4×105) of Walker 256 carcinoma cells can induce bone cancer pain from day 7 to day 21 after implantation into the right tibia of SD rats; (2) compared to the control group, 3×105, 3.5×105, and 4×105 Walker 256 carcinoma cells produced different pain manifestations, where the 3.5×105 dose of Walker 256 carcinoma cells resulted in the greatest bone cancer pain response; (3) the 3.5×105 dose induced the lowest mortality rate in rats; (4) Walker 256 carcinoma cells (3×105, 3.5×105, and 4×105) resulted in a significant decrease in the general condition and body weight of rats, where the 3.5×105 and 4×105 doses of carcinoma cells produced a greater effect than 3×105 dose of carcinoma cells; (5) progressive spontaneous pain, PWL, and mechanical threshold were exacerbated by 3.5×105 and 4×105 doses of carcinoma cells; (6) implantation of 3.5×105

  15. Rb Loss is Characteristic of Prostatic Small Cell Neuroendocrine Carcinoma

    Science.gov (United States)

    Tan, Hsueh-Li; Sood, Akshay; Rahimi, Hameed A.; Wang, Wenle; Gupta, Nilesh; Hicks, Jessica; Mosier, Stacy; Gocke, Christopher D.; Epstein, Jonathan I.; Netto, George J.; Liu, Wennuan; Isaacs, William B.; De Marzo, Angelo M.; Lotan, Tamara L.

    2014-01-01

    Purpose Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide diagnosis and therapy of this aggressive tumor. Experimental Design We examined the status of RB1, TP53 and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy number alteration analysis and sequencing of formalin fixed paraffin-embedded specimens. Results We found Rb protein loss in 90% (26/29) of small cell carcinoma cases with RB1 allelic loss in 85% (11/13) of cases. Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3/7) showed Rb protein loss. In contrast, only 7% (10/150) of primary high grade acinar carcinomas, 11% (4/35) of primary acinar carcinomas with neuroendocrine differentiation, and 15% (2/13) of metastatic castrate resistant acinar carcinomas showed Rb protein loss. Loss of PTEN protein was seen in 63% (17/27) of small cell carcinomas, with 38% (5/13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% (14/25) of small cell carcinomas, with 60% (6/10) of cases showing TP53 mutation. Conclusions Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by validated IHC assay. As Rb protein loss rarely occurs in high grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target. PMID:24323898

  16. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumour...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  17. Squamous cell carcinoma of the conjunctiva in Ilorin, Nigeria ...

    African Journals Online (AJOL)

    The aim was to determine the incidence of conjunctival squamous cell carcinoma at UITH over an 11 – year period. Nineteen patients (11males and 8 females) had histological confirmation of conjunctival squamous cell carcinoma out of 21 conjunctival specimens, representing 22.9% of all orbito-ocular tumours reviewed ...

  18. Characterizing the outcomes of metastatic papillary renal cell carcinoma

    DEFF Research Database (Denmark)

    Connor Wells, John; Donskov, Frede; Fraccon, Anna P

    2017-01-01

    Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were com...

  19. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumo...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  20. Squamous Cell Carcinoma of the Oral Cavity in the Elderly

    Directory of Open Access Journals (Sweden)

    Yi-Shing Leu

    2009-03-01

    Conclusion: Squamous cell carcinoma of the oral cavity did not have a significantly different outcome for elderly patients when compared with younger patients. Elderly patients with stage IVA squamous cell carcinoma of the oral cavity had poorer survival rates. When properly evaluated and monitored, conservative and conventional therapies seemed efficacious in the elderly.

  1. Squamous cell carcinoma of the temporal bone: results and management.

    NARCIS (Netherlands)

    Kunst, H.P.M.; Lavieille, J.P.; Marres, H.A.M.

    2008-01-01

    OBJECTIVE: Evaluation of the management and survival of patients treated for temporal bone squamous cell carcinoma. STUDY DESIGN: A retrospective analysis. SETTING: Tertiary care, academic referral center. PATIENTS: Twenty-eight patients underwent primary treatment for squamous cell carcinoma of the

  2. Large cell neuroendocrine carcinoma of the kidney with cardiac metastasis: a case report

    Directory of Open Access Journals (Sweden)

    Moeka Shimbori

    2017-10-01

    Full Text Available Abstract Background Primary large cell neuroendocrine carcinoma of the kidney is a rare and generally very aggressive disease. We present a case of a patient with primary large cell neuroendocrine carcinoma of the kidney with cardiac metastasis. Case presentation A 59-year-old Japanese man presented to his previous physician with hematuria. Computed tomography revealed masses in the heart and right kidney, and fluorodeoxyglucose-positron emission tomography showed abnormal uptake in the heart. A cardiac biopsy under transesophageal echocardiographic guidance revealed a metastatic tumor. Subsequently, multiple lung lesions were detected, and a right nephrectomy was performed after these metastases were suspected to have originated from renal carcinoma. Large cell neuroendocrine carcinoma of the kidney was ultimately diagnosed. Pancreatic metastasis was detected on computed tomography postoperatively. Three courses of chemotherapy with carboplatin and irinotecan were administered, and were temporarily effective against the metastatic lesions in the lungs and pancreas. However, our patient’s general condition deteriorated with the progression of the lesions, and he died 9 months after his initial examination. Conclusions Multi-agent chemotherapy, including platinum-based drugs was effective against large cell neuroendocrine carcinoma metastases, albeit only temporarily. This is the first reported case of large cell neuroendocrine carcinoma with cardiac metastasis.

  3. Progress in carbonate fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Krumpelt, M.; Roche, M.F.

    1995-08-01

    Our objective is to increase both the life and power of the molten carbonate fuel cell (MCFC) by developing improved components and designs. Current activities are as follows: (1) Development of lithium ferrate (LiFeO{sub 2}) and lithium cobaltate (LiCoO{sub 2}) cathodes for extended MCFC life, particularly in pressurized operation, where the present cathode, NiO, provides insufficient life; (2) Development of distributed-manifold MCFC designs for increased volumetric power density and decreased temperature gradients (and, therefore, increased life); (3) Development of components and designs appropriate for high-power-density operation (>2 kW/m{sup 2} and >100 kW/m{sup 3} in an integrated MCFC system); and (4) Studies of pitting corrosion of the stainless-steel interconnects and aluminized seals now being employed in the MCFC (alternative components will also be studied). Each of these activities has the potential to reduce the MCFC system cost significantly. Progress in each activity will be presented during the poster session.

  4. Intraventricular metastatic clear cell renal carcinoma.

    Science.gov (United States)

    Sava, I; Sava, Anca; Şapte, Elena; Mihailov, Claudia; Dumitrescu, Gabriela; Poeată, I; Sava, Florina; Haba, Danisia

    2013-01-01

    Intraventricular tumors represent a diagnostic problem, due to a wide range of differential diagnosis, with an important variability of tumoral histological types in adult and pediatric population. Patient, Our case is represented by a patient, aged 48 years, without any history of significant personal pathology, accusing nausea, vomiting, and intensive headache. In the morning, he became confused, having hallucinations for a short period of time, and has accused drowsiness for several weeks. Imaging (CT and MRI) shows a neoformation in the third ventricle, accompanied by bilateral lateral ventricles dilatation, with predominantly annular enhancement. During surgery, through the middle third transcallosal interhemispheric approach, it was revealed a reddish, well-demarcated intraventricular mass, well vascularized and with a firm consistency. Final pathologic diagnosis was metastatic clear cell renal carcinoma. Initial postoperative evolution was good, and then neurological and respiratory condition worsened as a bronchopneumonia lead to patient's death in 12 days after surgery. Clear cell carcinoma metastasis located in the third ventricle should be taken into consideration for patients presenting a single intraventricular lesion even they have no documented primary malignancy.

  5. Ovarian clear cell carcinoma with plasma cell-rich inflammatory stroma: a clear cell carcinoma subgroup with distinct clinicopathological features.

    Science.gov (United States)

    Kato, Noriko; Kurotaki, Hidekachi; Uchigasaki, Shinya; Fukase, Masayuki; Kurose, Akira

    2016-03-01

    Ovarian clear cell carcinoma has a unique stroma. Although a hyalinized or mucoid stroma is more common, the stroma sometimes shows a dense inflammatory infiltrate, simulating a dysgerminoma. The aim of this study was to analyse the character and significance of the inflammatory stroma. Twelve of 60 (20%) clear cell carcinomas showed an inflammatory stroma. The inflammatory stroma and hyalinized/mucoid stroma were mutually exclusive. Inflammatory cells were predominantly composed of CD138-positive plasma cells. As compared with the non-inflammatory cases, the epithelial component frequently showed a solid growth pattern and immunoreactivity for cyclooxygenase-2, one of the critical proinflammatory enzymes (P cell carcinoma cell lines into athymic nude mice. In particular, xenografts of one cell line (JHOC-5) were infiltrated by mature plasma cells, indicating that plasma cell differentiation was stimulated by JHOC-5 cells, independently of T lymphocytes. Clinicopathologically, the frequency of International Federation of Gynaecology and Obstetrics stage III was higher in the cases with an inflammatory stroma than in those without it (P cell carcinomas with an inflammatory stroma constitute a distinct clinicopathological subgroup. It is strongly suggested that tumour cells themselves are responsible for inducing inflammation and stimulating plasma cell differentiation in a paracrine manner. © 2015 The Authors. Histopathology Published by John Wiley & Sons Ltd.

  6. Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death.

    Science.gov (United States)

    Li, Sainan; Li, Jingjing; Dai, Weiqi; Zhang, Qinghui; Feng, Jiao; Wu, Liwei; Liu, Tong; Yu, Qiang; Xu, Shizan; Wang, Wenwen; Lu, Xiya; Chen, Kan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Fan, Xiaoming; Mo, Wenhui; Xu, Ling; Guo, Chuanyong

    2017-11-07

    Genistein is a natural isoflavone with many health benefits, including antitumour effects. Increased hypoxia-inducible factor 1 α (HIF-1α) levels and glycolysis in tumour cells are associated with an increased risk of mortality, cancer progression, and resistance to therapy. However, the effect of genistein on HIF-1α and glycolysis in hepatocellular carcinoma (HCC) is still unclear. Cell viability, apoptosis rate, lactate production, and glucose uptake were measured in HCC cell lines with genistein incubation. Lentivirus-expressed glucose transporter 1 (GLUT1) or/and hexokinase 2 (HK2) and siRNA of HIF-1α were used to test the direct target of genistein. Subcutaneous xenograft mouse models were used to measure in vivo efficacy of genistein and its combination with sorafenib. Genistein inhibited aerobic glycolysis and induced mitochondrial apoptosis in HCC cells. Neither inhibitors nor overexpression of HK2 or GLUTs enhance or alleviate this effect. Although stabiliser of HIF-1α reversed the effect of genistein, genistein no longer has effects on HIF-1α siRNA knockdown HCC cells. In addition, genistein enhanced the antitumour effect of sorafenib in sorafenib-resistant HCC cells and HCC-bearing mice. Genistein sensitised aerobic glycolytic HCC cells to apoptosis by directly downregulating HIF-1α, therefore inactivating GLUT1 and HK2 to suppress aerobic glycolysis. The inhibitory effect of genistein on tumour cell growth and glycolysis may help identify effective treatments for HCC patients at advanced stages.

  7. Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due to spinal metastases: a case report

    Directory of Open Access Journals (Sweden)

    Haffner Dieter

    2011-09-01

    Full Text Available Abstract Introduction Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have been reported previously. Case presentation We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma (squamous cell non-small cell lung carcinoma stage IV, T4N2M1, without epidermal growth factor receptor overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the bronchial carcinoma. No familial predisposition or toxin exposure was identified. Treatment following adult protocols consisted of surgical intervention for spinal metastases, first-line cisplatinum and gemcitabine, irradiation and second-line docetaxel. After a transient response our patient experienced disease progression and died about 10 months later. Conclusion Response and survival in our 16-year-old patient were similar to adult patients with stage IV non-small cell lung carcinoma.

  8. Direct FGF receptor 1 activation through an anti-idiotypic strategy mimicks the biological activity of FGF-2 and inhibits the progression of the bladder carcinoma derived from NBT-II cells.

    Science.gov (United States)

    Malavaud, Bernard; Pedron, Sandrine; Sordello, Sylvie; Mazerolles, Catherine; Billottet, Clotilde; Thiery, Jean-Paul; Jouanneau, Jacqueline; Plouët, Jean

    2004-09-02

    The hypothesis that tumor growth is angiogenesis-dependent has been documented by a considerable body of direct and indirect experimental data. Since the discovery of the vascular endothelial growth factor (VEGF), most attention has been focused on the VEGF system. Although fibroblast growth factors 1 and 2 (FGF-1 and FGF-2) can exert a strong angiogenic activity when they are supplied as a single pharmacological agent, their role in pathological angiogenesis in preclinical models remains controversial. To decipher the contribution of FGF receptors in various models of angiogenesis, we took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for FGFR-1 and FGFR-2 (AIdF-1 and AIdF-2). They mimicked FGF-1 and FGF-2 for receptor binding, signal transduction, proliferation of endothelial cells and differentiation of the bladder carcinoma cell NBT-II which expresses FGFR-2b but not FGFR-1. The constitutive expression of FGFR-1 allowed binding of FGF-2 and AIdF-2 and inhibition of the proliferation of NBT-II cells. AIdF-1 and AIdF-2 induced angiogenesis in the corneal pocket assay. Although FGFR-1 dimerization achieved by AIdF-2 injection led to highly differentiated and smaller NBT-II tumors, no sign of reduction of tumor angiogenesis was observed, thus suggesting that endothelial cells are resistant to FGF.

  9. Merkel cell carcinoma: A rare presentation

    Directory of Open Access Journals (Sweden)

    Prosanta Kumar Bhattacharjee

    2014-01-01

    Full Text Available A 33-year-old man presented with a lump at the right side of chest wall of 4 months duration which started bleeding suddenly from an ulcer at its center. Examination revealed a globular ulcerated mass 2 cm in diameter, on the anterior axillary fold, with adherent clot at its center. No regional lymphadenopathy was noted. Wide local excision with 2 cm margin was done. Biopsy report revealed malignant small round-cell tumor. Immunohistochemistry showed it to be cytokeratin-20-positive and S100-negative, suggesting the diagnosis of Merkel cell carcinoma. The patient did not receive any other adjuvant therapy. He is being followed-up for the last 4 years and has shown no features of recurrence so far.

  10. Bilateral hybrid oncocytoma and renal cell carcinoma.

    Science.gov (United States)

    Piplani, S; Kapur, B N; Sandhu, A S; Dhagat, P K; Kakkar, S; Singh, Samarjeet; Bhatoe, H S

    2012-06-01

    A 26-year-old female presented with abdominal pain and distension in 2003. Clinical evaluation and imaging were suggestive of bilateral benign renal solid masses. Fine needle aspiration showed tubular cells only. Patient was kept under periodic follow up. She reported 4 years later with increase in pain and size of masses, and underwent bilateral staged nephron sparing surgery. The histopathology was reported as bilateral oncocytoma. Two years after surgery, she developed epidural spinal cord compression and liver metastasis. A decompression laminectomy and biopsy revealed conventional renal cell carcinoma (RCC). To our knowledge this is the first case report of sporadic bilateral synchronous hybrid RCC and oncocytoma in a young woman, with spinal epidural metastasis.

  11. Overexpression of stefin A in human esophageal squamous cell carcinoma cells inhibits tumor cell growth, angiogenesis, invasion, and metastasis.

    Science.gov (United States)

    Li, Wendong; Ding, Fang; Zhang, Liyong; Liu, Zhongmin; Wu, Yu; Luo, Aiping; Wu, Min; Wang, Mingrong; Zhan, Qimin; Liu, Zhihua

    2005-12-15

    Evidence is accumulating that an inverse correlation exists between stefin A level and malignant progression. The aim of this study is to investigate the role of stefin A in human esophageal squamous cell carcinoma cells and to evaluate the possibility of stefin A for cancer therapy. We stably transfected stefin A cDNA into human EC9706 or KYSE150 esophageal squamous cell carcinoma cells. Subsequently, we evaluated the effect of stefin A overexpression on cell growth, cathepsin B activity, cell motility and invasion, tumor growth, and metastasis. Immunoanalysis was done to assess the expression of factor VIII and to support the localization of stefin A and cathepsin B. We also evaluated the effect of CA074Me, a selective membrane-permeant cathepsin B inhibitor. Both transfection of stefin A and treatment with 10 micromol/L CA074Me significantly reduced cathepsin B activity and inhibited the Matrigel invasion. Combination of both further reduced cathepsin B activity and inhibited the Matrigel invasion. Overexpression of stefin A delayed the in vitro and in vivo growth of cells and significantly inhibited lung metastasis compared with 50% of lung metastasis in xenograft mice from EC9706 or empty vector cells. Transfection with stefin A showed a dramatic reduction of factor VIII staining in the tumors of xenograft mice. Our data strongly indicate that stefin A plays an important role in the growth, angiogenesis, invasion, and metastasis of human esophageal squamous cell carcinoma cells and suggest that stefin A may be useful in cancer therapy.

  12. miR-125/Pokemon auto-circuit contributes to the progression of hepatocellular carcinoma.

    Science.gov (United States)

    Kong, Jing; Liu, Xiaoping; Li, Xiangqian; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2016-01-01

    Hepatocellular carcinoma (HCC) is a type of human malignant tumor occurring in hepatic tissues with high mortality. Patients benefit little from current therapeutic modalities, at least partially due to the lack of complete elucidation of molecular network regulating HCC. miR-125 and Pokemon are well-recognized tumor suppressor and oncogenes for HCC, respectively. However, the underlying mechanism by which the two genes exert their functions and the relationship between miR-125 and Pokemon is still unexplored yet. In this study, we found that there is an inverse association between miR-125 and Pokemon expression levels in HCC specimen and cell lines. Online database mining indicated that there are three putative mRNA recognition elements (MREs) of miR-125 within 3' untranslated region (3'UTR) of Pokemon. MREs of miR-125 confer the expression of luciferase with a miR-125-dependent fashion. The alteration in miR-125 abundance regulates the expression of Pokemon at both protein and mRNA levels. Overexpression of Pokemon is able to abrogate the inhibitory effect of miR-125 on HCC progression. Further study showed that Pokemon inhibits the expression of miR-125 by binding of recognition sites within its promoter. In conclusion, we found that there is an auto-regulatory circuit consisting of miR-125 and Pokemon, which promotes the progression of HCC and may be a promising therapeutic target in clinical HCC treatment.

  13. Actual proliferating index in oral squamous cell carcinoma and leukoplakia.

    Science.gov (United States)

    Chandak, Abhay R; Gadbail, Amol Ramchandra; Chaudhary, Minal S; Chandak, Shweta A; Wadhwani, Ritesh

    2011-08-01

      To examine the possible association between epithelial proliferation and disease progression in the oral mucosa using the actual proliferation index.   The actual proliferation index was measured by the Ki-67 labeling index and argyrophilic nucleolar organizer region count per nucleus. Immunohistochemistry was carried out for Ki-67 by using the molecular immunology borstel-1 clone in 20 leukoplakias, 20 oral squamous cell carcinomas, and 10 normal oral mucosae.   The argyrophilic nucleolar organizer region count per nucleus, Ki-67 labeling index, and actual proliferation index were significantly higher in oral squamous cell carcinoma, followed by leukoplakia and normal oral mucosa. Leukoplakia with dysplasia showed a significantly higher Ki-67 labeling index and actual proliferation index, compared to leukoplakia without dysphasia. There was a significant correlation of Bryne's histological malignancy grading with the argyrophilic nucleolar organizer region count and the Ki-67 labeling index. There was a significant positive correlation between the argyrophilic nucleolar organizer region count and the Ki-67 labeling index among all groups.   Leukoplakia or suspected epithelial dysplasia should be stained for argyrophilic nucleolar organizer regions and Ki-67. The actual proliferation index is not only useful as a prognostic factor, but could also be a promising treatment determining modality for patients with premalignant and malignant lesions. © 2011 Blackwell Publishing Asia Pty Ltd.

  14. Merkel cell carcinoma: banal-appearing, aggressive actor.

    Science.gov (United States)

    Bergstrom, Kendra Gail

    2011-07-01

    Merkel cell carcinoma is a rare but often deadly cutaneous malignancy. It carries a 40 percent five-year mortality rate, in contrast to 15 percent for malignant melanoma, and the incidence is increasing among older and immunosuppressed patients. Dermatologists need to be aware of the particular diagnostic and treatment challenges as the incidence increases. New data is helping to identify patients most at risk, accurately stage the tumor and to optimize treatment regimens. With the recent discovery of a virus as part of the etiology of this tumor, approaches to use the body's immune system to attack the tumor have potential to significantly increase survival rates in the future. Merkel Cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy. Its aggressive behavior, combined with its asymptomatic clinical presentation, means that tumors are often allowed to grow and spread before detection. As the tumor becomes better characterized and its etiology better understood, research is rapidly advancing in both pathogenesis and treatment. Since the discovery of a viral etiology for this tumor in 2008, progress is advancing rapidly.

  15. Novel immunotherapy approaches for metastatic urothelial and renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhiying Shao

    2016-10-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC and urothelial carcinoma (UC remains a major challenge. Past research has implicated the immune system in tumor surveillance of both malignancies, leading to the application of immunotherapy agents for both cancers. Among them, the most promising agents are the checkpoint blockade drugs, such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, programmed death receptor 1 (PD-1, and PD-1 ligand (PD-L1. In normal physiology, these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions, which is pivotal for maintaining self-tolerance. However, tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response, leading to disease progression and metastasis. Thus, there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and UC. To date, nivolumab (anti-PD-1 and atezolizumab (anti-PD-L1 have been approved for the treatment of metastatic RCC and UC, respectively. Despite these successes, challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this approach. In this report, we review existing data and research on immunotherapy in metastatic RCC and UC.

  16. Metastasized squamous cell carcinoma developed on lupus vulgaris.

    Science.gov (United States)

    Pătraşcu, V; Georgescu, Claudia Valentina; Tănase, Loredana Elena; Mogoantă, S S

    2008-01-01

    Lupus vulgaris (LV) is the most frequent cutaneous tuberculosis, representing more than 55% of the tuberculoses with this location. Malignization can occur after a long latency (10-30 years), in 1-2% of the cases, and it is mainly in squamous cell carcinoma. The histological exam is highly important in the observation of neoplasic transformations. The authors present a 59-years-old female patient, from the rural environment, working as a farmer, with lupus vulgaris developing since her first childhood years. It started at the age of 2 years, at the right ear lobule, after the empiric perforation for earrings. The evolution was progressive, eccentric, interesting the pinna and the right cheek in the meanwhile. At the first examination, in 2002, a diffuse mass of red-yellowish infiltration was found at the level of the right ear and the right cheek. In the following two years, an ulcero-vegetating tumor developed at the level of the right ear lobule, accompanied by the presence of a right retromandibular adenopathy, of about 1 cm, which was proved by the histopathologic exam to be a squamous cell carcinoma developed from a lupus vulgaris. After scraping out the right retromandibular ganglion, detected by palpation, a histological exam showed ganglion metastasis.

  17. MiR-138 Suppresses Cell Proliferation by Targeting Bag-1 in Gallbladder Carcinoma

    Science.gov (United States)

    Gong, Wei; Weng, Mingzhe; Quan, Zhiwei

    2015-01-01

    Background MiR-138 is frequently downregulated in different cancer types and is thought to be involved in the progression of tumorigenesis. However, the molecular mechanism of miR-138 involvement in gallbladder carcinoma still remains unknown. Methods The expression of miR-138 in 49 gallbladder carcinoma samples and paired normal gallbladder samples was analyzed using quantitative reverse transcription–polymerase chain reaction. The biological functions of miR-138 and Bag-1 (Bcl-2-associated athanogene-1) on cell proliferation were examined using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and apoptosis assays. Targets of miR-138 were predicted using bioinformatics and validated using luciferase reporter and Western blot analyses. The in vivo effects of miR-138 were examined using subcutaneous inoculation of gallbladder carcinoma cells in Balb/c nude mice. Results Compared with their paired normal gallbladder samples, the gallbladder carcinoma samples had decreased expression of miR-138 and increased expression of Bag-1. Overexpression of miR-138 inhibited the proliferation of gallbladder carcinoma cells. Bag-1 was defined as a novel target of miR-138. Both the inhibition of Bag-1 by miR-138 and the silencing of Bag-1 by siRNA led to alterations of apoptosis-related proteins such as Bcl-2 and Bax. Restoring expression of Bag-1 eliminates the effects of miR-138 on cell proliferation and apoptosis. Furthermore, overexpression of miR-138 markedly inhibited the growth of tumors in the gallbladder carcinoma xenograft model in nude mice. Conclusions Expression of miR-138 is frequently reduced in gallbladder carcinoma when compared to normal cells. Overexpression of miR-138 inhibited cell proliferation by directly suppressing the expression of Bag-1. These results suggest that miR-138 plays an important role in inhibiting the growth of gallbladder carcinoma. PMID:25962180

  18. Axitinib in metastatic renal cell carcinoma: single center experience

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    Agnieszka Buraczewska

    2017-01-01

    Full Text Available Aim of the study : Due to the emergence of new therapeutic opportunities in the second-line treatment of metastatic renal cell carcinoma, the choice of the appropriate medication requires consideration. Making the selection one should take into account the likelihood of response, the probability of toxicity, properties of the drug and the clinical characteristics of the patient. Aim of the work was to confirm antitumor efficacy of axitinib in patients with metastatic clear-cell renal-cell carcinoma in the second line treatment remaining under the care of our institution. The primary objective was to determine antitumor activity, secondary – to evaluate progression free survival, safety of the treatment and to analyse clinical characteristics of treated population. Results: Treatment records of 27 patients (9 females, 18 males treated from October 2014 to the present (July 2016 were reviewed. The median duration of treatment which corresponds to the time to disease progression in observed population was 6 months (range: under 1 month – 16 months. 1 patient (3.7% had got objective response (PR, partial remission. Clinical benefit rate (PR + SD (stable disease was 66%. 9 patients (33.33% experienced treatment toxicity only in the first degree of CTCAE (common toxicity criteria for adverse events, 11 patients (40.74% presented the second degree toxicity and 5 patients (18.5% – third degree. The most commonly reported treatment related adverse events were diarrhea (47%, fatigue (26%, hand-foot syndrome (26%, deterioration of blood pressure control (22.2%, abnormal liver function tests (18.5%, mucositis (11.1%.We observed 3 cases of unacceptable toxicity. Conclusions : Axitinib confirms its effectiveness also in situ ation outside clinical trials, however, it is characterized by significant toxicity. Therefore, qualification for treatment should take into account the clinical patient characteristics. Effective diagnosis and treatment of side

  19. Characterization of a human ovarian carcinoma cell line: UCI 101.

    Science.gov (United States)

    Fuchtner, C; Emma, D A; Manetta, A; Gamboa, G; Bernstein, R; Liao, S Y

    1993-02-01

    A new epithelial ovarian carcinoma cell line (UCI 101) has been established from the ascitic fluids and solid tumor of a patient with progressive papillary adenocarcinoma of the ovary shown previously to be refractory to combination chemotherapy consisting of cyclophosphamide, Adriamycin, and cisplatin as well as single-agent chemotherapy of taxol and high-dose cisplatin. The UCI 101 cell line grows well with an in vitro doubling time of 24 hr. The cell line expresses the B 72.3 (Tag 72), CA125, MH99 (ESA), and E29 (EMA) cell surface antigens and AE1/AE3 cytokeratins. This cell line overexpresses (as determined by immunocytochemistry) both p-glycoprotein and the epidermal growth factor receptor. The in vitro drug response to single agents including Adriamycin, cisplatin, dequalinium chloride, etoposide, 5-fluorouracil, taxol, and tumor necrosis factor was examined. Intraperitoneal transplantation of the cells into athymic mice resulted in foci of tumor on all peritoneal surfaces including the viscera and diaphragm ultimately leading to solid bulky disease with massive production of ascites. High levels of CA125 (> 500 units/ml) were detected in the serum of tumor-bearing mice. Cytogenetic analysis of cultured cells shows several marker chromosomes containing deletions, duplications, and translocations. Cytologic and histologic evaluation of the xenograft revealed morphological characteristics identical to those of the original tumor.

