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  1. Metallothionein gene expression in renal cell carcinoma

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    Deeksha Pal

    2014-01-01

    Full Text Available Introduction: Metallothioneins (MTs are a group of low-molecular weight, cysteine-rich proteins. In general, MT is known to modulate three fundamental processes: (1 the release of gaseous mediators such as hydroxyl radical or nitric oxide, (2 apoptosis and (3 the binding and exchange of heavy metals such as zinc, cadmium or copper. Previous studies have shown a positive correlation between the expression of MT with invasion, metastasis and poor prognosis in various cancers. Most of the previous studies primarily used immunohistochemistry to analyze localization of MT in renal cell carcinoma (RCC. No information is available on the gene expression of MT2A isoform in different types and grades of RCC. Materials and Methods: In the present study, total RNA was isolated from 38 histopathologically confirmed cases of RCC of different types and grades. Corresponding adjacent normal renal parenchyma was taken as control. Real-time polymerase chain reaction (RT PCR analysis was done for the MT2A gene expression using b-actin as an internal control. All statistical calculations were performed using SPSS software. Results: The MT2A gene expression was found to be significantly increased (P < 0.01 in clear cell RCC in comparison with the adjacent normal renal parenchyma. The expression of MT2A was two to three-fold higher in sarcomatoid RCC, whereas there was no change in papillary and collecting duct RCC. MT2A gene expression was significantly higher in lower grade (grades I and II, P < 0.05, while no change was observed in high-grade tumor (grade III and IV in comparison to adjacent normal renal tissue. Conclusion: The first report of the expression of MT2A in different types and grades of RCC and also these data further support the role of MT2A in tumorigenesis.

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

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    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.

  3. Microarray gene expression profiling and analysis in renal cell carcinoma

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    Sadhukhan Provash

    2004-06-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. Methods Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. Results Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR. Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. Conclusions This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most

  4. Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

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    Zhang Ping; Zhang Zhiyuan; Zhou Xiaojian; Qiu Weiliu; Chen Fangan; Chen Wantao

    2006-01-01

    Abstract Background Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. Methods A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differe...

  5. Identification and Characterization of Renal Cell Carcinoma Gene Markers

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    Louis S. Liou

    2007-01-01

    Full Text Available Microarray gene expression profiling has been used to distinguish histological subtypes of renal cell carcinoma (RCC, and consequently to identify specific tumor markers. The analytical procedures currently in use find sets of genes whose average differential expression across the two categories differ significantly. In general each of the markers thus identifi ed does not distinguish tumor from normal with 100% accuracy, although the group as a whole might be able to do so. For the purpose of developing a widely used economically viable diagnostic signature, however, large groups of genes are not likely to be useful. Here we use two different methods, one a support vector machine variant, and the other an exhaustive search, to reanalyze data previously generated in our Lab (Lenburg et al. 2003. We identify 158 genes, each having an expression level that is higher (lower in every tumor sample than in any normal sample, and each having a minimum differential expression across the two categorie at a signifi cance of 0.01. The set is highly enriched in cancer related genes (p = 1.6 × 10 – 12, containing 43 genes previously associated with either RCC or other types of cancer. Many of the biomarkers appear to be associated with the central alterations known to be required for cancer transformation. These include the oncogenes JAZF1, AXL, ABL2; tumor suppressors RASD1, PTPRO, TFAP2A, CDKN1C; and genes involved in proteolysis or cell-adhesion such as WASF2, and PAPPA.

  6. Genetic and epigenetic alterations of the blood group ABO gene in oral squamous cell carcinoma

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    Gao, Shan; Worm, Jesper; Guldberg, Per

    2004-01-01

    Loss of histo-blood group A and B antigen expression is a frequent event in oral carcinomas and is associated with decreased activity of glycosyltransferases encoded by the ABO gene. We examined 30 oral squamous cell carcinomas for expression of A and B antigens and glycosyltransferases. We also....... Collectively, we have identified molecular events that may account for loss of A/B antigen expression in 67% of oral squamous cell carcinomas....

  7. Expression of minichromosome maintenance genes in renal cell carcinoma

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    Zhong HB

    2017-11-01

    Full Text Available Hongbin Zhong,1,* Bin Chen,1,* Henrique Neves,2 Jinchun Xing,1 Youxin Ye,1 Ying Lin,1 Guohong Zhuang,3 Shu-Dong Zhang,4 Jiyi Huang,1,5 Hang Fai Kwok2 1Xiang’an Branch, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Faculty of Health Sciences, University of Macau, Taipa, Macau SAR; 3Medical College of Xiamen University, Xiamen, Fujian, People’s Republic of China; 4Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry, UK; 5The First Clinical School of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China *These authors contributed equally to this work Abstract: Minichromosome maintenance (MCM proteins play an essential role in DNA replication. They have been shown to be overexpressed in various types of cancer. However, the role of this family in renal cell carcinoma (RCC is widely unknown. In this study, we have identified a number of RCC datasets in the Gene Expression Omnibus database and also investigated the correlation between the expression levels of MCM genes and clinicopathological parameters. We found that the expression levels of MCM genes are positively correlated with one another. Expression levels of MCM2, MCM5, MCM6, and MCM7, but not of MCM3 and MCM4, were higher in RCC compared to paired adjacent normal tissue. Only the expression level of MCM4, but not of other MCMs, was positively correlated with tumor grade. In addition, a high-level expression of MCM2 in either primary tumor or metastases of RCC predicted a shorter disease-free survival time, while a high-level expression of MCM4 or MCM6 in primary tumor was also associated with poorer disease-free survival. Interestingly, we also demonstrated that patients with their primary RCC overexpressing 2 or more MCM genes had a shorter disease-free survival time, while those with RCC metastases overexpressing 3 or more MCM genes had a shorter

  8. Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

    International Nuclear Information System (INIS)

    Zhang, Ping; Zhang, Zhiyuan; Zhou, Xiaojian; Qiu, Weiliu; Chen, Fangan; Chen, Wantao

    2006-01-01

    Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differentiated tongue squamous cell carcinoma. Global gene expression in this resistant cell line and its sensitive parent cell line was analyzed using Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP pathway and cell cycle regulation were chosen to validate the microarray analysis results. Cell cycle distribution and apoptosis following cisplatin exposure were also investigated. Cisplatin resistance in Tca/cisplatin cells was stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis identified 38 genes that were up-regulated and 25 that were down-regulated in this cell line. Some were novel candidates, while others are involved in well-characterized mechanisms that could be relevant to cisplatin resistance, such as RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were involved in cisplatin resistance; 24-hour exposure to 10 μM cisplatin induced a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells. The Tca8113 cell line and its stable drug-resistant variant Tca/cisplatin provided a useful model for identifying candidate genes responsible for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our data provide a useful basis for screening candidate targets for early diagnosis and further intervention in cisplatin resistance

  9. Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

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    Zhang Ping

    2006-09-01

    Full Text Available Abstract Background Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. Methods A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differentiated tongue squamous cell carcinoma. Global gene expression in this resistant cell line and its sensitive parent cell line was analyzed using Affymetrix HG-U95Av2 microarrays. Candidate genes involved in DNA repair, the MAP pathway and cell cycle regulation were chosen to validate the microarray analysis results. Cell cycle distribution and apoptosis following cisplatin exposure were also investigated. Results Cisplatin resistance in Tca/cisplatin cells was stable for two years in cisplatin-free culture medium. The IC50 for cisplatin in Tca/cisplatin was 6.5-fold higher than that in Tca8113. Microarray analysis identified 38 genes that were up-regulated and 25 that were down-regulated in this cell line. Some were novel candidates, while others are involved in well-characterized mechanisms that could be relevant to cisplatin resistance, such as RECQL for DNA repair and MAP2K6 in the MAP pathway; all the genes were further validated by Real-time PCR. The cell cycle-regulated genes CCND1 and CCND3 were involved in cisplatin resistance; 24-hour exposure to 10 μM cisplatin induced a marked S phase block in Tca/cisplatin cells but not in Tca8113 cells. Conclusion The Tca8113 cell line and its stable drug-resistant variant Tca/cisplatin provided a useful model for identifying candidate genes responsible for the mechanism of cisplatin resistance in oral squamous cell carcinoma. Our data provide a useful basis for screening candidate targets for early diagnosis

  10. Nevoid basal cell carcinoma syndrome

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    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 ...

  11. Estrogen-Responsive Genes Overlap with Triiodothyronine-Responsive Genes in a Breast Carcinoma Cell Line

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    Nancy Bueno Figueiredo

    2014-01-01

    Full Text Available It has been well established that estrogen plays an important role in the progression and treatment of breast cancer. However, the role of triiodothyronine (T3 remains controversial. We have previously shown its capacity to stimulate the development of positive estrogen receptor breast carcinoma, induce the expression of genes (PR, TGF-alpha normally stimulated by estradiol (E2, and suppress genes (TGF-beta normally inhibited by E2. Since T3 regulates growth hormones, metabolism, and differentiation, it is important to verify its action on other genes normally induced by E2. Therefore, we used DNA microarrays to compare gene expression patterns in MCF-7 breast adenocarcinoma cells treated with E2 and T3. Several genes were modulated by both E2 and T3 in MCF-7 cells (Student’s t-test, P 2.0, pFDR < 0.05. We confirmed our microarray results by real-time PCR. Our findings reveal that certain genes in MCF-7 cells can be regulated by both E2 and T3.

  12. Breast Carcinoma Cells in Primary Tumors and Effusions Have Different Gene Array Profiles

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    Sophya Konstantinovsky

    2010-01-01

    Full Text Available The detection of breast carcinoma cells in effusions is associated with rapidly fatal outcome, but these cells are poorly characterized at the molecular level. This study compared the gene array signatures of breast carcinoma cells in primary carcinomas and effusions. The genetic signature of 10 primary tumors and 10 effusions was analyzed using the Array-Ready Oligo set for the Human Genome platform. Results for selected genes were validated using PCR, Western blotting, and immunohistochemistry. Array analysis identified 255 significantly downregulated and 96 upregulated genes in the effusion samples. The majority of differentially expressed genes were part of pathways involved in focal adhesion, extracellular matrix-cell interaction, and the regulation of the actin cytoskeleton. Genes that were upregulated in effusions included KRT8, BCAR1, CLDN4, VIL2, while DCN, CLDN19, ITGA7, and ITGA5 were downregulated at this anatomic site. PCR, Western blotting, and immunohistochemistry confirmed the array findings for BCAR1, CLDN4, VIL2, and DCN. Our data show that breast carcinoma cells in primary carcinomas and effusions have different gene expression signatures, and differentially express a large number of molecules related to adhesion, motility, and metastasis. These differences may have a critical role in designing therapy and in prognostication for patients with metastatic disease localized to the serosal cavities.

  13. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR

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    Kristiansen Glen

    2007-06-01

    Full Text Available Abstract Background Housekeeping genes are commonly used as endogenous reference genes for the relative quantification of target genes in gene expression studies. No conclusive systematic study comparing the suitability of different candidate reference genes in clear cell renal cell carcinoma has been published to date. To remedy this situation, 10 housekeeping genes for normalizing purposes of RT-PCR measurements already recommended in various studies were examined with regard to their usefulness as reference genes. Results The expression of the potential reference genes was examined in matched malignant and non-malignant tissue specimens from 25 patients with clear cell renal cell carcinoma. Quality assessment of isolated RNA performed with a 2100 Agilent Bioanalyzer showed a mean RNA integrity number of 8.7 for all samples. The between-run variations related to the crossing points of PCR reactions of a control material ranged from 0.17% to 0.38%. The expression of all genes did not depend on age, sex, and tumour stage. Except the genes TATA box binding protein (TBP and peptidylprolyl isomerase A (PPIA, all genes showed significant differences in expression between malignant and non-malignant pairs. The expression stability of the candidate reference genes was additionally controlled using the software programs geNorm and NormFinder. TBP and PPIA were validated as suitable reference genes by normalizing the target gene ADAM9 using these two most stably expressed genes in comparison with up- and down-regulated housekeeping genes of the panel. Conclusion Our study demonstrated the suitability of the two housekeeping genes PPIA and TBP as endogenous reference genes when comparing malignant tissue samples with adjacent normal tissue samples from clear cell renal cell carcinoma. Both genes are recommended as reference genes for relative gene quantification in gene profiling studies either as single gene or preferably in combination.

  14. Filaggrin Gene Mutations and Risk of Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Kaae, Jesper Rabølle; Thyssen, J P; Johansen, J D

    2013-01-01

    ) . Mice with knockdown of filaggrin, or lack of functional histidase, show decreased epidermal trans-UCA levels and increased UVB-induced skin damage (5) . FLG mutation carriers also have 10% increased serum vitamin D levels suggesting increased penetration of UVB (6) . We evaluated the prevalence of FLG......Basal cell carcinoma (BCC) is prevalent in lightly-pigmented Europeans. While ultraviolet (UV) radiation is an important risk factor, genetic predispositions to BCC have also been identified (1) . Atopic dermatitis (AD), a condition with a heritability that reaches 71-84%, might increase the risk...

  15. Squamous Cell Carcinoma

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    ... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

  16. Susceptible genes and molecular pathways related to heavy ion irradiation in oral squamous cell carcinoma cells

    International Nuclear Information System (INIS)

    Fushimi, Kazuaki; Uzawa, Katsuhiro; Ishigami, Takashi; Yamamoto, Nobuharu; Kawata, Tetsuya; Shibahara, Takahiko; Ito, Hisao; Mizoe, Jun-etsu; Tsujii, Hirohiko; Tanzawa, Hideki

    2008-01-01

    Background and purpose: Heavy ion beams are high linear energy transfer (LET) radiation characterized by a higher relative biologic effectiveness than low LET radiation. The aim of the current study was to determine the difference of gene expression between heavy ion beams and X-rays in oral squamous cell carcinoma (OSCC)-derived cells. Materials and methods: The OSCC cells were irradiated with accelerated carbon or neon ion irradiation or X-rays using three different doses. We sought to identify genes the expression of which is affected by carbon and neon ion irradiation using Affymetrix GeneChip analysis. The identified genes were analyzed using the Ingenuity Pathway Analysis Tool to investigate the functional network and gene ontology. Changes in mRNA expression in the genes were assessed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: The microarray analysis identified 84 genes that were modulated by carbon and neon ion irradiation at all doses in OSCC cells. Among the genes, three genes (TGFBR2, SMURF2, and BMP7) and two genes (CCND1 and E2F3), respectively, were found to be involved in the transforming growth factor β-signaling pathway and cell cycle:G1/S checkpoint regulation pathway. The qRT-PCR data from the five genes after heavy ion irradiation were consistent with the microarray data (P < 0.01). Conclusion: Our findings should serve as a basis for global characterization of radiation-regulated genes and pathways in heavy ion-irradiated OSCC

  17. Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

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    Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

    2017-11-01

    Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Identification of novel senescence-associated genes in ionizing radiation-induced senescent carcinoma cells

    International Nuclear Information System (INIS)

    Lee, Jae Seon; Kim, Bong Cho; Han, Na Kyung; Hong, Mi Na; Park, Su Min; Yoo, Hee Jung; Chu, In Sun; Lee, Sun Hee

    2009-01-01

    Cellular senescence is considered as a defense mechanism to prevent tumorigenesis. Ionizing radiation (IR) induces stress-induced premature senescence as well as apoptosis in various cancer cells. Senescent cells undergo functional and morphological changes including large and flattened cell shape, senescence-associated β-galactosidase (SA-βGal) activity, and altered gene expressions. Even with the recent findings of several gene expression profiles and supporting functional data, it is obscure that mechanism of IR-induced premature senescence in cancer cells. We performed microarray analysis to identify the common regulated genes in ionizing radiation-induced prematurely senescent human carcinoma cell lines

  19. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Guo, Guangwu; Gui, Yaoting; Gao, Shengjie

    2012-01-01

    We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of similar to 1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the u...

  20. Decreased expression of cell adhesion genes in cancer stem-like cells isolated from primary oral squamous cell carcinomas.

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    Mishra, Amrendra; Sriram, Harshini; Chandarana, Pinal; Tanavde, Vivek; Kumar, Rekha V; Gopinath, Ashok; Govindarajan, Raman; Ramaswamy, S; Sadasivam, Subhashini

    2018-05-01

    The goal of this study was to isolate cancer stem-like cells marked by high expression of CD44, a putative cancer stem cell marker, from primary oral squamous cell carcinomas and identify distinctive gene expression patterns in these cells. From 1 October 2013 to 4 September 2015, 76 stage III-IV primary oral squamous cell carcinoma of the gingivobuccal sulcus were resected. In all, 13 tumours were analysed by immunohistochemistry to visualise CD44-expressing cells. Expression of CD44 within The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma RNA-sequencing data was also assessed. Seventy resected tumours were dissociated into single cells and stained with antibodies to CD44 as well as CD45 and CD31 (together referred as Lineage/Lin). From 45 of these, CD44 + Lin - and CD44 - Lin - subpopulations were successfully isolated using fluorescence-activated cell sorting, and good-quality RNA was obtained from 14 such sorted pairs. Libraries from five pairs were sequenced and the results analysed using bioinformatics tools. Reverse transcription quantitative polymerase chain reaction was performed to experimentally validate the differential expression of selected candidate genes identified from the transcriptome sequencing in the same 5 and an additional 9 tumours. CD44 was expressed on the surface of poorly differentiated tumour cells, and within the The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma samples, its messenger RNA levels were higher in tumours compared to normal. Transcriptomics revealed that 102 genes were upregulated and 85 genes were downregulated in CD44 + Lin - compared to CD44 - Lin - cells in at least 3 of the 5 tumours sequenced. The upregulated genes included those involved in immune regulation, while the downregulated genes were enriched for genes involved in cell adhesion. Decreased expression of PCDH18, MGP, SPARCL1 and KRTDAP was confirmed by reverse transcription quantitative polymerase chain reaction. Lower expression of

  1. Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway.

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    Santos, Eliane Macedo Sobrinho; da Rocha, Rogério Gonçalves; Santos, Hércules Otacílio; Guimarães, Talita Antunes; de Carvalho Fraga, Carlos Alberto; da Silveira, Luiz Henrique; Batista, Paulo Ricardo; de Oliveira, Paulo Sérgio Lopes; Melo, Geraldo Aclécio; Santos, Sérgio Henrique; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

    2018-01-01

    Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Gene mutation in ATM/PI3K region of nasopharyngeal carcinoma cell lines

    International Nuclear Information System (INIS)

    Wang Hongmei; Wu Xinyao; Xia Yunfei

    2002-01-01

    Objective: To define the correlation between nasopharyngeal carcinoma (NPC) cell radiosensitivity and gene mutation in the ATM/PI3K coding region. Methods: The gene mutation in the ATM/PI3K region of nasopharyngeal carcinoma cell lines which vary in radiosensitivity, was monitored by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence-marked ddNTP cycle sequencing technique. Results: No gene mutation was detected in the ATM/PI3K region of either CNE1 or CNE2. Conclusion: Disparity in intrinsic radiosensitivity between different NPC cell lines depends on some other factors and mechanism without being related to ATM/PI3K mutations

  3. Basal Cell Carcinoma

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    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  4. Merkel Cell Carcinoma

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    ... Kids’ zone Video library Find a dermatologist Merkel cell carcinoma Overview Merkel cell carcinoma: This rare skin ... hard patch (1) or firm bump (2). Merkel cell carcinoma: Overview What is Merkel cell carcinoma? Merkel ...

  5. Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Nouhaud, François-Xavier; Blanchard, France; Sesboue, Richard; Flaman, Jean-Michel; Sabourin, Jean-Christophe; Pfister, Christian; Di Fiore, Frédéric

    2018-02-23

    Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC. The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs. Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Correlation of Slug gene expression with lymph node metastasis and invasion molecule expression in oral squamous cell carcinoma tissue

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    Shan-Ming Lu

    2017-10-01

    Full Text Available Objective: To study the correlation of Slug gene expression with lymph node metastasis and invasion molecule expression in oral squamous cell carcinoma tissue. Methods: Oral squamous cell carcinoma tissue surgical removed in Affiliated Stomatological Hospital of Nanjing Medical University between March 2015 and April 2017 was selected and divided into the oral squamous cell carcinoma tissue with neck lymph node metastasis and the oral squamous cell carcinoma tissues without lymph node metastasis according to the condition of lymph node metastasis. The expression of Slug, epithelial-mesenchymal transition molecules and invasion molecules in the oral squamous cell carcinoma tissue were detected. Results: Slug, N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with neck lymph node metastasis were significantly higher than those in oral squamous cell carcinoma tissue without lymph node metastasis while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue without lymph node metastasis; N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with high Slug expression were significantly higher than those in oral squamous cell carcinoma tissue with low Slug expression while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue with low Slug expression. Conclusion: The highly expressed Slug in oral squamous cell carcinoma tissue can promote the epithelial-mesenchymal transition and invasion of the cells to participate in the lymph node metastasis of tumor cells.

  7. Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling

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    Sterry Wolfram

    2006-08-01

    Full Text Available Abstract Background Carcinogenesis is a multi-step process indicated by several genes up- or down-regulated during tumor progression. This study examined and identified differentially expressed genes in cutaneous squamous cell carcinoma (SCC. Results Three different biopsies of 5 immunosuppressed organ-transplanted recipients each normal skin (all were pooled, actinic keratosis (AK (two were pooled, and invasive SCC and additionally 5 normal skin tissues from immunocompetent patients were analyzed. Thus, total RNA of 15 specimens were used for hybridization with Affymetrix HG-U133A microarray technology containing 22,283 genes. Data analyses were performed by prediction analysis of microarrays using nearest shrunken centroids with the threshold 3.5 and ANOVA analysis was independently performed in order to identify differentially expressed genes (p vs. AK and SCC were observed for 118 genes. Conclusion The majority of identified differentially expressed genes in cutaneous SCC were previously not described.

  8. Study on relationship between apoptosis-related genes and radiosensitivity of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Li Huixiang; Wang Yaohe; Shi Yonggang; Gao Dongling; Zhang Yunhan

    2000-01-01

    Objective: To observing the relationship between apoptosis-related genes bcl-2,c-myc, p53 and the radiosensitivity of esophageal squamous cell carcinoma. Methods: The expression levels of bcl-2, c-myc and p53 genes in 57 biopsy samples from patients of esophageal squamous cell carcinoma were detected with the LSAB immunohistochemistry method. All the patients were treated with radiotherapy. The radiotherapeutic effect in these patients was observed and the relation between gene expression and radiosensitivity was analyzed. Results: Compared with the bcl-2-negative group, the radiosensitivity of bcl-2-positive one was lower(P<0.01). The radiosensitivity of p53-positive group was slightly lower than that of the p53-negative one (P<0.05). The c-myc protein expression was not related to radiosensitivity. Conclusion: Detection and comprehensive analysis of bcl-2, c-myc and p53 protein expressions are useful in forecasting the radiotherapeutic effect on squamous cell carcinoma of esophagus

  9. Gene targeting associated with the radiation sensitivity in squamous cell carcinoma by using microarray analysis

    International Nuclear Information System (INIS)

    Nimura, Yoshinori; Kumagai, Ken; Kouzu, Yoshinao; Higo, Morihiro; Kato, Yoshikuni; Seki, Naohiko; Yamada, Shigeru

    2005-01-01

    In order to identify a set of genes related to radiation sensitivity of squamous cell carcinoma (SCC) and establish a predictive method, we compared expression profiles of radio-sensitive/radio-resistant SCC cell lines, using the in-house cDNA microarray consisting of 2,201 human genes derived from full-length enriched SCC cDNA libraries and the Human oligo chip 30 K (Hitachi Software Engineering). Surviving fractions (SF) after irradiation of heavy iron were calculated by colony formation assay. Three pairs (TE2-TE13, YES5-YES6, and HSC3-HSC2), sensitive (SF1 0.6), were selected for the microarray analysis. The results of cDNA microarray analysis showed that 20 genes in resistant cell lines and 5 genes in sensitive cell lines were up regulated more than 1.5-fold compared with sensitive and resistant cell lines respectively. Fourteen out of 25 genes were confirmed the gene expression profiles by real-time polymerase chain reaction (PCR). Twenty-seven genes identified by Human oligo chip 30 K are candidate for the markers to distinguish radio-sensitive from radio-resistant. These results suggest that the isolated 27 genes are the candidates that might be used as specific molecular markers to predict radiation sensitivity. (author)

  10. Reference genes for gene expression analysis by real-time reverse transcription polymerase chain reaction of renal cell carcinoma.

    Science.gov (United States)

    Bjerregaard, Henriette; Pedersen, Shona; Kristensen, Søren Risom; Marcussen, Niels

    2011-12-01

    Differentiation between malignant renal cell carcinoma and benign oncocytoma is of great importance to choose the optimal treatment. Accurate preoperative diagnosis of renal tumor is therefore crucial; however, existing imaging techniques and histologic examinations are incapable of providing an optimal differentiation profile. Analysis of gene expression of molecular markers is a new possibility but relies on appropriate standardization to compare different samples. The aim of this study was to identify stably expressed reference genes suitable for the normalization of results extracted from gene expression analysis of renal tumors. Expression levels of 8 potential reference genes (ATP5J, HMBS, HPRT1, PPIA, TBP, 18S, GAPDH, and POLR2A) were examined by real-time reverse transcription polymerase chain reaction in tumor and normal tissue from removed kidneys from 13 patients with renal cell carcinoma and 5 patients with oncocytoma. The expression levels of genes were compared by gene stability value M, average gene stability M, pairwise variation V, and coefficient of variation CV. More candidates were not suitable for the purpose, but a combination of HMBS, PPIA, ATP5J, and TBP was found to be the best combination with an average gene stability value M of 0.9 and a CV of 0.4 in the 18 tumors and normal tissues. A combination of 4 genes, HMBS, PPIA, ATP5J, and TBP, is a possible reference in renal tumor gene expression analysis by reverse transcription polymerase chain reaction. A combination of four genes, HMBS, PPIA, ATP5J and TBP, being stably expressed in tissues from RCC is possible reference genes for gene expression analysis.

  11. hTERT promoter mediating gene therapy in laryngeal squamous carcinomas cells in vitro

    International Nuclear Information System (INIS)

    Liao Zhengkai; Zhou Yunfeng; Zhou Fuxiang; Luo Zhiguo; Xiong Jie; Bao Jie; Xie Conghua; Liu Shiquan

    2007-01-01

    Objective: To investigate the relationship among hTERT promoter activity, hTERT mRNA expression, and telomerase activity (TA) in laryngeal squamous carcinomas cell lines, and to evaluate the usefulness of hTERT promoter mediated gene therapy. Methods: After plasmids pGL3-hTERTp were transfected, hTEBT promoter activity, hTERT mRNA expression and TA were determined by luciferase assay, RT-PCR and TRAP-PCR-ELISA, respectively. Plasmid phTERTp-HRP was constructed and transfected, HRP expression was determined by RT-PCR and competent peroxidase activity was confirmed by enzyme activity assay. The cytotoxicity and radiosensitivity of phTERTp-HRP/IAA were determined by clonogenic assay. Results: The relative levels of hTERT promoter activity, hTERT mRNA expression and TA in Hep2R cells were 1.37-fold, 1.43-fold and 1.81-fold compared with Hep2R cells, hTERT promoter activity was closely associated with hTERT mRNA expression and TA levels (P SF 2 ) was 1.24 (Hep2R cells) and 1.20 (Hep 2cells), the parameter a of with or without IAA incubation were 0.090, 0.020 (Hep2R)and 0.099, 0.042 (Hep2). Conclusions: hTERT promoter is applicable in mediating gene therapy in different radiosensitive laryngeal squamous carcinomas cells. hTERTp-HRP/IAA gene therapy may be a promising supplementary method for radiotherapy of laryngeal squamous-cell carcinomas. (authors)

  12. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

    International Nuclear Information System (INIS)

    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O.; Knebel Doeberitz, M. von

    1998-01-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [de

  13. Alteration in gene expression profile and oncogenicity of esophageal squamous cell carcinoma by RIZ1 upregulation.

    Science.gov (United States)

    Dong, Shang-Wen; Li, Dong; Xu, Cong; Sun, Pei; Wang, Yuan-Guo; Zhang, Peng

    2013-10-07

    To investigate the effect of retinoblastoma protein-interacting zinc finger gene 1 (RIZ1) upregulation in gene expression profile and oncogenicity of human esophageal squamous cell carcinoma (ESCC) cell line TE13. TE13 cells were transfected with pcDNA3.1(+)/RIZ1 and pcDNA3.1(+). Changes in gene expression profile were screened and the microarray results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Nude mice were inoculated with TE13 cells to establish ESCC xenografts. After two weeks, the inoculated mice were randomly divided into three groups. Tumors were injected with normal saline, transfection reagent pcDNA3.1(+) and transfection reagent pcDNA3.1(+)/RIZ1, respectively. Tumor development was quantified, and changes in gene expression of RIZ1 transfected tumors were detected by RT-PCR and Western blotting. DNA microarray data showed that RIZ1 transfection induced widespread changes in gene expression profile of cell line TE13, with 960 genes upregulated and 1163 downregulated. Treatment of tumor xenografts with RIZ1 recombinant plasmid significantly inhibited tumor growth, decreased tumor size, and increased expression of RIZ1 mRNA compared to control groups. The changes in gene expression profile were also observed in vivo after RIZ1 transfection. Most of the differentially expressed genes were associated with cell development, supervision of viral replication, lymphocyte costimulatory and immune system development in esophageal cells. RIZ1 gene may be involved in multiple cancer pathways, such as cytokine receptor interaction and transforming growth factor beta signaling. The development and progression of esophageal cancer are related to the inactivation of RIZ1. Virus infection may also be an important factor.

  14. Effect of suicidal gene combined with irradiation on esophageal carcinoma cell line

    International Nuclear Information System (INIS)

    Pan Jianji; Wang Jiezhong; Zheng Tianrong; Zheng Qiuhong

    2005-01-01

    Objective: As generally known that non-cytotoxic pro-drag can be transformed into cytotoxic drug by suicide gene, this work is to investigate the effect of Coli cytosine deaminase/5-fluorocytosine suicide gene (CD/5-FC) used alone or combined with irradiation in esophageal carcinoma cell line(EC). Methods: CD gene was amplified from Coli DNA genome library with PCR technique, with the eukaryotic vector pcDNA3.1-CD then constructed. ECl09 cells were transfected with pcDNA3.1-CD by liposome method. The cytotoxic effect, bystander effect and radiosensitization effect of CD/5-FC in ECl09 was analyzed. Results: The transfection of CD gene into ECl09 and its transcription was confirmed by RT-PCR method. In vitro, 5-FC showed significantly cytotoxic effect on the EPC cell transfected with CD gene. After adding 5-FC , the survival rate of cultured cell containing 5 % transfect CD gene cell was 41.8 % ± 14.2% while that in the control group was 94.6 ± 4.3 %, (t=3.14, P < 0.05). The survival rate of cultured cell containing 10% transfected CD gene cell was 37.8 ± 4.4% compared to 95.6% ± 5.4% in the control group, (t=9.75, P<0.01). CD/5-FC showed significant radiosen-sitization effect, the survival fraction of CD transfected cell was much lower in 5-FC combined with irradiation, when compared with 5-FC alone and radiotherapy alone group together, (F=11.50, P < 0.01 ). When it was compared with 5-FC alone group and irradiation alone group separately, the difference was also significant( F=4.11, P < 0.05 and F10.53, P < 0.01, respectively). Conclusions: Suicide gene CD/5-FC shows conspicuous by-stander effect and radiosensitization effect. (authors)

  15. Epigenetic silencing of MAL, a putative tumor suppressor gene, can contribute to human epithelium cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Jun

    2010-11-01

    Full Text Available Abstract Background To identify new and useful candidate biomarkers in head and neck squamous cell carcinoma (HNSCC, we performed a genome-wide survey and found that Myelin and lymphocyte-associated protein (MAL was a gene that was markedly down-regulated in HNSCC. Hence, we investigated the mechanism of MAL silencing and the effects of MAL on the proliferation, invasion, and apoptotic potential in HNSCC. Results MAL was significantly down-regulated in 91.7% of HNSCC specimens at the mRNA level as compared with adjacent normal tissues (P = 0.0004. Moreover, the relative transcript levels of the MAL gene were remarkably decreased by five-fold in nine HNSCC cell lines as compared with normal head and neck epithelium cells. MAL gene expression was restored in 44%, 67%, and 89% in HNSCC cell lines treated with TSA, 5-Aza-dC, and TSA plus 5-Aza-dC, respectively. Furthermore, bisulfate-treated DNA sequencing demonstrated that the two CpG islands (that is, M1 and M2 located in MAL promoter region were completely methylated in the HNSCC cell lines (CpG methylated ratio was more than 90%, and only one CpG island (that is, M1 was partially methylated in HNSCC tissues (CpG methylated ratio between 20% and 90%. A significant reduction in cell proliferation and a change in the cell cycle profile were also observed in MAL transfectants. Matrigel assay demonstrated that the invasiveness of HNSCC cells significantly decreased. A significant increase in the population of apoptotic cells was observed in MAL transfected cells. The exogenous expression of the MAL gene suppressed malignant phenotypes, while the cell death induced by MAL gene transfer was a result of apoptosis as demonstrated by the induction of cleavage of the poly (that is, ADP-ribose polymerase. Additionally, tumor growth was suppressed in cells expressing MAL as compared with cells not expressing MAL. Conclusion Our data suggest that the epigenetic inactivation of MAL, as a candidate tumor

  16. An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Genta Sawada

    Full Text Available Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC. Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used to predict driver genes.We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort.We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC.Our integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target.

  17. ING Genes Work as Tumor Suppressor Genes in the Carcinogenesis of Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Xiaohan Li

    2011-01-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer in the world. The evolution and progression of HNSCC are considered to result from multiple stepwise alterations of cellular and molecular pathways in squamous epithelium. Recently, inhibitor of growth gene (ING family consisting of five genes, ING1 to ING5, was identified as a new tumor suppressor gene family that was implicated in the downregulation of cell cycle and chromatin remodeling. In contrast, it has been shown that ING1 and ING2 play an oncogenic role in some cancers, this situation being similar to TGF-β. In HNSCC, the ING family has been reported to be downregulated, and ING translocation from the nucleus to the cytoplasm may be a critical event for carcinogenesis. In this paper, we describe our recent results and briefly summarize current knowledge regarding the biologic functions of ING in HNSCC.

  18. Radiosensitization effect of recombinant adenoviral-mediated PUMA gene on pancreatic carcinoma cells

    International Nuclear Information System (INIS)

    Zhu Dongming; Zhang Kejun; Li Dechun; Zhu Xuefeng; Yang Yong

    2009-01-01

    Objective: To study the effect of PUMA gene mediated by recombinant adenovirus vector combined with radiation on the pancreatic carcinoma. Methods: The PANC-1 cells were infected with Ad- PUMA (MOI=10, 50 and 100, respectively) for 48 h. The expression of PUMA mRNA and protein was detected by RT-PCR and Western blot, respectively. PANC-1 cells were divided into 4 groups: control group, transfection group, irradiation group and combined treatment group. The cell growth inhibition rate and apoptotic rate of PANC-1 cells were assessed by MTT assay and flow cytometry. Human pancreatic carcinomas were transplanted subcutaneously in nude mice, which were randomized into 4 groups: control group, transfection group, irradiation group and combined treatment group. Tumor growth rate and apoptotic index at different time points were recorded in 35 days. Results: The expression of PUMA mRNA and protein was increased with the increase of MOI of Ad-PUMA, which was does-dependant (MOI=10, mRNA=0.46± 0.02, protein=0.75± 0.09; MOI=50, mRNA=1.12±0.09, protein=1.01±0.18; MOI=100, mRNA=1.50±0.08, protein= 1.80±0.15; P 3 , (39.5±9.23)mm 3 , (33.6±10.3)mm 3 and (52.0±11.43)mm 3 , respectively, P<0.05]. And the apoptotic index was increased in the same manner (AI=0.43±0.05, 0.29±0.10, 0.24±0.05 and 0.00±0.00, respectively, P<0.05). Conclusions: Recombinant adenoviral-mediated PUMA gene combined with irradiation could increase the cell-killing effect on pancreatic carcinoma. It is better than that of either one kind of therapy. (authors)

  19. [Study of testicular cancer gene expression in samples of oral leukoplakia and squamous cell carcinoma of the mouth].

    Science.gov (United States)

    Skorodumova, L O; Muraev, A A; Zakharova, E S; Shepelev, M V; Korobko, I V; Zaderenko, I A; Ivanov, S Iu; Gnuchev, N V; Georgiev, G P; Larin, S S

    2012-01-01

    Cancer-testis (CT) antigens are normally expressed mostly in human germ cells, there is also an aberrant expression in some tumor cells. This expression profile makes them potential tumor growth biomarkers and a promising target for tumor immunotherapy. Specificity of CT genes expression in oral malignant and potentially malignant diseases, e.g. oral leukoplakia, is not yet studied. Data on CT genes expression profile in leukoplakia would allow developing new diagnostic methods with potential value for immunotherapy and prophylaxis of leukoplakia malignization. In our study we compared CT genes expression in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma. We are the first to describe CT genes expression in oral leukoplakia without dysplasia. This findings make impossible differential diagnosis of oral leukoplakia and squamous cell carcinoma on the basis of CT genes expression. The prognostic value of CT genes expression is still unclear, therefore the longitudinal studies are necessary.

  20. Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute

    2004-01-01

    in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported......Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly...

  1. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

    DEFF Research Database (Denmark)

    Gui, Yaoting; Guo, Guangwu; Huang, Yi

    2011-01-01

    frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.......Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we...

  2. 3-Deazaneplanocin A suppresses aggressive phenotype-related gene expression in an oral squamous cell carcinoma cell line

    International Nuclear Information System (INIS)

    Hatta, Mitsutoki; Naganuma, Kaori; Kato, Kenichi; Yamazaki, Jun

    2015-01-01

    In tumor tissues, alterations of gene expression caused by aberrant epigenetic modifications confer phenotypic diversity on malignant cells. Although 3-deazaneplanocin A (DZNep) has been shown to reactivate tumor suppressor genes in several cancer cells, it remains unclear whether DZNep attenuates the malignant phenotypes of oral squamous cell carcinoma (OSCC) cells. In this study, we investigated the effect of DZNep on the expression of genes related to aggressive phenotypes, such as epithelial–mesenchymal transition, in OSCC cells. We found that DZNep reduced the cellular levels of polycomb group proteins (EZH2, SUZ12, BMI1, and RING1A) and the associated trimethylation of Lys27 on histone H3 and monoubiquitination of Lys119 on histone H2A in the poorly differentiated OSCC cell line SAS. Immunocytochemical staining demonstrated that DZNep induced the reorganization of filamentous actin and the membrane localization of E-cadherin associated with cell–cell adhesions. We also found an inhibitory effect of DZNep on cell proliferation using a WST assay. Finally, quantitative RT-PCR analysis demonstrated that genes involved in the aggressive phenotypes (TWIST2, EGFR, ACTA2, TGFB1, WNT5B, and APLIN) were down-regulated, whereas epithelial phenotype genes (CDH1, CLDN4, IVL, and TGM1) were up-regulated in SAS cells treated with DZNep. Collectively, our findings suggest that DZNep reverses the aggressive characteristics of OSCC cells through the dynamic regulation of epithelial plasticity via the reprogramming of gene expression patterns. - Highlights: • DZNep reduced PcG proteins and associated histone modifications in OSCC cells. • DZNep enhanced cell–cell adhesion indicative of epithelial phenotype in OSCC cells. • DZNep suppressed the aggressive phenotype-related gene expression in OSCC cells. • DZNep activated the gene expression of epithelial markers in OSCC cells.

  3. 3-Deazaneplanocin A suppresses aggressive phenotype-related gene expression in an oral squamous cell carcinoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Hatta, Mitsutoki, E-mail: hatta@college.fdcnet.ac.jp [Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka (Japan); Naganuma, Kaori [Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, Fukuoka (Japan); Kato, Kenichi; Yamazaki, Jun [Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka (Japan)

    2015-12-04

    In tumor tissues, alterations of gene expression caused by aberrant epigenetic modifications confer phenotypic diversity on malignant cells. Although 3-deazaneplanocin A (DZNep) has been shown to reactivate tumor suppressor genes in several cancer cells, it remains unclear whether DZNep attenuates the malignant phenotypes of oral squamous cell carcinoma (OSCC) cells. In this study, we investigated the effect of DZNep on the expression of genes related to aggressive phenotypes, such as epithelial–mesenchymal transition, in OSCC cells. We found that DZNep reduced the cellular levels of polycomb group proteins (EZH2, SUZ12, BMI1, and RING1A) and the associated trimethylation of Lys27 on histone H3 and monoubiquitination of Lys119 on histone H2A in the poorly differentiated OSCC cell line SAS. Immunocytochemical staining demonstrated that DZNep induced the reorganization of filamentous actin and the membrane localization of E-cadherin associated with cell–cell adhesions. We also found an inhibitory effect of DZNep on cell proliferation using a WST assay. Finally, quantitative RT-PCR analysis demonstrated that genes involved in the aggressive phenotypes (TWIST2, EGFR, ACTA2, TGFB1, WNT5B, and APLIN) were down-regulated, whereas epithelial phenotype genes (CDH1, CLDN4, IVL, and TGM1) were up-regulated in SAS cells treated with DZNep. Collectively, our findings suggest that DZNep reverses the aggressive characteristics of OSCC cells through the dynamic regulation of epithelial plasticity via the reprogramming of gene expression patterns. - Highlights: • DZNep reduced PcG proteins and associated histone modifications in OSCC cells. • DZNep enhanced cell–cell adhesion indicative of epithelial phenotype in OSCC cells. • DZNep suppressed the aggressive phenotype-related gene expression in OSCC cells. • DZNep activated the gene expression of epithelial markers in OSCC cells.

  4. Regulation and patterns of endogenous and exogenous gene expression during differentiation of embryonal carcinoma cells

    International Nuclear Information System (INIS)

    Astigiano, S.; Sherman, M.I.; Abarzua, P.

    1989-01-01

    Embryonal carcinoma (EC) cells offer an interesting model system for evaluating differentiation because the cells are pluripotent, thus resembling germ cells and embryonic stem cells, and because a number of agents have been defined that are capable of promoting the differentiation of these cells. This chapter examines how EC cells might be triggered to differentiate, with emphasis on retinoic acid because this compound is a potent, naturally occurring inducer that has been studied extensively in this system. The nature of alterations in gene expression during EC cell differentiation is reviewed from the perspective of evaluating whether these changes are likely to be responsible for, or a result of, the differentiation event. Finally, the authors consider in molecular terms why EC cells, but not their differentiated derivatives, are refractory to the expression of many viral genomes following infection. Based upon these studies, they propose that fundamental changes in gene expression that are observed when differentiation is triggered in EC cells are likely to be due to the disappearance or neutralization of strong repressor elements

  5. Frequency of p53 Gene Mutation and Protein Expression in Oral Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Ara, N.; Atique, M.; Ahmed, S.; Bukhari, S. G. A.

    2014-01-01

    Objective: To determine the frequency of p53 gene mutation and protein expression in Oral Squamous Cell Carcinoma (OSCC) and to establish correlation between the two. Study Design: Analytical study. Place and Duration of Study: Histopathology Department and Molecular Biology Laboratory, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from May 2010 to May 2011. Methodology: Thirty diagnosed cases of OSCC were selected by consecutive sampling. Seventeen were retrieved from the record files of the AFIP, and 13 fresh/frozen sections were selected from patients reporting to the Oral Surgery Department, Armed Forces Institute of Dentistry (AFID). Gene p53 mutation was analyzed in all the cases using PCRSSCP analysis. DNA was extracted from the formalin-fixed and paraffin-embedded tissue sections and fresh/frozen sections. DNA thus extracted was amplified by polymerase chain reaction. The amplified products were denatured and finally analyzed by gel electrophoresis. Gene mutation was detected as electrophoretic mobility shift. The immunohistochemical marker p53 was applied to the same 30 cases and overexpression of protein p53 was recorded. Results: Immunohistochemical expression of marker p53 was positive in 67% (95% Confidence Interval (CI) 48.7 - 80.9) of the cases. Mutations of the p53 gene were detected in 23% (95% CI 11.5 - 41.2) of the OSCC. No statistically significant correlation was found between p53 gene mutation and protein p53 expression (rs = - 0.057, p = 0.765). Conclusion: A substantial number of patients have p53 gene mutation (23%) and protein p53 expression (67%) in oral squamous cell carcinoma (OSCC). (author)

  6. Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data

    International Nuclear Information System (INIS)

    Lenburg, Marc E; Liou, Louis S; Gerry, Norman P; Frampton, Garrett M; Cohen, Herbert T; Christman, Michael F

    2003-01-01

    Renal cell carcinoma is a common malignancy that often presents as a metastatic-disease for which there are no effective treatments. To gain insights into the mechanism of renal cell carcinogenesis, a number of genome-wide expression profiling studies have been performed. Surprisingly, there is very poor agreement among these studies as to which genes are differentially regulated. To better understand this lack of agreement we profiled renal cell tumor gene expression using genome-wide microarrays (45,000 probe sets) and compare our analysis to previous microarray studies. We hybridized total RNA isolated from renal cell tumors and adjacent normal tissue to Affymetrix U133A and U133B arrays. We removed samples with technical defects and removed probesets that failed to exhibit sequence-specific hybridization in any of the samples. We detected differential gene expression in the resulting dataset with parametric methods and identified keywords that are overrepresented in the differentially expressed genes with the Fisher-exact test. We identify 1,234 genes that are more than three-fold changed in renal tumors by t-test, 800 of which have not been previously reported to be altered in renal cell tumors. Of the only 37 genes that have been identified as being differentially expressed in three or more of five previous microarray studies of renal tumor gene expression, our analysis finds 33 of these genes (89%). A key to the sensitivity and power of our analysis is filtering out defective samples and genes that are not reliably detected. The widespread use of sample-wise voting schemes for detecting differential expression that do not control for false positives likely account for the poor overlap among previous studies. Among the many genes we identified using parametric methods that were not previously reported as being differentially expressed in renal cell tumors are several oncogenes and tumor suppressor genes that likely play important roles in renal cell

  7. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O. [Lab. de Radiobiologie, Service de Radio-Oncologie, CHUV, Lausanne (Switzerland); Knebel Doeberitz, M. von [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Inst. fuer Virusforschung

    1998-02-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [Deutsch] Das Ziel dieser Studie lag darin, die Rolle der HPV-18-Gene E6 und E7 in bezug auf die Strahlenempfindlichkeit von menschlichen Zervixkarzinomzellen zu untersuchen. Wir verwendeten zwei menschliche Zervixkarzinomzellinien, C4-1 und SW 756, in welchen die Expression der viralen Gene HPV 18 E6 und E7 mit Dexamethason moduliert werden kann: In C4-1 bewirkt die Behandlung mit Dexamethason eine Erhoehung der Expression dieser Gene, in SW 756 eine Verminderung. Die Wirkung auf die Wachstumsfaehigkeit der Zellen und auf die Wachstumshemmung durch die Bestrahlung wurde unter Verwendung eines klonogenen Assays bestimmt. Dexamethason bewirkte eine erhoehte Wachstumsfaehigkeit der C4-1 Zellen, ohne die Wachstumsfaehigkeit der SW-756-Zellen zu beeinflussen, wie schon frueher beschrieben. Die Resistenz beider Zellinien gegenueber Bestrahlung wurde erhoeht. Somit besteht in den C4-1-Zellen eine Korrelation der Expression der viralen Gene mit der Zunahme der Strahlenresistenz, wogegen in den SW-756-Zellen die Abnahme der Expression im Gegensatz zu

  8. Detection of the E7 transform gene of human papilloma virus type 16 in human oral squamous cell carcinoma.

    Science.gov (United States)

    Wang, J; Li, J; Huang, H; Fu, Y

    1998-12-01

    To determine, with the use of polymerase chain reaction, the prevalence of human papillomavirus (HPV) 16 in 30 patients with primary oral squamous cell carcinoma (OSCC) and 30 healthy control patients. DNA was extracted from freshly frozen tumor tissues of 30 patients with primary oral squamous cell carcinoma and from the oral mucosa of 30 controls. A pair of specific primers of the E7 early gene of HPV 16 were designed. PCR products were run by 1.5% agarose gel and the results of electrophoresis were photographed. HPV 16 was detected in 36.7% (11/30) of oral squamous cell carcinoma patients and 11.1% (4/30) of controls. HPV 16 has a significant association with oral squamous cell carcinoma. However, the role HPV 16 plays in the tumorigenesis of oral cancer and its clinical significance remain to be investigated.

