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  1. Translational research in ovarian carcinoma : cell biological aspects of drug resistance and tumor aggressiveness

    NARCIS (Netherlands)

    Zee, Ate Gerard Jan van der

    1994-01-01

    In this thesis diverse cell biological features that in cultured (ovarian) tumor cells have been linked to drug resistance and/or tumor aggressiveness are studied in tumor specimens of epithelial ovarian carcinomas.

  2. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR

    Institute of Scientific and Technical Information of China (English)

    Xiao-qing TANG; Hu BI; Jian-qiang FENG; Jian-guo CAO

    2005-01-01

    Aim: To investigate the reversal effects of curcumin on multidrug resistance (MDR)in a resistant human gastric carcinoma cell line. Methods: The cytotoxic effect of vincristine (VCR) was evaluated by MTT assay. The cell apoptosis induced by VCR was determined by propidium iodide (PI)-stained flow cytometry (FCM) and a morphological assay using acridine orange (AO)/ethidium bromide (EB) dual staining. P-glycoprotein (P-gp) function was demonstrated by the accumulation and efflux of rhodamine123 (Rh123) using FCM. The expression of P-gp and the activation of caspase-3 were measured by FCM using fluorescein isothiocyanate (FITC)-conjugated anti-P-gp and anti-cleaved caspase-3 antibodies, respectively.Results: Curcumin, at concentrations of 5 μmol/L, 10 μmol/L, or 20 μmol/L, had no cytotoxic effect on a parent human gastric carcinoma cell line (SGC7901) or its VCR-resistant variant cell line (SGC7901/VCR). The VCR-IC50 value of the SGC7901/VCR cells was 45 times more than that of the SGC7901cells and the SGC7901/VCR cells showed apoptotic resistance to VCR. SGC7901/VCR cells treated with 5μmol/L, 10 μmol/L, or 20 μmol/L curcumin decreased the IC50 value of VCR and promoted VCR-mediated apoptosis in a dose-dependent manner. Curcumin (10μmol/L) increased Rh 123 accumulation and inhibited the efflux of Rh 123 in S GC7901/VCR cells, but did not change the accumulation and efflux of Rh123 in SGC7901cells. P-gp was overexpressed in SGC7901/VCR cells, whereas it was downregulated after a 24-h treatment with curcumin (10 μmol/L). Resistant cells treated with 1μmol/L VCR alone showed 77% lower levels of caspase-3 activation relative to SGC7901 cells, but the activation of caspase-3 in the resistant cell line increased by 44% when cells were treated with VCR in combination with curcumin.Conclusion: Curcumin can reverse the MDR of the human gastric carcinoma SGC7901/VCR cell line. This might be associated with decreased P-gp function and expression, and the promotion of

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  5. Altered cell cycle regulation helps stem-like carcinoma cells resist apoptosis

    OpenAIRE

    Dalton Stephen; Chappell James

    2010-01-01

    Abstract Reemergence of carcinomas following chemotherapy and/or radiotherapy is not well understood, but a recent study in BMC Cancer suggests that resistance to apoptosis resulting from altered cell cycle regulation is crucial. See research article: http://biomedcentral.com/1471-2407/10/166

  6. Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells.

    OpenAIRE

    Roninson, I B; Chin, J E; Choi, K. G.; Gros, P.; Housman, D.E.; Fojo, A; Shen, D. W.; Gottesman, M M; Pastan, I

    1986-01-01

    The ability of tumor cells to develop simultaneous resistance to structurally different cytotoxic drugs constitutes a major problem in cancer chemotherapy. It was previously demonstrated that multidrug-resistant Chinese hamster cell lines contain an amplified, transcriptionally active DNA sequence designated mdr. This report presents evidence that multidrug-resistant sublines of human KB carcinoma cells, selected for resistance to either colchicine, vinblastine, or Adriamycin (doxorubicin), d...

  7. Radiation- and chemoinduced multidrug resistance in colon carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Bartkowiak, Detlef; Stempfhuber, Michael; Wiegel, Thomas; Bottke, Dirk [Dept. of Radiotherapy and Radiooncology, Univ. of Ulm (Germany)

    2009-12-15

    Background and purpose: radiation can induce multidrug resistance (MDR) and thus interfere with simultaneous or subsequent chemotherapy. In SW620 colon carcinoma cells, the interrelation of various biological endpoints of MDR was analyzed and the potential of fractionated irradiation and chemoselection to evoke MDR was compared. Material and methods: to induce/select an MDR phenotype, SW620 were exposed to either 27 Gy in 1.8-Gy daily fractions or to 50% inhibiting concentrations of doxorubicin or cisplatin, given over 6-15 weeks. Expression of genes involved in MDR, including glutathione metabolism, was determined by semiquantitative RT-PCR (reverse transcription-polymerase chain reaction). Efflux was analyzed by flow cytometry after staining with rhodamine-123 or 5-chloromethyl fluorescein diacetate. Apoptosis was monitored after pulse exposure to doxorubicin or cisplatin. Colony-forming assays were performed under continuous drug exposure. Results: a pronounced gene induction was found in MRP2 after cisplatin selection and up to 3 weeks after radiation. LRP was activated only shortly after radiation. Radiation enhanced rhodamine-123 efflux to a similar extent as short-term chemoselection but not as much as long-term drug exposure. Drug-induced apoptosis was slightly delayed in preirradiated cells. Clonogenic growth in the progeny of irradiated cells was less sensitive to cisplatin but not to doxorubicin. Conclusion: fractionated radiation can induce an MDR phenotype in SW620. However, long-term drug exposure establishes a more efficient selection. Various endpoints are not fully concordant regarding the extent of MDR. Posttranscriptional modifications, pleiotropic regulation, and alternative pathways may cause these discrepancies. (orig.)

  8. Role of Mitochondrial Translocation of Telomerase in Hepatocellular Carcinoma Cells with Multidrug Resistance

    OpenAIRE

    Ling, Xianlong; Wen, Lei; Zhou, Yuan

    2012-01-01

    Multidrug resistance (MDR) is a major obstacle of cancer chemotherapy. This study aimed to investigate the role of mitochondrial translocation of telomerase (hTERT) in MDR of human hepatocellular carcinoma (HCC) cells. In this study, three HCC cell lines (SK-Hep1/CDDP1 cells, SK-Hep1/CDDP2 cells and SK-Hep1/CDDP3 cells) with differential resistance index (RI) to cisplatin (CDDP) were induced by pulse treatment of SK-Hep1 (human hepatocellular cell line) with CDDP in vitro. The RI of SK-Hep1/C...

  9. Role of Mitochondrial Translocation of Telomerase in Hepatocellular Carcinoma Cells with Multidrug Resistance

    Directory of Open Access Journals (Sweden)

    Xianlong Ling, Lei Wen, Yuan Zhou

    2012-01-01

    Full Text Available Multidrug resistance (MDR is a major obstacle of cancer chemotherapy. This study aimed to investigate the role of mitochondrial translocation of telomerase (hTERT in MDR of human hepatocellular carcinoma (HCC cells. In this study, three HCC cell lines (SK-Hep1/CDDP1 cells, SK-Hep1/CDDP2 cells and SK-Hep1/CDDP3 cells with differential resistance index (RI to cisplatin (CDDP were induced by pulse treatment of SK-Hep1 (human hepatocellular cell line with CDDP in vitro. The RI of SK-Hep1/CDDP1 cells, SK-Hep1/CDDP2 cells and SK-Hep1/CDDP3 cells was 5.14, 8.66, and 14.25, respectively, and all the cell lines showed cross-resistance to Doxorubicin (DOX and 5-Fuorouracil (5-FU. The apoptosis rates in drug-resistant cells were significantly reduced. Cell cycle analysis revealed the ratio of drug-resistant cells in G2/M and S phases increased, while that in G1 phase decreased. Immunofluorescence staining and Western blot assay demonstrated, with the gradual elevation in RI, increasing hTERT translocated from the nuclei to the mitochondria, while real-time PCR indicated the shortening of telomere length in drug-resistant cells under the chemotherapeutic stress and the reduction of damaged mtDNA with the increase in RI. Furthermore, JC-1 staining also indicated the reduction of mitochondrial membrane potential in drug-resistant cells. The mitochondrial translocation of hTERT increases in multidrug-resistant cells and exerts protective effect on mitochondrial function. Drug-resistant tumor cells escape from apoptosis through hTERT-mediated mitochondrial protection. Mitochondrial translocation of hTERT may serve as an underlying mechanism of MDR.