  20. A child with xeroderma pigmentosum for excision of basal cell carcinoma.

    Science.gov (United States)

    Mulimani, Sridevi M; Talikoti, Dayanand G

    2013-10-01

    Xeroderma pigmentosum (XP) is characterized by hypersensitivity to sunlight, ocular involvement, and progressive neurological complications. These manifestations are due to a cellular hypersensitivity to ultraviolet radiation leading to a defect in repair of DNA by the process of nucleotide excision repair. Basal cell carcinoma which is rare in children can occur with XP. Though the XP induced changes are predominately dermatologic, pose several challenges in anaesthetic management. Hence, we are reporting a 9-year-old child with XP scheduled for excision of basal cell carcinoma under general anaesthesia.

  1. A child with xeroderma pigmentosum for excision of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sridevi M Mulimani

    2013-01-01

    Full Text Available Xeroderma pigmentosum (XP is characterized by hypersensitivity to sunlight, ocular involvement, and progressive neurological complications. These manifestations are due to a cellular hypersensitivity to ultraviolet radiation leading to a defect in repair of DNA by the process of nucleotide excision repair. Basal cell carcinoma which is rare in children can occur with XP. Though the XP induced changes are predominately dermatologic, pose several challenges in anaesthetic management. Hence, we are reporting a 9-year-old child with XP scheduled for excision of basal cell carcinoma under general anaesthesia.

  2. Primary Small Cell Carcinoma of the Upper Urinary Tract

    Directory of Open Access Journals (Sweden)

    Victor Ka-Siong Kho

    2010-03-01

    Full Text Available We report a case of primary extrapulmonary small cell carcinoma of the distal ureter, with a synchronous small cell carcinoma of the ipsilateral renal pelvis. These tumors, rarely reported in the urinary tract, are locally aggressive and have a poor prognosis. A 77-year-old male bedridden patient presented with fever and chills with left side-flank pain for 3 days. Following a diagnosis of ureteral urothelial carcinoma, hand-assisted laparoscopic nephroureterectomy with bladder cuff excision was carried out. Adjuvant chemotherapy was given after pathologic report of primary small cell carcinoma of the distal ureter and a synchronous small cell carcinoma of the ipsilateral renal pelvis. After 3 cycles of combination chemotherapy, the patient died 4 months postoperatively due to sepsis.

  3. Association of esophageal candidiasis and squamous cell carcinoma.

    Science.gov (United States)

    Delsing, C E; Bleeker-Rovers, C P; van de Veerdonk, F L; Tol, J; van der Meer, J W M; Kullberg, B J; Netea, M G

    2012-01-01

    Chronic esophageal candidiasis is an infection that is mostly seen in immunocompromised conditions, among which is chronic mucocutaneous candidiasis (CMC). Recently an association between CMC and esophageal carcinoma has been reported. Here we present two patients with chronic esophageal candidiasis who developed esophageal squamous cell carcinoma and we discuss the etiologic role of Candida-induced nitrosamine production, the loss of STAT1 function and impaired tumor surveillance and T-lymphocyte function in the development of esophageal carcinoma.

  4. THE AUTHOR’S EXPERIENCE IN USING BEVACIZUMAB PLUS INTERFERON ALFA-2A IN PATIENTS WITH DISSEMINATED RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2010-01-01

    Full Text Available Target therapy is a main approach to treating metastatic renal cell carcinoma. Bevacizumab plus interferon alfa-2A is now standard first-line options for patients with previously untreated, good or intermediate prognosis (using the Memorial Sloan-Kettering Cancer Center criteria. We have presented our experience in using bevacisumab plus interferon alfa-2A in patients with metastatic renal cell carcinoma. Median progression-free survival and overall survival were 10 months and 22 months, respectively.

  5. THE AUTHOR’S EXPERIENCE IN USING BEVACIZUMAB PLUS INTERFERON ALFA-2A IN PATIENTS WITH DISSEMINATED RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2014-08-01

    Full Text Available Target therapy is a main approach to treating metastatic renal cell carcinoma. Bevacizumab plus interferon alfa-2A is now standard first-line options for patients with previously untreated, good or intermediate prognosis (using the Memorial Sloan-Kettering Cancer Center criteria. We have presented our experience in using bevacisumab plus interferon alfa-2A in patients with metastatic renal cell carcinoma. Median progression-free survival and overall survival were 10 months and 22 months, respectively.

  6. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

    Science.gov (United States)

    Cohen, Philip R

    2017-03-22

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  7. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma

    Science.gov (United States)

    2017-01-01

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  8. Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

    Science.gov (United States)

    Severi, Tamara; van Malenstein, Hannah; Verslype, Chris; van Pelt, Jos F

    2010-01-01

    Hepatocellular carcinoma (HCC) is a major health problem worldwide responsible for 500 000 deaths annually. A number of risk factors are associated with either the induction of the disease or its progression; these include infection with hepatitis B or C virus, alcohol consumption, non-alcoholic steatohepatitis and certain congenital disorders. In around 80% of the cases, HCC is associated with cirrhosis or advanced fibrosis and with inflammation and oxidative stress. In this review we focus firstly on the different risk factors for HCC and summarize the mechanisms by which each is considered to contribute to HCC. In the second part we look at the molecular processes involved in cancer progression. HCC development is recognized as a multistep process that normally develops over many years. Over this period several mutations accumulate in the cell and that stimulate malign transformation, growth, and metastatic behavior. Over the recent years it has become evident that not only the tumor cell itself but also the tumor microenviroment plays a major role in the development of a tumor. There is a direct link between the role of inflammation and cirrhosis with this microenviroment. Both in vitro and in vivo it has been shown that tumor formation and metastatic properties are linked to epithelial-mesenchymal transition (EMT), a process by which facillitates the tumor cell's attempts to migrate to a more favourable microenviroment. Several groups have analyzed the gene expression in HCC and its surrounding tissue by microarray and this has resulted in the molecular classification into a distinct number of classes. Here we also found a role for hypoxia induced gene expression leading to a clinically more aggressive gene expression in HCC. Molecular analysis also helped to identify important cellular pathways and possible therapeutic targets. The first molecule that in this way has shown clinical application for liver cancer is the multikinase inhibitor sorafenib, others

  9. Metastatic papillary carcinoma thyroid co-existing with oral cavity squamous cell carcinoma: A case report and review of literature

    OpenAIRE

    Roshan K. Verma; Nishikanta Tripathi; Pallavi Aggarwal; Naresh K. Panda

    2014-01-01

    The incidental discovery of metastatic papillary carcinoma thyroid in lymph node while the patient is being investigated for primary squamous cell carcinoma of the oral cavity is an unusual clinical situation and the appropriate management in such clinical situation is controversial and confusing. We report a case of a 65 year old male with primary squamous cell carcinoma of alveolus with bilateral neck nodes. Fine needle aspiration cytology showed metastatic squamous cell carcinoma in lymph ...

  10. Metastatic renal cell carcinoma to the thyroid gland.

    Science.gov (United States)

    Duggal, Neal Murari; Horattas, Mark C

    2008-11-01

    To examine the presentation, diagnosis, and appropriate management of renal clear cell carcinoma metastasis to the thyroid gland. We describe a clinical case of solitary thyroid metastasis from renal clear cell carcinoma and present a comprehensive review of the related English-language literature. Common patterns of presentation and generalized overall management recommendations are evaluated and summarized. Eight years after nephrectomy for renal carcinoma at age 61 years, a man presented with a thyroid mass. Cytology and histopathologic surgical findings were consistent with a solitary metastasis most compatible with metastatic clear cell carcinoma from his previous renal carcinoma. After left thyroid lobectomy and isthmusectomy, the patient remains disease-free 5 years later. Although uncommon, nearly 150 cases of clinically recognized metastatic renal cell carcinoma to the thyroid have been reported in the English-language literature. Metastatic disease from the kidney to the thyroid gland can occur more than 20 years after nephrectomy with the average time interval being 7.5 years. Obtaining a full clinical history in any patient who presents with a thyroid nodule is essential to allow consideration of possible metastatic disease from previous primary tumor. Metastatic disease to the thyroid gland can be correctly diagnosed preoperatively. If metastatic renal cancer is limited to the thyroid gland only, prompt, appropriate surgical intervention can be curative. Metastatic renal carcinoma to the thyroid should be considered in any patient presenting with a thyroid mass and a medical history of renal cell carcinoma.

  11. Corellation of p53 expressions and histopathological grading in oral cavity squamous cell carcinoma

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    Silvi Kintawati

    2016-09-01

    Full Text Available Background: Squamous cell carcinoma is a malignancy of oral cavity mostly occurred and can also metastasize. p53 gene is a tumor suppressor gene that plays an important role in carcinogenesis. The role of wild-type p53 is very important in suppressing the formation of a malignancy. p53 also has many other important functions. p53 is a suppressor of tumor/ cancer progression through the response of cell cycle to DNA damage and by giving time to repair DNA prior to replication of genes. p53 mutation, mostly occurs in a malignancy, so earlier histopathological transformation can be detected by observing p53 mutation. The prognosis of squamous cell carcinoma in oral cavity, therefore, depends on histopathological grading and clinical staging of the tumor. To enforce the histopathological grading, in addition based on histopathology differentiation, the earlier histopathological transformation can also be assessed. Purpose: This study aimed to determine the correlation of p53 expressions and histopathological grading in oral cavity squamous cell carcinoma. Method: This study was a retrospective study on 20 cases of oral cavity squamous cell carcinoma examined at Department of Pathology Anatomy in Hasan Sadikin Hospital in Bandung. Immunohistochemical examination was then performed using p53 antibodies to determine the correlation of p53 expression and histopathological grading in oral cavity squamous cell carcinoma to predict prognosis. Result: The overall results showed that there was no correlation between p53 expression and histopathological grading in oral cavity squamous cell carcinoma of the oral cavity although there was a very strong correlation between p53 expression and histopathological grading I (p<0.01. Conclusion: It can be concluded that there was no correlation between p53 expression and histopathological grading in oral cavity squamous cell carcinoma. Thus, p53 expression cannot be used to predict a prognosis.

  12. Cathepsin K Is Present in Invasive Oral Tongue Squamous Cell Carcinoma In Vivo and In Vitro

    Science.gov (United States)

    Bitu, Carolina C.; Kauppila, Joonas H.; Bufalino, Andréia; Nurmenniemi, Sini; Teppo, Susanna; Keinänen, Meeri; Vilen, Suvi-Tuuli; Lehenkari, Petri; Nyberg, Pia; Coletta, Ricardo D.; Salo, Tuula

    2013-01-01

    Objectives Cathepsin K, a lysosomal cysteine protease, is expressed in the tumor microenvironment (TME) of skin carcinoma, but nothing is known about cathepsin K in oral tongue squamous cell carcinoma (OTSCC). Our aim was to describe the expression of cathepsin K in invasive OTSCC in vitro and in a series of clinical cancer specimens. Materials and Methods OTSCC invasion in vitro was studied using invasive HSC-3 tongue carcinoma cells in 3D organotypic models. In total, 121 mobile tongue OTSCCs and 10 lymph node metastases were analyzed for cathepsin K expression. The association between cathepsin K expression and clinicopathological factors was evaluated. Results Cysteine protease inhibitor E64 and cathepsin K silencing significantly (p<0.0001) reduced HSC-3 cell invasion in the 3D models. Cathepsin K was expressed in a majority of carcinoma and metastatic cells, but the expression pattern in carcinoma cells did not correlate with clinical parameters. Instead, the weak expression of cathepsin K in the invasive TME front correlated with increased overall recurrence (p<0.05), and in early-stage tumors this pattern predicted both cancer recurrence and cancer-specific mortality (p<0.05 and p<0.005, respectively). Conclusions Cathepsin K is expressed in OTSCC tissue in both carcinoma and TME cells. Although the diminished activity and expression in aggressive tongue HSC-3 cells reduced 3D invasion in vitro, the amount of cathepsin K in carcinoma cells was not associated with the outcome of cancer patients. Instead, cathepsin K in the invasive TME front seems to have a protective role in the complex progression of tongue cancer. PMID:23951042

  13. Cathepsin K is present in invasive oral tongue squamous cell carcinoma in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Carolina C Bitu

    Full Text Available OBJECTIVES: Cathepsin K, a lysosomal cysteine protease, is expressed in the tumor microenvironment (TME of skin carcinoma, but nothing is known about cathepsin K in oral tongue squamous cell carcinoma (OTSCC. Our aim was to describe the expression of cathepsin K in invasive OTSCC in vitro and in a series of clinical cancer specimens. MATERIALS AND METHODS: OTSCC invasion in vitro was studied using invasive HSC-3 tongue carcinoma cells in 3D organotypic models. In total, 121 mobile tongue OTSCCs and 10 lymph node metastases were analyzed for cathepsin K expression. The association between cathepsin K expression and clinicopathological factors was evaluated. RESULTS: Cysteine protease inhibitor E64 and cathepsin K silencing significantly (p<0.0001 reduced HSC-3 cell invasion in the 3D models. Cathepsin K was expressed in a majority of carcinoma and metastatic cells, but the expression pattern in carcinoma cells did not correlate with clinical parameters. Instead, the weak expression of cathepsin K in the invasive TME front correlated with increased overall recurrence (p<0.05, and in early-stage tumors this pattern predicted both cancer recurrence and cancer-specific mortality (p<0.05 and p<0.005, respectively. CONCLUSIONS: Cathepsin K is expressed in OTSCC tissue in both carcinoma and TME cells. Although the diminished activity and expression in aggressive tongue HSC-3 cells reduced 3D invasion in vitro, the amount of cathepsin K in carcinoma cells was not associated with the outcome of cancer patients. Instead, cathepsin K in the invasive TME front seems to have a protective role in the complex progression of tongue cancer.

  14. Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wheat, Rachel [School of Cancer Sciences and CR UK Centre for Cancer Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); Roberts, Claudia [School of Cancer Sciences and CR UK Centre for Cancer Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); University Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Waterboer, Tim [Infection and Cancer Program, DKFZ (German Cancer Research Centre), 69120 Heidelberg (Germany); Steele, Jane [Human Biomaterials Resource Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); Marsden, Jerry [University Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Steven, Neil M., E-mail: n.m.steven@bham.ac.uk [School of Cancer Sciences and CR UK Centre for Cancer Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); University Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Blackbourn, David J., E-mail: n.m.steven@bham.ac.uk [Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH (United Kingdom)

    2014-05-06

    Merkel cell carcinoma (MCC) is an aggressive poorly differentiated neuroendocrine cutaneous carcinoma associated with older age, immunodeficiency and Merkel cell polyomavirus (MCPyV) integrated within malignant cells. The presence of intra-tumoural CD8+ lymphocytes reportedly predicts better MCC-specific survival. In this study, the distribution of inflammatory cells and properties of CD8+ T lymphocytes within 20 primary MCC specimens were characterised using immunohistochemistry and multicolour immunofluorescent staining coupled to confocal microscopy. CD8+ cells and CD68+ macrophages were identified in 19/20 primary MCC. CD20+ B cells were present in 5/10, CD4+ cells in 10/10 and FoxP3+ cells in 7/10 specimens. Only two specimens had almost no inflammatory cells. Within specimens, inflammatory cells followed the same patchy distribution, focused at the edge of sheets and nodules and, in some cases, more intense in trabecular areas. CD8+ cells were outside vessels on the edge of tumour. Those few within malignant sheets typically lined up in fine septa not contacting MCC cells expressing MCPyV large T antigen. The homeostatic chemokine CXCL12 was expressed outside malignant nodules whereas its receptor CXCR4 was identified within tumour but not on CD8+ cells. CD8+ cells lacked CXCR3 and granzyme B expression irrespective of location within stroma versus malignant nodules or of the intensity of the intra-tumoural infiltrate. In summary, diverse inflammatory cells were organised around the margin of malignant deposits suggesting response to aberrant signaling, but were unable to penetrate the tumour microenvironment itself to enable an immune response against malignant cells or their polyomavirus.

  15. [Differential proteomics research on exosomes derived from tongue squamous cell carcinoma cells and normal mucosa cells].

    Science.gov (United States)

    Han, Xinsheng; Zhang, Zhuoyuan; Huang, Yi; Xia, Yichao; Li, Longjiang

    2014-06-01

    This study aimed to explore further the mechanisms of tongue squamous cell carcinoma (TSCC) cell recurrence, metastasis, and diffusion, as well as to establish the experimental basis for the molecular biology research on TSSC. We intend to complete our objective through differential proteomics and preliminary analysis protein expression of exosomes derived from TSCC and normal mucosa cells. We acquired cultured supernatant fluid in vitro in the laboratory by culturing TSCC (tongue cancer Tca8113 cell line) and human normal mucosa cells (HOK cell line). The exosomes were separated and purified through differential centrifugation. Furthermore, the different protein expressions were identified through dielectrophoresis and mass spectrometry. The functions of the different protein expressions were identified through an online database search. TSCC and human normal mucosa cells secrete a large amount of capsule bubble structure substances in vitro, as confirmed by electron microscopy and surface markers heat shock protein-70 and major histocompatibility complex class 1. A total of 16 oral cancer cell-derived exosomes that expressed quantity more than two times, twelve that increased their expression levels, and four that cut their expressions were identified through the differential proteomics research on the two groups. Differential proteins that were verified through the online database serve an important function in exosome formation and in the progress of cancer.

  16. Expression of GLUT-1 in oral squamous cell carcinoma in tobacco and non-tobacco users.

    Science.gov (United States)

    Azad, Neha; Kumari Maurya, Malti; Kar, Meenakshi; Goel, Madhu Mati; Singh, Ajay Kumar; Sagar, Mala; Mehrotra, Divya; Kumar, Vijay

    2016-01-01

    GLUTs are a family of proteins that mediate glucose transport through the membrane, expressed in head and neck squamous cell carcinoma. GLUT-1 positivity in malignant cells indicates increased proliferative activity, energy requirements, aggressive behaviour and poor radiation response. To observe the expression of GLUT-1 protein in oral squamous cell carcinoma in tobacco and non-tobacco users and to correlate the expression with histopathological grading and pathological staging. 50 cases (25 tobacco and 25 non-tobacco) of oral squamous cell carcinoma, selected during period of August 2014 to July 2015. Histopathological grading, TNM and staging were done. Immunohistochemical staining was performed using standard protocol for paraffin embedded sections. Analysis was performed on SPSS software (Windows version 17.0). Significant association of GLUT-1 expression was found with history of tobacco (p GLUT-1 expression in stage II, stage III and stage IV was found as compared to stage I. GLUT-1 immunoexpression also shows progressive switch from membranous to cytoplasmic to combined location correlating with histopathologic grade and pTNM stage. GLUT-1 expression correlates significantly with histological grade and pTNM staging of oral squamous cell carcinoma. It also significantly correlates with tobacco addiction. Thus, GLUT-1 expression may serve as a biomarker for patients of oral squamous cell carcinoma.

  17. Nucleophosmin expression in renal cell carcinoma and oncocytoma.

    Science.gov (United States)

    Sari, Aysegul; Calli, Aylin; Altinboga, Aysegul Aksoy; Pehlivan, Fatma Seher; Gorgel, Sacit Nuri; Balci, Ugur; Ermete, Murat; Dincel, Cetin; Cakalagaoglu, Fulya

    2012-03-01

    The objective of this study was to investigate nucleophosmin/B23 (NPM) expression in renal cell carcinomas (RCC) and renal oncocytomas. The expression of NPM was studied by immunohistochemical methods on 59 RCCs, 9 oncocytomas, and 19 tumour-negative renal tissues. The expression was assessed relative to various clinicopathological variables and histological subtypes, to determine its potential role as a prognostic and diagnostic marker. All tumours showed nuclear staining, and a minority also exhibited cytoplasmic immunoreactivity. Two patterns of nuclear staining were observed: nuclear staining with a prominent nucleolus (nucleolar staining) and nuclear staining without a prominent nucleolus. There were significant differences, in both nuclear staining and cytoplasmic NPM expression, between oncocytomas and chromophobe RCCs (p oncocytomas. A statistically significant correlation was discovered between nucleolar staining and nuclear grade (p oncocytoma and chromophobe RCC. In addition, increased nucleolar NPM expression in RCCs appears to be associated with tumour progression. © 2011 The Authors. APMIS © 2011 APMIS.

  18. Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy

    Science.gov (United States)

    Sun, Cheng; Sun, Hao-yu; Xiao, Wei-hua; Zhang, Cai; Tian, Zhi-gang

    2015-01-01

    The mechanisms linking hepatitis B virus (HBV) and hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) remain largely unknown. Natural killer (NK) cells account for 25%–50% of the total number of liver lymphocytes, suggesting that NK cells play an important role in liver immunity. The number of NK cells in the blood and tumor tissues of HCC patients is positively correlated with their survival and prognosis. Furthermore, a group of NK cell-associated genes in HCC tissues is positively associated with the prolonged survival. These facts suggest that NK cells and HCC progression are strongly associated. In this review, we describe the abnormal NK cells and their functional impairment in patients with chronic HBV and HCV infection, which contribute to the progression of HCC. Then, we summarize the association of NK cells with HCC based on the abnormalities in the numbers and phenotypes of blood and liver NK cells in HCC patients. In particular, the exhaustion of NK cells that represents lower cytotoxicity and impaired cytokine production may serve as a predictor for the occurrence of HCC. Finally, we present the current achievements in NK cell immunotherapy conducted in mouse models of liver cancer and in clinical trials, highlighting how chemoimmunotherapy, NK cell transfer, gene therapy, cytokine therapy and mAb therapy improve NK cell function in HCC treatment. It is conceivable that NK cell-based anti-HCC therapeutic strategies alone or in combination with other therapies will be great promise for HCC treatment. PMID:26073325

  19. Centrosome abnormalities in head and neck squamous cell carcinoma (HNSCC).

    Science.gov (United States)

    Reiter, Rudolf; Gais, Peter; Steuer-Vogt, Miriam K; Boulesteix, Anne-Laure; Deutschle, Tom; Hampel, Regina; Wagenpfeil, Stefan; Rauser, Sandra; Walch, Axel; Bink, Karin; Jutting, Uta; Neff, Frauke; Arnold, Wolfgang; Hofler, Heinz; Pickhard, Anja

    2009-02-01

    Numerical and structural centrosome abnormalities play a critical role in the tumor progression of in head and neck squamous cell carcinoma (HNSCC) and may provide useful information as a prognostic factor for these patients. Centrosome alterations are often linked with aneuploidy, cell transformation, and tumor progress. We investigated centrosome abnormalities in HNSCC and correlated these variables to clinicopathological parameters and clinical follow up data of the patients. Retrospective analysis of numerical and structural alterations of centrosomes in tumor tissues and corresponding normal epithelium (n=50 and 31, respectively). Immunohistochemistry was performed using an anti-gamma-tubulin antibody. Image acquisition was done by an Orthoplan microscope, centrosomes were segmented interactively, and area as well as mean optical density was measured. Aneuploidy was evaluated by fluorescence in situ hybridization in a subset of cases (n=29). Numerical and structural centrosome abnormalities differed significantly between normal squamous epithelium and tumor cells (both P<0.0001). Especially numerical centrosome abnormalities were significantly associated with T category and tumor stage (both P<0.0001) and the occurrence of distant metastasis (P=0.002 and P=0.019, respectively). Numerical centrosome abnormalities correlated also with disease free survival of the patients (P=0.032) as well as shorter overall survival (P=0.003).