  9. Gene Expression Differences Predict Treatment Outcome of Merkel Cell Carcinoma Patients

    Directory of Open Access Journals (Sweden)

    Loren Masterson

    2014-01-01

    Full Text Available Due to the rarity of Merkel cell carcinoma (MCC, prospective clinical trials have not been practical. This study aimed to identify biomarkers with prognostic significance. While sixty-two patients were identified who were treated for MCC at our institution, only seventeen patients had adequate formalin-fixed paraffin-embedded archival tissue and followup to be included in the study. Patients were stratified into good, moderate, or poor prognosis. Laser capture microdissection was used to isolate tumor cells for subsequent RNA isolation and gene expression analysis with Affymetrix GeneChip Human Exon 1.0 ST arrays. Among the 191 genes demonstrating significant differential expression between prognostic groups, keratin 20 and neurofilament protein have previously been identified in studies of MCC and were significantly upregulated in tumors from patients with a poor prognosis. Immunohistochemistry further established that keratin 20 was overexpressed in the poor prognosis tumors. In addition, novel genes of interest such as phospholipase A2 group X, kinesin family member 3A, tumor protein D52, mucin 1, and KIT were upregulated in specimens from patients with poor prognosis. Our pilot study identified several gene expression differences which could be used in the future as prognostic biomarkers in MCC patients.

  10. Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model

    KAUST Repository

    Essack, Magbubah

    2012-10-26

    Background: Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.Results: Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.Conclusion: To the best of our knowledge our study is the first

  11. Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model

    KAUST Repository

    Essack, Magbubah; MacPherson, Cameron Ross; Schmeier, Sebastian; Bajic, Vladimir B.

    2012-01-01

    Background: Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.Results: Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.Conclusion: To the best of our knowledge our study is the first

  12. Oral Rigosertib for Squamous Cell Carcinoma

    Science.gov (United States)

    2017-06-22

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

  13. Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma

    OpenAIRE

    Ricketts, Christopher J.; Morris, Mark R.; Gentle, Dean; Brown, Michael; Wake, Naomi; Woodward, Emma R.; Clarke, Noel; Latif, Farida; Maher, Eamonn R.

    2012-01-01

    In order to identify novel candidate tumor suppressor genes (TSGs) implicated in renal cell carcinoma (RCC), we performed genome-wide methylation profiling of RCC using the HumanMethylation27 BeadChips to assess methylation at >14,000 genes. Two hundred and twenty hypermethylated probes representing 205 loci/genes were identified in genomic CpG islands. A subset of TSGs investigated in detail exhibited frequent tumor methylation, promoter methylation associated transcriptional silencing an...

  14. Gene therapy of thyroid carcinoma

    International Nuclear Information System (INIS)

    Zheng Wei; Tan Jian

    2007-01-01

    Normally, differentiated thyroid carcinoma(DTC) is a disease of good prognosis, but about 30% of the tumors are dedifferentiate, which are inaccessible to standard therapeutic procedures such as 'operation, 131 I therapy and thyroid hormone'. Both internal and abroad experts are researching a new therapy of dedifferentiated thyroid carcinoma--gene therapy. Many of them utilize methods of it, but follow different strategies: (1) transduction of the thyroid sodium/iodide transporter gene to make tissues that do not accumulate iodide treatable by 131 I therapy; (2) strengthening of the anti-tumor immune response; (3) suicide gene therapy; (4) depression the generation of tumor cells; (5) gene therapy of anti- vascularization. (authors)

  15. Impacts of CA9 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

    Directory of Open Access Journals (Sweden)

    Shian-Shiang Wang

    Full Text Available Carbonic anhydrase 9 (CA9 is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the effect of CA9 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC and the clinicopathological status.A total of 442 participants, including 221 healthy people and 221 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms (SNPs of the CA9 gene were assessed by a real-time PCR with the TaqMan assay. After adjusting for other co-variants, the individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk of developing UCC than did wild-type (CC carriers. Furthermore, UCC patients who carried at least one A allele at rs1048638 had a higher invasive stage risk (p< 0.05 than did patients carrying the wild-type allele. Moreover, among the UCC patients with smoker, people with at least one A allele of CA9 polymorphisms (rs1048638 had a 4.75-fold (95% CI = 1.204-18.746 increased risk of invasive cancer.The rs1048638 polymorphic genotypes of CA9 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with CA9 variants in carcinogenesis of UCC in Taiwan.

  16. Upregulation of metastasis-associated gene 2 promotes cell proliferation and invasion in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Wu MH

    2016-03-01

    Full Text Available Minhua Wu,1,2,* Xiaoxia Ye,2,* Xubin Deng,3,* Yanxia Wu,4 Xiaofang Li,4 Lin Zhang11Department of Histology and Embryology, Southern Medical University, Guangzhou, 2Department of Histology and Embryology, Guangdong Medical University, Zhanjiang, 3Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University, Guangzhou, 4Pathological Diagnosis and Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China*These authors contributed equally to this workAims: Metastasis-associated gene 2 (MTA2 is reported to play an important role in tumor progression, but little is known about the role of MTA2 in nasopharyngeal carcinoma (NPC. The aim of the study was to explore the expression and function of MTA2 in NPC.Methods: Expression of MTA2 in NPC tissues and cell lines was detected by immunohistochemistry and Western blotting. Relationship between MTA2 expression and clinicopathological features was analyzed. Stable MTA2-overexpressing and MTA2-siliencing NPC cells were established by transfection with plasmids encoding MTA2 cDNA and lentivirus-mediated short hairpin RNA, respectively. Cell viability was determined by Cell Counting Kit-8 and colony formation assay. Cell migration ability was evaluated by wound healing and transwell invasion assay. The impact of MTA2 knockdown on growth and metastasis of CNE2 cells in vivo was determined by nude mouse xenograft models. Expression of several Akt pathway proteins was detected by Western blotting.Results: MTA2 was upregulated in NPC tissues and three NPC cell lines detected (CNE1, CNE2, and HNE1. MTA2 expression was related to clinical stage and lymph node metastasis of patients with NPC. MTA2 upregulation promoted proliferation and invasion of CNE1 cells, while MTA2 depletion had opposite effects on CNE2 cells. Moreover, MTA2 depletion suppressed growth and metastasis of CNE2 cells in vivo. MTA2 overexpression

  17. Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Gao, S.; Worm, J.; Guldberg, P.

    2004-01-01

    The DBCCR1 gene at chromosome 9q33 has been identified as a candidate tumour suppressor, which is frequently targeted by promoter hypermethylation in bladder cancer. Here, we studied the possible involvement of DBCCR1 in the development of oral squamous cell carcinoma. DNA from 34 tumours...

  18. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu

    2014-01-01

    To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells.

  19. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

    International Nuclear Information System (INIS)

    Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J.

    2014-01-01

    To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells

  20. Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas.

    Science.gov (United States)

    Kleb, Brittany; Estécio, Marcos R H; Zhang, Jiexin; Tzelepi, Vassiliki; Chung, Woonbok; Jelinek, Jaroslav; Navone, Nora M; Tahir, Salahaldin; Marquez, Victor E; Issa, Jean-Pierre; Maity, Sankar; Aparicio, Ana

    2016-03-03

    Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR(-)SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR(-)SCPC cell lines. We conclude that the epigenome of AR(-) is distinct from that of AR(+) castration-resistant prostate carcinomas, and that the AR(-) phenotype can be reversed with epigenetic drugs.

  1. PTCH1 gene haplotype association with basal cell carcinoma after transplantation.

    Science.gov (United States)

    Begnini, A; Tessari, G; Turco, A; Malerba, G; Naldi, L; Gotti, E; Boschiero, L; Forni, A; Rugiu, C; Piaserico, S; Fortina, A B; Brunello, A; Cascone, C; Girolomoni, G; Gomez Lira, M

    2010-08-01

    Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. To search for novel common polymorphisms in the proximal 5' regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. Single locus analysis showed no significant association. Haplotype T(1686)-T(3944) appeared to confer a significantly higher risk for BCC development (odds ratio 2.98, 95% confidence interval 2.55-3.48; P = 0.001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5'UTR. Two novel alleles of the -4 (CGG)(n) microsatellite were identified. No association of this microsatellite with BCC was observed. Haplotypes containing T(1686)-T(3944) alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5

  2. Stratification of clear cell renal cell carcinoma (ccRCC) genomes by gene-directed copy number alteration (CNA) analysis.

    Science.gov (United States)

    Thiesen, H-J; Steinbeck, F; Maruschke, M; Koczan, D; Ziems, B; Hakenberg, O W

    2017-01-01

    Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

  3. Down-regulation of the expression of CCAAT/enhancer binding protein α gene in cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Pan, Zemin; Shao, Renfu; Zheng, Weinan; Zhang, Jinli; Gao, Rui; Li, Dongmei; Guo, Xiaoqing; Han, Hu; Li, Feng; Qu, Shen

    2014-01-01

    Cervical carcinoma is the second most common cancer and is an important cause of death in women worldwide. CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that regulate cellular differentiation and proliferation in a variety of tissues. However, the role of C/EBPα gene in cervical cancer is still not clear. We investigated the expression of C/EBPα gene in cervical squamous cell carcinoma. C/EBPα mRNA level was measured by real-time quantitative RT-PCR in cervical cancer tissues and their adjacent normal tissues. C/EBPα protein level was measured by immunohistochemistry. Methylation in the promoter of C/EBPα gene was detected by MALDI TOF MassARRAY. We transfected HeLa cells with C/EBPα expression vector. C/EBPα expression in HeLa cells was examined and HeLa cell proliferation was measured by MTT assay and HeLa cells migration was analyzed by matrigel-coated transwell migration assays. There were significant difference in C/EBPα protein expression between chronic cervicitis and cervical carcinoma (P < 0.001). CEBPα mRNA level was significantly lower in cervical cancer tissues than in normal cervical tissues (P < 0.01). Methylation of the promoter of CEBPα gene in CpG 5, CpG-14.15, CpG-19.20 were significantly higher in cervical cancer than in normal cervical tissues (P < 0.05, P < 0.01, P < 0.05, respectively). CEBPα pcDNA3.1 construct transfected into HeLa cells inhibited cell proliferation and decreased cell migration. Our results indicate that reduced C/EBPα gene expression may play a role in the development of cervical squamous cell carcinoma

  4. Trichloroethylene exposure and somatic mutations of the VHL gene in patients with Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Fevotte Joelle

    2007-11-01

    Full Text Available Abstract Background We investigated the association between exposure to trichloroethylene (TCE and mutations in the von Hippel-Lindau (VHL gene and the subsequent risk for renal cell carcinoma (RCC. Methods Cases were recruited from a case-control study previously carried out in France that suggested an association between exposures to high levels of TCE and increased risk of RCC. From 87 cases of RCC recruited for the epidemiological study, 69 were included in the present study. All samples were evaluated by a pathologist in order to identify the histological subtype and then be able to focus on clear cell RCC. The majority of the tumour samples were fixed either in formalin or Bouin's solutions. The majority of the tumours were of the clear cell RCC subtype (48 including 2 cystic RCC. Mutation screening of the 3 VHL coding exons was carried out. A descriptive analysis was performed to compare exposed and non exposed cases of clear cell RCC in terms of prevalence of mutations in both groups. Results In the 48 cases of RCC, four VHL mutations were detected: within exon 1 (c.332G>A, p.Ser111Asn, at the exon 2 splice site (c.463+1G>C and c.463+2T>C and within exon 3 (c.506T>C, p.Leu169Pro. No difference was observed regarding the frequency of mutations in exposed versus unexposed groups: among the clear cell RCC, 25 had been exposed to TCE and 23 had no history of occupational exposure to TCE. Two patients with a mutation were identified in each group. Conclusion This study does not confirm the association between the number and type of VHL gene mutations and exposure to TCE previously described.

  5. Kinase Gene Expression Profiling of Metastatic Clear Cell Renal Cell Carcinoma Tissue Identifies Potential New Therapeutic Targets.

    Directory of Open Access Journals (Sweden)

    Pooja Ghatalia

    Full Text Available Kinases are therapeutically actionable targets. Kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR and mammalian target of rapamycin (mTOR improve outcomes in metastatic clear cell renal cell carcinoma (ccRCC, but are not curative. Metastatic tumor tissue has not been comprehensively studied for kinase gene expression. Paired intra-patient kinase gene expression analysis in primary tumor (T, matched normal kidney (N and metastatic tumor tissue (M may assist in identifying drivers of metastasis and prioritizing therapeutic targets. We compared the expression of 519 kinase genes using NanoString in T, N and M in 35 patients to discover genes over-expressed in M compared to T and N tissue. RNA-seq data derived from ccRCC tumors in The Cancer Genome Atlas (TCGA were used to demonstrate differential expression of genes in primary tumor tissue from patients that had metastasis at baseline (n = 79 compared to those that did not develop metastasis for at least 2 years (n = 187. Functional analysis was conducted to identify key signaling pathways by using Ingenuity Pathway Analysis. Of 10 kinase genes overexpressed in metastases compared to primary tumor in the discovery cohort, 9 genes were also differentially expressed in TCGA primary tumors with metastasis at baseline compared to primary tumors without metastasis for at least 2 years: EPHB2, AURKA, GSG2, IKBKE, MELK, CSK, CHEK2, CDC7 and MAP3K8; p<0.001. The top pathways overexpressed in M tissue were pyridoxal 5'-phosphate salvage, salvage pathways of pyrimidine ribonucleotides, NF-kB signaling, NGF signaling and cell cycle control of chromosomal replication. The 9 kinase genes validated to be over-expressed in metastatic ccRCC may represent currently unrecognized but potentially actionable therapeutic targets that warrant functional validation.

  6. Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa

    DEFF Research Database (Denmark)

    Gao, Shan; Nielsen, Boye Schnack; Krogdahl, Annelise

    2010-01-01

    cells in oral carcinomas by immunohistochemistry, we found that PAI-1 was expressed in 18 of the 20 patients, mainly by cancer cells. Two showed PAI-1 positive stromal cells surrounding the tumor areas and five showed PAI-1 positive cells in tumor-adjacent normal epithelium. By real-time RT-PCR analysis......A high level of plasminogen activator inhibitor-1 (PAI-1 or SERPINE1) in tumor extracts is a marker of a poor prognosis in human cancers, including oral carcinomas. However, the mechanisms responsible for the upregulation of PAI-1 in cancers remain unclear. Investigating specific PAI-1 expressing...

  7. Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma

    Science.gov (United States)

    Ghita, Mihaela Adriana; Voiculescu, Suzana; Rosca, Adrian E.; Moraru, Liliana; Greabu, Maria

    2016-01-01

    Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC. PMID:27578920

  8. Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Mihai Lupu

    2016-01-01

    Full Text Available Basal cell carcinoma (BCC is the world’s leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC.

  9. Differential transfection efficiency rates of the GM-CSF gene into human renal cell carcinoma lines by lipofection.

    Science.gov (United States)

    Hernández, A; Zöller, K; Enczmann, J; Ebert, T; Schmitz-Draeger, B; Ackermann, R; Wernet, P

    1997-01-01

    One of the major questions in any gene therapy approach is the selection of the appropriate vector system. Here, the optimization of a gene transfer protocol for renal cell carcinoma using lipofection as a nonviral gene transduction system was evaluated. To select the promoter which gives the highest expression, different plasmids which are able to express Escherichia coli beta-galactosidase gene as a reporter gene under the control of different promoters were tested: human cytomegalovirus promoter (pCMVbeta), simian virus 40 promoter (pSVbeta), adenovirus promoter (ADbeta), and herpes simplex virus thymidine kinase promoter (TKbeta). The pCMVbeta revealed the highest expression of the beta-gal gene in the renal cell carcinoma (RCC) lines. Thus this CMV promoter was selected for the expression of the granulocyte-macrophage colony stimulator factor (GM-CSF) gene. Three different lipids (LipofectAmine, LipofectAce, and Lipofectin) were compared for their transduction efficiency, and the optimal conditions for quantitatively high lipofection rates were established. The consistently best results regarding gene expression as well as viability of the RCC lines were obtained when Lipofectin was used. Gene expression was monitored by a specific enzyme-linked immunosorbent assay and functionally validated by a cell proliferation test. The GM-CSF expression profile showed a peak at 48 hours after transfection and was still detectable after 5 days. Here the feasibility of efficient lipofection of the GM-CSF gene into RCC lines is demonstrated. Most importantly, considerable differences in the relative quantity of GM-CSF gene transfer into the different RCC lines was observed here. This may be of critical relevance for the design of any clinical gene transduction protocol in tumor cell vaccination attempts.

  10. 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 ...

  11. The prognostic implications of growth-related gene product β in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Tang, Mingming; Xu, Xinjiang; Chen, Juanjuan; Huang, Jiangfei; Jiang, Bin; Han, Liang

    2017-09-01

    Growth-related gene product β (GROβ) is an angiogenic chemokine that belongs to the CXC chemokine family, and a number of studies have suggested that GROβ is associated with tumor development and progression. However, a number of studies have investigated the association between GROβ expression and the clinical attributes of laryngeal squamous cell carcinoma (LSCC). In the present study, one-step quantitative polymerase chain reaction and immunohistochemistry analysis were used to detect GROβ expression and evaluate the association between its expression and the clinicopathological characteristics of LSCC. The results demonstrated that the GROβ mRNA and protein expression levels were significantly increased in LSCC compared with the corresponding non-cancerous tissues. GROβ protein expression in LSCC was associated with tumor-node-metastasis stage, lymph node metastasis and histopathological grade. The Kaplan-Meier method and Cox multi-factor analysis indicated that high GROβ expression, lymph node metastasis and histopathological grade were significantly associated with poor survival of patients with LSCC. These data indicated that GROβ may be a novel prognostic biomarker of LSCC.

  12. Tyrosine kinase domain mutations of EGFR gene in head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Vatte C

    2017-03-01

    Full Text Available Chittibabu Vatte,1 Ali M Al Amri,2 Cyril Cyrus,1 Shahanas Chathoth,1 Sadananda Acharya,3 Tariq Mohammad Hashim,4 Zhara Al Ali,2 Saleh Tawfeeq Alshreadah,2 Ahmed Alsayyah,4 Amein K Al-Ali5 1Department of Genetic Research, Institute for Research and Medical Consultation, University of Dammam, Dammam, 2Department of Internal Medicine, King Fahd Hospital of the University, University of Dammam, Al-Khobar, 3Department of Stemcell Research, Institute for Research and Medical Consultation, 4Department of Pathology, King Fahd Hospital of the University, University of Dammam, Al-Khobar, 5Department of Biochemistry, College of Medicine, University of Dammam, Dammam, Kingdom of Saudi Arabia Background: Epidermal growth factor receptor (EGFR is a commonly altered gene that is identified in various cancers, including head and neck squamous cell carcinoma (HNSCC. Therefore, EGFR is a promising molecular marker targeted by monoclonal antibodies and small molecule inhibitors targeting the tyrosine kinase (TK domain. Objective: The objective of this study was to investigate the spectrum of mutations in exons 18, 19, 20, and 21 of the EGFR gene in HNSCC patients. Materials and methods: This retrospective study included 47 confirmed HNSCC cases. Mutations in the TK domain, exons 18, 19, 20, and 21 of the EGFR gene, were detected by Scorpion® chemistry and ARMS® technologies on Rotor-Gene Q real-time polymerase chain reaction.Results: The tumors exhibited EGFR-TK domain mutations in 57% of cases. Four cases of T790M mutations were reported for the first time among HNSCC patients. Out of the total mutations, L861Q (exon 21, exon 20 insertions and deletions of exon 19 accounted for the majority of mutations (21%, 19%, and 17%, respectively. EGFR mutation status was correlated with the higher grade (P=0.026 and advanced stage (P=0.034 of HNSCC tumors.Conclusion: Higher frequency of EGFR-TK domain mutations together with the presence of the T790M mutation suggests

  13. Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling.

    Science.gov (United States)

    Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute; Blake, Jonathon; Schwager, Christian; Ansorge, Wilhelm; Nielsen, John E; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

    2004-07-15

    Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly expressed in testicular CIS, including many never reported in testicular neoplasms. Expression was further verified by semiquantitative reverse transcription-PCR and in situ hybridization. Among the highest expressed genes were NANOG and POU5F1, and reverse transcription-PCR revealed possible changes in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported as unstable in cultured ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS. Moreover, the findings are consistent with an early prenatal origin of TGCTs and thus suggest that etiologic factors operating in utero are of primary importance for the incidence trends of TGCTs. Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs.

  14. Spatially Fractionated Radiation Induces Cytotoxicity and Changes in Gene Expression in Bystander and Radiation Adjacent Murine Carcinoma Cells

    Science.gov (United States)

    Asur, Rajalakshmi S.; Sharma, Sunil; Chang, Ching-Wei; Penagaricano, Jose; Kommuru, Indira M.; Moros, Eduardo G.; Corry, Peter M.; Griffin, Robert J.

    2012-01-01

    Radiation-induced bystander effects have been extensively studied at low doses, since evidence of bystander induced cell killing and other effects on unirradiated cells were found to be predominant at doses up to 0.5 Gy. Therefore, few studies have examined bystander effects induced by exposure to higher doses of radiation, such as spatially fractionated radiation (GRID) treatment. In the present study, we evaluate the ability of GRID treatment to induce changes in GRID adjacent (bystander) regions, in two different murine carcinoma cell lines following exposure to a single irradiation dose of 10 Gy. Murine SCK mammary carcinoma cells and SCCVII squamous carcinoma cells were irradiated using a brass collimator to create a GRID pattern of nine circular fields 12 mm in diameter with a center-to-center distance of 18 mm. Similar to the typical clinical implementation of GRID, this is approximately a 50:50 ratio of direct and bystander exposure. We also performed experiments by irradiating separate cultures and transferring the medium to unirradiated bystander cultures. Clonogenic survival was evaluated in both cell lines to determine the occurrence of radiation-induced bystander effects. For the purpose of our study, we have defined bystander cells as GRID adjacent cells that received approximately 1 Gy scatter dose or unirradiated cells receiving conditioned medium from irradiated cells. We observed significant bystander killing of cells adjacent to the GRID irradiated regions compared to sham treated controls. We also observed bystander killing of SCK and SCCVII cells cultured in conditioned medium obtained from cells irradiated with 10 Gy. Therefore, our results confirm the occurrence of bystander effects following exposure to a high-dose of radiation and suggest that cell-to-cell contact is not required for these effects. In addition, the gene expression profile for DNA damage and cellular stress response signaling in SCCVII cells after GRID exposure was studied

  15. Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma.

    Science.gov (United States)

    Sobrinho Santos, Eliane Macedo; Guimarães, Talita Antunes; Santos, Hércules Otacílio; Cangussu, Lilian Mendes Borborema; de Jesus, Sabrina Ferreira; Fraga, Carlos Alberto de Carvalho; Cardoso, Claudio Marcelo; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; Gomez, Ricardo Santiago; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

    2017-05-01

    Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma-induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.

  16. Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling

    Directory of Open Access Journals (Sweden)

    Hong-tao Song

    2014-01-01

    Full Text Available To investigate the role of AEG-1 in glycolysis and tumorigenesis, we construct myc-AEG-1 expression vector and demonstrate a novel mechanism that AEG-1 may increase the activity of AMPK by Thr172 phosphorylation. The higher expression levels of AEG-1 in colorectal carcinoma cells were found but showed significant difference in different cell lines. To study the role of AEG-1 in colorectal cells, myc-AEG-1 vector was constructed and transfected into NCM460 colonic epithelial cells. We observed consistent increasing of glucose consumption and lactate production, typical features of anaerobic glycolysis, suggesting that AEG-1 may promote anaerobic glycolysis. Moreover, we noted that AMPK phosphorylation at Thr172 as well as pPFK2 (Ser466 was increased in NCM460 cells overexpressing AEG-1. Compound C may block AMPK and PFK2 phosphorylation in both control and AEG-1-overexpressed cells and decrease the glucose consumption and lactate production. The present findings indicated that reduced AEG-1 protein levels by RNAi may decrease the glucose consumption and lactate production in HCT116 colorectal carcinoma cells. The present identified AEG-1/AMPK/PFK2 glycolysis cascade may be essential to cell proliferation and tumor growth. The present results may provide us with a mechanistic insight into novel targets controlled by AEG-1, and the components in the AEG-1/AMPK/PFK2 glycolysis process may be targeted for the clinical treatment of cancer.

  17. Methylation of 10 miRNA genes in clear cell renal cell carcinoma and their diagnostic value

    Directory of Open Access Journals (Sweden)

    V. I. Loginov

    2017-01-01

    Full Text Available Introduction. Clear cell renal cell carcinoma (ccRCC is characterized by the high (30–40 % of cases frequency of lethal outcomes which at metastasis reaches 90 %. Lack of efficient diagnostics at early stages of a disease indicates the need of searching on new ccRCC markers.Objective: for definition of methylation role of some tumor suppressor microRNA (miRNA genes in ccRCC pathogenesis and progression and marker identification for ccRCC diagnostics and metastasis predictions.Materials and methods. The alterations of methylation status of 10 miRNA genes were determined by methylation specific polymerase chain reaction in tumor DNA samples and matched histologically unchanged tissues from 70 patients with ccRCC, as well as in DNA samples of kidney tissues from 19 post-mortal individuals without cancer history. Methylation of MIR MIR-107, -130b and -148a genes in ccRCC was studied for the first time.Results. It was shown that 8 miRNA genes (MIR-9-1/3, -34b/c, -124a-1/2/3, -129-2, -130b were methylated in ccRCC tumors with significantly higher frequency than in the matched histologically unchanged kidney tissues. It was established the association of methylation of 4 miRNA genes (MIR-107, -124a-3, -129-2, -130b with ccRCC progression (stage, tumor size, differentiation grade, including metastasis in the lymph nodes or distant organs, revealed for MIR-107 and -129-2. The association of MIR-107 and -130b methylation with progression of ccRCC is shown for the first time. Potential marker systems are made for ccRCC diagnostics using tumor biopsy; according to the ROC analysis, systems from 4 and 5 genes (MIR-9-1, -4b/c, -124a-3, -129-2/with addition of MIR-130b are characterized by high clinical sensitivity of 90 % and specificity of 94 % (area under ROC curve 0.93 and 0.94. Conclusion. The received results will form the basis of noninvasive ccRCC diagnostics further development. To conclude, it is shown the association of methylation of 9

  18. High-resolution Melting Analysis for Gene Scanning of Adenomatous Polyposis Coli (APC) Gene With Oral Squamous Cell Carcinoma Samples.

    Science.gov (United States)

    Chang, Ya-Sian; Lin, Chien-Yu; Yang, Shu-Fen; Ho, Cheng Mao; Chang, Jan-Gowth

    2016-02-01

    There have been many different mutations reported for the large adenomatous polyposis coli (APC) tumor suppressor gene. APC mutations result in inactivation of APC tumor suppressor action, allowing the progression of tumorigenesis. The present study utilized a highly efficient method to identify APC mutations and investigated the association between the APC genetic variants Y486Y, A545A, T1493T, and D1822V and susceptibility to oral squamous cell carcinoma (OSCC). High-resolution melting (HRM) analysis was used to characterize APC mutations. Genomic DNA was extracted from 83 patient specimens of OSCC and 50 blood samples from healthy control subjects. The 14 exons and mutation cluster region of exon 15 were screened by HRM analysis. All mutations were confirmed by direct DNA sequencing. Three mutations and 4 single nucleotide polymorphisms (SNPs) were found in this study. The mutations were c.573T>C (Y191Y) in exon 5, c.1005A>G (L335L) in exon 9, and c.1488A>T (T496T) in exon 11. Two SNPs, c.4479G>A (T1493T) and c.5465A>T (D1822V), were located in exon 15, whereas c.1458T>C (Y486Y) and c.1635G>A (A545A) were located in exon 11 and 13, respectively. There was no observed association between OSCC risk and genotype for any of the 4 APC SNPs. The mutation of APC is rare in Taiwanese patients with OSCC. HRM analysis is a reliable, accurate, and fast screening method for APC mutations.

  19. Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa

    DEFF Research Database (Denmark)

    Gao, Shan; Nielsen, Boye Schnack; Krogdahl, Annelise

    2010-01-01

    , 17 of 20 patients with oral carcinoma were found to have between 2.5- and 50-fold increased tumor PAI-1 mRNA level, as compared with the matched tumor-adjacent normal tissues. The PAI-1 mRNA level in connective tissues from 15 healthy volunteers was similar to the level in tumor-adjacent normal...... tissues, but the level in epithelium was 5- to 10-fold lower. Analyzing DNA methylation of 25 CpG sites within 960 bp around the transcription initiation site of the SERPINE1 gene by bisulfite sequencing, we did the surprising observation that both tumors and tumor-adjacent normal tissue had a significant...... level of methylation, whereas there was very little methylation in tissue from healthy volunteers, suggesting that tumor-adjacent normal tissue already contains transformation-associated epigenetic changes. However, there was no general inverse correlation between PAI-1 mRNA levels and SERPINE1 gene...

  20. Mitochondrial damage and cholesterol storage in human hepatocellular carcinoma cells with silencing of UBIAD1 gene expression

    Directory of Open Access Journals (Sweden)

    Carlos R. Morales

    2014-01-01

    Full Text Available Heterozygous mutations in the UBIAD1 gene cause Schnyder corneal dystrophy characterized by abnormal cholesterol and phospholipid deposits in the cornea. Ubiad1 protein was recently identified as Golgi prenyltransferase responsible for biosynthesis of vitamin K2 and CoQ10, a key protein in the mitochondrial electron transport chain. Our study shows that silencing UBIAD1 in cultured human hepatocellular carcinoma cells causes dramatic morphological changes and cholesterol storage in the mitochondria, emphasizing an important role of UBIAD1 in mitochondrial function.

  1. Identification of Differentially Expressed Genes Induced by Aberrant Methylation in Oral Squamous Cell Carcinomas Using Integrated Bioinformatic Analysis

    Directory of Open Access Journals (Sweden)

    Xiaoqi Zhang

    2018-06-01

    Full Text Available Oral squamous cell carcinoma (OSCC is a malignant disease. Methylation plays a key role in the etiology and pathogenesis of OSCC. The goal of this study was to identify aberrantly methylated differentially expressed genes (DEGs in OSCCs, and to explore the underlying mechanisms of tumorigenesis by using integrated bioinformatic analysis. Gene expression profiles (GSE30784 and GSE38532 were analyzed using the R software to obtain aberrantly methylated DEGs. Functional enrichment analysis of screened genes was performed using the DAVID software. Protein–protein interaction (PPI networks were constructed using the STRING database. The cBioPortal software was used to exhibit the alterations of genes. Lastly, we validated the results with the Cancer Genome Atlas (TCGA data. Twenty-eight upregulated hypomethylated genes and 24 downregulated hypermethylated genes were identified. These genes were enriched in the biological process of regulation in immune response, and were mainly involved in the PI3K-AKT and EMT pathways. Additionally, three upregulated hypomethylated oncogenes and four downregulated hypermethylated tumor suppressor genes (TSGs were identified. In conclusion, our study indicated possible aberrantly methylated DEGs and pathways in OSCCs, which could improve the understanding of the underlying molecular mechanisms. Aberrantly methylated oncogenes and TSGs may also serve as biomarkers and therapeutic targets for the precise diagnosis and treatment of OSCCs in the future.

  2. Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review.

    Science.gov (United States)

    Kim, Bum Jun; Kim, Jung Han; Kim, Hyeong Su; Zang, Dae Young

    2017-02-21

    The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: 'kidney or renal', 'carcinoma or cancer or neoplasm or malignancy', 'von Hippel-Lindau or VHL', 'alteration or mutation or methylation', and 'prognostic or predictive'. There were six studies fulfilling inclusion criteria and a total of 633 patients with clear cell RCC were included in the study: 244 patients who received anti-vascular endothelial growth factor (VEGF) therapy in the predictive value analysis and 419 in the prognostic value analysis. Out of 663 patients, 410 (61.8%) had VHL alteration. The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy. There was also no correlation between the VHL alteration and overall survival (HR = 0.80 [95% CI, 0.56-1.14], P = 0.21). In conclusion, this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell RCC.

  3. Giant basal cell carcinoma Carcinoma basocelular gigante

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    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.

  4. Promoter hypermethylation of DNA repair genes MLH1 and MSH2 in adenocarcinomas and squamous cell carcinomas of the lung

    Directory of Open Access Journals (Sweden)

    A. Gomes

    2014-01-01

    Full Text Available Five years survival of lung cancer is 16%, significantly lower than in prostate (99.9%, breast (88.5% and colon (64.1% carcinomas. When diagnosed in the surgical stage it increases to 50% but this group only comprises 14–16% of the cases. DNA methylation has emerged as a potential cancer-specific biomarker. Hypermethylation of CpG islands located in the promoter regions of tumour suppressor genes is now firmly established as an important mechanism for gene inactivation.This retrospective study included 40 squamous cell carcinomas and 40 adenocarcinomas in various surgical TNM stages to define methylation profile and possible silencing of DNA repair genes – MLH1 and MSH2 – using Methylation-Specific PCR and protein expression by immunohistochemistry in tumoural tissue, preneoplastic lesions and respiratory epithelium with normal histological features.The protein expression of MLH1 and MSH2 genes, in the available preneoplastic lesions and in normal cylindrical respiratory epithelium appeared reduced. The frequency of promoter hypermethylation found on these DNA repair genes was elevated, with a higher prevalence of methylation of MLH1 gene in 72% of squamous cell carcinoma. The differences are not so obvious for MSH2 promoter hypermethylation. No correlation was found among the status of methylation, the protein expression and the clinicopathological characteristics.With a larger study, a better characterization of the hypermethylation status of neoplastic and preneoplastic lesions in small biopsies would be achieved, inherent to tumour histology, heterogeneity and preservation, and finally differences in the study population to elucidate other possible mechanisms of altered expression of the hMLH1 and hMSH. Resumo: A sobrevivência aos cinco anos no cancro do pulmão é de 16%, significativamente inferior que nos carcinomas na próstata (99,9%, mama (88,5% e cólon (64,1%. Quando diagnosticado na fase cir

  5. Depletion of Pokemon gene inhibits hepatocellular carcinoma cell growth through inhibition of H-ras.

    Science.gov (United States)

    Zhang, Quan-Le; Tian, De-An; Xu, Xiang-Jiang

    2011-01-01

    Pokemon is a transcription repressor which plays a critical role in cell transformation and malignancy. However, little is known about its effect on the development and progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression of Pokemon in human HCC tissues and the biological behavior of Pokemon in HCC cells in which it is overexpressed. We also explored the expression of potential downstream cofactors of Pokemon. Reverse transcription polymerase chain reaction and Western blot analysis were used to investigate the expression of Pokemon in tissues of 30 HCC patients. We then examined cell proliferation or apoptosis and β-catenin or H-ras expression in Pokemon-depleted HepG(2) cells using DNA vector-based RNA interference technology. Pokemon was markedly expressed in 22/30 (73.3%) HCC tissues, with expression levels higher than in adjacent normal liver tissues (p Pokemon inhibited proliferation of HepG(2) or induced apoptosis. Also, H-ras expression decreased to a large extent. Pokemon exerts its oncogenic activity in the development of HCC by promoting cancer cell growth and reducing apoptosis, and the effect may be mediated by H-ras. Copyright © 2011 S. Karger AG, Basel.

  6. Inhibition of human esophageal squamous cell carcinomas by targeted silencing of tumor enhancer genes: an overview

    International Nuclear Information System (INIS)

    Islamian, Jalil Pirayesh; Mohammadi, Mohsen; Baradaran, Behzad

    2014-01-01

    Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy. Novel strategies are needed to boost the oncologic outcome. Recent advances in the molecular biology of esophageal cancer have documented the role of genetic alterations in tumorigenesis. Oncogenes serve a pivotal function in tumorigenesis. Targeted therapies are directed at the unique molecular signature of cancer cells for enhanced efficacy with low toxicity. RNA interference (RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Related results have shown that targeting oncogenes with siRNAs, specifically the mRNA, effectively reduces tumor cell proliferation and induces apoptotic cell death. This article will briefly review studies on silencing tumor enhancer genes related to the induction of esophageal cancer

  7. Gene expression profiling in circulating cells (ctcs) of breast carcinoma patients

    Czech Academy of Sciences Publication Activity Database

    Kološtová, K.; Pinterová, D.; Tesařová, P.; Mikulová, V.; Kubecová, M.; Brychta, M.; Rusňáková, Vendula; Kasimir-Bauer, S.; Kubista, Mikael

    2010-01-01

    Roč. 21, suppl. 4 (2010), s. 49-59 ISSN 0923-7534 Institutional research plan: CEZ:AV0Z50520701 Keywords : Circulating tumor cells * Breast cancer * Gene expression profiling Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.452, year: 2010

  8. Amplification of epidermal growth factor receptor gene in renal cell carcinoma

    DEFF Research Database (Denmark)

    El-Hariry, Iman; Powles, Thomas; Lau, Mike R

    2010-01-01

    Expression of epidermal growth factor receptor (EGFR) may be of prognostic value in renal cell cancer (RCC). Gene amplification of EGFR was investigated in a cohort of 315 patients with advanced RCC from a previously reported randomised study. Using fluorescent in situ hybridisation, only 2...

  9. 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.

  10. Network analysis of genes involved in the enhancement of hyperthermia sensitivity by the knockdown of BAG3 in human oral squamous cell carcinoma cells.

    Science.gov (United States)

    Yunoki, Tatsuya; Tabuchi, Yoshiaki; Hayashi, Atsushi; Kondo, Takashi

    2016-07-01

    BCL2-associated athanogene 3 (BAG3), a co-chaperone of the heat shock 70 kDa protein (HSPA) family of proteins, is a cytoprotective protein that acts against various stresses, including heat stress. The aim of the present study was to identify gene networks involved in the enhancement of hyperthermia (HT) sensitivity by the knockdown (KD) of BAG3 in human oral squamous cell carcinoma (OSCC) cells. Although a marked elevation in the protein expression of BAG3 was detected in human the OSCC HSC-3 cells exposed to HT at 44˚C for 90 min, its expression was almost completely suppressed in the cells transfected with small interfering RNA against BAG3 (siBAG) under normal and HT conditions. The silencing of BAG3 also enhanced the cell death that was increased in the HSC-3 cells by exposure to HT. Global gene expression analysis revealed many genes that were differentially expressed by >2-fold in the cells exposed to HT and transfected with siBAG. Moreover, Ingenuity® pathways analysis demonstrated two unique gene networks, designated as Pro-cell death and Anti-cell death, which were obtained from upregulated genes and were mainly associated with the biological functions of induction and the prevention of cell death, respectively. Of note, the expression levels of genes in the Pro-cell death and Anti-cell death gene networks were significantly elevated and reduced in the HT + BAG3-KD group compared to those in the HT control group, respectively. These results provide further insight into the molecular mechanisms involved in the enhancement of HT sensitivity by the silencing of BAG3 in human OSCC cells.

  11. A comparative Analysis by SAGE of Gene Expression Profiles of Esophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Jantine W. P. M. van Baal

    2008-01-01

    Full Text Available Esophageal adenocarcinoma (EA and esophageal squamous cell carcinoma (ESCC are the two main types of esophageal cancer. Despite extensive research the exact molecular basis of these cancers is unclear. Therefore we evaluated the transcriptome of EA in comparison to non-dysplastic Barrett’s esophagus (BE, the metaplastic epithelium that predisposes for EA, and compared the transcriptome of ESCC to normal esophageal squamous epithelium. For obtaining the transcriptomes tissue biopsies were used and serial analysis of gene expression (SAGE was applied. Validation of results by RT-PCR and immunoblotting was performed using tissues of an additional 23 EA and ESCC patients. Over 58,000 tags were sequenced. Between EA and BE 1013, and between ESCC and normal squamous epithelium 1235 tags were significantly differentially expressed (p < 0.05. The most up-regulated genes in EA compared to BE were SRY-box 4 and Lipocalin2, whereas the most down-regulated genes in EA were Trefoil factors and Annexin A10. The most up-regulated genes in ESCC compared to normal squamous epithelium were BMP4, E-Cadherin and TFF3. The results could suggest that the BE expression profile is closer related to normal squamous esophagus then to EA. In addition, several uniquely expressed genes are identified.

  12. [Adenovirus-mediated delivery of nm23-H1 gene inhibits growth of colorectal carcinoma cell line Lovo].

    Science.gov (United States)

    Wang, Qi; He, Xueling; Liu, Yan; Yin, Hailin

    2010-12-01

    This experimental study sought to find out the inhibitory effects of Ad-GFP-nm23-H1 on proliferation and metastasis of human colorectal carcinoma cell line Lovo, and, further, to gain an insight into some theoretical and methodical basis for instituting nm23-H1 gene therapy of cancers. MTT assay and Transwell chamber were used to detect the rates of proliferation and invasion as well as the adhesion of Lovo cells in vitro. The results demonstrated that the proliferation inhibition rates of Lovo cells treated with Ad-GFP-nm23-H1 of 10(10) PFU/ml, 10(9) PFU/ml and 10(8) PFU/ml were 84.9% +/- 1.51%, 48.5% +/- 7.23% and 22.5% +/- 5.47%, that the adherence inhibition rates of Lovo cells treated with Ad-GFP-nm23-H1 of 10(10) PFU/ml, 10(9) PFU/ml and 10(8) PFU/ml were 70.3% +/- 2.40%, 60.1% +/- 5.68% and 18.5% +/- 3.61%, and that the invasiveness inhibition rates of Lovo cells treated with Ad-GFP-nm23-H1 of 10(10) PFU/ml, 10(9) PFU/ml and 10(8) PFU/ml were 83.2% +/- 5.71%, 52.2% +/- 6.94% and 28.1% +/- 8.21%. These data suggested that Ad-GFP-nm23-H1 exerted significant inhibitory effects on the proliferation and metastasis of human colorectal carcinoma cell line Lovo in a dose-dependent way.

  13. Gene expression profiling analysis of CRTC1-MAML2 fusion oncogene-induced transcriptional program in human mucoepidermoid carcinoma cells

    International Nuclear Information System (INIS)

    Chen, Jie; Li, Jian-Liang; Chen, Zirong; Griffin, James D.; Wu, Lizi

    2015-01-01

    Mucoepidermoid carcinoma (MEC) arises from multiple organs and accounts for the most common types of salivary gland malignancies. Currently, patients with unresectable and metastatic MEC have poor long-term clinical outcomes and no targeted therapies are available. The majority of MEC tumors contain a t(11;19) chromosomal translocation that fuses two genes, CRTC1 and MAML2, to generate the chimeric protein CRTC1-MAML2. CRTC1-MAML2 displays transforming activity in vitro and is required for human MEC cell growth and survival, partially due to its ability to constitutively activate CREB-mediated transcription. Consequently, CRTC1-MAML2 is implicated as a major etiologic molecular event and a therapeutic target for MEC. However, the molecular mechanisms underlying CRTC1-MAML2 oncogenic action in MEC have not yet been systematically analyzed. Elucidation of the CRTC1-MAML2-regulated transcriptional program and its underlying mechanisms will provide important insights into MEC pathogenesis that are essential for the development of targeted therapeutics. Transcriptional profiling was performed on human MEC cells with the depletion of endogenous CRTC1-MAML2 fusion or its interacting partner CREB via shRNA-mediated gene knockdown. A subset of target genes was validated via real-time RT-PCR assays. CRTC1-MAML2-perturbed molecular pathways in MEC were identified through pathway analyses. Finally, comparative analysis of CRTC1-MAML2-regulated and CREB-regulated transcriptional profiles was carried out to assess the contribution of CREB in mediating CRTC1-MAML2-induced transcription. A total of 808 differentially expressed genes were identified in human MEC cells after CRTC1-MAML2 knockdown and a subset of known and novel fusion target genes was confirmed by real-time RT-PCR. Pathway Analysis revealed that CRTC1-MAML2-regulated genes were associated with network functions that are important for cell growth, proliferation, survival, migration, and metabolism. Comparison of CRTC

  14. Development and confirmation of potential gene classifiers of human clear cell renal cell carcinoma using next-generation RNA sequencing.

    Science.gov (United States)

    Eikrem, Oystein S; Strauss, Philipp; Beisland, Christian; Scherer, Andreas; Landolt, Lea; Flatberg, Arnar; Leh, Sabine; Beisvag, Vidar; Skogstrand, Trude; Hjelle, Karin; Shresta, Anjana; Marti, Hans-Peter

    2016-12-01

    A previous study by this group demonstrated the feasibility of RNA sequencing (RNAseq) technology for capturing disease biology of clear cell renal cell carcinoma (ccRCC), and presented initial results for carbonic anhydrase-9 (CA9) and tumor necrosis factor-α-induced protein-6 (TNFAIP6) as possible biomarkers of ccRCC (discovery set) [Eikrem et al. PLoS One 2016;11:e0149743]. To confirm these results, the previous study is expanded, and RNAseq data from additional matched ccRCC and normal renal biopsies are analyzed (confirmation set). Two core biopsies from patients (n = 12) undergoing partial or full nephrectomy were obtained with a 16 g needle. RNA sequencing libraries were generated with the Illumina TruSeq ® Access library preparation protocol. Comparative analysis was done using linear modeling (voom/Limma; R Bioconductor). The formalin-fixed and paraffin-embedded discovery and confirmation data yielded 8957 and 11,047 detected transcripts, respectively. The two data sets shared 1193 of differentially expressed genes with each other. The average expression and the log 2 -fold changes of differentially expressed transcripts in both data sets correlated, with R²   =   .95 and R²   =   .94, respectively. Among transcripts with the highest fold changes were CA9, neuronal pentraxin-2 and uromodulin. Epithelial-mesenchymal transition was highlighted by differential expression of, for example, transforming growth factor-β 1 and delta-like ligand-4. The diagnostic accuracy of CA9 was 100% and 93.9% when using the discovery set as the training set and the confirmation data as the test set, and vice versa, respectively. These data further support TNFAIP6 as a novel biomarker of ccRCC. TNFAIP6 had combined accuracy of 98.5% in the two data sets. This study provides confirmatory data on the potential use of CA9 and TNFAIP6 as biomarkers of ccRCC. Thus, next-generation sequencing expands the clinical application of tissue analyses.

  15. Bilateral papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

    2001-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

  16. Stages of Merkel Cell Carcinoma

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key ...

  17. 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.

  18. Down-regulation of SMT3A gene expression in association with DNA synthesis induction after X-ray irradiation in nevoid basal cell carcinoma syndrome (NBCCS) cells

    International Nuclear Information System (INIS)

    Sugaya, Shigeru; Nakanishi, Hiroshi; Tanzawa, Hideki; Sugita, Katsuo; Kita, Kazuko; Suzuki, Nobuo

    2005-01-01

    Fibroblast cells derived from nevoid basal carcinoma syndrome (NBCCS) patients show increased levels of DNA synthesis after X-ray irradiation. Genes, whose expression is modulated in association with the DNA synthesis induction, were searched by using PCR-based mRNA differential display analysis in one of the NBCCS cell lines, NBCCS1 cells. Decreased levels of SMT3A gene expression were found in X-ray-irradiated NBCCS1 cells. This decrease was also shown by RT-PCR analysis in another cell line, NBCCS3 cells. In addition to NBCCS cells, normal fibroblast cells showed the DNA synthesis induction after X-ray irradiation when they were treated with antisense oligonucleotides (AO) for SMT3A. However, treatment of normal fibroblasts with the random oligonucleotides (RO) resulted in decreased levels of DNA synthesis after X-ray irradiation. Thus, down-regulation of SMT3A gene expression may be involved in the DNA synthesis induction after X-ray irradiation in the NBCCS cells at least tested

  19. Down-regulation of SMT3A gene expression in association with DNA synthesis induction after X-ray irradiation in nevoid basal cell carcinoma syndrome (NBCCS) cells

    Energy Technology Data Exchange (ETDEWEB)

    Sugaya, Shigeru [Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Nakanishi, Hiroshi [Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Tanzawa, Hideki [Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Sugita, Katsuo [Department of Clinical Medicine, Faculty of Education, Chiba University, 1-33 Yayoi, Inage-ku, Chiba 263-8522 (Japan); Kita, Kazuko [Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Suzuki, Nobuo [Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan)]. E-mail: nobuo@faculty.chiba-u.jp

    2005-10-15

    Fibroblast cells derived from nevoid basal carcinoma syndrome (NBCCS) patients show increased levels of DNA synthesis after X-ray irradiation. Genes, whose expression is modulated in association with the DNA synthesis induction, were searched by using PCR-based mRNA differential display analysis in one of the NBCCS cell lines, NBCCS1 cells. Decreased levels of SMT3A gene expression were found in X-ray-irradiated NBCCS1 cells. This decrease was also shown by RT-PCR analysis in another cell line, NBCCS3 cells. In addition to NBCCS cells, normal fibroblast cells showed the DNA synthesis induction after X-ray irradiation when they were treated with antisense oligonucleotides (AO) for SMT3A. However, treatment of normal fibroblasts with the random oligonucleotides (RO) resulted in decreased levels of DNA synthesis after X-ray irradiation. Thus, down-regulation of SMT3A gene expression may be involved in the DNA synthesis induction after X-ray irradiation in the NBCCS cells at least tested.