  10. Role of mitochondrial translocation of telomerase in hepatocellular carcinoma cells with multidrug resistance.

    Science.gov (United States)

    Ling, Xianlong; Wen, Lei; Zhou, Yuan

    2012-01-01

    Multidrug resistance (MDR) is a major obstacle of cancer chemotherapy. This study aimed to investigate the role of mitochondrial translocation of telomerase (hTERT) in MDR of human hepatocellular carcinoma (HCC) cells. In this study, three HCC cell lines (SK-Hep1/CDDP1 cells, SK-Hep1/CDDP2 cells and SK-Hep1/CDDP3 cells) with differential resistance index (RI) to cisplatin (CDDP) were induced by pulse treatment of SK-Hep1 (human hepatocellular cell line) with CDDP in vitro. The RI of SK-Hep1/CDDP1 cells, SK-Hep1/CDDP2 cells and SK-Hep1/CDDP3 cells was 5.14, 8.66, and 14.25, respectively, and all the cell lines showed cross-resistance to Doxorubicin (DOX) and 5-Fuorouracil (5-FU). The apoptosis rates in drug-resistant cells were significantly reduced. Cell cycle analysis revealed the ratio of drug-resistant cells in G2/M and S phases increased, while that in G1 phase decreased. Immunofluorescence staining and Western blot assay demonstrated, with the gradual elevation in RI, increasing hTERT translocated from the nuclei to the mitochondria, while real-time PCR indicated the shortening of telomere length in drug-resistant cells under the chemotherapeutic stress and the reduction of damaged mtDNA with the increase in RI. Furthermore, JC-1 staining also indicated the reduction of mitochondrial membrane potential in drug-resistant cells. The mitochondrial translocation of hTERT increases in multidrug-resistant cells and exerts protective effect on mitochondrial function. Drug-resistant tumor cells escape from apoptosis through hTERT-mediated mitochondrial protection. Mitochondrial translocation of hTERT may serve as an underlying mechanism of MDR. PMID:22991493

  11. Increased sensitivity of an adriamycin-resistant human small cell lung carcinoma cell line to mitochondrial inhibitors

    NARCIS (Netherlands)

    de Jong, Steven; Holtrop, M; de Vries, H; de Vries, Liesbeth; Mulder, N H

    1992-01-01

    The energy metabolism of an atypical multidrug resistant human small cell lung carcinoma cell line (GLC4/ADR) was studied. The glycolytic rate was 30% reduced and the glucose-6-phosphate dehydrogenase activity 2-fold increased in GLC4/ADR compared to the parental sensitive line (GLC4). Although mito

  12. Silibinin reverses drug resistance in human small-cell lung carcinoma cells

    Science.gov (United States)

    Sadava, David; Kane, Susan E.

    2014-01-01

    Small-cell lung carcinoma (SCLC) has a dismal prognosis in part because of multidrug resistance (MDR). Silibinin is a flavonolignan extracted from milk thistle (Silybum marianum), extracts of which are used in traditional medicine. We tested the effects of silibinin on drug-sensitive (H69) and multi-drug resistant (VPA17) SCLC cells. VPA17 cells did not show resistance to silibinin (IC50 = 60µM for H69 and VPA17). Flow cytometry analysis after incubation in 30 µM silibinin showed no changes in cell cycle phases in VPA17 or H69 cells compared with untreated cells. Silibinin (30 µM) incubation was pro-apoptotic in VPA17 cells after >3 days, as measured by ELISA of BUdR labeled DNA fragments. Apoptosis was also indicated by an increase in caspase-3 specific activity and decrease in survivin in VPA17 MDR cells. VPA17 cells had increased Pgp -mediated efflux of calcein acetoxymethyl ester (calcein AM); however, this was inhibited in cells pre-incubated in silibinin for 5 days. Pre-incubation of VPA17 cells in 30 µM silibinin for 5 days also reversed resistance to etoposide (IC50 = 5.50 uM to 0.65 µM) and doxorubicin (IC50 = 0.620 µM to 0.035 µM). The possible synergistic relationship between silibinin and chemotherapy drugs was determined by exposure of VPA17 cells to 1:1 ratios of their respective IC50 values, with serial dilutions at 0.25–2.0 × IC50 and calculation of the combination index (CI). Silibinin and etoposide showed synergism (CI = 0.46 at ED50), as did silibinin and doxorubicin (CI = 0.24 at ED50). These data indicate that in SCLC, silibinin is pro-apoptotic, reverses MDR and acts synergistically with chemotherapy drugs. Silibinin, a non-toxic natural product may be useful in the treatment of drug-resistant SCLC. PMID:23879966

  13. Establishment and characterization of a paclitaxel‑resistant human esophageal carcinoma cell line.

    Science.gov (United States)

    Wang, Cong; Guo, Liu-Bin; Ma, Jun-Yuan; Li, Yong-Mei; Liu, Hong-Min

    2013-11-01

    The aim of this study was to establish a new paclitaxel (PTX)-resistant human esophageal squamous carcinoma (ESCC) cell line and investigate its biological characteristics. The resistant cell line (EC109/Taxol) was developed in vitro by intermittent exposure of the human ESCC cell line EC109 to a high concentration of PTX with time-stepwise increment over a period of 6 months. The MTT assay was performed to test the drug resistance of EC109 and EC109/Taxol cells. The morphological features were observed using inverted microscopy and apoptosis was measured by flow cytometry (FCM) and Hoechst 33258 fluorescence staining. Cell growth curves and colony formation of EC109 and EC109/Taxol cells were compared. FCM was also used to determine the distribution of the cell cycle. The protein levels of Bcl-2, Bax, Procaspase-3 and P-gp were detected by western blotting. P-gp activity was evaluated by Rh123 accumulation and efflux assay. In vivo resistance characterization was investigated. EC109/Taxol cells were 67.2-fold resistant to PTX in comparison with EC109 cells, and also exhibited cross-resistance to 5-fluorouracil (5-FU), cisplatin (CDDP) and epirubicin (EPI). FCM and Hoechst 33258 fluorescence staining confirmed that EC109 cells treated with PTX showed significantly higher percentage of apoptotic cells compared to EC109/Taxol cells. Simultaneously, EC109/Taxol cells exhibited changes in morphology, proliferation rate, doubling time, cell cycle distribution and colony formation rate were detected as compared with EC109 cells. The resistant cell line overexpressed Bcl-2, Procaspase-3 and P-gp protein, and showed decreased Bax expression. Further, EC109/Taxol cells did not change PTX resistance in vivo. This is the first report on the establishment of an EC109/Taxol cell line with higher resistance. Bcl-2, Bax, Procaspase-3 and P-gp are involved in the resistance of cell lines to PTX, which are invaluable tools to study the resistance of anticancer drugs and to identify

  14. Harnessing the p53-PUMA Axis to Overcome DNA Damage Resistance in Renal Cell Carcinoma

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    Xiaoguang Zhou

    2014-12-01

    Full Text Available Resistance to DNA damage–induced apoptosis is a hallmark of cancer and a major cause of treatment failure and lethal disease outcome. A tumor entity that is largely resistant to DNA-damaging therapies including chemo- or radiotherapy is renal cell carcinoma (RCC. This study was designed to explore the underlying molecular mechanisms of DNA damage resistance in RCC to develop strategies to resensitize tumor cells to DNA damage–induced apoptosis. Here, we show that apoptosis-resistant RCC cells have a disconnect between activation of p53 and upregulation of the downstream proapoptotic protein p53 upregulated modulator of apoptosis (PUMA. We demonstrate that this disconnect is not caused by gene-specific repression through CCCTC-binding factor (CTCF but instead by aberrant chromatin compaction. Treatment with an HDAC inhibitor was found to effectively reactivate PUMA expression on the mRNA and protein level and to revert resistance to DNA damage–induced cell death. Ectopic expression of PUMA was found to resensitize a panel of RCC cell lines to four different DNA-damaging agents tested. Remarkably, all RCC cell lines analyzed were wild-type for p53, and a knockdown was likewise able to sensitize RCC cells to acute genotoxic stress. Taken together, our results indicate that DNA damage resistance in RCC is reversible, involves the p53-PUMA axis, and is potentially targetable to improve the oncological outcomes of RCC patients.