  20. Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Charles, E-mail: Charles_Lin@health.qld.gov.au [Cancer Care Services, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia); Tripcony, Lee; Keller, Jacqui [Cancer Care Services, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia); Poulsen, Michael [Mater Hospital, Brisbane, Queensland (Australia); Martin, Jarad [St. Andrews Hospital, Toowoomba, Queensland (Australia); Jackson, James; Dickie, Graeme [Cancer Care Services, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia)

    2012-01-01

    Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

  1. S100A11 regulates renal carcinoma cell proliferation, invasion, and migration via the EGFR/Akt signaling pathway and E-cadherin.

    Science.gov (United States)

    Liu, Lin; Miao, Long; Liu, Yang; Qi, Aihua; Xie, Ping; Chen, Jiacun; Zhu, Haitao

    2017-05-01

    S100A11 is a S100 protein family member that contributes to cancer progression. Upregulated in human renal cancer tissues, S100A11 may be a prognostic marker for clear cell renal cell carcinoma, but how it functions in cancer is uncertain. Thus, we studied S100A11 and noted knockdown of S100A11 using short hairpin RNA, which inhibited proliferation, invasion, and migration of renal carcinoma cells as well as increased expression of E-cadherin and decreased expression of epidermal growth factor receptor/Akt in renal carcinoma cells. Therefore, S100A11 may be a key molecular target for treating renal carcinoma.

  2. The dermatoscopic universe of basal cell carcinoma

    Science.gov (United States)

    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

  3. Basal cell carcinomas of the eyelids.

    Science.gov (United States)

    Allali, J; D'Hermies, F; Renard, G

    2005-01-01

    Basal cell carcinomas (BCC) are the more frequent malignant tumors seen in France as in other western countries. They represent 20% of eyelid tumors and 90% of eyelid malignancies. Due to their local growth, problems may arise when treating BCC, and curative exeresis must be the preferred choice each time it is possible. BCC of the eyelids have a high risk of recurrence. Recurrences are more aggressive, infiltrative and destructive and have a considerably poorer rate of cure than primary tumors. Eyelid reconstructions can entail use of complex methods which should only be carried out by a trained ophthalmologist who is also able to treat any associated age-related ocular pathologies. BCC is the most common cause leading to eyelid reconstructive surgery; a surgery which has a triple objective: tumor removal, functionality and an esthetic outcome. Copyright (c) 2005 S. Karger AG, Basel.

  4. Duodenal Bleeding from Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Tarun Rustagi

    2011-04-01

    Full Text Available 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.

  5. Subungual squamous cell carcinoma: A case study.

    Science.gov (United States)

    Neill, Cory J

    2017-01-01

    The purpose of this case study is to describe a dosimetric delivery of radiation to a superficial disease process involving the skin and bone of the distal finger. A 76-year-old male patient presented with a subungual squamous cell carcinoma (SCC) of the left distal index finger with bony involvement. The patient refused conventional surgical treatment but agreed to external beam radiation therapy (EBRT). There is a gap in the current literature describing how to successfully immobilize fingers and which EBRT modality is dosimetrically advantageous in treating them. The construction of a simple immobilization method with the patient in a reproducible position is described. The use of photons and electrons were compared ultimately showing photons to be dosimetrically advantageous. Long-term efficacy of the treatment was not evaluated because of patient noncompliance. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  6. Oral squamous cell carcinoma around dental implants.

    Science.gov (United States)

    Czerninski, Rakefet; Kaplan, Ilana; Almoznino, Galit; Maly, Alexander; Regev, Eran

    2006-10-01

    It is well documented that oral squamous cell carcinoma (OSCC) is related to risk factors such as smoking and alcohol consumption as well as premalignant lesions and conditions such as leukoplakia, oral lichen planus (OLP), and previous malignancy of the upper respiratory system and gastrointestinal tract. Osseointegrated dental implants are rarely reported in association with OSCC. This article presents 2 cases of OSCC adjacent to dental implants in patients at risk for oral cancer--1 was a heavy smoker with OLP; the other had a history of previous oral and colon cancer. Six additional cases of malignancy adjacent to dental implants were retrieved from the literature; the majority of cases had at least 1 recognized risk factor for oral cancer. Although such cases are rarely reported, patients at risk for oral cancer, especially those with multiple existing risk factors, that present with failing dental implants should be thoroughly evaluated to rule out the presence of malignancy disguised as peri-implant disease.

  7. Unilateral Blepharoptosis From Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Federico Greco

    2016-12-01

    Full Text Available Blepharoptosis is the drooping or inferior displacement of the upper eyelid. Blepharoptosis can be either congenital or acquired. Tumour metastasis is one of the acquired causes of blepharoptosis. The lungs, locoregional lymph nodes, bone and liver are the usual sites of metastases of renal cell carcinoma (RCC; however, unusual locations of RCC have also been reported. Herein, we describe a case of a 47-year-old man with unilateral ptosis and blurred vision due to metastatic RCC. We describe the different causes of blepharopstosis, the path that led to the diagnosis, and how RCC can metastasize to unusual anatomical regions such as the orbit. Symptoms such as exophthalmos, lid edema, diplopia, ptosis, cranial nerve paralysis or blurred vision may mime a benign disease; however, they could also be the symptoms of a systemic malignancy.

  8. Squamous cell carcinoma arising from neglected meningocele.

    Science.gov (United States)

    Wani, Abrar A; Raswan, Uday K; Malik, Nayil K; Ramzan, Altaf U; Lone, Iqbal

    2016-01-01

    A neural tube defect (NTD) is a common congenital anomaly with an incidence of 6.57-8.21 per 1000 live births. Patients usually present early because of obvious swelling or due to neurological deficit. However, neglecting the obvious cystic swelling on the back till its transformation into malignant tumor is rare. We describe a case of malignant transformation of meningocele in a 60-year-old man. Magnetic resonance imaging showed sacral meningocele. Neurological examination revealed intact motor and sensory examination with normal bladder and bowel function. There were no signs of meningitis and hydrocephalus. Excision was done and biopsy revealed it as squamous cell carcinoma. Meningocele should be treated early and possibility of malignant change should be kept in mind in neglected cases presenting in adulthood.

  9. Metabolic alterations in renal cell carcinoma.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Interval Squamous Cell Carcinoma of the Rectum

    Directory of Open Access Journals (Sweden)

    Daryl Ramai

    2017-06-01

    Full Text Available Squamous cell carcinoma (SCC of the rectum is a rare clinical entity with an incidence rate of 0.1–0.25% per 1,000 cases. Though its etiology and pathogenesis remains unclear, it has been associated with chronic inflammation and infections. Herein, we report a case of an 82-year-old female who presented with a 2-month history of worsening abdominal pain, hematochezia, and bilateral inguinal lymphadenopathy with right-sided purulent discharge. Two years prior, she had had an unremarkable screening colonoscopy which met all quality indicators. Abdominal CT scan showed an irregular rectal mass with bulky pelvic and retroperitoneal adenopathy. Colonoscopy revealed one large circumferential nonobstructing lesion in the rectum. Endoscopic ultrasound confirmed its origin from the rectal wall with an enlarged perirectal lymph node. Cold biopsy followed by histopathology revealed SCC of the rectum.

  11. Rising incidence of Merkel cell carcinoma

    DEFF Research Database (Denmark)

    Lyhne, Dorte; Lock-Andersen, Jørgen; Dahlstrøm, Karin

    2011-01-01

    , and to investigate the incidence. We suggest guidelines for treatment. First we reviewed the medical records of 51 patients diagnosed with MCC from 1995 until 2006 in eastern Denmark. The nation-wide incidence of MCC was extracted from the Danish Cancer Registry for the calculations for the period 1986-2003. We......Abstract Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark...... reviwed published papers about MCC based on a MEDLINE search. Fourteen of the 51 patients developed recurrence, and 37 (73%) died during the study period. Mean follow-up was 13 months (range 1-122). A total of 153 patients were identified in the Danish Cancer Registry, and showed that incidence rates had...

  12. Incidence of Mast Cells in Oral Squamous Cell Carcinoma: A Short Study

    Directory of Open Access Journals (Sweden)

    A. Anuradha

    2014-01-01

    Full Text Available Mast cells are regarded as complex and multifunctional cells, playing a significant role in immunopathology and a substantial role in tumor angiogenesis. Angiogenesis is a complex process that is tightly regulated by various growth factors in which mast cells act directly by releasing angiogenic factors and henceforth promoting tumor growth and metastasis. The aim of this study is to evaluate the number of mast cells in tissue sections of oral squamous cell carcinoma (OSCC in comparison with normal mucosa. A total of 40 cases (20 OSCC and 20 normal mucosa were stained with 1% toluidine blue and the quantitative analysis was done by using light microscope under 400x magnification. A significant increase in the mast cell count was observed in the sections of OSCC when compared to normal mucosa suggesting their contributing role in tumor growth and progression.

  13. Synergistic anti-tumor effect of KLF4 and curcumin in human gastric carcinoma cell line.

    Science.gov (United States)

    Ji, Jun; Wang, He-Shuang; Gao, Yan-Yan; Sang, Li-Min; Zhang, Li

    2014-01-01

    Kruppel-like factor 4 is a transcription factor which plays an important role in development and progression of various carcinomas. Curcumin characterized by excellent anti-cancer properties is regarded as a serviceable natural compound used in carcinoma therapy. This study aimed at exploring the impact of KLF4 overexpression in cooperation with curcumin on the proliferation, apoptosis and invasion of human gastric carcinoma BGC- 823 cells. Flow cytometry analysis, CCK-8 assays, transwell assays and Western blot results showed that KLF4 overexpression combined with curcumin had significant anti-proliferation, pro-apoptosis and anti-invasion effects on BGC-823 cells. We also found that KLF4 had synergistic effects with curcumin, better promoting apoptosis and inhibiting proliferation and invasion of gastric carcinona cells. These results indicate that KLF4 could be used as a potential therapeutic target; curcumin could act as an auxiliary and provide a promising therapeutic strategy in stomach cancer.

  14. Squamous cell carcinoma of the breast tissue: a case report

    OpenAIRE

    Rubens José Pereira; Wilson Garcia Pereira; Luiz Fernando Jubé Ribeiro; Rita de Cássia Alencar; Vera Saddi; Geraldo Silva Queiroz; Ruffo Freitas Júnior

    1999-01-01

    O carcinoma espinocelular do parênquima mamário é um tipo raro de neoplasia, representando menos de 1% de todos os carcinomas mamários. Esse trabalho relata a condução de um caso diagnosticado e tratado no Serviço de Ginecologia e Mama do Hospital Araújo Jorge/ACCG. São discutidos a apresentação clínica, o diagnóstico e o prognóstico destes tumores.Squamous cell carcinoma of the mammary tissue is a very rare neoplasm, representing less than 1% of all breast carcinomas. The present study repor...

  15. Transitional Bladder Cell Carcinoma Spreading to the Skin

    Directory of Open Access Journals (Sweden)

    W. Kerkeni

    2017-02-01

    Full Text Available Cutaneous metastases from bladder malignancies are rare. We report the case of a 74 year old man who underwent cysto-prostatectomy and adjuvant chemotherapy for a pT3b N+ bladder transitional cell carcinoma. Four months later, he presented with skin disseminated pigmented lesions. Skin biopsy confirmed cutaneous metastasis from urothelial carcinoma.

  16. Primary squamous cell carcinoma of stomach: A rare entity - case ...

    African Journals Online (AJOL)

    Very few case reports of pure squamous cell carcinoma (SCC) of stomach are available in the world literature. The exact pathology of this uncommon carcinoma in stomach remains unknown. This is an additional case report of SCC in an elderly female arising in the gastric antrum. She underwent distal gastrectomy, ...

  17. squamous cell carcinoma of the conjunctiva in benin city, nigeria

    African Journals Online (AJOL)

    the last 1 was a student. The farmers were from the rural areas while the student and engineer were from Benin City (urban). Table I: Squamous Cell Carcinoma Of The Conjunctiva. Sex Age Visual Duration of Tvpe of. Acuity Svmptoms Carcinoma l M 65years NLP 5 years Invasive. 2 M SOyears NLP 5 months Invasive.

  18. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  19. Tumor and Stromal-Based Contributions to Head and Neck Squamous Cell Carcinoma Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Markwell, Steven M.; Weed, Scott A., E-mail: scweed@hsc.wvu.edu [Department of Neurobiology and Anatomy, Program in Cancer Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506 (United States)

    2015-02-27

    Head and neck squamous cell carcinoma (HNSCC) is typically diagnosed at advanced stages with evident loco-regional and/or distal metastases. The prevalence of metastatic lesions directly correlates with poor patient outcome, resulting in high patient mortality rates following metastatic development. The progression to metastatic disease requires changes not only in the carcinoma cells, but also in the surrounding stromal cells and tumor microenvironment. Within the microenvironment, acellular contributions from the surrounding extracellular matrix, along with contributions from various infiltrating immune cells, tumor associated fibroblasts, and endothelial cells facilitate the spread of tumor cells from the primary site to the rest of the body. Thus far, most attempts to limit metastatic spread through therapeutic intervention have failed to show patient benefit in clinic trails. The goal of this review is highlight the complexity of invasion-promoting interactions in the HNSCC tumor microenvironment, focusing on contributions from tumor and stromal cells in order to assist future therapeutic development and patient treatment.

  20. Amyloid in basal cell carcinoma and seborrheic keratosis

    DEFF Research Database (Denmark)

    Olsen, K E; Westermark, Per

    1994-01-01

    The frequency of amyloid substance was studied in two different types of skin tumours: basal cell carcinoma and seborrheic keratosis. In 9 out of 49 cases of seborrheic keratosis amyloid substance was found. In the basal cell carcinomas, 194 out of 260 cases showed amyloid deposits, a rate...... that is higher than that previously reported. The basal cell carcinoma material was further studied regarding the amount of amyloid, mitotic rate, degree of apoptosis and the age of the patients. There was no correlation between the amount of amyloid and the mitotic rate, or the degree of apoptosis...

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

    Science.gov (United States)

    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.

  2. Chromosome abnormalities in squamous cell carcinoma of the urethra.

    Science.gov (United States)

    Fadl-Elmula, I; Gorunova, L; Mandahl, N; Elfving, P; Heim, S

    1998-09-01

    Cytogenetic analysis of short-term cultured cells from a urethral squamous cell carcinoma showed the tumor to have an abnormal, karyotypically complex near-diploid clone as well as its near-tetraploid duplicate. This is the first urethral carcinoma with chromosomal abnormalities to be reported. Chromosomes Y, 2, 3, 4, 6, 7, 8, 11, and 20 were all involved in numerical and/or structural rearrangements. Of particular interest was the fact that no rearrangements of chromosomes 9 and 17, both almost ubiquitously involved in transitional cell carcinoma of the urinary tract, were seen.

  3. Squamous cell carcinoma of temporal bone: four case reports

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    Lee, Jun Ha; Sung, Ki Joon; Sim, Young; Shim, Sue Yoen; Yoon, Byoung Moon [Wonju College of Medicine, Yonsei University, Wonju (Korea, Republic of)

    2000-04-01

    We report the CT findings of four cases of squamous cell carcinoma, paying special attention to the epicenter of the lesion and the pattern of bony destruction. All four patients had a past history of chronic otitis media. Squamous cell carcinoma affected mainly the hypotympanum and inferior wall of the external auditory canal. and in all cases revealed an irregular pattern of bony destruction. Irregular destruction of the tegmen tympani occurred in two cases. In cases of squamous cell carcinoma, CT findings suggesting involvement of the promontory are usually noted. (author)

  4. Is cutaneous leishmaniasis a risk factor for basal cell carcinoma?

    Science.gov (United States)

    Chisti, M; Almasri, R; Hamadah, I

    2016-05-01

    Basal cell carcinoma (BCC) is the most common epithelial neoplasm of skin. Risk factors for the development of BCC include intermittent intense sun exposure, radiation therapy, family history of BCC, immune suppression and fair complexion, especially red hair. It can originate in scars like small pox, vaccination, chicken pox or surgical scars. We present a case of basal cell carcinoma arising in a leishmania scar on the nose, sixty years after the primary lesion. Although rare, BCC's have arisen in leishmania scars. Thus the possibility of basal cell carcinoma should be considered while dealing with such patients. Even though a causal relationship, if any, cannot be ascertained at present.

  5. Renal Cell Carcinoma Presenting with Cutaneous Metastasis: A Case Report

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    Nilufer Onak Kandemir

    2010-01-01

    Full Text Available Renal cell carcinoma is the most common kidney tumor in adults. Cutaneous metastasis is a rare first symptom of the disease. This paper describes the diagnosis of a renal cell carcinoma that was indicated by cutaneous metastasis in the head and neck region, and considers the etiopathogenesis of such cases. A careful skin examination is important to detect cutaneous metastasis associated with renal cell carcinomas. Metastatic skin lesions in the head and neck region must be taken into consideration during a differential diagnosis.

  6. Renal Cell Carcinoma Presenting with Cutaneous Metastasis: A Case Report

    Science.gov (United States)

    Onak Kandemir, Nilufer; Barut, Figen; Yılmaz, Kıvanç; Tokgoz, Husnu; Hosnuter, Mubin; Ozdamar, Sukru Oguz

    2010-01-01

    Renal cell carcinoma is the most common kidney tumor in adults. Cutaneous metastasis is a rare first symptom of the disease. This paper describes the diagnosis of a renal cell carcinoma that was indicated by cutaneous metastasis in the head and neck region, and considers the etiopathogenesis of such cases. A careful skin examination is important to detect cutaneous metastasis associated with renal cell carcinomas. Metastatic skin lesions in the head and neck region must be taken into consideration during a differential diagnosis. PMID:20811607

  7. Carrageenan delays cell cycle progression in human cancer cells in vitro demonstrated by FUCCI imaging.

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    Prasedya, Eka Sunarwidhi; Miyake, Masao; Kobayashi, Daisuke; Hazama, Akihiro

    2016-08-04

    Carrageenan is a sulfated polysaccharide that exists in red seaweeds recently shown to have anticancer properties. Previous findings show various effects of carrageenan suppressing tumor cell growth. One of the hallmarks of cancer is uncontrolled proliferation, a consequence of loss of normal cell-cycle control, that underlies tumor growth. Recently there is an increasing interest in potential anticancer agents that affect cell cycle in cancer cells. Thus, in this study we investigated the effects of carrageenan on the tumor cell cycle. Using human cervical carcinoma cells (HeLa) cells as and human umbilical vein endothelial cells (HUVEC), the cytotoxic effects of kappa carrageenan (k-CO) and lambda carrageenan (λ-CO) at the concentrations of 250-2500 μg/mL were observed. Cell viability was determined using the MTT assay while cell death rates were determined using staining with calcein-AM/propidium iodide. Cell-cycle profile and progression were demonstrated with HeLa cells expressing FUCCI (fluorescence ubiquitination-based cell-cycle indicator) probes (HeLa-FUCCI). Carrageenan had no significant effect on HUVEC (normal cells). In contrast both forms of carrageenan were cytotoxic towards HeLa cells (cancer cells). Furthermore, according to cell-cycle analysis with FUCCI cells, the cell cycle of HeLa cells was delayed in specific phases due to different carrageenan treatments. Considering these results, it could be suggested that carrageenan affects the cell-cycle of HeLa cells not only by arresting the cell cycle in specific phases but also by delaying the time needed for the cell to progress through the cell cycle. Additionally, different types of carrageenans have different effects on cell cycle progression. This effect of carrageenan towards cancer cells could possibly be developed into a tumor cell-specific anticancer agent.

  8. Detection of squamous carcinoma cells using gold nanoparticles

    Science.gov (United States)

    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.

  9. EZH2 promotes cell proliferation by regulating the expression of RUNX3 in laryngeal carcinoma.

    Science.gov (United States)

    Lian, Rong; Ma, Huimin; Wu, Zhiyan; Zhang, Guozheng; Jiao, Lei; Miao, Wenjie; Jin, Qianqian; Li, Ruixue; Chen, Ping; Shi, Haixu; Yu, Wenfa

    2017-08-09

    Enhancer of zeste homolog 2 (EZH2) is a highly conserved histone methyltransferase, which is overexpressed in different types of cancers such as breast and prostate cancer. It is reported that EZH2 can directly down-regulate RUNX3 by increasing histone H3 methylation. However, the role of EZH2 in the development and progression of laryngeal carcinoma has not yet been investigated, and the relationship between EZH2 and RUNX3 in laryngeal carcinoma is rarely reported. The current study aims to determine the role of EZH2 in the progression of laryngeal carcinoma, and investigate the interaction between EZH2 and the tumor suppressor RUNX3. Our study found that EZH2 is overexpressed in laryngeal carcinoma patients, and silencing EZH2 by EZH2 siRNA significantly inhibited the proliferation of laryngeal carcinoma cells. Besides, we also found that RUNX3 is repressed in laryngeal carcinoma patients. Moreover, RUNX3 as a downstream target protein of EZH2 is up-regulated by EZH2 siRNA accompanied by a decrease in the trimethylation modification pattern of H3K27. RUNX3 siRNA inhibits the decreased proliferation induced by EZH2 siRNA. Furthermore, β-catenin protein expression is down-regulated by EZH2 siRNA and up-regulated by RUNX3 siRNA, and RUNX3 siRNA inhibits the down-regulation effect of EZH2 siRNA on β-catenin protein expression. Additionally, the Wnt/β-catenin activator BIO reverses the inhibitory effect of EZH2 siRNA on Hep-2 cell proliferation. Taken together, our results suggest that EZH2 regulates cell proliferation potentially by targeting RUNX3 through the Wnt/β-catenin signaling pathway in laryngeal carcinoma.

  10. Autologous dendritic cells combined with cytokine-induced killer cells in the treatment of metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Jin-chao ZHANG

    2016-10-01

    Full Text Available Objective  To evaluate the clinical efficacy, the immune function and follow-up observation of autologous dendritic cells (DCs combined with cytokine-induced killer (CIK cells in the treatment of metastatic renal cell carcinoma. Methods  Peripheral blood mononuclear cells (PBMCs were collected from 27 patients with metastatic renal cell carcinoma, and cultured in vitro to produce DCs and CIK cells. After sterility test, phenotypic characterization by flow cytometry and cell count, the produced DCs and CIK cells were then returned to the patient. DCs were given subcutaneously on day 7, 9, 11 and 13 respectively, after PBMCs collection, and CIK cells were given intravenously on day 11 and 13 respectively. This treatment regimen was repeated at a 3 months interval until the disease progresses. Clinical outcomes and immune function were recorded during the treatment period. Results  After DCs-CIK cells treatment, clinical efficacy showed an objective response rate (ORR of 37%, a disease control rate (DCR of 85% and 2 years overall survival rate of 81.5%. There were no significant changes of T cell subsets including CD3 +CD4+CD8–, CD3+CD4–CD8+, CD3+CD19–, CD3–CD19+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD3+HLA-DR–, CD3+HLA-DR+, CD3+CD28+CD8+ and Th2 cells except CD3+CD4+CD25+ T cells (Treg cells and Th1 in peripheral blood between pre-and post-treatment. No serious adverse events were observed. Conclusion  DCs-CIK cells immunotherapy provides a safe and effective treatment approach for patients with metastatic renal cell carcinoma, and may improve the immunosuppression status and enhance the anti-tumor immunity without obvious adverse reaction. DOI: 10.11855/j.issn.0577-7402.2016.10.07

  11. Clear cell papillary renal cell carcinoma: micro-RNA expression profiling and comparison with clear cell renal cell carcinoma and papillary renal cell carcinoma.

    Science.gov (United States)

    Munari, Enrico; Marchionni, Luigi; Chitre, Apurva; Hayashi, Masamichi; Martignoni, Guido; Brunelli, Matteo; Gobbo, Stefano; Argani, Pedram; Allaf, Mohamad; Hoque, Mohammad O; Netto, George J

    2014-06-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. Micro-RNAs (miRNAs) are small noncoding RNAs that play a crucial role in regulating gene expression and are involved in various biological processes, including cancer development. To better understand the biology of this tumor, we aimed to analyze the miRNA expression profile of a set of CCPRCC using microarray and quantitative reverse transcription-polymerase chain reaction. A total of 15 cases diagnosed as CCPRCC were used in this study. Among the most differentially expressed miRNA in CCPRCC, we found miR-210, miR-122, miR-34a, miR-21, miR-34b*, and miR-489 to be up-regulated, whereas miR-4284, miR-1202, miR-135a, miR-1973, and miR-204 were down-regulated compared with normal renal parenchyma. To identify consensus of differentially regulated miRNA between CCPRCC, CCRCC, and PRCC, we additionally determined differential miRNA expression using 2 publically available microarray data sets from the NCBI Gene Expression Omnibus database (GSE41282 and GSE3798). This comparison revealed that the miRNA expression profile of CCPRCC shows some overlapping characteristics between CCRCC and PRCC. Moreover, CCPRCC lacks dysregulation of important miRNAs typically associated with aggressive behavior. In summary, we describe the miRNA expression profile of a relatively infrequent type of renal cancer. Our results may help in understanding the molecular underpinning of this newly recognized entity. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Clinicopathological evaluation of radiation induced basal cell carcinoma

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    Meibodi Naser

    2008-01-01

    Full Text Available Background: Development of skin neoplasms is one of the most important chronic complications of radiation therapy. Basal cell carcinoma (BCC is the most frequent carcinoma occurring at the region of the body to which radiotherapy was delivered. Aim: The aim of this study was to evaluate clinical and histological aspects of basal cell carcinoma in patients with a history of radiotherapy. Materials and Methods: Medical records and microscopic slides of 80 patients with basal cell carcinoma who had received radiotherapy (1996-2006 were reviewed in pathology department of Imam Reza hospital of Mashhad, Iran. Collected data were analyzed statistically using descriptive test. Results: 60 men and 20 women were included, majority of them in their sixties. Plaque was the most common clinical pattern of basal cell carcinoma. Fifty one percent of the patients had pigmented and 42.5% had multiple lesions. Scalp was the most common site of involvement. Histologically, macronodular and pigmented carcinoma were the most predominant forms of basal cell carcinoma. Discussion: Majority of patients had scalp involvement and multiple lesions. Nodular and pigmented forms were the most common histological findings. We suggest the need for close supervision in patients with a history of radio therapy in the past.