  20. Core I gene is overexpressed in Hürthle and non-Hürthle cell microfollicular adenomas and follicular carcinomas of the thyroid

    International Nuclear Information System (INIS)

    Máximo, Valdemar; Preto, Ana; Crespo, Ana; Rocha, Ana Sofia; Machado, José Carlos; Soares, Paula; Sobrinho-Simões, Manuel

    2004-01-01

    Most of the steps involved in the initiation and progression of Hürthle (oncocytic, oxyphilic) cell carcinomas of the thyroid remain unknown. Using differential display and semiquantitative RT-PCR we found, among other alterations, overexpression of the gene encoding the Core I subunit of the complex III of the mitochondrial respiratory chain in a follicular carcinoma composed of Hürthle cells. Similar high levels of Core I gene expression were detected in nine follicular carcinomas (seven with Hürthle cell features), in seven microfollicular adenomas (one with Hürthle cell features) and in one micro/macrofollicular adenoma, in contrast to a lower/normal expression in nine papillary carcinomas (three with Hürthle cell features) and five macrofollicular adenomas (one of which displaying Hürthle cell features). No significative correlation was found between Core I overexpression and the proliferative activity of the lesions. We conclude that Core I overexpression in thyroid tumours is not associated with malignancy, Hürthle cells or proliferative activity. The pathogenetic mechanism linking Core I overexpression to the microfollicular pattern of growth of thyroid tumours remains to be clarified

  1. [Influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin].

    Science.gov (United States)

    Shen, Congxiang; Liu, Yanhui; Wen, Zhong; Yang, Keke; Li, Guanxue; Zhang, Shenhua; Zhang, Xinyu

    2015-06-23

    To explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin. Transfected nasopharyngeal carcinoma 5-8F cell lines with pCDH-CMV-PinX1-copGFP vector constructed by lentivirus to generate Lenti-PinX1-5-8F cells containing PinX1 gene, using Lenti-Ctrl-5-8F cell (blank vector without PinX1 gene was used to transfect 5-8F cell lines) and 5-8F cell as controls. Expression of PinX1 gene, telomerase activity, the inhibition of cancer cells proliferation, combined anticancer effect with Cisplatin and the expression of lung resistance protein (LRP) and Bcl-2 were detected with fluorescent quantitation polymerase chain reaction (PCR), flow cytometry, thiazolyl blue (MTT) method, areole test, Western blot and drug sensitivity test, respectively, in four groups (Lenti-PinX1-5-8F cell + Cisplatin, Lenti-PinX1-5-8F cell, Cisplatin and 5-8F cell) so as to explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin. The telomerase activity in Lenti-PinX1-5-8F cell (0.146 ± 0.004) was lower than those in the other two control cells (Lenti-Ctrl-5-8F cell: 0.967 ± 0.016, 5-8F cell: 1.000 ± 0.034, both P Cisplatin after lower level telomerase activity induced by PinX1 gene. Proliferation index (PI) (%) in Lenti-PinX1-5-8F cell + Cisplatin (14.39 ± 3.66) was also less than the other groups (Lenti-PinX1-5-8F cell, Cisplatin and 5-8F cell groups, 32.97 ± 3.00, 31.18 ± 4.24 and 47.19 ± 4.19, all P Cisplatin, which may be mediated by the down-regulation of telomerase activity and the inhibition of LRP and Bcl-2 gene in nasopharyngeal carcinoma cells.

  2. Intraosseous acinic cell carcinoma

    African Journals Online (AJOL)

    2011-12-17

    Dec 17, 2011 ... Salivary gland tumors are also known to develop within jaw bones, arising within the jaw as a ... Treatment of acinic cell carcinoma in most cases is surgical. High recurrence rates ... Panoramic radiograph [Figure 3] showed a ...

  3. Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Nicolai Skovbjerg Arildsen

    2017-05-01

    Full Text Available ObjectiveOvarian clear cell carcinomas (OCCCs constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30–50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes. Increased knowledge of OCCC-specific genetic aberrations may help in guiding development of targeted treatments and ultimately improve patient outcome.MethodsGene expression profiling of formalin-fixed, paraffin-embedded (FFPE tissue from a cohort of the major ovarian cancer subtypes (cohort 1; n = 67 was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL bead arrays, followed by pathway, gene module score, and gene ontology analyses, respectively. A second FFPE cohort of 10 primary OCCCs was analyzed by targeted DNA sequencing of a panel of 60 cancer-related genes (cohort 2. Non-synonymous and non-sense variants affecting single-nucleotide variations and insertions or deletions were further analyzed. A tissue microarray of 43 OCCCs (cohort 3 was used for validation by immunohistochemistry and chromogenic in situ hybridization.ResultsGene expression analyses revealed a distinct OCCC profile compared to other histological subtypes, with, e.g., ERBB2, TFAP2A, and genes related to cytoskeletal actin regulation being overexpressed in OCCC. ERBB2 was, however, not overexpressed on the protein level and ERBB2 amplification was rare in the validation cohort. Targeted deep sequencing revealed non-synonymous variants or insertions/deletions in 11/60 cancer-related genes. Genes involved in chromatin remodeling, including ARID1A, SPOP, and KMT2D were frequently mutated across OCCC tumors.ConclusionOCCCs appear

  4. Exome sequencing of oral squamous cell carcinoma in users of Arabian snuff reveals novel candidates for driver genes.

    Science.gov (United States)

    Al-Hebshi, Nezar Noor; Li, Shiyong; Nasher, Akram Thabet; El-Setouhy, Maged; Alsanosi, Rashad; Blancato, Jan; Loffredo, Christopher

    2016-07-15

    The study sought to identify genetic aberrations driving oral squamous cell carcinoma (OSCC) development among users of shammah, an Arabian preparation of smokeless tobacco. Twenty archival OSCC samples, 15 of which with a history of shammah exposure, were whole-exome sequenced at an average depth of 127×. Somatic mutations were identified using a novel, matched controls-independent filtration algorithm. CODEX and Exomedepth coupled with a novel, Database of Genomic Variant-based filter were employed to call somatic gene-copy number variations. Significantly mutated genes were identified with Oncodrive FM and the Youn and Simon's method. Candidate driver genes were nominated based on Gene Set Enrichment Analysis. The observed mutational spectrum was similar to that reported by the TCGA project. In addition to confirming known genes of OSCC (TP53, CDKNA2, CASP8, PIK3CA, HRAS, FAT1, TP63, CCND1 and FADD) the analysis identified several candidate novel driver events including mutations of NOTCH3, CSMD3, CRB1, CLTCL1, OSMR and TRPM2, amplification of the proto-oncogenes FOSL1, RELA, TRAF6, MDM2, FRS2 and BAG1, and deletion of the recently described tumor suppressor SMARCC1. Analysis also revealed significantly altered pathways not previously implicated in OSCC including Oncostatin-M signalling pathway, AP-1 and C-MYB transcription networks and endocytosis. There was a trend for higher number of mutations, amplifications and driver events in samples with history of shammah exposure particularly those that tested EBV positive, suggesting an interaction between tobacco exposure and EBV. The work provides further evidence for the genetic heterogeneity of oral cancer and suggests shammah-associated OSCC is characterized by extensive amplification of oncogenes. © 2016 UICC.

  5. Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing.

    Directory of Open Access Journals (Sweden)

    Satoshi Iizuka

    Full Text Available Head and neck squamous cell carcinoma (HNSCC exhibits increased expression of cyclin D1 (CCND1. Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial small guide RNA (sgRNA. In this study, we designed several sgRNAs targeting human cyclin D1 mRNA to examine growth inhibition of HNSCC cells. Transfection of certain sgRNAs decreased levels of cyclin D1 mRNA and protein in HSC-2 and HSC-3 cells, and also inhibited their proliferation. The combination of these sgRNAs and cisplatin showed more than additive inhibition of cancer cell growth. These findings demonstrate that TRUE gene silencing of cyclin D1 leads to inhibition of the growth of HNSCC cells and suggest that these sgRNAs alone or combined with cisplatin may be a useful new therapy for HNSCCs.

  6. The gene expression profiles of canine mammary cancer cells grown with carcinoma-associated fibroblasts (CAFs as a co-culture in vitro

    Directory of Open Access Journals (Sweden)

    Król Magdalena

    2012-03-01

    Full Text Available Abstract Background It is supposed that fibroblasts present in tumour microenvironment increase cancer invasiveness and its ability to metastasize but the mechanisms have not been clearly defined yet. Thus, the current study was designed to assess changes in gene expression in five various cancer cell lines grown as a co-culture with the carcinoma-associated fibroblasts (CAFs in vitro. Results A carcinoma-associated fibroblast cell line was isolated from a canine mammary cancer. Then, a co-culture of cancer cells with the CAFs was established and maintained for 72 hrs. Having sorted the cells, a global gene expression in cancer cells using DNA microarrays was examined. The analysis revealed an up-regulation of 100 genes and a down-regulation of 106 genes in the cancer cells grown as a co-culture with the CAFs in comparison to control conditions. The PANTHER binomial statistics tool was applied to determine statistically over-manifested pathways (p Conclusion The results of the current study showed that the co-culturing of cancer cells and the CAFs caused significant changes to the cancer gene expression. The presence of the CAFs in a microenvironment of cancer cells promotes adhesion, angiogenesis and EMT.

  7. Evaluation of EGFR, KRAS and BRAF gene mutations in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Omer Bayrak

    2014-08-01

    Full Text Available A subset of renal cell carcinoma (RCC patients has been shown to respond to anti-EGFR therapy. As KRAS and BRAF mutations are associated with poor response to anti-EGFR therapy in some cancers, it has been suggested that screening for KRAS and BRAF mutations in RCC may be a promising strategy to identify patients who might respond to EGFR-targeted therapy. The aim of this study was to investigate the mutation status of EGFR, KRAS and BRAF in RCC patients. Renal tumors and normal renal samples from forty-eight patients who underwent radical or partial nephrectomy for kidney cancer were used in this study. Histological classification of the tumors was performed according to International Union against Cancer (UICC / American Joint Committee on Cancer (AJCC classification. Seventeen patients (48% had clear-cell RCC, 7 (20% had chromophobe RCC, and 11 patients (32% had papillary RCC. DNA isolated from the samples was subjected to melting curve mutation analysis for EGFR, BRAF and KRAS using ABI-3130 DNA sequencer. DNA sequencing analysis of RCC samples, when compared with morphologically normal matched regions, did not show any exon mutations. Our results do not support the notion that EGFR, KRAS and BRAF might be mutated in RCC. Normal 0 false false false TR X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0cm; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-ansi-language:TR; mso-fareast-language:EN-US;}

  8. Effect of the p53 gene status on the sensitivity of oral squamous cell carcinoma cells to boron neutron capture therapy

    International Nuclear Information System (INIS)

    Fujita, Y.; Kamida, A.; Kato, I.; Yura, Y.; Ono, K.; Suzuki, M.; Sakurai, Y.; Ohnishi, T.; Ohnishi, K.

    2006-01-01

    The role of the p53 gene in the sensitivity of oral squamous cell carcinoma (SCC) to boron neutron capture therapy (BNCT) had not been studied. We examined the effect of boronophenylalanine (BPA)-mediated BNCT on oral SCC cells showing either wild-type p53 (SAS/neo) or mutated-type p53 (SAS/mp53). Survival ratio of cells was determined by colony formation. Cell viability was measured by MTT assay. Apoptotic cells were evaluated by flow cytometric analysis and nuclear DNA staining. When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo cells as compared with SAS/mp53. The proportion of apoptotic cells with DNA fragmentation was also increased in the cells with functional p53. These results suggest that oral SCC cells with mutated p53 cells are more resistant to BNCT than those with wild-type p53. BNCT must inhibit oral SCC cells in p53-dependent and p53-independent mechanisms. (author)

  9. Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

    DEFF Research Database (Denmark)

    Salonen, Jonna; Rajpert-De Meyts, E; Mannisto, Susanna

    2010-01-01

    Testicular germ cell cancer is the most common malignancy among young males. The pre-invasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular deve...... development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms....

  10. Combination therapy and evaluation of therapeutic effect in hepatocellular carcinoma cell using triple reporter genes; containing for NIS, HSV1-sr39tk and GFP

    Energy Technology Data Exchange (ETDEWEB)

    Lee, You La; Lee, Yong Jin; Ahn, Sohn Joo; Ahn, Byeong Cheol; Lee, Sang Woo; Yoo, Jeong Soo; Lee, Jae Tae [Kyungpook National University, Daegu (Korea, Republic of)

    2007-07-01

    To identify therapeutic effect after combine Sodium Iodine Symporter (NIS) and Mutant Herpes-simplex virus type 1 sr39tk (HSV1-sr39tk) expression in hepatocellular carcinoma cell, we transfected triple gene and investigated the properties of these gene ability in hepatocellular carcinoma cell line. After making vector with gene encoding a fusion protein comprised of HSV1-sr39tk and green florescence protein (GFP), to make triple reporter genes NIS gene was further fused to the vector using IRES vector. The vector expressing triple reporter gene was transfected to the Huh-7 cell line using liposome. Functions of hNIS and HSV1-sr39tk expression were confirmed by radio iodine uptake with and without perchlorate and [3H]-penciclovir (3-H PCV) uptake, respectively. To evaluate therapeutic effect in vitro, GCV and I-131 was treated in Huh-7/NTG cell and dual therapy performed. An animal imaging acquired using Optix and microPET in vivo. I-125 uptake was increased up to 100-fold compare to that of non-transfected cells. The transfected cell accumulated H-3 PCV up to 53 times higher at 2 hour than that of non-transfected cells. With fluorescence microscopy, green fluorescence was detected in the transfected cell. In cytotoxic studies, the cell viability of Huh-7/NTG cell was decreased to 41 % of control cell at 10ug/ml GCV concentrations. The survival rate of the Huh-7/NTG cell treated with I-131 decreased up to 16%. In I-131 and GCV dual therapy, Huh-7/NTG cell survival rate decreased up to 4%. In animal studies, Huh-7/NTG tumors showed higher uptake of 18F-FHBG and I-124 than Huh-7 tumors. GFP signal is also higher in Huh-7/NTG tumor than control. We successfully constructed a vector with delivery two therapeutic genes and one reporter gene and transfected the vector to a Huh-7 cell. The hepatocellular carcinoma cell transfected with the vector can be treated with GCV and I-131. The effect of dual gene therapy could be easily assessed by the optical reporter gene imaging.

  11. Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival

    International Nuclear Information System (INIS)

    Tomita, Masaki; Ayabe, Takanori; Matsuzaki, Yasunori; Edagawa, Masao; Maeda, Masayuki; Shimizu, Tetsuya; Hara, Masaki; Onitsuka, Toshio

    2001-01-01

    We assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma. Formalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody. Expression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87). In patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion

  12. Molecular biologic study about the non-small cell lung carcinoma (2) : p53 gene alteration in non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Park, Jong Ho; Zo, Jae Ill; Paik, Hee Jong; Kim, Mi Hee

    1996-12-01

    The main purpose of this research was to identify of the p53 and 3p gene alteration in non-small cell lung cancer patients residing in Korea. Furthermore, we analyzed the relationship between the p53 and 3p gene alterations and the clinicopathologic results of lung cancer patients. And we have investigated the role of PCR-LOH in analyzing tumor samples for LOH of defined chromosomal loci. We have used the 40 samples obtained from the lung cancer patients who were diagnosed and operated curatively at Korea Cancer Center Hospital. We have isolated the high molecular weight. DNA from the tumors and normal tissues. And we have amplified the DNA with PCR method and used the microsatellite assay method to detect the altered p53 and 3p gene. The conclusions were as follow: 1) The 3p gene alteration was observed in 9/39 (23.1%) and p53 gene alteration was observed in 15/40 (37.5%) of resected non-small cell lung cancer. 2) There was no correlations between the 3p or p53 gene alterations and prognosis of patients, but further study is necessary. 3) PCR-LOH is a very useful tool for analyzing small amount of tumor samples for loss of heterozygosity of defined chromosomal loci. (author). 10 refs

  13. Analysis of gene expression data from non-small cell lung carcinoma cell lines reveals distinct sub-classes from those identified at the phenotype level.

    Directory of Open Access Journals (Sweden)

    Andrew R Dalby

    Full Text Available Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process. The final clustering into sub-classes was carried out in a conservative manner such that sub-classes were consistent across all three normalisation methods. If there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC.

  14. Lack of a Functional VHL Gene Product Sensitizes Renal Cell Carcinoma Cells to the Apoptotic Effects of the Protein Synthesis Inhibitor Verrucarin A

    Directory of Open Access Journals (Sweden)

    Girma M. Woldemichael

    2012-08-01

    Full Text Available Verrucarin A (VA is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC.

  15. Lack of a functional VHL gene product sensitizes renal cell carcinoma cells to the apoptotic effects of the protein synthesis inhibitor verrucarin A.

    Science.gov (United States)

    Woldemichael, Girma M; Turbyville, Thomas J; Vasselli, James R; Linehan, W Marston; McMahon, James B

    2012-08-01

    Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC.

  16. Lack of a Functional VHL Gene Product Sensitizes Renal Cell Carcinoma Cells to the Apoptotic Effects of the Protein Synthesis Inhibitor Verrucarin A12

    Science.gov (United States)

    Woldemichael, Girma M; Turbyville, Thomas J; Vasselli, James R; Linehan, W Marston; McMahon, James B

    2012-01-01

    Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC. PMID:22952429

  17. Promoter hypermethylation of the RECK gene is associated with its low expression and poor survival of esophageal squamous cell carcinoma

    Science.gov (United States)

    Zhu, Jing; Ling, Yang; Xu, Yun; Lu, Mingzhu; Liu, Yongping; Zhang, Changsong

    2017-01-01

    The present study aimed to investigate the association between the methylation status of the reversion-inducing cysteine-rich protein with kazal motifs (RECK) gene and its mRNA expression levels in patients with esophageal squamous cell carcinoma (ESCC). The methylation status of RECK was analyzed by methylation-specific polymerase chain reaction (PCR), and RECK mRNA expression levels were analyzed by quantitative PCR, in 310 paired ESCC tissues. The mean RECK methylation index (MI) was 0.65 in ESCCs and 0.49 in non-tumor samples. There was a significant association between RECK methylation and the American Joint Committee on Cancer stage and lymph node metastasis in ESCC (P0.16; mean-∆∆Cq=−2.85) compared with those with hypomethylation of the RECK gene (∆MI ≤0.16; mean-∆∆Ct=−0.83), and there was a significant difference in the mRNA expression levels of RECK between those with N0–1 and N2–3 lymph node metastasis (P<0.0001). A significant correlation was observed between RECK mRNA expression levels, the MI of RECK and poor postoperative survival (P=0.0003; P<0.0001). The results of the present study suggested that promoter hypermethylation may be an important factor for loss of RECK mRNA expression and may be an indicator of poor survival in ESCC. PMID:28454343

  18. Pseudogene PHBP1 promotes esophageal squamous cell carcinoma proliferation by increasing its cognate gene PHB expression.

    Science.gov (United States)

    Feng, Feiyue; Qiu, Bin; Zang, Ruochuan; Song, Peng; Gao, Shugeng

    2017-04-25

    Natural antisense transcripts (NATs) as one of the most diverse classes of long noncoding RNAs (lncRNAs), have been demonstrated involved in fundamental biological processes in human. Here, we reported that human prohibitin gene pseudogene 1 (PHBP1) was upregulated in ESCC, and increased PHBP1 expression in ESCC was associated with clinical advanced stage. Functional experiments showed that PHBP1 knockdown inhibited ESCC cells proliferation, colony formation and xenograft tumor growth in vitro and in vivo by causing cell-cycle arrest at the G1-G0 phase. Mechanisms analysis revealed that PHBP1 transcript as an antisense transcript of PHB is partially complementary to PHB mRNA and formed an RNA-RNA hybrid with PHB, consequently inducing an increase of PHB expression at both the mRNA and protein levels. Furthermore, PHBP1 expression is strongly correlated with PHB expression in ESCC tissues. Collectively, this study elucidates an important role of PHBP1 in promoting ESCC partly via increasing PHB expression.

  19. Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.

    Directory of Open Access Journals (Sweden)

    Magdalena B Wozniak

    Full Text Available Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05 mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA project and identified 60% (402 of the downregulated and 74% (469 of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.

  20. Expression of cancer stem markers could be influenced by silencing of p16 gene in HeLa cervical carcinoma cells.

    Science.gov (United States)

    Wu, H; Zhang, J; Shi, H

    2016-01-01

    Effect of the tumor suppression gene p16 on the biological characteristics of HeLa cervical carcinoma cells was explored. The expression of p16 protein was increased in HeLa tumor sphere cells, and no significant difference in tumor spheres from the first to the fourth passages. Compared with those of parental HeLa cells, the proportion of CD44+/CD24- and ABCG2+ cells increased significantly in tumor spheres. However after the cells were silenced by the p16-sh289 vector, expression of P16 protein and the cell number of CD44+/CD24- and ABCG2+ decreased. Moreover, HeLa cells with p16 gene silencing showed decreased abilities of sphere formation and matrigel invasion. More HeLa cells with p16 gene silence were needed for tumor formation in nude mice. Tumor size and weight in mouse model established with p16 gene silenced HeLa cells were less than those with HeLa parental cell model. The present results indicate that silencing of the p16 gene inhibits expression of cancer stem cell markers and tumorigenic ability of HeLa cells.

  1. Alteration of runt-related transcription factor 3 gene expression and biologic behavior of esophageal carcinoma TE-1 cells after 5-azacytidine intervention.

    Science.gov (United States)

    Wang, Shuai; Liu, Hong; Akhtar, Javed; Chen, Hua-Xia; Wang, Zhou

    2013-01-01

    5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at 50 μM had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.

  2. Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiao; Zhou, Hao; Duan, Na; Liu, Yongkang; Wang, Zhongqiu [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Zhu, Qingqiang [Medical School of Yangzhou University, Department of Medical Imaging, Subei People' s Hospital, Yangzhou (China); Li, Baoxin [Gulou Hospital, Department of Radiology, Nanjing (China); Cui, Wenjing [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Nanjing University Medical School, Department of Radiology, Jinling Hospital, Nanjing (China); Kundra, Vikas [The University of Texas, M.D. Anderson Cancer Center, Department of Radiology, Houston, TX (United States)

    2017-02-15

    To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. (orig.)

  3. Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wang, Xi; Niu, Haitao; Fan, Qingxia; Lu, Ping; Ma, Changwu; Liu, Wei; Liu, Ying; Li, Weiwei; Hu, Shaoxuan; Ling, Yun; Guo, Lei; Ying, Jianming; Huang, Jing

    2016-04-26

    This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients.Immunohistochemistry and fluorescence in situ hybridization (FISH) was used to assess EGFR expression and gene amplification status in 193 patients with ESCC. We also examined the association between EGFR overexpression and the efficacy of a novel EGFR TKI, icotinib, in 62 ESCC patients.Of the 193 patients, 95 (49.2%) patients showed EGFR overexpression (3+), and 47(24.4%) patients harbored EGFR FISH positivity. EGFR overexpression was significantly correlated with clinical stage and lymph node metastasis (picotinib, the response rate was 17.6% for patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors (p=0.341). Furthermore, all cases responded to icotinib showed EGFR overexpression.In conclusion, our study suggests that EGFR overexpression might potentially be used in predicting the efficacy in patients treated with Icotinib. These data have implications for both clinical trial design and therapeutic strategies.

  4. The correlations between alteration of p16 gene and clinicopathological factors and prognosis in squamous cell carcinomas of the buccal mucosa.

    Science.gov (United States)

    Dong, Yuying; Wang, Jie; Dong, Fusheng; Wang, Xu; Zhang, Yinghuai

    2012-07-01

    To evaluate relationships between the alteration of p16 gene and the clinical status and prognosis of the patients with squamous cell carcinoma of the buccal mucosa. Thirty buccal cancers were included in the analysis. Deletion analysis was performed by PCR. Point mutation analysis was used by PCR-SSCP and direct sequencing. Methylation-specific PCR methods were adopted for the evaluation of p16 methylation. The correlation between alteration of p16 gene and clinicopathological factors buccal cancer was evaluated by Fisher's exact test. Kaplan-Meier and Cox regression were used to investigate the relationship between p16 alteration and survival time. The frequency of p16 alteration was 63.3% in buccal carcinomas. P16 deletion was associated significantly with tumor size (P = 0.01). P16 point mutation was associated significantly with differentiation (P = 0.006). P16 methylation was associated significantly with nodes metastasis (P = 0.027). The overall survival rate of 30 buccal carcinomas was 53.3%. The Log-rank test (P = 0.021) and univariate Cox regression analysis (P = 0.030) revealed that p16 methylation was significantly associated with the overall survival rate. Multivariate analysis showed that p16 deletion, p16 mutation, and p16 methylation were not statistically significant. The alterations of p16 gene may play a major role in malignancy and development and metastases of buccal carcinoma and may be an excellent marker of aggressive clinical behavior. P16 methylation has a prognostic value in buccal carcinoma but not an independent prognosis factor. P16 point mutation and p16 deletion have not prognostic significance in buccal carcinoma. © 2012 John Wiley & Sons A/S.

  5. Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?

    Science.gov (United States)

    Williamson, Sean R; Grignon, David J; Cheng, Liang; Favazza, Laura; Gondim, Dibson D; Carskadon, Shannon; Gupta, Nilesh S; Chitale, Dhananjay A; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam

    2017-03-01

    Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics.

  6. The effects of human TSH receptor gene transfection on iodide uptake and thyroid-specific gene expression in poorly differentiated thyroid carcinoma cell line

    International Nuclear Information System (INIS)

    Hou Shasha; Wang Hui; Feng Fang; Lin Ning; Fu Hongliang; Du Xueliang; Wu Jingchuan

    2011-01-01

    Objective: To investigate the changes of iodide uptake and the expression of thyroid-specific genes in poorly differentiated follicular thyroid carcinoma (FTC) cells after transfection of human TSH receptor (hTSHR) gene in vitro. Methods: The recombinant eukaryotic expression plasmid PcDNA3.1/hTSHR-cDNA was transformed into DH 5a bacterial for amplification and then the recombinant plasmid was extracted. The recombinant was identified with PCR amplifying, restriction enzyme digestion analysis and DNA sequencing. The recombinant plasmid pcDNA3.1/hTSHR was transfected into FTC-133 cell line by lipofectin method in vitro. Immunofluorescence, iodide uptake studies and real time-PCR were applied to detect target protein expression. Statistical analysis was performed with t-test using SPSS 13.0 software. Results: Kpn I and Xba I restriction enzyme digestion, PCR amplifying and DNA sequencing confirmed that pcDNA3.1/hTSHR was successfully constructed. After transfection of the recombinant plasmid pcDNA3.1/hTSHR-cDNA and the stimulation of hTSH, the tumor cells displayed the expression of hTSHR protein at cell surface and cytoplasm. The iodine uptake in pcDNA3.1/hTSHR transfected cells was 2.9 times higher than that of control(pcDNA3.1(+) transfected cells) group(t = 28.63, P<0.01). The expression of TSHR, NIS, TPO and Tg (mRNA levels) in pcDNA3.1/hTSHR transfected cells were also significantly elevated by 1.74 (t =5.959, P<0.01), 7.2 (t =3.807, P<0.05), 2.88 (t=4.769, P<0.01) and 2.67 times (t=6.388, P<0.01) respectively compared to those of the control group. Conclusion: The study demonstrates that iodide uptake may be reactivated by hTSHR receptor gene transfection in poorly differentiated FTC cell. (authors)

  7. Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma.

    NARCIS (Netherlands)

    Wang, X.; Niu, H.; Fan, Q.; Lu, P.; Ma, C.; Liu, W.; Liu, Y.; Li, W.; Hu, S.; Ling, Y.; Guo, L.; Ying, J.; Huang, J.

    2016-01-01

    This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients.Immunohistochemistry and fluorescence in situ

  8. 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.

  9. 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.

  10. Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.

    Science.gov (United States)

    Kikuchi, Kentaro; Noguchi, Yoshihiro; de Rivera, Michelle Wendoline Garcia-Niño; Hoshino, Miyako; Sakashita, Hideaki; Yamada, Tsutomu; Inoue, Harumi; Miyazaki, Yuji; Nozaki, Tadashige; González-López, Blanca Silvia; Ide, Fumio; Kusama, Kaoru

    2016-03-01

    A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.

  11. Merkel cell carcinoma: is this a true carcinoma?

    Science.gov (United States)

    Jankowski, Marek; Kopinski, Piotr; Schwartz, Robert; Czajkowski, Rafal

    2014-11-01

    Recent years have brought an enhanced understanding of Merkel cell carcinoma (MCC) biology, especially with regard to the Merkel cell polyoma virus as a causative agent. Differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative MCC in morphology; gene expression, miRNA profiles and prognosis have been reported. Origin of MCC is controversial. Presence of neurosecretory granules has suggested that these carcinomas originate from one of the neurocrest derivatives, most probably Merkel cells; the name Merkel cell carcinoma is now widely accepted. Expression of PGP 9.5, chromogranin A and several neuropeptides, initially regarded as specific markers for neural and neuroendocrine cells, has recently been shown in a subset of lymphomas. MCC commonly expresses terminal deoxynucleotidyl transferase and PAX5. Their co-expression under physiologic circumstances is restricted to pro/pre-B cells and pre-B cells. These findings lead to the hypothesis by zur Hausen et al. that MCC originates from early B cells. This review was intended to critically appraise zur Hausen's hypothesis and discuss the possibility that MCC is a heterogenous entity with distinct subtypes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. The 434(G>C) polymorphism in the eosinophil cationic protein gene and its association with tissue eosinophilia in oral squamous cell carcinomas

    DEFF Research Database (Denmark)

    Pereira, Michele C; Oliveira, Denise T; Olivieri, Eloísa H R

    2010-01-01

    OBJECTIVE: The aim of this study was to investigate the prevalence of the Eosinophil cationic protein (ECP)-gene polymorphism 434(G>C) in oral squamous cell carcinoma (OSCC) patients and its association with tumor-associated tissue eosinophilia (TATE), demographic, clinical, and microscopic...... of ECP-gene polymorphism 434(G>C) with TATE, demographic, clinical, and microscopic variables in OSCC patients. Disease-free survival and overall survival were calculated by the Kaplan-Meier product-limit actuarial method and the comparison of the survival curves were performed using log rank test...

  13. Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells.

    Science.gov (United States)

    Schwertheim, Suzan; Wein, Frederik; Lennartz, Klaus; Worm, Karl; Schmid, Kurt Werner; Sheu-Grabellus, Sien-Yi

    2017-07-01

    The therapy of unresectable advanced thyroid carcinomas shows unfavorable outcome. Constitutive nuclear factor-κB (NF-κB) activation in thyroid carcinomas frequently contributes to therapeutic resistance; the radioiodine therapy often fails due to the loss of differentiated functions in advanced thyroid carcinomas. Curcumin is known for its anticancer properties in a series of cancers, but only few studies have focused on thyroid cancer. Our aim was to evaluate curcumin's molecular mechanisms and to estimate if curcumin could be a new therapeutic option in advanced thyroid cancer. Human thyroid cancer cell lines TPC-1 (papillary), FTC-133 (follicular), and BHT-101 (anaplastic) were treated with curcumin. Using real-time PCR analysis, we investigated microRNA (miRNA) and mRNA expression levels. Cell cycle, Annexin V/PI staining, and caspase-3 activity analysis were performed to detect apoptosis. NF-κB p65 activity and cell proliferation were analyzed using appropriate ELISA-based colorimetric assay kits. Treatment with 50 μM curcumin significantly increased the mRNA expression of the differentiation genes thyroglobulin (TG) and sodium iodide symporter (NIS) in all three cell lines and induced inhibition of cell proliferation, apoptosis, and decrease of NF-κB p65 activity. The miRNA expression analyses showed a significant deregulation of miRNA-200c, -21, -let7c, -26a, and -125b, known to regulate cell differentiation and tumor progression. Curcumin arrested cell growth at the G2/M phase. Curcumin increases the expression of redifferentiation markers and induces G2/M arrest, apoptosis, and downregulation of NF-κB activity in thyroid carcinoma cells. Thus, curcumin appears to be a promising agent to overcome resistance to the conventional cancer therapy.

  14. Gene therapy and radionuclides targeting therapy in mammary carcinoma

    International Nuclear Information System (INIS)

    Song Jinhua

    2003-01-01

    Breast carcinoma's gene therapy is a hotspot in study of the tumor's therapy in the recent years. Currently the major therapy methods that in the experimentative and primary clinical application phases include immunological gene therapy, multidrug resistance gene therapy, antisense oligonucleotide therapy and suicide gene therapy. The gene targeting brachytherapy, which is combined with gene therapy and radiotherapy has enhanced the killer effects of the suicide gene and nuclide in tumor cells. That has break a new path in tumor's gene therapy. The further study in this field will step up it's space to the clinical application

  15. Squamous cell carcinoma - invasive (image)

    Science.gov (United States)

    This irregular red nodule is an invasive squamous cell carcinoma (a form of skin cancer). Initial appearance, shown here, may be very similar to a noncancerous growth called a keratoacanthoma. Squamous cell cancers ...

  16. Biomarker MicroRNAs for Diagnosis of Oral Squamous Cell Carcinoma Identified Based on Gene Expression Data and MicroRNA-mRNA Network Analysis

    Science.gov (United States)

    Zhang, Hui; Li, Tangxin; Zheng, Linqing

    2017-01-01

    Oral squamous cell carcinoma is one of the most malignant tumors with high mortality rate worldwide. Biomarker discovery is critical for early diagnosis and precision treatment of this disease. MicroRNAs are small noncoding RNA molecules which often regulate essential biological processes and are good candidates for biomarkers. By integrative analysis of both the cancer-associated gene expression data and microRNA-mRNA network, miR-148b-3p, miR-629-3p, miR-27a-3p, and miR-142-3p were screened as novel diagnostic biomarkers for oral squamous cell carcinoma based on their unique regulatory abilities in the network structure of the conditional microRNA-mRNA network and their important functions. These findings were confirmed by literature verification and functional enrichment analysis. Future experimental validation is expected for the further investigation of their molecular mechanisms. PMID:29098014

  17. Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

    International Nuclear Information System (INIS)

    Zacapala-Gómez, Ana Elvira; Del Moral-Hernández, Oscar; Villegas-Sepúlveda, Nicolás; Hidalgo-Miranda, Alfredo; Romero-Córdoba, Sandra Lorena

    2016-01-01

    We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

  18. Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

    Energy Technology Data Exchange (ETDEWEB)

    Zacapala-Gómez, Ana Elvira, E-mail: zak_ana@yahoo.com.mx [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Del Moral-Hernández, Oscar, E-mail: odelmoralh@gmail.com [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Villegas-Sepúlveda, Nicolás, E-mail: nvillega@cinvestav.mx [Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D.F., México (Mexico); Hidalgo-Miranda, Alfredo, E-mail: ahidalgo@inmegen.gob.mx [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); Romero-Córdoba, Sandra Lorena, E-mail: sromero_cordoba@hotmail.com [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); and others

    2016-01-15

    We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

  19. Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration.

    Science.gov (United States)

    Muller, Marie; Guillaud-Bataille, Marine; Salleron, Julia; Genestie, Catherine; Deveaux, Sophie; Slama, Abdelhamid; de Paillerets, Brigitte Bressac; Richard, Stéphane; Benusiglio, Patrick R; Ferlicot, Sophie

    2018-02-06

    cell carcinoma from type 2 papillary renal cell carcinoma with efficient FH gene. Our findings are crucial in identifying who should be referred to Cancer Genetics clinics for genetic counseling and testing.

  20. Cutaneous Squamous Cell Carcinoma.

    Science.gov (United States)

    Parekh, Vishwas; Seykora, John T

    2017-09-01

    Cutaneous squamous cell carcinoma (cSCC) is a malignant neoplasm of the skin characterized by an aberrant proliferation of keratinocytes. Cutaneous SCC is the second most common malignancy globally, and usually arises in the chronically sun-damaged skin of elderly white individuals. From a pathologist's perspective, it is important to differentiate cSCC from the benign and reactive squamoproliferative lesions and identify the high-risk features associated with aggressive tumor behavior. In this article, we provide an up-to-date overview of cSCC along with its precursor lesions and important histologic variants, with a particular emphasis on the histopathologic features and molecular pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. MO-DE-207B-05: Predicting Gene Mutations in Renal Cell Carcinoma Based On CT Imaging Features: Validation Using TCGA-TCIA Datasets

    Energy Technology Data Exchange (ETDEWEB)

    Chen, X; Zhou, Z; Thomas, K; Wang, J [UT Southwestern Medical Center, Dallas, TX (United States)

    2016-06-15

    Purpose: The goal of this work is to investigate the use of contrast enhanced computed tomographic (CT) features for the prediction of mutations of BAP1, PBRM1, and VHL genes in renal cell carcinoma (RCC). Methods: For this study, we used two patient databases with renal cell carcinoma (RCC). The first one consisted of 33 patients from our institution (UT Southwestern Medical Center, UTSW). The second one consisted of 24 patients from the Cancer Imaging Archive (TCIA), where each patient is connected by a unique identi?er to the tissue samples from the Cancer Genome Atlas (TCGA). From the contrast enhanced CT image of each patient, tumor contour was first delineated by a physician. Geometry, intensity, and texture features were extracted from the delineated tumor. Based on UTSW dataset, we completed feature selection and trained a support vector machine (SVM) classifier to predict mutations of BAP1, PBRM1 and VHL genes. We then used TCIA-TCGA dataset to validate the predictive model build upon UTSW dataset. Results: The prediction accuracy of gene expression of TCIA-TCGA patients was 0.83 (20 of 24), 0.83 (20 of 24), and 0.75 (18 of 24) for BAP1, PBRM1, and VHL respectively. For BAP1 gene, texture feature was the most prominent feature type. For PBRM1 gene, intensity feature was the most prominent. For VHL gene, geometry, intensity, and texture features were all important. Conclusion: Using our feature selection strategy and models, we achieved predictive accuracy over 0.75 for all three genes under the condition of using patient data from one institution for training and data from other institutions for testing. These results suggest that radiogenomics can be used to aid in prognosis and used as convenient surrogates for expensive and time consuming gene assay procedures.

  2. Renal cell carcinoma in childhood

    International Nuclear Information System (INIS)

    Zanier, J.F.C.; Ramos, C.O.P.; Pereira, A.A.

    1990-01-01

    The authors present five cases of renal cell carcinoma in children, describing its aspects on excretory urography, ultra-sonography and computerized tomography. The clinical, pathological and radiological features are compared with those of the literature. (author)

  3. Analysis of Gene Expression Profiles of Microdissected Cell Populations Indicates that Testicular Carcinoma In situ Is an Arrested Gonocyte

    DEFF Research Database (Denmark)

    Sonne, S. B.; Almstrup, K.; Dalgaard, M.

    2009-01-01

    samples of each tissue type were used for the analyses. Unique expression patterns for these developmentally very related cell types revealed that CIS cells were very similar to gonocytes because only five genes distinguished these two cell types. We did not find indications that CIS was derived from....... speculate that disturbed development of somatic cells in the fetal testis may play a role in allowing undifferentiated cells to survive in the postnatal testes. The further development of CIS into invasive germ cell tumors may depend on signals from their postpubertal niche of somatic cells, including...

  4. Estimation of groin recurrence risk in patients with squamous cell vulvar carcinoma by the assessment of marker gene expression in the lymph nodes

    Directory of Open Access Journals (Sweden)

    Kowalewska Magdalena

    2012-06-01

    Full Text Available Abstract Background Regional lymph node (LN status is a well-known prognostic factor for vulvar carcinoma (VC patients. Although the reliable LN assessment in VC is crucial, it presents significant diagnostic problems. We aimed to identify specific mRNA markers of VC dissemination in the LN and to address the feasibility of predicting the risk of nodal recurrence by the patterns of gene expression. Methods Sentinel and inguinal LN samples from 20 patients who had undergone surgery for stage T1-3, N0-2, M0 primary vulvar squamous cell carcinoma were analyzed. Gene expression profiles were assessed in four metastatic [LN(+] and four histologically negative [LN(−] lymph node samples obtained from four VC patients, by the Affymetrix U133 Plus 2.0 gene expression microarrays. Of the set of genes of the highest expression in the metastatic LNs compared to LN(−, seven candidate marker genes were selected: PERP, S100A8, FABP5, SFN, CA12, JUP and CSTA, and the expression levels of these genes were further analyzed by the real-time reverse transcription polymerase chain reaction (qRT-PCR in 71 LN samples. Results All of the seven genes in question were significantly increased in LN(+ compared to LN(− samples. In the initial validation of the seven putative markers of metastatic LN, the Cox proportional hazard model pointed to SFN, CA12 and JUP expression to significantly relate to the time to groin recurrence in VC patients. Conclusions Our findings first provided evidence that SFN, CA12 and JUP have a potential of marker genes for the prediction of the groin recurrence LN in VC patients.

  5. Loss of Mitochondrial Tumor Suppressor Genes Expression Is Associated with Unfavorable Clinical Outcome in Head and Neck Squamous Cell Carcinoma: Data from Retrospective Study.

    Directory of Open Access Journals (Sweden)

    Ishrat Mahjabeen

    Full Text Available Mitochondrial genes play important roles in cellular energy metabolism, free radical generation, and apoptosis. Dysregulation of these genes have long been suspected to contribute to the generation of reactive oxygen species (ROS, increased proliferation and progression of cancer. A family of orthologues of yeast silent information regulator 3 (SIRT3, 4 (SIRT4 and mitochondrial tumor suppressor 1 (MTUS1 are important mitochondrial tumor suppressor genes which play an important role in the progression of multiple cancers. However, their role in the development of oxidative stress, enhanced proliferation and progression of head and neck squamous cell carcinoma (HNSCC has not yet been studied. In this study we aimed to test the association between reduced mitochondrial tumor suppressor genes' activities and enhancement in tissue oxidative stress and cell proliferation in HNSCC cases. The expression of mitochondrial tumor suppressor genes (SIRT3, SIRT4 and MTUS1, mitochondrial DNA repair gene (OGG1-2a and a proliferation marker (Ki-67 was studied in a study cohort of 120 HNSCC patients and controls with reverse transcriptase polymerase chain reaction (RT-PCR and real-time PCR (qPCR in order to determine the potential prognostic significance of these genes. A statistically significant downregulation of SIRT3 (p<0.001, SIRT4 (p<0.0001, MTUS1 (p<0.002 and OGG1 (p<0.0001 was observed in HNSCC compared to control samples. Ki-67 was also overexpressed (p<0.0001 in HNSCC versus control samples. Additionally, to explore gene-gene relationship, we observed a positive spearmen correlation between SIRT3 versus SIRT4 (r = 0.523***, p<0.0001, SIRT3 versus MTUS1 (r = 0.273***, p<0.001, SIRT3 versus OGG1-2a (r = 0.213*, p<0.03, SIRT4 versus OGG1 (r = 0.338***, p<0.0001 and MTUS1 versus OGG1-2a (r = 0.215*, p<0.03 in HNSCC cases. A negative spearman correlation was observed between OGG1 versus Ki-67 (r = -0.224**, p<0.01 and OGG1-2a versus Ki-67 (r = -0.224**, p<0

  6. Next-Generation Sequencing to Detect Deletion of RB1 and ERBB4 Genes in Chromophobe Renal Cell Carcinoma: A Potential Role in Distinguishing Chromophobe Renal Cell Carcinoma from Renal Oncocytoma.

    Science.gov (United States)

    Liu, Qingqing; Cornejo, Kristine M; Cheng, Liang; Hutchinson, Lloyd; Wang, Mingsheng; Zhang, Shaobo; Tomaszewicz, Keith; Cosar, Ediz F; Woda, Bruce A; Jiang, Zhong

    2018-04-01

    Overlapping morphologic, immunohistochemical, and ultrastructural features make it difficult to diagnose chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). Because ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to identify genetic markers that distinguish ChRCC from RO by using next-generation sequencing (NGS). NGS for hotspot mutations or gene copy number changes was performed on 12 renal neoplasms, including seven ChRCC and five RO cases. Matched normal tissues from the same patients were used to exclude germline variants. Rare hotspot mutations were found in cancer-critical genes (TP53 and PIK3CA) in ChRCC but not RO. The NGS gene copy number analysis revealed multiple abnormalities. The two most common deletions were tumor-suppressor genes RB1 and ERBB4 in ChRCC but not RO. Fluorescence in situ hybridization was performed on 65 cases (ChRCC, n = 33; RO, n = 32) to verify hemizygous deletion of RB1 (17/33, 52%) or ERBB4 (11/33, 33%) in ChRCC, but not in RO (0/32, 0%). In total, ChRCCs (23/33, 70%) carry either a hemizygous deletion of RB1 or ERBB4. The combined use of RB1 and ERBB4 fluorescence in situ hybridization to detect deletion of these genes may offer a highly sensitive and specific assay to distinguish ChRCC from RO. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Lee, Jae Seo

    2006-01-01

    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

  8. Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.

    Science.gov (United States)

    Kehrmann, Angela; Truong, Ha; Repenning, Antje; Boger, Regina; Klein-Hitpass, Ludger; Pascheberg, Ulrich; Beckmann, Alf; Opalka, Bertram; Kleine-Lowinski, Kerstin

    2013-01-01

    The fusion between human tumorigenic cells and normal human diploid fibroblasts results in non-tumorigenic hybrid cells, suggesting a dominant role for tumor suppressor genes in the generated hybrid cells. After long-term cultivation in vitro, tumorigenic segregants may arise. The loss of tumor suppressor genes on chromosome 11q13 has been postulated to be involved in the induction of the tumorigenic phenotype of human papillomavirus (HPV)18-positive cervical carcinoma cells and their derived tumorigenic hybrid cells after subcutaneous injection in immunocompromised mice. The aim of this study was the identification of novel cellular genes that may contribute to the suppression of the tumorigenic phenotype of non-tumorigenic hybrid cells in vivo. We used cDNA microarray technology to identify differentially expressed cellular genes in tumorigenic HPV18-positive hybrid and parental HeLa cells compared to non-tumorigenic HPV18-positive hybrid cells. We detected several as yet unknown cellular genes that play a role in cell differentiation, cell cycle progression, cell-cell communication, metastasis formation, angiogenesis, antigen presentation, and immune response. Apart from the known differentially expressed genes on 11q13 (e.g., phosphofurin acidic cluster sorting protein 1 (PACS1) and FOS ligand 1 (FOSL1 or Fra-1)), we detected novel differentially expressed cellular genes located within the tumor suppressor gene region (e.g., EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) and leucine rich repeat containing 32 (LRRC32) (also known as glycoprotein-A repetitions predominant (GARP)) that may have potential tumor suppressor functions in this model system of non-tumorigenic and tumorigenic HeLa x fibroblast hybrid cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Using logistic regression to improve the prognostic value of microarray gene expression data sets: application to early-stage squamous cell carcinoma of the lung and triple negative breast carcinoma.

    Science.gov (United States)

    Mount, David W; Putnam, Charles W; Centouri, Sara M; Manziello, Ann M; Pandey, Ritu; Garland, Linda L; Martinez, Jesse D

    2014-06-10

    Numerous microarray-based prognostic gene expression signatures of primary neoplasms have been published but often with little concurrence between studies, thus limiting their clinical utility. We describe a methodology using logistic regression, which circumvents limitations of conventional Kaplan Meier analysis. We applied this approach to a thrice-analyzed and published squamous cell carcinoma (SQCC) of the lung data set, with the objective of identifying gene expressions predictive of early death versus long survival in early-stage disease. A similar analysis was applied to a data set of triple negative breast carcinoma cases, which present similar clinical challenges. Important to our approach is the selection of homogenous patient groups for comparison. In the lung study, we selected two groups (including only stages I and II), equal in size, of earliest deaths and longest survivors. Genes varying at least four-fold were tested by logistic regression for accuracy of prediction (area under a ROC plot). The gene list was refined by applying two sliding-window analyses and by validations using a leave-one-out approach and model building with validation subsets. In the breast study, a similar logistic regression analysis was used after selecting appropriate cases for comparison. A total of 8594 variable genes were tested for accuracy in predicting earliest deaths versus longest survivors in SQCC. After applying the two sliding window and the leave-one-out analyses, 24 prognostic genes were identified; most of them were B-cell related. When the same data set of stage I and II cases was analyzed using a conventional Kaplan Meier (KM) approach, we identified fewer immune-related genes among the most statistically significant hits; when stage III cases were included, most of the prognostic genes were missed. Interestingly, logistic regression analysis of the breast cancer data set identified many immune-related genes predictive of clinical outcome. Stratification of

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

    Science.gov (United States)

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

    2014-12-01

    Merkel cell carcinoma is believed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly understood events. Transcriptional profiling using cDNA microarrays was performed on cells from MCPy-negative and MCPy-positive Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and some downregulated genes. The extensive list of genes that were identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial–mesenchymal transition and cancer-stem cell trait as biological end points

    Energy Technology Data Exchange (ETDEWEB)

    Narang, Himanshi, E-mail: narangh@barc.gov.in [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Kumar, Amit [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Bhat, Nagesh [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Pandey, Badri N.; Ghosh, Anu [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

    2015-10-15

    Highlights: • Biological effectiveness of proton and gamma irradiation is compared in A549 cells. • Proton irradiation is two times more cytotoxic than gamma irradiation. • It alters ten times more number of early genes, as observed by microarray study. • It does not enhance cell migration, invasion and adhesion, unlike gamma irradiation. • It was more effective in reducing the percentage of cancer stem cell like cells. - Abstract: Proton beam therapy is a cutting edge modality over conventional gamma radiotherapy because of its physical dose deposition advantage. However, not much is known about its biological effects vis-a-vis gamma irradiation. Here we investigated the effect of proton- and gamma- irradiation on cell cycle, death, epithelial-mesenchymal transition (EMT) and “stemness” in human non-small cell lung carcinoma cells (A549). Proton beam (3 MeV) was two times more cytotoxic than gamma radiation and induced higher and longer cell cycle arrest. At equivalent doses, numbers of genes responsive to proton irradiation were ten times higher than those responsive to gamma irradiation. At equitoxic doses, the proton-irradiated cells had reduced cell adhesion and migration ability as compared to the gamma-irradiated cells. It was also more effective in reducing population of Cancer Stem Cell (CSC) like cells as revealed by aldehyde dehydrogenase activity and surface phenotyping by CD44{sup +}, a CSC marker. These results can have significant implications for proton therapy in the context of suppression of molecular and cellular processes that are fundamental to tumor expansion.