  15. Interdependence of Gemcitabine Treatment, Transporter Expression, and Resistance in Human Pancreatic Carcinoma Cells

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    Wolfgang Hagmann

    2010-09-01

    Full Text Available Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment of pancreatic cancer. Our previous experimental chemotherapy studies have shown that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU alters the cellular transporter expression profile and that modulation of the expression of multidrug resistance protein 5 (MRP5; ABCC5 influences the chemoresistance of these tumor cells. Here, we studied the influence of acute and chronic gemcitabine treatment on the expression of relevant uptake and export transporters in pancreatic carcinoma cells by reverse transcription-polymerase chain reaction (RT-PCR, quantitative RT-PCR, and immunoblot analyses. The specific role of MRP5 in cellular gemcitabine sensitivity was studied by cytotoxicity assays using MRP5-overexpressing and MRP5-silenced cells. Exposure to gemcitabine (12 nM for 3 days did not alter the messenger RNA (mRNA expression of MRP1, MRP3, MRP5, and equilibrative nucleoside transporter 1 (ENT1, whereas high dosages of the drug (20 µM for 1 hour elicited up-regulation of these transporters in most cell lines studied. In cells with acquired gemcitabine resistance (up to 160 nM gemcitabine, the mRNA or protein expression of the gemcitabine transporters MRP5 and ENT1 was upregulated in several cell lines. Combined treatment with 5-FU and gemcitabine caused a 5- to 40-fold increase in MRP5 and ENT1 expressions. Cytotoxicity assays using either MRP5-overexpressing (HEK and PANC-1 or MRP5-silenced (PANC1/shMRP5 cells indicated that MRP5 contributes to gemcitabine resistance. Thus, our novel data not only on drug-induced alterations of transporter expression relevant for gemcitabine uptake and export but also on the link between gemcitabine sensitivity and MRP5 expression may lead to improved strategies of future chemotherapy regimens using gemcitabine in pancreatic carcinoma patients.

  16. Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma.

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    Chi T Viet

    Full Text Available Cisplatin resistance in head and neck squamous cell carcinoma (HNSCC reduces survival. In this study we hypothesized that methylation of key genes mediates cisplatin resistance. We determined whether a demethylating drug, decitabine, could augment the anti-proliferative and apoptotic effects of cisplatin on SCC-25/CP, a cisplatin-resistant tongue SCC cell line. We showed that decitabine treatment restored cisplatin sensitivity in SCC-25/CP and significantly reduced the cisplatin dose required to induce apoptosis. We then created a xenograft model with SCC-25/CP and determined that decitabine and cisplatin combination treatment resulted in significantly reduced tumor growth and mechanical allodynia compared to control. To establish a gene classifier we quantified methylation in cancer tissue of cisplatin-sensitive and cisplatin-resistant HNSCC patients. Cisplatin-sensitive and cisplatin-resistant patient tumors had distinct methylation profiles. When we quantified methylation and expression of genes in the classifier in HNSCC cells in vitro, we showed that decitabine treatment of cisplatin-resistant HNSCC cells reversed methylation and gene expression toward a cisplatin-sensitive profile. The study provides direct evidence that decitabine restores cisplatin sensitivity in in vitro and in vivo models of HNSCC. Combination treatment of cisplatin and decitabine significantly reduces HNSCC growth and HNSCC pain. Furthermore, gene methylation could be used as a biomarker of cisplatin-resistance.

  17. Lipocalin 2 Enhances Migration and Resistance against Cisplatin in Endometrial Carcinoma Cells.

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    Tsutomu Miyamoto

    Full Text Available Lipocalin 2 (LCN2 is a secretory protein that is involved in various physiological processes including iron transport. We previously identified LCN2 as an up-regulated gene in endometrial carcinoma, and found that the overexpression of LCN2 and its receptor, SLC22A17, was associated with a poor prognosis. However, the functions and mechanism of action of LCN2 currently remain unclear.The LCN2-overexpressing endometrial carcinoma cell lines, HHUA and RL95-2, and LCN2-low-expressing one, HEC1B, were used. The effects of LCN2 on cell migration, cell viability, and apoptosis under various stresses, including ultraviolet (UV irradiation and cisplatin treatment, were examined using the scratch wound healing assay, WST-1 assay, and Apostrand assay, respectively.LCN2-silencing using shRNA method significantly reduced the migration ability of cells (p<0.05. Cytotoxic stresses significantly decreased the viability of LCN2-silenced cells more than that of control cells. In contrast, LCN2 overexpression was significantly increased cisplatin resistance. These effects were canceled by the addition of the iron chelator, deferoxamine. After UV irradiation, the expression of phosphorylated Akt (pAkt was decreased in LCN2-silenced cells, and the PI3K inhibitor canceled the difference induced in UV sensitivity by LCN2. The cisplatin-induced expression of pAkt was not affected by LCN2; however, the expression of p53 and p21 was increased by LCN2-silencing.These results indicated that LCN2 was involved in the migration and survival of endometrial carcinoma cells under various stresses in an iron-dependent manner. The survival function of LCN2 may be exerted through the PI3K pathway and suppression of the p53-p21 pathway. These functions of LCN2 may increase the malignant potential of endometrial carcinoma cells.

  18. Small cell carcinoma of vulva. Curative multimodal treatment in face of resistance to initial standard chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Eckert, Franziska; Bamberg, Michael; Mueller, Arndt-Christian [Dept. of Radiooncology, Eberhard Karls Univ. of Tuebingen (Germany); Fehm, Tanja [Gynecologic Clinic, Eberhard Karls Univ. of Tuebingen (Germany)

    2010-09-15

    Background and Purpose: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease, which has a slightly better prognosis than small cell lung cancer, but still dismal. Gynecologic small cell malignancies tend to show a better survival than similar histologies of other regions. However, of five reported cases of vulvar manifestation only one patient was disease-free at the time of publication with limited follow-up. Case Report: The authors describe a case of locally advanced small cell vulva carcinoma infiltrating the anal sphincter and urethra with spread to inguinal lymph nodes treated by radiochemotherapy and regional hyperthermia. After three cycles of carboplatin/etoposide, computed tomography and magnetic resonance imaging indicated only little regressive transformations but overall stable disease. Surgical options were excluded. Therefore, curative radiotherapy to a total dose of > 65 Gy to macroscopic tumor, chemotherapy with cisplatin weekly, and regional hyperthermia were performed. Acute severe toxicity was limited to skin reactions. Despite the disadvantageous situation with inguinal lymph node metastases and chemoresistance, the multimodal therapy yielded a 5-year disease-free survival. Conclusion: Thus, the trimodal regimen of radiochemotherapy plus regional hyperthermia offered a curative chance in spite of resistance to the standard chemotherapy for irresectable, locally advanced small cell carcinoma of the vulva. Therefore, this approach merits further evaluation for limited disease of EPSCC. (orig.)