  13. Primary small cell carcinoma of the esophagus.

    Science.gov (United States)

    Lv, Jima; Liang, Jun; Wang, Jinwan; Wang, Luhua; He, Jie; Xiao, Zefen; Yin, Weibo

    2008-12-01

    Primary small cell esophageal carcinoma (SCEC) is a rare and aggressive disease for which there is no recommended standard treatment at this time. A total of 126 patients with SCEC, diagnosed histologically between May 1985 and June 2005 at our institution, were analyzed retrospectively. All were staged according to the Veterans' Administration Lung Study Group staging system. The TNM system for esophageal carcinoma (6th edition, American Joint Committee on Cancer) was also used for those who underwent esophagectomies. SPSS (10.0) software was used for statistical analysis. Cox's hazard regression model was performed to identify prognostic factors. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. The chi2 test was performed to examine frequencies between different groups. Through a median follow-up of 13 months, 108 patients died, 10 were alive, and 8 were lost to follow-up. Of the entire study population, the overall median survival time (MST) and 1-, 3-, and 5-year overall survival rates were 12.5 months and 52.2%, 15.9%, and 12.2%, respectively. For limited disease, the MST and 1-, 2-, and 3-year overall survival rates were 14.0 months and 62.1%, 30.8%, and 22.4%, respectively; for extensive disease, the respective values were 7.0 months and 29.3%, 13.6%, and 2.7% (p = 0.0001). The MST of 14.5 months for cases who received chemotherapy was superior to that of 5.2 months for cases who did not (p = 0.0001). Tumor stage, length of the primary lesion, and chemotherapy, but not surgery were independent prognostic factors in a multivariate analysis. SCEC is systemic disease. Tumor stage and chemotherapy were independent prognostic factors. Systemic therapy, based on chemotherapy with radiotherapy, is recommended.

  14. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

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    Daniel Y.C. Heng

    2011-12-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

  15. Prp19 Arrests Cell Cycle via Cdc5L in Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Huang, Renzheng; Xue, Ruyi; Qu, Di; Yin, Jie; Shen, Xi-Zhong

    2017-04-07

    Pre-mRNA processing factor 19 (Prp19) is involved in many cellular events including pre-mRNA processing and DNA damage response. Recently, it has been identified as a candidate oncogene in hepatocellular carcinoma (HCC). However, the role of Prp19 in tumor biology is still elusive. Here, we reported that Prp19 arrested cell cycle in HCC cells via regulating G2/M transition. Mechanistic insights revealed that silencing Prp19 inhibited the expression of cell division cycle 5-like (Cdc5L) via repressing the translation of Cdc5L mRNA and facilitating lysosome-mediated degradation of Cdc5L in HCC cells. Furthermore, we found that silencing Prp19 induced cell cycle arrest could be partially resumed by overexpressing Cdc5L. This work implied that Prp19 participated in mitotic progression and thus could be a promising therapeutic target of HCC.

  16. Unclassified Renal Cell Carcinoma With Medullary Phenotype Versus Renal Medullary Carcinoma: Lessons From Diagnosis in an Italian Man Found to Harbor Sickle Cell Trait.

    Science.gov (United States)

    Colombo, Piergiuseppe; Smith, Steven C; Massa, Simona; Renne, Salvatore L; Brambilla, Simona; Peschechera, Roberto; Graziotti, Pierpaolo; Roncalli, Massimo; Amin, Mahul B

    2015-11-01

    Medullary carcinoma is a rare malignant tumor of the kidney. It affects individuals of African descent and all cases reported show evidence of sickle cell trait. We reviewed an unusual carcinoma arising in a white man, the ninth in the literature. The tumor demonstrated features associated with renal medullary carcinoma, or unclassified renal cell carcinoma, medullary phenotype as recently described; the presence of sickle cell trait confirmed the diagnosis of medullary carcinoma. This case is helpful in the differential diagnosis with non-sickle cell associated "renal cell carcinoma, unclassified with medullary phenotype," and study of this spectrum of tumors is ongoing.

  17. The role of glutathione transferases in renal cell carcinoma

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    Ćorić Vesna

    2016-01-01

    Full Text Available Mounting evidence suggest that members of the subfamily of cytosolic glutathione S-transferases (GSTs possess roles far beyond the classical glutathione-dependent enzymatic conjugation of electrophilic metabolites and xenobiotics. Namely, monomeric forms of certain GSTs are capable of forming protein: protein interactions with protein kinases and regulate cell apoptotic pathways. Due to this dual functionality of cytosolic GSTs, they might be implicated in both the development and the progression of renal cell carcinoma (RCC. Prominent genetic heterogeneity, resulting from the gene deletions, as well as from SNPs in the coding and non-coding regions of GST genes, might affect GST isoenzyme profiles in renal parenchyma and therefore serve as a valuable indicator for predicting the risk of cancer development. Namely, GSTs are involved in the biotransformation of several compounds recognized as risk factors for RCC. The most potent carcinogen of polycyclic aromatic hydrocarbon diol epoxides, present in cigarette smoke, is of benzo(apyrene (BPDE, detoxified by GSTs. So far, the relationship between GST genotype and BPDE-DNA adduct formation, in determining the risk for RCC, has not been evaluated in patients with RCC. Although the association between certain individual and combined GST genotypes and RCC risk has been debated in a the literature, the data on the prognostic value of GST polymorphism in patients with RCC are scarce, probably due to the fact that the molecular mechanism supporting the role of GSTs in RCC progression has not been clarified as yet.

  18. The role of miR-372 in ovarian carcinoma cell proliferation.

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    Guan, Xue; Zong, Zhi-Hong; Chen, Shuo; Sang, Xiu-Bo; Wu, Dan-Dan; Wang, Li-Li; Liu, Yao; Zhao, Yang

    2017-08-15

    MicroRNA-372 has been shown to be associated with multiple tumors' development and progression, by regulating the expression of proteins involved in cell cycle and apoptosis. However, the specific mechanism and function of miR-372 in ovarian carcinoma are not clear. Our study explored the role of miR-372 in ovarian carcinoma cell cycle and proliferation. MiR-372 expression was quantified in normal ovarian tissue, benign tumors, primary ovarian carcinomas and metastatic omentum by qRT-PCR. MTT assay and plate clone formation assay were performed to evaluate the cell viability and proliferation. EDU assay and cell apoptosis assay were also used to determine cell growth. We used Western Blot to analysis expression of the known miR-372 targets. We found that miR-372 expression was significantly lower in ovarian carcinoma than normal ovarian tissues and benign tumors. Moreover, miR-372 overexpression showed significant inhibition of cell proliferation and promoted cell apoptosis. Western Blot revealed that miR-372 downregulated the expression of ATAD2, LATS2, P62, DKK1 and cyclinA1 to inhibit the proliferation of cells. Our findings indicate that miR-372 has a prominent role in inhibiting tumor growth and it is a valuable target for ovarian cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Extensive Presentation of Penile Carcinoma Cuniculatum a Variant of Squamous Cell Carcinoma With Low Malignant Potential

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    Mohabe A. Vinson

    2016-09-01

    Full Text Available Carcinoma cuniculatum is an uncommon variation of squamous cell carcinoma (SCC has been documented in a few cases at various locations of the body such as penis, foot, jaw, oropharynx and esophagus. In this case, a 79-year-old male presents with a penile mass, which he underwent a total penectomy. Histology of the mass was defined as carcinoma cuniculatum with negative margins and no lymphovascular invasion. This variant of SCC rarely metastasizes. A joint decision was made to observe lymph nodes. It is important to differentiate the different SCC because patient care can be guided based on the pathology.

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

    Science.gov (United States)

    2017-03-01

    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 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

  1. ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas.

    Science.gov (United States)

    Adams, April; Warner, Kristy; Pearson, Alexander T; Zhang, Zhaocheng; Kim, Hong Sun; Mochizuki, Daiki; Basura, Gregory; Helman, Joseph; Mantesso, Andrea; Castilho, Rogério M; Wicha, Max S; Nör, Jacques E

    2015-09-29

    A small sub-population of cells characterized by increased tumorigenic potential, ability to self-renew and to differentiate into cells that make up the tumor bulk, has been characterized in some (but not all) tumor types. These unique cells, namedcancer stem cells, are considered drivers of tumor progression in these tumors. The purpose of this work is to understand if cancer stem cells play a functional role in the tumorigenesis of salivary gland mucoepidermoid carcinomas. Here, we investigated the expression of putative cancer stem cell markers (ALDH, CD10, CD24, CD44) in primary human mucoepidermoid carcinomas by immunofluorescence, in vitro salisphere assays, and in vivo tumorigenicity assays in immunodeficient mice. Human mucoepidermoid carcinoma cells (UM-HMC-1, UM-HMC-3A, UM-HMC-3B) sorted for high levels of ALDH activity and CD44 expression (ALDHhighCD44high) consistently formed primary and secondary salispheres in vitro, and showed enhanced tumorigenic potential in vivo (defined as time to tumor palpability, tumor growth after palpability), when compared to ALDHlowCD44low cells. Cells sorted for CD10/CD24, and CD10/CD44 showed varying trends of salisphere formation, but consistently low in vivo tumorigenic potential. And finally, cells sorted for CD44/CD24 showed inconsistent results in salisphere formation and tumorigenic potential assays when different cell lines were evaluated. Collectively, these data demonstrate that salivary gland mucoepidermoid carcinomas contain a small population of cancer stem cells with enhanced tumorigenic potential and that are characterized by high ALDH activity and CD44 expression. These results suggest that patients with mucoepidermoid carcinoma might benefit from therapies that ablate these highly tumorigenic cells.

  2. Carcinoma espinocelular de reto: relato de caso Squamous cell carcinoma of the rectum: a case report

    Directory of Open Access Journals (Sweden)

    Juliana Magalhães Lopes

    2010-03-01

    Full Text Available O Carcinoma Espinocelular de Reto é entidade extremamente rara e seu comportamento biológico permanece desconhecido. O tratamento pode variar entre radio e quimioterapia isoladamente ou complementar ao tratamento cirúrgico. Relatamos caso de carcinoma espinocelular de reto superior, tratado com radio e quimioterapia, com regressão total da lesão.Squamous cell carcinoma of the rectum is a extremely rare neoplasm and its biological behavior remains unknown. Treatment varies from surgery with and without adjuvant therapy to chemotherapy and radiotherapy alone. We present a patient with squamous cell carcinoma of the superior rectum who underwent chemo and radiotherapy exclusively, with total regression of the tumor.

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

    Science.gov (United States)

    Lo Muzio, Lorenzo

    2008-11-25

    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

  4. Nevoid basal cell carcinoma syndrome (Gorlin syndrome

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    Lo Muzio Lorenzo

    2008-11-01

    Full Text Available Abstract 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

  5. Gene expression of IQGAPs and Ras families in an experimental mouse model for hepatocellular carcinoma: a mechanistic study of cancer progression.

    Science.gov (United States)

    Zoheir, Khairy M A; Abd-Rabou, Ahmed A; Harisa, Gamaleldin I; Ashour, Abdelkader E; Ahmad, Sheikh Fayaz; Attia, Sabry M; Bakheet, Saleh A; Abdel-Hamied, Hala E; Abd-Allah, Adel R; Kumar, Ashok

    2015-01-01

    IQGAPs genes play critical role in either induction or suppression of cancer and its progression, however the relationship between Ras genes and these genes are still unclear. In this study, we tried to understand the mechanistic action of IQGAPs genes and its correlation with Ras genes in mouse hepatic cancer model. The genetic expressions of IQGAP1, IQGAP2, IQGAP3, Hras, Kras, Nras, Mras, Caspase3, and BAX were followed in both hepatocellular carcinoma and normal liver cells of Balbc mice. Genotoxic agent diethylnitrosamine (DEN)-induced hepatic cancer model was induced in male mice and recorded the occurrence of hepatocellular carcinoma by morphological and histological changes in the liver. It was observed that mRNA expressions of IQGAP1, Hras, Kras, Nras, Mras, Caspase3, and BAX genes were highly elevated in hepatocellular carcinoma cells when compared with normal liver cells, additionally their expressions increased by concentrating the dose of DEN. While, the expressions of IQGAP2 and IQGAP3 were significantly decreased in hepatocellular carcinoma cells when compared with normal liver cells, as well as their expressions decreased more with increasing the dose of DEN. It was concluded from this study that IQGAP1 has a strong signaling relationship with Ras genes in induction of cancer and it is considered as a key gene for induction or suppression of the hepatocellular carcinoma.

  6. Comparison of Immunohistochemical Expression of Antiapoptotic Protein Survivin in Normal Oral Mucosa, Oral Leukoplakia, and Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Negi, Amita; Puri, Abhiney; Gupta, Rakhi; Nangia, Rajat; Sachdeva, Alisha; Mittal, Megha

    2015-01-01

    Background. Oral squamous cell carcinoma is the sixth most frequent malignant tumor worldwide and the third most common cancers in developing countries. Oral leukoplakia is the best-known precursor lesion of oral squamous cell carcinoma. The aim of the present study was to compare immunohistochemical expression of antiapoptotic protein survivin in normal oral mucosa, oral leukoplakia, and oral squamous cell carcinoma. Method. Total 45 specimens of formalin fixed paraffin embedded tissue blocks, 15 in each of the following: normal oral mucosa, leukoplakia, and oral squamous cell carcinoma were used for the study. Immunohistochemical reaction for survivin protein was performed for the 4 µm thick histological sections taken on positively charged slides. Results. 20% normal mucosa cases, 53.33% cases of leukoplakia, and 80% of oral squamous cell carcinoma were found out to be survivin positive. One way ANOVA test indicated statistically significant difference of survivin expression between the three different groups (p oral epithelial dysplasia and squamous cell carcinoma samples indicate that survivin protein expression may be an early event in initiation and progression of oral squamous cell carcinoma.

  7. Ovarian Small Cell Carcinoma Hypercalcemic Type: A Case Report

    LENUS (Irish Health Repository)

    Rahma, M B.

    2016-09-01

    A 31-year-old female was diagnosed with small cell carcinoma of the ovary hypercalcaemic type (OSCCHT) post left oophorectomy. This is a rare aggressive ovarian tumour of which less than 300 cases were reported.

  8. Lactic acidosis and small cell carcinoma of the lung.

    Science.gov (United States)

    Sheriff, D. S.

    1986-01-01

    Two patients with small cell carcinoma of the lung who presented with lactic acidosis are described. Hepatocellular failure due to extensive metastases may be the cause of acute lactic acidosis. PMID:3012499

  9. [Paraneoplastic syndromes in three patients with renal cell carcinoma

    NARCIS (Netherlands)

    Steffens, M.G.; Mulder, P.H.M. de; Mulders, P.F.A.

    2004-01-01

    Renal cell carcinoma was diagnosed in three male patients, 45, 53 and 52 years of age. In addition, they had paraneoplastic symptoms: hypercalcaemia, hyperglycaemia and elevated hepatic enzyme levels, respectively. All three patients underwent tumour nephrectomy, after which the paraneoplastic

  10. Squamous cell carcinoma arising in mature cystic teratoma of ovary

    Directory of Open Access Journals (Sweden)

    Ranu Patni

    2014-01-01

    Full Text Available Squamous cell carcinoma of the ovary is a rare condition and usually arises in mature cystic teratoma (MCT or dermoid cyst of the ovary. The reported incidence of malignant transformation in MCT is approximately 2%. A case of squamous cell carcinoma arising in a dermoid cyst of the ovary presenting at an early stage is presented here. A 53-year-old postmenopausal lady, presented with the complaint of pain in right lower abdomen since one month and a large complex abdomino-pelvic mass on examination and investigations. Final histopathology was reported as squamous cell carcinoma of left ovary arising from dermoid cyst and a benign dermoid cyst in the right ovary. The patient was assigned to squamous cell carcinoma of the ovary arising in a mature cystic teratoma, surgical stage Ic2. In view of the poor prognosis, adjuvant chemotherapy was started.

  11. Renal cell carcinoma in pregnancy: Still a management challenge

    National Research Council Canada - National Science Library

    Akpayak, I.C; Shuiabu, S.I; Ofoha, C.G; Dakum, N.K; Ramyil, V.M

    2015-01-01

    Background: Renal cell carcinoma during pregnancy is uncommon. We present a rare case, highlighting the dilemma faced by the patient and the challenge of deciding the appropriate management option. Patient...

  12. A case of renal cell carcinoma and angiomyolipoma in an ...

    African Journals Online (AJOL)

    Abstract. We describe a case of renal cell carcinoma in the right kidney together with an angiomyolipoma in the left kidney, encountered in an adolescent girl at Potchefstroom Provincial Hospital, North West Province, South Africa.

  13. Understanding Papillary Renal Cell Carcinoma | Center for Cancer Research

    Science.gov (United States)

    Renal cell carcinoma (RCC), the most common form of kidney cancer in adults, is not a single disease but rather a collection of different tumor types driven by distinct genetic changes that arise within the same tissue.

  14. Oropharyngeal squamous cell carcinoma: a unique disease on the rise?

    NARCIS (Netherlands)

    van Monsjou, Hester S.; Balm, Alfons J. M.; van den Brekel, Michiel M.; Wreesmann, Volkert B.

    2010-01-01

    Despite successful efforts to control tobacco and alcohol consumption in the western world, several developed countries report rising oropharyngeal squamous cell carcinoma (OPSCC) incidence figures, specifically in young individuals. Similar to anogenital cancers, a significant proportion of OPSCC

  15. Genetics Home Reference: head and neck squamous cell carcinoma

    Science.gov (United States)

    ... Enable Javascript to view the expand/collapse boxes. Description Squamous cell carcinoma is a cancer that arises ... that infection with certain strains of human papillomavirus (HPV) is linked to the development of HNSCC. HPV ...

  16. New agents in treatment of metastatic renal cell carcinoma

    National Research Council Canada - National Science Library

    Jakub Zolnierek; Pawel Nurzynski; Piotr Rzepecki

    2007-01-01

      As renal cell carcinoma appears to be resistant to conventional treatment modalities and results of cytokine-based immunotherapy are far from satisfactory, there is desperate need for new active agents to be discovered...

  17. Wnt Signaling in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2016-06-01

    Full Text Available 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.

  18. Mutational Analysis of Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Erstad, Derek J. [Department of Surgery, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 (United States); Cusack, James C. Jr., E-mail: jcusack@mgh.harvard.edu [Division of Surgical Oncology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 (United States)

    2014-10-17

    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.

  19. Merkel Cell Carcinoma in Immunosuppressed Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Janice E. [Mayo Clinic College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States); Brewer, Jerry D., E-mail: brewer.jerry@mayo.edu [Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States)

    2014-06-27

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. The infectivity of Merkel cell polyomavirus (MCPyV), an apparent agent in MCC development, may be exacerbated with impaired immune responses. This paper reviews relevant data regarding the role of immunosuppression in the development of MCC and describes modes of immunodeficient states. Because of the inherently low incidence rate of MCC, several case studies and series are also briefly mentioned to provide a more comprehensive summary of MCC in the setting of immunosuppression. We describe immunosuppressed patients who have experienced excessive UV radiation, organ transplantation, human immunodeficiency virus infection/AIDS, autoimmune diseases, and lymphoproliferative disorders. Iatrogenic forms of immunosuppression are also highlighted. Studies that quantify risks consistently report that individuals with a history of solid organ transplantation, autoimmune diseases, AIDS, and/or lymphoproliferative diseases have a significantly elevated risk of developing MCC. Overall, immunocompromised patients also appear to have an early onset and more aggressive course of MCC, with poorer outcomes. Recommendations for multidisciplinary approaches are proposed to effectively prevent and manage MCC in these patients.

  20. Breast carcinoma with osteoclast-like giant cells

    DEFF Research Database (Denmark)

    Gjerdrum, L M; Lauridsen, M C; Sørensen, Flemming Brandt

    2001-01-01

    Primary carcinoma with osteoclast-like giant cells is a very rare tumour of the female breast. The clinical course, histological, immunohistochemical and ultrastructural features of 61 cases of invasive duct carcinoma with osteoclast-like multinucleated giant cells (OMGCs) are reviewed and a new...... in the literature have shown that 86% of patients with these tumours are still alive after 5 years. Histologically, these tumours are invasive ductal carcinomas with OMGCs next to the neoplastic glands and within their lumen. Signs of recent and past haemorrhage are ubiquitously present in the highly vascularized...

  1. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

    Science.gov (United States)

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-03-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (Pepithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

  2. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

    OpenAIRE

    Yuan, Zhi-xiang; Mo, Jingxin; Zhao, Guixian; Shu, Gang; Fu, Hua-Lin; Wei ZHAO

    2016-01-01

    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rati...

  3. Autopsy case of squamous cell carcinoma arising from pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Saijo, Noboru; Maeda, Ken (Rumoi City General Hospital, Hokkaido (Japan)); Kita, Shinichiro; Ishigaki, Seishi; Sone, Hisao

    1983-02-01

    An 80-year-old male patient was admitted complaining of abdominal mass. The mass showed a large doughnut shape in scintigraphy with /sup 67/Ga and a honeycomb appearance in abdominal echography. Continuous fever, ascitis and anuria caused the patient to be inoperable and death occurred. Postmortem examination revealed a rare case of squamous cell carcinoma arising from pancreas. Diagnosis for the squamous cell carcinoma of the pancreas was discussed in this paper.

  4. Acinic Cell Carcinoma in Minor Salivary Glands of Retromolar

    OpenAIRE

    KOYUNCU, Mehmet; Atmaca, Sinan; Bedri KANDEMİR; ÇAKIL, Bünyamin

    2009-01-01

    Acinic cell carcinoma (ACC) is a rare malignant tumor of the salivary glands. ACC of the minor salivary glands is very rare. In the oral cavity, minor salivary gland tumors are rarely seen in the inferior anatomic regions like the retromolar trigone and the floor of mouth compared to the superior regions like the palate. We present a retromolar trigone ACC, a rare location in the oral cavity and discuss the relevant reports in the literature. Key words: Acinic cell carcinoma, minor salivar...

  5. Nevoid Basal Cell Carcinoma Syndrome and Hairy Skin Patches.

    Science.gov (United States)

    Notay, Manisha; Kamangar, Faranak; Awasthi, Smita; Fazel, Nasim

    2017-03-01

    We report a case of an increasing number of discrete patches of darkly pigmented terminal hair in a patient with nevoid basal cell carcinoma syndrome. This case adds to a small case series of three patients which have previously reported this observation. We report this case to highlight hairy patches as an important clinical feature associated with nevoid basal cell carcinoma syndrome. © 2017 Wiley Periodicals, Inc.

  6. Nevoid basal cell carcinoma syndrome; Naevoid Basalzellkarzinom-Syndrom

    Energy Technology Data Exchange (ETDEWEB)

    Grgic, A.; Heinrich, M.; Heckmann, M.; Kramann, B. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie; Aliani, S. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Klinik fuer Kinder- und Jugendmedizin; Dill-Mueller, D. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Hautklinik und Poliklinik; Uder, M. [Erlange-Nuernberg Univ. (Germany). Inst. fuer Diagnostische Radiologie

    2005-07-01

    Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal-dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, calcification of the falx cerebri, and spine and rib anomalies. The combination of clinical, imaging, and histological findings is helpful in identifying NBCCS patients. Imaging plays a crucial role in evaluation of these patients. We present a wide variety of clinical and radiological findings characteristic of this disease. (orig.)

  7. Targeted therapy for orbital and periocular basal cell carcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Yin, Vivian T; Pfeiffer, Margaret L; Esmaeli, Bita

    2013-01-01

    To review the literature on targeted therapy for orbital and periocular basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) and provide examples of patients recently treated with such therapy. The authors reviewed the literature on clinical results of targeted therapy and the molecular basis for targeted therapy in orbital and periocular BCC and cutaneous SCC. The authors also present representative cases from their practice. Mutation in the patched 1 gene (PTCH1) has been implicated in BCC, and overexpression of epidermal growth factor receptor (EGFR) has been shown in SCC. Vismodegib, an inhibitor of smoothened, which is activated upon binding of hedgehog to Ptc, has been shown to significantly decrease BCC tumor size or even produce complete resolution, especially in cases of basal cell nevus syndrome. Similarly, EGFR inhibitors have been shown to significantly decrease SCC tumor size in cases of locally advanced and metastatic disease. The authors describe successful outcomes after vismodegib treatment in a patient with basal cell nevus syndrome with numerous bulky lesions of the eyelid and periocular region and erlotinib (EGFR inhibitor) treatment in a patient with SCC who was deemed not to be a good surgical candidate because of advanced SCC of the orbit with metastasis to the regional lymph nodes, advanced age, and multiple medical comorbidities. Targeted therapy using hedgehog pathway and EGFR inhibitors shows significant promise in treatment of orbital and periocular BCC and cutaneous SCC, respectively. Such targeted therapy may be appropriate for patients who are not good candidates for surgery.

  8. Primary Colonic Signet Ring Cell Carcinoma Presenting Carcinocythemia: An Autopsy Case

    Directory of Open Access Journals (Sweden)

    Ryosuke Misawa

    2008-09-01

    Full Text Available Primary colorectal signet ring cell carcinoma (SRCC is a rare but distinctive type of mucin-producing adenocarcinoma of the large intestine with still controversial clinicopathological features and prognosis. We encountered primary colonic SRCC in a 51-year-old Japanese man with extensive bone metastasis ultimately leading to carcinocythemia before the initiation of chemotherapy and surgical intervention. Three days before death, besides progressive disseminated intravascular coagulation that had been present on admission, hematological examination showed sudden leukocytosis with nonhematopoietic cells that subsequently turned out to be signet ring cells (SRCs. Carcinocythemia, the presence of circulating cancer cells in peripheral blood, is considered to be a rare but an ominous phenomenon occurring in the advanced stage of certain types of cancers, particularly mammary lobular carcinoma. It can be assumed that carcinoma cells lacking intercellular cohesiveness and polarized cell membrane organization, including SRCs as well as lobular carcinoma cells, can readily get access to the peripheral circulation; however, to our knowledge, this is the first report of primary colorectal SRCC that presented carcinocythemia. Extensive bone metastatic sites, in the present case, may have functioned as a reservoir of circulating SRCs.