  12. [Effect of Biejiajian Pills on Wnt/β-catenin signal pathway and DKK-1 and FrpHe gene expressions in hepatocellular carcinoma cells].

    Science.gov (United States)

    He, Songqi; Cheng, Yang; Zhu, Yun; Fan, Qin; Sun, Haitao; Jia, Wenyan

    2013-01-01

    To investigate the effect of Biejiajian Pills on Wnt signal pathway and its inhibitory gene (DKK-1 and FrpHe) expressions and explore the mechanism underlying the action of Biejiajian Pills to suppress the invasiveness of hepatocellular carcinoma. Twenty-four Wistar rats were randomized equally into 3 groups for gavage of normal saline and Biejiajian Pills at 20- and 10-fold clinical doses for 3 days. Blood samples were then collected from the rats, and the serum was separated and added in HepG2 cell cultures. After 48 h of culture, the cells were collected to determine the cellular content of β-catenin protein using flow cytometry and detect DKK-1 and FrpHe mRNA expressions using qRT-PCR. HepG2 cells cultured in the presence of sera from rats fed with Biejiajian Pills showed significantly lowered β-catenin protein expression and obvious down-regulation of DKK-1 mRNA expression, and the effect was correlated with the doses of the drug administered. The expression of FrpHe mRNA showed no significant differences between the 3 groups. Biejiajian Pills can effectively inhibit the invasiveness and migration of hepatocellular carcinoma cells, which is closely related to decreased expressions of β-catenin and DKK-1 to cause block of the Wnt/β-catenin signal pathway.

  13. GENE EXPRESSION PROFILING OF HUMAN LIVER CARCINOMA (HepG2) CELLS EXPOSED TO THE MARINE TOXIN OKADAIC ACID

    Science.gov (United States)

    Fieber, Lynne A.; Greer, Justin B.; Guo, Fujiang; Crawford, Douglas C.; Rein, Kathleen S.

    2012-01-01

    The marine toxin, okadaic acid (OA) is produced by dinoflagellates of the genera Prorocentrum and Dinophysis and is the causative agent of the syndrome known as diarrheic shellfish poisoning (DSP). In addition, OA acts as both a tumor promoter, attributed to OA-induced inhibition of protein phosphatases as well as an inducer of apoptosis. To better understand the potentially divergent toxicological profile of OA, the concentration dependent cytotoxicity and alterations in gene expression on the human liver tumor cell line HepG2 upon OA exposure were determined using RNA microarrays, DNA fragmentation, and cell proliferation assays as well as determinations of cell detachment and cell death in different concentrations of OA. mRNA expression was quantified for approximately 15,000 genes. Cell attachment and proliferation were both negatively correlated with OA concentration. Detached cells displayed necrotic DNA signatures but apoptosis also was broadly observed. Data suggest that OA has a concentration dependent effect on cell cycle, which might explain the divergent effects that at low concentration OA stimulates genes involved in the cell cycle and at high concentrations it stimulates apoptosis. PMID:23172983

  14. Upregulation of HPV E6 and E7 genes in human cervix carcinoma cell lines leads to both an increase in radiation resistance and alterations in apoptosis

    International Nuclear Information System (INIS)

    Kamradt, M.; Krueger, E.; McCall, A.; Manker, C.; Rudnick, S.; Erlich, E.; Khodarev, N; Vaughan, A.T.M.

    1996-01-01

    Purpose: Stage I-III cervical cancer is commonly treated with external beam radiotherapy with curative intent. We have shown that the presence of the artificial steroid dexamethasone can increase the radiation resistance of HPV+ve cervical tumors. Dexamethasone treatment enhances cell proliferation by upregulation of HPV 18 E6 and E7 genes through a glucocorticoid responsive element within the HPV promoter region. The goal of this study is to understand the mechanism whereby steroid treatment produces enhanced radioresistance in cervical tumors. Methods: Four cervical tumor cell lines and one squamous carcinoma cell line (SQ-20B) were used. Each cell line was exposed to 0 - 8 Gy of gamma irradiation in the presence or absence of 1 μM dexamethasone (Dx) and assayed for cell survival using a clonogenic assay. Parallel samples were examined by fluorescence microscopy after Triton X-100 permeabilization and propidium iodide staining 1, 2 and 4 days post irradiation. Nuclei containing the characteristic multi-lobular structure and condensed appearance of apoptosis were recorded. To confirm the presence of apoptosis in these cells a terminal deoxynucleotide transferase staining reaction was carried out to label the free DNA ends characteristic of apoptosis. Results: Administration of Dx increased radiation resistance in all HPV+ve E6 and E7 expressing cell lines studied, a similar effect was seen in two additional HPV 18+ve cervical carcinoma cell lines ME180 and MS751 (data not shown). No effect was seen in the HPV-ve cell lines, or C41 K6 containing anti-sense E6 and E7 genes. Introduction of the anti-sense E6 and E7 sequences into C41 did not affect their ability to undergo radiation-induced apoptosis though Dx administration reduced the amount of apoptosis seen. Conversely, Dx treatment of the HeLa cell line increased radioresistance but did not affect the ability of these cells to engage apoptosis. Conclusion: All (5) cervical cell lines studied containing HPV 18

  15. Cytotoxic effects induced by interferon-ω gene lipofection through ROS generation and mitochondrial membrane potential disruption in feline mammary carcinoma cells.

    Science.gov (United States)

    Villaverde, Marcela Solange; Targovnik, Alexandra Marisa; Miranda, María Victoria; Finocchiaro, Liliana María Elena; Glikin, Gerardo Claudio

    2016-08-01

    Progress in comparative oncology promises advances in clinical cancer treatments for both companion animals and humans. In this context, feline mammary carcinoma (FMC) cells have been proposed as a suitable model to study human breast cancer. Based on our previous data about the advantages of using type I interferon gene therapy over the respective recombinant DNA derived protein, the present work explored the effects of feline interferon-ω gene (fIFNω) transfer on FMC cells. Three different cell variants derived from a single spontaneous highly aggressive FMC tumor were successfully established and characterized. Lipofection of the fIFNω gene displayed a significant cytotoxic effect on the three cell variants. The extent of the response was proportional to ROS generation, mitochondrial membrane potential disruption and calcium uptake. Moreover, a lower sensitivity to the treatment correlated with a higher malignant phenotype. Our results suggest that fIFNω lipofection could offer an alternative approach in veterinary oncology with equal or superior outcome and with less adverse effects than recombinant fIFNω therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Effects and mechanism of integrin-β1 gene expression inhibited by shRNA in invasion of pancreatic carcinoma PANC-1 cells.

    Science.gov (United States)

    Yu, Feng; Li, Hua; Bu, Xuefeng; Zhang, Yongjun

    2012-01-01

    To investigate the effects of integrin-β1 gene expression inhibited by shRNA on invasion of pancreatic carcinoma PANC-1 cells in vitro. The eukaryotic expression plasmid of short hairpin RNA (shRNA) targeting integrin-β1 gene (integrin-β1-shRNA) was constructed and transfected into PANC-1 cells. The expressions of integrin-β1 mRNA and protein were detected by real-time quantitative polymerase chain reaction (PCR) and western blot assay, respectively. The invasive ability of PANC-1 cells was observed with a transwell cell culture chamber and the expressions of MMP-2 and MMP-9 were assayed. Compared to the untransfected group, recombinant expression plasmid integrin-β1-shRNA resulted in reduction of integrin-β1 mRNA and protein by 78.58%±7.24% and 92.88%±3.18%, respectively and the average number of invading PANC-1 cells were decreased from 52±5 to 21±4 (pPANC-1 cells in vitro significantly.

  17. An eleven gene molecular signature for extra-capsular spread in oral squamous cell carcinoma serves as a prognosticator of outcome in patients without nodal metastases.

    Science.gov (United States)

    Wang, Weining; Lim, Weng Khong; Leong, Hui Sun; Chong, Fui Teen; Lim, Tony K H; Tan, Daniel S W; Teh, Bin Tean; Iyer, N Gopalakrishna

    2015-04-01

    Extracapsular spread (ECS) is an important prognostic factor for oral squamous cell carcinoma (OSCC) and is used to guide management. In this study, we aimed to identify an expression profile signature for ECS in node-positive OSCC using data derived from two different sources: a cohort of OSCC patients from our institution (National Cancer Centre Singapore) and The Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) cohort. We also sought to determine if this signature could serve as a prognostic factor in node negative cancers. Patients with a histological diagnosis of OSCC were identified from an institutional database and fresh tumor samples were retrieved. RNA was extracted and gene expression profiling was performed using the Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. RNA sequence data and corresponding clinical data for the TCGA HNSCC cohort were downloaded from the TCGA Data Portal. All data analyses were conducted using R package and SPSS. We identified an 11 gene signature (GGH, MTFR1, CDKN3, PSRC1, SMIM3, CA9, IRX4, CPA3, ZSCAN16, CBX7 and ZFP3) which was robust in segregating tumors by ECS status. In node negative patients, patients harboring this ECS signature had a significantly worse overall survival (p=0.04). An eleven gene signature for ECS was derived. Our results also suggest that this signature is prognostic in a separate subset of patients with no nodal metastasis Further validation of this signature on other datasets and immunohistochemical studies are required to establish utility of this signature in stratifying early stage OSCC patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Mesenchymal stem cells are efficiently transduced with adenoviruses bearing type 35-derived fibers and the transduced cells with the IL-28A gene produces cytotoxicity to lung carcinoma cells co-cultured.

    Science.gov (United States)

    Suzuki, Takeo; Kawamura, Kiyoko; Li, Quanhai; Okamoto, Shinya; Tada, Yuji; Tatsumi, Koichiro; Shimada, Hideaki; Hiroshima, Kenzo; Yamaguchi, Naoto; Tagawa, Masatoshi

    2014-09-25

    Transduction of human mesenchymal stem cells (MSCs) with type 5 adenoviruses (Ad5) is limited in the efficacy because of the poor expression level of the coxsackie adenovirus receptor (CAR) molecules. We examined a possible improvement of Ad-mediated gene transfer in MSCs by substituting the fiber region of type 5 Ad with that of type 35 Ad. Expression levels of CAR and CD46 molecules, which are the major receptors for type 5 and type 35 Ad, respectively, were assayed with flow cytometry. We constructed vectors expressing the green fluorescent protein gene with Ad5 or modified Ad5 bearing the type 35 fiber region (AdF35), and examined the infectivity to MSCs with flow cytometry. We investigated anti-tumor effects of MSCs transduced with interleukin (IL)-28A gene on human lung carcinoma cells with a colorimetric assay. Expression of IL-28A receptors was tested with the polymerase chain reaction. A promoter activity of transcriptional regulatory regions in MSCs was determined with a luciferase assay and a tumor growth-promoting ability of MSCs was tested with co-injection of human tumor cells in nude mice. MSCs expressed CD46 but scarcely CAR molecules, and subsequently were transduced with AdF35 but not with Ad5. Growth of MSCs transduced with the IL-28A gene remained the same as that of untransduced cells since MSCs were negative for the IL-28A receptors. The IL-28A-transduced MSCs however suppressed growth of lung carcinoma cells co-cultured, whereas MSCs transduced with AdF35 expressing the β-galactosidase gene did not. A regulatory region of the cyclooygenase-2 gene possessed transcriptional activities greater than other tumor promoters but less than the cytomegalovirus promoter, and MSCs themselves did not support tumor growth in vivo. AdF35 is a suitable vector to transduce MSCs that are resistant to Ad5-mediated gene transfer. MSCs infected with AdF35 that activate an exogenous gene by the cytomegalovirus promoter can be a vehicle to deliver the gene product

  19. Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes.

    Science.gov (United States)

    Tian, Ying; Arai, Eri; Gotoh, Masahiro; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Kanai, Yae

    2014-10-20

    The CpG island methylator phenotype (CIMP) of clear cell renal cell carcinomas (ccRCCs) is characterized by accumulation of DNA methylation at CpG islands and poorer patient outcome. The aim of this study was to establish criteria for prognostication of patients with ccRCCs using the ccRCC-specific CIMP marker genes. DNA methylation levels at 299 CpG sites in the 14 CIMP marker genes were evaluated quantitatively in tissue specimens of 88 CIMP-negative and 14 CIMP-positive ccRCCs in a learning cohort using the MassARRAY system. An additional 100 ccRCCs were also analyzed as a validation cohort. Receiver operating characteristic curve analysis showed that area under the curve values for the 23 CpG units including the 32 CpG sites in the 7 CIMP-marker genes, i.e. FAM150A, ZNF540, ZNF671, ZNF154, PRAC, TRH and SLC13A5, for discrimination of CIMP-positive from CIMP-negative ccRCCs were larger than 0.95. Criteria combining the 23 CpG units discriminated CIMP-positive from CIMP-negative ccRCCs with 100% sensitivity and specificity in the learning cohort. Cancer-free and overall survival rates of patients with CIMP-positive ccRCCs diagnosed using the criteria combining the 23 CpG units in a validation cohort were significantly lower than those of patients with CIMP-negative ccRCCs (P = 1.41 × 10-5 and 2.43 × 10-13, respectively). Patients with CIMP-positive ccRCCs in the validation cohort had a higher likelihood of disease-related death (hazard ratio, 75.8; 95% confidence interval, 7.81 to 735; P = 1.89 × 10-4) than those with CIMP-negative ccRCCs. The established criteria are able to reproducibly diagnose CIMP-positive ccRCCs and may be useful for personalized medicine for patients with ccRCCs.

  20. Keap1/Nrf2 pathway in kidney cancer : frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma

    NARCIS (Netherlands)

    Fabrizio, Federico Pio; Costantini, Manuela; Copetti, Massimiliano; la Torre, Annamaria; Sparaneo, Angelo; Fontana, Andrea; Poeta, Luana; Gallucci, Michele; Sentinelli, Steno; Graziano, Paolo; Parente, Paola; Pompeo, Vincenzo; De Salvo, Laura; Simone, Giuseppe; Papalia, Rocco; Picardo, Francesco; Balsamo, Teresa; Flammia, Gerardo Paolo; Trombetta, Domenico; Pantalone, Angela; Kok, Klaas; Paranita, Ferronika; Muscarella, Lucia Anna; Fazio, Vito Michele

    2017-01-01

    The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal

  1. 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

  2. General Information about Merkel Cell Carcinoma

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key ...

  3. Primary orbital squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ana L. Campos Arbulú

    2017-02-01

    Full Text Available Primary orbital squamous cell carcinoma is a rare entity. There is little published literature. We report a case of primary squamous cell carcinoma of the orbital soft tissues. Surgical resection offered the best treatment for the patient. Complete resection of the lesion was achieved. The patient received adjuvant radiotherapy due to the proximity of the lesion to the surgical margins. Surgical treatment is feasible and should be considered as part of the surgeon's arsenal. However, therapeutic decisions must be made on a case-by-case basis

  4. Gene and miRNA expression signature of Lewis lung carcinoma LLC1 cells in extracellular matrix enriched microenvironment

    International Nuclear Information System (INIS)

    Stankevicius, Vaidotas; Vasauskas, Gintautas; Bulotiene, Danute; Butkyte, Stase; Jarmalaite, Sonata; Rotomskis, Ricardas; Suziedelis, Kestutis

    2016-01-01

    The extracellular matrix (ECM), one of the key components of tumor microenvironment, has a tremendous impact on cancer development and highly influences tumor cell features. ECM affects vital cellular functions such as cell differentiation, migration, survival and proliferation. Gene and protein expression levels are regulated in cell-ECM interaction dependent manner as well. The rate of unsuccessful clinical trials, based on cell culture research models lacking the ECM microenvironment, indicates the need for alternative models and determines the shift to three-dimensional (3D) laminin rich ECM models, better simulating tissue organization. Recognized advantages of 3D models suggest the development of new anticancer treatment strategies. This is among the most promising directions of 3D cell cultures application. However, detailed analysis at the molecular level of 2D/3D cell cultures and tumors in vivo is still needed to elucidate cellular pathways most promising for the development of targeted therapies. In order to elucidate which biological pathways are altered during microenvironmental shift we have analyzed whole genome mRNA and miRNA expression differences in LLC1 cells cultured in 2D or 3D culture conditions. In our study we used DNA microarrays for whole genome analysis of mRNA and miRNA expression differences in LLC1 cells cultivated in 2D or 3D culture conditions. Next, we indicated the most common enriched functional categories using KEGG pathway enrichment analysis. Finally, we validated the microarray data by quantitative PCR in LLC1 cells cultured under 2D or 3D conditions or LLC1 tumors implanted in experimental animals. Microarray gene expression analysis revealed that 1884 genes and 77 miRNAs were significantly altered in LLC1 cells after 48 h cell growth under 2D and ECM based 3D cell growth conditions. Pathway enrichment results indicated metabolic pathway, MAP kinase, cell adhesion and immune response as the most significantly altered

  5. Von Hippel-Lindau tumor suppressor gene loss in renal cell carcinoma promotes oncogenic epidermal growth factor receptor signaling via Akt-1 and MEK-1.

    Science.gov (United States)

    Lee, S Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W Marston; Bottaro, Donald P; Vasselli, James R

    2008-10-01

    Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-alpha (TGF-alpha), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knock-down cells had escaped shRNA suppression. EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen.

  6. Von Hippel-Lindau Tumor Suppressor Gene Loss in Renal Cell Carcinoma Promotes Oncogenic Epidermal Growth Factor Receptor Signaling via Akt-1 and MEK1

    Science.gov (United States)

    Lee, S. Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W. Marston; Bottaro, Donald P.; Vasselli, James R.

    2008-01-01

    Objectives Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-α (TGF-α), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Methods Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. Results RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knockdown cells had escaped shRNA suppression. Conclusions EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen. PMID:18243508

  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. Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    Bazrafshani, Mohammad Reza R; Nowshadi, Pouriaali A; Shirian, Sadegh; Daneshbod, Yahya; Nabipour, Fatemeh; Mokhtari, Maral; Hosseini, Fatemehsadat; Dehghan, Somayeh; Saeedzadeh, Abolfazl; Mosayebi, Ziba

    2016-02-01

    Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation-dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin-fixed paraffin-embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5-8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  9. Squamous Cell Carcinoma Antigen-encoding Genes SERPINB3/B4 as Potentially Useful Markers for the Stratification of HNSCC Tumours.

    Science.gov (United States)

    Saidak, Zuzana; Morisse, Mony Chenda; Chatelain, Denis; Sauzay, Chloé; Houessinon, Aline; Guilain, Nelly; Soyez, Marion; Chauffert, Bruno; Dakpé, Stéphanie; Galmiche, Antoine

    2018-03-01

    The squamous cell carcinoma antigen (SCCA), encoded by the genes SERPINB3/B4, is a tumour marker produced by head and neck squamous cell carcinoma (HNSCC). We aimed to examine SERPINB3/B4 mRNA levels and its clinical significance in the therapeutic context. We retrieved mRNA expression levels, clinical, pathological and genomic data for 520 HNSCC from The Cancer Genome Atlas (TCGA). HNSCC tumours express high levels of SERPINB3/B4 mRNA. SERPINB3 expression differs depending on Human papillomavirus (HPV) infection status, primary tumour location, grade and differentiation, extension to lymph nodes and extracapsular spread. Interestingly, we observed an association between SERPINB3/B4 and the presence of tumour immune infiltrate as well as the expression of the immune checkpoint regulators PD-L1/PD-L2 that depended on HPV status. Our findings point to potential interest of SERPINB3/B4 for the stratification of HNSCC patients in the therapeutic context. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Nevoid basal cell carcinoma syndrome with medulloblastoma in an African-American boy: A rare case illustrating gene-environment interaction

    Energy Technology Data Exchange (ETDEWEB)

    Korczak, J.F.; Goldstein, A.M. [National Institutes of Health, Bethesda, MD (United States); Kase, R.G. [Westat Inc., Rockville, MD (United States)] [and others

    1997-03-31

    We present an 8-year-old African-American boy with medulloblastoma and nevoid basal cell carcinoma syndrome (NBCCS) who exhibited the radiosensitive response of basal cell carcinoma (BCC) formation in the area irradiated for medulloblastoma. Such a response is well-documented in Caucasian NBCCS patients with medulloblastoma. The propositus was diagnosed with medulloblastoma at the age of 2 years and underwent surgery, chemotherapy, and craniospinal irradiation. At the age of 6 years, he was diagnosed with NBCCS following his presentation with a large odontogenic keratocyst of the mandible, pits of the palms and soles and numerous BCCs in the area of the back and neck that had been irradiated previously for medulloblastoma. Examination of other relatives showed that the propositus mother also had NBCCS but was more mildly affected; in particular, she had no BCCs. This case illustrates complex gene-environment interaction, in that increased skin pigmentation in African-Americans is presumably protective against ultraviolet, but not ionizing, radiation. This case and other similar cases in the literature show the importance of considering NBCCS in the differential diagnosis of any patient who presents with a medulloblastoma, especially before the age of 5 years, and of examining other close relatives for signs of NBCCS to determine the patient`s at-risk status. Finally, for individuals who are radiosensitive, protocols that utilize chemotherapy in lieu of radiotherapy should be considered. 27 refs., 4 figs.

  11. Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population.

    Science.gov (United States)

    da Silva Calixto, Poliane; Lopes, Otávio Sérgio; Dos Santos Maia, Mayara; Herrero, Sylvia Satomi Takeno; Longui, Carlos Alberto; Melo, Cynthia Germoglio Farias; de Carvalho Filho, Ivan Rodrigues; Soares, Leonardo Ferreira; de Medeiros, Arnaldo Correia; Delatorre, Plínio; Khayat, André Salim; Burbano, Rommel Rodriguez; Lima, Eleonidas Moura

    2018-07-01

    Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraíba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific - PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P molecular markers for BCC.

  12. 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....

  13. Effects of HAb18G/CD147 knockout on hepatocellular carcinoma cells in vitro using a novel zinc-finger nuclease-targeted gene knockout approach.

    Science.gov (United States)

    Li, Hong-Wei; Yang, Xiang-Min; Tang, Juan; Wang, Shi-Jie; Chen, Zhi-Nan; Jiang, Jian-Li

    2015-03-01

    HAb18G/CD147 belongs to the immunoglobulin superfamily and predominantly functions as an inducer of matrix metalloproteinase secretion for tumor invasion and metastasis. This study was designed to investigate the effects of HAb18G/CD147 knockout on hepatocellular carcinoma cells using zinc-finger nuclease (ZFNs)-targeted gene knockout approach. The HCC cell line SMMC-7721 was used for ZFNs-targeted cleavage of the HAb18G/CD147 gene. RT-PCR and Western blot assays were used to detect HAb18G/CD147 expression. HAb18G phenotypic changes following HAb18G/CD147 knockout in SMMC-K7721 cells were assessed using tumor cell adhesion, invasion, migration and colony formation and flow cytometric assays. These data demonstrated that tumor cell adhesion, invasion, migration, and colony formation capabilities of SMMC-K7721 were significantly reduced compared to parental cells or SMMC-7721 with re-expression of HAb18G/CD147 protein transfected with HAb18G/CD147 cDNA. Moreover, knockout of HAb18G/CD147 expression also induced SMMC-K7721 cells to undergo apoptosis compared to SMMC-7721 and SMMC-R7721 (P CD147 reduced p53 levels in SMMC-R7721 cells, possibly through inhibition of the PI3K-Akt-MDM2 signaling pathway. The findings provide a novel insight into the mechanisms underlying HAb18G/CD147-induced progression of HCC cells.

  14. Primary microcephaly gene MCPH1 shows signatures of tumor suppressors and is regulated by miR-27a in oral squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Thejaswini Venkatesh

    Full Text Available Mutations in the MCPH1 (microcephalin 1 gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC samples, and observed that 14/71 (19.72% informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22% and 19/25 (76% OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10% tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3'-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a.

  15. Identification of Subtype-Specific Prognostic Genes for Early-Stage Lung Adenocarcinoma and Squamous Cell Carcinoma Patients Using an Embedded Feature Selection Algorithm.

    Directory of Open Access Journals (Sweden)

    Suyan Tian

    Full Text Available The existence of fundamental differences between lung adenocarcinoma (AC and squamous cell carcinoma (SCC in their underlying mechanisms motivated us to postulate that specific genes might exist relevant to prognosis of each histology subtype. To test on this research hypothesis, we previously proposed a simple Cox-regression model based feature selection algorithm and identified successfully some subtype-specific prognostic genes when applying this method to real-world data. In this article, we continue our effort on identification of subtype-specific prognostic genes for AC and SCC, and propose a novel embedded feature selection method by extending Threshold Gradient Descent Regularization (TGDR algorithm and minimizing on a corresponding negative partial likelihood function. Using real-world datasets and simulated ones, we show these two proposed methods have comparable performance whereas the new proposal is superior in terms of model parsimony. Our analysis provides some evidence on the existence of such subtype-specific prognostic genes, more investigation is warranted.

  16. The effects of combining ionizing radiation and adenovirus-mediated p53 gene transfer in human nasopharyngeal carcinoma cell lines

    International Nuclear Information System (INIS)

    Liu Feifei; Li Jianhua; Lax, Stuart; Klamut, Henry

    1997-01-01

    Purpose/Objective: We have previously demonstrated that the introduction of human recombinant wild-type p53 carried by the adenoviral vector (Ad5CMV-p53) into two human nasopharyngeal carcinoma (NPC) cell lines (CNE-1 and CNE-2Z) resulted in significant cytotoxicity. In the current work, we wanted to evaluate the results of this strategy when combined with ionizing radiation (XRT). Materials and Methods: CNE-1, CNE-2Z, and a normal human nasopharyngeal fibroblast strain KS1, were infected with iso-effective doses of 2, 6 and 6 pfu/cell of Ad5CMV-p53 respectively. XRT was administered 24 hours post-infection, to coincide with the time of maximal recombinant p53 expression. Western blot analyses were conducted for p53, p21 WAF1/CIP1 , bax and bcl-2. Cell viability was evaluated using both the MTT and clonogenic assays. Presence of apoptosis was determined by using DNA agarose gel electrophoresis. Results: We observed that the combination of Ad5CMV-p53 + XRT (2, 4, and 6 Gy) resulted in an approximately 1-log greater level of cytotoxicity compared to that observed with XRT alone for both NPC cell lines. The MTT assay indicated sparing of the KS1 cells when subjected to the identical treatments. XRT alone stimulated minimal p53 expression; Ad5CMV-p53 alone induced significant recombinant p53 expression, which was not further enhanced by the addition of XRT. Similar observations were made for p21 WAF1/CIP1 expression. No changes were observed for bax and bcl-2 expression with any of these treatments. Apoptosis was induced following 4 Gy of XRT alone, but was observed earlier, at 2 Gy when combined with Ad5CMV-p53. Conclusion: Additional cytotoxicity was observed for the NPC cell lines when XRT was combined with Ad5CMV-p53 infection, with concurrent sparing of normal cells (KS1). This cytotoxicity also appeared to be mediated through the induction of the apoptotic pathway. These results support our previous observation of the potential application of this strategy in the

  17. 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.

  18. The p16INK4alpha/p19ARF gene mutations are infrequent and are mutually exclusive to p53 mutations in Indian oral squamous cell carcinomas.

    Science.gov (United States)

    Kannan, K; Munirajan, A K; Krishnamurthy, J; Bhuvarahamurthy, V; Mohanprasad, B K; Panishankar, K H; Tsuchida, N; Shanmugam, G

    2000-03-01

    Eighty-seven untreated primary oral squamous cell carcinomas (SCCs) associated with betel quid and tobacco chewing from Indian patients were analysed for the presence of mutations in the commonly shared exon 2 of p16INK4alpha/p19ARF genes. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing analysis were used to detect mutations. SSCP analysis indicated that only 9% (8/87) of the tumours had mutation in p16INK4alpha/p19ARF genes. Seventy-two tumours studied here were previously analysed for p53 mutations and 21% (15/72) of them were found to have mutations in p53 gene. Only one tumour was found to have mutation at both p53 and p16INK4alpha/p19ARF genes. Thus, the mutation rates observed were 21% for p53, 9% for p16INK4alpha/p19ARF, and 1% for both. Sequencing analysis revealed two types of mutations; i) G to C (GCAG to CCAG) transversion type mutation at intron 1-exon 2 splice junction and ii) another C to T transition type mutation resulting in CGA to TGA changing arginine to a termination codon at p16INK4alpha gene codon 80 and the same mutation will alter codon 94 of p19ARF gene from CCG to CTG (proline to leucine). These results suggest that p16INK4alpha/p19ARF mutations are less frequent than p53 mutations in Indian oral SCCs. The p53 and p16INK4alpha/p19ARF mutational events are independent and are mutually exclusive suggesting that mutational inactivation of either p53 or p16INK4alpha/p19ARF may alleviate the need for the inactivation of the other gene.

  19. Multiple gastrointestinal metastases of Merkel cell carcinoma.

    Science.gov (United States)

    Poškus, Eligijus; Platkevičius, Gediminas; Simanskaitė, Vilma; Rimkevičiūtė, Ernesta; Petrulionis, Marius; Strupas, Kestutis

    2016-01-01

    Merkel cell carcinoma is an aggressive skin malignancy. Primary Merkel cell carcinomas are treated by wide radical excision with or without adjuvant radiotherapy, while benefits of adjuvant chemotherapy remain doubtful. There are only several cases of gastrointestinal metastases of Merkel cell carcinoma reported so far. We report a case of recurrent Merkel cell carcinoma with metastases to the stomach and the small intestines after wide excision of primary Merkel cell carcinoma. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. 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.

  1. 4β-Hydroxywithanolide E Modulates Alternative Splicing of Apoptotic Genes in Human Hepatocellular Carcinoma Huh-7 Cells.

    Science.gov (United States)

    Lee, Chien-Chin; Chang, Wen-Hsin; Chang, Ya-Sian; Liu, Ting-Yuan; Chen, Yu-Chia; Wu, Yang-Chang; Chang, Jan-Gowth

    2017-08-04

    Alternative splicing is a mechanism for increasing protein diversity from a limited number of genes. Studies have demonstrated that aberrant regulation in the alternative splicing of apoptotic gene transcripts may contribute to the development of cancer. In this study, we isolated 4β-Hydroxywithanolide E (4bHWE) from the traditional herb Physalis peruviana and investigated its biological effect in cancer cells. The results demonstrated that 4bHWE modulates the alternative splicing of various apoptotic genes, including HIPK3, SMAC/DIABLO, and SURVIVIN. We also discovered that the levels of SRSF1 phospho-isoform were decreased and the levels of H3K36me3 were increased in 4bHWE treatment. Knockdown experiments revealed that the splicing site selection of SMAC/DIABLO could be mediated by changes in the level of H3K36me3 in 4bHWE-treated cells. Furthermore, we extended our study to apoptosis-associated molecules, and detected increased levels of poly ADP-ribose polymerase cleavage and the active form of CASPASE-3 in 4bHWE-induced apoptosis. In vivo experiments indicated that the treatment of tumor-bearing mice with 4bHWE resulted in a marked decrease in tumor size. This study is the first to demonstrate that 4bHWE affects alternative splicing by modulating splicing factors and histone modifications, and provides a novel view of the antitumor mechanism of 4bHWE.

  2. Low expression of N-myc downstream-regulated gene 2 in oesophageal squamous cell carcinoma correlates with a poor prognosis

    International Nuclear Information System (INIS)

    Cao, Wei; Yu, Guozheng; Lu, Qiang; Zhang, Juliang

    2013-01-01

    It is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC). The aim of this study was to examine the underlying clinical significance of NDRG2 expression in ESCC patients and to investigate the effects of NDRG2 up-regulation on ESCC cell growth in vitro and in vivo. Immunohistochemistry was used to determine the level of NDRG2 expressions in ESCC tissue, which was then compared to specific clinicopathological features in the patient and tissue specimens. Factors associated with patient survival were analysed. Moreover, the effects of up-regulating NDRG2 expression on the growth of an ESCC cell line were examined by MTT, colony formation, DNA replication activity and nude mouse model assays. Notably low expression of NDRG2 in ESCC patients was inversely associated with clinical stage, NM classification, histological differentiation and patients’ vital status (all P < 0.05). ESCC patients expressing high levels of NDRG2 exhibited a substantially higher 5-year overall survival rate than NDRG2-negative patients. Furthermore, NDRG2 over-expression reduced the proliferation, colony formation and DNA replication activity in ESCC cells, as well as inhibiting the growth of ESCC cells in vivo. The present experiments demonstrated that NDRG2 may be a diagnostic and prognostic marker in patients with ESCC, and up-regulation of NDRG2 might act as a promising therapeutic strategy for aggressive ESCC

  3. CEBPG transcription factor correlates with antioxidant and DNA repair genes in normal bronchial epithelial cells but not in individuals with bronchogenic carcinoma

    International Nuclear Information System (INIS)

    Mullins, D'Anna N; Crawford, Erin L; Khuder, Sadik A; Hernandez, Dawn-Alita; Yoon, Youngsook; Willey, James C

    2005-01-01

    Cigarette smoking is the primary cause of bronchogenic carcinoma (BC), yet only 10–15% of heavy smokers develop BC and it is likely that this variation in risk is, in part, genetically determined. We previously reported a set of antioxidant genes for which transcript abundance was lower in normal bronchial epithelial cells (NBEC) of BC individuals compared to non-BC individuals. In unpublished studies of the same NBEC samples, transcript abundance values for several DNA repair genes were correlated with these antioxidant genes. From these data, we hypothesized that antioxidant and DNA repair genes are co-regulated by one or more transcription factors and that inter-individual variation in expression and/or function of one or more of these transcription factors is responsible for inter-individual variation in risk for BC. The putative transcription factor recognition sites common to six of the antioxidant genes were identified through in silico DNA sequence analysis. The transcript abundance values of these transcription factors (n = 6) and an expanded group of antioxidant and DNA repair genes (n = 16) were measured simultaneously by quantitative PCR in NBEC of 24 non-BC and 25 BC individuals. CEBPG transcription factor was significantly (p < 0.01) correlated with eight of the antioxidant or DNA repair genes in non-BC individuals but not in BC individuals. In BC individuals the correlation with CEBPG was significantly (p < 0.01) lower than that of non-BC individuals for four of the genes (XRCC1, ERCC5, GSTP1, and SOD1) and the difference was nearly significant for GPX1. The only other transcription factor correlated with any of these five target genes in non-BC individuals was E2F1. E2F1 was correlated with GSTP1 among non-BC individuals, but in contrast to CEBPG, there was no significant difference in this correlation in non-BC individuals compared to BC individuals. We conclude that CEBPG is the transcription factor primarily responsible for regulating

  4. Expression of the Long Intergenic Non-Protein Coding RNA 665 (LINC00665) Gene and the Cell Cycle in Hepatocellular Carcinoma Using The Cancer Genome Atlas, the Gene Expression Omnibus, and Quantitative Real-Time Polymerase Chain Reaction.

    Science.gov (United States)

    Wen, Dong-Yue; Lin, Peng; Pang, Yu-Yan; Chen, Gang; He, Yun; Dang, Yi-Wu; Yang, Hong

    2018-05-05

    BACKGROUND Long non-coding RNAs (lncRNAs) have a role in physiological and pathological processes, including cancer. The aim of this study was to investigate the expression of the long intergenic non-protein coding RNA 665 (LINC00665) gene and the cell cycle in hepatocellular carcinoma (HCC) using database analysis including The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and quantitative real-time polymerase chain reaction (qPCR). MATERIAL AND METHODS Expression levels of LINC00665 were compared between human tissue samples of HCC and adjacent normal liver, clinicopathological correlations were made using TCGA and the GEO, and qPCR was performed to validate the findings. Other public databases were searched for other genes associated with LINC00665 expression, including The Atlas of Noncoding RNAs in Cancer (TANRIC), the Multi Experiment Matrix (MEM), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) networks. RESULTS Overexpression of LINC00665 in patients with HCC was significantly associated with gender, tumor grade, stage, and tumor cell type. Overexpression of LINC00665 in patients with HCC was significantly associated with overall survival (OS) (HR=1.47795%; CI: 1.046-2.086). Bioinformatics analysis identified 469 related genes and further analysis supported a hypothesis that LINC00665 regulates pathways in the cell cycle to facilitate the development and progression of HCC through ten identified core genes: CDK1, BUB1B, BUB1, PLK1, CCNB2, CCNB1, CDC20, ESPL1, MAD2L1, and CCNA2. CONCLUSIONS Overexpression of the lncRNA, LINC00665 may be involved in the regulation of cell cycle pathways in HCC through ten identified hub genes.

  5. Squamous Cell Carcinoma In Situ Overlying Merkel Cell Carcinoma.

    Science.gov (United States)

    McGowan, Maria A; Helm, Matthew F; Tarbox, Michelle B

    2016-11-01

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neoplasm that has exhibited an exponential increase in incidence in the past 3 decades. Combined MCC and cutaneous squamous cell carcinoma (SCC/MCC) is an uncommon variant of MCC that exhibits worse prognosis than pure MCC. To describe the clinical presentation, dermoscopy, and histology of an unusual subtype of combined SCC/MCC. A 73-year-old white woman presented with an ulcerated and violaceous 10-mm plaque on her right jawline that had been present for 2 to 3 months. On dermoscopy, the lesion was predominantly milky pink to red with peripheral crusting and large-caliber polymorphous vessels. Histology revealed SCC in situ above and adjacent to MCC. The tumor was excised with clear margins, and sentinel lymph node scintography was negative for nodal involvement. © The Author(s) 2016.

  6. The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells.

    Science.gov (United States)

    Koochekpour, S; Jeffers, M; Wang, P H; Gong, C; Taylor, G A; Roessler, L M; Stearman, R; Vasselli, J R; Stetler-Stevenson, W G; Kaelin, W G; Linehan, W M; Klausner, R D; Gnarra, J R; Vande Woude, G F

    1999-09-01

    Loss of function in the von Hippel-Lindau (VHL) tumor suppressor gene occurs in familial and most sporadic renal cell carcinomas (RCCs). VHL has been linked to the regulation of cell cycle cessation (G(0)) and to control of expression of various mRNAs such as for vascular endothelial growth factor. RCC cells express the Met receptor tyrosine kinase, and Met mediates invasion and branching morphogenesis in many cell types in response to hepatocyte growth factor/scatter factor (HGF/SF). We examined the HGF/SF responsiveness of RCC cells containing endogenous mutated (mut) forms of the VHL protein (VHL-negative RCC) with that of isogenic cells expressing exogenous wild-type (wt) VHL (VHL-positive RCC). We found that VHL-negative 786-0 and UOK-101 RCC cells were highly invasive through growth factor-reduced (GFR) Matrigel-coated filters and exhibited an extensive branching morphogenesis phenotype in response to HGF/SF in the three-dimensional (3D) GFR Matrigel cultures. In contrast, the phenotypes of A498 VHL-negative RCC cells were weaker, and isogenic RCC cells ectopically expressing wt VHL did not respond at all. We found that all VHL-negative RCC cells expressed reduced levels of tissue inhibitor of metalloproteinase 2 (TIMP-2) relative to the wt VHL-positive cells, implicating VHL in the regulation of this molecule. However, consistent with the more invasive phenotype of the 786-0 and UOK-101 VHL-negative RCC cells, the levels of TIMP-1 and TIMP-2 were reduced and levels of the matrix metalloproteinases 2 and 9 were elevated compared to the noninvasive VHL-positive RCC cells. Moreover, recombinant TIMPs completely blocked HGF/SF-mediated branching morphogenesis, while neutralizing antibodies to the TIMPs stimulated HGF/SF-mediated invasion in vitro. Thus, the loss of the VHL tumor suppressor gene is central to changes that control tissue invasiveness, and a more invasive phenotype requires additional genetic changes seen in some but not all RCC lines. These

  7. p53 immunostaining is correlated with reduced survival and is not correlated with gene mutations in resected pulmonary large cell carcinomas

    Directory of Open Access Journals (Sweden)

    L.M. Massoni Neto

    2007-08-01

    Full Text Available Malignancy of pulmonary large cell carcinomas (LCC increases from classic LCC through LCC with neuroendocrine morphology (LCCNM to large cell neuroendocrine carcinomas (LCNEC. However, the histological classification has sometimes proved to be difficult. Because the malignancy of LCC is highly dependent on proteins with functions in the cell cycle, DNA repair, and apoptosis, p53 has been targeted as a potentially useful biological marker. p53 mutations in lung cancers have been shown to result in expression and protein expression also occurs in the absence of mutations. To validate the importance of both p53 protein expression (by immunostaining and p53 gene mutations in lung LCC (by PCR-single strand conformational polymorphism analysis of exons 5, 6, 7, and 8 and to study their relationships with clinical factors and sub-classification we investigated the correlation of p53 abnormalities in 15 patients with LCC (5 classic LCC, 5 LCNEC, and 5 LCCNM who had undergone resection with curative intent. Of these patients, 5/15 expressed p53 and none had mutant p53 sequences. There was a negative survival correlation with positive p53 immunostaining (P = 0.05. After adjustment for stage, age, gender, chemotherapy, radiotherapy, and histological subtypes by multivariate analysis, p53 expression had an independent impact on survival. The present study indicates that p53 assessment may provide an objective marker for the prognosis of LCC irrespective of morphological variants and suggests that p53 expression is important for outcome prediction in patients with the early stages of LCC. The results reported here should be considered to be initial results because tumors from only 15 patients were studied: 5 each from LCC, LCNEC and LCCNM. This was due to the rarity of these specific diseases.

  8. Promoter hypermethylation of CDKN2A, MGMT, MLH1, and DAPK genes in laryngeal squamous cell carcinoma and their associations with clinical profiles of the patients.

    Science.gov (United States)

    Pierini, Stefano; Jordanov, Stanislav H; Mitkova, Atanaska V; Chalakov, Ivan J; Melnicharov, Mincho B; Kunev, Kuncho V; Mitev, Vanio I; Kaneva, Radka P; Goranova, Teodora E

    2014-08-01

    Laryngeal squamous cell carcinoma (laryngeal SCC) is a frequently occurring cancer of the head and neck area. Epigenetic changes of tumor-related genes contribute to its genesis and progression. We assessed promoter methylation status of the selected genes (CDKN2A, MGMT, MLH1, and DAPK) using methylation-sensitive high resolution melting (MS-HRM) in 100 patients with laryngeal SCC and studied the correlations with clinical characteristics. The prevalence of promoter methylation in MGMT, CDKN2A, MLH1, and DAPK was 59 of 97 (60.8%), 46 of 97 (47.4%), 45 of 97 (46.4%), and 41 of 97 patients (42.3%), respectively. Significantly increased methylation of CDKN2A was observed in heavy smokers. Epigenetic inactivation of CDKN2A and MLH1 were found to be associated with lymph node involvement. An inverse correlation was present between MLH1 methylation and alcohol consumption. Our results strongly suggest that deregulation of p16-associated, and MLH1-associated pathways, because of promoter hypermethylation, is associated with increased cancer cell migration, tumor invasiveness, and, thus, aggressive phenotype. Copyright © 2013 Wiley Periodicals, Inc.

  9. 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

  10. A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

    Science.gov (United States)

    Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

    1999-01-01

    We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

  11. Update on Merkel Cell Carcinoma.

    Science.gov (United States)

    Harms, Paul W

    2017-09-01

    Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine malignancy. Merkel cell polyomavirus, a tumorigenic DNA virus, is present in most MCC tumors, with implications for tumor biology, diagnosis, and management. Merkel cell polyomavirus-negative tumors have a high burden of UV-signature mutations, similar to melanoma. The histopathologic diagnosis of MCC requires immunohistochemistry to exclude morphologically similar entities. Therapies for advanced disease are currently lacking. Here, the features of MCC are reviewed, including recent molecular discoveries with implications for improved therapy for advanced disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and immunohistochemistry

    International Nuclear Information System (INIS)

    Sato-Kuwabara, Yukie; Neves, José I; Fregnani, José HTG; Sallum, Rubens A; Soares, Fernando A

    2009-01-01

    Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent neoplasia in Brazil. It is usually associated with a poor prognosis because it is often at an advanced stage when diagnosed and there is a high frequency of lymph node metastases. It is important to know what prognostic factors can facilitate diagnosis, optimize therapeutic decisions, and improve the survival of these patients. A member of the epidermal growth factor receptor (EGFR) family, c-erbB-2, has received much attention because of its therapeutic implications; however, few studies involving fluorescence in situ hybridization (FISH) analysis of HER-2/neu gene amplification and protein expression in ESCC have been conducted. The aim of this study was to verify the presence of HER-2/neu gene amplification using FISH, and to correlate the results with immunohistochemical expression and clinical-pathological findings. One hundred and ninety-nine ESCC cases were evaluated using the Tissue Microarray (TMA) technique. A polyclonal antibody against c-erbB-2 was used for immunohistochemistry. Analyses were based on the membrane staining pattern. The results were classified according to the Herceptest criteria (DAKO): negative (0/1+), potential positive (2+) and positive (3+). The FISH reactions were performed according to the FISH HER2 PharmDx (DAKO) protocol. In each case, 100 tumor nuclei were evaluated. Cases showing a gene/CEN17 fluorescence ratio ≥ 2 were considered positive for gene amplification. The c-erbB-2 expression was negative in 117/185 cases (63.2%) and positive in 68 (36.8%), of which 56 (30.3%) were 2+ and 12 (6.5%) were 3+. No significant associations were found among protein expression, clinicopathological data and overall survival. Among the 47 cases analyzed, 38 (80.9%) showed no gene amplification while 9 (19.1%) showed amplification, as demonstrated by FISH. Cases that were negative (0/1+) and potential positive (2+) for c-erbB-2 expression by immunohistochemistry showed no

  13. Merkel cell carcinoma in an immunosuppressed patient.

    Science.gov (United States)

    Góes, Heliana Freitas de Oliveira; Lima, Caren Dos Santos; Issa, Maria Cláudia de Almeida; Luz, Flávio Barbosa; Pantaleão, Luciana; Paixão, José Gabriel Miranda da

    2017-01-01

    Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

  14. BRCA1 is expressed in uterine serous carcinoma (USC) and controls insulin-like growth factor I receptor (IGF-IR) gene expression in USC cell lines.

    Science.gov (United States)

    Amichay, Keren; Kidron, Debora; Attias-Geva, Zohar; Schayek, Hagit; Sarfstein, Rive; Fishman, Ami; Werner, Haim; Bruchim, Ilan

    2012-06-01

    The insulin-like growth factor I receptor (IGF-IR) and BRCA1 affect cell growth and apoptosis. Little information is available about BRCA1 activity on the IGF signaling pathway. This study evaluated the effect of BRCA1 on IGF-IR expression. BRCA1 and IGF-IR immunohistochemistry on archival tissues (35 uterine serous carcinomas [USCs] and 17 metastases) were performed. USPC1 and USPC2 cell lines were transiently cotransfected with an IGF-IR promoter construct driving a luciferase reporter gene and a BRCA1 expression plasmid. Endogenous IGF-IR levels were evaluated by Western immunoblotting. We found high BRCA1 and IGF-IR protein expression in primary and metastatic USC tumors. All samples were immunostained for BRCA1-71% strongly stained; and 33/35 (94%) were stained positive for IGF-IR-2 (6%) strongly stained. No difference in BRCA1 and IGF-IR staining intensity was noted between BRCA1/2 mutation carriers and noncarriers. Metastatic tumors stained more intensely for BRCA1 than did the primary tumor site (P = 0.041) and with borderline significance for IGF-IR (P = 0.069). BRCA1 and IGF-IR staining did not correlate to survival. BRCA1 expression led to 35% and 54% reduction in IGF-IR promoter activity in the USPC1 and USCP2 cell lines, respectively. Western immunoblotting showed a decline in phosphorylated IGF-IR and phosphorylated AKT in both transiently and stably transfected cells. BRCA1 and IGF-IR are highly expressed in USC tumors. BRCA1 suppresses IGF-IR gene expression and activity. These findings suggest a possible biological link between the BRCA1 and the IGF-I signaling pathways in USC. The clinical implications of this association need to be explored.