  19. Small cell carcinoma of vulva. Curative multimodal treatment in face of resistance to initial standard chemotherapy

    International Nuclear Information System (INIS)

    Background and Purpose: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease, which has a slightly better prognosis than small cell lung cancer, but still dismal. Gynecologic small cell malignancies tend to show a better survival than similar histologies of other regions. However, of five reported cases of vulvar manifestation only one patient was disease-free at the time of publication with limited follow-up. Case Report: The authors describe a case of locally advanced small cell vulva carcinoma infiltrating the anal sphincter and urethra with spread to inguinal lymph nodes treated by radiochemotherapy and regional hyperthermia. After three cycles of carboplatin/etoposide, computed tomography and magnetic resonance imaging indicated only little regressive transformations but overall stable disease. Surgical options were excluded. Therefore, curative radiotherapy to a total dose of > 65 Gy to macroscopic tumor, chemotherapy with cisplatin weekly, and regional hyperthermia were performed. Acute severe toxicity was limited to skin reactions. Despite the disadvantageous situation with inguinal lymph node metastases and chemoresistance, the multimodal therapy yielded a 5-year disease-free survival. Conclusion: Thus, the trimodal regimen of radiochemotherapy plus regional hyperthermia offered a curative chance in spite of resistance to the standard chemotherapy for irresectable, locally advanced small cell carcinoma of the vulva. Therefore, this approach merits further evaluation for limited disease of EPSCC. (orig.)

  20. 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 P

    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....

  1. Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells.

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    Paolo B Abada

    Full Text Available Although testicular germ cell tumors are generally quite responsive to treatment with cisplatin, a small fraction of them acquire resistance during therapy. Even when cisplatin treatment is successful the patient is often left with a residual teratoma at the site of the primary tumor suggesting that cisplatin may trigger differentiation in some tumors. Using the human embryonal carcinoma cell line NTera2/D1, we confirmed that exposure to the differentiating agent retinoic acid produced a reduction in pluripotency markers NANOG and POU5F1 (Oct3/4 and an acute concentration-dependent increase in resistance to both cisplatin and paclitaxel that reached as high as 18-fold for cisplatin and 61-fold for paclitaxel within four days. A two day exposure to cisplatin also produced a concentration-dependent decrease in the expression of the NANOG and POU5F1 and increased expression of three markers whose levels increase with differentiation including Nestin, SCG10 and Fibronectin. In parallel, exposure to cisplatin induced up to 6.2-fold resistance to itself and 104-fold resistance to paclitaxel. Paclitaxel did not induce differentiation or resistance to either itself or cisplatin. Neither retinoic acid nor cisplatin induced resistance in cervical or prostate cancer cell lines or other germ cell tumor lines in which they failed to alter the expression of NANOG and POU5F1. Forced expression of NANOG prevented the induction of resistance to cisplatin by retinoic acid. We conclude that cisplatin can acutely induce resistance to itself and paclitaxel by triggering a differentiation response in pluripotent germ cell tumor cells.

  2. Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells.

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    Abada, Paolo B; Howell, Stephen B

    2014-01-01

    Although testicular germ cell tumors are generally quite responsive to treatment with cisplatin, a small fraction of them acquire resistance during therapy. Even when cisplatin treatment is successful the patient is often left with a residual teratoma at the site of the primary tumor suggesting that cisplatin may trigger differentiation in some tumors. Using the human embryonal carcinoma cell line NTera2/D1, we confirmed that exposure to the differentiating agent retinoic acid produced a reduction in pluripotency markers NANOG and POU5F1 (Oct3/4) and an acute concentration-dependent increase in resistance to both cisplatin and paclitaxel that reached as high as 18-fold for cisplatin and 61-fold for paclitaxel within four days. A two day exposure to cisplatin also produced a concentration-dependent decrease in the expression of the NANOG and POU5F1 and increased expression of three markers whose levels increase with differentiation including Nestin, SCG10 and Fibronectin. In parallel, exposure to cisplatin induced up to 6.2-fold resistance to itself and 104-fold resistance to paclitaxel. Paclitaxel did not induce differentiation or resistance to either itself or cisplatin. Neither retinoic acid nor cisplatin induced resistance in cervical or prostate cancer cell lines or other germ cell tumor lines in which they failed to alter the expression of NANOG and POU5F1. Forced expression of NANOG prevented the induction of resistance to cisplatin by retinoic acid. We conclude that cisplatin can acutely induce resistance to itself and paclitaxel by triggering a differentiation response in pluripotent germ cell tumor cells. PMID:24475288

  3. Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy.

    Science.gov (United States)

    Gilaberte, Yolanda; Milla, Laura; Salazar, Nerea; Vera-Alvarez, Jesús; Kourani, Omar; Damian, Alejandra; Rivarola, Viviana; Roca, Maria José; Espada, Jesús; González, Salvador; Juarranz, Angeles

    2014-09-01

    Photodynamic therapy (PDT) is widely used to treat non-melanoma skin cancer. However, some patients affected with squamous cell carcinoma (SCC) do not respond adequately to PDT with methyl-δ-aminolevulinic acid (MAL-PDT) and the tumors acquire an infiltrative phenotype and became histologically more aggressive, less differentiated, and more fibroblastic. To search for potential factors implicated in SCC resistance to PDT, we have used the SCC-13 cell line (parental) and resistant SCC-13 cells obtained by repeated MAL-PDT treatments (5th and 10th PDT-resistant generations). Xenografts assays in immunodeficient mice showed that the tumors generated by resistant cells were bigger than those induced by parental cells. Comparative genomic hybridization array (aCGH) showed that the three cell types presented amplicons in 3p12.1 CADM2, 7p11.2 EFGR, and 11q13.3 CCND1 genes. The 5th and 10th PDT-resistant cells showed an amplicon in 5q11.2 MAP3K1, which was not present in parental cells. The changes detected by aCGH on CCND1, EFGR, and MAP3K1 were confirmed in extracts of SCC-13 cells by reverse-transcriptase PCR and by western blot, and by immunohistochemistry in human biopsies from persistent tumors after MAL-PDT. Our data suggest that genomic imbalances related to CCND1, EFGR, and particularly MAP3K1 seem to be involved in the development of the resistance of SCC to PDT.

  4. Taxotere resistance in SUIT Taxotere resistance in pancreatic carcinoma cell line SUIT 2 and its sublines

    Institute of Scientific and Technical Information of China (English)

    Bin Liu; Edgar Staren; Takeshi Iwamura; Hubert Appert; John Howard

    2001-01-01

    AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC). METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and its sublines (S-007, S-013, S-020,S-028 and TXT selected SUIT-2 cell line, S2/TXT) to TXT.Mdr1 (P-gp), multidrug resistance associated protein (MRP), lung resistance protein (LRP) and β-tubulin isotype gene expressions were detected by RT-PCR. The functionality of P-gp and MRP was tested using their specific blocker verapamil ( Ver ) and indomethacin ( IMC ),respectively. The transporter activity of P-gp was also confirmed by Rhodamine 123 accumulation assay. RESULTS: S-020 and S2/TXT were found to be significantly resistant to TXT(19 and 9.5-fold to their parental cell line SUIT-2, respectively ). RT-PCR demonstrated strong expression of Mdr1 in these two cell lines, but weaker expression or no expression in other cells lines. MRP and LRP expressions were found in most of these cell lines. The TXT-resistance in S2-020 and S2/TXT could be reversed almost completely by Ver, but not by IMC. Flow cytometry showed that Ver increased the accumulation of Rhodamine-123 in these two cell lines. Compared with S-020 and SUIT-2,the levels of β-tubulin isotype II, III expreesions in S-2/TXTwere increased remarkably. CONCLUSION: The both intrinsic and acquired TXT-related drugresistance in these PAC cell lines is mainly mediated by P-gp, but had no relationship to MRP and LRP expressions.The increases of β-tubulin isotype II, III might be collateral changes that occur when the SUIT-2 cells are treated with TXT.