  9. Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    2017-01-01

    Full Text Available The carcinogenic potential of phenobarbital (PB was assessed in a mouse line carrying a mutant Mmh allele of the Mmh/Ogg1 gene encoding the enzyme oxoguanine DNA glycosylase (Ogg1 responsible for the repair of 8-hydroxy-2′-deoxyguanosine (8-OHdG. Mmh homozygous mutant (Ogg1−/− and wild-type (Ogg1+/+ male and female, 10-week-old, mice were treated with 500 ppm PB in diet for 78 weeks. Hepatocellular carcinomas (HCCs were found in PB-treated Ogg1−/− mice, while Ogg1+/+ animals developed only hepatocellular adenomas (HCAs at the same rate. This was coordinated with PB-induced significant elevation of 8-OHdG formation in DNA and cell proliferation in adjacent liver of Ogg1−/− mice. Proteome analysis predicted activation of transcriptional factor Nrf2 in the livers and HCAs of PB-administered Ogg1+/+ mice; however, its activation was insufficient or absent in the livers and HCCs of Ogg1−/− mice, respectively. Significant elevation of phase I and II metabolizing enzymes was demonstrated in both Ogg1−/− and Ogg1+/+ animals. Treatment of Ogg1−/− mice with PB resulted in significant elevation of cell proliferation in the liver. These results indicate that PB induced progression from HCA to HCC in Ogg1−/− mice, due to persistent accumulation of DNA oxidative base modifications and suppression of Nrf2-mediated oxidative stress response, resulting in significant elevation of cell proliferation.

  10. Histological, Immunohistological, and Clinical Features of Merkel Cell Carcinoma in Correlation to Merkel Cell Polyomavirus Status

    Directory of Open Access Journals (Sweden)

    T. Jaeger

    2012-01-01

    Full Text Available Merkel cell carcinoma is a rare, but highly malignant tumor of the skin with high rates of metastasis and poor survival. Its incidence rate rises and is currently about 0.6/100000/year. Clinical differential diagnoses include basal cell carcinoma, cyst, amelanotic melanoma, lymphoma and atypical fibroxanthoma. In this review article clinical, histopathological and immunhistochemical features of Merkel cell carcinoma are reported. In addition, the role of Merkel cell polyomavirus is discussed.

  11. Expression of heat shock protein70 in oral submucous fibrosis and oral squamous cell carcinoma: An immunohistochemical study

    Directory of Open Access Journals (Sweden)

    M Thubashini

    2011-01-01

    Conclusion: HSP70 is synthesized upon stress situations arising in cells of all living organisms. Expression of HSP70 indicates that stress plays an important role as a predisposing factor in oral submucous fibrosis and its subsequent progression to oral squamous cell carcinoma.

  12. Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma

    Science.gov (United States)

    Pulitzer, Melissa P; Brannon, A Rose; Berger, Michael F; Louis, Peter; Scott, Sasinya N; Jungbluth, Achim A; Coit, Daniel G; Brownell, Isaac; Busam, Klaus J

    2016-01-01

    Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven ‘pure’ Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52–89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression. PMID:26022453

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

    Science.gov (United States)

    2017-11-15

    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

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

    Science.gov (United States)

    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.

  15. Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

    Directory of Open Access Journals (Sweden)

    Eline Boghaert

    2014-12-01

    Full Text Available Ductal carcinoma in situ (DCIS is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo, but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

  16. Mogoltacin enhances vincristine cytotoxicity in human transitional cell carcinoma (TCC) cell line.

    Science.gov (United States)

    Behnam Rassouli, F; Matin, M M; Iranshahi, M; Bahrami, A R; Neshati, V; Mollazadeh, S; Neshati, Z

    2009-03-01

    Bladder cancer is the second common cancer of the genitourinary system throughout the world and intravesical chemotherapy is usually used to reduce tumour recurrence and progression. Human transitional cell carcinoma (TCC) is an epithelial-like adherent cell line originally established from primary bladder carcinoma. Here we report the effect of mogoltacin, a sesquiterpene coumarin from Ferula badrakema on TCC cells. Mogoltacin was isolated from the fruits of F. badrakema, using silica gel column chromatography and preparative thin layer chromatography. Mogoltacin did not have any significant cytotoxicity effect on neoplastic TCC cells at 16, 32, 64, 128, 200 and 600 microg ml(-1) concentrations. In order to analyse its combination effect, TCC cells were cultured in the presence of various combining concentrations of mogoltacin and vincristine. Cells were then observed for morphological changes (by light microscopy) and cytotoxicity using MTT assay. The effect of mogoltacin on vincristine toxicity was studied after 24, 48 and 72 h of drug administration. The results of MTT assay showed that mogoltacin can significantly enhance the cytotoxicity of vincristine and confirmed the morphological observations. Results revealed that combination of 40 microg ml(-1) vincristine with 16 microg ml(-1) mogoltacin increased the cytotoxicity of vincristine after 48 h by 32.8%.

  17. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Nicolas, E-mail: simplissimus@gmx.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de [Department of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Splittstoesser, Vera, E-mail: Veri.sp@web.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de [Department of Internal Medicine, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg (Germany); Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. Black-Right-Pointing-Pointer We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. Black-Right-Pointing-Pointer We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

  18. Distinct population of highly malignant cells in a head and neck squamous cell carcinoma cell line established by xenograft model

    Directory of Open Access Journals (Sweden)

    Jan Chia-Ing

    2009-11-01

    Full Text Available Abstract The progression and metastasis of solid tumors, including head and neck squamous cell carcinoma (HNSCC, have been related to the behavior of a small subpopulation of cancer stem cells. Here, we have established a highly malignant HNSCC cell line, SASVO3, from primary tumors using three sequential rounds of xenotransplantation. SASVO3 possesses enhanced tumorigenic ability both in vitro and in vivo. Moreover, SASVO3 exhibits properties of cancer stem cells, including that increased the abilities of sphere-forming, the number of side population cells, the potential of transplanted tumor growth and elevated expression of the stem cell marker Bmi1. Injection of SASVO3 into the tail vein of nude mice resulted in lung metastases. These results are consistent with the postulate that the malignant and/or metastasis potential of HNSCC cells may reside in a stem-like subpopulation.

  19. Stromal-epithelial crosstalk provides a suitable microenvironment for the progression of ovarian cancer cells in vitro.

    Science.gov (United States)

    Fu, Shilong; Dong, Lihua; Sun, Wei; Xu, Yi; Gao, Li; Miao, Yi

    2013-11-01

    The tumor microenvironment plays an important role in the progression of cancer. This study focused on carcinoma-associated fibroblasts (CAFs) and stromal-epithelial interaction between CAFs and epithelial ovarian carcinoma (EOC) cells. We isolated and established primary cultures of CAFs and co-cultured CAFs and EOC cells in vitro. The co-culture conditioned medium (CC-CM) was harvested and its influence on EOC cells was examined. Cytokine, chemokine, and growth factor levels were screened using a biotin label-based human antibody array system. We found that the stromal-epithelial crosstalk provided a suitable microenvironment for the progression of ovarian cancer cells in vitro.

  20. Nuclear morphometry in canine acanthomatous ameloblastomas and squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    M Martano

    2009-06-01

    Full Text Available The aim of this study was to evaluate whether morphometrical analysis can be of diagnostic value for canine acanthomatous ameloblastoma. We calculated, by means of an automated image analyser, some morphometric nuclear parameters, in particular: mean nuclear area (MNA, mean nuclear perimeter (MNP, maximum and minimum diameters (MDx and MDm coefficient of variation of the nuclear area (NACV, largest to smallest dimension ratio (LS ratio, and form factor (FF, in 8 canine acanthomatous ameloblastomas, and we compared these morphometric data to those of 13 squamous cell carcinomas of canine gingiva. The results indicated a progressive increase of the MNA, NACV, MNP and MDm proceeding from acanthomatous ameloblastomas (MNA: 42.11±8.74; NACV: 28,36±7,23; MNP: 24.18± 2.68; MDm: 5.69±0.49 to squamous cell carcinomas (MNA:49,69±9,10; NACV: 30,89±7,75; MNP: 25.63±2.54; MDm: 6.64±0.73. On the contrary, the LS ratio and the FF resulted greater in acanthomatous ameloblastomas (LS ratio: 1,63±0,12; FF: 1,13±0,002 than in SCCs (LS ratio: 1,40±0,12; FF:0.91±0.38. Moreover, the MNA, MNP,MDx and MDm resulted similar (MNA: p=0.89; MNP: p=0,65; MDm: p=0,16; MDx: p=0,13 in a subset of four acanthomatous ameloblastomas with cellular atypia (MNA:49,01±6,88; MNP: 26,28±1,99; MDm: 6.08±0.41; MDx: 10.18±0.88 and in squamous cell carcinomas (MNA:49.69±9,10; MNP: 25.63±2.54; MDm: 6.64±0.73; MDx: 9.26±1.05. While the NACV values resulted higher in typical acanthomatous ameloblastoma (29,99±6,06 than in atypical acanthomatous ameloblastoma (26,74±8,84 and similar to those of the SCCs (30,89±7,75. These results seem to confirm that acanthomatous ameloblastoma is a malignant or potentially malignant lesion and emphasizes that nuclear morphometry analysis can be an useful diagnostic and prognostic method in canine oral pathology.

  1. Mast cells dysregulate apoptotic and cell cycle genes in mucosal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Davis Paul

    2006-12-01

    Full Text Available Abstract Background Mucosal squamous cell carcinoma of the head and neck is a disease of high mortality and morbidity. Interactions between the squamous cell carcinoma and the host's local immunity, and how the latter contributes to the biological behavior of the tumor are unclear. In vivo studies have demonstrated sequential mast cell infiltration and degranulation during squamous cell carcinogenesis. The degree of mast cell activation correlates closely with distinct phases of hyperkeratosis, dysplasia, carcinoma in-situ and invasive carcinoma. However, the role of mast cells in carcinogenesis is unclear. Aim This study explores the effects of mast cells on the proliferation and gene expression profile of mucosal squamous cell carcinoma using human mast cell line (HMC-1 and human glossal squamous cell carcinoma cell line (SCC25. Methods HMC-1 and SCC25 were co-cultured in a two-compartment chamber, separated by a polycarbonate membrane. HMC-1 was stimulated to degranulate with calcium ionophore A23187. The experiments were done in quadruplicate. Negative controls were established where SCC25 were cultured alone without HMC-1. At 12, 24, 48 and 72 hours, proliferation and viability of SCC25 were assessed with MTT colorimetric assay. cDNA microarray was employed to study differential gene expression between co-cultured and control SCC25. Results HMC-1/SCC25 co-culture resulted in suppression of growth rate for SCC-25 (34% compared with 110% for the control by 72 hours, p Conclusion We show that mast cells have a direct inhibitory effect on the proliferation of mucosal squamous cell carcinoma in vitro by dysregulating key genes in apoptosis and cell cycle control.

  2. Collecting Duct Carcinoma of the Kidney Mimicking Invasive Transitional Cell Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Joo Nam; Lim, Hyung Guhn; Lim, Sung Chul [Chosun University College of Medicine, Gwangju (Korea, Republic of)

    2007-06-15

    Approximately 100 cases of collecting duct carcinoma have been reported in the medical literature. We herein report on a case of collecting duct carcinoma of the kidney in a 75-year-old patient. The abdominal sonography depicted a relatively poorly defined 7x6 cm sized, isoechoic mass lesion, as compared to the normal parenchyma, at the left kidney lower pole and the affected kidney showed preservation of the reniform shape. CT revealed a heterogeneous poorly defined low-attenuation mass that was mainly located in the medulla with involvement of the cortex and the lower half of the renal pelvis. Retrograde ureter opyelography showed a filling defect at the lower renal pelvis and severe narrowing of the left proximal ureter. We initially thought this lesion was invasive transitional cell carcinoma. Subsequent surgery confirmed a collecting duct carcinoma

  3. Renal Preservation Therapy for Renal Cell Carcinoma

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    Yichun Chiu

    2012-01-01

    Full Text Available Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC for 20 years. Nowadays partial nephrectomy (PN is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN. Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN and robot assisted laparoscopic partial nephrectomy (RPN. On the other hand, thermoablative therapy and cryoablation also play an important role in the renal preservation therapy to improve the patient procedural tolerance. Novel modalities, but limited to small number of patients, include high-intensity ultrasound (HIFU, radiosurgery, microwave therapy (MWT, laser interstitial thermal therapy (LITT, and pulsed cavitational ultrasound (PCU. Although initial results are encouraging, their real clinical roles are still under evaluation. On the other hand, active surveillance (AS has also been advocated by some for patients who are unfit for surgery. It is reasonable to choose the best therapeutic method among varieties of treatment modalities according to patients' age, physical status, and financial aid to maximize the treatment effect among cancer control, patient morbidity, and preservation of renal function.

  4. Current MR imaging of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sae Lin; Sung, Seuk Jae [Dept. of Radiology, Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

    2016-08-15

    Renal cell carcinoma (RCC) consists of approximately 85-90% of renal masses, and its incidence is increasing due to widespread use of modern imaging modalities such as ultrasonography or computed tomography. Computed tomography has served an important role in the diagnosis and staging of RCC; however, recent advances in magnetic resonance imaging (MRI) techniques have considerably improved our ability to predict tumor biology beyond the morphologic assessment. Multiparametric MRI protocols include standard sequences tailored for the morphologic evaluation and acquisitions that provide information about the tumor microenvironment such as diffusion-weighted imaging and dynamic contrast-enhanced MRI. The role of multiparametric MRI in the evaluation of RCC now extends to preoperative characterization of RCC subtypes, histologic grade, and quantitative assessment of tumor response to targeted therapies in patients with metastatic disease. Herein, the clinical applications and recent advances in MRI applied to RCC are reviewed along with its merits and demerits. We aimed to review MRI techniques and image analysis that can improve the management of patients with RCC. Familiarity with the advanced MRI techniques and various imaging findings of RCC would also facilitate optimal clinical recommendations for patients.

  5. [Vismodegib Therapy for Periocular Basal Cell Carcinoma].

    Science.gov (United States)

    Keserü, M; Green, S; Dulz, S

    2017-01-01

    Background Basal cell carcinoma (BCC) is the commonest periorbital tumour. Mohs' micrographic surgery and secondary reconstruction is the therapeutic gold standard for periorbital BCC. In cases of inoperability for any reason, therapeutic alternatives are needed. Since the approval of vismodegib, an orally administered, targeted BCC therapy is available. Nevertheless there is little information on the use of vismodegib for periorbital BCC. Patients and Methods In a retrospective study, we analysed the data of 4 patients treated with vismodegib since 2014. The patients' mean age before starting therapy was 87 years. The mean maximum tumour diameter was 22.0 mm. Results The median follow-up was 17 months. The median treatment duration was 7.5 months. In 75 % of patients, complete clinical remission of BCC was achieved. In 25 % of patients, interim stabilisation of tumour growth was possible. The most common side effect of therapy was muscle spasm. Conclusion Vismodegib is an effective treatment option for patients with periorbital BCC, in whom surgical treatment is not possible for any reason. Georg Thieme Verlag KG Stuttgart · New York.

  6. Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Rachna Raman

    2015-01-01

    Full Text Available Localized renal cell carcinoma (RCC is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

  7. Low Mast Cell Density Predicts Poor Prognosis in Oral Squamous Cell Carcinoma and Reduces Survival in Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Attramadal, Cecilie Gjøvaag; Kumar, Sheeba; Gao, Jian; Boysen, Morten Ebbe; Halstensen, Trond Sundby; Bryne, Magne

    2016-10-01

    The cellular composition of the tumor microenvironment (TME) at the invading front of oral squamous cell carcinomas (OSCCs) may reflect biologically important cancer features and host responses, and thus be related to disease progression. The TME density of mast cells (MCs), macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells were quantified at the invasive front and analyzed regarding their relation to disease recurrence in patients with small T1/2N0M0 OSCCs. mRNA for MC-specific proteins were analyzed in a second patient cohort with head and neck squamous cell carcinoma (HNSCC). Samples from 62 patients with T1/2N0M0 OSCC were immunohistochemically stained and scored for the cellular expression of mast/stem cell growth factor receptor (c-KIT) (MCs), CD68 (macrophages), α-smooth muscle actin (α-SMA) (CAFs) and CD31 (endothelial cells) and this was analyzed according to disease recurrence. Data from The Cancer Genome Atlas database were used to examine mRNA expression profiles and clinical data of patients with 399 HNSCC. Increased MC density at the invasive front was significantly associated with reduced disease recurrence, as none of the patients with high MC density experienced relapse. Moreover, increased expression of mRNA for MC specific markers as c-KIT, and α-, β-, and δ-tryptases and the MC-stimulating factor, stem cell factor (SCF), was significantly associated with good prognosis in patients with HNSCC. Decreased MC density at the invasive front may reflect tumor biology related to disease progression and prognosis. Counting MCs seems to be an easy and practical tool, that could be utilized for prognostic evaluation. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. An FNA pitfall: Mammary analog secretory carcinoma mistaken for acinic cell carcinoma due to cytoplasmic granules

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    Nouf Hijazi, MD

    2014-12-01

    Full Text Available In the salivary gland, a key differential feature of Mammary analog secretory carcinoma (MASC from acinic cell carcinoma (ACC is the lack of cytoplasmic granules. We report a case of a parotid mass incorrectly diagnosed on fine needle aspirate as acinic cell carcinoma due to many cells with basophilic granules suggesting serous acinar differention. Tumor resection revealed a tumor consistent with low grade adenocarcinoma that had eosinophilic, microvacuolar cytoplasm with distinct basophilic granules staining with PASD and mucicarmine. The diagnosis of MASC was confirmed with stains for GCDF-15, mammoglobin, and S100 and FISH consistent with a t(12;15 translocation. Relying on the absence of cytoplasmic granules as a feature to distinguish ACC from MASC is a diagnostic pitfall.

  9. studies on ocular squamous cell carcinoma among horses in borno ...

    African Journals Online (AJOL)

    Dr Olaleye

    medial canthus of the left eye, and at it was discoid in shape with an area of alopecia surrounding it. Microscopic examination of the masses revealed squamous cell carcinoma characterized by large numbers of squamous epithelial cells arranged in whorls with scanty keratin at the centre. Come of the cells appeared in ...

  10. Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

    Science.gov (United States)

    2015-01-01

    Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented

  11. MicroRNA-144 inhibits hepatocellular carcinoma cell proliferation ...

    Indian Academy of Sciences (India)

    MicroRNA 144 (miR-144), a small non-coding RNA, is frequently dysregulated in human several tumour progression,but its role and the underlying mechanisms in hepatocellular carcinoma (HCC) is poorly investigated. In thepresent study, the expression of miR-144 was firstly analysed in datasets derived from GSE21362 ...

  12. Basal cell carcinoma vs basaloid squamous cell carcinoma of the skin: an immunohistochemical reappraisal.

    Science.gov (United States)

    Webb, David V; Mentrikoski, Mark J; Verduin, Lindsey; Brill, Louis B; Wick, Mark R

    2015-04-01

    Typical cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are morphologically dissimilar. It is well known, however, that poorly differentiated SCC may assume a basaloid phenotype, complicating the histologic distinction between these 2 neoplasms. Selected immunohistochemical stains have been used in the past to aid in that differential diagnosis. In the current study, additional markers were evaluated to determine whether they would be helpful in that regard. Twenty-nine cases of metatypical (squamoid) BCC (MBCC) and 25 examples of basaloid SCC (BSCC) were studied using the antibodies Ber-EP4 and MOC-31 as well as a plant lectin preparation from Ulex europaeus I (UEA-1). The resulting immunostains were interpreted independently by 3 pathologists, and the results showed that MBCCs demonstrated strong and diffuse staining for Ber-EP4 (25/29) and MOC-31 (29/29). In contrast, BSCCs tended to be only sporadically reactive for both markers (4/25 and 1/25 cases, respectively). Labeling for UEA-1 was observed in almost all BSCCs (24/25), but only 6 of 29 cases of MBCC showed limited, focal staining with that lectin. These data suggest that MOC-31 is a useful marker in the specified differential diagnosis, especially when used together with UEA-1. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib.

    Science.gov (United States)

    Bhutani, Tina; Abrouk, Michael; Sima, Camelia S; Sadetsky, Natalia; Hou, Jeannie; Caro, Ivor; Chren, Mary-Margaret; Arron, Sarah T

    2017-10-01

    Vismodegib is a first-in-class agent targeting the hedgehog signaling pathway for treatment of patients with locally advanced basal cell carcinoma (BCC) and metastatic BCC. There have been concerns about the development of squamous cell carcinoma (SCC) in patients treated with this drug. We sought to determine whether treatment with vismodegib is associated with an increase in the risk of cutaneous SCC. In this retrospective cohort study, patients treated with vismodegib as part of phase I and II clinical studies were compared with participants from the University of California, San Francisco, Nonmelanoma Skin Cancer Cohort who received standard therapy for primary BCC. In total, 1675 patients were included in the analysis, and the development of SCC after vismodegib exposure was assessed. The use of vismodegib was not associated with an increased risk of subsequent development of SCC (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28-1.16). Covariates including age, sex, history of previous nonmelanoma skin cancer, and number of visits per year were significantly associated with the development of SCC. A limitation of the study was that a historic control cohort was used as a comparator. Vismodegib was not associated with an increased risk of subsequent SCC when compared with standard surgical treatment of BCC. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  14. An Aggressive Signet Ring Cell Carcinoma of the Prostate in a Japanese Man

    Directory of Open Access Journals (Sweden)

    Yasuhiro Hashimoto

    2011-10-01

    Full Text Available Signet ring cell carcinoma (SRCC of the prostate is rare, with approximately 100 case reports to date. Here we report a very aggressive case of SRCC of the prostate in a Japanese man. The patient received estramustine, docetaxel, and carboplatin combination chemotherapy, followed by TS-1 and CPT-11 combination therapy. Unfortunately, the disease progressed, and he died of general metastatic disease treated over 16 month with systemic chemotherapy.

  15. A child with xeroderma pigmentosum for excision of basal cell carcinoma

    OpenAIRE

    Mulimani, Sridevi M.; Talikoti, Dayanand G.

    2013-01-01

    Xeroderma pigmentosum (XP) is characterized by hypersensitivity to sunlight, ocular involvement, and progressive neurological complications. These manifestations are due to a cellular hypersensitivity to ultraviolet radiation leading to a defect in repair of DNA by the process of nucleotide excision repair. Basal cell carcinoma which is rare in children can occur with XP. Though the XP induced changes are predominately dermatologic, pose several challenges in anaesthetic management. Hence, we...

  16. Report of a Rare Case of Papillary Thyroid Carcinoma Associated with Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Sh. Borzouei

    2012-10-01

    Full Text Available Introduction: Papillary thyroid cancer (PTC is the most common well-differentiated cancer of the thyroid. Only in few cases of PTC entity of renal cell carcinoma has been observed in patients affected with PTC. Case Report: In this study we report a case of sporadic PTC and renal cell carcinoma in a 63 year-old woman. Conclusion: After surgery the patient was hospitalized for 1 month in ICU section. 3 months after being discharged from the hospital, she was still in a good condition and is under the follow-up treatment.(Sci J Hamadan Univ Med Sci 2012; 19 (3:75-77

  17. BRAF-activated non-protein coding RNA (BANCR advances the development of esophageal squamous cell carcinoma via cell cycle

    Directory of Open Access Journals (Sweden)

    Yang Chunxia

    2017-04-01

    Full Text Available Esophageal carcinoma is one of the important lethal tumors in the world, but the mechanism of esophageal cancer progression is still unclear. The long non-coding RNAs are known to regulate tumor progression. Here we report that BRAF-activated nonprotein coding RNA (BANCR is associated with the development of esophageal squamous cell carcinoma (ESCC. The expression levels of BANCR in 132 ESCC tumor tissues detected by quantitative real-time PCR were significantly higher than that in the adjacent normal tissues. The expression level of BANCR was down-regulated by transfecting small interrupting RNA against BANCR (BANCR siRNA in Eca109 cells. Eca109 and TE-1 cells transfected with BANCR siRNA led to the delayed cell cycles compared to the cells transfected with negative control siRNA. Moreover, MTT assays demonstrated that Eca109 cells transfected with BANCR siRNA resulted in the inhibition of cell proliferation. These results suggested that BANCR advances the development and progression of ESCC cells through regulating their cell cycles.

  18. [Exenteration of the Orbit for Basal Cell Carcinoma].

    Science.gov (United States)

    Furdová, A; Horkovičová, K; Krčová, I; Krásnik, V

    2015-08-01

    Primary treatment of basal cell carcinoma of the lower eyelid and the inner corner is essentially surgical, but advanced lesions require extensive surgical interventions. In some cases it is necessary to continue with the mutilating surgery--exenteration of the orbit. In this work we evaluate the indications of radical solutions in patients with basal cell carcinoma invading the orbit and the subsequent possibility for individually made prosthesis to cover the defect of the cavity. Indications to exenteration of the orbit in patients with basal cell carcinoma findings in 2008-2013. Case report of 2 patients. In period 2008-20013 at the Dept. of Ophthalmology, Comenius University in Bratislava totally 221 patients with histologically confirmed basal cell carcinoma of the eyelids and the inner corner were treated. In 5 cases (2.7 %) with infiltration of the orbit the radical surgical procedure, exenteration was necessary. In 3 patients exenteration was indicated as the first surgical procedure in the treatment of basal cell carcinoma, since they had never visited ophthalmologist before only at in the stage of infiltration of the orbit (stage T4). In one case was indicated exenteration after previous surgical interventions and relapses. After healing the cavity patients got individually prepared epithesis. Surgical treatment of basal cell carcinoma involves the radical removal of the neoplasm entire eyelid and stage T1 or T2 can effectively cure virtually all tumors with satisfactory cosmetic and functional results. In advanced stages (T4 stage) by infiltrating the orbit by basal cell carcinoma exenteration of the orbit is necessary. This surgery is a serious situation for the patient and also for his relatives. Individually made prosthesis helps the patient to be enrolled to the social environment.