  15. Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Chakraborty, Sanjukta; Mohiyuddin, SM Azeem; Gopinath, KS; Kumar, Arun

    2008-01-01

    Despite extensive research, the five-year survival rate of oral squamous cell carcinoma (OSCC) patients has not improved. Effective treatment of OSCC requires the identification of molecular targets and signaling pathways to design appropriate therapeutic strategies. Several genes from the mTOR signaling pathway are known to be dysregulated in a wide spectrum of cancers. However, not much is known about the involvement of this pathway in tumorigenesis of OSCC. We therefore investigated the role of the tumor suppressor genes, TSC1 and TSC2, and other members of this pathway in tumorigenesis of OSCC. Expression of genes at the RNA and protein levels was examined by semi-quantitative RT-PCR and western blot analyses, respectively. Loss of heterozygosity was studied using matched blood and tumor DNA samples and microsatellite markers from the TSC1, TSC2 and PTEN candidate regions. The effect of promoter methylation on TSC gene expression was studied by treating cells with methyltransferase inhibitor 5-azacytidine. Methylation status of the TSC2 promoter in tissue samples was examined by combined bisulfite restriction analysis (COBRA). The semi-quantitative RT-PCR analysis showed downregulation of TSC1, TSC2, EIF4EBP1 and PTEN, and upregulation of PIK3C2A, AKT1, PDPK1, RHEB, FRAP1, RPS6KB1, EIF4E and RPS6 in tumors. A similar observation was made for AKT1 and RPS6KB1 expression in tumors at the protein level. Investigation of the mechanism of downregulation of TSC genes identified LOH in 36.96% and 39.13% of the tumors at the TSC1 and TSC2 loci, respectively. No mutation was found in TSC genes. A low LOH rate of 13% was observed at the PTEN locus. Treatment of an OSCC cell line with the methyltransferase inhibitor 5-azacytidine showed a significant increase in the expression of TSC genes, suggesting methylation of their promoters. However, the 5-azacytidine treatment of non-OSCC HeLa cells showed a significant increase in the expression of the TSC2 gene only. In order

  16. 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...

  17. Bifidobacterium breve as a delivery vector of IL-24 gene therapy for head and neck squamous cell carcinoma in vivo.

    Science.gov (United States)

    Wang, L; Vuletic, I; Deng, D; Crielaard, W; Xie, Z; Zhou, K; Zhang, J; Sun, H; Ren, Q; Guo, C

    2017-11-01

    Beneficial bacteria are becoming ever more popular gene delivery method for hypoxia-tumor targeting in vivo. In this study we investigated the therapeutic effect of new recombinant Bifidobacterium breve strain expressing interleukin (IL)-24 gene (B. breve-IL24) on head and neck tumor xenograft in mice. Briefly, B. breve transformants were obtained through electro-transformation. Bacteria-tumor-targeting ability were analyzed in vivo over different time points (1, 3 and 7 days post-bacteria injection). Furthermore, the therapeutic effect of bacteria on tumor cells in vivo were analyzed as follows: 30 Balb/c nude mice bearing subcutaneous tumor were randomly divided in three groups (Drug group, green fluorescent protein (GFP) group and Saline group). The therapy lasted for 2 weeks and included B. breve-IL24 administration via tail vein for Drug group, B. breve-GFP for GFP group and phosphate buffered saline for Saline group. The tumor growth was monitored using standard caliper technique, while the apoptosis induction in vivo was analyzed by Real-time Positron Emission Tomography/Computed Tomography (PET/CT) imaging ([18F]-ML-10 tracer). At the end of the experiment, tumor tissues were collected and analyzed by western blotting. Briefly, our results suggested that our new recombinant bacterium has the capability of targeting tumor tissue in vivo. As for the therapeutic effect, our new strain has revealed to be a promising therapeutic approach against tumor growth in vivo. Briefly, higher tumor growth inhibition and higher tumor cell apoptosis induction were observed in Drug group compared with the GFP and Saline groups. To conclude, a new recombinant strain B. breve-IL24 offers a novel, safe and clinically acceptable therapeutic approach for tumor therapy in vivo.

  18. Validation of the 16-Gene Recurrence Score in patients with locoregional, high-risk renal cell carcinoma from a phase 3 trial of adjuvant sunitinib.

    Science.gov (United States)

    Rini, Brian I; Escudier, Bernard; Martini, Jean-Francois; Magheli, Ahmed; Svedman, Christer; Lopatin, Margarita; Knezevic, Dejan; Goddard, Audrey D; Febbo, Phillip G; Li, Rachel; Lin, Xun; Valota, Olga; Staehler, Michael; Motzer, Robert J; Ravaud, Alain

    2018-05-17

    Adjuvant sunitinib prolonged disease-free survival (DFS) (hazard ratio [HR] 0.76) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov NCT00375674). The 16-gene Recurrence Score (RS) assay was previously developed and validated to estimate risk for disease recurrence in patients with RCC post-nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored association of RS results with prediction of sunitinib benefit. The analysis was prospectively designed with prespecified genes, algorithm, endpoints, and analytical methods. Primary RCC was available from 212 patients with informed consent; primary analysis focused on patients with T3 RCC. Gene expression was quantitated by RT-PCR. Time to recurrence (TTR), DFS, and renal cancer-specific survival (RCSS) were analyzed using Cox proportional hazards regression. Results: Baseline characteristics were similar between patients with and without RS results, and between the sunitinib and placebo arms among patients with RS results. RS results predicted TTR, DFS, and RCSS in both arms, with the strongest results observed in the placebo arm. When high versus low RS groups were compared, HR for recurrence was 9.18 (95% CI, 2.15-39.24; P < 0.001) in the placebo arm; interaction of RS results with treatment was not significant. Conclusions: The strong prognostic performance of the 16-gene RS assay was confirmed in S-TRAC, and the RS assay is now supported by level IB evidence. RS results may help identify patients at high risk for recurrence who may derive higher absolute benefit from adjuvant therapy. Copyright ©2018, American Association for Cancer Research.

  19. Promoter hypermethylation-induced transcriptional down-regulation of the gene MYCT1 in laryngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Yang, Min; Li, Wei; Liu, Yi-Ying; Fu, Shuang; Qiu, Guang-Bin; Sun, Kai-Lai; Fu, Wei-Neng

    2012-01-01

    MYCT1, previously named MTLC, is a novel candidate tumor suppressor gene. MYCT1 was cloned from laryngeal squamous cell cancer (LSCC) and has been found to be down-regulated in LSCC; however, the regulatory details have not been fully elucidated. Here, we sought to investigate the methylation status of the CpG islands of MYCT1 and mRNA levels by bisulfite-specific PCR (BSP) based on sequencing restriction enzyme digestion, reverse transcription and real-time quantitative polymerase chain reaction (RQ-PCR). The function of specific sites in the proximal promoter of MYCT1 in LSCC was measured by transient transfection, luciferase assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). The results suggested hypermethylation of 12 CpG sites of the promoter in both laryngeal cancer tissues and the laryngeal cancer line Hep-2 cell. The hypermethylation of the site CGCG (−695 to −692), which has been identified as the c-Myc binding site, was identified in laryngeal cancer tissues (59/73) compared to paired mucosa (13/73); in addition, statistical analysis revealed that the methylation status of this site significantly correlated with cancer cell differentiation(p < 0.01). The mRNA level of MYCT1 increased in Hep-2 cells treated with 5-aza-C (p < 0.01). The luciferase activity from mutant transfectants pGL3-MYCT1m (−852/+12, mut-695-C > A, mut-693-C > G) was significantly reduced compared with the wild type pGL3-MYCT1 (−852/+12), while the luciferase activity from wild transfectants pGL3-MYCT1 (−852/+12) rose after 5-aza treatment in Hep-2 cells. Finally, EMSA and ChIP confirmed that the methylation of the CGCG (−695 to −692) site prevented c-Myc from binding of the site and demethylation treatment of the 5′ flanking region of MYCT1 by 5-aza induced the increased occupation of the core promoter by c-Myc (p < 0.01). In summary, this study concluded that hypermethylation contributed to the transcriptional down

  20. 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.

  1. Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma.

    Science.gov (United States)

    Hynds, Robert E; Janes, Sam M

    2017-09-01

    Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491-3. ©2017 AACR See related article by Pagano et al., p. 514 . ©2017 American Association for Cancer Research.

  2. 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.

  3. High E6 Gene Expression Predicts for Distant Metastasis and Poor Survival in Patients With HPV-Positive Oropharyngeal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Khwaja, Shariq S.; Baker, Callie; Haynes, Wesley; Spencer, Christopher R.; Gay, Hiram; Thorstad, Wade [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Adkins, Douglas R. [Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri (United States); Nussenbaum, Brian [Department of Otolaryngology – Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Chernock, Rebecca D. [Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri (United States); Lewis, James S. [Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee (United States); Wang, Xiaowei, E-mail: xwang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2016-07-15

    Purpose: Patients with human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC) have a favorable prognosis. As a result, de-escalation clinical trials are under way. However, approximately 10% of patients will experience distant recurrence even with standard-of-care treatment. Here, we sought to identify novel biomarkers to better risk-stratify HPV-positive patients with OPSCC. Methods and Materials: Gene expression profiling by RNA sequencing (RNA-seq) and quantitative polymerase chain reaction was performed on HPV-positive OPSCC primary tumor specimens from patients with and without distant metastasis (DM). Results: RNA-seq analysis of 39 HPV-positive OPSCC specimens revealed that patients with DM had 2-fold higher E6 gene expression levels than did patients without DM (P=.029). This observation was confirmed in a validation cohort comprising 93 patients with HPV-positive OPSCC. The mean normalized E6 expression level in the 17 recurring primary specimens was 13 ± 2 compared with 8 ± 1 in the remaining 76 nonrecurring primaries (P=.001). Receiver operating characteristic analysis established an E6 expression level of 7.3 as a cutoff for worse recurrence-free survival (RFS). Patients from this cohort with high E6 gene expression (E6-high) (n=51, 55%) had more cancer-related deaths (23% vs 2%, P<.001) and DM (26% vs 5%, P<.001) than did patients with low E6 gene expression (E6-low) (n=42, 45%). Kaplan-Meier survival analysis revealed that E6-high had worse RFS (95% vs 69%, P=.004) and cancer-specific survival (97% vs 79%, P=.007). E6-high maintained statistical significance in multivariate regression models balancing surgery, chemotherapy, nodal stage, and smoking status. Gene set enrichment analysis demonstrated that tumors with high E6 expression were associated with P53, epidermal growth factor receptor, activating transcription factor-2, and transforming growth factor-β signaling pathways. Conclusion: High E6 gene expression

  4. Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: Metastasis or second primary?

    NARCIS (Netherlands)

    Geurts, Tom W.; Nederlof, Petra M.; van den Brekel, Michiel W. M.; van't Veer, Laura J.; de Jong, Daphne; Hart, August A. M.; van Zandwijk, Nico; Klomp, Houke; Balm, Alfons J. M.; van Velthuysen, Marie-Louise F.

    2005-01-01

    Purpose: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. Experimental Design: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a

  5. Genetic inactivation of the Fanconi anemia gene FANCC identified in the hepatocellular carcinoma cell line HuH-7 confers sensitivity towards DNA-interstrand crosslinking agents

    Directory of Open Access Journals (Sweden)

    Bassermann Florian

    2010-05-01

    Full Text Available Abstract Background Inactivation of the Fanconi anemia (FA pathway through defects in one of 13 FA genes occurs at low frequency in various solid cancer entities among the general population. As FA pathway inactivation confers a distinct hypersensitivity towards DNA interstrand-crosslinking (ICL-agents, FA defects represent rational targets for individualized therapeutic strategies. Except for pancreatic cancer, however, the prevalence of FA defects in gastrointestinal (GI tumors has not yet been systematically explored. Results A panel of GI cancer cell lines was screened for FA pathway inactivation applying FANCD2 monoubiquitination and FANCD2/RAD51 nuclear focus formation and a newly identified FA pathway-deficient cell line was functionally characterized. The hepatocellular carcinoma (HCC line HuH-7 was defective in FANCD2 monoubiquitination and FANCD2 nuclear focus formation but proficient in RAD51 focus formation. Gene complementation studies revealed that this proximal FA pathway inactivation was attributable to defective FANCC function in HuH-7 cells. Accordingly, a homozygous inactivating FANCC nonsense mutation (c.553C > T, p.R185X was identified in HuH-7, resulting in partial transcriptional skipping of exon 6 and leading to the classic cellular FA hypersensitivity phenotype; HuH-7 cells exhibited a strongly reduced proliferation rate and a pronounced G2 cell cycle arrest at distinctly lower concentrations of ICL-agents than a panel of non-isogenic, FA pathway-proficient HCC cell lines. Upon retroviral transduction of HuH-7 cells with FANCC cDNA, FA pathway functions were restored and ICL-hypersensitivity abrogated. Analyses of 18 surgical HCC specimens yielded no further examples for genetic or epigenetic inactivation of FANCC, FANCF, or FANCG in HCC, suggesting a low prevalence of proximal FA pathway inactivation in this tumor type. Conclusions As the majority of HCC are chemoresistant, assessment of FA pathway function in HCC could

  6. Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu).

    Science.gov (United States)

    Luan, Jinwei; Li, Xianglan; Guo, Rutao; Liu, Shanshan; Luo, Hongyu; You, Qingshan

    2016-06-01

    Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses. Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. Furthermore, ClueGO was used for pathway enrichment analysis of genes in the PPI network. Total 2,040 and 297 DEGs were identified in FaDu cells treated with 8 Gy X-ray or 8 Gy X-ray + RITA, respectively. PARP3 and NEIL1 were enriched in base excision repair, and CDK1 was enriched in p53 signaling pathway. RFC2 and EZH2 were identified as RITA genes. In the PPI network, many interaction relationships were identified (e.g., RFC2-CDK1, EZH2-CDK1 and PARP3-EZH2). ClueGO analysis showed that RFC2 and EZH2 were related to cell cycle. RFC2, EZH2, CDK1, PARP3 and NEIL1 may be associated, and together enhance the susceptibility of FaDu cells treated with RITA to the deleterious effects of X-ray.

  7. Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu)

    International Nuclear Information System (INIS)

    Luan, Jinwei; Li, Xianglan; Guo, Rutao; Liu, Shanshan; Luo, Hongyu; You, Qingshan

    2016-01-01

    Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses. Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. Furthermore, ClueGO was used for pathway enrichment analysis of genes in the PPI network. Total 2,040 and 297 DEGs were identified in FaDu cells treated with 8 Gy X-ray or 8 Gy X-ray + RITA, respectively. PARP3 and NEIL1 were enriched in base excision repair, and CDK1 was enriched in p53 signaling pathway. RFC2 and EZH2 were identified as RITA genes. In the PPI network, many interaction relationships were identified (e.g., RFC2-CDK1, EZH2-CDK1 and PARP3-EZH2). ClueGO analysis showed that RFC2 and EZH2 were related to cell cycle. RFC2, EZH2, CDK1, PARP3 and NEIL1 may be associated, and together enhance the susceptibility of FaDu cells treated with RITA to the deleterious effects of X-ray

  8. Transforming capacity of two novel genes JS-1 and JS-2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma.

    Science.gov (United States)

    Fatima, Sarwat; Chui, Chung H; Tang, Wing K; Hui, Kin S; Au, Ho W; Li, Wing Y; Wong, Mei M; Cheung, Filly; Tsao, S W; Lam, King Y; Beh, Philip S L; Wong, John; Law, Simon; Srivastava, Gopesh; Ho, Kwok P; Chan, Albert S C; Tang, Johnny C O

    2006-01-01

    Esophageal squamous cell carcinoma (ESCC) has a high mortality rate and geographic differences in incidence. Previous studies of comparative genomic hybridization (CGH) showed that chromosomal 5p is frequently amplified in cell lines and primary ESCC of Hong Kong Chinese origin. In this report, attempt was made to study two novel genes, named as JS-1 and JS-2, which are located in chromosome 5p15.2 and are 5' upstream to delta catenin for their roles in molecular pathogenesis of ESCC. Eleven cell lines, 27 primary ESCC cases and multiple human tissue cDNA panels (MTC) of digestive system were studied for the expression level of JS-1 and JS-2 by RT-PCR. The full-length cDNA sequences of JS-1 and JS-2 were determined from a non-tumor esophageal epithelial cell line by 3' and 5' rapid amplification of cDNA ends (RACE). The transforming capacity of JS-1 and JS-2 was also investigated by transfecting NIH 3T3 cells with the expression vector pcDNA3.1(-) cloned with the full coding sequences and it was followed by the study of foci formation of the transfected cells under confluence growth and the anchorage-independent growth in soft agar. Forty-five percent (5/11) and 18% (2/11) of the ESCC cell lines showed overexpression of JS-1 and JS-2 respectively, while 55% (15/27) and 14% (3/22) primary ESCC cases showed overexpression of JS-1 and JS-2 respectively. JS-1 overexpression was most common in patients with stage II ESCC (6/27; 22%) whereas JS-2 was only overexpressed in a dysplastic lesion (1/22; 4%) and stage III tumors (2/22; 9%). The expression levels of JS-1 and JS-2 are both low in normal esophageal tissues. Overexpression of JS-1 in NIH 3T3 cells caused foci formation in confluence growth and colony formation in soft agar but not for JS-2. A high grade sarcoma was formed in the athymic nude mice when NIH 3T3 cells overexpressing JS-1 were injected subcutaneously. Our results thus indicate that the frequent overexpression of JS-1 in ESCC and its transforming

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

    Science.gov (United States)

    ... and neck squamous cell carcinoma Head and neck squamous cell carcinoma Printable PDF Open All Close All Enable Javascript ... Consumer Version: Overview of Mouth, Nose, and Throat Cancers Orphanet: Squamous cell carcinoma of head and neck University of Michigan ...

  10. Transcriptomic dissection of tongue squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Schwartz Joel L

    2008-02-01

    Full Text Available Abstract Background The head and neck/oral squamous cell carcinoma (HNOSCC is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC. Results Genome-wide transcriptomic profiles were obtained for 53 primary OTSCCs and 22 matching normal tissues. Genes that exhibit statistically significant differences in expression between OTSCCs and normal were identified. These include up-regulated genes (MMP1, MMP10, MMP3, MMP12, PTHLH, INHBA, LAMC2, IL8, KRT17, COL1A2, IFI6, ISG15, PLAU, GREM1, MMP9, IFI44, CXCL1, and down-regulated genes (KRT4, MAL, CRNN, SCEL, CRISP3, SPINK5, CLCA4, ADH1B, P11, TGM3, RHCG, PPP1R3C, CEACAM7, HPGD, CFD, ABCA8, CLU, CYP3A5. The expressional difference of IL8 and MMP9 were further validated by real-time quantitative RT-PCR and immunohistochemistry. The Gene Ontology analysis suggested a number of altered biological processes in OTSCCs, including enhancements in phosphate transport, collagen catabolism, I-kappaB kinase/NF-kappaB signaling cascade, extracellular matrix organization and biogenesis, chemotaxis, as well as suppressions of superoxide release, hydrogen peroxide metabolism, cellular response to hydrogen peroxide, keratinization, and keratinocyte differentiation in OTSCCs. Conclusion In summary, our study provided a transcriptomic signature for OTSCC that may lead to a diagnosis or screen tool and provide the foundation for further functional validation of these specific candidate genes for OTSCC.

  11. 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.

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

    Science.gov (United States)

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

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. Copyright © 2016 Elsevier GmbH. All rights reserved.

  13. Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array

    Directory of Open Access Journals (Sweden)

    Goldstein Alisa M

    2006-11-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. Results Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP array, including loss of heterozygosity (LOH and copy number alterations (CNA, for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods – using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT software – and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q, including 20 novel LOH regions (10 kb to 4.26 Mb. Fifteen CNA-loss regions (200 kb to 4.3 Mb and 36 CNA-gain regions (200 kb to 9.3 Mb were also identified. Conclusion These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

  14. The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin.

    LENUS (Irish Health Repository)

    Flanagan, Annabelle M

    2007-04-01

    Skin cancer, the most common cancer in the general population, is strongly associated with exposure to the ultraviolet component of sunlight. To investigate the relationship between DNA damage processing and skin tumour development, we determined the POLH status of a cohort of skin cancer patients. The human POLH gene encodes DNA polymerase eta (poleta), which normally carries out accurate translesion synthesis past the major UV-induced photoproduct, the dithymine cyclobutane dimer. In the absence of active poleta in xeroderma pigmentosum variant (XPV) patients, mutations accumulate at sites of UV-induced DNA damage, providing the initiating step in skin carcinogenesis. Forty patients diagnosed with skin cancer were genotyped for polymorphisms in the POLH protein-coding sequence, using glycosylase-mediated polymorphism detection (GMPD) and direct DNA sequencing of POLH PCR products derived from white blood cell genomic DNA. All individuals carried the wild-type POLH sequence. No POLH mutations were identified in genomic DNA from skin tumours derived from 15 of these patients. As determined by RT-PCR, POLH mRNA was expressed in all normal and skin tumour tissue examined. Poleta protein was also detectable by Western blotting, in two matched normal and skin tumour extracts. An alternatively spliced form of POLH mRNA, lacking exon 2, was more readily detected in skin tissue than in white blood cells from the same patient. Real-time PCR was used to quantify POLH expression in matched normal and skin tumour-derived mRNA from a series of patients diagnosed with either basal or squamous cell carcinoma. Compared to matched normal skin tissue from the same patient, 1 of 7 SCC, and 4 of 10 BCC tumours examined showed at least a 2-fold reduction in POLH expression, while 1 of 7 SCC, and 3 of 10 BCC tumours showed at least a 2-fold increase in POLH expression. Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies

  15. Neglected basal cell carcinoma on scalp

    Directory of Open Access Journals (Sweden)

    Sudip Sarkar

    2016-01-01

    Full Text Available Giant basal cell carcinoma (BCC is a very rare entity. Usually, they occur due to the negligence of the patient. Local or distant metastasis is present in most cases. Here, we present a case of giant BCC that clinically resembled squamous cell carcinoma and demonstrated no metastasis at presentation.

  16. Combination therapies in oral squamous cell carcinomas

    International Nuclear Information System (INIS)

    Krishnamurthi, S.; Shanta, V.

    1982-01-01

    The clinical trials are reported involving combined radiotherapy and chemotherapy in oral squamous cell carcinomas. Bleomycin was the only drug that potentiated radiation response in buccal squamous cell carcinomas. The response of the primary tumors was consistent, predictable and reproducible. The following drugs or chemicals were used: synkavit, methotrexate, metronidazole, bleomycin, pepleomycin, and hyperbaric oxygen. The results and their comparison is given in tables

  17. Dose dependent activation of retinoic acid-inducible gene-I promotes both proliferation and apoptosis signals in human head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jingzhou Hu

    Full Text Available The retinoic-acid-inducible gene (RIG-like receptor (RLR family proteins are major pathogen reorganization receptors (PRR responsible for detection of viral RNA, which initiates antiviral response. Here, we evaluated the functional role of one RLR family member, RIG-I, in human head and neck squamous cell carcinoma (HNSCC. RIG-I is abundantly expressed both in poorly-differentiated primary cancer and lymph node metastasis, but not in normal adjacent tissues. Activation of RIG-I by transfection with low dose of 5'-triphosphate RNA (3p-RNA induces low levels of interferon and proinflammatory cytokines and promotes NF-κB- and Akt-dependent cell proliferation, migration and invasion. In contrast, activation of RIG-I by a high dose of 3p-RNA induces robust mitochondria-derived apoptosis accompanied by decreased activation of Akt, which is independent of the interferon and TNFα receptor, but can be rescued by over-expression of constitutively active Akt. Furthermore, co-immunoprecipitation experiments indicate that the CARD domain of RIG-I is essential for inducing apoptosis by interacting with caspase-9. Together, our results reveal a dual role of RIG-I in HNSCC through regulating activation of Akt, in which RIG-I activation by low-dose viral dsRNA increases host cell survival, whereas higher level of RIG-I activation leads to apoptosis. These findings highlight the therapeutic potential of dsRNA mediated RIG-I activation in the treatment of HNSCC.

  18. Identification of the Key Genes and Pathways in Esophageal Carcinoma.

    Science.gov (United States)

    Su, Peng; Wen, Shiwang; Zhang, Yuefeng; Li, Yong; Xu, Yanzhao; Zhu, Yonggang; Lv, Huilai; Zhang, Fan; Wang, Mingbo; Tian, Ziqiang

    2016-01-01

    Objective . Esophageal carcinoma (EC) is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods . 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression level of DEGs in EC. Results . A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion . The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis.

  19. Identification of the Key Genes and Pathways in Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    Peng Su

    2016-01-01

    Full Text Available Objective. Esophageal carcinoma (EC is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods. 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs were screened by bioinformatics analysis. Gene Ontology (GO enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG enrichment, and protein-protein interaction (PPI network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR was used to verify the expression level of DEGs in EC. Results. A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion. The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis.

  20. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

    Science.gov (United States)

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

    2016-01-14

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

  1. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

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

    2016-01-01

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

  2. Scalp squamous cell carcinoma in xeroderma pigmentosum.

    Science.gov (United States)

    Awan, Basim A; Alzanbagi, Hanadi; Samargandi, Osama A; Ammar, Hossam

    2014-02-01

    Xeroderma pigmentosum is a rare autosomal-recessive disorder that appears in early childhood. Squamous cell carcinoma is not uncommon in patients with xeroderma pigmentosum and mostly involving the face, head, neck, and scalp. However, squamous cell carcinoma of the scalp may exhibit an aggressive course. Here, we present a huge squamous cell carcinoma of the scalp in a three-years-old child with xeroderma pigmentosum. In addition, we illustrate the challenges of a child with xeroderma pigmentosum who grows up in a sunny environment where the possibility of early onset of squamous cell carcinoma is extremely high in any suspected skin lesion. In xeroderma pigmentosum patients, squamous cell carcinoma of the scalp can present early and tends to be unusually aggressive. In sunny areas, proper education to the patient and their parents about ultra-violet light protection and early recognition of any suspicious lesion could be life-saving.

  3. Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study.

    NARCIS (Netherlands)

    Huang, J.; Fan, Q.; Lu, P.; Ying, J.; Ma, C.; Liu, W.; Liu, Y.; Tan, F.; Sun, Y

    2016-01-01

    INTRODUCTION: Epidermal growth factor receptor (EGFR) has been reported to be overexpressed and amplified in a high percentage of patients with esophageal squamous cell carcinoma (ESCC). The activity of icotinib, an EGFR tyrosine kinase inhibitor, was assessed in previously treated ESCC with EGFR

  4. Cyclin D1 gene polymorphism as a risk factor for squamous cell carcinoma of the upper aerodigestive system in non-alcoholics

    DEFF Research Database (Denmark)

    Nishimoto, Ines Nobuko; Pinheiro, Nidia Alice; Rogatto, Silvia Regina

    2004-01-01

    Squamous cell carcinoma of the upper aerodigestive tract (UADT) is associated with environmental factors, especially tobacco and alcohol consumption. Genetic factors, including cyclin D1 (CCND1) polymorphism have been suggested to play an important role in tumorigenesis and progression of UADT...

  5. Genomic instability in human actinic keratosis and squamous cell carcinoma

    Science.gov (United States)

    Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

    2011-01-01

    OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

  6. 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.

  7. Identification of Human Cutaneous Basal Cell Carcinoma Cancer Stem Cells.

    Science.gov (United States)

    Morgan, Huw; Olivero, Carlotta; Patel, Girish K

    2018-04-20

    The cancer stem cell model states that a subset of tumor cells, called "cancer stem cells," can initiate and propagate tumor growth through self-renewal, high proliferative capacity, and their ability to recreate tumor heterogeneity. In basal cell carcinoma (BCC), we have shown that tumor cells that express the cell surface protein CD200 fulfill the cancer stem cell hypothesis. CD200+ CD45- BCC cells represent 0.05-3.96% of all BCC cells and reside in small clusters at the tumor periphery. Using a novel, reproducible in vivo xenograft growth assay, we determined that tumor-initiating cell (TIC) frequencies are approximately 1 per 1.5 million unsorted BCC cells. The CD200+ CD45- BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200+ CD45- cells, representing ~1500-fold enrichment. The methods used to identify and purify CD200+ CD45- BCC cells, as well as characterize gene expression, are described herein.

  8. Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0260 TITLE: Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets PRINCIPAL INVESTIGATOR: Carla Kim... Cell Carcinoma Stem Cells as Immunotherapy Targets 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0260 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT Lung squamous cell carcinoma (SCC) is the second most common type of lung cancer, and immunotherapy is a promising new

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  10. Axillary basal cell carcinoma in patients with Goltz-Gorlin syndrome: report of basal cell carcinoma in both axilla of a woman with basal cell nevus syndrome and literature review.

    Science.gov (United States)

    Cohen, Philip R

    2014-08-17

    Basal cell carcinoma of the axilla, an area that is not usually exposed to the sun, is rare. Individuals with basal cell nevus syndrome, a disorder associated with a mutation in the patch 1 (PTCH1) gene, develop numerous basal cell carcinomas. To describe a woman with basal cell nevus syndrome who developed a pigmented basal cell carcinoma in each of her axilla and to review the features of axillary basal cell carcinoma patients with Goltz-Gorlin syndrome. Pubmed was used to search the following terms: axillary basal cell carcinoma and basal cell nevus syndrome. The papers and their citations were evaluated. Basal cell nevus syndrome patients with basal cell carcinoma of the axilla were observed in two women; this represents 2.5% (2 of 79) of the patients with axillary basal cell carcinoma. Both women had pigmented tumors that were histologically nonaggressive. The cancers did not recur after curettage or excision. Basal cell carcinoma of the axilla has only been described in 79 individuals; two of the patients were women with pigmented tumors who had basal cell nevus syndrome. Similar to other patients with axillary basal cell carcinoma, the tumors were histologically nonaggressive and did not recur following treatment. Whether PTCH1 gene mutation predisposes basal cell nevus patients to develop axillary basal cell carcinomas remains to be determined.

  11. Somatic INK4a-ARF locus mutations: a significant mechanism of gene inactivation in squamous cell carcinomas of the head and neck.

    Science.gov (United States)

    Poi, M J; Yen, T; Li, J; Song, H; Lang, J C; Schuller, D E; Pearl, D K; Casto, B C; Tsai, M D; Weghorst, C M

    2001-01-01

    The INK4a-ARF locus is located on human chromosome 9p21 and is known to encode two functionally distinct tumor-suppressor genes. The p16(INK4a) (p16) tumor-suppressor gene product is a negative regulator of cyclin-dependent kinases 4 and 6, which in turn positively regulate progression of mammalian cells through the cell cycle. The p14(ARF) tumor-suppressor gene product specifically interacts with human double minute 2, leading to the subsequent stabilization of p53 and G(1) arrest. Previous investigations analyzing the p16 gene in squamous cell carcinomas of the head and neck (SCCHNs) have suggested the predominate inactivating events to be homozygous gene deletions and hypermethylation of the p16 promoter. Somatic mutational inactivation of p16 has been reported to be low (0-10%, with a combined incidence of 25 of 279, or 9%) and to play only a minor role in the development of SCCHN. The present study examined whether this particular mechanism of INK4a/ARF inactivation, specifically somatic mutation, has been underestimated in SCCHN by determining the mutational status of the p16 and p14(ARF) genes in 100 primary SCCHNs with the use of polymerase chain reaction technology and a highly sensitive, nonradioactive modification of single-stranded conformational polymorphism (SSCP) analysis termed "cold" SSCP. Exons 1alpha, 1beta, and 2 of INK4a/ARF were amplified using intron-based primers or a combination of intron- and exon-based primers. A total of 27 SCCHNs (27%) exhibited sequence alterations in this locus, 22 (22%) of which were somatic sequence alterations and five (5%) of which were a single polymorphism in codon 148. Of the 22 somatic alterations, 20 (91%) directly or indirectly involved exon 2, and two (9%) were located within exon 1alpha. No mutations were found in exon 1beta. All 22 somatic mutations would be expected to yield altered p16 proteins, but only 15 of them should affect p14(ARF) proteins. Specific somatic alterations included microdeletions or

  12. Immunohistochemical and DNA sequencing analysis on human mismatch repair gene MLH1 in cervical squamous cell carcinoma with LOH of this gene

    NARCIS (Netherlands)

    Hu, X.; Guo, Z.; Pang, T.; Li, Q.; Afink, G.; Pontén, J.

    2000-01-01

    BACKGROUND: The human MLH1 gene (hMLH1) is one of the DNA mismatch repair genes. Defects in these genes are believed to be the underlying cause of microsatellite instability (MSI). MSI has been demonstrated in many human cancers such as colon cancer and some female-specific tumors. The hMLH1 gene

  13. Insights into significant pathways and gene interaction networks in peripheral blood mononuclear cells for early diagnosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Jian Xin Jiang

    2016-01-01

    Conclusions: Using identified DEGs, significantly changed biological processes such as nucleic acid metabolic process and KEGG pathways such as cytokine-cytokine receptor interaction in PBMCs of HCC patients were identified. In addition, several important hub genes, for example, CUL4A, and interleukin (IL 8 were also uncovered.

  14. Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

    Directory of Open Access Journals (Sweden)

    Terrenato Irene

    2010-09-01

    Full Text Available Abstract Background Several studies demonstrated that epidermal growth factor receptor (EGFR gene copy number (GCN correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC and to anti-EGFR monoclonal antibodies (MoAbs in metastatic colorectal cancer (CRC. In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic in situ hybridization (CISH is an alternative technique to fluorescence in situ hybridization (FISH, but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC of lung nodules has not yet been established. Methods We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas and 13 lung metastases from CRC. Results Of the 33 FNAC analyzed by CISH, 27 (82% presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30% showed a low polysomy, 15 (45% a high polysomy and 2 (6% NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p Conclusions Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung.

  15. Novel gene fusion of PRCC-MITF defines a new member of MiT family translocation renal cell carcinoma: clinicopathological analysis and detection of the gene fusion by RNA sequencing and FISH.

    Science.gov (United States)

    Xia, Qiu-Yuan; Wang, Xiao-Tong; Ye, Sheng-Bing; Wang, Xuan; Li, Rui; Shi, Shan-Shan; Fang, Ru; Zhang, Ru-Song; Ma, Heng-Hui; Lu, Zhen-Feng; Shen, Qin; Bao, Wei; Zhou, Xiao-Jun; Rao, Qiu

    2018-04-01

    MITF, TFE3, TFEB and TFEC belong to the same microphthalmia-associated transcription factor family (MiT). Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harbouring TFE3 gene fusions and t(6;11) RCC harbouring a MALAT1-TFEB gene fusion. The 2016 World Health Organisation classification of renal neoplasia grouped these two neoplasms together under the category of MiT family translocation RCC. RCCs associated with the other two MiT family members, MITF and TFEC, have rarely been reported. Herein, we identify a case of MITF translocation RCC with the novel PRCC-MITF gene fusion by RNA sequencing. Histological examination of the present tumour showed typical features of MiT family translocation RCCs, overlapping with Xp11 translocation RCC and t(6;11) RCC. However, this tumour showed negative results in TFE3 and TFEB immunochemistry and split fluorescence in-situ hybridisation (FISH) assays. The other MiT family members, MITF and TFEC, were tested further immunochemically and also showed negative results. RNA sequencing and reverse transcription-polymerase chain reaction confirmed the presence of a PRCC-MITF gene fusion: a fusion of PRCC exon 5 to MITF exon 4. We then developed FISH assays covering MITF break-apart probes and PRCC-MITF fusion probes to detect the MITF gene rearrangement. This study both proves the recurring existence of MITF translocation RCC and expands the genotype spectrum of MiT family translocation RCCs. © 2017 John Wiley & Sons Ltd.

  16. 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.

  17. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    OpenAIRE

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

  18. Radioresistance-related signaling pathways in nasopharyngeal carcinoma cells

    International Nuclear Information System (INIS)

    Guo Ya; Zhu Xiaodong; Qu Song; Su Fang; Wang Qi; Zhang Wei

    2011-01-01

    Objective: To study the difference of gene expression profile between the radioresistant human nasopharyngeal carcinoma cell line CNE-2R and CNE-2, and to screen the signaling pathway associated with radioresistance of nasopharyngeal carcinoma. Methods: The radioresistant nasopharyngeal carcinoma cell line CNE-2R was constructed from the original cell line CNE-2. CNE-2R and CNE-2 cells were cultured and administered with 60 Co γ-ray irradiation at the dose of 400 cGy for 15 times. Human-6v 3.0 whole genome expression profile was used to screen the differentially expressed genes. Bioinformatic analysis was used to identify the pathways related to radioresistance. Results: The number of the differentially expressed genes that were found in these 2 experiments was 374. The Kegg pathway and Biocarta pathway analysis of the differentially expressed genes showed the biological importance of Toll-like receptor signaling pathway and IL-1 R-mediated signal transduction pathway to the radioresistance of the CNE-2R cells and the significant differences of 13 genes in these 2 pathways,including JUN, MYD88, CCL5, CXCL10, STAT1, LY96, FOS, CCL3, IL-6, IL-8, IL-1α, IL-1β, and IRAK2 (t=13.47-66.57, P<0.05). Conclusions: Toll-like receptor signaling pathway and IL-1R-mediated signal transduction pathway might be related to the occurrence of radioresistance. (authors)

  19. 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.

  20. Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands

    Czech Academy of Sciences Publication Activity Database

    Hrubá, E.; Vondráček, Jan; Líbalová, Helena; Topinka, Jan; Bryja, Vítězslav; Souček, Karel; Machala, M.

    2011-01-01

    Roč. 206, č. 2 (2011), s. 178-188 ISSN 0378-4274 R&D Projects: GA ČR(CZ) GA310/07/0961; GA ČR(CZ) GA524/09/1337 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : LNCaP cells * AhR ligands * WNT5A Subject RIV: BO - Biophysics Impact factor: 3.230, year: 2011

  1. Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2018-04-10

    Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Hypopharynx; Squamous Cell Carcinoma of the Paranasal Sinus; Head and Neck Squamous Cell Carcinoma; Squamous Cell Cancer; Head and Neck Carcinoma

  2. Treatment Options by Stage (Merkel Cell Carcinoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... common for Merkel cell carcinoma to recur. Treatment Option Overview Key Points There are different types of ...

  3. Treatment Option Overview (Merkel Cell Carcinoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... common for Merkel cell carcinoma to recur. Treatment Option Overview Key Points There are different types of ...

  4. Merkel Cell Carcinoma Therapeutic Update.

    Science.gov (United States)

    Cassler, Nicole M; Merrill, Dean; Bichakjian, Christopher K; Brownell, Isaac

    2016-07-01

    Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. Adjuvant RT to the primary excision site and regional lymph node bed may improve locoregional control. However, newer studies confirm that patients with biopsy-negative sentinel lymph nodes may not benefit from regional RT. Advanced MCC currently lacks a highly effective treatment as responses to chemotherapy are not durable. Recent work suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients. At the same time, high-throughput sequencing studies have demonstrated significant differences in the mutational profiles of tumors with and without the Merkel cell polyomavirus (MCV). An important secondary endpoint in the ongoing immunotherapy trials for MCC will be determining if there is a response difference between the virus-positive MCC tumors that typically lack a large mutational burden and the virus-negative tumors that have a large number of somatic mutations and predicted tumor neoantigens. Interestingly, sequencing studies have failed to identify a highly recurrent activated driver pathway in the majority of MCC tumors. This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations.

  5. Introducing Cytology-Based Theranostics in Oral Squamous Cell Carcinoma: A Pilot Program.

    Science.gov (United States)

    Patrikidou, Anna; Valeri, Rosalia Maria; Kitikidou, Kyriaki; Destouni, Charikleia; Vahtsevanos, Konstantinos

    2016-04-01

    We aimed to evaluate the feasibility and reliability of brush cytology in the biomarker expression profiling of oral squamous cell carcinomas within the concept of theranostics, and to correlate this biomarker profile with patient measurable outcomes. Markers representative of prognostic gene expression changes in oral squamous cell carcinoma was selected. These markers were also selected to involve pathways for which commercially available or investigational agents exist for clinical application. A set of 7 markers were analysed by immunocytochemistry on the archival primary tumour material of 99 oral squamous cell carcinoma patients. We confirmed the feasibility of the technique for the expression profiling of oral squamous cell carcinomas. Furthermore, our results affirm the prognostic significance of the epidermal growth factor receptor (EGFR) family and the angiogenic pathway in oral squamous cell carcinoma, confirming their interest for targeted therapy. Brush cytology appears feasible and applicable for the expression profiling of oral squamous cell carcinoma within the concept of theranostics, according to sample availability.

  6. Merkel cell polyomavirus and Merkel cell carcinoma.

    Science.gov (United States)

    DeCaprio, James A

    2017-10-19

    Merkel cell polyomavirus (MCPyV) causes the highly aggressive and relatively rare skin cancer known as Merkel cell carcinoma (MCC). MCPyV also causes a lifelong yet relatively innocuous infection and is one of 14 distinct human polyomaviruses species. Although polyomaviruses typically do not cause illness in healthy individuals, several can cause catastrophic diseases in immunocompromised hosts. MCPyV is the only polyomavirus clearly associated with human cancer. How MCPyV causes MCC and what oncogenic events must transpire to enable this virus to cause MCC is the focus of this essay.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

  7. Establishment of a hepatocellular carcinoma cell line expressing dual reporter genes: sodium iodide symporter (NIS) and enhanced green fluorescence protein (EGFP)

    International Nuclear Information System (INIS)

    Kwak, Won Jung; Koo, Bon Chul; Kwon, Mo Sun

    2007-01-01

    Dual reporter gene imaging has several advantages for more sophisticated molecular imaging studies such as gene therapy monitoring. Herein, we have constructed hepatoma cell line expressing dual reporter genes of sodium iodide symporter (NIS) and enhanced green fluorescence protein (EGFP), and the functionalities of the genes were evaluated in vivo by nuclear and optical imaging. A pRetro-PN vector was constructed after separating NIS gene from pcDNA-NIS. RSV-EGFP-WPRE fragment separated from pLNRGW was cloned into pRetro-PN vector. The final vector expressing dual reporter genes was named pRetro-PNRGW. A human hepatoma (HepG2) cells were transfected by the retrovirus containing NIS and EGFP gene (HepG2-NE). Expression of NIS gene was confirmed by RT-PCR, radioiodine uptake and efflux studies. Expression of EGFP was confirmed by RT-PCR and fluorescence microscope. The HepG2 and HepG2-NE cells were implanted in shoulder and hindlimb of nude mice, then fluorescence image, gamma camera image and I-124 microPET image were undertaken. The HepG2-NE cell was successfully constructed. RT-PCR showed NIS and EGFP mRNA expression. About 50% of cells showed fluorescence. The iodine uptake of NIS-expressed cells was about 9 times higher than control. In efflux study, T 1/2 of HepG2-NE cells was 9 min. HepG2-NE xenograft showed high signal-to-background fluorescent spots and higher iodine-uptake compared to those of HepG2 xenograft. A hepatoma cell line expressing NIS and EGFP dual reporter genes was successfully constructed and could be used as a potential either by therapeutic gene or imaging reporter gene

  8. Eyelid Squamous Cell Carcinoma in a Dog

    Directory of Open Access Journals (Sweden)

    Chang-hyun Song1§, Sae-kwang Ku2§, Hwan-soo Jang3, Eun-young Kye, Sung-ho Yun, Kwang-ho Jang and Young-sam Kwon*

    2012-06-01

    Full Text Available A 10-year-old, female, Yorkshire Terrier was presented with a left lower eyelid mass. No other abnormality was detected on affected eye in a general eye examination. The mass was surgically removed and histologically diagnosed as a squamous cell carcinoma. The advancement flap used in this case may be an appropriate therapeutic choice for eyelid squamous cell carcinoma in dogs.

  9. Squamous cell carcinoma arising in an odontogenic cyst

    International Nuclear Information System (INIS)

    Yu, Jae Jung; Hwang, Eui Hwan; Lee, Sang Rae; Choi, Jeong Hee

    2003-01-01

    Squamous cell carcinoma arising in an odontogenic cyst is uncommon. The diagnosis of carcinoma arising in a cyst requires that there must be an area of microscopic transition from the benign epithelial cyst lining to the invasive squamous cell carcinoma. We report a histopathologically proven case of squamous cell carcinoma arising in a residual mandibular cyst in a 54-year-old woman.

  10. Gingival squamous cell carcinoma: A diagnostic impediment

    Directory of Open Access Journals (Sweden)

    Rekha Rani Koduganti

    2012-01-01

    Full Text Available Oral squamous cell carcinomas represent 3% of cancers in men and 2% of cancers in women. More than 90% of oral cancer occurs in people older than 45 years Lesions of gingiva account for approximately 10% of the oral squamous cell carcinomas and may present clinically as an area of ulceration, exophytic mass, or red/white speckled patches. The proximity to the underlying periosteum may invite early bone invasion. Carcinoma of gingiva constitutes an extremely important group of neoplasms as the lesion frequently mimics the reactive and inflammatory conditions affecting the periodontium, delaying the diagnosis and making the prognosis of the patient poorer. A rare case of gingival squamous cell carcinoma has been reported here, in a 40 Year old male patient. Careful recording of the case history and results of clinical examination, radiographic, and laboratory investigations, along with a critical review of similar conditions led to the diagnosis, and treatment was initiated.

  11. Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma.

    Science.gov (United States)

    Ferrarotto, Renata; Cardnell, Robert; Su, Shirley; Diao, Lixia; Eterovic, A Karina; Prieto, Victor; Morrisson, William H; Wang, Jing; Kies, Merrill S; Glisson, Bonnie S; Byers, Lauren Averett; Bell, Diana

    2018-03-23

    Patients with metastatic Merkel cell carcinoma are treated similarly to small cell lung cancer (SCLC). Poly ADP-ribose polymerase-1 (PARP1) is overexpressed in SCLC and response to PARP inhibitors have been reported in patients with SCLC. Our study explores PARP as a therapeutic target in Merkel cell carcinoma. We evaluated PARP1 expression and Merkel cell polyomavirus (MCPyV) in 19 patients with Merkel cell carcinoma. Target exome-sequencing was performed in 14 samples. Sensitivity to olaparib was tested in 4 Merkel cell carcinoma cell lines. Most Merkel cell carcinomas (74%) express PARP1 at high levels. Mutations in DNA-damage repair genes were identified in 9 samples (64%), occurred exclusively in head neck primaries, and correlated with TP53/RB1 mutations. The TP53/RB1 mutations were more frequent in MCPyV-negative tumors. Sensitivity to olaparib was seen in the Merkel cell carcinoma line with highest PARP1 expression. Based on PARP1 overexpression, DNA-damage repair gene mutations, platinum sensitivity, and activity of olaparib in a Merkel cell carcinoma line, clinical trials with PARP inhibitors are warranted in Merkel cell carcinoma. © 2018 Wiley Periodicals, Inc.

  12. [Effect of Biejiajian Pills on Wnt signal pathway molecules β-catenin and GSK-3β and the target genes CD44v6 and VEGF in hepatocellular carcinoma cells].

    Science.gov (United States)

    Sun, Haitao; He, Songqi; Wen, Bin; Jia, Wenyan; Fan, Eryan; Zheng, Yan

    2014-10-01

    To investigate the effect of Biejiajian Pills on the expressions of the signal molecules and target genes of Wnt signal pathway in HepG2 cells and explore the mechanisms by which Biejiajian pills suppress the invasiveness of hepatocellular carcinoma. HepG2 cells were cultured for 48 h in the presence of serum collected from rats fed with Biejiajian Pills. The expressions of β-catenin, GSK-3β and P-GSK-3β in the cultured cells were assessed by Western blotting and the expressions of CD44v6 and VEGF were detected using immunohistochemistry. HepG2 cells cultured with the serum of rats fed with Biejiajian Pills showed lowered expressions of β-catenin protein both in the cytoplasm and the nuclei with also inhibition of phosphorylation of GSK-3β and reduced expression of CD44v6 and VEGF. Biejiajian Pills can significantly reduce the expression of β-catenin by decreasing the phosphorylation of GSK-3β and blocking the Wnt/β-catenin signaling pathway to cause down-regulation of the target genes CD44v6 and VEGF, which may be one of the molecular mechanisms by which Biejiajian Pills suppress the proliferation and invasiveness of hepatocellular carcinoma.

  13. 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 b...

  14. 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.