  5. Overexpression of β-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Li, Long; Liu, Hai-Chao; Wang, Cheng; Liu, Xiqiang; Hu, Feng-Chun; Xie, Nan; Lü, Lanhai; Chen, Xiaohua; Huang, Hong-Zhang

    2016-01-01

    Abnormal expression of β-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression of β-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect of β-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines with β-catenin knockin and knockdown. In this study, we found that higher expression level of β-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels of β-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation of β-catenin could also be observed by confocal microscope analysis. Stable cell lines with CTNNB1 knockin and knockdown were established to further investigate the potential role and mechanism of β-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression of β-catenin promoted cisplatin resistance in OSCC in vitro and in vivo. We confirmed that GSK-3β, C-myc, Bcl-2, P-gp, and MRP-1 were involved in β-catenin-mediated drug resistance. Our findings indicate that the Wnt/β-catenin signaling pathway may play important roles in cisplatin resistance in OSCC. PMID:27529071

  6. Arsenite-loaded nanoparticles inhibit PARP-1 to overcome multidrug resistance in hepatocellular carcinoma cells.

    Science.gov (United States)

    Liu, Hanyu; Zhang, Zongjun; Chi, Xiaoqin; Zhao, Zhenghuan; Huang, Dengtong; Jin, Jianbin; Gao, Jinhao

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the highest incidences in cancers; however, traditional chemotherapy often suffers from low efficiency caused by drug resistance. Herein, we report an arsenite-loaded dual-drug (doxorubicin and arsenic trioxide, i.e., DOX and ATO) nanomedicine system (FeAsOx@SiO2-DOX, Combo NP) with significant drug synergy and pH-triggered drug release for effective treatment of DOX resistant HCC cells (HuH-7/ADM). This nano-formulation Combo NP exhibits the synergistic effect of DNA damage by DOX along with DNA repair interference by ATO, which results in unprecedented killing efficiency on DOX resistant cancer cells. More importantly, we explored the possible mechanism is that the activity of PARP-1 is inhibited by ATO during the treatment of Combo NP, which finally induces apoptosis of HuH-7/ADM cells by poly (ADP-ribosyl) ation suppression and DNA lesions accumulation. This study provides a smart drug delivery strategy to develop a novel synergistic combination therapy for effectively overcome drug- resistant cancer cells. PMID:27484730

  7. Arsenite-loaded nanoparticles inhibit PARP-1 to overcome multidrug resistance in hepatocellular carcinoma cells

    Science.gov (United States)

    Liu, Hanyu; Zhang, Zongjun; Chi, Xiaoqin; Zhao, Zhenghuan; Huang, Dengtong; Jin, Jianbin; Gao, Jinhao

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the highest incidences in cancers; however, traditional chemotherapy often suffers from low efficiency caused by drug resistance. Herein, we report an arsenite-loaded dual-drug (doxorubicin and arsenic trioxide, i.e., DOX and ATO) nanomedicine system (FeAsOx@SiO2-DOX, Combo NP) with significant drug synergy and pH-triggered drug release for effective treatment of DOX resistant HCC cells (HuH-7/ADM). This nano-formulation Combo NP exhibits the synergistic effect of DNA damage by DOX along with DNA repair interference by ATO, which results in unprecedented killing efficiency on DOX resistant cancer cells. More importantly, we explored the possible mechanism is that the activity of PARP-1 is inhibited by ATO during the treatment of Combo NP, which finally induces apoptosis of HuH-7/ADM cells by poly (ADP-ribosyl) ation suppression and DNA lesions accumulation. This study provides a smart drug delivery strategy to develop a novel synergistic combination therapy for effectively overcome drug- resistant cancer cells. PMID:27484730

  8. Giant Lysosomes as a Chemotherapy Resistance Mechanism in Hepatocellular Carcinoma Cells.

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    Federico Colombo

    Full Text Available Despite continuous improvements in therapeutic protocols, cancer-related mortality is still one of the main problems facing public health. The main cause of treatment failure is multi-drug resistance (MDR: simultaneous insensitivity to different anti-cancer agents, the underlying molecular and biological mechanisms of which include the activity of ATP binding cassette (ABC proteins and drug compartmentalisation in cell organelles. We investigated the expression of the main ABC proteins and the role of cytoplasmic vacuoles in the MDR of six hepatocellular carcinoma (HCC cell lines, and confirmed the accumulation of the yellow anti-cancer drug sunitinib in giant (four lines and small cytoplasmic vacuoles of lysosomal origin (two lines. ABC expression analyses showed that the main ABC protein harboured by all of the cell lines was PGP, whose expression was not limited to the cell membrane but was also found on lysosomes. MTT assays showed that the cell lines with giant lysosomes were more resistant to sorafenib treatment than those with small lysosomes (p<0.01, and that verapamil incubation can revert this resistance, especially if it is administered after drug pre-incubation. The findings of this study demonstrate the involvement of PGP-positive lysosomes in drug sequestration and MDR in HCC cell lines. The possibility of modulating this mechanism using PGP inhibitors could lead to the development of new targeted strategies to enhance HCC treatment.

  9. CD40L induces multidrug resistance to apoptosis in breast carcinoma and lymphoma cells through caspase independent and dependent pathways

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    Blay Jean-Yves

    2006-03-01

    Full Text Available Abstract Background CD40L was found to reduce doxorubicin-induced apoptosis in non Hodgkin's lymphoma cell lines through caspase-3 dependent mechanism. Whether this represents a general mechanism for other tumor types is unknown. Methods The resistance induced by CD40L against apoptosis induced by a panel of cytotoxic chemotherapeutic drugs in non Hodgkin's lymphoma and breast carcinoma cell lines was investigated. Results Doxorubicin, cisplatyl, etoposide, vinblastin and paclitaxel increased apoptosis in a dose-dependent manner in breast carcinoma as well as in non Hodgkin's lymphoma cell lines. Co-culture with irradiated L cells expressing CD40L significantly reduced the percentage of apoptotic cells in breast carcinoma and non Hodgkin's lymphoma cell lines treated with these drugs. In breast carcinoma cell lines, these 5 drugs induced an inconsistent increase of caspase-3/7 activity, while in non Hodgkin's lymphoma cell lines all 5 drugs increased caspase-3/7 activity up to 28-fold above baseline. Co-culture with CD40L L cells reduced (-39% to -89% the activation of caspase-3/7 induced by these agents in all 5 non Hodgkin's lymphoma cell lines, but in none of the 2 breast carcinoma cell lines. Co culture with CD40L L cells also blocked the apoptosis induced by exogenous ceramides in breast carcinoma and non Hodgkin's lymphoma cell lines through a caspase-3-like, 8-like and 9-like dependent pathways. Conclusion These results indicate that CD40L expressed on adjacent non tumoral cells induces multidrug resistance to cytotoxic agents and ceramides in both breast carcinoma and non Hodgkin's lymphoma cell lines, albeit through a caspase independent and dependent pathway respectively.