  19. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

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    Franck Chiappini

    2012-01-01

    Full Text Available 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.

  20. Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Yiquan Wang

    2017-12-01

    Full Text Available Background/Aims: Benzotriazole (BTR and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. Methods: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR were carried out to detect the expression levels of BTR-related genes. Results: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B. In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. Conclusion: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.

  1. Association of esophageal candidiasis and squamous cell carcinoma

    OpenAIRE

    Delsing, C.E.; Bleeker-Rovers, C.P.; Veerdonk, F.L. van de; Tol, J.; van der Meer, J.W.M.; Kullberg, B. J.; Netea, M. G.

    2012-01-01

    Chronic esophageal candidiasis is an infection that is mostly seen in immunocompromised conditions, among which is chronic mucocutaneous candidiasis (CMC). Recently an association between CMC and esophageal carcinoma has been reported. Here we present two patients with chronic esophageal candidiasis who developed esophageal squamous cell carcinoma and we discuss the etiologic role of Candida-induced nitrosamine production, the loss of STAT1 function and impaired tumor surveillance and T-lymph...

  2. Carcinoma verrucoso: uma variante clínico-histopatológica do carcinoma espinocelular Verrucous carcinoma: a clinical-histopathologic variant of squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Maurício Zanini

    2004-10-01

    Full Text Available O carcinoma verrucoso é uma rara e indolente forma do carcinoma espinocelular descrita por Ackerman em 1948. Sua localização preferencial é a cavidade oral. Clinicamente manifesta-se como lesão verrucosa, de progressivo e lento crescimento e bom prognóstico. O tratamento de escolha é a exérese cirúrgica, devendo o paciente ser regularmente acompanhado devido ao risco de recorrências.Verrucous carcinoma is a rare and indolent variant of the squamous cell carcinoma described by Ackerman in 1948. The oral cavity is a most common site. Clinically, it presents most often as a slow-growing verrucous lesion. The prognosis is good. Treatment of choice is surgery. Patients require frequent reevaluation because recurrences may occur.

  3. Tumor-derived exosomes enhance invasion and metastasis of salivary adenoid cystic carcinoma cells.

    Science.gov (United States)

    Hou, Jin; Wang, Fangyuan; Liu, Xiaohao; Song, Mengyang; Yin, Xuemin

    2018-02-01

    Tumor-derived exosomes (TDE) have been shown to participate in different steps of the dissemination of cancer cells. However, the role of salivary adenoid cystic carcinoma-derived (SACC-derived) exosomes had not been documented in SACC. The study aims to explore the functions of SACC-derived TDE in SACC progression and investigate potential mechanisms. Salivary adenoid cystic carcinoma cell line SACC-83 was used to generate TDE. Afterward, SACC-83 or HUVECs were cocultured with or without TDE. Tumor migration, tumor invasion, and endothelial permeability were examined by wound healing assay, tumor invasion assay, endothelial permeability assay, and tumor cell transendothelial migration assay, respectively. Moreover, the expression levels of cell junction-related proteins were examined by qRT-PCR and Western blot. Salivary adenoid cystic carcinoma -83-derived exosomes were taken up by their host cells. Meanwhile, TDE increased migration and invasion capacity of SACC-83 cells and enhanced endothelial cell permeability. Furthermore, we demonstrated that the expression of cell junction-related proteins (Claudins and ZO-1) was downregulated, which is presumably involved in the TDE-mediated promotion of migration, invasion, and metastasis. The results suggested that SACC cell-derived exosomes were loaded with individual components that could enhance invasiveness and induce microenvironment changes, thus promoting SACC aggression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. [Progress in microencapsulation of stem cells].

    Science.gov (United States)

    Ye, Li; Wang, Shibin

    2010-12-01

    For the regenerative therapy of refractory diseases, stem cells have become an excellent source of seed cells due to their strong self-renewal and multi-differentiation abilities. Microcapsules can provide a three-dimensional growth environment with a good immunoisolation and biocompatibility for cells, and the microencapsulation of stem cells provides a new technical support for large-scale cell culture with high activities in vitro and long-term preservation, consequently opening up a new alternative for cell transplantation. In this review, we first outlined the development of microencapsulation, then introduced the present materials and methods for the microencapsulation of stem cells and its immunoisolation, and discussed the progress in microencapsulation technology, various types of stem cell used in recent years in details. Finally, we addressed perspectives of stem cell microencapsulation technology.

  5. Genetic alterations in head and neck squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Nagai M.A.

    1999-01-01

    Full Text Available The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations and tumor suppressor gene inactivation (loss of function mutations, leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.

  6. Adenoid squamous cell carcinoma of the oral cavity.

    Science.gov (United States)

    Terada, Tadashi

    2012-01-01

    Because immunohistochemical features of adenoid squamous cell carcinoma (AdSCC) of the oral cavity is unclear, the author reports herein AdSCC in the gingival with an emphasis on immunohistochemical features. A 73-year-old woman presented with a left lower gingival tumor. The tumor was mildly elevated tumor measuring 1.5 x 1.5 x 0.5 cm. Dentist's diagnosis was granulation tissue, and a biopsy was taken. The biopsy showed proliferation of carcinoma cells arranged in cords, and squamous and tubular differentiations were noted in places. The biopsy diagnosis was adenosquamous carcinoma. Tumor excision with resection of mandibular bone was performed. The resected tissue showed a mixture and squamous cell carcinoma and tubular formation. Gradual merges between the two and acantholytic features of the squamous cell carcinoma element were seen. Both components were free from mucins. Both components were positive for pancytokeratins (AE1/3, CAM5.2) +++, cytokeratin (CK) 5/6 +, CK34βE12 ++, CK7 +, CK14 +++, CEA +, CA19-9 +, CA125 +, p53 +++, p63 +++, KIT + and MUC1 ++. Both components were negative for CK8, CK18, CK19, CK20, EMA, vimentin, TTF-1, desmin, myoglobin, S100 protein, melanosome, smooth muscle actin, CD34, CDX2, CD10, chromogranin, synaptophysin, NSE, CD56, lysozyme, CD68, MDM2, PDGFRA, MUC2, MUC5AC, and MUC6. Since both components were positive for squmaous cell carcinoma markers (CD5/6, CK34βE12, and p63) and adenocarcinoma markers (CEA, CA19-9, CA125, MUC1), this case of AdSCC appears an intermediate form between adenocarcinoma and squamous cell carcinoma. The margins were negative. No metastasis was found by imaging techniques. The patient is now free from tumor and is followed up carefully.

  7. Orbital invasion by periocular basal cell carcinoma.

    Science.gov (United States)

    Leibovitch, Igal; McNab, Alan; Sullivan, Timothy; Davis, Garry; Selva, Dinesh

    2005-04-01

    To present a large series of patients with orbital invasion by periocular basal cell carcinoma (BCC). Retrospective, noncomparative, interventional case series. All cases diagnosed with orbital invasion by periocular BCC between January 1985 and July 2004 in 3 Orbital Units in Australia. The clinical records of all patients were reviewed. Patients' demographics, clinical presentation, histologic subtypes, treatment modalities, recurrence rate, and tumor-related death. There were 64 patients (49 males) with a mean age of 70+/-13 years. Most tumors (84.4%) were recurrent or previously incompletely excised, and the medial canthus was most frequently involved (56.2%). Signs suggestive of orbital involvement included a mass with bone fixation (35.7%), limitation of ocular motility (30.4%), and globe displacement (17.6%). There were no signs suggestive of orbital invasion in 35.7%. Most patients (51.6%) had infiltrative histologic findings, and perineural invasion was present in 19.3%. Treatment modalities were mainly exenteration alone or combined with radiotherapy. During a mean follow-up period of 3.6 years, 3 cases of recurrence (4.7%) were diagnosed. Only 1 patient (1.6%) died from tumor-related causes. Orbital invasion by periocular BCC is an uncommon event that may be associated with significant ocular morbidity and, rarely, death. Because orbital invasion may often be clinically silent, clinicians need to be alert to the possibility in high-risk tumors and consider appropriate imaging. Surgical treatment with exenteration or excision, with or without radiotherapy, results in a low recurrence and mortality rate.

  8. p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

    Science.gov (United States)

    McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

    2014-01-01

    Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

  9. Prognostic significance of extensive necrosis in renal cell carcinoma.

    Science.gov (United States)

    Collins, Jennifer; Epstein, Jonathan I

    2017-08-01

    Few studies using the current classification of renal cell carcinoma (RCC) have looked at a large number of cases with near total necrosis. We identified 21 cases of resections of RCC with >90% necrosis from the archives of Johns Hopkins Hospital between 2000 and 2015. Patients' mean age was 59 years (43-77) with 16 men (76%); 12 cases (57%) were papillary RCC, 4 clear cell papillary RCC (19%), 4 clear cell RCC (19%), and 1 unclassified with sarcomatoid differentiation (5%). International Society of Urological Pathology (ISUP) nucleolar grade was grade 1 (9 cases) or grade 2 (9 cases). Two cases were ISUP nucleolar grade 3, and 1 case was grade 4. Pathological stage was low (pT1-2) in 20 (95%) with the unclassified RCC with sarcomatoid differentiation RCC stage pT3a. Mean tumor size was 6.3 cm (1.2-17). In 52% (11) of cases, it was difficult to identify viable tumor, requiring multiple sections; 4 cases of papillary RCC were diagnosed in part due to necrotic tumor "ghost" architecture. Follow-up was available in 17 cases (81%) with a mean follow-up of 59 months. Thirteen patients (62%) are alive without disease. The patient with unclassified carcinoma with sarcomatoid differentiation died of cancer, and 2 died due to causes unrelated to cancer. One patient (5%) with low-grade clear cell RCC developed metastases but had a contralateral RCC. In the setting of a low-grade RCC, extensive necrosis does not have an adverse prognosis. In summary, our data, together with a prior study from our institution, comprise one of the largest cohorts of extensively (>90%) necrotic RCCs and suggests that in the setting of a low-grade RCC, it portends a good prognosis (only 2/36 cases showing progression (6%) on follow-up). However, we did identify a single case of high-grade RCC with an adverse prognosis and therefore, careful attention to tumor grade and classification is critical. The presence of tumor necrosis as a prognosticator in RCCs is complex, and despite its well

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Amygdalin inhibits the growth of renal cell carcinoma cells in vitro.

    Science.gov (United States)

    Juengel, Eva; Thomas, Anita; Rutz, Jochen; Makarevic, Jasmina; Tsaur, Igor; Nelson, Karen; Haferkamp, Axel; Blaheta, Roman A

    2016-02-01

    Although amygdalin is used by many cancer patients as an antitumor agent, there is a lack of information on the efficacy and toxicity of this natural compound. In the present study, the inhibitory effect of amygdalin on the growth of renal cell carcinoma (RCC) cells was examined. Amygdalin (10 mg/ml) was applied to the RCC cell lines, Caki-1, KTC-26 and A498, for 24 h or 2 weeks. Untreated cells served as controls. Tumor cell growth and proliferation were determined using MTT and BrdU tests, and cell cycle phases were evaluated. Expression of the cell cycle activating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1 and D3 as well as of the cell cycle inhibiting proteins p19 and p27 was examined by western blot analysis. Surface expression of the differentiation markers E- and N-cadherin was also investigated. Functional blockade by siRNA was used to determine the impact of several proteins on tumor cell growth. Amygdalin treatment caused a significant reduction in RCC cell growth and proliferation. This effect was correlated with a reduced percentage of G2/M-phase RCC cells and an increased percentage of cells in the G0/1-phase (Caki-1 and A498) or cell cycle arrest in the S-phase (KTC-26). Furthermore, amygdalin induced a marked decrease in cell cycle activating proteins, in particular cdk1 and cyclin B. Functional blocking of cdk1 and cyclin B resulted in significantly diminished tumor cell growth in all three RCC cell lines. Aside from its inhibitory effects on growth, amygdalin also modulated the differentiation markers, E- and N-cadherin. Hence, exposing RCC cells to amygdalin inhibited cell cycle progression and tumor cell growth by impairing cdk1 and cyclin B expression. Moreover, we noted that amygdalin affected differentiation markers. Thus, we suggest that amygdalin exerted RCC antitumor effects in vitro.

  12. Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions

    NARCIS (Netherlands)

    Parwani, Anil V.; Geradts, Joseph; Caspers, Eric; Offerhaus, G. Johan; Yeo, Charles J.; Cameron, John L.; Klimstra, David S.; Maitra, Anirban; Hruban, Ralph H.; Argani, Pedram

    2003-01-01

    Gallbladder carcinomas can be highly lethal neoplasms. Relatively little is known about the genetic abnormalities that underlie these tumors, particularly with respect to their timing hi neoplastic progression. The authors evaluated 5 noninvasive dysplasias and 33 invasive gallbladder carcinomas (6

  13. A case of small cell carcinoma of the vagina

    Directory of Open Access Journals (Sweden)

    Ryosuke Tamura

    2013-12-01

    Full Text Available Primary small cell carcinoma of the vagina is quite rare, and a standard treatment has not been established yet. Herein, we report a case of an 81-year-old woman who was diagnosed with a vaginal tumor without continuity with the uterine cervix. Histopathological diagnosis indicated alveolar solid growth of nuclear chromatin-rich atypical cells with a high N/C ratio and a partially recognized rosette-like structure, suggesting a differentiated neuroendocrine system. Chromogranin A and synapto- physin were positive. Stage I vaginal small cell carcinoma localized to the vagina was diagnosed. The tumor disappeared by radiation monotherapy with external beam irradiation and endocavitary irradiation. The patient remains alive without any disease 1 year and 8 months after the treatment, suggesting the efficacy of radiotherapy in small cell carcinoma of the vagina.

  14. Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

    OpenAIRE

    Srisomsap, Chantragan; Sawangareetrakul, Phannee; Subhasitanont, Pantipa; Chokchaichamnankit, Daranee; Chiablaem, Khajeelak; Bhudhisawasdi, Vaharabhongsa; Wongkham, Sopit; Svasti, Jisnuson

    2009-01-01

    Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) occur with relatively high incidence in Thailand. The secretome, proteins secreted from cancer cells, are potentially useful as biomarkers of the diseases. Proteomic analysis was performed on the secreted proteins of cholangiocarcinoma (HuCCA-1) and hepatocellular carcinoma (HCC-S102, HepG2, SK-Hep-1, and Alexander) cell lines. The secretomes of the five cancer cell lines were analyzed by SDS-PAGE combined with LC/MS/MS. Sixty-eight...

  15. Current diagnosis and treatment of basal cell carcinoma.

    Science.gov (United States)

    Alter, Mareike; Hillen, Uwe; Leiter, Ulrike; Sachse, Michael; Gutzmer, Ralf

    2015-09-01

    Basal cell carcinoma represents is most common tumor in fair-skinned individuals. In Germany, age-standardized incidence rates are 63 (women) and 80 (men) per 100,000 population per year. Early lesions may be difficult to diagnose merely on clinical grounds. Here, noninvasive diagnostic tools such as optical coherence tomography and confocal laser scanning microscopy may be helpful. The clinical diagnosis is usually confirmed by histology. Standard therapy consists of complete excision with thorough histological examination, either by means of micrographic surgery or, depending on tumor size and location as well as infiltration, using surgical margins of 3-5 mm or more. In particular, multiple basal cell carcinomas (such as in Gorlin-Goltz syndrome) and locally advanced as well as rarely also metastatic basal cell carcinoma may pose a therapeutic challenge. In superficial basal cell carcinoma, nonsurgical therapies such as photodynamic therapy or topical agents may be considered. In case of locally advanced or metastatic basal cell carcinoma, an interdisciplinary tumor board should issue therapeutic recommendations. These include radiation therapy as well as systemic therapy with a hedgehog inhibitor. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  16. Squamous cell carcinoma of the eyelid treated with photodynamic therapy.

    Science.gov (United States)

    Rossi, R; Puccioni, M; Mavilia, L; Campolmi, P; Mori, M; Cappuccini, A; Reali, E F; Cappugi, P

    2004-06-01

    The ocular tissues can be the site of a number of malignant tumors in adults. Approximately 5% to 10% of all skin tumors occur in the eyelid. Incidence studies indicate that basal cell carcinoma is the most frequent malignant eyelid tumor (90%) followed by squamous cell carcinoma (9%). A 55-year-old man presented a squamous cell carcinoma (SCC) of 8 mm diameter, localized in the middle third of the lower eyelid, 3 mm under the eyelid margin on the eyelids. The histopathologic examination of a biopsy specimen showed the typical features of squamous cell carcinoma. Photodynamic therapy (PDT) with topical 5-aminolevulic acid (ALA) after Frost suture was employed. Very good results were obtained with rapid healing, without invasiveness, and without anesthesia. There was no evidence of scar formation and no signs of recurrence at 6 months follow-up. Many therapeutic methods have been suggested for squamous cell carcinoma of the eyelid. We consider photodynamic treatment of eyelid skin malignancies to be of great interest and it may represent an interesting future perspective for their management especially when surgical intervention cannot be tolerated by the patient.

  17. A rare bladder cancer - small cell carcinoma: review and update

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Small cell carcinoma of the bladder (SCCB is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC. Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease ( or = cT4bN+M+ should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients. The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB.

  18. Human papilloma virus prevalence in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E

    2007-08-01

    To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

  19. Nivolumab-induced myasthenia gravis in a patient with squamous cell lung carcinoma: Case report.

    Science.gov (United States)

    Chen, Yu-Hsiu; Liu, Feng-Cheng; Hsu, Chang-Hung; Chian, Chih-Feng

    2017-07-01

    Nivolumab (Nivo) is an immune checkpoint inhibitor that has been used to treat advanced melanoma, nonsmall cell lung carcinoma, and renal cell carcinoma since 2015. Nivo is associated with several side effects, including hepatitis, pneumonitis, acute renal failure, endocrine disorder, and other immune-related adverse events. Here, we describe the case of a 65-year-old man with squamous cell lung carcinoma who developed myasthenia gravis (MG) after a third Nivo infusion. A 65-year-old man with advanced squamous cell lung carcinoma developed ptosis, diplopia, drop head, and general weakness 5 days after a third Nivo infusion. We diagnosed him with Nivo-related MG and myositis based on clinical symptoms, elevation of muscle enzymes, negativity for autoantibodies and exclusion of other diagnoses. Steroid treatment with methylprednisolone 1 mg/kg/d and pyridostigmine 60 mg twice a day was administered beginning at admission; however, the patient's condition progressively worsened, despite treatment. Respiratory failure developed 2 weeks after admission, and his family declined the use of a mechanical ventilator. The patient died on day 27 after the third Nivo infusion. Nivo-related MG should be highly suspected in patients who develop ptosis, diplopia, and general weakness. The corresponding treatments include discontinuation of Nivo and steroid treatment with plasmapheresis. The disease course may be rapid and fatal. This report stresses the importance of awareness of this rare and lethal adverse effect while using nivolomab immunotherapy.

  20. Prolyl hydroxylase PHD3 enhances the hypoxic survival and G1 to S transition of carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Heidi Högel

    Full Text Available Hypoxia restricts cell proliferation and cell cycle progression at the G1/S interface but at least a subpopulation of carcinoma cells can escape the restriction. In carcinoma hypoxia may in fact select for cells with enhanced hypoxic survival and increased aggressiveness. The cellular oxygen sensors HIF proline hydroxylases (PHDs adapt the cellular functions to lowered environmental oxygen tension. PHD3 isoform has shown the strongest hypoxic upregulation among the family members. We detected a strong PHD3 mRNA expression in tumors of head and neck squamous cell carcinoma (HNSCC. The PHD3 expression associated with expression of hypoxic marker gene. Using siRNA in cell lines derived from HNSCC we show that specific inhibition of PHD3 expression in carcinoma cells caused reduced cell survival in hypoxia. The loss of PHD3, but not that of PHD2, led to marked cell number reduction. Although caspase-3 was activated at early hypoxia no induction of apoptosis was detected. However, hypoxic PHD3 inhibition caused a block in cell cycle progression. Cell population in G1 phase was increased and the population in S phase reduced demonstrating a block in G1 to S transition under PHD3 inhibition. In line with this, the level of hyperphosphorylated retinoblastoma protein Rb was reduced by PHD3 knock-down in hypoxia. PHD3 loss led to increase in cyclin-dependent kinase inhibitor p27 expression but not that of p21 or p16. The data demonstrated that increased PHD3 expression under hypoxia enhances cell cycle progression and survival of carcinoma cells.

  1. A role for ADAM12 in breast tumor progression and stromal cell apoptosis

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Frohlich, Camilla; Albrechtsen, Reidar

    2005-01-01

    of stromal fibroblasts in tumor initiation and progression has been elucidated. Here, we show that stromal cell apoptosis occurs in human breast carcinoma but is only rarely seen in nonmalignant breast lesions. Furthermore, we show that ADAM12, a disintegrin and metalloprotease up-regulated in human breast...... cancer, accelerates tumor progression in a mouse breast cancer model. ADAM12 does not influence tumor cell proliferation but rather confers both decreased tumor cell apoptosis and increased stromal cell apoptosis. This dual role of ADAM12 in governing cell survival is underscored by the finding that ADAM......12 increases the apoptotic sensitivity of nonneoplastic cells in vitro while rendering tumor cells more resistant to apoptosis. Together, these results show that the ability of ADAM12 to influence apoptosis may contribute to tumor progression....

  2. [Effect of Sunitinib therapy on immune function of patients with advanced renal cell carcinoma].

    Science.gov (United States)

    Xian, P; Li, Y; Zhou, H; Luo, H; Liu, N; Dai, J Y

    2016-10-01

    Objective: To evaluate the effect of Sunitinib therapy on immune function of patient with advanced renal cell carcinoma. Methods: A total of 27 patient with advanced renal cell carcinoma who received Sunitinib therapy in Chongqing Cancer Hospital from July 2010 to July 2014 were recruited in a prospective cohort study.Nineteen were male patients and 8 were female patients aged from 36 to 75 years with mean age of (58±7)years.Twenty-five cases were renal clear cell carcinoma, the other two cases were papillary renal cell carcinoma and Xp11.2 translocation renal cell carcinoma.According to MSKCC terminal prognosis scoring recommend by NCCN: 22 cases were in low risk, 5 cases were in high risk.All the patient took Sunitinib 50 mg orally once daily for 4 weeks, followed-up by 2 weeks.Flow cytometry was used to detect the levels of CD3 + , CD8 + , CD4 + T lymphocyte, NK cell and B lymphocyte in peripheral blood of patients before taking medicine.The levels of CD3 + , CD8 + , CD4 + T lymphocyte, NK cell, B lymphocyte in peripheral blood were detected again after 4 weeks, 6 weeks, 10 weeks and the disease progression.Paired t -test was used to analyze the data comparison of two groups, mean comparison in groups was conducted with repeated measurements analysis of variance, and the pairwise comparison was performed with LSD- t method. Results: The levels of CD3 + , CD8 + T lymphocyte, NK cell, B lymphocyte were significantly increased after the therapy of Sunitinib for 1 cycle(I-J was 212±22, 163±18, 59±12, 13.8±1.4, respectively, all P cell, B lymphocyte were significantly increased after the therapy of Sunitinib for 2 cycles(I-J was 362±43, 299±28, 91±19, 28.1±3.9, respectively, all P 0.05). CD4 + /CD8 + was significantly decreased after the therapy of Sunitinib for 1 cycle, and it went on decreasing after the therapy of Sunitinib for 2 cycles(I-J was -0.31±0.03, -0.44±0.04, respectively, all P Disease progression occurred in 10 cases during the follow

  3. Culture and Characterization of Circulating Endothelial Progenitor Cells in Patients with Renal Cell Carcinoma.

    Science.gov (United States)

    Gu, Wenyu; Sun, Wei; Guo, Changcheng; Yan, Yang; Liu, Min; Yao, Xudong; Yang, Bin; Zheng, Junhua

    2015-07-01

    Although emerging evidence demonstrates increased circulating endothelial progenitor cells in patients with solid tumors, to our knowledge it is still unknown whether such cells can be cultured from patients with highly angiogenic renal cell carcinoma. We cultured and characterized circulating endothelial progenitor cells from patients with renal cell carcinoma. The circulating endothelial progenitor cell level (percent of CD45(-)CD34(+) VEGF-R2(+) cells in total peripheral blood mononuclear cells) was quantified in 47 patients with renal cell carcinoma and 40 healthy controls. Peripheral blood mononuclear cells were then isolated from 33 patients with renal cell carcinoma and 30 healthy controls to culture and characterize circulating endothelial progenitor cells. The circulating endothelial progenitor cell level was significantly higher in patients with renal cell carcinoma than in healthy controls (0.276% vs 0.086%, p cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p culture success rate (87.8% vs 40.0% of participants) and the number of colonies (10.06 vs 1.83) were significantly greater for patients than for controls (each p cell level correlated positively with the number of patient colonies (r = 0.762, p Cells cultured from patients and controls showed a similar growth pattern, immunophenotype, ability to uptake Ac-LDL and bind lectin, and form capillary tubes in vitro. However, significantly more VEGF-R2(+) circulating endothelial progenitor cells were found in preparations from patients with renal cell carcinoma than from healthy controls (21.1% vs 13.4%, p cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results indicate the important significance of VEGF-R2(+) circulating endothelial progenitors in patients with renal cell carcinoma. Copyright © 2015 American Urological Association Education and Research

  4. Fractal analysis of internal and peripheral textures of small peripheral bronchogenic carcinomas in thin-section computed tomography: comparison of bronchioloalveolar cell carcinomas with nonbronchioloalveolar cell carcinomas.