  15. Metastatic renal cell carcinoma in the nasopharynx.

    Science.gov (United States)

    Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

    2013-01-01

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

  16. Metastatic renal cell carcinoma in the nasopharynx

    Directory of Open Access Journals (Sweden)

    Yavuz Atar

    2013-01-01

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

  17. Apoptosis, proliferation and p53, cyclin D1, and retinoblastoma gene expression in relation to radiation response in transitional cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Moonen, Luc; Ong, Francisca; Gallee, Maarten; Verheij, Marcel; Horenblas, Simon; Hart, Augustinus A.M.; Bartelink, Harry

    2001-01-01

    Purpose: To determine whether the apoptotic index, the Ki67 index, and the expression of the p53, cyclin D1, and retinoblastoma genes correlate with local control, overall survival, and time to distant metastases in invasive bladder cancer treated with external beam radiation. Methods and Materials: Paraffin-embedded pretreatment biopsies from 83 patients with invasive transitional cell carcinoma of the bladder were scored morphologically for apoptosis and immunohistochemically for Ki67, p53, cyclin D1, and retinoblastoma gene expression. Survival analysis methods were used to assess overall survival, local control, and freedom from distant metastases. A multiple proportional hazard (PH) regression analysis was performed to study the prognostic value of the above mentioned biologic parameters (all divided into two categories, except Ki67) in addition to classical prognostic factors such as T stage, histologic grade, multifocality of the tumor, and completeness of transurethral resection. All patients were treated with external beam radiation as sole treatment. Median follow-up for the 19 patients still living was 7.5 years. Results: Apoptotic index varied from 0% to 3.4% with a mean of 0.8% and a median of 0.6%. Ki67 index varied from 0% to 60% with a mean of 14% and a median of 12%. P53 protein was detectable in 61% of the tumors. Overexpression of cyclin D1 was observed in 39% of the tumors and loss of retinoblastoma protein in 23% of the tumors. High Ki67 index was found to be significantly associated with p53 expression (p=0.04) and cyclin D1 overexpression (p=0.023). Cyclin D1 overexpression was found more often in Rb-positive tumors than in Rb-negative tumors (p=0.006). Other associations between the markers are less clear. Biologic markers were not correlated with T stage or grade. In the PH analysis local control was found to be significantly better for tumors with wild-type p53 (p=0.028). Also, tumors with an apoptotic index above the median value (0

  18. Small cell type neuroendocrine carcinoma colliding with squamous cell carcinoma at esophagus

    Science.gov (United States)

    Yang, Luoluo; Sun, Xun; Zou, Yabin; Meng, Xiangwei

    2014-01-01

    Collision tumor is an extremely rare tumor which defined as the concrescence of two distinct primaries neoplasms. We report here a case of collision tumor at lower third esophagus composed of small cell type neuroendocrine carcinoma (NEC), which is an very rare, highly aggressive and poorly prognostic carcinoma and squamous cell carcinoma (SqCC). In our case, pathologically, the small cell carcinoma display the characteristic of small, round, ovoid or spindle-shaped tumor cells with scant cytoplasm, which colliding with a moderately differentiated squamous cell carcinoma. Immunohistochemical staining demonstrated positive activities for CD56, synaptophysin, 34βE12, CK 5/6, ki-67 (70%-80%), but negative for CD99, chromogranin A, and TTF-1. Accurate diagnosis was made base on these findings. PMID:24817981

  19. The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-aza-2'-deoxycytidine.

    Science.gov (United States)

    Alleman, Wade G; Tabios, Ray L; Chandramouli, Gadisetti V R; Aprelikova, Olga N; Torres-Cabala, Carlos; Mendoza, Arnulfo; Rogers, Craig; Rodgers, Craig; Sopko, Nikolai A; Linehan, W Marston; Vasselli, James R

    2004-10-15

    Clear cell renal carcinoma (ccRCC) is strongly associated with loss of the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene is functionally lost through hypermethylation in up to 19% of sporadic ccRCC cases. We theorized that re-expressing VHL silenced by methylation in ccRCC cells, using a hypo-methylating agent, may be an approach to treatment in patients with this type of cancer. We test the ability of two hypo-methylating agents to re-express VHL in cell culture and in mice bearing human ccRCC and evaluate the effects of re-expressed VHL in these models. Real-time reverse transcription-PCR was used to evaluate the ability of zebularine and 5-aza-2'-deoxycytidine (5-aza-dCyd) to re-express VHL in four ccRCC cell lines with documented VHL gene silencing through hypermethylation. We evaluated if the VHL re-expressed after hypo-methylating agent treatment could recreate similar phenotypic changes in ccRCC cells observed when the VHL gene is re-expressed via transfection in cell culture and in a xenograft mouse model. Finally we evaluate global gene expression changes occurring in our cells, using microarray analysis. 5-Aza-dCyd was able to re-express VHL in our cell lines both in culture and in xenografted murine tumors. Well described phenotypic changes of VHL expression including decreased invasiveness into Matrigel, and decreased vascular endothelial growth factor and glucose transporter-1 expression were observed in the treated lines. VHL methylated ccRCC xenografted tumors were significantly reduced in size in mice treated with 5-aza-dCyd. Mice bearing nonmethylated but VHL-mutated tumors showed no tumor shrinkage with 5-aza-dCyd treatment. Hypo-methylating agents may be useful in the treatment of patients having ccRCC tumors consisting of cells with methylated VHL.

  20. Clinicopathological characteristics of head and neck Merkel cell carcinomas.

    Science.gov (United States)

    Knopf, Andreas; Bas, Murat; Hofauer, Benedikt; Mansour, Naglaa; Stark, Thomas

    2017-01-01

    There are still controversies about the therapeutic strategies and subsequent outcome in head and neck Merkel cell carcinoma. Clinicopathological data of 23 Merkel cell carcinomas, 93 cutaneous head and neck squamous cell carcinomas (HNSCCs), 126 malignant melanomas, and 91 primary parotid gland carcinomas were comprehensively analyzed. Merkel cell carcinomas were cytokeratin 20 (CK20)/neuron-specific enolase (NSE)/chromogranin A (CgA)/synaptophysin (Syn)/thyroid transcription factor-1 (TTF-1)/MIB1 immunostained. All Merkel cell carcinomas underwent wide local excision. Parotidectomy/neck dissection was performed in 40%/33% cutaneous Merkel cell carcinoma and 100%/100% in parotid gland Merkel cell carcinoma. Five-year recurrence-free interval (RFI)/overall survival (OS) was significantly higher in malignant melanoma (81/80%) than in cutaneous Merkel cell carcinoma/HNSCC. Interestingly, 5-year RFI/OS was significantly higher in Merkel cell carcinoma (61%/79%) than in HNSCC (33%/65%; p Merkel cell carcinoma and parotid gland carcinomas, nor in the immunohistochemical profile. Five-year RFI/OS was significantly better in cutaneous Merkel cell carcinoma when compared with TNM classification matched HNSCC. Five-year RFI/OS was comparable in parotid gland Merkel cell carcinoma and other primary parotid gland malignancies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 92-97, 2017. © 2016 Wiley Periodicals, Inc.

  1. Nevoid basal cell carcinoma syndrome (Gorlin syndrome

    Directory of Open Access Journals (Sweden)

    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

  2. Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

    DEFF Research Database (Denmark)

    Du, Peina; Huang, Peide; Huang, Xuanlin

    2017-01-01

    Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study...

  3. Overexpression of Periostin and Lumican in Esophageal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Kashyap, Manoj Kumar; Marimuthu, Arivusudar; Peri, Suraj; Kumar, Ghantasala S. Sameer; Jacob, Harrys K.C.; Prasad, Thottethodi Subrahmanya Keshava; Mahmood, Riaz; Kumar, K. V. Veerendra; Kumar, M. Vijaya; Meltzer, Stephen J.; Montgomery, Elizabeth A.; Kumar, Rekha V.; Pandey, Akhilesh

    2010-01-01

    To identify biomarkers for early detection for esophageal squamous cell carcinoma (ESCC), we previously carried out a genome-wide gene expression profiling study using an oligonucleotide microarray platform. This analysis led to identification of several transcripts that were significantly upregulated in ESCC compared to the adjacent normal epithelium. In the current study, we performed immunohistochemical analyses of protein products for two candidates genes identified from the DNA microarray analysis, periostin (POSTN) and lumican (LUM), using tissue microarrays. Increased expression of both periostin and lumican was observed in 100% of 137 different ESCC samples arrayed on tissue microarrays. Increased expression of periostin and lumican was observed in carcinoma as well as in stromal cell in the large majority of cases. These findings suggest that these candidates can be investigated in the sera of ESCC patients using ELISA or multiple reaction monitoring (MRM) type assays to further explore their utility as biomarkers

  4. Co-ordinate loss of protein kinase C and multidrug resistance gene expression in revertant MCF-7/Adr breast carcinoma cells.

    Science.gov (United States)

    Budworth, J; Gant, T W; Gescher, A

    1997-01-01

    The aim of this study was to investigate the link between protein kinase C (PKC) and multidrug resistance (mdr) phenotype. The expression of both was studied in doxorubicin-resistant MCF-7/Adr cells as they reverted to the wild-type phenotype when cultured in the absence of drug. The following parameters were measured in cells 4, 10, 15, 20 and 24 weeks after removal of doxorubicin; (1) sensitivity of the cells towards doxorubicin; (2) levels of P-glycoprotein (P-gp) and MDR1 mRNA; (3) levels and cellular localization of PKC isoenzyme proteins alpha, theta and epsilon; and (4) gene copy number of PKC-alpha and MDR1 genes. Cells lost their resistance gradually with time, so that by week 24 they had almost completely regained the drug sensitivity seen in wild-type MCF-7 cells. P-gp levels measured by Western blot mirrored the change in doxorubicin sensitivity. By week 20, P-gp had decreased to 18% of P-gp protein levels at the outset, and P-gp was not detectable at week 24. Similarly, MDR1 mRNA levels had disappeared by week 24. MCF-7/Adr cells expressed more PKCs-alpha and -theta than wild-type cells and possessed a different cellular localization of PKC-epsilon. The expression and distribution pattern of these PKCs did not change for up to 20 weeks, but reverted back to that seen in wild-type cells by week 24. MDR1 gene amplification remained unchanged until week 20, but then was lost precipitously between weeks 20 and 24. The PKC-alpha gene was not amplified in MCF-7/Adr cells. The results suggest that MCF-7/Adr cells lose MDR1 gene expression and PKC activity in a co-ordinate fashion, consistent with the existence of a mechanistic link between MDR1 and certain PKC isoenzymes.

  5. 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.

  6. Polysomy and amplification of chromosome 7 defined for EGFR gene in squamous cell carcinoma of the lung together with exons 19 and 21 wild type Carcinoma epidermóide do pulmão: Polissomia e amplificação do cromossoma 7 e do gene EGRF com forma wild type nos exões 19 e 21

    Directory of Open Access Journals (Sweden)

    Patrícia Couceiro

    2010-06-01

    Full Text Available Purpose: The epidermal growth factor receptor (EGFR is overexpressed in the majority of nonsmall-cell lung cancers (NSCLC and is a major target specific EGFR tyrosine kinase inhibitors (TKIs developed and used for the treatment of advanced NSCLC. A number of biological factors are also associated with EGFR-TKIs responsiveness. This study was focused on EGFR somatic mutations and amplifications in squamous cell lung cancer. Material and methods: Representative sections of squamous cell carcinoma were selected from 54 surgical specimens from formalin-fixed paraffin-embedded tissues and submitted to TMA construction. Determination of EGFR protein expression was done by immunohistochemistry( IHC (Zymed, Laboratories. Fluorescence in situ hybridization (FISH was performed with LSI EGFR/CEP 7 (Vysis; Abbott Molecular, USA. Genomic DNA was extracted from 48 cases and exon 19 was amplified by polymerase chain reaction (PCR for search deletions and point mutations for exon 21. All cases expressed high weigh cytokeratin and were observed negativity for CK7, CD56 and chromogranin. Results: EGFR protein overexpression was identified in 49 cases, by the application of Hirsh’s scoring system. The chromosome 7 and EGFR gene were analyzed by FISH and scored according to Cappuzzo’s method that showed high polysomy in 31 cases and amplification in 7 cases. Deletion in exon 19 of EGFR was detected in 3 cases of 48 samples; the exon 21 of EGFR was expressed in its wild type by RFLP in all cases. Conclusions: Detection of common EGFR deletion and mutation showed to be a rare event in Squamous cell carcinoma of the lung. While EGFR mutation is the most effective molecular predictor or sensitivity in patients with advanced NSCLC submitted to EGFR-TKIs treatment, amplification and polysomy is the most effective molecular predictor for EGFR-TKIs responsiveness in squamous cell carcinoma, when valida ted isolated from the group of NSCLC.Objectivo: O receptor do

  7. New York esophageal squamous cell carcinoma-1 and cancer immunotherapy.

    Science.gov (United States)

    Esfandiary, Ali; Ghafouri-Fard, Soudeh

    2015-01-01

    New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

  8. Metastatic Squamous Cell Carcinoma of the Stomach.

    Science.gov (United States)

    Hamzaoui, Lamine; Bouassida, Mahdi; Kilani, Houda; Medhioub, Mouna; Chelbi, Emna

    2015-11-01

    Primary squamous cell carcinoma of the stomach is very rare. Its pathogenesis is unclear and the treatment strategy is controversial. We report an agressive primary squamous cell carcinoma of the stomach with liver and lung metastases in a 55-year-old man. The patient presented with a 1-month history of abdominal pain, vomiting and weight loss. Abdominal ultrasound revealed multiple liver metastases. Endoscopic examination showed two tumour masses on the fundus of the stomach. Biopsy of the lesions revealed squamous cell carcinoma of the stomach. Chest x-ray showed multiple large pulmonary nodules highly suggestive of pulmonary metastases. The patient died ten days after he was admitted because of progression of the tumour and before any therapeutic decision.

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

    Science.gov (United States)

    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

  10. Radioresistance related genes screened by protein-protein interaction network analysis in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zhu Xiaodong; Guo Ya; Qu Song; Li Ling; Huang Shiting; Li Danrong; Zhang Wei

    2012-01-01

    Objective: To discover radioresistance associated molecular biomarkers and its mechanism in nasopharyngeal carcinoma by protein-protein interaction network analysis. Methods: Whole genome expression microarray was applied to screen out differentially expressed genes in two cell lines CNE-2R and CNE-2 with different radiosensitivity. Four differentially expressed genes were randomly selected for further verification by the semi-quantitative RT-PCR analysis with self-designed primers. The common differentially expressed genes from two experiments were analyzed with the SNOW online database in order to find out the central node related to the biomarkers of nasopharyngeal carcinoma radioresistance. The expression of STAT1 in CNE-2R and CNE-2 cells was measured by Western blot. Results: Compared with CNE-2 cells, 374 genes in CNE-2R cells were differentially expressed while 197 genes showed significant differences. Four randomly selected differentially expressed genes were verified by RT-PCR and had same change trend in consistent with the results of chip assay. Analysis with the SNOW database demonstrated that those 197 genes could form a complicated interaction network where STAT1 and JUN might be two key nodes. Indeed, the STAT1-α expression in CNE-2R was higher than that in CNE-2 (t=4.96, P<0.05). Conclusions: The key nodes of STAT1 and JUN may be the molecular biomarkers leading to radioresistance in nasopharyngeal carcinoma, and STAT1-α might have close relationship with radioresistance. (authors)

  11. Merkel Cell Carcinoma Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Merkel cell carcinoma treatment options include surgery, radiation therapy, and chemotherapy. Get detailed information about the diagnosis and treatment of newly diagnosed and recurrent Merkel cell carcinoma in this summary for clinicians.

  12. Renal cell carcinoma presenting as mandibular metastasis

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadnia

    2013-01-01

    Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

  13. Reliability of chromogenic in situ hybridization for epidermal growth factor receptor gene copy number detection in non-small-cell lung carcinomas: a comparison with fluorescence in situ hybridization study.

    Science.gov (United States)

    Yoo, Seol Bong; Lee, Hyun Ju; Park, Jung Ok; Choe, Gheeyoung; Chung, Doo Hyun; Seo, Jeong-Wook; Chung, Jin-Haeng

    2010-03-01

    Fluorescence in situ hybridization (FISH) has been known to be the most representative and standardized test for assessing gene amplification. However, FISH requires a fluorescence microscope, the signals are labile and rapidly fade over time. Recently, chromogenic in situ hybridization (CISH) has emerged as a potential alternative to FISH. The aim of this study is to test the reliability of CISH technique for the detection of epidermal growth factor receptor (EGFR) gene amplification in non-small-cell lung carcinomas (NSCLC), to compare CISH results with FISH. A total of 277 formalin-fixed and paraffin embedded NSCLC tissue samples were retrieved from the surgical pathology archives at Seoul National University Bundang Hospital. CISH and FISH examinations were performed to test EGFR gene amplification status. There was high concordance in the assessment of EGFR gene copy number between CISH and FISH tests (Kappa coefficient=0.83). Excellent concordance was shown between two observers on the interpretation of the CISH results (Kappa coefficient=0.90). In conclusion, CISH result is highly reproducible, accurate and practical method to determine EGFR gene amplification in NSCLC. In addition, CISH allows a concurrent analysis of histological features of the tumors and gene copy numbers.

  14. Basal Cell Carcinoma Arising in a Tattooed Eyebrow

    Science.gov (United States)

    Lee, Jong-Sun; Park, Jin; Kim, Seong-Min; Kim, Han-Uk

    2009-01-01

    Malignant skin tumors, including squamous cell carcinoma and malignant melanoma, have occurred in tattoos. Seven documented cases of basal cell carcinoma associated with tattoos have also been reported in the medical literature. We encountered a patient with basal cell carcinoma in a tattooed eyebrow. We report on this case as the eighth reported case of a patient with basal cell carcinoma arising in a tattooed area. PMID:20523804

  15. Ekspresi produk gen laten virus epstein-barr pada karsinoma sel skuamosa rongga mulut (The expressions of latent gene product of epstein-barr virus in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Theresia Indah Budhy S

    2005-06-01

    Full Text Available Squamous cell carcinoma (SCC is a type of cancer often found in oral cavity and the area of head and neck at about 90%. Based on the geographical incidence oral SCC (OSCC has many types of different emerging. This case probably has connection with ethnic group, habit and social and economical condition. In East Java, the incidence is about 2.64% and it increases every year. The virus is known as one of the main factors that result in this disease. Epstein-Barr virus (EBV has potential capability of carcinogenesis. EBV is the family of herpesviridae that can infect cell through the linking of CD 21 receptor of the epithel with glycol protein 350/220 of the virus capsule. After primary infection, the virus will form latent-gene in human cell. Periodically, the latent-gene product can disturb proliferation and apoptotic regulator. In Indonesia, the expression of EBV latent geneproduct in the OSCC has not been reported yet. This study wanted to know the expression of EBV latent gene product found in the OSCC. This study found 25 cases of OSCC in which 17 were infected by EBV. Detection of EBV infection could be done by insitu hybridization to identify RNA EBV (EBER. To find the expression of EBV latent gene product, immunohistochemical analysis was done. The conclusion was that the emerging of expression of EBV latent gene product in OSCC were latent membrane protein-1 (LMP-1, EBV nuclear antigen-1 (EBNA-1 and RNA EBV (EBER. They were 28.28%, 25.26% and 46.47%. It was suggested to do the following research on OSCC infected by EBV and the emerging of expression of EBV latent gene product with regulator gene of proliferation and apoptotic in OSCC.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases

    International Nuclear Information System (INIS)

    Lee, Ja-Rang; Kwon, Chae Hwa; Choi, Yuri; Park, Hye Ji; Kim, Hyun Sung; Jo, Hong-Jae; Oh, Nahmgun; Park, Do Youn

    2016-01-01

    Despite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood. In order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver). The gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells. The present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma. The online version of this article (doi:10.1186/s12885-016-2596-3) contains supplementary material, which is available to authorized users

  18. Asymptomatic renal cell carcinoma incidentally detected by abdominal CT

    International Nuclear Information System (INIS)

    Yoneda, Fumio; Miyake, Noriaki; Tsujimura, Haruhiro; Nakajima, Mikio; Akiyama, Hajime

    1987-01-01

    Four cases of renal cell carcinoma that were incidentally detected by abdominal CT are reported. Abdominal CT was performed during gastro-intestinal examination in two patients and for suspected liver disease in the other two. No patient had symptoms of renal cell carcinoma, or hematuria. In all cases, the histopathological diagnosis was renal cell carcinoma of a low stage. (author)

  19. Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu

    Directory of Open Access Journals (Sweden)

    Luan Jinwei

    2016-06-01

    Full Text Available Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA-enhancing X-ray susceptibility in FaDu cells.

  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. Clinical presentation of renal cell carcinoma

    International Nuclear Information System (INIS)

    Rehman, R.A.; Ashraf, S.; Jamil, N.

    2015-01-01

    Most common malignant tumour of the kidney is Renal Cell Carcinoma (RCC) and is known for its unpredictable clinical behaviour. Aetiology and risk factors are not completely understood. Extensive workup is being done in the understanding of the disease, especially to diagnose early and to treat promptly. The objective of this study was to determine the clinical presentation and pathological pattern of RCC. Methods: After approval from ethical committee a retrospective review of records was conducted extending from January 2012 to January 2014 to identify clinical characteristics of renal cell carcinomas. The study included all renal cancer patients presented to Sheikh Zayed Hospital Lahore with in this specified period. The data was retrieved regarding, history, physical examination and necessary investigations such as ultrasonography of abdomen and pelvis and CT scan of abdomen and pelvis. Results: There were total of 50 cases. The male to female ratio was 3:2. Mean age of patients were 52.38 (18-93) years old. Most common clinical presentation was gross haematuria(66%).The mean tumour size was 8.34 (3-24) cm. Tumour histology were clear cell (84%), papillary transitional cell carcinoma (12%) and oncosytoma contributed 4%. Conclusion: We observed that large number of the patients with RCC presented with haematuria and most of them were male. Common pathological type was clear cell carcinoma. (author)

  2. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2011-05-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC).

  3. Selective in vivo radiosensitization by 5-fluorocytosine of human colorectal carcinoma cells transduced with the E. coli cytosine deaminase (CD) gene

    International Nuclear Information System (INIS)

    Gabel, M.; Kim, J.H.; Kolozsvary, A.; Khil, M.; Freytag, S.

    1998-01-01

    Purpose: The E. coli cytosine deaminase (CD) gene encodes an enzyme capable of converting the nontoxic prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), a known radiosensitizer. Having previously shown that combined CD suicide gene therapy and radiation (RT) results in pronounced radiosensitization in vitro, we progressed to in vivo studies of combined therapy. Methods and Materials: WiDr human colon cancer cells were transduced in vitro with the CD gene and cells expressing CD were selected for use as xenografts in a nude mouse model. After administration of 5-FC, tumors received 10-30 Gy local field radiation (RT) and tumor growth delay was compared to control animals receiving either 5-FU, 5-FC, or RT alone. Results: Maximal growth delay was seen in mice treated with 5-FC for 6 consecutive days prior to RT. Combined treatment with 15 Gy radiation resulted in a dose-modifying factor (DMF) of 1.50, and a greater DMF was observed with higher doses of radiation. There was no appreciable toxicity using this new approach. In contrast, a similar treatment of combined 5-FU and radiation resulted in considerable toxicity and no appreciable radiosensitization. Conclusion: The present results show that combined suicide gene therapy and RT results in pronounced antitumor effect without any notable toxicity. This indicates that the CD gene may be useful in the development of novel treatment strategies combining radiation and gene therapy in the treatment of locally advanced cancers

  4. Evidence that expression of a mutated p53 gene attenuates apoptotic cell death in human gastric intestinal-type carcinomas in vivo.

    Science.gov (United States)

    Ishida, M; Gomyo, Y; Ohfuji, S; Ikeda, M; Kawasaki, H; Ito, H

    1997-05-01

    To examine in vivo the validity of the results of experiments in vitro, we analyzed the relationship between p53 gene status and apoptotic cell death of human gastric intestinal-type adenocarcinomas. Surgical specimens were classified into two categories: 18 gastric cancers with nuclear p53 protein (A), and 17 gastric cancers without nuclear p53 protein (B). Polymerase chain reaction-single strand conformation polymorphism disclosed a shifted band that corresponded to a mutation in the p53 gene in 13 cases (72%) in category A and 3 cases (18%) in category B, the frequency being significantly higher in the former (P terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The TUNEL index [TI; (the number of TUNEL-positive apoptotic cells/the total number of tumor cells) x 100] was 3.8 +/- 1.4% in category A and 4.9 +/- 1.2% in category B, the value being significantly lower in the former (P gastric cancer, in accordance with the previous in vitro finding that p53 gene mutation provides a possible selective advantage for tumor cell proliferation, and (2) apoptosis is related not only to expression of p53 and the stage of the cell cycle, but also to p53-independent and cell cycle-independent events.

  5. Long term storage in liquid nitrogen leads to only minor phenotypic and gene expression changes in the mammary carcinoma model cell line BT474.

    Science.gov (United States)

    Fazekas, Judit; Grunt, Thomas W; Jensen-Jarolim, Erika; Singer, Josef

    2017-05-23

    Cancer cell lines are indispensible surrogate models in cancer research, as they can be used off-the-shelf, expanded to the desired extent, easily modified and exchanged between research groups for affirmation, reproduction or follow-up experiments.As malignant cells are prone to genomic instability, phenotypical changes may occur after certain passages in culture. Thus, cell lines have to be regularly authenticated to ensure data quality. In between experiments these cell lines are often stored in liquid nitrogen for extended time periods.Although freezing of cells is a necessary evil, little research is performed on how long-term storage affects cancer cell lines. Therefore, this study investigated the effects of a 28-year long liquid nitrogen storage period on BT474 cells with regard to phenotypical changes, differences in cell-surface receptor expression as well as cytokine and gene expressional variations. Two batches of BT474 cells, one frozen in 1986, the other directly purchased from ATCC were investigated by light microscopy, cell growth analysis, flow cytometry and cytokine as well as whole-transcriptome expression profiling. The cell lines were morphologically indifferent and showed similar growth rates and similar cell-surface receptor expression. Transcriptome analysis revealed significant differences in only 26 of 40,716 investigated RefSeq transcripts with 4 of them being up-regulated and 22 down-regulated. This study demonstrates that even after very long periods of storage in liquid nitrogen, cancer cell lines display only minimal changes in their gene expression profiles. However, also such minor changes should be carefully assessed before continuation of experiments, especially if phenotypic alterations can be additionally observed.

  6. Epigenetic Dysregulation in Laryngeal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Thian-Sze Wong

    2012-01-01

    Full Text Available Laryngeal carcinoma is a common head and neck cancer with poor prognosis. Patients with laryngeal carcinoma usually present late leading to the reduced treatment efficacy and high rate of recurrence. Despite the advance in the use of molecular markers for monitoring human cancers in the past decades, there are still no reliable markers for use to screen laryngeal carcinoma and follow the patients after treatment. Epigenetics emerged as an important field in understanding the biology of the human malignancies. Epigenetic alterations refer to the dysregulation of gene, which do not involve the alterations of the DNA sequence. Major epigenetic changes including methylation imbalance, histone modification, and small RNA dysregulation could play a role in the development of human malignancies. Global epigenetic change is now regarded as a molecular signature of cancer. The characteristics and behavior of a cancer could be predicted based on the specific epigenetic pattern. We here provide a review on the understanding of epigenetic dysregulation in laryngeal carcinoma. Further knowledge on the initiation and progression of laryngeal carcinoma at epigenetic level could promote the translation of the knowledge to clinical use.

  7. Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells.

    Science.gov (United States)

    Al-Eryani, Kamal; Cheng, Jun; Abé, Tatsuya; Maruyama, Satoshi; Yamazaki, Manabu; Babkair, Hamzah; Essa, Ahmed; Saku, Takashi

    2015-07-01

    Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

    Science.gov (United States)

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

  9. 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...

  10. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  11. Basal Cell Carcinoma: 10 Years of Experience

    International Nuclear Information System (INIS)

    Cigna, E.; Tarallo, M.; Maruccia, M.; Sorvillo, V.; Pollastrini, A.; Scuderi, N.

    2011-01-01

    Introduction. Basal cell carcinoma (BCC) is a locally invasive malignant epidermal tumour. Incidence is increasing by 10% per year; incidence of metastases is minimal, but relapses are frequent (40%-50%). The complete excision of the BCC allows reduction of relapse. Materials and Methods. The study cohort consists of 1123 patients underwent surgery for basal cell carcinoma between 1999 and 2009. Patient and tumor characteristics recorded are: age; gender; localization (head and neck, trunk, and upper and lower extremities), tumor size, excisional margins adopted, and relapses. Results. The study considered a group of 1123 patients affected by basal cell carcinoma. Relapses occurred in 30 cases (2,67%), 27 out of 30 relapses occurred in noble areas, where peripheral margin was <3mm. Incompletely excised basal cell carcinoma occurred in 21 patients (1,87%) and were treated with an additional excision. Discussion. Although guidelines indicate 3mm peripheral margin of excision in BCC <2cm, in our experience, a margin of less than 5mm results in a high risk of incomplete excisions

  12. Granuloma Inguinale Simulating Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    M Z Mani

    1981-01-01

    Full Text Available A case of extensive granuloma inguinale simulating squamous cell carcinoma is described. There was past history of urethritis leading to a urethral fistula. The ulcer healed almost completely within 19 days of receiving streptomycin injections. The patient had associated scabies and presumably also had latent syphillis (His VDRL was reactive in 1:8 dilution. The patient belonged to Madhya Pradesh.

  13. Basal cell carcinoma on the left cheek

    International Nuclear Information System (INIS)

    Jancar, B.

    2007-01-01

    A 91-year-old female patient was treated with irradiation for histologically confirmed basal cell carcinoma on the left cheek. The tumour, measuring 3 x 3 cm, with the depth of 2 cm, was extending up to the lower lid of the left eye. (author)

  14. Merkel cell carcinoma of the abdominal wall

    International Nuclear Information System (INIS)

    Dunlop, P.; Sapp, H.; Walsh, N.M.G.; Logan, P.M.

    1998-01-01

    Merkel cell carcinoma is a rare highly malignant tumour. There have been previous descriptions of the CT appearances of this tumour, but to our knowledge this is the first MRI description. MRI may be a more sensitive method of initial evaluation of the local extension of the primary tumour. (orig.)

  15. Vulvar basal cell carcinoma, a rare location

    Directory of Open Access Journals (Sweden)

    Cornelia Nitipir

    2018-05-01

    Full Text Available Basal Cell Carcinoma is the most common human malignant neoplasm. Vulvar basal cell carcinoma is rare, accounting for less than 5% of all vulvar neoplasms. Vulvar basal cell carcinomas are usually diagnosed late because they are often asymptomatic and tend to grow at slow rates. They are usually diagnosed late because they are often asymptomatic. However, these tumours may appear in areas which are normally covered with ultraviolet light. We present the case of a 60 years old woman diagnosed with invasive breast cancer for which she underwent surgery followed by chemotherapy and radiotherapy. The patient presented to our department with an ulcerated vulvar lesion. On inspection, the tumour measured 3/2 cm and was located on the left labium majus. The biopsy confirmed the diagnosis of vulvar basal cell carcinoma and a wide local excision was performed with no relapse at one year. In conclusion, early detection of BCC’s is critical to allow complete surgical cure so any abnormality on the vulva should be biopsied. A wide safety margin of 1cm should be achieved when resecting the tumour and the physician should keep in mind that the BCC’s of the vulva has a high recurrence rate. Previous chemotherapy is not associated with this type of non-melanoma skin cancer.

  16. Cardiac Metastasis in Renal Cell Carcinoma

    African Journals Online (AJOL)

    abp

    2015-10-21

    Oct 21, 2015 ... Metastatic disease of the heart is over twenty times more common than primary heart tumors [1]. They are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Cardiac involvement in renal cell carcinoma (RCC) commonly arises from direct ...

  17. Squamous cell carcinoma in bladder extrophy

    OpenAIRE

    Cabral-Ribeiro, J; Silva, C; Sousa, L; Pérez García, D; Ribeiro dos Santos, A

    2005-01-01

    Bladder extrophy is a rare congenital malformation that nowadays is surgically corrected in neonatal period. We present a case report of a 71-year-old male with a verrucous squamous cell carcinoma arising in a classical uncorrected form of bladder extrophy.

  18. Presumed choroidal metastasis of Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III; Rossitch, G.; Dutton, J.J.

    1990-01-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma

  19. Merkel cells carcinoma of the aged patient

    International Nuclear Information System (INIS)

    Levy, A.; Assouline, A.; Mazeron, J.J.; Chargari, C.; Krzisch, C.

    2009-01-01

    The carcinoma at Merkel cells is a rare and aggressive skin cancer, principally of the aged adult. The surgery is the fundamental treatment. The interest of the adjuvant radiotherapy is discussed for the aged patient. In the limits of this retrospective analysis, the postoperative radiotherapy appeared to bring a similar benefit as for younger patients. (N.C.)

  20. CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

    International Nuclear Information System (INIS)

    Lee, Chang Hee; Cho, Seong Beum; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung

    1994-01-01

    The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

  1. The relationship among human papilloma virus infection, survivin, and p53 gene in lung squamous carcinoma tissue

    International Nuclear Information System (INIS)

    Yue-Hua Wang; De-jie Chen; Tie-Nan Yi

    2010-01-01

    To study the relationship between the infection of human papillomavirus (HPV) type 16, type 18, the expression of survivin, and the mutation of p53 gene in lung squamous carcinoma tissue for the research of pathogenesis of lung carcinoma.This study was carried out at the Laboratory of Molecular Biology, Xiangfan Central Hospital of Hubei Province, China from September 2008 to May 2010. Forty-five specimens of lung squamous carcinoma tissue confirmed by histopathology were the excisional specimens taken by the Thoracic Surgery of Xiangfan Central Hospital. Normal tissue, closely adjacent to the fresh carcinoma specimens, was used as the control group for p53 gene mutation analysis. Sixteen surgical excisional specimens of benign lung disease were used as a control group of non-carcinomatous diseases. Human papillomavirus DNA were detected by polymerase chain reaction (PCR), and we used the PCR-single-strand conformation polymorphism-ethidium bromide (PCR-SSCP-EB) method to detect the mutations of the p53 gene. The expression of the survivin gene was detected by immunohistochemistry methods. Approximately 68.9% of 45 lung squamous carcinoma tissue had p53 gene mutations. The mutation rate of exon 5-8 p53 were 15.6%, 17.8%, 15.6% and 20%. Approximately 42.2% of lung squamous cell carcinoma samples were shown to be positive for HPV DNA expression and 62.2% were positive for survivin expression. There was an inverse correlation between the presence of HPV infections and mutations of p53 gene; and the mutations of p53 gene and expression of survivin had a positive relationship. Mutation of p53 gene and HPV infection may facilitate each other in the generation of lung squamous cell carcinoma. Abnormal expression of the survivin gene may take part in the onset and progression of lung squamous cell carcinoma (Author).

  2. Squamous cell carcinoma of the breast: a case report

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    Hofstee Mans

    2008-12-01

    Full Text Available Abstract 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 carcinoma. After the operation the pathological examination revealed a primary squamous cell carcinoma of the breast. Conclusion The presentation of squamous cell carcinoma could be similar to that of an adenocarcinoma. However, a squamous cell carcinoma of the breast could also develop from a complicated breast cyst or abscess. Therefore, pathological examination of these apparent benign abnormalities is mandatory.

  3. Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2–q29 in squamous cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Kang, Ji Un; Koo, Sun Hoe; Kwon, Kye Chul; Park, Jong Woo; Kim, Jin Man

    2009-01-01

    The underlying genetic alterations for squamous cell carcinoma (SCC) and adenocarcinoma (AC) carcinogenesis are largely unknown. High-resolution array- CGH was performed to identify the differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC). On a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2–q29, 12p13.2–p13.33, and 19p13.3, as well as losses at 3p26.2–p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2–q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at the 3q26.2–q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Many significant genes at the 3q26.2–q29 regions previously linked to a specific histology, such as EVI1,MDS1, PIK3CA and TP73L, were observed in SCC (P < 0.05). In addition, we identified the following possible target genes (> 30% of patients) at 3q26.2–q29: LOC389174 (3q26.2),KCNMB3 (3q26.32),EPHB3 (3q27.1), MASP1 and SST (3q27.3), LPP and FGF12 (3q28), and OPA1,KIAA022,LOC220729, LOC440996,LOC440997, and LOC440998 (3q29), all of which were significantly targeted in SCC (P < 0.05). Among these same genes, high-level amplifications were detected for the gene, EPHB3, at 3q27.1, and MASP1 and SST, at 3q27.3 (18, 18, and 14%, respectively). Quantitative real time PCR demonstrated array CGH detected potential candidate genes that were over expressed in SCCs. Using whole-genome array CGH, we have successfully identified significant differences and unique information of chromosomal signatures prevalent between the SCC and AC subtypes of NSCLC. The newly identified candidate target genes may prove to be highly attractive candidate molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the

  4. Human Papilloma Virus and Esophageal Squamous Cell Carcinoma

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    Hayedeh Haeri

    2013-04-01

    Full Text Available Human papilloma virus (HPV has been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in substantial number of esophageal SCCs in our region is unlikely.

  5. Human papilloma virus and esophageal squamous cell carcinoma.

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    Hayedeh Haeri

    2014-03-01

    Full Text Available Human papillomavirus (HPV has also been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in the substantial number of esophageal SCCs in our region is unlikely.

  6. CRISPR/Cas9-Mediated Genomic Deletion of the Beta-1, 4 N-acetylgalactosaminyltransferase 1 Gene in Murine P19 Embryonal Carcinoma Cells Results in Low Sensitivity to Botulinum Neurotoxin Type C.

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    Kentaro Tsukamoto

    Full Text Available Botulinum neurotoxins produced by Clostridium botulinum cause flaccid paralysis by inhibiting neurotransmitter release at peripheral nerve terminals. Previously, we found that neurons derived from the murine P19 embryonal carcinoma cell line exhibited high sensitivity to botulinum neurotoxin type C. In order to prove the utility of P19 cells for the study of the intracellular mechanism of botulinum neurotoxins, ganglioside-knockout neurons were generated by deletion of the gene encoding beta-1,4 N-acetylgalactosaminyltransferase 1 in P19 cells using the clustered regularly interspaced short palindromic repeats combined with Cas9 (CRISPR/Cas9 system. By using this system, knockout cells could be generated more easily than with previous methods. The sensitivity of the generated beta-1,4 N-acetylgalactosaminyltransferase 1-depleted P19 neurons to botulinum neurotoxin type C was decreased considerably, and the exogenous addition of the gangliosides GD1a, GD1b, and GT1b restored the susceptibility of P19 cells to botulinum neurotoxin type C. In particular, addition of a mixture of these three ganglioside more effectively recovered the sensitivity of knockout cells compared to independent addition of GD1a, GD1b, or GT1b. Consequently, the genome-edited P19 cells generated by the CRISPR/Cas9 system were useful for identifying and defining the intracellular molecules involved in the toxic action of botulinum neurotoxins.

  7. Cutaneous metastasis of bilateral renal cell carcinoma.

    Science.gov (United States)

    Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin

    2013-01-01

    Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.

  8. Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma

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    Fengju Chen

    2016-03-01

    Full Text Available On the basis of multidimensional and comprehensive molecular characterization (including DNA methalylation and copy number, RNA, and protein expression, we classified 894 renal cell carcinomas (RCCs of various histologic types into nine major genomic subtypes. Site of origin within the nephron was one major determinant in the classification, reflecting differences among clear cell, chromophobe, and papillary RCC. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes. Differences in patient survival and in alteration of specific pathways (including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR could further distinguish the subtypes. Immune checkpoint markers and molecular signatures of T cell infiltrates were both highest in the subtype associated with aggressive clear cell RCC. Differences between the genomic subtypes suggest that therapeutic strategies could be tailored to each RCC disease subset.

  9. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    International Nuclear Information System (INIS)

    Klopfleisch, Robert; Lenze, Dido; Hummel, Michael; Gruber, Achim D

    2010-01-01

    Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a

  10. Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses

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    Myklebost Ola

    2007-01-01

    Full Text Available Abstract Background Despite the fact that metastases are the leading cause of colorectal cancer deaths, little is known about the underlying molecular changes in these advanced disease stages. Few have studied the overall gene expression levels in metastases from colorectal carcinomas, and so far, none has investigated the peritoneal carcinomatoses by use of DNA microarrays. Therefore, the aim of the present study is to investigate and compare the gene expression patterns of primary carcinomas (n = 18, liver metastases (n = 4, and carcinomatoses (n = 4, relative to normal samples from the large bowel. Results Transcriptome profiles of colorectal cancer metastases independent of tumor site, as well as separate profiles associated with primary carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of chromosome arm 5p are common in peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2, and ZNF622 mapping to this region were overexpressed in the tumors. Expression signatures stratified on TP53 mutation status were identified across all tumors regardless of stage. Furthermore, the gene expression levels for the in vivo tumors were compared with an in vitro model consisting of cell lines representing all three tumor stages established from one patient. Conclusion By statistical analysis of gene expression data from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are able to identify genetic patterns associated with the different stages of tumorigenesis.

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

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

    2015-01-01

    Currently, non-small cell lung carcinomas are primarily classified by light microscopy. However, recent studies have shown that poorly-differentiated tumors are more accurately classified by immunohistochemistry. In this study, we investigated the use of immunohistochemical analysis in reclassifying lung carcinomas that were originally diagnosed as squamous cell carcinoma. Tumor slides and blocks were available for histologic evaluation, and tissue microarrays were constructed from 480 patients with resected lung carcinomas originally diagnosed as squamous cell carcinoma between 1999 and 2009. Immunohistochemistry for p40, p63, thyroid transcription factor-1 (TTF-1; clone SPT24 and 8G7G3/1), Napsin A, Chromogranin A, Synaptophysin, and CD56 were performed. Staining intensity (weak, moderate, or strong) and distribution (focal or diffuse) were also recorded. Of all, 449 (93.5%) patients were confirmed as having squamous cell carcinomas; the cases were mostly diffusely positive for p40 and negative for TTF-1 (8G7G3/1). Twenty cases (4.2%) were reclassified as adenocarcinoma since they were positive for TTF-1 (8G7G3/1 or SPT24) with either no or focal p40 expression, and all of them were poorly-differentiated with squamoid morphology. In addition, 1 case was reclassified as adenosquamous carcinoma, 4 cases as large cell carcinoma, 4 cases as large cell neuroendocrine carcinoma, and 2 cases as small cell carcinoma. In poorly-differentiated non-small cell lung carcinomas, an accurate distinction between squamous cell carcinoma and adenocarcinoma cannot be reliably determined by morphology alone and requires immunohistochemical analysis, even in resected specimens. Our findings suggest that TTF-1 8G7G3/1 may be better suited as the primary antibody in differentiating adenocarcinoma from squamous cell carcinoma. PMID:25871623

  12. Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

    Science.gov (United States)

    Messai, Yosra; Gad, Sophie; Noman, Muhammad Zaeem; Le Teuff, Gwenael; Couve, Sophie; Janji, Bassam; Kammerer, Solenne Florence; Rioux-Leclerc, Nathalie; Hasmim, Meriem; Ferlicot, Sophie; Baud, Véronique; Mejean, Arnaud; Mole, David Robert; Richard, Stéphane; Eggermont, Alexander M M; Albiges, Laurence; Mami-Chouaib, Fathia; Escudier, Bernard; Chouaib, Salem

    2016-10-01

    Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We

  13. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    Science.gov (United States)

    Barkla, D H; Whitehead, R H; Foster, H; Tutton, P J

    1988-09-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells.

  14. Implementation of plaid model biclustering method on microarray of carcinoma and adenoma tumor gene expression data

    Science.gov (United States)

    Ardaneswari, Gianinna; Bustamam, Alhadi; Sarwinda, Devvi

    2017-10-01

    A Tumor is an abnormal growth of cells that serves no purpose. Carcinoma is a tumor that grows from the top of the cell membrane and the organ adenoma is a benign tumor of the gland-like cells or epithelial tissue. In the field of molecular biology, the development of microarray technology is used in the data store of disease genetic expression. For each of microarray gene, an amount of information is stored for each trait or condition. In gene expression data clustering can be done with a bicluster algorithm, thats clustering method which not only the objects to be clustered, but also the properties or condition of the object. This research proposed Plaid Model Biclustering as one of biclustering method. In this study, we discuss the implementation of Plaid Model Biclustering Method on microarray of Carcinoma and Adenoma tumor gene expression data. From the experimental results, we found three biclusters are formed by Carcinoma gene expression data and four biclusters are formed by Adenoma gene expression data.

  15. Gene-expression Classifier in Papillary Thyroid Carcinoma

    DEFF Research Database (Denmark)

    Londero, Stefano Christian; Jespersen, Marie Louise; Krogdahl, Annelise

    2016-01-01

    BACKGROUND: No reliable biomarker for metastatic potential in the risk stratification of papillary thyroid carcinoma exists. We aimed to develop a gene-expression classifier for metastatic potential. MATERIALS AND METHODS: Genome-wide expression analyses were used. Development cohort: freshly...

  16. Predictive gene signatures: molecular markers distinguishing colon adenomatous polyp and carcinoma.

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    Janice E Drew

    Full Text Available Cancers exhibit abnormal molecular signatures associated with disease initiation and progression. Molecular signatures could improve cancer screening, detection, drug development and selection of appropriate drug therapies for individual patients. Typically only very small amounts of tissue are available from patients for analysis and biopsy samples exhibit broad heterogeneity that cannot be captured using a single marker. This report details application of an in-house custom designed GenomeLab System multiplex gene expression assay, the hCellMarkerPlex, to assess predictive gene signatures of normal, adenomatous polyp and carcinoma colon tissue using archived tissue bank material. The hCellMarkerPlex incorporates twenty-one gene markers: epithelial (EZR, KRT18, NOX1, SLC9A2, proliferation (PCNA, CCND1, MS4A12, differentiation (B4GANLT2, CDX1, CDX2, apoptotic (CASP3, NOX1, NTN1, fibroblast (FSP1, COL1A1, structural (ACTG2, CNN1, DES, gene transcription (HDAC1, stem cell (LGR5, endothelial (VWF and mucin production (MUC2. Gene signatures distinguished normal, adenomatous polyp and carcinoma. Individual gene targets significantly contributing to molecular tissue types, classifier genes, were further characterised using real-time PCR, in-situ hybridisation and immunohistochemistry revealing aberrant epithelial expression of MS4A12, LGR5 CDX2, NOX1 and SLC9A2 prior to development of carcinoma. Identified gene signatures identify aberrant epithelial expression of genes prior to cancer development using in-house custom designed gene expression multiplex assays. This approach may be used to assist in objective classification of disease initiation, staging, progression and therapeutic responses using biopsy material.

  17. CpG location and methylation level are crucial factors for the early detection of oral squamous cell carcinoma in brushing samples using bisulfite sequencing of a 13-gene panel.

    Science.gov (United States)

    Morandi, Luca; Gissi, Davide; Tarsitano, Achille; Asioli, Sofia; Gabusi, Andrea; Marchetti, Claudio; Montebugnoli, Lucio; Foschini, Maria Pia

    2017-01-01

    Oral squamous cell carcinoma (OSCC) is usually diagnosed at an advanced stage and is commonly preceded by oral premalignant lesions. The mortality rates have remained unchanged (50% within 5 years after diagnosis), and it is related to tobacco smoking and alcohol intake. Novel molecular markers for early diagnosis are urgently needed. The purpose of this study was to evaluate the diagnostic value of methylation level in a set of 18 genes by bisulfite next-generation sequencing. With minimally invasive oral brushing, 28 consecutive OSCC, one squamous cell carcinoma with sarcomatoid features, six high-grade squamous intraepithelial lesions (HGSIL), 30 normal contralateral mucosa from the same patients, and 65 healthy donors were evaluated for DNA methylation analyzing 18 target genes by quantitative bisulfite next-generation sequencing. We further evaluated an independent cohort (validation dataset) made of 20 normal donors, one oral fibroma, 14 oral lichen planus (OLP), three proliferative verrucous leukoplakia (PVL), and two OSCC. Comparing OSCC with normal healthy donors and contralateral mucosa in 355 CpGs, we identified the following epigenetically altered genes: ZAP70 , ITGA4 , KIF1A , PARP15 , EPHX3 , NTM , LRRTM1 , FLI1 , MIR193 , LINC00599 , PAX1 , and MIR137HG showing hypermethylation and MIR296 , TERT , and GP1BB showing hypomethylation . The behavior of ZAP70 , GP1BB , H19 , EPHX3 , and MIR193 fluctuated among different interrogated CpGs. The gap between normal and OSCC samples remained mostly the same (Kruskal-Wallis P values < 0.05), but the absolute values changed conspicuously. ROC curve analysis identified the most informative CpGs, and we correctly stratified OSCC and HGSIL from normal donors using a multiclass linear discriminant analysis in a 13-gene panel (AUC 0.981). Only the OSCC with sarcomatoid features was negative. Three contralateral mucosa were positive, a sign of a possible field cancerization. Among imprinted genes, only MIR296

  18. RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

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    Elisangela Giachini

    2017-06-01

    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

  19. Identification of genes differentially expressed in testes containing carcinoma in situ

    DEFF Research Database (Denmark)

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

    2004-01-01

    Virtually all testicular germ cell tumours originate from a common precursor, the carcinoma in situ (CIS) cell. The precise nature of the molecular mechanisms leading to CIS remains largely unknown. We performed the first systematic analysis of gene expression in testis with CIS compared to normal...... the novel expressed sequence tag (EST) OIC1 (Overexpressed In CIS). The genes could be grouped functionally into genes involved in cell growth, proliferation, differentiation, immunological response, and genes with unknown biological function. Examples of overexpressed genes are SFRP1 that is involved...... to testicular development (e.g. DCN, IGFBP6, SFRP1, SALL1), supporting our hypothesis that the origin of CIS is probably associated with disturbances of the fetal development of the testis....