  10. Co-cultivation of murine BMDCs with 67NR mouse mammary carcinoma cells give rise to highly drug resistant cells

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    Zänker Kurt S

    2011-06-01

    Full Text Available Abstract Background Tumor tissue resembles chronically inflamed tissue. Since chronic inflammatory conditions are a strong stimulus for bone marrow-derived cells (BMDCs it can be assumed that recruitment of BMDCs into cancer tissue should be a common phenomenon. Several data have outlined that BMDC can influence tumor growth and metastasis, e.g., by inducing a paracrine acting feedback loop in tumor cells. Likewise, cell fusion and horizontal gene transfer are further mechanisms how BMDCs can trigger tumor progression. Results Hygromycin resistant murine 67NR-Hyg mammary carcinoma cells were co-cultivated with puromycin resistant murine BMDCs from Tg(GFPU5Nagy/J mice. Isolation of hygromycin/puromycin resistant mBMDC/67NR-Hyg cell clones was performed by a dual drug selection procedure. PCR analysis revealed an overlap of parental markers in mBMDC/67NR-Hyg cell clones, suggesting that dual resistant cells originated by cell fusion. By contrast, both STR and SNP data analysis indicated that only parental 67NR-Hyg alleles were found in mBMDC/67NR-Hyg cell clones favoring horizontal gene transfer as the mode of origin. RealTime-PCR-array analysis showed a marked up-regulation of Abcb1a and Abcb1b ABC multidrug transporters in mBMDC/67NR-Hyg clones, which was verified by Western Blot analysis. Moreover, the markedly increased Abcb1a/Abcb1b expression was correlated to an efficient Rhodamine 123 efflux, which was completely inhibited by verapamil, a well-known Abcb1a/Abcb1b inhibitor. Likewise, mBMDCs/67NR-Hyg clones revealed a marked resistance towards chemotherapeutic drugs including 17-DMAG, doxorubicin, etoposide and paclitaxel. In accordance to Rhodamine 123 efflux data, chemotherapeutic drug resistance of mBMDC/67NR-Hyg cells was impaired by verapamil mediated blockage of Abc1a/Abcb1b multidrug transporter function. Conclusion Co-cultivation of mBMDCs and mouse 67NR-Hyg mammary carcinoma cells gave rise to highly drug resistant cells. Even

  11. Basal Cell Carcinoma (BCC)

    Science.gov (United States)

    ... epithelioma, is the most common form of skin cancer. Basal cell carcinoma usually occurs on sun-damaged skin, especially ... other health issues. Infiltrating or morpheaform basal cell carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive ...

  12. HYPERTHERMIC POTENTIATION OF CISPLATIN TOXICITY IN A HUMAN SMALL-CELL LUNG-CARCINOMA CELL-LINE AND A CISPLATIN-RESISTANT SUBLINE

    NARCIS (Netherlands)

    HETTINGA, JVE; LEMSTRA, W; MEIJER, C; MULDER, NH; KONINGS, AWT; DEVRIES, EGE; KAMPINGA, HH

    1994-01-01

    A human small cell lung carcinoma cell line (GLC4) and its subline with in vitro acquired cisplatin (cDDP) resistance (GLC4-cDDP) were used to study the applicability of hyperthermia to interfere with acquired cDDP resistance. GLC4 and GLC4-cDDP did not differ in heat sensitivity (clonogenic ability

  13. Establishment of hepatocellular carcinoma multidrug resistant monoclone cell line HepG2/mdr1

    Institute of Scientific and Technical Information of China (English)

    CHEN Yong-bing; XIE Jian-guo; YANG Jia-yin; YAN Lü-nan; YAN Mao-lin; GONG Jian-ping; XIA Ren-pin; LIU Li-xin; LI Ning; LU Shi-chun; ZHANG Jing-guang; ZENG Dao-bing

    2007-01-01

    Background The multidrug resistance (MDR) associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell (HCC) patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1.Methods The 4.5-kb mdr1 cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCI-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein (Pgp) in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated.Results The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed.The PCR analysis showed that the specific fragment of mdr1 cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were (59.7±7.9)% and (12.28±2.09)%, respectively, compared with (16.9±3.2)% and (3.07±1.06)% in HepG2 cells.In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours.Conclusion The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the

  14. Effects of autophagy on multidrug resistance of drug resistant LoVo/Adr cells of colon carcinoma

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    Qiang MA

    2013-11-01

    Full Text Available Objective To observe the effects of autophagy on multidrug resistance (MDR of drug resistant LoVo/Adr cells of colon carcinoma. Methods The formation of autophagosomes was monitored with transmission electron microscopy, and autophagy rate was measured with the aid of MDC staining and flow cytometry. IC50 value of adriamycin (ADR on colon carcinoma cells was detected by MTT assay. The mRNA level of MDR1 gene was measured by RT-PCR, and P-gp protein expression was detected by Western blotting. Results The sporadic autophagosomes or green epoptic dots were found to distribute in LoVo/Adr cells with an autophagy rate of 3.1%±0.5%. A large number of autophagosomes were seen after being treated with ADR or rapamycin (RAPA with the autophagy rates of 33.6%±5.1% and 45.2%±6.1%, respectively (P<0.05. After being treated with ADR combining RAPA, autophagosomes appeared abundantly with an autophagy rate of 76.2%±7.4%, which was significantly higher than that when treated with ADR or RAPA alone (P<0.05. The IC50 value of LoVo/Adr cells on ADR was 3.05±0.52mg/L, which decreased to 1.12±0.21mg/L after being treated with RAPA (P<0.01. RAPA could reverse MDR with a reversal ratio of 2.26. High expression of mRNA and protein of MDR1 gene were observed in LoVo/Adr cells. When treated with RAPA, the expression of MDR1 mRNA decreased from 1.42±0.31 to 0.54±0.20 (P<0.05, and the expression of P-gp protein also decreased significantly from 0.67±0.14 to 0.15±0.08 (P<0.01. Conclusion MDR LoVo/Adr cell shows a low autophagic activity, and RAPA can reverse MDR by increasing autophagy activity. The reversal path might be related with the increase of cell autophagic death and the decrease in MDR1 gene expression in LoVo/Adr cells. DOI: 10.11855/j.issn.0577-7402.2013.11.007

  15. Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma.

    Science.gov (United States)

    Pricl, Sabrina; Cortelazzi, Barbara; Dal Col, Valentina; Marson, Domenico; Laurini, Erik; Fermeglia, Maurizio; Licitra, Lisa; Pilotti, Silvana; Bossi, Paolo; Perrone, Federica

    2015-02-01

    Basal cell carcinomas (BCCs) and a subset of medulloblastomas are characterized by loss-of-function mutations in the tumor suppressor gene, PTCH1. PTCH1 normally functions by repressing the activity of the Smoothened (SMO) receptor. Inactivating PTCH1 mutations result in constitutive Hedgehog pathway activity through uncontrolled SMO signaling. Targeting this pathway with vismodegib, a novel SMO inhibitor, results in impressive tumor regression in patients harboring genetic defects in this pathway. However, a secondary mutation in SMO has been reported in medulloblastoma patients following relapse on vismodegib to date. This mutation preserves pathway activity, but appears to confer resistance by interfering with drug binding. Here we report for the first time on the molecular mechanisms of resistance to vismodegib in two BCC cases. The first case, showing progression after 2 months of continuous vismodegib (primary resistance), exhibited the new SMO G497W mutation. The second case, showing a complete clinical response after 5 months of treatment and a subsequent progression after 11 months on vismodegib (secondary resistance), exhibited a PTCH1 nonsense mutation in both the pre- and the post-treatment specimens, and the SMO D473Y mutation in the post-treatment specimens only. In silico analysis demonstrated that SMO(G497W) undergoes a conformational rearrangement resulting in a partial obstruction of the protein drug entry site, whereas the SMO D473Y mutation induces a direct effect on the binding site geometry leading to a total disruption of a stabilizing hydrogen bond network. Thus, the G497W and D473Y SMO mutations may represent two different mechanisms leading to primary and secondary resistance to vismodegib, respectively. PMID:25306392

  16. miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liang [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Tang, Yanping [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Wang, Jian [Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Yan, Zhongjie [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China); Xu, Ruxiang, E-mail: RuxiangXu@yahoo.com [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China)

    2013-06-14

    Highlights: •miR-421 is upregulated in nasopharyngeal carcinoma. •miR-421 induces cell proliferation and apoptosis resistance. •FOXO4 is a direct and functional target of miR-421. -- Abstract: microRNAs have been demonstrated to play important roles in cancer development and progression. Hence, identifying functional microRNAs and better understanding of the underlying molecular mechanisms would provide new clues for the development of targeted cancer therapies. Herein, we reported that a microRNA, miR-421 played an oncogenic role in nasopharyngeal carcinoma. Upregulation of miR-421 induced, whereas inhibition of miR-421 repressed cell proliferation and apoptosis resistance. Furthermore, we found that upregulation of miR-421 inhibited forkhead box protein O4 (FOXO4) signaling pathway following downregulation of p21, p27, Bim and FASL expression by directly targeting FOXO4 3′UTR. Additionally, we demonstrated that FOXO4 expression is critical for miR-421-induced cell growth and apoptosis resistance. Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.