    Science.gov (United States)

    Kido, Shoji; Kuriyama, Keiko; Higashiyama, Masahiko; Kasugai, Tsutomu; Kuroda, Chikazumi

    2003-01-01

    To analyze the internal and peripheral textures of small peripheral bronchogenic carcinomas (analysis. Thin-section computed tomography images from 70 patients with bronchogenic carcinomas (61 adenocarcinomas and 9 squamous cell carcinomas) were used. Regions of interest (ROIs) with a matrix size of 32 x 32 (0.326 mm per pixel) were selected manually on the lung-nodule interfaces and within the nodules on HRCT images. Three-dimensional density surfaces based on CT values of ROIs were characterized by fractal dimensions (FDs). When all the bronchogenic carcinomas were divided into bronchioloalveolar cell carcinomas (BACs) and other bronchogenic carcinomas (nonBACs), there were significant differences between BACs and nonBACs in the FDs obtained from the internal textures (mean: 2.38 +/- 0.05 versus 2.19 +/- 0.05; Ptextures (mean: 2.16 +/- 0.01 versus 2.06 +/- 0.01; Ptextures of BACs that reveal ground-glass opacities are more complicated than those of nonBACs. The FDs can differentiate between small localized BACs, which have a good prognosis, and nonBACs, which have a poor prognosis. Fractal analysis is promising for characterization of small peripheral pulmonary bronchogenic carcinomas based on radiographic features of HRCT images.

  5. Squamous cell carcinoma of the breast : a case report

    NARCIS (Netherlands)

    Flikweert, Elvira R.; Hofstee, Mans; Liem, Mike S. L.

    2008-01-01

    Background: Squamous cells are normally not found inside the breast, so a primary squamous cell carcinoma of the breast is an exceptional phenomenon. There is a possible explanation for these findings. Case presentation: A 72-year-old woman presented with a breast abnormality suspected for breast

  6. Clinical and therapeutic aspects of extrapulmonary small cell carcinoma

    NARCIS (Netherlands)

    Walenkamp, Annemiek M. E.; Sonke, Gabe S.; Sleijfer, Dirk T.

    Extrapulmonary small cell carcinoma (EPSCC) is usually treated similarly to small cell lung cancer. Differences in aetiology, clinical course, frequency of brain metastases, and survival, however, warrant a differential therapeutic approach. In this review, we focus on the treatment of the most

  7. Head/Neck Squamous Cell Carcinoma: - Prevention Strategy ...

    African Journals Online (AJOL)

    ... northern Nigeria from 2000 to 2010. The authors also reviewed strategy for cancer prevention with special emphasis to tobacco cigarette as the major risk factors. Search; head and neck tomours, squamous cell tomours, strategies for prevention. Key Words:-Squamous cell carcinoma, Tobacco cigarette, Northern Nigeria ...

  8. Quantitative multiphoton imaging for guiding basal-cell carcinoma removal

    Science.gov (United States)

    Lin, Sung-Jan; Hsu, Chih-Jung; Wu, Ruei-Jr; Kuo, Chien-Jui; Chen, Jau-Shiuh; Chan, Jung-Yi; Lin, Wei-Chou; Jee, Shiou-Hwa; Dong, Chen-Yuan

    2007-02-01

    For secure removal of the basal cell carcinoma tissue, the technique of Mohs' micrographic surgery is often used. However, Mohs' micrographic surgery is time-consuming. In this work, we evaluate the ability of multiphoton fluorescence (MF) and second harmonic generation (SHG) imaging to discriminate the borders of human basal cell carcinoma. Morphologically, basal cell carcinomas are featured by clumps of autofluorecent cells with relatively large nuclei and marked peripheral palisading in the dermis. In contrast, SHG from collagen contributes largely to the multiphoton signal in normal dermis. Within the cancer stroma, SHG signals diminish and are replaced by autofluorescent signals. The results suggest that normal collagen structures responsible for SHG have been altered in the cancer stroma and may reflect an up-regulated collagenolytic activity of cancer cells. To better delineate the cancer cells and cancer stroma from normal dermis, a quantitative MF to SHG index (MFSI) is developed. We demonstrate that this index can be used to differentiate cancer cells and adjacent cancer stroma from normal dermis. Our work shows that MF and SHG imaging can be an alternative for the real-time guidance of the secure removal of basal cell carcinoma.

  9. Squamous Cell Carcinoma Arising in a Testicular Teratoma and ...

    African Journals Online (AJOL)

    Khan and Bagchi: Testicular squamous cell carcinoma with umbilical nodule tumors is usually localized in retroperitoneal lymph nodes including aortic, common iliac and caval nodes.[8]. In metastatic sites, the somatic-type malignancies have a poor prognosis. They do not respond to germ cell tumor chemotherapy; surgical ...

  10. TCP10L acts as a tumor suppressor by inhibiting cell proliferation in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zuo, Jie; Cai, Hao; Wu, Yanhua; Ma, Haijie; Jiang, Wei; Liu, Chao; Han, Dingding; Ji, Guoqing [State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433 (China); Yu, Long, E-mail: longyu@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433 (China); Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China)

    2014-03-28

    Highlights: • TCP10L was down-regulated in clinical hepatocellular carcinoma (HCC). • Expression of TCP10L correlated significantly with tumor size and Milan criteria. • Overexpression of TCP10L attenuated growth of HCC cells both in vitro and in vivo. • Knocking down TCP10L promoted cell proliferation and tumorigenesis of HCC cells. - Abstract: TCP10L (T-complex 10 (mouse)-like) has been identified as a liver and testis-specific gene. Although a potential transcriptional suppression function of TCP10L has been reported previously, biological function of this gene still remains largely elusive. In this study, we reported for the first time that TCP10L was significantly down-regulated in clinical hepatocellular carcinoma (HCC) samples when compared to the corresponding non-tumorous liver tissues. Furthermore, TCP10L expression was highly correlated with advanced cases exceeding the Milan criteria. Overexpression of TCP10L in HCC cells suppressed colony formation, inhibited cell cycle progression through G0/G1 phase, and attenuated cell growth in vivo. Consistently, silencing of TCP10L promoted cell cycle progression and cell growth. Therefore, our study has revealed a novel suppressor role of TCP10L in HCC, by inhibiting proliferation of HCC cells, which may facilitate the diagnosis and molecular therapy in HCC.

  11. Association of decreased expression of the macrophage scavenger receptor MARCO with tumor progression and poor prognosis in human hepatocellular carcinoma.

    Science.gov (United States)

    Sun, Haoyu; Song, Jiaxi; Weng, Chenchun; Xu, Jing; Huang, Mei; Huang, Qiang; Sun, Rui; Xiao, Weihua; Sun, Cheng

    2017-05-01

    The macrophage receptor with collagenous structure (MARCO) belongs to the scavenger receptor family; however, few studies have assessed their potentials in modulating inflammatory signaling other than the typical function of pattern recognition and phagocytic clearance. Interestingly, RNA-Seq analyses of hepatocellular carcinoma (HCC) have identified MARCO as one of the top 30 differentially expressed genes between cancerous and adjacent noncancerous tissues. However, no research has been performed to study MARCO in liver cancer. MARCO protein expression was evaluated by immunostaining liver tissue specimens collected from 88 HCC patients, 10 liver cirrhosis patients, 6 metastatic patients, and 5 healthy controls. All sections were reviewed by blinded observers followed by the interpretation of integral optical density per area as a measure of protein intensity. We observed significantly decreased expression of MARCO in intratumoral tissues of HCC compared with expression in peritumoral tissues. The expression of MARCO declined progressively as the disease condition was aggravated, with the highest expression found in healthy controls and the lowest found in patients with HCC metastasis. Furthermore, MARCO expression decreased along with tumor progression. MARCO + cells co-localized with CD68 + cells, indicating predominant expression on macrophages. The overall survival rate was significantly increased in patients with high intratumoral MARCO expression compared with that of patients with low intratumoral MARCO expression. Our study is the first to demonstrate an association between MARCO expression and the progression and prognosis of HCC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  12. Third-line Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

    Science.gov (United States)

    Wells, J Connor; Stukalin, Igor; Norton, Craig; Srinivas, Sandy; Lee, Jae Lyun; Donskov, Frede; Bjarnason, Georg A; Yamamoto, Haru; Beuselinck, Benoit; Rini, Brian I; Knox, Jennifer J; Agarwal, Neeraj; Ernst, D Scott; Pal, Sumanta K; Wood, Lori A; Bamias, Aristotelis; Alva, Ajjai S; Kanesvaran, Ravindran; Choueiri, Toni K; Heng, Daniel Y C

    2017-02-01

    The use of third-line targeted therapy (TTT) in metastatic renal cell carcinoma (mRCC) is not well characterized and varies due to the lack of robust data to guide treatment decisions. This study examined the use of third-line therapy in a large international population. To evaluate the use and efficacy of targeted therapy in a third-line setting. Twenty-five international cancer centers provided consecutive data on 4824 mRCC patients who were treated with an approved targeted therapy. One thousand and twelve patients (21%) received TTT and were included in the analysis. Patients were analyzed for overall survival (OS) and progression-free survival using Kaplan-Meier curves, and were evaluated for overall response. Cox regression analyses were used to determine the statistical association between OS and the six factors included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. Subgroup analysis was performed on patients stratified by their IMDC prognostic risk status. Everolimus was the most prevalent third-line therapy (27.5%), but sunitinib, sorafenib, pazopanib, temsirolimus, and axitinib were all utilized in over ≥9% of patients. Patients receiving any TTT had an OS of 12.4 mo, a progression-free survival of 3.9 mo, and 61.1% of patients experienced an overall response of stable disease or better. Patients not receiving TTT had an OS of 2.1 mo. Patients with favorable- (7.2%) or intermediate-risk (65.3%) disease had the highest OS with TTT, 29.9 mo and 15.5 mo, respectively, while poor-risk (27.5%) patients survived 5.5 mo. Results are limited by the retrospective nature of the study. TTT remains highly heterogeneous. The IMDC prognostic criteria can be used to stratify third-line patients. TTT use in favorable- and intermediate-risk patients was associated with the greatest OS. Patients with favorable- and intermediate-prognostic criteria disease treated with third-line targeted therapy have an associated

  13. Fatal Metastatic Cutaneous Squamous Cell Carcinoma Evolving from a Localized Verrucous Epidermal Nevus

    Directory of Open Access Journals (Sweden)

    Hassan Riad

    2013-10-01

    Full Text Available A malignant transformation is known to occur in many nevi such as a sebaceous nevus or a basal cell nevus, but a verrucous epidermal nevus has only rarely been associated with neoplastic changes. Keratoacanthoma, multifocal papillary apocrine adenoma, multiple malignant eccrine poroma, basal cell carcinoma and cutaneous squamous cell carcinoma (CSCC have all been reported to develop from a verrucous epidermal nevus. CSCC has also been reported to arise from other nevoid lesions like a nevus comedonicus, porokeratosis, a sebaceous nevus, an oral sponge nevus and an ichthyosiform nevus with CHILD syndrome. Here we report a case of progressive poorly differentiated CSCC arising from a localized verrucous epidermal nevus, which caused both spinal cord and brain metastasis.

  14. A case of squamous cell carcinoma of lung presenting with paraneoplastic type of acanthosis nigricans

    Directory of Open Access Journals (Sweden)

    Subhasis Mukherjee

    2011-01-01

    Full Text Available A 70-years-old male presented with blackening of both hands and face for last six months which was progressive and attended dermatology outpatients department. Dermatologist opined the skin lesions as acanthosis nigricans. He was referred to our department to evaluate for any underlying internal malignancy as he was a smoker. His chest X-ray revealed right sided hilar prominence with a mid zone cavity with fluid level. Fibreoptic bronchoscopy was done, there was one ulcerative growth in right middle lobe bronchus. Biopsy from the ulcer revealed probable squamous cell carcinoma. CT scan of thorax was also done and CT guided FNAC of Rt lung lesion yielded non small cell carcinoma. His skin lesions were also biopsied and diagnosis of acanthosis nigricans was confirmed. Here we report a case of acanthosis nigricans associated with non-small cell cancer of lung.

  15. Expression of C4.4A in precursor lesions of pulmonary adenocarcinoma and squamous cell carcinoma

    DEFF Research Database (Denmark)

    Jacobsen, Benedikte; Santoni-Rugiu, Eric; Illemann, Martin

    2012-01-01

    The protein C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor, is a potential new biomarker in non-small cell lung cancer, with high levels of expression recently shown to correlate to poor survival of adenocarcinoma patients. In this study, C4.4A immunoreactivity...... in precursor lesions of lung squamous cell carcinoma and adenocarcinoma was investigated by stainings with a specific anti-C4.4A antibody. In the transformation from normal bronchial epithelium to squamous cell carcinoma, C4.4A was weakly expressed in basal cell hyperplasia but dramatically increased...... finding that C4.4A expression levels do not provide prognostic information on the survival of squamous cell carcinoma patients. In the progression from normal alveolar epithelium to peripheral adenocarcinoma, we observed an unexpected, distinct cytoplasmic staining for C4.4A in a fraction of atypical...

  16. Axitinib controlled metastatic renal cell carcinoma for 5 years.

    Science.gov (United States)

    Takayama, Tatsuya; Nagata, Masao; Kai, Fumitake; Sugiyama, Takayuki; Ozono, Seiichiro

    2013-07-01

    We present two patients with a long-term response to axitinib for cytokine-refractory metastatic renal cell carcinoma. One patient has had a continuing partial response for 58 months with cytokine-intolerant metastatic renal cell carcinoma and the other patient has had continuing stable disease accompanied by a mixed response for 57 months with cytokine-refractory and intolerant metastatic renal cell carcinoma. The condition of hypertension as an adverse event markedly depended on whether or not axitinib was administered. The patients responded to axitinib with an elevation of diastolic blood pressure to 90 mmHg or higher until 2 weeks after starting axitinib. To get a long-term response to axitinib, it may be important to control well the balance between treatment effect and adverse events while using drug withdrawal.

  17. An Unusual Location of Basal Cell Carcinoma: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Birgül Tepe

    2012-06-01

    Full Text Available Basal cell carcinoma is the most common malignant skin tumour. Chronic sun exposure is considered as the main etiologic factor in its development. Although it mainly occurs on sun-exposed areas as the face and neck, it rarely develops on the forearms and/or arms. The etiologic factors which affect the anatomic distribution of basal cell carcinoma are not well-known. Here we report two patients who developed basal cell carcinoma on the forearm. None of the patients had a specific etiologic factor except for chronic sunlight exposure. The aim of our report is to show that this prevalant cutaneous malignancy can be encountered in rare/unusual areas. (Turk J Dermatol 2012; 6: 51-4

  18. Oral squamous cell carcinoma. Cytometric parameters of prognostic interest.

    Science.gov (United States)

    Saiz-Bustillo, Ramón; Corchero-Martín, Guadalupe; García-Montesinos-Perea, Belén; Gonzalez-Terán, Tomás; Sánchez-Santolino, Sergio

    2005-01-01

    The present study was made in order to find possible prognostic factors in oral squamous cell carcinoma, given that it is a frequent disease (3-4% of all malignant tumors) and is the cause of a high morbidity and mortality which justifies any attempt to contribute something towards the understanding of this pathology. 81 oral squamous cell carcinomas, treated with the same procedure, and retrieved from the archive of the Hospital Universitario Marqués de Valdecilla (Santander) were studied. Flow cytometry was carried out on 67 of the samples. No statistically significant differences were found between the cellular proliferative index and the mitotic index, ploidy and the S-phase factor. Likewise, none of the cytometric variables studied presented any association with the appearance of local relapse, distant metastases or survival. These variables cannot be used as a prognostic factors in squamous cell carcinomas of the oral cavity.

  19. A Case Report of Squamous Cell Carcinoma of Gallbladder

    Directory of Open Access Journals (Sweden)

    A. Dehghan

    2005-10-01

    Full Text Available Introduction : Epithelial cell carcinoma is the most common malignant neoplasm of gallbladder , but squamous cell carcinoma (SCC is rare.Case Report: Following the diagnosis of hydropsy of gallbladder in a sonography of a 60 years-old woman, cholesistectomy was performed. On macroscopic pathological examination, brownish deformed gallbladder was seen. After opening, on mucosal surface there was a cream, elastic polypoid tumoral lesion (2×1×0.5 cm. On microscopic evaluation, a pattern of pure and differentiated invasive Squamous Cell Carcinoma was diagnosed. Conclusion: During the last twenty-two years, this has been the first report of SCC of gallbladder from province of Hamadan with incidence of 2.8% in Iran. This case can be used in hystogenesis of SCC of gallbladder.

  20. Squamous cell carcinoma of the lateral nail fold.

    Science.gov (United States)

    Figus, A; Kanitkar, S; Elliot, D

    2006-04-01

    The digital nail complex is occasionally involved by squamous cell carcinoma. The published literature has either been indiscriminating of the site of origin of this tumour within the nail complex or has concentrated attention on the nail bed as the site of pathology. Tumours originating in the lateral nail fold can be clearly differentiated from those of the nail bed itself. This study identifies six cases of squamous cell carcinoma arising in the lateral nail fold. While surgical convention remains to amputate the digital tip for squamous cell carcinoma of any part of the nail complex, the dermatological literature identifies that local surgery can be curative for these tumours, when presenting early and without bone involvement, although offering no discussion of reconstruction. Reconstruction is desirable and methods of achieving this following local excision of lateral nail fold tumours are illustrated in this series.

  1. Agrin and Perlecan Mediate Tumorigenic Processes in Oral Squamous Cell Carcinoma

    Science.gov (United States)

    Kawahara, Rebeca; Granato, Daniela C.; Carnielli, Carolina M.; Cervigne, Nilva K.; Oliveria, Carine E.; Martinez, César A. R.; Yokoo, Sami; Fonseca, Felipe P.; Lopes, Marcio; Santos-Silva, Alan R.; Graner, Edgard; Coletta, Ricardo D.; Leme, Adriana Franco Paes

    2014-01-01

    Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels. PMID:25506919

  2. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial

    DEFF Research Database (Denmark)

    Choueiri, Toni K; Escudier, Bernard; Powles, Thomas

    2016-01-01

    BACKGROUND: Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous V...

  3. High frequency of loss of heterozygosity in vulval intraepithelial neoplasia (VIN) is associated with invasive vulval squamous cell carcinoma (VSCC)

    NARCIS (Netherlands)

    B.P.L. Wijnhoven (Bas); E.W. Lindstedt (Eric); M. Abbou; Y. Ijzendoorn (Ynske); R.R. de Krijger (Ronald); H.W. Tilanus (Hugo); W.N.M. Dinjens (Winand)

    2001-01-01

    textabstractVulval intraepithelial neoplasia (VIN) is thought to be the premalignant phase of human papillomavirus (HPV)-associated vulval squamous cell carcinoma (VSCC). Various molecular events have been suggested as markers for progression from VIN to VSCC, but loss of heterozygosity (LOH) in

  4. Are primary renal cell carcinoma and metastases of renal cell carcinoma the same cancer?

    Science.gov (United States)

    Semeniuk-Wojtaś, Aleksandra; Stec, Rafał; Szczylik, Cezary

    2016-05-01

    Metastasis is a process consisting of cells spreading from the primary site of the cancer to distant parts of the body. Our understanding of this spread is limited and molecular mechanisms causing particular characteristics of metastasis are still unknown. There is some evidence that primary renal cell carcinoma (RCC) and metastases of RCC exhibit molecular differences that may effect on the biological characteristics of the tumor. Some authors have detected differences in clear cell and nonclear cell component between these 2 groups of tumors. Investigators have also determined that primary RCC and metastases of RCC diverge in their range of renal-specific markers and other protein expression, gene expression pattern, and microRNA expression. There are also certain proteins that are variously expressed in primary RCCs and their metastases and have effect on clinical outcome, e.g., endothelin receptor type B, phos-S6, and CD44. However, further studies are needed on large cohorts of patients to identify differences representing promising targets for prognostic purposes predicting disease-free survival and the metastatic burden of a patient as well as their suitability as potential therapeutic targets. To sum up, in this review we have attempted to summarize studies connected with differences between primary RCC and its metastases and their influence on the biological characteristics of renal cancer. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. A Novel Protein Is Lower Expressed in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ruili Guan

    2014-04-01

    Full Text Available Engrailed-2 (EN2 has been identified as a candidate oncogene in breast cancer and prostate cancer. It is usually recognized as a mainly nuclear staining in the cells. However, recent studies showed a cytoplasmic staining occurred in prostate cancer, bladder cancer and clear cell renal cell carcinoma. The inconsistency makes us confused. To clarify the localization and expression of EN2 in renal cell carcinoma, anti-EN2 antibody (ab28731 and anti-EN2 antibody (MAB2600 were used for immunohistochemistry (IHC respectively. Interestingly, we found that EN2 detected by ab28731 was mainly presented in cytoplasm while EN2 detected by MAB2600 was mainly presented in nucleus. To further investigate the different patterns observed above, lysates from full-length EN2 over expression in HEK293T cells were used to identify which antibody the EN2 molecule bound by western blot. Results showed ab28731 did not react with the lysates. For this reason, the novel specific protein detected by ab28731 was not the EN2 molecule and was named nonEN2. Then using the renal carcinoma tissue microarray and renal tissues, we found that the protein expression levels of nonEN2 in kidney tumor tissues was significantly lower than that in kidney normal tissues (p < 0.05, so was in renal cell lines. Taken together, nonEN2 is lower expressed and may play an important role in renal cell carcinoma.

  6. Distinct genetic alterations in small cell carcinoma from different anatomic sites.

    Science.gov (United States)

    Zheng, Xiaoyong; Liu, Delong; Fallon, John T; Zhong, Minghao

    2015-01-01

    Small cell carcinoma (SmCC) is a distinct clinicopathological entity first described in the lung. It represents approximately 15% of all bronchogenic carcinoma. Extrapulmonary small cell carcinoma (EPSmCC) morphologically indistinguishable from small cell lung cancer (SCLC) was first reported in 1930. Since its first description, EPSmCC has been reported in virtually all anatomical sites, including: gynecologic organs (ovary and cervix); genitourinary organs (urinary bladder and prostate); the gastrointestinal tract (esophagus); skin (Merkel cell carcinoma) and head and neck region. Regardless of the anatomic sites, all SmCCs have similar, if not identical, histo-pathology features and immunohistochemical profile. SmCC is one of the most aggressive malignancies. The molecular mechanisms underlying its development and progression remain poorly understood. Herein, we reviewed the literature in SmCC in respect to its site of occurrence, clinical features, immunohistochemical characteristics. SmCCs have heterogeneous molecular mutations. Dinstinct genetic alterations associated with SmCC from different body sites were reviewed. Some genetic alterations such as RB1, TP53 are commonly seen in different origins of SmCC. Other genes with site specificity were also summarized, such as bladder SmCC with TERT promoter mutations; prostate SmCC with ERG translocations; ovarian SmCC with SMARCA4 mutations; Merkel cell carcinoma (skin) and cervical SmCC with Merkel cell polyomavirus (MCV or MCPyV) and human papillomavirus (HPV). Further studies are needed to employ a genetically oriented approach for the diagnosis and therapy of SmCC.

  7. Squamous Cell Carcinoma of the Nasal Vestibule

    DEFF Research Database (Denmark)

    Horsmans, J D; Godballe, C; Jørgensen, K E

    1999-01-01

    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...

  8. Quantitative diffusion-weighted MRI parameters and human papillomavirus status in oropharyngeal squamous cell carcinoma

    NARCIS (Netherlands)

    Schouten, C.S.; Graaf, P. de; Bloemena, E.; Witte, B.I.; Braakhuis, B.J.; Brakenhoff, R.H.; Leemans, C.R.; Castelijns, J.A.; Bree, R. de

    2015-01-01

    BACKGROUND AND PURPOSE: Patients with human papillomavirus-positive oropharyngeal squamous cell carcinomas have a better survival rate than those with human papillomavirus-negative oropharyngeal squamous cell carcinomas. DWI characterizes biologically relevant tumor features, and the generated ADC

  9. MCPIP1 contributes to clear cell renal cell carcinomas development.

    Science.gov (United States)

    Ligeza, Janusz; Marona, Paulina; Gach, Natalia; Lipert, Barbara; Miekus, Katarzyna; Wilk, Waclaw; Jaszczynski, Janusz; Stelmach, Andrzej; Loboda, Agnieszka; Dulak, Jozef; Branicki, Wojciech; Rys, Janusz; Jura, Jolanta

    2017-08-01

    Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues. Using Caki-1 cells as a model, we analyzed the role of MCPIP1 in cancer development. We showed that MCPIP1 expression depends on the proteasome activity; however, hypoxia and hypoxia inducible factor 2 alfa (HIF2α) are key factors lowering MCPIP1 expression. Furthermore, we found that MCPIP1 negatively regulates HIF1α and HIF2α levels and in the case of the last one, the mechanism is based on the regulation of the half time of transcript coding for HIF2α. Enhanced expression of MCPIP1 in Caki-1 cells results in a downregulation of transcripts encoding VEGFA, GLUT1, and IL-6. Furthermore, MCPIP1 decreases the activity of mTOR and protein kinase B (Akt) in normoxic conditions. Taken together, MCPIP1 contributes to the ccRCC development.

  10. [A case of synchronous contralateral renal cell carcinoma and urothelial carcinoma].