  20. Squamous cell carcinoma in situ after irradiation

    International Nuclear Information System (INIS)

    Kambara, Takeshi; Nishiyama, Takafumi; Yamada, Rie; Nagatani, Tetsuo; Nakajima, Hiroshi; Sugiyama, Asami

    1997-01-01

    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)

  1. Linear Basal Cell Carcinoma: A Case Report

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    Yuko Ichinokawa

    2011-07-01

    Full Text Available Basal cell carcinoma (BCC presents with diverse clinical features, and several morphologic and histologic variants of BCC have been reported [Sexton et al.: J Am Acad Dermatol 1990;23:1118–1126]. Linear BCC was first described as a new clinical subtype in 1985 by Lewis [Int J Dematol 1985;24:124–125]. Here, we present a case of linear BCC that we recently encountered in an elderly Japanese patient, and review other cases reported in Japan.

  2. Avelumab Impresses in Merkel Cell Carcinoma.

    Science.gov (United States)

    2017-06-01

    The PD-L1 inhibitor avelumab-approved by the FDA in March for the treatment of Merkel cell carcinoma-demonstrated a high number of durable responses in an international, open-label, prospective phase II study. The results of the study, which supported the FDA's decision, were presented in April at the American Association for Cancer Research (AACR) Annual Meeting 2017. ©2017 American Association for Cancer Research.

  3. Papillary renal cell carcinoma in allograft kidney

    International Nuclear Information System (INIS)

    Roy, Catherine; El Ghali, Sofiane; Buy, Xavier; Gangi, Afshin; Lindner, Veronique

    2005-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. Its occurrence in allograft transplanted kidney has not been debated in the literature. We report two pathologically proven cases and discuss the clinical hypothesis for such neoplasms and the aspect on MR images. The paramagnetic effect of the iron associated with an absence of signal coming from calcifications is a plausible explanation for this unusual hypointense appearance on T2-weighted sequence. (orig.)

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

    Science.gov (United States)

    Gudiseva, Swetha; Chitturi, Raviteja; Anumula, Vamsikrishna; Poosarla, Chandrashekar; Baddam, Venkat Ramana Reddy

    2017-01-01

    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. PMID:28435394

  5. 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.

  6. CT features of nonfunctioning islet cell carcinoma

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    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.

  7. 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.

  8. Cabozantinib (advanced renal cell carcinoma)

    Science.gov (United States)

    ... cancer cells.Cabozantinib is also available as a capsule (Cometriq) to treat a certain type of thyroid ... vomiting material that is bloody or looks like coffee grounds menstrual bleeding that is heavier than usual ...

  9. 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

  10. Anogenital squamous cell carcinoma in neglected patient.

    Science.gov (United States)

    Svecova, D; Havrankova, M; Weismanova, E; Babal, P

    2012-01-01

    Skin squamous cell carcinomas (SCCs) are arguably the second most common carcinoma of the skin and are responsible for the majority of non-melanoma skin cancer deaths. Gynecologist treated a Caucasian 56-years old female patient for genital wart with podophyllotoxin cream. She did not achieve complete response and therefore she has interrupted the therapy and the collaboration with the gynecologist. At the time of evaluation the lesion had a size of man's palm in anogenital region and showed characteristic features of neoplasm. The regional lymph nodes have produced infiltrated painful bubo. PCR analysis for HPV proved negative. Histopathology revealed well-differentiated squamous cell keratinizing carcinoma from the tumor as well as from the regional lymph node packet. Staging computed tomography scans proved negative and pelvis scans disclosed regional lymphadenopathy underlying the tumor. Palliative radiation therapy (by linear accelerator) was administered for the oversized tumor to the total TD 50.0Gy. The patient died 6 months after diagnostic assessment from cardio-respiratory failure. Staging computed tomography before her death did not disclose distinct metastases in her inner organs. Well-differentiated squamous cell keratinizing carcinoma could be growing endophytically affecting the underlying adipose tissue and musculature, with spreading into the regional lymph nodes. The rate of metastases into inner organs seems to vary according to the aggressiveness and metastatic behavior of each SCC. The case report calls for attention to the importance of collaboration among various specialists assisting in the diagnosis and management of skin neoplasm (Fig. 5, Ref. 12). Full Text in PDF www.elis.sk.

  11. Herbal medicine Guan Chang Fu Fang enhances 5-fluorouracil cytotoxicity and affects drug-associated genes in human colorectal carcinoma cells.

    Science.gov (United States)

    Yu, Chen; Liu, Shen-Lin; Qi, Ming-Hao; Zou, Xi; Wu, Jian; Zhang, Jing

    2015-02-01

    Guan Chang Fu Fang (GCFF) is a natural compound, which is extracted from three medicinal plants, Agrimonia pilosa Ledeb ., Patrinia scabiosaefolia and Solanum nigrum L . GCFF has demonstrated clinical efficacy in the treatment of colon cancer. At present, 5-fluorouracil (5-FU) is the primary active chemotherapeutic agent used for treating colon cancer. Using median-effect and apoptosis analyses, fluorescence microscopy and western blotting, the present study analyzed the association between GCFF and 5-FU in the human colon adenocarcinoma LoVo cell line. The effect of GCFF on the expression of chemotherapeutic agent-associated genes was also investigated. The results of the synergistic analysis revealed that GCFF exhibited a significant effect upon 5-FU-associated cytotoxicity within the LoVo cell line. This effect was observed over a broad dose-inhibition range (5-95%), but was particularly significant in the lower concentrations. The flow cytometry results revealed that low doses of GCFF or 5-FU induced S-phase arrest, as did a low-dose combination of the two drugs. After 48 h, GCFF significantly suppressed the expression levels of the chemotherapeutic agent resistance-associated genes within the colon cancer cells. The western blot analysis revealed that the combined effects of 5-FU and GCFF were due to a regulation of the B-cell lymphoma-2 family of proteins. The findings of the present study suggested that GCFF, when combined with 5-FU, has the potential to be a novel, chemotherapeutic compound for the treatment of colon cancer.

  12. SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK: NEW AVENUES OF TREATMENT?

    Directory of Open Access Journals (Sweden)

    T. Braunschweig

    2013-01-01

    Full Text Available Squamous cell carcinoma of the head and neck counts for 3 % of all cancers in men and half of this number less in women with a 5-year survival of 61 %. While the number of laryngeal carcinoma is decreasing, carcinoma of the oral cavity related to an infection by the human papilloma virus (HPV, high-risk subtypes is increasing, especially in younger patients. HPV related squamous cell carcinomas show better survival data, especially in regard to recurrence free rates or secondary carcinoma of adjacent locations. Squamous cell carcinomas related to the presence of HPV DNA material is almost exclusively found in carcinoma of the oral cavity and oropharyngeal mucosa. Much less frequently HPV is present in hypopharyngeal carcinomas and even less number of cases of squamous cell carcinoma with proof for HPV in the nasopharynx and larynx. In case of evidence for HPV DNA; most cases are positively tested for subtype 16, followed by subtype 18. As a surrogate immunhistochemical marker, p16 INK4A is stained positive, cytoplasmic and nuclear. In a small study by ourselves, we found a positive correlation in 100 % of p16 INK4A positivity and positive HPV testing. Oral squamous cell carcinoma is more frequently related to HPV in patients below 50 years of age with a prevalence of ca. 20 %. Whilst HPV high-risk positive carcinomas show very few mutations in single signalling molecules of the downstream receptor tyrosin kinase pathways, HPV negative carcinomas show in many cases a chaotic DNA mutation type with typical mutations in tumor suppressor genes, as p53 and CDKN2A. This pattern is often seen in carcinoma types develop from a summation of accidental mutations often caused by toxins (e.g. inhaled cigarette smoke. However, it is discussed and under investigation whether a subset of head and neck squamous cell carcinomasdevelop from so called driver mutations, as are called mutations in critical members of signalling pathways and receptor tyrosin kinases

  13. Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study.

    Science.gov (United States)

    Huang, Jing; Fan, Qingxia; Lu, Ping; Ying, Jianming; Ma, Changwu; Liu, Wei; Liu, Ying; Tan, Fenlai; Sun, Yan

    2016-06-01

    Epidermal growth factor receptor (EGFR) has been reported to be overexpressed and amplified in a high percentage of patients with esophageal squamous cell carcinoma (ESCC). The activity of icotinib, an EGFR tyrosine kinase inhibitor, was assessed in previously treated ESCC with EGFR overexpression or amplification. For this phase 2, single-arm, multicenter trial undertaken at six hospitals in China, we included Chinese patients with previously treated, histologically confirmed advanced ESCC and EGFR overexpression (immunohistochemical staining sore of 3+) or amplification (positive fluorescence in situ hybridization result). These patients received oral icotinib (250 mg, three times daily).The primary end point was the proportion of patients with objective responses as assessed by an independent radiology review committee. Between December 5, 2013, and May 28, 2015, a total of 281 patients were screened. Fifty-four eligible patients were enrolled. Nine responses were observed, including one complete response and eight partial responses, and 16 patients had stable disease, resulting in a 16.7% objective response rate (95% confidence interval [CI]: 6.7-26.6) and 46.3% disease control rate (95% CI: 33.0-59.6). The median progression-free survival and overall survival times were 52 (95% CI: 40-95) days and 153 (95% CI: 139-218) days, respectively. A total of 43 patients experienced at least one adverse event, but most were only grade 1 to 2 in severity. The most frequent was rash (48.1%), followed by diarrhea (22.2%). Icotinib showed favorable activity in patients with advanced, previously treated ESCC with EGFR overexpression or amplification. These findings suggest further research into EGFR overexpression or amplification for selecting responsive patients. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  14. Mechanism of enhanced responses after combination photodynamic therapy (cPDT) in carcinoma cells involves C/EBP-mediated transcriptional upregulation of the coproporphyrinogen oxidase (CPO) gene

    Science.gov (United States)

    Anand, Sanjay; Hasan, Tayyaba; Maytin, Edward V.

    2013-03-01

    Photodynamic therapy (PDT) with aminolevulinate (ALA) is widely accepted as an effective treatment for superficial carcinomas and pre-cancers. However, PDT is still suboptimal for deeper tumors, mainly due to inadequate ALA penetration and subsequent conversion to PpIX. We are interested in improving the effectiveness of photodynamic therapy (PDT) for deep tumors, using a combination approach (cPDT) in which target protoporphyrin (PpIX) levels are significantly enhanced by differentiation caused by giving Vitamin D or methotrexate (MTX) for 3 days prior to ALAPDT. In LNCaP and MEL cells, a strong correlation between inducible differentiation and expression of C/EBP transcription factors, as well as between differentiation and mRNA levels of CPO (a key heme-synthetic enzyme), indicates the possibility of CPO transcriptional regulation by the C/EBPs. Sequence analysis of the first 1300 base pairs of the murine CPO upstream region revealed 15 consensus C/EBP binding sites. Electrophoretic Mobility Shift Assays (EMSA) proved that these sites form specific complexes that have strong, moderate or weak affinities for C/EBPs. However, in the context of the full-length CPO promoter, inactivation of any type of site (strong or weak) reduced CPO promoter activity (luciferase assay) to nearly the same extent, suggesting cooperative interactions. A comparative analysis of murine and human CPO promoters revealed possible protein-protein interactions between C/EBPs and several neighboring transcription factors such as NFkB, Sp1, AP-1, CBP/p300 and CREB (an enhanceosome complex). Overall, these results confirm that C/EBP's are important for CPO expression via complex mechanisms which upregulate PpIX and enhance the outcome of cPDT.

  15. Basal Cell Carcinomas in Gorlin Syndrome: A Review of 202 Patients

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Jones

    2011-01-01

    Full Text Available Gorlin syndrome (Naevoid Basal Cell Carcinoma Syndrome is a rare autosomal dominant syndrome caused by mutations in the PTCH gene with a birth incidence of approximately 1 in 19,000. Patients develop multiple basal cell carcinomas of the skin frequently in early life and also have a predisposition to additional malignancies such as medulloblastoma. Gorlin Syndrome patients also have developmental defects such as bifid ribs and other complications such as jaw keratocysts. We studied the incidence and frequency of basal cell carcinomas in 202 Gorlin syndrome patients from 62 families and compared this to their gender and mutation type. Our data suggests that the incidence of basal cell carcinomas is equal between males and females and the mutation type cannot be used to predict disease burden.

  16. Basal Cell Carcinomas in Gorlin Syndrome: A Review of 202 Patients

    International Nuclear Information System (INIS)

    Jones, E. A.; Shenton, A.; Evans, D. G.; Sajid, M. I.

    2011-01-01

    Gorlin syndrome (Naevoid Basal Cell Carcinoma Syndrome) is a rare autosomal dominant syndrome caused by mutations in the PTCH gene with a birth incidence of approximately 1 in 19,000. Patients develop multiple basal cell carcinomas of the skin frequently in early life and also have a predisposition to additional malignancies such as medulloblastoma. Gorlin Syndrome patients also have developmental defects such as bifid ribs and other complications such as jaw keratocysts. We studied the incidence and frequency of basal cell carcinomas in 202 Gorlin syndrome patients from 62 families and compared this to their gender and mutation type. Our data suggests that the incidence of basal cell carcinomas is equal between males and females and the mutation type cannot be used to predict disease burden

  17. 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

  18. Squamous cell carcinoma of the oral cavity

    International Nuclear Information System (INIS)

    Lindeloev, B.; Kirkegaard, J.; Hansen, H.S.; Copenhagen Univ. Hospital

    1990-01-01

    Three hundred and four patients with squamous cell carcinomas of the oral cavity were treated at the Finsen Institute in cooperation with the ENT-surgical departments between 1978 and 1982. The primary treatment consisted of radiotherapy alone in 74%, surgery alone in 4%, and a combination of radiotherapy and surgery in 15% of the patients. 2% received other treatment (cryotherapy), 5% did not complete the planned radiotherapy, and 1% were not treated at all. Of 203 patients with tumour remnant or first recurrence, 45% were operated, 2% received radiotherapy, and 2% combined treatment. This treatment strategy made 38% of the patients free of disease in the follow-up period (3 1/2 to 8 years) or until the patients died from other causes. Fifty-nine percent of the patients died from their oral carcinomas. Tumour size (T), lymph node status (N), and tumour stage were as expected important prognostic factors. (orig.)

  19. Nitric Oxide Synthase Type III Overexpression By Gene Therapy Exerts Antitumoral Activity In Mouse Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Raúl González

    2015-08-01

    Full Text Available Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO synthase type III (NOS-3 overexpression induces cell death in hepatoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. Hepa 1-6 cells were used for in vitro and in vivo experiments. The first generation adenovirus was designed to overexpress NOS-3 (or GFP and luciferase cDNA under the regulation of murine alpha-fetoprotein (AFP and Rous Sarcoma Virus (RSV promoters, respectively. Both adenoviruses were administered through the tail vein two weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-Luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8 activity in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by l-NAME or p53 siRNA. The tail vein infusion of AFP-NOS- 3/RSV-Luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

  20. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kato, H.; Torigoe, T.

    1977-01-01

    A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care

  1. Mutational analysis of FLASH and PTPN13 genes in colorectal carcinomas.

    Science.gov (United States)

    Jeong, Eun Goo; Lee, Sung Hak; Yoo, Nam Jin; Lee, Sug Hyung

    2008-01-01

    The Fas-Fas ligand system is considered a major pathway for induction of apoptosis in cells and tissues. FLASH was identified as a pro-apoptotic protein that transmits apoptosis signal during Fas-mediated apoptosis. PTPN13 interacts with Fas and functions as both suppressor and inducer of Fas-mediated apoptosis. There are polyadenine tracts in both FLASH (A8 and A9 in exon 8) and PTPN13 (A8 in exon 7) genes that could be frameshift mutation targets in colorectal carcinomas. Because genes encoding proteins in Fas-mediated apoptosis frequently harbor somatic mutations in cancers, we explored the possibility as to whether mutations of FLASH and PTPN13 are a feature of colorectal carcinomas. We analysed human FLASH in exon 8 and PTPN13 in exon 7 for the detection of somatic mutations in 103 colorectal carcinomas by a polymerase chain reaction (PCR)- based single-strand conformation polymorphism (SSCP). We detected two mutations in FLASH gene, but none in PTPN13 gene. However, the two mutations were not frameshift (deletion or insertion) mutations in the polyadenine tracts of FLASH. The two mutations consisted of a deletion mutation (c.3734-3737delAGAA) and a missense mutation (c.3703A>C). These data indicate that frameshift mutation in the polyadenine tracts in both FLASH and PTPN13 genes is rare in colorectal carcinomas. Also, the data suggest that both FLASH and PTPN13 mutations in the polyadenine tracts may not have a crucial role in the pathogenesis of colorectal carcinomas.

  2. 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

  3. 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.......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...... studies of vitamin D's effect on TCC cells in vitro are necessary before the efficacy of treatment with vitamin D analogues in TCC can be evaluated in patients....

  4. 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.

  5. Carcinoma in situ testis, the progenitor of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Rajpert-De Meyts, E; Daugaard, G

    2005-01-01

    Testicular germ cell tumours (TGCT), including seminomas, embryonal carcinomas, teratomas and yolk sac tumours, have a common precursor, the carcinoma in situ (CIS) cell. Recent gene expression studies displaying close similarity of CIS cells to embryonic stem cells support the longstanding theory...... should be made to obtain diagnosis at the CIS stage, as intervention is possible before an invasive tumour develops, thus reducing the necessity for intensive therapy. CIS may be suspected in patients with an assumed extragonadal GCT or cryptorchidism, and in intersex patients and selected cases...

  6. Function of oval cells in hepatocellular carcinoma in rats.

    Science.gov (United States)

    Fang, Chi-Hua; Gong, Jia-Qing; Zhang, Wei

    2004-09-01

    To study oval cells' pathological characteristics and relationship with the occurrence of hepatocellular carcinoma (HCC); to observe the form and structural characteristics of oval cells; to explore the expression characteristics of C-kit, PCNA mRNA and c-myc gene during the occurrence and development of HCC and the effect of ulinastatin (UTI) on C-kit and PCNA expression. One hundred and twenty-five SD rats fed on 3,3'-diaminobenzidine (DAB) to construct HCC models were divided into control group, cancer-inducing group and UTI intervention group. In each group, rat liver samples were collected at weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 respectively to study pathological distribution characteristics of oval cells in the process of carcinogenesis under optical microscope. Oval cells were separated by the methods of improved density gradient centrifugation and their structural characteristics were observed under optical microscope and electronic microscope respectively; the oval cells expressing C-kit and PCNA in the collected samples were observed by the methods of immunohistochemistry and image analysis and the expression of c-myc mRNA was also detected by reverse transcription polymerase chain reaction (RT-PCR). Oval cells proliferated firstly in the portal area then gradually migrated into hepatic parenchyma in the inducing group and intervention group. The oval cells distributed inside and outside the carcinoma nodes. The oval cells presented the characteristics of undifferentiated cells: a high ratio of nucleolus and cellular plasm and obvious nucleoli, rare organelle in plasm. Only a few mitochondria and endoplasmic reticulum and some villus-like apophysis on surface of cells could be seen. Cells stained with C-kit and PCNA antibody were mainly oval cells distributed in the portal area. The expression of c-myc mRNA increased with the progression of HCC. However, in the intervention group, UTI could retard its increase. Oval cells work throughout

  7. Basaloid squamous cell carcinoma of the esophagus.

    Science.gov (United States)

    Chen, Shao-Bin; Weng, Hong-Rui; Wang, Geng; Yang, Jie-Sheng; Yang, Wei-Ping; Li, Hua; Liu, Di-Tian; Chen, Yu-Ping

    2012-07-01

    Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics. No standard treatment has been established. This retrospective study was designed to investigate the clinical and pathological characteristics, diagnosis, treatment, and prognosis of esophageal BSCC. Clinical data were retrospectively analyzed from 26 patients with pathologically confirmed esophageal BSCC who underwent transthoracic esophagectomy with lymphadenectomy between January 1995 and June 2010 at the Cancer Hospital of Shantou University Medical College. Clinicopathologic data between BSCC patients and different histologic grades of esophageal squamous cell carcinoma (ESCC) patients were statistically compared by means of the χ(2) test or Fisher's exact test. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. Microscopically, BSCC was characterized by a nesting, lobular, or trabecular arrangement of small crowded cells with scant cytoplasm. None of the histologic specimens taken at preoperative esophagoscopy were diagnosed as BSCC. The median survival time (MST) of the 26 patients was 29.0 months (95% confidence interval, 9.0-49.0), and the 1-, 3-, and 5-year overall survival rates were 73.1, 42.7, and 36.6%, respectively. The MST for BSCC patients was significantly lower than that of well-differentiated SCC patients (P = 0.024), but there were no significant differences between the MST for BSCC patients and that of moderately or poorly differentiated SCC patients (P > 0.05). BSCC of the esophagus is a rare but distinctive disease and is prone to be misdiagnosed by endoscopic biopsy. The prognosis is poorer than well-differentiated SCC, but similar to moderately or poorly differentiated SCC.

  8. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils...... incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  9. Nonsurgical Treatment Options for Basal Cell Carcinoma

    International Nuclear Information System (INIS)

    Lien, M. H.; Sondak, V. K.; Sondak, V. K.

    2011-01-01

    Basal cell carcinoma (BCC) remains the most common form of non melanoma 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.

  10. 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.

  11. 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.

  12. Basal cell carcinoma after radiation therapy

    International Nuclear Information System (INIS)

    Shimbo, Keisuke; Terashi, Hiroto; Ishida, Yasuhisa; Tahara, Shinya; Osaki, Takeo; Nomura, Tadashi; Ejiri, Hirotaka

    2008-01-01

    We reported two cases of basal cell carcinoma (BCC) that developed after radiation therapy. A 50-year-old woman, who had received an unknown amount of radiation therapy for the treatment of intracranial germinoma at the age of 22, presented with several tumors around the radiation ulcer. All tumors showed BCC. A 33-year-old woman, who had received an unknown amount of radiation therapy on the head for the treatment of leukemia at the age of 2, presented with a black nodule within the area of irradiation. The tumor showed BCC. We discuss the occurrence of BCC after radiation therapy. (author)

  13. Postoperative radiotherapy for merkel cell carcinoma

    International Nuclear Information System (INIS)

    Inoue, Kazuya; Asakawa, Isao; Katayama, Emiko; Kajitani, Chikae; Tamamoto, Tetsuro; Hasegawa, Masatoshi; Fukumoto, Takaya; Asada, Hideo

    2014-01-01

    Seven patients with Merkel cell carcinoma (MCC) who visited our department of radiation oncology from February 2005 to July 2011 received postoperative radiotherapy (50-60 Gy). All patients were alive without recurrence (median follow-up period: 47.6 (14.7-88.4) months). All of them had grade 2 dermatitis, and one grade 2 oral mucositis and three grade 2 lymphedema were observed. No adverse event grade 3 (CTCAE v4.0) or over was observed. In our hospital, clinical results of postoperative radiotherapy for MCC were fairly good, and adverse events were acceptable during the follow-up period. (author)

  14. 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.

  15. 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

  16. 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.

  17. Genomic portfolio of Merkel cell carcinoma as determined by comprehensive genomic profiling: implications for targeted therapeutics.

    Science.gov (United States)

    Cohen, Philip R; Tomson, Brett N; Elkin, Sheryl K; Marchlik, Erica; Carter, Jennifer L; Kurzrock, Razelle

    2016-04-26

    Merkel cell carcinoma is an ultra-rare cutaneous neuroendocrine cancer for which approved treatment options are lacking. To better understand potential actionability, the genomic landscape of Merkel cell cancers was assessed. The molecular aberrations in 17 patients with Merkel cell carcinoma were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine, Cambridge, MA) using next-generation sequencing (182 or 236 genes) and analyzed by N-of-One, Inc. (Lexington, MA). There were 30 genes harboring aberrations and 60 distinct molecular alterations identified in this patient population. The most common abnormalities involved the TP53 gene (12/17 [71% of patients]) and the cell cycle pathway (CDKN2A/B, CDKN2C or RB1) (12/17 [71%]). Abnormalities also were observed in the PI3K/AKT/mTOR pathway (AKT2, FBXW7, NF1, PIK3CA, PIK3R1, PTEN or RICTOR) (9/17 [53%]) and DNA repair genes (ATM, BAP1, BRCA1/2, CHEK2, FANCA or MLH1) (5/17 [29%]). Possible cognate targeted therapies, including FDA-approved drugs, could be identified in most of the patients (16/17 [94%]). In summary, Merkel cell carcinomas were characterized by multiple distinct aberrations that were unique in the majority of analyzed cases. Most patients had theoretically actionable alterations. These results provide a framework for investigating tailored combinations of matched therapies in Merkel cell carcinoma patients.

  18. Merkel cell polyomavirus infection and Merkel cell carcinoma.

    Science.gov (United States)

    Liu, Wei; MacDonald, Margo; You, Jianxin

    2016-10-01

    Merkel cell polyomavirus is the only polyomavirus discovered to date that is associated with a human cancer. MCPyV infection is highly prevalent in the general population. Nearly all healthy adults asymptomatically shed MCPyV from their skin. However, in elderly and immunosuppressed individuals, the infection can lead to a lethal form of skin cancer, Merkel cell carcinoma. In the last few years, new findings have established links between MCPyV infection, host immune response, and Merkel cell carcinoma development. This review discusses these recent discoveries on how MCPyV interacts with host cells to achieve persistent infection and, in the immunocompromised population, contributes to MCC development. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Clinicopathological and Targeted Exome Gene Features of a Patient with Metastatic Acinic Cell Carcinoma of the Parotid Gland Harboring an ARID2 Nonsense Mutation and CDKN2A/B Deletion

    Directory of Open Access Journals (Sweden)

    Wayne A. Warner

    2015-01-01

    Full Text Available We describe the presentation, treatment, clinical outcome, and targeted genome analysis of a metastatic salivary acinic cell carcinoma (AciCC. A 71-year-old male presented with a 3 cm right tail of a parotid lesion, first detected as a nodule by the patient seven months earlier. He had a right total parotidectomy with cranial nerve VII resection, right facial nerve resection and grafting, resection of the right conchal cartilage, and right modified radical neck dissection. The primary tumor revealed AciCC with two distinct areas: a well-differentiated component with glandular architecture and a dedifferentiated component with infiltrative growth pattern associated with prominent stromal response, necrosis, perineural invasion, and cellular pleomorphism. Tumor staging was pT4 N0 MX. Immunohistochemistry staining showed pankeratin (+, CD56 (−, and a Ki67 proliferation index of 15%. Upon microscopic inspection, 49 local lymph nodes resected during parotidectomy were negative for cancer cells. Targeted sequencing of the primary tumor revealed deletions of CDKN2A and CDKN2B, a nonsense mutation in ARID2, and single missense mutations of unknown significance in nine other genes. Despite postoperative localized radiation treatment, follow-up whole body PET/CT scan showed lung, soft tissue, bone, and liver metastases. The patient expired 9 months after resection of the primary tumor.

  20. Gene-silencing effects of anti-survivin siRNA delivered by RGDV-functionalized nanodiamond carrier in the breast carcinoma cell line MCF-7.

    Science.gov (United States)

    Bi, Yanzhao; Zhang, Yifan; Cui, Chunying; Ren, Lulu; Jiang, Xueyun

    Nanodiamond (ND) is a renowned material in nonviral small interfering RNA (siRNA) carrier field due to its unique physical, chemical, and biological properties. In our previous work, it was proven that ND could deliver siRNA into cells efficiently and downregulate the expression of desired protein. However, synthesizing a high-efficient tumor-targeting carrier using ND is still a challenge. In this study, a novel carrier, NDCONH(CH 2 ) 2 NH-VDGR, was synthesized for siRNA delivery, and its properties were characterized with methods including Fourier transform infrared spectrometry, transmission electron microscopy, scanning electron microscopy, gel retardation assay, differential scanning calorimetry, confocal microscopy, releasing test, real-time polymerase chain reaction (PCR) assay, enzyme-linked immunosorbent assay (ELISA), flow cytometry, cytotoxicity assay, and gene-silencing efficacy assay in vitro and in vivo. The mechanism of NDCONH(CH 2 ) 2 NH-VDGR/survivin-siRNA-induced tumor apoptosis was evaluated via flow cytometer assay using Annexin V-fluorescein isothiocyanate/propidium iodide staining method. The NDCONH(CH 2 ) 2 NH-VDGR/survivin-siRNA nanoparticle with 60-110 nm diameter and 35.65±3.90 mV zeta potential was prepared. For real-time PCR assay, the results showed that the expression of survivin mRNA was reduced to 46.77%±6.3%. The expression of survivin protein was downregulated to 48.49%±2.25%, as evaluated by ELISA assay. MTT assay showed that NDCONH(CH 2 ) 2 NH-VDGR/survivin-siRNA had an inhibitory effect on MCF-7 cell proliferation. According to these results, the survivin-siRNA could be delivered, transported, and released stably, which benefits in increasing the gene-silencing effect. Therefore, as an siRNA carrier, NDCONH(CH 2 ) 2 NH-VDGR was suggested to be used in siRNA delivery system and in cancer treatments.

  1. Gene-silencing effects of anti-survivin siRNA delivered by RGDV-functionalized nanodiamond carrier in the breast carcinoma cell line MCF-7

    Directory of Open Access Journals (Sweden)

    Bi YZ

    2016-11-01

    Full Text Available Yanzhao Bi, Yifan Zhang, Chunying Cui, Lulu Ren, Xueyun Jiang School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China Abstract: Nanodiamond (ND is a renowned material in nonviral small interfering RNA (siRNA carrier field due to its unique physical, chemical, and biological properties. In our previous work, it was proven that ND could deliver siRNA into cells efficiently and downregulate the expression of desired protein. However, synthesizing a high-efficient tumor-targeting carrier using ND is still a challenge. In this study, a novel carrier, NDCONH(CH22NH-VDGR, was synthesized for siRNA delivery, and its properties were characterized with methods including Fourier transform infrared spectrometry, transmission electron microscopy, scanning electron microscopy, gel retardation assay, differential scanning calorimetry, confocal microscopy, releasing test, real-time polymerase chain reaction (PCR assay, enzyme-linked immunosorbent assay (ELISA, flow cytometry, cytotoxicity assay, and gene-silencing efficacy assay in vitro and in vivo. The mechanism of NDCONH(CH22NH-VDGR/survivin-siRNA-induced tumor apoptosis was evaluated via flow cytometer assay using Annexin V–fluorescein isothiocyanate/propidium iodide staining method. The NDCONH(CH22NH-VDGR/survivin-siRNA nanoparticle with 60–110 nm diameter and 35.65±3.90 mV zeta potential was prepared. For real-time PCR assay, the results showed that the expression of survivin mRNA was reduced to 46.77%±6.3%. The expression of survivin protein was downregulated to 48.49%±2.25%, as evaluated by ELISA assay. MTT assay showed that NDCONH(CH22NH-VDGR/survivin-siRNA had an inhibitory effect on MCF-7 cell proliferation. According to these results, the survivin-siRNA could be delivered, transported, and released stably, which benefits in increasing the gene-silencing effect. Therefore, as an siRNA carrier, NDCONH(CH22NH-VDGR was suggested

  2. 4 gene expression in hepatocellular carcinoma (HCC)

    African Journals Online (AJOL)

    Gamalat El Gedawy

    2016-06-06

    Jun 6, 2016 ... Subjects and methods: This study was conducted on 30 HCC patients, 20 chronic liver disease ...... [26] Huang CS, Yu W, Cui H, Wang YJ, Zhang L, Han F, et al. ... Y. Involvement of programmed cell death 4 in transforming.

  3. High frequency of p 16 promoter methylation in non-small cell lung carcinomas from Chile

    Directory of Open Access Journals (Sweden)

    LEDA M GUZMAN

    2007-01-01

    Full Text Available The inactivation of tumour suppressor genes by aberrant methylation of promoter regions has been described as a frequent event in neoplasia development, including lung cancer. The p16 gene is a tumour suppressor gene involved in the regulation of cell cycle progression that has been reported to be inactivated by promoter methylation in lung carcinomas at variable frequencies around the world in a smoking habit dependent manner. The purpose of this study was to investigate the methylation status of the promoter region of the p16 gene in 74 non-small cell lung carcinomas from Chile. The frequency of p16 gene inactivation by promoter methylation was determined as 79.7% (59/74. When we considered histological type, we observed that p16 promoter methylation was significantly higher in squamous cell carcinomas (30/33, 91% compared with adenocarcinomas (21/30, 70% (p=0.029. In addition, no association between p16 promoter methylation and gender, age or smoking habit was found (p=0.202, 0.202 and 0.147 respectively. Our results suggest that p16 promoter hypermethylation is a very frequent event in non-small cell lung carcinomas from Chile and could be smoking habit-independent

  4. Primary Squamous Cell Carcinoma of Stomach: A Rare Entity ...

    African Journals Online (AJOL)

    Schmidt C, Schmid A, Lüttges JE, Kremer B, Henne-Bruns D. Primary squamous cell carcinoma of the stomach. Report of a case and review of literature. Hepatogastroenterology 2001;48:1033-6. 5. Muto M, Hasebe T, Muro K, Boku N, Ohtsu A, Fujii T, et al. Primary squamous cell carcinoma of the stomach: A case report with ...

  5. 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...

  6. 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 ...

  7. induced acute cytotoxicity in human cervical epithelial carcinoma cells

    African Journals Online (AJOL)

    Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

  8. Identification of key pathways and genes influencing prognosis in bladder urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Ning X

    2017-03-01

    Full Text Available Xin Ning, Yaoliang Deng Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, People’s Republic of China Background: Genomic profiling can be used to identify the predictive effect of genomic subsets for determining prognosis in bladder urothelial carcinoma (BUC after radical cystectomy. This study aimed to investigate potential gene and pathway markers associated with prognosis in BUC.Methods: A microarray dataset of BUC was obtained from The Cancer Genome Atlas database. Differentially expressed genes (DEGs were identified by DESeq of the R platform. Kaplan–Meier analysis was applied for prognostic markers. Key pathways and genes were identified using bioinformatics tools, such as gene set enrichment analysis, gene ontology, the Kyoto Encyclopedia of Genes and Genomes, gene multiple association network integration algorithm (GeneMANIA, Search Tool for the Retrieval of Interacting Genes/Proteins, and Molecular Complex Detection.Results: A comparative gene set enrichment analysis of tumor and adjacent normal tissues suggested BUC tumorigenesis resulted mainly from enrichment of cell cycle and DNA damage and repair-related biological processes and pathways, including TP53 and mitotic recombination. Two hundred and fifty-six genes were identified as potential prognosis-related DEGs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the potential prognosis-related DEGs were enriched in angiogenesis, including the cyclic adenosine monophosphate biosynthetic process, cyclic guanosine monophosphate-protein kinase G, mitogen-activated protein kinase, Rap1, and phosphoinositide-3-kinase-AKT signaling pathway. Nine hub genes, TAGLN, ACTA2, MYH11, CALD1, MYLK, GEM, PRELP, TPM2, and OGN, were identified from the intersection of protein–protein interaction and GeneMANIA networks. Module analysis of protein–protein interaction and GeneMANIA networks mainly showed

  9. Primary peritoneal clear cell carcinoma versus ovarian carcinoma versus malignant transformation of endometriosis: a vexing issue.

    Science.gov (United States)

    Insabato, Luigi; Natella, Valentina; Somma, Anna; Persico, Marcello; Camera, Luigi; Losito, Nunzia Simona; Masone, Stefania

    2015-05-01

    Peritoneum is a site for both primary and secondary tumors. Primary peritoneal tumors are fairly rare. The most common primary tumors of the peritoneum are malignant mesothelioma and serous papillary adenocarcinoma. Clear cell carcinoma of the peritoneum is extremely rare and often misdiagnosed as mesothelioma, serous carcinoma, or metastatic adenocarcinoma, so it represents a diagnostic challenge for both clinicians and pathologists. Up to date, to the best of our knowledge, only 11 cases of primary peritoneal clear cell carcinoma have been reported in the English literature. Distinguishing this tumor of the peritoneum versus ovarian carcinoma can be problematic. Herein, we report a rare case of primary peritoneal clear cell carcinoma occurring in a 49-year-old woman, along with a review of the literature. © The Author(s) 2015.

  10. 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......, 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...... 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...

  11. Treatment of early glottic squamous cell carcinoma

    International Nuclear Information System (INIS)

    Rikimaru, Fumihide; Matsuo, Mioko; Higaki, Yuichiro; Tomita, Kichinobu

    2011-01-01

    We treat early glottic squamous cell carcinoma with chemoradiation and evaluate the effects of the chemoradiation at the dose of 30-40 Gy as an intermediate evaluation. To investigate the need for this intermediate evaluation, we retrospectively analyzed 97 patients, 92 men and 5 women aged 36 to 86 years, with glottic squamous cell carcinoma at stage I and II treated at our institution from January 2000 to May 2007. The three-year survival rate was 98% in all cases, 100% in T1a, 93% in T1b and 94% in T2. The three-year preservation rate of the larynx was 92% in all cases, 98% in T1a, 93% in T1b and 83% in T2. In the intermediate evaluation, complete response was 78% in T1a, 85% in T1b and 53% in T2. In cases of larynx preservation, the recurrence rate of the primary site was significantly higher in cases without complete response in the intermediate evaluation than in cases with complete response (p<0.05). It seemed that the not complete response case in the intermediate evaluation paid attention to a primary tumor recurrence in particular and needed careful follow-up. (author)

  12. Detection of large deletion in human BRCA1 gene in human breast carcinoma MCF-7 cells by using DNA-Silver Nanoclusters

    Science.gov (United States)

    Borghei, Yasaman-Sadat; Hosseini, Morteza; Ganjali, Mohammad Reza

    2018-01-01

    Here we describe a label-free detection strategy for large deletion mutation in breast cancer (BC) related gene BRCA1 based on a DNA-silver nanocluster (NC) fluorescence upon recognition-induced hybridization. The specific hybridization of DNA templated silver NCs fluorescent probe to target DNAs can act as effective templates for enhancement of AgNCs fluorescence, which can be used to distinguish the deletion of BRCA1 due to different fluorescence intensities. Under the optimal conditions, the fluorescence intensity of the DNA-AgNCs at emission peaks around 440 nm (upon excitation at 350 nm) increased with the increasing deletion type within a dynamic range from 1.0 × 10-10 to 2.4 × 10-6 M with a detection limit (LOD) of 6.4 × 10-11 M. In this sensing system, the normal type shows no significant fluorescence; on the other hand, the deletion type emits higher fluorescence than normal type. Using this nanobiosensor, we successfully determined mutation using the non-amplified genomic DNAs that were isolated from the BC cell line.

  13. NDRG2 gene copy number is not altered in colorectal carcinoma

    DEFF Research Database (Denmark)

    Lorentzen, Anders Blomkild; Mitchelmore, Cathy

    2017-01-01

    AIM To investigate if the down-regulation of N-myc Downstream Regulated Gene 2 (NDRG2) expression in colorectal carcinoma (CRC) is due to loss of the NDRG2 allele(s). METHODS The following were investigated in the human colorectal cancer cell lines DLD-1, LoVo and SW-480: NDRG2 mRNA expression...... levels using quantitative reverse transcription-polymerase chain reaction (qRT-PCR); interaction of the MYC gene-regulatory protein with the NDRG2 promoter using chromatin immunoprecipitation; and NDRG2 promoter methylation using bisulfite sequencing. Furthermore, we performed qPCR to analyse the copy...... numbers of NDRG2 and MYC genes in the above three cell lines, 8 normal colorectal tissue samples and 40 CRC tissue samples. RESULTS As expected, NDRG2 mRNA levels were low in the three colorectal cancer cell lines, compared to normal colon. Endogenous MYC protein interacted with the NDRG2 core promoter...

  14. Which Are the Cells of Origin in Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Tilling, T.; Moll, I.

    2012-01-01

    Merkel cell carcinoma (MCC), a highly aggressive skin tumour with increasing incidence, is associated with the newly discovered Merkel cell polyoma virus (MCPyV). Studies on MCC and MCPyV as well as other risk factors have significantly increased our knowledge of MCC pathogenesis, but the cells of origin, which could be important targets in future therapies, are still unknown. Merkel cells (MCs), the neuroendocrine cells of the skin, were believed to be at the origin of MCC due to their phenotypic similarities. However, for several reasons, for example, heterogeneous differentiation of MCCs and post mitotic character of MCs, it is not very likely that MCC develops from differentiated MCs. Skin stem cells, probably from the epidermal lineage, are more likely to be cells of origin in MCC. Future studies will have to address these questions more directly in order to identify the physiological cells which are transformed to MCC cells.

  15. Epidermal Growth Factor Receptor and K-RAS status in two cohorts of squamous cell carcinomas

    International Nuclear Information System (INIS)

    Van Damme, Nancy; Pauwels, Patrick; Peeters, Marc; Deron, Philippe; Van Roy, Nadine; Demetter, Pieter; Bols, Alain; Dorpe, Jo Van; Baert, Filip; Van Laethem, Jean-Luc; Speleman, Franki

    2010-01-01

    With the availability of effective anti-EGFR therapies for various solid malignancies, such as non-cell small lung cancer, colorectal cancer and squamous cell carcinoma of the head and neck, the knowledge of EGFR and K-RAS status becomes clinically important. The aim of this study was to analyse EGFR expression, EGFR gene copy number and EGFR and K-RAS mutations in two cohorts of squamous cell carcinomas, specifically anal canal and tonsil carcinomas. Formalin fixed, paraffin-embedded tissues from anal and tonsil carcinoma were used. EGFR protein expression and EGFR gene copy number were analysed by means of immunohistochemistry and fluorescence in situ hybridisation. The somatic status of the EGFR gene was investigated by PCR using primers specific for exons 18 through 21. For the K-RAS gene, PCR was performed using exon 2 specific primers. EGFR immunoreactivity was present in 36/43 (83.7%) of anal canal and in 20/24 (83.3%) of tonsil squamous cell carcinomas. EGFR amplification was absent in anal canal tumours (0/23), but could be identified in 4 of 24 tonsil tumours. From 38 anal canal specimens, 26 specimens were successfully analysed for exon 18, 30 for exon 19, 34 for exon 20 and 30 for exon 21. No EGFR mutations were found in the investigated samples. Thirty samples were sequenced for K-RAS exon 2 and no mutation was identified. From 24 tonsil specimens, 22 were successfully analysed for exon 18 and all 24 specimens for exon 19, 20 and 21. No EGFR mutations were found. Twenty-two samples were sequenced for K-RAS exon 2 and one mutation c.53C > A was identified. EGFR mutations were absent from squamous cell carcinoma of the anus and tonsils, but EGFR protein expression was detected in the majority of the cases. EGFR amplification was seen in tonsil but not in anal canal carcinomas. In our investigated panel, only one mutation in the K-RAS gene of a tonsil squamous cell carcinoma was identified. This indicates that EGFR and K-RAS mutation analysis is not

  16. Epidermal Growth Factor Receptor and K-RAS status in two cohorts of squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Van Laethem Jean-Luc

    2010-05-01

    Full Text Available Abstract Background With the availability of effective anti-EGFR therapies for various solid malignancies, such as non-cell small lung cancer, colorectal cancer and squamous cell carcinoma of the head and neck, the knowledge of EGFR and K-RAS status becomes clinically important. The aim of this study was to analyse EGFR expression, EGFR gene copy number and EGFR and K-RAS mutations in two cohorts of squamous cell carcinomas, specifically anal canal and tonsil carcinomas. Methods Formalin fixed, paraffin-embedded tissues from anal and tonsil carcinoma were used. EGFR protein expression and EGFR gene copy number were analysed by means of immunohistochemistry and fluorescence in situ hybridisation. The somatic status of the EGFR gene was investigated by PCR using primers specific for exons 18 through 21. For the K-RAS gene, PCR was performed using exon 2 specific primers. Results EGFR immunoreactivity was present in 36/43 (83.7% of anal canal and in 20/24 (83.3% of tonsil squamous cell carcinomas. EGFR amplification was absent in anal canal tumours (0/23, but could be identified in 4 of 24 tonsil tumours. From 38 anal canal specimens, 26 specimens were successfully analysed for exon 18, 30 for exon 19, 34 for exon 20 and 30 for exon 21. No EGFR mutations were found in the investigated samples. Thirty samples were sequenced for K-RAS exon 2 and no mutation was identified. From 24 tonsil specimens, 22 were successfully analysed for exon 18 and all 24 specimens for exon 19, 20 and 21. No EGFR mutations were found. Twenty-two samples were sequenced for K-RAS exon 2 and one mutation c.53C > A was identified. Conclusion EGFR mutations were absent from squamous cell carcinoma of the anus and tonsils, but EGFR protein expression was detected in the majority of the cases. EGFR amplification was seen in tonsil but not in anal canal carcinomas. In our investigated panel, only one mutation in the K-RAS gene of a tonsil squamous cell carcinoma was identified

  17. Squamous cell carcinoma following radiation therapy for the infiltrative thymoma

    International Nuclear Information System (INIS)

    Ozawa, Shinji; Kitao, Takeshi

    1992-01-01

    This report represents one case of infiltrative thymoma followed by squamous cell carcinoma of the lungs. A 69-year-old man suffered from infiltrative thymoma which reduced by the radiation therapy. Seven years later its replase and the onset of squamous cell carcinoma were found simultaneously. Infiltrative thymoma metastasized not only to the mediastinum but also to the liver and bronchus. Squamous cell carcinoma developed in the right upper lobe. In spite of chemotherapy against them, the patient died. There are many cases in which infiltrative thymoma is accompanied by squamous cell carcinoma of the lung simultaneously; however, secondary onset of squamous cell carcinoma after the radiation therapy of infiltrative thymoma is rare. Secondary carcinogenesis of this case was considered to be closely related with immunological abnormalities caused by thymoma, effects of radiation, smoking and so on. (author)

  18. CT staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Spina, Juan C.; Garcia, Adriana T.; Rogondino, Jose; Spina, Juan C. h; Vidales, Valeria; Troiani, Guillermo; Iotti, Alejandro; Venditti, Julio

    2002-01-01

    Objective: To assess the usefulness of computerized tomography (CT) in the characterization of renal masses, in order to stage them, determine their prognosis and their appropriate clinical and/or surgical management. Material and Methods: Between 1988 and 2001, we selected 63 patients with renal tumors that had been examined by pathology. Patient's ages ranged from 16 to 88 years (25 women, 38 men). The studies were performed with a sequential helical CT, using 5 mm thickness sections every 5mm evaluating the cortico medullar and nephrographic phases. Renal tumors were characterized and staged without any knowledge about the pathological findings; subsequently the tomographic characteristics were compared to such findings. The following characteristics were evaluated: 1) mixed solid-cystic nature; 2) size; 3) borders; 4) enhancement; 5) necrosis; 6) hemorrhage; 7) central scar; 8) presence of fat; 9) collecting system; 10) capsular invasion; 11) perirenal fat invasion; 12) vessels; 13) Gerota's fascia; 14) lymph nodes; and 15) local and/or distant metastases. Results: Of the 63 tumors, 2 were complicated cysts; of the 61 remaining tumors, 10 were angiomyolipomas, 1 was a renal lymphoma, 1 was a focal xantogranulomatose pyelonephritis, 1 was a metanephric adenoma, 3 papillary renal cell carcinoma (RCC), 4 transitional cell tumors, 4 oncocytomas, 37 clear cell renal carcinoma. The CT could correctly characterize the 2 cystic tumors as such, as well as the 9 angiomyolipomas and the 4 transitional cell tumors. The 48 other tumors (1 angiomyolipoma, 1 lymphoma, 1 focal xantogranulomatose pyelonephritis, 1 metanephric adenoma, 3 papillary RCC, 4 oncocytomas, and 37 cell renal carcinomas) remaining were characterized as renal adenocarcinomas and CT staged. Conclusion: CT is a useful method to characterize renal masses since it determines their solid-cystic or fatty structure; aiding in many cases to define a surgical treatment. For the CT staging of renal tumors, the

  19. Synchronous presentation of nasopharyngeal and renal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Cem Boruban

    2006-06-01

    Full Text Available We report a rare case of synchronous presentation of nasopharyngeal and renal cell carcinomas in a-50-year old male patient with long standing smoking history. The patient was initially presented with a diagnosis of nasopharyngeal carcinoma. During staging process, the abdominal computed tomography detected a right renal solid mass, 6.5 cm in diameter, originating from posterior portion of the right renal cortex. Right radical nephrectomy was performed and pathological examination revealed renal cell carcinoma. Smoking was thought to be a risk factor for both cancers. Systemic evaluation of kidney should not be discarded in patients diagnosed with nasopharyngeal carcinoma living in western countries with a smoking history.

  20. 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.

  1. Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas.