  17. Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

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    de Vries Elisabeth GE

    2011-01-01

    Full Text Available Abstract Background rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5. Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Methods Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. Results SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN

  18. Comparison of the multi-drug resistant human hepatocellular carcinoma cell line Bel-7402/ADM model established by three methods

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    Zhong Xingguo

    2010-08-01

    Full Text Available Abstract Background To compare the biological characteristics of three types of human hepatocellular carcinoma multi-drug resistant cell sub-lines Bel-7402/ADM models established by three methods. Methods Established human hepatocellular carcinoma adriamycin (ADM multi-drug resistant cell sub-lines models Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS by three methods of in vitro concentration gradient increased induction, nude mice liver-implanted induction and subcutaneous-implanted induction respectively. Phase contrast microscopy was used to observe the cells and the MTT (methyl thiazolyl tetrazolium method was used to detect drug resistance of the three different sub-lines of cells. Results The three groups of drug resistant cells, Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS generated cross-resistance to ADM and CDDP (cis-Diaminedichloroplatinum, but showed a significant difference in resistance to Bel-7402 IC50 value (P V, 46 h (Bel-7402/ADML, and 45 h (Bel-7402/ADMS. The excretion rates of ADM were significantly increased compared with the parent cell (34.14% line and were 81.06% (Bel-7402/ADMV, 66.56% (Bel-7402/ADML and 61.56% (Bel-7402/ADMS. Expression of P-gp and MRP in the three groups of resistant cells was significantly enhanced (P P > 0.05. Conclusions Stable resistance was involved in the resistant cell line model established by the above three methods. Liver implantation was a good simulation of human hepatocellular and proved to be an ideal model with characteristics similar to human hepatocellular biology and the pharmacokinetics of anticancer drugs.

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

    Science.gov (United States)

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

    2016-06-01

    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. PMID:27398205

  20. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne – case report and literature review

    OpenAIRE

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P.

    2016-01-01

    Key Clinical Message 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.

  1. Up-regulated manganese superoxide dismutase expression increases apoptosis resistance in human esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    HU Hai; WANG Ming-rong; LUO Man-li; DU Xiao-li; FENG Yan-bin; ZHANG Yu; SHEN Xiao-ming; XU Xin; CAI Yan; HAN Ya-ling

    2007-01-01

    Background Esophageal cancer is one of the most common malignancies in the world.In order to identify the proteins associated with esophageal squamous cell carcinomas(ESCC),we analyzed the protein profiles of ESCC cases with tumor and matched adjacent normal tissues.Methods Two-dimensional electrophoresis(2-DE)was carried out to analyze the protein profiles.Dysregulated protein spots were identified by Matrix-Assisted Laser Desorption Ionization Time-of-Flight(MALDI-TOF)and verified by liquid chromatography/electrospray ionization ion trap-mass spectrometry/mass spectrometry(LC-ESI-IT MS).RT-PCR and immunohistochemistry on tissue microarray were performed to confirm the gene dysregulation in esophageal cancerous tissues.RNA interference (RNAi)was used to knock down the gene expression in ESCC cell lines.Apoptosis assay with annexin V-FITC/PI staining was conducted and cells were analyzed by flow cytometry.Results 2-DE showed that two protein spots with approximate molecular weights and different pl were elevated in 12 out of 18 ESCCs as compared to the corresponding normal tissues.Both the two spots were identified as MnSOD by MALDI-TOF and were verified by LC-ESI-IT MS.MnSOD overexpression was detected in 14 tumors out of 24 cases by RT-PCR and 52 tumors out of 116 cases by immunohistochemistry comparing to normal epithelia.siRNA-mediated silencing of MnSOD in KYSE450 and KYSE150 cell lines revealed that MnSOD protected ESCC cells from apoptosis induced by ultraviolet(UV)and doxorubicin(DOX).Conclusions These findings suggest that there existed two isoforms of MnSOD protein in normal and tumor esophageal tissues.MnSOD was overexpressed in ESCC and its up-regulation in esophageal cancer cells was associated with apoptosis resistance.

  2. 14-3-3σ confers cisplatin resistance in esophageal squamous cell carcinoma cells via regulating DNA repair molecules.

    Science.gov (United States)

    Lai, Kenneth K Y; Chan, Kin Tak; Choi, Mei Yuk; Wang, Hector K; Fung, Eva Y M; Lam, Ho Yu; Tan, Winnie; Tung, Lai Nar; Tong, Daniel K H; Sun, Raymond W Y; Lee, Nikki P; Law, Simon

    2016-02-01

    Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in Asia. Cisplatin is commonly used in chemoradiation for unresectable ESCC patients. However, the treatment efficacy is diminished in patients with established cisplatin resistance. To understand the mechanism leading to the development of cisplatin resistance in ESCC, we compared the proteomes from a cisplatin-resistant HKESC-2R cell line with its parental-sensitive counterpart HKESC-2 to identify key molecule involved in this process. Mass spectrometry analysis detected 14-3-3σ as the most abundant molecule expressed exclusively in HKESC-2R cells, while western blot result further validated it to be highly expressed in HKESC-2R cells when compared to HKESC-2 cells. Ectopic expression of 14-3-3σ increased cisplatin resistance in HKESC-2 cells, while its suppression sensitized SLMT-1 cells to cisplatin. Among the molecules involved in drug detoxification, drug transportation, and DNA repair, the examined DNA repair molecules HMGB1 and XPA were found to be highly expressed in HKESC-2R cells with high 14-3-3σ expression. Subsequent manipulation of 14-3-3σ by both overexpression and knockdown approaches concurrently altered the expression of HMGB1 and XPA. 14-3-3σ, HMGB1, and XPA were preferentially expressed in cisplatin-resistant SLMT-1 cells when compared to those more sensitive to cisplatin. In ESCC patients with poor response to cisplatin-based chemoradiation, their pre-treatment tumors expressed higher expression of HMGB1 than those with response to such treatment. In summary, our results demonstrate that 14-3-3σ induces cisplatin resistance in ESCC cells and that 14-3-3σ-mediated cisplatin resistance involves DNA repair molecules HMGB1 and XPA. Results from this study provide evidences for further work in researching the potential use of 14-3-3σ and DNA repair molecules HMGB1 and XPA as biomarkers and therapeutic targets for ESCC.

  3. The antioxidant protein PARK7 plays an important role in cell resistance to Cisplatin-induced apoptosis in case of clear cell renal cell carcinoma.