    Science.gov (United States)

    Soda, Tetsuji; Nishimura, Kenji; Kobayashi, Yasuyuki; Kato, Taigo; Tokugawa, Shigeki; Kishikawa, Hidefumi; Ihara, Hideari; Ichikawa, Yasuji

    2009-08-01

    A 63-year-old man was admitted to our hospital with gross hematuria. Abdominal computed tomography showed an 80mm right renal tumor, 31mm left renal tumor, and 30 mm splenic tumor. Cystoscopy revealed a papillary tumor around the left orifice. Right radical nephrectomy and splenectomy were performed. Histological examination findings showed that the right renal tumor was a renal cell carcinoma, clear cell type, G1, INFalpha, pT2, ly0, v0, and that the splenic tumor was an arteriovenous fistula. Next, transurethral resection of the bladder tumor was performed and a histological examination showed urothelial carcinoma. Magnetic resonance imaging indicated that the left renal tumor was a renal pelvic cancer. Left total nephroureterectomy and cystectomy were performed, and the histological diagnosis was urothelial carcinoma, G3, pT3, ly1, v2. Following the operation, hemodialysis was introduced. It is rare for a renal cell carcinoma and contralateral renal pelvic cancer to occur simultaneously, as only 15 cases including the present have been reported in Japan.

  11. Pretreatment serum squamous cell carcinoma antigen : A newly identified prognostic factor in early-stage cervical carcinoma

    NARCIS (Netherlands)

    Duk, JM; Groenier, KH; deBruijn, HWA; Hollema, H; tenHoor, KA; vanderZee, AGJ; Aalders, JG

    Purpose: To investigate the prognostic value of pretreatment serum squamous cell carcinoma antigen (SCC-ag) levels in patients with cervical squamous cell carcinoma in relation to well-established conventional risk factors. Patients and Methods: Sere from 653 women treated for squamous cervical

  12. Reduced nuclear and ectopic cytoplasmic expression of lysyl oxidase-like 2 is associated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Li, Tian-Yu; Xu, Li-Yan; Wu, Zhi-Yong; Liao, Lian-Di; Shen, Jin-Hui; Xu, Xiu-E; Du, Ze-Peng; Zhao, Qing; Li, En-Min

    2012-07-01

    Lysyl oxidase family members have various roles in cancer progression. The aim of this study was to investigate their expression and clinical significance in esophageal squamous cell carcinoma. We examined messenger RNA expression of lysyl oxidase family members including lysyl oxidase and lysyl oxidase-like proteins (lysyl oxidase L) in 10 esophageal squamous cell carcinoma cell lines and 83 pairs of tumor samples by quantitative real-time polymerase chain reaction. All except lysyl oxidase L3 were expressed at high levels in esophageal squamous cell carcinoma, but only lysyl oxidase L2 was associated with lymph node metastasis (P = .034). We examined lysyl oxidase L2 protein further by immunohistochemistry staining in 178 surgically resected esophageal squamous cell carcinoma tissue samples. The protein manifested decreased nuclear expression and increased cytoplasmic expression. Moreover, these 2 events both had significant correlation with the presence of lymph node metastasis (P = .001 and P lysyl oxidase L2 were significantly lower than those of the patients with esophageal squamous cell carcinoma with the reverse expression pattern (P = .040 or P = .022). Multivariate analyses revealed that nuclear expression of lysyl oxidase L2 was an independent prognostic factor for esophageal squamous cell carcinoma. These results suggest that lysyl oxidase L2 exerts a critical effect on esophageal squamous cell carcinoma progression and can be a predictive marker of lymph node metastasis and outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration.

    Science.gov (United States)

    Takagi, Kiyoshi; Miki, Yasuhiro; Tanaka, Sota; Hashimoto, Chiaki; Watanabe, Mika; Sasano, Hironobu; Ito, Kiyoshi; Suzuki, Takashi

    2016-01-01

    Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains, and associated with wide variety of biological process such as food intake and energy homeostasis. Recently, NUCB2 has been implicated in not only normal human tissues but also some kinds of human malignancies. However, its clinical and/or biological significance has largely remained unknown in endometrial carcinomas. We therefore immunolocalized NUCB2 protein in 87 endometrial carcinoma tissues and examined its clinical significance. NUCB2 immunoreactivity was detected in 19 out of 87 (22%) of endometrial carcinoma cases examined, and positively correlated with Ki67 labeling index, while there was no significant correlation between NUCB2 and stage, histological grade, and progesterone receptor status. Furthermore, NUCB2 immunoreactivity was significantly correlated with increased risk of recurrence and worse clinical outcome regardless of stage or histological grade. Subsequent multivariate analyses did reveal that NUCB2 immunoreactivity was an independent prognostic factor for both disease-free survival and endometrial cancer specific survival. In vitro experiments demonstrated that knockdown of NUCB2 using specific siRNA for NUCB2 significantly impaired cell proliferation and migration of the endometrial carcinoma cell lines, Ishikawa and Sawano cells, and that nesfatin-1 treatment significantly promoted cell proliferation and migration in Ishikawa cells. These findings possibly suggested that NUCB2 and/or nesfatin-1 had pivotal roles in the progression of endometrial carcinomas. Immunohistochemical NUCB2 status may therefore serve as a potent biomarker for endometrial carcinomas.

  14. Biology of Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Michele Milella, Alessandra Felici

    2011-01-01

    Full Text Available In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1 even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2 prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3 although we have successfully identified classes of drugs (or molecular mechanisms of action that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4 finally (and perhaps most importantly, even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer

  15. Oxidative stress indicated by elevated expression of Nrf2 and 8-OHdG promotes hepatocellular carcinoma progression.

    Science.gov (United States)

    Ma-On, Chakriwong; Sanpavat, Anapat; Whongsiri, Patcharawalai; Suwannasin, Surasit; Hirankarn, Nattiya; Tangkijvanich, Pisit; Boonla, Chanchai

    2017-04-01

    Reactive oxygen species (ROS) is excessively generated in tumors creating an oxidative stress in tumor microenvironment. We investigated hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and 8-hydroxydeoxyguanosine (8-OHdG) in hepatocellular carcinoma (HCC) patients, and asked if ROS epigenetically upregulated Nrf2 and enhanced aggressiveness in HCC cells. Expression of Nrf2 (n = 100) and 8-OHdG (n = 53) was remarkably increased in HCC tissues compared with the noncancerous hepatic tissues. Elevated expression of 8-OHdG was associated with poor survival in HCC patients. H2O2, as ROS representative, provoked oxidative stress in HepG2 cells, indicated by increased protein carbonyl content and decreased total antioxidant capacity. Nrf2 expression and 8-OHdG formation were markedly increased in the H2O2-treated cells compared with the untreated control. Co-treatment with antioxidants, tocopheryl acetate (TA) and S-adenosylmethionine (SAM) effectively attenuated expression of Nrf2 and 8-OHdG in H2O2-treated cells. HepG2 cells treated with H2O2 had significantly higher migration and invasion capabilities than the untreated control cells, and this aggressiveness was significantly inhibited by TA and SAM. Bisulfite sequencing revealed that CpG dinucleotides in Nrf2 promoter were unmethylated in the H2O2-treated cells similar to the untreated control. In conclusion, robust histological evidence of increased antioxidative response and oxidative DNA damage in human HCC tissues was demonstrated. Elevated oxidative DNA lesion 8-OHdG was associated with shorter survival. Experimentally, ROS enhanced Nrf2 expression, 8-OHdG formation and tumor progression in HCC cells. These effects were inhibited by antioxidants. Therefore, oxidative stress-reducing regimens might be beneficial to diminish the ROS-induced HCC progression.

  16. Recurrent eyelid basal cell carcinoma with sclerochoroidal infiltration: echographic findings.

    Science.gov (United States)

    Mantovani, E; Doro, D; Milizia, E; Steindler, P

    1998-01-01

    In an 82-year-old woman with a recurrent right lid basal cell carcinoma infiltrating the upper temporal orbit, a solid yellowish lesion was found ophthalmoscopically in the superotemporal periphery of the right eye. On standardized echography examination, the 2.5-mm elevated subretinal lesion was medium to high reflective with irregular structure, whereas the adjacent orbital mass was medium to low reflective and the sclera was thinned with at least one passage between the orbital and ocular lesions. To our knowledge, this is the first echographic report of sclerochoroidal infiltration from a lid basal cell carcinoma.

  17. Metastatic transitional cell carcinoma of the tibia radiologically mimicking osteosarcoma.

    LENUS (Irish Health Repository)

    Cunningham, Laurence Patrick

    2013-01-01

    We report a case of a 73-year-old lady with transitional cell carcinoma and no evidence of metastatic disease presenting with gradual weight loss, pretibial swelling and painful weightbearing. Investigations revealed a lesion of the right tibial diaphysis. The radiological and clinical appearance was that of primary osteosarcoma. Biopsy results revealed metastatic transitional cell carcinoma of the tibia. Intramedullary nailing was performed which relieved pain on weightbearing. The patient declined radiotherapy and was started on a palliative care regimen. This case illustrates the importance of histological diagnosis in the treatment of diaphyseal lesions.

  18. Isolated pancreatic metastases from a bronchogenic small cell carcinoma.

    LENUS (Irish Health Repository)

    Walshe, T

    2012-01-31

    We describe the case of a 60 year old female smoker who presented with a three month history of weight loss (14 Kg), generalized abdominal discomfort and malaise. Chest radiography demonstrated a mass projected inferior to the hilum of the right lung. Computed Tomography of thorax confirmed a lobulated lesion in the right infrahilar region and subsequent staging abdominal CT demonstrated a low density lesion in the neck of the pancreas. Percutaneous Ultrasound guided pancreatic biopsy was performed, histology of which demonstrated pancreatic tissue containing a highly necrotic small cell undifferentiated carcinoma consistent with metastatic small cell carcinoma of the bronchus.

  19. Renal cell carcinoma in patient with crossed fused renal ectopia

    Directory of Open Access Journals (Sweden)

    Ozgur Cakmak

    2016-01-01

    Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

  20. Oral squamous cell carcinoma in a coyote (Canis latrans).

    Science.gov (United States)

    Bernstein, K S; Schelling, S H

    1999-06-01

    A 19-yr-old spayed female coyote (Canis latrans) was evaluated for an elliptical swelling of the skin beneath its right eye and an elevated mass that involved the soft and hard palate and gingivae around the upper right carnassial tooth and molars. Histopathologic analysis revealed a squamous cell carcinoma, and a postmortem examination revealed no evidence of vascular invasion or dissemination to the regional lymph nodes or viscera. This report describes the biology and progresion of an oral squamous cell carcinoma in an aged captive coyote.

  1. Percutaneous and laparoscopic assisted cryoablation of small renal cell carcinomas

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Borre, Michael

    Aim: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Materials and methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made....... Of the 10 patients with residual tumor, 8 patients were reablated and 2 patients were referred to oncological treatment. Cancer specific survival was 100%. Overall survival was 91%. Complications: 8 pt. had minor bleeding in relation to cryoneedle removal, requiring Tachosil®. 1 pt. had subcutaneous...

  2. Nevoid Basal Cell Carcinoma Syndrome : A Case Report

    Directory of Open Access Journals (Sweden)

    K Rajanikanth

    2004-01-01

    Full Text Available The nevoid basal cell carcinoma syndrome (NBCCS or Gorlin - Goltz syndrome is an autosomal disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. The major organ systems involved are skin, bones, central nervous system, eyes, gonads and endocrine. This particular syndrome is extensively described in the literature under different names. However, there are only few cases reported in the Indian literature. An unusual case of a 33-year old male with large odontogenic keratocyst involving impacted canine in the mandible, along with multiple cysts and impacted teeth in the maxilla; bifid rib and vertebral anomalies has been described.

  3. Metastatic Renal Cell Carcinoma to Jejunum: An Unusual Case Presentation

    Directory of Open Access Journals (Sweden)

    Igor Medic

    2017-07-01

    Full Text Available The small intestine is a very uncommon and peculiar site for metastasis from renal cell carcinoma (RCC. We present a clinical presentation of insidious and unusual development of a jejunal metastasis while having stable disease in a remainder of metastatic sites, in a patient undergoing immunotherapy with nivolumab. Due to the extreme rarity of metastatic renal cell carcinoma to the lumen of the small bowel, it is easy to overlook and misdiagnose symptoms of this pathologic entity, particularly when the remainder of metastatic disease responds well to ongoing therapy.

  4. Basal cell carcinoma in two Hermann's tortoises (Testudo hermanni).

    Science.gov (United States)

    Hellebuyck, Tom; Ducatelle, Richard; Bosseler, Leslie; Van Caelenberg, Annemie; Versnaeyen, Han; Chiers, Koen; Martel, An

    2016-11-01

    Neoplastic disorders are frequently encountered in the practice of reptile medicine. Herein we report the clinical behavior, antemortem diagnosis, and histopathologic characteristics of a recurrent intraoral keratinizing basal cell carcinoma (BCC) and a metastatic BCC of the carapace in 2 Hermann's tortoises (Testudo hermanni). Although squamous cell carcinomas (SCCs) in tortoises show similar predilection sites and gross pathologic features, the BCCs described in our report were characterized by a remarkably fast and highly infiltrative growth in comparison to SCCs. Accordingly, early diagnosis including reliable discrimination from SCC is essential toward the management of this neoplastic entity in tortoises. © 2016 The Author(s).

  5. Cutaneous Squamous Cell Carcinoma with Invasion through Ear Cartilage

    Directory of Open Access Journals (Sweden)

    Julie Boisen

    2016-01-01

    Full Text Available Cutaneous squamous cell carcinoma of the ear represents a high-risk tumor location with an increased risk of metastasis and local tissue invasion. However, it is uncommon for these cancers to invade through nearby cartilage. Cartilage invasion is facilitated by matrix metalloproteases, specifically collagenase 3. We present the unusual case of a 76-year-old man with an auricular squamous cell carcinoma that exhibited full-thickness perforation of the scapha cartilage. Permanent sections through the eroded cartilage confirmed tumor invasion extending to the posterior ear skin.

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

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang, E-mail: wenfang64@hotmail.com; Zhang, Yi, E-mail: syzi960@yahoo.com

    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.

  7. A retrospective evaluation of non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Ali İnal

    2012-12-01

    Full Text Available Objectives: Lung cancer is the most common amongcancer-related deaths in worldwide. Non-small cell lungcancer represents between 80% and 85% of all lung cancercases. Epidemiologic and demographic characteristicsof lung cancer may differ between the sexes in thesame community and between communities. This studypurposes to determine demographic, epidemiological andclinical characteristics of clinic follow-up study of lungcancer patients as retrospectively.Materials and methods: Total 741 patients with nonsmallcell lung cancer who histopathologically diagnosed,treated and followed-up in Dicle University Faculty ofMedicine, Department of Medical Oncology, between2000 and 2012, were retrospectively evaluatedResults: 662 of patients (89.3% were males and 79(10.7% females. Male/female ratio was 8.4. The medianpatient age was 60.0 (28-93 years. The histopathologicaltypes were as follows; 34.8% squamous cell carcinoma,29.1% adenocarcinoma, 2% large cell carcinomaand 34.1% unspecified non-small cell lung carcinoma.Smoking rate in men was found as %92.2, and 10.1%in female patients. Stage of patients was 11.4% in localstage, 35.6% was in locally advanced and 53% was inmetastatic stage.Conclusions: Ratio of squamous cell carcinoma and advancedstage in our study were higher than previous dataof studies from Turkey. However, the other clinical andpathological findings were compatible with our country’sand world data.Key words: Non-Small cell lung carcinoma, histologictype, epidemiology

  8. Safety and clinical efficacy of everolimus in the treatment of advanced renal cell carcinoma (RCC

    Directory of Open Access Journals (Sweden)

    Rohan Shahani

    2010-06-01

    Full Text Available Rohan Shahani, Kevin G Kwan, Anil KapoorDivision of Urology, Department of Surgery, St. Joseph’s Healthcare Hamilton and McMaster University, Hamilton, Ontario, CanadaAbstract: Renal cell carcinoma (RCC is one of the most lethal genitourinary malignancies. Recently, there has been a paradigm shift in the management of advanced RCC. New targeted therapies including vascular endothelial growth factor (VEGF and mammalian target of rapamycin (mTOR inhibitors have been developed which have shown promising results in a patient population who otherwise had very few options for treatment. The first mTOR inhibitor, temsirolimus, an intravenous prodrug, has shown improved overall survival in poor prognosis patients. More recently, an oral mTOR inhibitor, everolimus (RAD 001, has been developed which has been shown to delay disease progression in patients with metastatic RCC who have progressed on other targeted therapies. Although a survival advantage in phase III trials is seen with everolimus, associated systemic toxicities, while generally well tolerated, are not insignificant. These include mucositis, hyperglycemia, hyperlipidemia, and pneumonitis. Despite the side effects, emerging evidence points to everolimus as the optimal second-line treatment for patients with advanced renal cell carcinoma.Keywords: metastatic renal cell carcinoma, everolimus, mTOR inhibitors, VEGF inhibitors

  9. Rapid induction of senescence in human cervical carcinoma cells

    Science.gov (United States)

    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.

  10. Expression of ZNF396 in basal cell carcinoma.

    Science.gov (United States)

    Bai, Juncheng; Kito, Yusuke; Okubo, Hiroshi; Nagayama, Tomoko; Takeuchi, Tamotsu

    2014-05-01

    Zfp191 represses differentiation and keeps various cells in the stem/progenitor stage. Here, we report that a Zfp191 homolog protein, ZNF396, is expressed in basal cell carcinoma (BCC) and possibly represses the expression of a Notch system effector molecule, Hes1 (hairy and enhancer of split-1), and prevents BCC cells from undergoing Notch-mediated squamous cell differentiation. ZNF396 immunoreactivity was found in the nucleus of 35 of 38 cutaneous BCC and 4 of 74 squamous cell carcinoma tissue specimens. In non-tumorous epidermal tissues, ZNF396 immunoreactivity was restricted in basal cells. siRNA-mediated silencing of ZNF396 induced the expression of Notch2, Hes1, and involucrin in cultured BCC cells. Finally, we found that siRNA-mediated silencing of ZNF396 gene inhibited the proliferation of TE354.T basal cell carcinoma cells. ZNF396 might repress Notch-Hes1 signaling axis and prevent tumor cells from undergoing squamous differentiation in BCC.

  11. Reprogramming cancer cells: overview & current progress.

    Science.gov (United States)

    Lim, Kian Lam; Teoh, Hoon Koon; Choong, Pei Feng; Teh, Hui Xin; Cheong, Soon Keng; Kamarul, Tunku

    2016-07-01

    Cancer is a disease with genetic and epigenetic origins, and the possible effects of reprogramming cancer cells using the defined sets of transcription factors remain largely uninvestigated. In the handful of publications available so far, findings have shown that reprogramming cancer cells changed the characteristics of the cells to differ from the parental cancer cells. These findings indicated the possibility of utilizing reprogramming technology to create a disease model in the laboratory to be used in studying the molecular pathogenesis or for drug screening of a particular cancer model. Despite numerous methods employed in generating induced pluripotent stem cells (iPSCs) from cancer cells only a few studies have successfully reprogrammed malignant human cells. In this review we will provide an overview on i) methods to reprogram cancer cells, ii) characterization of the reprogrammed cancer cells, and iii) the differential effects of reprogramming on malignancy, epigenetics and response of the cancer cells to chemotherapeutic agents. Continued technical progress in cancer cell reprogramming technology will be instrumental for more refined in vitro disease models and ultimately for the development of directed and personalized therapy for cancer patients in the future.

  12. SENP1 promotes proliferation of clear cell renal cell carcinoma through activation of glycolysis.

    Science.gov (United States)

    Dong, Baijun; Gao, Yujing; Kang, Xunlei; Gao, Hongchang; Zhang, Jin; Guo, Hua; You, Mingjian J; Xue, Wei; Cheng, Jinke; Huang, Yiran

    2016-12-06

    Metabolic shift toward aerobic glycolysis is a fundamental element contributing to the development and progression of clear cell renal cell carcinoma (ccRCC). We and others previously observed enhanced glycolysis and diminished tricarboxylic acid (TCA) cycle activity in ccRCC tissue. Here, by integrated gene expression and metabolomic analyses of 36 matched pairs of tumor and adjacent normal tissues, we showed that expression of Sentrin/SUMO-specific protease 1 (SENP1) is positively associated with glycolysis levels in ccRCC. Moreover, SENP1 knockdown in RCC4/VHL cells downregulated expression of key glycolytic enzymes under normoxic and hypoxic conditions and inhibited cell proliferation under hypoxic conditions, possibly due to ineffective deSUMOylation and stablization of Hif-1α related to the SENP-1 deficiency. Finally, SENP1 expression correlated positively with tumor pathological grade and was an indicator of poor overall survival and advanced tumor progression in ccRCC. Altered VHL gene function is found in 60-90% ccRCC cases of ccRCC, but therapies targeting VHL-related signaling pathways have been ineffective, spurring exploration of alternative pathological signaling events. Our results provide a possible mechanistic explanation for the role of SENP1 in the initiation and development of ccRCC with normal VHL activity, and identifies SENP1 as a potential treatment target for the disease.

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  17. Cox-2 gene overexpression in ureteral stump urothelial carcinoma following nephrectomy for renal cell carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Chang Wei-Pin

    2012-01-01

    Full Text Available Abstract Introduction A primary ureteral stump tumor after a nephrectomy is rare; urothelial carcinoma of the ureteral stump after a nephrectomy for renal cell carcinoma is even rarer. A thorough review of the literature indicated that only seven cases have previously been reported. In this study, we report the first Taiwanese case of urothelial carcinoma of the ureteral stump after a nephrectomy. It is also the first female case in the literature. The relationship between inflammatory genes, medication history and ureteral stump carcinoma after a nephrectomy for renal cell carcinoma has not been reported. Case presentation A 72-year-old Asian Taiwanese women with chronic hepatitis C, liver cirrhosis and chronic kidney disease underwent a hand-assisted laparoscopic radical nephrectomy in 2001 due to renal cell carcinoma. Nine years later, she was diagnosed with ureteral stump urothelial carcinoma. Genetic and medication surveys were performed. Importantly, our patient had taken Chinese herbal drugs for more than 10 years and the inflammatory gene, Cox-2, was highly expressed in this patient. This is the first report to study the relationship between the Cox-2 gene and ureteral stump carcinoma after a nephrectomy for renal cell carcinoma. Conclusion Long-term multiple use of Chinese herbal drugs could be one of the important risk factors for developing urothelial cancer. Close functional coupling between Chinese herbal drugs, Cox-2 gene activation and urothelial cancer should be further investigated.

  18. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Paolo Aiello

    2014-01-01

    Full Text Available The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

  19. Altered cell cycle response of drug-resistant lung carcinoma cells to doxorubicin.

    Science.gov (United States)

    O'Loughlin, C; Heenan, M; Coyle, S; Clynes, M

    2000-06-01

    The effect of doxorubicin treatment on cell cycle parameters in asynchronous populations of multidrug-resistant human lung carcinoma cell lines was investigated. A sensitive (DLKP-SQ) and three resistant (DLKP-SQ A250 10p#7, DLKP-A2B and DLKP-A5F) variants of a human lung carcinoma cell line DLKP were exposed to equitoxic concentrations of doxorubicin. The latter three were 8-fold, 30-fold and 300-fold resistant to doxorubicin, respectively. Irreversible G2/M arrest in sensitive (DLKP-SQ) cells was observed 24 h after initiation of doxorubicin treatment. In resistant variants, G2/M arrest occurred at 12-16 h with a subsequent bypass of the G2/M arrest to re-emerge and accumulate in G1. This transient G2/M arrest and subsequent progression into G1 indicated an inefficient checkpoint for monitoring DNA damage induced by doxorubicin treatment. Caffeine treatment could bypass the G2/M block in DLKP-SQ cells. Doxorubicin treatment did not alter cyclin B or cdc2 protein levels, the ability of cdc2 to form complexes with cyclin B or the levels of cyclin B bound to cdc2. The G2/M arrest seen in sensitive cells was associated with an increase in inhibitory phosphorylation of Tyr15 on cdc2. In contrast, tyrosine 15 phosphorylation did not change in resistant variants after drug treatment and a general increase in cdc2 kinase activity was seen. Cdc25C levels were not altered following drug treatment.

  20. Vismodegib and the hedgehog pathway: a new treatment for basal cell carcinoma.

    Science.gov (United States)

    Cirrone, Frank; Harris, Christy S

    2012-10-01

    Vismodegib is an oral inhibitor of the Hedgehog pathway approved by the US Food and Drug Administration. It is the first systemic treatment for patients with locally advanced or metastatic basal cell carcinoma that is not amenable to surgery and radiation. This is the first drug to use the Hedgehog pathway to inhibit the proliferation of tumors and is also implicated in the development of other cancers such as medulloblastoma. The goal of this review was to summarize the development, pharmacology, efficacy, and safety of vismodegib. Relevant English-language literature was identified and then evaluated based on results from database searches of MEDLINE and EMBASE from 1975 to June 19, 2012. The terms searched included, but were not limited to, vismodegib, Erivedge, GDC-0449, basal cell carcinoma, and 2-chloro-N-[4-chloro-3-(pyridin-2-yl)phenyl]-4-(methylsulfonyl)benzamide. Additional literature was identified by assessing the reference lists of previously identified articles and through abstracts presented by the American Society of Clinical Oncology. A total of 70 full text citations were identified although two national conference proceedings were then excluded. An additional 10 published abstracts were also identified. A Phase II, nonrandomized, multicenter, international study demonstrated a 30.3% objective response rate in metastatic basal cell carcinoma and a 42.9% objective response rate in locally advanced basal cell carcinoma. The adverse effect profile for vismodegib is similar to other identified Hedgehog pathway inhibitors; muscle cramps (71.7%), alopecia (63.8%), and dysgeusia (55.1%) were the most common adverse effects seen in trials. A Phase II, randomized, placebo-controlled trial in Gorlin syndrome patients with basal cell carcinoma concluded that vismodegib was significantly better than placebo at reducing new basal cell carcinoma lesions (P basal cell carcinoma or where resection would be cosmetically disadvantageous, vismodegib is an effective