    Directory of Open Access Journals (Sweden)

    Hye-Eun Kim

    Full Text Available Genomic changes frequently occur in cancer cells during tumorigenesis from normal cells. Using the Illumina Human NS-12 single-nucleotide polymorphism (SNP chip to screen for gene copy number changes in primary hepatocellular carcinomas (HCCs, we initially detected amplification of 35 genes from four genomic regions (1q21-41, 6p21.2-24.1, 7p13 and 8q13-23. By integrated screening of these genes for both DNA copy number and gene expression in HCC and colorectal cancer, we selected CENPF (centromere protein F/mitosin, GMNN (geminin, DNA replication inhibitor, CDK13 (cyclin-dependent kinase 13, and FAM82B (family with sequence similarity 82, member B as common cancer genes. Each gene exhibited an amplification frequency of ~30% (range, 20-50% in primary HCC (n = 57 and colorectal cancer (n = 12, as well as in a panel of human cancer cell lines (n = 70. Clonogenic and invasion assays of NIH3T3 cells transfected with each of the four amplified genes showed that CENPF, GMNN, and CDK13 were highly oncogenic whereas FAM82B was not. Interestingly, the oncogenic activity of these genes (excluding FAM82B was highly correlated with gene-copy numbers in tumor samples (correlation coefficient, r>0.423, indicating that amplifications of CENPF, GMNN, and CDK13 genes are tightly linked and coincident in tumors. Furthermore, we confirmed that CDK13 gene copy number was significantly associated with clinical onset age in patients with HCC (P = 0.0037. Taken together, our results suggest that coincidently amplified CDK13, GMNN, and CENPF genes can play a role as common cancer-driver genes in human cancers.

  2. 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.

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

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    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.

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

    International Nuclear Information System (INIS)

    Fischer, Nicolas; Göke, Friederike; Splittstößer, Vera; Lankat-Buttgereit, Brigitte; Müller, Stefan C.; Ellinger, Jörg

    2012-01-01

    Highlights: ► The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. ► We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. ► 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.

  5. Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling.

    Science.gov (United States)

    Nan, Ning; Chen, Qi; Wang, Yu; Zhai, Xu; Yang, Chuan-Ce; Cao, Bin; Chong, Tie

    2017-10-01

    To explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling. Gene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes. In this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway - oxidative phosphorylation. We identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Multiple squamous cell carcinomas within the head and neck region

    International Nuclear Information System (INIS)

    Sato, Katsuro; Hanazawa, Hideyuki; Sato, Yuichiro; Takahashi, Sugata

    2004-01-01

    Clinical features of multiple squamous cell carcinoma (SCC) cases within the head and neck that were treated in our department during the recent 10 years are discussed. Multiple SCCs arose in 6.6% of the cases with primary SCC; 67% of the cases had two carcinomas, and 33% had more than three carcinomas. The most common site of the multiple SCCs was the oral cavity (54%). The most frequent interval between treatment of previous carcinoma and diagnosis of subsequent carcinoma was simultaneous, but more than 5 years' interval was observed in 36% of the patients. The most common initial treatment of the carcinoma was irradiation, but the ratio of surgery increased for subsequent carcinomas. Prognosis of the patients with more than three carcinomas was not worse than that of patients with two carcinomas. Therefore, early diagnosis of the subsequent carcinomas based on careful long-term observation in the head and neck is necessary for follow-up of the patients with SCC of the head and neck. Treatment strategies considering the treatment of subsequent carcinomas are needed for the patients with primary head and neck SCC. (author)

  7. Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

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    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.

  8. Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Wheat, Rachel; Roberts, Claudia; Waterboer, Tim; Steele, Jane; Marsden, Jerry; Steven, Neil M.; Blackbourn, David J.

    2014-01-01

    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

  9. 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.

  10. Collision tumor of Small Cell Carcinoma and Squamous Cell Carcinoma of maxillary sinus

    Directory of Open Access Journals (Sweden)

    Irfan Sugianto

    2016-06-01

    Full Text Available Two kinds of different malignant tumors occurring within the same organ is defined as collision tumor. Small Cell Carcinoma (SmCC is high-grade derived from neuroendocrine cell tumors, occurance in the head and neck is rare. Squamous Cell Carcinoma (SCC is the most common malignancies encountered in head and neck area, but the occuranceof collision tumor is very rare. This report describe a 82 year-old woman patient with a SmCC and SCC that occurred in the maxillary sinus. CT was performed including with enhancement, MRI examination was T1WI, STIR and contrast enhancement. We also conducted analysis of Dynamic Contrast Enhancement (DCE. Histopathologic examination revealed small cell carcinoma. A distant metastasis was not detected. After patient received chemoradiotherapy (CCRT, most of  tumorwas reduced although a part of the tumor was remained. Pathological examination of surgery tumor specimen revealed that specimen consisted of SCC and SmCC was disappeared, and six months after surgery, the patient suffered tumor recurrence and multiple metastasis to the organs in the abdomen. This time we have to report that the experience one cases that are considered collision cancer of SmCC and SCC that occurred in the maxillary sinus.

  11. Gene therapy for carcinoma of the breast: Genetic immunotherapy

    International Nuclear Information System (INIS)

    Strong, Theresa V

    2000-01-01

    Advances in gene transfer technology have greatly expanded the opportunities for developing immunotherapy strategies for breast carcinoma. Genetic immunotherapy approaches include the transfer of genes encoding cytokines and costimulatory molecules to modulate immune function, as well as genetic immunization strategies which rely on the delivery of cloned tumor antigens. Improved gene transfer vectors, coupled with a better understanding of the processes that are necessary to elicit an immune response and an expanding number of target breast tumor antigens, have led to renewed enthusiasm that effective immunotherapy may be achieved. It is likely that immunotherapeutic interventions will find their greatest clinical application as adjuvants to traditional first-line therapies, targeting micrometastatic disease and thereby reducing the risk of cancer recurrence

  12. 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

  13. A case report of renal cell carcinoma in a dog

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    A.-S. Paşca

    2013-10-01

    Full Text Available Mix renal carcinoma was noticed during the necropsic examination of a 14 year old mix breed female. Tumours were bilateral and metastasis was noticed in the spleen and myocard. Histological examination evidenced morphological aspects characteristic to the mixt renal carcinoma. Histological aspects described in this individual characterize renal cell carcinoma, also known as renal adenocarcinoma, hypernephroma or, in older literature, Grawitz tumour.

  14. Squamous cell carcinoma of penis in patient with incipient neurosyphilis

    Directory of Open Access Journals (Sweden)

    D. V. Zaslavsky

    2016-01-01

    Full Text Available Squamous cell carcinoma of the skin (SSCC is one of the most common malignant skin tumors. Syphilis is a sexually transmitted disease caused by Treponema pallidum, with human beings as the only host. The combination of syphilis and squamous cell carcinoma of the skin is not uncommon, particularly if the lesions are located on different parts of the body. However, simultaneous development of the chancre and squamous cell carcinoma of the glans penis seems exceptional. Considering rarity of the manifestation observed we feel the rare case of combined syphilis and squamous cell skin cancer is of interest.

  15. Merkel Cell Carcinoma Metastatic to Pleural Fluid: A Case Report

    Directory of Open Access Journals (Sweden)

    Ye-Young Rhee

    2018-05-01

    Full Text Available Merkel cell carcinoma (MCC is a rare aggressive neuroendocrine carcinoma of the skin that shows locoregional or distant metastasis. Metastasis of MCC to body cavity effusion is extremely rare; only three cases have been reported so far. Metastatic MCC in effusion cytology shows small blue round cells with fine stippled chromatin like other small blue round cell tumors such as small cell lung carcinoma or lymphoma. The diagnosis of metastatic MCC can grant patients good chances at recently advanced therapeutic options. Here, we present a case of metastatic MCC to pleural effusion with characteristic single file-like pattern.

  16. Merkel Cell Carcinoma Metastatic to Pleural Fluid: A Case Report.

    Science.gov (United States)

    Rhee, Ye-Young; Kim, Soo Hee; Kim, Eun Kyung; Kim, Se Hoon

    2018-05-01

    Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine carcinoma of the skin that shows locoregional or distant metastasis. Metastasis of MCC to body cavity effusion is extremely rare; only three cases have been reported so far. Metastatic MCC in effusion cytology shows small blue round cells with fine stippled chromatin like other small blue round cell tumors such as small cell lung carcinoma or lymphoma. The diagnosis of metastatic MCC can grant patients good chances at recently advanced therapeutic options. Here, we present a case of metastatic MCC to pleural effusion with characteristic single file-like pattern.

  17. Rare Case of Duodenal Metastasis From Pulmonary Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Zain Memon DO

    2017-10-01

    Full Text Available Pulmonary squamous cell carcinoma is the second most common non–small cell malignancy of the lung. It commonly metastasizes to the adrenal glands, bone, liver, brain, and kidneys. Most occurrences of metastatic squamous cell carcinoma involving the gastrointestinal tract originate from primary lung tumors. Metastasis to the duodenum, however, is exceedingly rare, with very few cases of stomach or duodenal involvement described in the literature. We report the case of a patient with stage IV pulmonary squamous cell carcinoma metastasizing to the duodenum with an uncommon presentation to add to the paucity of literature available regarding this rare finding.

  18. [Merkel cell carcinoma: cutaneous manifestation of a highly malignant pre-/pro-B cell neoplasia? : Novel concept about the cellular origin of Merkel cell carcinoma].

    Science.gov (United States)

    Sauer, C M; Chteinberg, E; Rennspiess, D; Kurz, A K; Zur Hausen, A

    2017-03-01

    Merkel cell carcinoma (MCC) is a relatively rare but highly malignant non-melanoma skin cancer of the elderly and immunosuppressed patients. The discovery of the Merkel cell polyomavirus (MCPyV) in 2008 significantly impacted the understanding of the etiopathogenesis of MCC. MCPyV is clonally integrated into the MCC genome and approximately 80% of MCC are MCPyV-positive. Recent results of clinical trials using blockade of the PD-1 immune modulatory pathway are promising for the future treatment of MCC. Despite this major progress of the past few years, the cellular origin of MCC still remains obscure. Based on histomorphology, gene expression profiling, and molecular analyses, we have recently hypothesized that MCC originates from pre‑/pro-B cells. Here we review putative cells of MCC, including Merkel cells, (epi‑)dermal stem cells, and pro‑/pre-B cells. In the present work, the focus is on the concept of pre‑/pro-B cells as the cellular origin of MCC, which might also impact the understanding of other human small cell malignancies of unknown cellular origin, such as small cell carcinomas of the lung and other anatomical locations. In addition, this concept might pave the way for novel treatment options, especially for advanced MCC.

  19. 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.

  20. Expression and Clinicopathological Significance of Mel-18 and Bmi-1 in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Ji, Huaijun; Cao, Ming; Ren, Kunlun; Sun, Ningbo; Wang, Wei; Zhu, Qiang; Zang, Qi; Jiang, Zhongmin

    2017-01-01

    The Polycomb group genes are a general class of regulators that are responsible for maintaining homeotic gene expression throughout cell division. Polycomb group expression plays an important role in oncogenesis of several types of human cancer. Melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 are key Polycomb group proteins. Studies have shown that melanoma nuclear protein 18 is a potential tumor suppression, and B-cell-specific Moloney leukemia virus insert site 1 is overexpressed in several human malignancies. However, the roles of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in esophageal squamous cell carcinoma are still unclear. In this study, we analyzed the expression levels of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in 89 esophageal cancer tissues and paired normal mucosal tissues using immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction analyses. We found that the expression of melanoma nuclear protein 18 in the carcinoma tissues was significantly lower than that in the noncancerous mucosal tissues ( P .05). B-cell-specific Moloney leukemia virus insert site 1 expression was strongly correlated with the degree of differentiation, clinical stage, and lymph node metastasis ( P .05). Moreover, there was a negative correlation between melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 expressions in esophageal squamous cell carcinoma ( P < .05). Our study suggests that melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 may play a crucial role in esophageal squamous cell carcinoma. Melanoma nuclear protein 18 or B-cell-specific Moloney leukemia virus insert site 1 may be a potential biomarker for diagnosis and prognosis of esophageal squamous cell carcinoma.

  1. Epidemiology, molecular epidemiology, and risk factors for renal cell carcinoma

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    Chiara Paglino

    2011-12-01

    Full Text Available Despite only accounting for approximately 2% of all new primary cancer cases, renal cell carcinoma (RCC incidence has dramatically increased over time. Incidence rates vary greatly according to geographic areas, so that it is extremely likely that exogenous risk factors could play an important role in the development of this cancer. Several risk factors have been linked with RCC, including cigarette smoking, obesity, hypertension (and antihypertensive drugs, chronic kidney diseases (also dialysis and transplantation, as well as the use of certain analgesics. Furthermore, although RCC has not generally been considered an occupational cancer, several types of occupationally-derived exposures have been implicated in its pathogenesis. These include exposure to asbestos, chlorinated solvents, gasoline, diesel exhaust fumes, polycyclic aromatic hydrocarbons, printing inks and dyes, cadmium and lead. Finally, families with a predisposition to the development of renal neoplasms were identified and the genes involved discovered and characterized. Therefore, there are now four well-characterized, genetically determined syndromes associated with an increased incidence of kidney tumors, i.e., Von Hippel Lindau (VHL, Hereditary Papillary Renal Carcinoma (HPRC, Birt-Hogg-Dubé Syndrome (BHD, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC. This review will address present knowledge about the epidemiology, molecular epidemiology and risk factors of RCC.

  2. Origin of clear cell carcinoma: nature or nurture?

    Science.gov (United States)

    Kolin, David L; Dinulescu, Daniela M; Crum, Christopher P

    2018-02-01

    A rare but serious complication of endometriosis is the development of carcinoma, and clear cell and endometrioid carcinomas of the ovary are the two most common malignancies which arise from endometriosis. They are distinct diseases, characterized by unique morphologies, immunohistochemical profiles, and responses to treatment. However, both arise in endometriosis and can share common mutations. The overlapping mutational profiles of clear cell and endometrioid carcinomas suggest that their varied histologies may be due to a different cell of origin which gives rise to each type of cancer. Cochrane and colleagues address this question in a recent article in this journal. They show that a marker of ovarian clear cell carcinoma, cystathionine gamma lyase, is expressed in ciliated cells. Similarly, they show that markers of secretory cells (estrogen receptor and methylenetetrahydrofolate dehydrogenase 1) are expressed in ovarian endometrioid carcinoma. Taken together, they suggest that endometrioid and clear cell carcinomas arise from cells related to secretory and ciliated cells, respectively. We discuss Cochrane et al's work in the context of other efforts to determine the cell of origin of gynecological malignancies, with an emphasis on recent developments and challenges unique to the area. These limitations complicate our interpretation of tumor differentiation; does it reflect nature imposed by a specific cell of origin or nurture, by either mutation(s) or environment? Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  3. Gene therapy for carcinoma of the breast: Genetic ablation strategies

    International Nuclear Information System (INIS)

    Curiel, David T

    2000-01-01

    The gene therapy strategy of mutation compensation is designed to rectify the molecular lesions that are etiologic for neoplastic transformation. For dominant oncogenes, such approaches involve the functional knockout of the dysregulated cellular control pathways provoked by the overexpressed oncoprotein. On this basis, molecular interventions may be targeted to the transcriptional level of expression, via antisense or ribozymes, or post-transcriptionally, via intracellular single chain antibodies (intrabodies). For carcinoma of the breast, these approaches have been applied in the context of the disease linked oncogenes erbB-2 and cyclin D 1 , as well as the estrogen receptor. Neoplastic revision accomplished in modal systems has rationalized human trials on this basis

  4. 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.

  5. Merkel Cell Carcinoma: An Update and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Hiroshi Uchi

    2018-03-01

    Full Text Available Merkel cell carcinoma (MCC is a rare but aggressive skin cancer with frequent metastasis and death. MCC has a mortality rate of 30%, making it more lethal than malignant melanoma, and incidence of MCC has increased almost fourfold over the past 20 years in the USA. MCC has long been considered to be an immunogenic cancer because it occurs more frequently in immunosuppressed patients from organ transplant and HIV infection than in those with immunocompetent. Chronic UV light exposure and clonal integration of Merkel cell polyomavirus (MCPyV are two major causative factors of MCC. Approximately 80% of MCC are associated with MCPyV, and T cells specific for MCPyV oncoproteins are present in the blood and tumors of patients. Several studies have shown that a subset of MCCs express PD-1 on tumor-infiltrating lymphocytes and express PD-L1 on tumor cells, which suggests an endogenous tumor-reactive immune response that might be unleashed by anti-PD-1 or anti-PD-L1 drugs.

  6. Subungual squamous cell carcinoma: A case study

    Energy Technology Data Exchange (ETDEWEB)

    Neill, Cory J., E-mail: coryjneill@gmail.com

    2017-07-01

    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.

  7. Sequential Therapy in Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Bradford R Hirsch

    2016-04-01

    Full Text Available The treatment of metastatic renal cell carcinoma (mRCC has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network's Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future.

  8. Imaging in Patients with Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Enzenhofer, E.; Ubl, P.; Czerny, C.; Erovic, B. M.

    2013-01-01

    Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumor of the skin with a mortality rate of approximately 25% (Peloschek et al., 2010). Accurate assessment of nodal involvement in patients with MCC predicts significantly overall outcome (Smith et al., 2012 and Ortin-Perez et al., 2007). Due to the rarity of this highly aggressive disease, only a few imaging reports on MCC were published, and subsequently still to date no accepted imaging algorithm for MCC is available. For primary staging of MCC, general recommendations have included ultrasonography, chest X-ray CT, and MRI, but recent articles show that the use of sentinel node and FDG-PET/PET-CT is gaining more and more importance

  9. Merkel cell carcinoma with seborrheic keratosis: A unique association.

    Science.gov (United States)

    Anand, Murthy S; Krishnamurthy, Shantha; Ravindranath, Suvarna; Ranganathan, Jyothi

    2018-01-01

    Merkel cell carcinoma (MCC) is a rare, clinically aggressive neuroendocrine carcinoma of the skin; MCC is 40 times less common as compared to melanoma. The most frequently reported sites have been the head and neck, extremities, and trunk. Potential mimics include malignant melanoma, lymphoma, or metastatic small cell (neuroendocrine) carcinomas. Histopathology of MCC resembles small cell carcinoma both morphologically and on IHC. The possible cell of origin was proposed as the Merkel cell, which functions as a mechanoreceptor. It has a high chance of local recurrence, regional and distant spread. In recent times, Merkel cell polyomavirus has been implicated as the causative agent for this tumor. The same agent has a reported etiologic association with other skin lesions, including seborrheic keratosis.

  10. Watermelon stomach, hemorrhagic pericarditis, small cell carcinoma of the lung and synchronous squamous cell carcinoma of the tongue base

    Directory of Open Access Journals (Sweden)

    A. Murinello

    2010-07-01

    Full Text Available Based on a case of gastric antral vascular ectasia (watermelon stomach that was associated with hemorrhagic pericarditis, small cell lung carcinoma with mediastinal lymph node metastases and a synchronous squamous cell carcinoma of the base of the tongue, the authors made a review of the clinical, endoscopic and histopathological aspects of this type of gastropathy, and its association with other diseases, and of the results of its endoscopic therapy. The causes of hemorrhagic pericarditis are considered, emphasizing the necessity to know if the effusion has a malignant etiology. To the best of our knowledge the association of watermelon stomach to small cell lung carcinoma and squamous cell carcinoma of the base of the tongue has not yet been described. Extensive metastases to mediastal lymph nodes are common to small cell lung carcinoma. Resumo: Baseados num caso de gastropatia antral com ectasia vascular (estômago em melancia associado a pericardite hemorrágica e a um carcinoma de pequenas células do pulmão com metástases ganglionares ao longo do mediastino e a um carcinoma pavimentocelular síncrono da base da língua, os autores fazem uma revisão dos aspectos clínicos, endoscópicos e histopatológicos deste tipo de gastropatia, da sua associação a outras doenças e das possibilidades terapêuticas actuais por via endoscópica. Referem-se igualmente as causas mais frequentes de pericardite hemorrágica, salientando-se a necessidade de esclarecer se o derrame é ou não de origem neoplásica. Não está referida na literatura a associação deste tipo de gastropatia ao carcinoma de pequenas células do pulmão nem ao carcinoma pavimento-celular da base da língua. A invasão extensa dos gânglios mediastínicos pelo carcinoma de pequenas células do pulmão é ocorrência frequente. Key-words: Gastric antral vascular ectasia, watermelon stomach, small cell lung carcinoma, oat cell lung carcinoma, squamous cell carcinoma of the base

  11. Efficiency of lipofection combined with hyperthermia in Lewis lung carcinoma cells and a rodent pleural dissemination model of lung carcinoma.

    Science.gov (United States)

    Okita, Atsushi; Mushiake, Hiroyuki; Tsukuda, Kazunori; Aoe, Motoi; Murakami, Masakazu; Andou, Akio; Shimizu, Nobuyoshi

    2004-06-01

    We have previously reported that hyperthermia at 41 degrees C enhanced lipofection-mediated gene transduction into cultured cells. In this study, we adapted hyperthermia technique to novel cationic liposome (Lipofectamine 2000) mediated gene transfection into Lewis lung carcinoma cells in vitro and in vivo. In vitro, transfection efficiencies were 38.9+/-3.3% by lipofection alone and 52.1+/-2.6% by lipofection with hyperthermia for 30 min, and 62.5+/-5.5% and 81.4+/-3.2% for 1 h, respectively. Hyperthermia significantly enhanced gene transfection efficiency 1.2-1.4 times more than that with lipofection only. We also evaluated the effect of hyperthermia with a pleural dissemination model of lung carcinoma of mice. We developed a model which was well-tolerated with hyperthermia with lipofection by the mice. In spite of repeated treatments, transfection efficiencies were very low and we could not show the augmentation of gene transfection by hyperthermia. Though Lipofectamine 2000 showed strong gene transduction effect and hyperthermia augmented its effect in vitro, further evaluation is needed to adapt both techniques in vivo.

  12. 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

  13. Ultrastructural proof of polyomavirus in Merkel cell carcinoma tumour cells and its absence in small cell carcinoma of the lung.

    Directory of Open Access Journals (Sweden)

    Charlotte T A H Wetzels

    Full Text Available BACKGROUND: A new virus called the Merkel Cell Polyomavirus (MCPyV has recently been found in Merkel Cell Carcinoma (MCC. MCC is a rare aggressive small cell neuroendocrine carcinoma primarily derived from the skin, morphologically indistinguishable from small cell lung carcinoma (SCLC. So far the actual presence of the virus in MCC tumour cells on a morphological level has not been demonstrated, and the presence of MCPyV in other small cell neuroendocrine carcinomas has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: We investigated MCC tissue samples from five patients and SCLCs from ten patients for the presence of MCPyV-DNA by PCR and sequencing. Electron microscopy was used to search ultrastructurally for morphological presence of the virus in MCPyV-DNA positive samples. MCPyV was detected in two out of five primary MCCs. In one MCC patient MCPyV-DNA was detected in the primary tumour as well as in the metastasis, strongly suggesting integration of MCPyV in the cellular DNA of the tumour in this patient. In the primary MCC of another patient viral particles in tumour cell nuclei and cytoplasm were identified by electron microscopy, indicating active viral replication in the tumour cells. In none of the SCLCs MCPyV-DNA was detected. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that MCPyV is an oncogenic polyomavirus in humans, and is potentially causally related to the development of MCC but not to the morphological similar SCLC.

  14. Five cases of squamous cell carcinoma induced by irradiation

    International Nuclear Information System (INIS)

    Omoto, Kayo; Tani, Tasaburo; Nagata, Hiroyuki; Kohda, Mamoru; Ueki, Hiroaki

    1985-01-01

    Five cases of squamous cell carcinoma (skin) induced by irradiation are reported. Three cases had been given radiotherapy for benign skin disorders, tinea pedis, lichen Vidal, and dermatitis papillaris capillitis. The other two cases were medical doctors who had developed carcinoma as the result of advanced radiodermatitis. (author)

  15. Humeral Metastasis in a case of Squamous Cell Carcinoma - a ...

    African Journals Online (AJOL)

    A rare case of squamous cell carcinoma with metastasis to distal acral skeleton – humerus within two months of diagnosis of the primary is being reported. The metastasis to the bones from carcinoma cervix is uncommon especially in the distal appendicular skeleton. A 47 years female came with spontaneous fracture of ...

  16. TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Wang, Shumin; Ma, Ning; Murata, Mariko; Huang, Guangwu; Zhang, Zhe; Xiao, Xue; Zhou, Xiaoying; Huang, Tingting; Du, Chunping; Yu, Nana; Mo, Yingxi; Lin, Longde; Zhang, Jinyan

    2010-01-01

    Epigenetic silencing of tumor suppressor genes play important roles in NPC tumorgenesis. Tissue factor pathway inhibitor-2 (TFPI-2), is a protease inhibitor. Recently, TFPI-2 was suggested to be a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. In this study, we investigated whether TFPI-2 was inactivated epigenetically in nasopharyngeal carcinoma (NPC). Transcriptional expression levels of TFPI-2 was evaluated by RT-PCR. Methylation status were investigated by methylation specific PCR and bisulfate genomic sequencing. The role of TFPI-2 as a tumor suppressor gene in NPC was addressed by re-introducing TFPI-2 expression into the NPC cell line CNE2. TFPI-2 mRNA transcription was inactivated in NPC cell lines. TFPI-2 was aberrantly methylated in 66.7% (4/6) NPC cell lines and 88.6% (62/70) of NPC primary tumors, but not in normal nasopharyngeal epithelia. TFPI-2 expression could be restored in NPC cells after demethylation treatment. Ectopic expression of TFPI-2 in NPC cells induced apoptosis and inhibited cell proliferation, colony formation and cell migration. Epigenetic inactivation of TFPI-2 by promoter hypermethylation is a frequent and tumor specific event in NPC. TFPI-2 might be considering as a putative tumor suppressor gene in NPC

  17. MiR-21 expression in the tumor stroma of oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Hedbäck, Nora; Jensen, David H; Specht, Lena

    2014-01-01

    Oral squamous cell carcinoma (OSCC) patients have a high mortality rate; thus, new clinical biomarkers and therapeutic options are needed. MicroRNAs (miRNAs) are short noncoding RNAs that regulate posttranscriptional gene expression and are commonly deregulated in OSCC and other cancers. Micro......-stage) in a multivariate analysis. In summary, we have shown that miR-21 is located in the carcinoma cells, stroma and blood vessels of tumors, and its expression specifically in the stromal compartment has a negative prognostic value in OSCC....

  18. Glycomic and sialoproteomic data of gastric carcinoma cells overexpressing ST3GAL4

    DEFF Research Database (Denmark)

    Mereiter, Stefan; Magalhães, Ana; Adamczyk, Barbara

    2016-01-01

    Gastric carcinoma MKN45 cells stably transfected with the full-length ST3GAL4 gene were characterised by glycomic and sialoproteomic analysis. Complementary strategies were applied to assess the glycomic alterations induced by ST3GAL4 overexpression. The N- and O-glycome data were generated in two......-MS/MS identification was performed. This analysis identified 47 proteins with significantly increased sialylation. The data in this article is associated with the research article published in Biochim Biophys Acta "Glycomic analysis of gastric carcinoma cells discloses glycans as modulators of RON receptor tyrosine...... kinase activation in cancer" [1]....

  19. Next generation sequencing of Cytokeratin 20-negative Merkel cell carcinoma reveals ultraviolet-signature mutations and recurrent TP53 and RB1 inactivation.

    Science.gov (United States)

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

    2016-03-01

    Merkel cell carcinoma is a rare but highly aggressive cutaneous neuroendocrine carcinoma. Cytokeratin 20 (CK20) is expressed in ~95% of Merkel cell carcinomas and is useful for distinction from morphologically similar entities including metastatic small-cell lung carcinoma. Lack of CK20 expression may make diagnosis of Merkel cell carcinoma more challenging, and has unknown biological significance. Approximately 80% of CK20-positive Merkel cell carcinomas are associated with the oncogenic Merkel cell polyomavirus. Merkel cell carcinomas lacking Merkel cell polyomavirus display distinct genetic changes from Merkel cell polyomavirus-positive Merkel cell carcinoma, including RB1 inactivating mutations. Unlike CK20-positive Merkel cell carcinoma, the majority of CK20-negative Merkel cell carcinomas are Merkel cell polyomavirus-negative, suggesting CK20-negative Merkel cell carcinomas predominantly arise through virus-independent pathway(s) and may harbor additional genetic differences from conventional Merkel cell carcinoma. Hence, we analyzed 15 CK20-negative Merkel cell carcinoma tumors (10 Merkel cell polyomavirus-negative, four Merkel cell polyomavirus-positive, and one undetermined) using the Ion Ampliseq Comprehensive Cancer Panel, which assesses copy number alterations and mutations in 409 cancer-relevant genes. Twelve tumors displayed prioritized high-level chromosomal gains or losses (average 1.9 per tumor). Non-synonymous high-confidence somatic mutations were detected in 14 tumors (average 11.9 per tumor). Assessing all somatic coding mutations, an ultraviolet-signature mutational profile was present, and more prevalent in Merkel cell polyomavirus-negative tumors. Recurrent deleterious tumor suppressor mutations affected TP53 (9/15, 60%), RB1 (3/15, 20%), and BAP1 (2/15, 13%). Oncogenic activating mutations included PIK3CA (3/15, 20%), AKT1 (1/15, 7%) and EZH2 (1/15, 7%). In conclusion, CK20-negative Merkel cell carcinoma display overlapping genetic changes

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas.

    Science.gov (United States)

    Showler, Kaye; Nishimura, Mayumi; Daino, Kazuhiro; Imaoka, Tatsuhiko; Nishimura, Yukiko; Morioka, Takamitsu; Blyth, Benjamin J; Kokubo, Toshiaki; Takabatake, Masaru; Fukuda, Maki; Moriyama, Hitomi; Kakinuma, Shizuko; Fukushi, Masahiro; Shimada, Yoshiya

    2017-03-01

    The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells. The negative pathway regulator Inpp4b was significantly downregulated in both groups, compared with in normal mammary tissue, and radiation-induced carcinomas also showed a significant decrease in Pten expression, while the chemically induced carcinomas showed a decrease in Pik3r1 and Pdk1. Significant upregulation of the positive regulators Erbb2 and Pik3ca was observed only in chemically induced carcinomas. However, no genes showed clear correlations with AKT phosphorylation levels, except in individual carcinomas. Only rare carcinomas showed mutations in PI3K/AKT pathway genes, yet these carcinomas did not exhibit stronger AKT phosphorylation. Thus, while AKT phosphorylation is a common feature of rat mammary carcinomas induced by radiation or a canonical chemical carcinogen, the mutation of key genes in the pathways or permanent changes to gene expression of particular signaling proteins do not explain the pathway activation in the advanced cancers. Although AKT signaling likely facilitates cancer development and growth in rat mammary carcinomas, it is unlikely that permanent disruption of the PI3K/AKT pathway genes is a major causal event in radiation carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  2. Gene expression profiling distinguishes between spontaneous and radiation-induced rat mammary carcinomas

    International Nuclear Information System (INIS)

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Kakinuma, Shizuko; Shimada, Yoshiya; Yamashita, Satoshi; Ushijima, Toshikazu

    2008-01-01

    The ability to distinguish between spontaneous and radiation-induced cancers in humans is expected to improve the resolution of estimated risk from low dose radiation. Mammary carcinomas were obtained from Sprague-Dawley rats that were either untreated (n=45) or acutely γ-irradiated (1 Gy; n=20) at seven weeks of age. Gene expression profiles of three spontaneous and four radiation-induced carcinomas, as well as those of normal mammary glands, were analyzed by microarrays. Differential expression of identified genes of interest was then verified by quantitative polymerase chain reaction (qPCR). Cluster analysis of global gene expression suggested that spontaneous carcinomas were distinguished from a heterogeneous population of radiation-induced carcinomas, though most gene expressions were common. We identified 50 genes that had different expression levels between spontaneous and radiogenic carcinomas. We then selected 18 genes for confirmation of the microarray data by qPCR analysis and obtained the following results: high expression of Plg, Pgr and Wnt4 was characteristic to all spontaneous carcinomas; Tnfsf11, Fgf10, Agtr1a, S100A9 and Pou3f3 showed high expression in a subset of radiation-induced carcinomas; and increased Gp2, Areg and Igf2 expression, as well as decreased expression of Ca3 and noncoding RNA Mg1, were common to all carcinomas. Thus, gene expression analysis distinguished between spontaneous and radiogenic carcinomas, suggesting possible differences in their carcinogenic mechanism. (author)

  3. 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

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

    International Nuclear Information System (INIS)

    Lee, Jun Ha; Sung, Ki Joon; Sim, Young; Shim, Sue Yoen; Yoon, Byoung Moon

    2000-01-01

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  6. Merkel Cell Carcinoma: Interdisciplinary Management of a Rare Disease

    International Nuclear Information System (INIS)

    Schneider, S.; Thurnher, D.; Erovic, B. M.

    2013-01-01

    The goal of this paper is to review contemporary multidisciplinary treatment with reference to Milkier cell carcinoma. Management of this rare but highly aggressive skin cancer is a complex undertaking that necessitates an understanding of its etiology, epidemiology, clinical presentation, and the coordinated work of several clinical specializations. Recent Findings. The contemporary literature employs a multidisciplinary approach to achieve the best patient's treatment. Conclusion. This paper presents an algorithm for contemporary management for the rare and aggressive Merkel cell carcinoma. Multidisciplinary approach in a tumor center provides high-quality care for patients with Merkel cell carcinoma.

  7. treatment of Merkel cell carcinoma: a report of four cases

    International Nuclear Information System (INIS)

    Song Yongwen; Liu Xinfan; Wang Xiaozhen; Li Yexiong

    2002-01-01

    Objective: To study the clinical characteristics and progress so as to establish a better therapeutic principle for Merkel cell carcinoma. Methods: Manifestations and results of 4 Merkel cell carcinoma patients treated, with review of relevant papers is presented. Results: Among these 4 patients, local recurrence developed in 2, regional lymphatic metastasis in 3 and distant metastasis in 2. One of them died of the disease. Conclusions: High risks of local recurrence and regional/distant metastasis feature Merkel cell carcinoma. We recommend postoperative radiotherapy for stage I disease and radiotherapy combined with chemotherapy for resected stage II and stage III disease

  8. The neuroendocrine (Merkel cell) carcinoma of head and neck

    International Nuclear Information System (INIS)

    Weidauer, H.; Altmannsberger, H.M.

    1987-01-01

    The neuroendocrine carcinoma of the skin has its histogenetic origin in Merkel cells and a preference in head and neck area in the seventh decade of life. The definitive diagnosis can be made with a combination of electron microscopy and immunohistochemistry. Merkel cell carcinoma is a primary cutaneous neoplasma and is rarely found on the lips or gingiva. Operation and radiation are the therapy of choice. The value of an additional antineoplastic chemotherapy in the treatment of Merkel cell carcinoma is still controversial. Although long survival times had been described in literature the occurrence of local relapses and metastases demands for frequent controls. (orig.) [de

  9. Merkel Cell Carcinoma: Interdisciplinary Management of a Rare Disease

    Directory of Open Access Journals (Sweden)

    Sven Schneider

    2013-01-01

    Full Text Available Background. The goal of this paper is to review contemporary multidisciplinary treatment with reference to Merkel cell carcinoma. Management of this rare but highly aggressive skin cancer is a complex undertaking that necessitates an understanding of its etiology, epidemiology, clinical presentation, and the coordinated work of several clinical specializations. Recent Findings. The contemporary literature employs a multidisciplinary approach to achieve the best patient's treatment. Conclusion. This paper presents an algorithm for contemporary management for the rare and aggressive Merkel cell carcinoma. Multidisciplinary approach in a tumor center provides high-quality care for patients with Merkel cell carcinoma.

  10. Squamous Cell Carcinoma of the Hilar Bile Duct

    Directory of Open Access Journals (Sweden)

    Ippei Yamana

    2011-08-01

    Full Text Available We herein report a rare case of squamous cell carcinoma of the hilar bile duct. A 66-year-old Japanese male patient was admitted to our hospital because of appetite loss and jaundice. Abdominal computed tomography revealed an enhanced mass measuring 10 × 30 mm in the hilar bile duct region. After undergoing biliary drainage, the patient underwent extended right hepatic lobectomy with regional lymph nodes dissection. The tumor had invaded the right portal vein. Therefore, we also performed resection and reconstruction of the portal vein. Histopathologically, the carcinoma cells exhibited a solid structure with differentiation to squamous cell carcinoma with keratinization and intercellular bridges. Immunohistochemical staining of the tumor cells revealed positive cytokeratin staining and negative CAM 5.2 staining. Based on these findings, a definitive diagnosis of well-differentiated squamous cell carcinoma of the hilar bile duct was made.

  11. Radiation sensitivity of Merkel cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, J.H.; Ramsay, J.R.; Birrell, G.W. [Queensland Institute of Medical Research (Australia)] [and others

    1995-07-30

    Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after {gamma} irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to {gamma} irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution. 25 refs., 3 figs., 1 tab.

  12. Radiation sensitivity of Merkell cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Leonard, J. Helen; Ramsay, Jonathan R.; Kearsley, John H.; Birrell, Geoff W.

    1995-01-01

    Purpose: Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Methods and Materials: Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after γ irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. Results: We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to γ irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Conclusion: Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution

  13. The somatic genomic landscape of chromophobe renal cell carcinoma.

    Science.gov (United States)

    Davis, Caleb F; Ricketts, Christopher J; Wang, Min; Yang, Lixing; Cherniack, Andrew D; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C; Hacker, Kathryn E; Bhanot, Gyan; Gordenin, Dmitry A; Chu, Andy; Gunaratne, Preethi H; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A; Bristow, Christopher A; Donehower, Lawrence A; Wallen, Eric M; Smith, Angela B; Tickoo, Satish K; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S; Hsieh, James J; Choueiri, Toni K; Hakimi, A Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A Gordon; Laird, Peter W; Henske, Elizabeth P; Kwiatkowski, David J; Park, Peter J; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A; Linehan, W Marston; Gibbs, Richard A; Rathmell, W Kimryn; Creighton, Chad J

    2014-09-08

    We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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. Molecular analysis of primary gastric cancer, corresponding xenografts, and 2 novel gastric carcinoma cell lines reveals novel alterations in gastric carcinogenesis

    NARCIS (Netherlands)

    Milne, Anya N. A.; Sitarz, Robert; Carvalho, Ralph; Polak, Mirjam M.; Ligtenberg, Madolijn; Pauwels, Patrick; Offerhaus, G. Johan A.; Weterman, Marian A. J.

    2007-01-01

    We report the molecular characterization of 8 primary gastric carcinomas, corresponding xenografts, and 2 novel gastric carcinoma cell lines. We compared the tumors and cell lines, with respect to histology, immunohistochemistry, copy number, and hypermethylation of up to 38 genes using

  16. Clinicopathological evaluation of radiation induced basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  17. Tumor suppressor BLU inhibits proliferation of nasopharyngeal carcinoma cells by regulation of cell cycle, c-Jun N-terminal kinase and the cyclin D1 promoter

    International Nuclear Information System (INIS)

    Zhang, Xiangning; Liu, Hui; Li, Binbin; Huang, Peichun; Shao, Jianyong; He, Zhiwei

    2012-01-01

    Tumor suppressor genes function to regulate and block tumor cell proliferation. To explore the mechanisms underlying the tumor suppression of BLU/ZMYND10 gene on a frequently lost human chromosomal region, an adenoviral vector with BLU cDNA insert was constructed. BLU was re-expressed in nasopharyngeal carcinoma cells by transfection or viral infection. Clonogenic growth was assayed; cell cycle was analyzed by flow cytometry-based DNA content detection; c-Jun N-terminal kinase (JNK) and cyclin D1 promoter activities were measured by reporter gene assay, and phosphorylation was measured by immunoblotting. The data for each pair of groups were compared with Student t tests. BLU inhibits clonogenic growth of nasopharyngeal carcinoma cells, arrests cell cycle at G1 phase, downregulates JNK and cyclin D1 promoter activities, and inhibits phosphorylation of c-Jun. BLU inhibits growth of nasopharyngeal carcinoma cells by regulation of the JNK-cyclin D1 axis to exert tumor suppression

  18. [Epidemiology and risk factors of the esophageal squamous cell carcinoma].

    Science.gov (United States)

    Szumiło, Justyna

    2009-01-01

    Esophageal carcinoma is the eighth most common malignancy in the world. In most countries, including Poland, the squamous cell carcinoma is a predominant histological type. It is characterized by extreme diversity in geographical distribution and incidence. High incidence is noted in regions located along with so-called "Asian esophageal cancer belt" beginning from eastern Turkey through Caspian littoral countries, northern Afghanistan to Central and Eastern Asia, as well as in Japan, South Africa and some South American countries. In Western Europe the highest incidence is observed in France, Portugal and northern Italy. Poland belongs to low-incidence countries with the age-standardized annual incidence exceeding 4.5 and 0.7/100,000, for men and women respectively. Etiology of the cancer is multi-factorial. In western countries the most important risk factors are tobacco smoking and alcohol consumption, and to a lesser extent, an inappropriate diet. In other countries, a diet lacking of fresh vegetables and fruits with vitamin and mineral deficiency and high level of sodium chloride, carbohydrates and animal fats is a predominant factor. Furthermore, preserving and processing food which facilitates accumulation of carcinogens, special dietary habits and viral infections are also attributed to the development of cancer. More recently, the significance of genetically determined increased susceptibility of some individuals versus environmental factors has been stressed. Previous studies proved the relationship between cancer susceptibility and polymorphisms in genes encoding some important molecules engaged in carcinogens metabolism or DNA repair.

  19. Treatment of early glassy cell carcinoma of uterine cervix

    International Nuclear Information System (INIS)

    Kim, Ok Bae; Kim, Jin Hee; Choi, Tae Jin

    2006-01-01

    The purpose of this study was to investigate the clinical findings, treatment, and outcome of patients with glassy cell carcinoma of cervix. We reviewed all cases of glassy cell carcinoma of the uterine cervix confirmed and treated at the Dongsan Medical Center, Keimyung University, between January 1993 and December 2005. There were 7 cases with histopathologically confirmed gassy cell carcinoma. A tumor was diagnosed as glassy cell carcinoma if over 50% of the tumor cell type displayed glassy cell features. Six patients with stage IB had radical hysterectomy and bilateral pelvic node dissection, and 2 of them received adjuvant external pelvic irradiation with concurrent chemotherapy. Remaining one patient with stage IIA had curative concurrent chemoradiotherapy with external pelvic irradiation and brachytherapy. There were 7 patients diagnosed as glassy cell carcinoma among the 3,745 (0.2%) patients of carcinoma of uterine cervix. The mean age of 7 patients was 44 years with range of 35 to 53 years of age. The most frequent symptom was vaginal bleeding (86%). By the punch biopsy undertaken before treatment of 7 cases, 2 only cases could diagnose as glassy cell carcinoma of uterine cervix, but remaining of them confirmed by surgical pathological examination. The mean follow up duration was 73 months with range of 13 to 150 months. All 7 patients were alive without disease after treatment. Glassy cell carcinoma of the uterine cervix is a distinct clinicopathologic entity that demonstrates an aggressive biologic behavior. However for early-stage disease, we may have more favorable clinical outcome with radical surgery followed by chemoradiotherapy

  20. Facial skin follllicular hyperkeratosis of patients with basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    M. V. Zhuchkov

    2016-01-01

    Full Text Available This article provides a clinical observation of paraneoplastic syndrome of a patient with basal cell carcinoma of skin. Authors present clinical features of the described for the first time, paraneoplastic retentional follicular hyperkeratosis of facial area.

  1. Leukemoid reaction associated with transitional cell carcinoma: A ...

    African Journals Online (AJOL)

    Leukemoid reaction associated with transitional cell carcinoma: A case report ... Nigerian Journal of Clinical Practice ... At 3 months later, patient was admitted to our 21 22 hospital with the complaints of the left leg edema, diagnosed as pelvic

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Merkel Cell Carcinoma in Immunosuppressed Patients

    International Nuclear Information System (INIS)

    Ma, Janice E.; Brewer, Jerry D.

    2014-01-01

    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

  7. 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.

  8. Mutational Analysis of Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Erstad, Derek J.; Cusack, James C. Jr.

    2014-01-01

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

  9. CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Zhang, Heyu; Nan, Xu; Li, Xuefen; Chen, Yan; Zhang, Jianyun; Sun, Lisha; Han, Wenlin; Li, Tiejun

    2014-01-01

    Highlights: • Down-regulation of CMTM5 expression in OSCC tissues was found. • The promoter methylation status of CMTM5 was measured. • CMTM5-v1 inhibited cell proliferation and migration and induced apoptosis. • CMTM5 might act as a putative tumor suppressor gene in OSCC. - Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma

  10. CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Heyu [Central Laboratory, Peking University School of Stomatology, Beijing (China); Nan, Xu [Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing (China); Li, Xuefen [Central Laboratory, Peking University School of Stomatology, Beijing (China); Chen, Yan; Zhang, Jianyun [Department of Oral Pathology, Peking University School of Stomatology, Beijing (China); Sun, Lisha [Central Laboratory, Peking University School of Stomatology, Beijing (China); Han, Wenlin [Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing (China); Li, Tiejun, E-mail: litiejun22@vip.sina.com [Department of Oral Pathology, Peking University School of Stomatology, Beijing (China)

    2014-05-02

    Highlights: • Down-regulation of CMTM5 expression in OSCC tissues was found. • The promoter methylation status of CMTM5 was measured. • CMTM5-v1 inhibited cell proliferation and migration and induced apoptosis. • CMTM5 might act as a putative tumor suppressor gene in OSCC. - Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma.

  11. Mesenchymal stem cells enhance the metastasis of 3D-cultured hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    Liu, Chang; Liu, Yang; Xu, Xiao-xi; Guo, Xin; Sun, Guang-wei; Ma, Xiao-jun

    2016-01-01

    Accumulating evidences have demonstrated that mesenchymal stem cells (MSC) could be recruited to the tumor microenvironment. Umbilical cord mesenchymal stem cells (UCMSC) were attractive vehicles for delivering therapeutic agents against cancer. Nevertheless, the safety of UCMSC in the treatment of tumors including hepatocellular carcinoma (HCC) was still undetermined. In this study, an in vitro co-culture system was established to evaluate the effect of UCMSC on the cell growth, cancer stem cell (CSC) characteristics, drug resistance, metastasis of 3D-cultured HCC cells, and the underlying mechanism was also investigated. It was found that after co-cultured with UCMSC, the metastatic ability of 3D-cultured HCC cells was significantly enhanced as indicated by up-regulation of matrix metalloproteinase (MMP), epithelial-mesenchymal transition (EMT)-related genes, and migration ability. However, cell growth, drug resistance and CSC-related gene expression of HCC cells were not affected by UCMSC. Moreover, EMT was reversed, MMP-2 expression was down-regulated, and migration ability of HCC cell was significantly inhibited when TGF-β receptor inhibitor SB431542 was added into the co-culture system. Therefore, these data indicated that UCMSC could significantly enhance the tumor cell metastasis, which was due to the EMT of HCC cells induced by TGF-β. The online version of this article (doi:10.1186/s12885-016-2595-4) contains supplementary material, which is available to authorized users

  12. Tumor-produced, active Interleukin-1 β regulates gene expression in carcinoma-associated fibroblasts

    International Nuclear Information System (INIS)

    Dudas, Jozsef; Fullar, Alexandra; Bitsche, Mario; Schartinger, Volker; Kovalszky, Ilona; Sprinzl, Georg Mathias; Riechelmann, Herbert

    2011-01-01

    Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1β (IL1-β) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-β expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-β processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-β. IL1-β signaling was investigated by western blot and immunocytochemistry. IL1-β-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-β, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NFκBα. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-β reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-β-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-β in the tumor cells leads to IL1-β-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-β. PDL fibroblasts possess receptor for IL1-β, and its expression is increased 4.56-times in the presence of SCC-25 tumor cells. IL1-β receptor expression in

  13. Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Dudas, Jozsef, E-mail: Jozsef.Dudas@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullar, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Bitsche, Mario, E-mail: Mario.Bitsche@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Schartinger, Volker, E-mail: Volker.Schartinger@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: Herbert.Riechelmann@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

    2011-09-10

    Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the

  14. 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.

  15. Depletion of cutaneous macrophages and dendritic cells promotes growth of basal cell carcinoma in mice.

    Science.gov (United States)

    König, Simone; Nitzki, Frauke; Uhmann, Anja; Dittmann, Kai; Theiss-Suennemann, Jennifer; Herrmann, Markus; Reichardt, Holger M; Schwendener, Reto; Pukrop, Tobias; Schulz-Schaeffer, Walter; Hahn, Heidi

    2014-01-01

    Basal cell carcinoma (BCC) belongs to the group of non-melanoma skin tumors and is the most common tumor in the western world. BCC arises due to mutations in the tumor suppressor gene Patched1 (Ptch). Analysis of the conditional Ptch knockout mouse model f