    Science.gov (United States)

    Trivedi, Rachana; Dihazi, Gry H; Eltoweissy, Marwa; Mishra, Durga P; Mueller, Gerhard A; Dihazi, Hassan

    2016-08-01

    Clear cell renal cell carcinoma (ccRCC) is the most malignant tumor in the adult kidney. Many factors are responsible for the development and progression of this tumor. Increased reactive oxygen species accumulation and altered redox status have been observed in cancer cells and this biochemical property of cancer cells can be exploited for therapeutic benefits. In earlier work we identified and characterize Protein DJ-1 (PARK7) as an oxidative stress squevenger in renal cells exposed to oxidative stress. To investigate whether the PARK7 or other oxidative stress proteins play a role in the renal cell carcinoma and its sensitivity or resistance to cytostatic drug treatment, differential proteomics analysis was performed with a cell model for clear cell renal carcinoma (Caki-2 and A498). Caki-2 cells were treated with cisplatin and differentially expressed proteins were investigated. The cisplatin treatment resulted in an increase in reactive oxygen species accumulation and ultimately apoptosis of Caki-2 and A498 cells. In parallel, the apoptotic effect was accompanied by a significant downregulation of antioxidant proteins especially PARK7. Knockdown of PARK7 using siRNA and overexpression using plasmid highlights the role of PARK7 as a key player in renal cell carcinoma response to cisplatin induced apoptosis. Overexpression of PARK7 resulted in significant decrease in apoptosis, whereas knockdown of the protein was accompanied by an increase in apoptosis in Caki-2 and A498 cells treated with cisplatin. These results highlights for the first time the important role of PARK7 in cisplatin induced apoptosis in clear renal cell carcinoma cells. PMID:27112662

  4. Adenovirus-mediated ING4 expression reduces multidrug resistance of human gastric carcinoma cells in vitro and in vivo.

    Science.gov (United States)

    Mao, Zong-Lei; He, Song-Bing; Sheng, Wei-Hua; Dong, Xiao-Qiang; Yang, Ji-Cheng

    2013-11-01

    Chemotherapy is the primary treatment for both resectable and advanced gastric carcinoma, yet multiple drug resistance (MDR) of gastric carcinoma remains a significant therapeutic obstacle. The development of novel strategies to reduce MDR in gastric carcinoma would yield a better outcome following chemotherapy. ING4, a member of the inhibitor of growth (ING) tumor-suppressor family, possesses antitumor and radiosensitization or chemosensitization effects in a variety of human cancers. The present study investigated the effects and possible mechanisms of action of adenovirus-mediated ING4 (AdVING4) on the reversion of human gastric carcinoma cell MDR in vitro and in vivo in nude mouse xenografts. The data showed that the expression of ING4 mRNA and protein was dramatically downregulated (or lost) in gastric carcinoma SGC7901/CDDP cells after CDDP-induced MDR phenotype and in the parental SGC7901 cells. AdVING4‑induced ING4 expression reversed MDR and induced apoptosis of SGC7901/CDDP cells in vitro and in vivo in the SGC7901/CDDP xenograft tumors. Furthermore, AdVING4 substantially downregulated the expression of MDR-related proteins P-gp and MRP1 and apoptosis‑related proteins Bcl-2 and survivin, but upregulated the expression of apoptosis-related protein Bax in the SGC7901/CDDP xenograft tissues. The reversion effects elicited by AdVING4 on gastric cancer cell MDR were closely associated with the downregulation of ATP-binding cassette transporters and activation of apoptotic pathways. Thus, these findings suggest that AdVING4 may be a feasible modulator for the MDR phenotype of gastric carcinoma cells. PMID:23969950

  5. Nevoid Basal Cell Carcinoma Syndrome

    Science.gov (United States)

    ... Nevoid Basal Cell Carcinoma Syndrome Request Permissions Nevoid Basal Cell Carcinoma Syndrome Approved by the Cancer.Net Editorial Board , 04/2016 What is Nevoid Basal Cell Carcinoma Syndrome? Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is ...

  6. Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in oesophageal squamous cell carcinoma

    OpenAIRE

    Yamasaki, M; Makino, T; Masuzawa, T; Kurokawa, Y.; Miyata, H.; Takiguchi, S; K. Nakajima; Fujiwara, Y.; Matsuura, N; M. Mori; Doki, Y

    2011-01-01

    Background: Although multidrug resistance protein 2 (MRP2) confers chemoresistance in some cancer types, its implication on oesophageal squamous cell carcinoma (ESCC) remains unclear. Methods: We evaluated MRP2 expression by immunohistochemistry and RT–PCR using 81 resected specimens from ESCC patients who did or did not receive neo-adjuvant chemotherapy (NACT), including 5-fluorouracil, doxorubicin, and cisplatin (CDDP). Correlation between MRP2 expression and response to chemotherapy was al...

  7. ESTABLISHMENT OF INTRAPERITONEAL TRANSPLANTATION MODEL OF CISPLATIN-RESISTANT OVARIAN CARCINOMA CELL IN SCID MICE

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui; ZHAO Qun; ZUO Lian-fu; WANG Xiao-ling; WANG Yong-jun; JIA Jin-hua; KANG Shan

    2006-01-01

    Objective: to develop an intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP cell in severe combined immunodeficiency (SCID) mouse and to study its biologic characteristics. Methods: Sixteen qualified C.B17/SCID mouse were divided into two groups randomly. Human ovarian carcinoma SKOV3 or SKOV3/CDDP cells were injected intraperitoneally into the SCID mouse at the amount of 1×107 cells (0.5 mL) per mouse. The behaviors of mice,tumor growth and morphology were analyzed. The expression of cancer antigen 125 (CA125), GST-π and Topo-Ⅱ were examined by immunohistochemical method. Results: In this experimental study, transplanted tumors are formed in 100%SCID mice in the two groups. The morphology, growth pattern and CA125 secretion of SKOV3/CDDP group were as same as those of SKOV3 group. It shows that the tumors of the two groups kept the characteristics of ovaries serosity papillary adenocarcinoma. Compared with SKOV3 group, the expression of GST-π and Topo-Ⅱ gene in SKOV3/CDDP group were significantly higher (P<0.05). Conclusion: An intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP in SCID mice has been developed successfully. It may be an ideal animal model for biotherapy research of ovarian carcinoma as it can simulate the biological behavior of peritoneal metastasis of human ovarian carcinoma and the drug tolerance is maintained.

  8. Magnesium homeostasis in colon carcinoma LoVo cells sensitive or resistant to doxorubicin.

    Science.gov (United States)

    Castiglioni, Sara; Cazzaniga, Alessandra; Trapani, Valentina; Cappadone, Concettina; Farruggia, Giovanna; Merolle, Lucia; Wolf, Federica I; Iotti, Stefano; Maier, Jeanette A M

    2015-11-13

    Neoplastic cells accumulate magnesium, an event which provides selective advantages and is frequently associated with TRPM7 overexpression. Little is known about magnesium homeostasis in drug-resistant cancer cells. Therefore, we used the colon cancer LoVo cell model and compared doxorubicin-resistant to sensitive cells. In resistant cells the concentration of total magnesium is higher while its influx capacity is lower than in sensitive cells. Accordingly, resistant cells express lower amounts of the TRPM6 and 7, both involved in magnesium transport. While decreased TRPM6 levels are due to transcriptional regulation, post-transcriptional events are involved in reducing the amounts of TRPM7. Indeed, the calpain inhibitor calpeptin markedly increases the levels of TRPM7 in resistant cells. In doxorubicin-sensitive cells, silencing TRPM7 shifts the phenotype to one more similar to resistant cells, since in these cells silencing TRPM7 significantly decreases the influx of magnesium, increases its intracellular concentration and increases resistance to doxorubicin. On the other hand, calpain inhibition upregulates TRPM7, decreases intracellular magnesium and enhances the sensitivity to doxorubicin of resistant LoVo cells. We conclude that in LoVo cells drug resistance is associated with alteration of magnesium homeostasis through modulation of TRPM7. Our data suggest that TRPM7 expression may be an additional undisclosed player in chemoresistance.

  9. Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Sheng-Dean Luo

    2015-01-01

    Full Text Available Background. Osteopontin (OPN is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC in humans has not yet been investigated. Methods. We enrolled 121 patients with locally advanced stage IVA/B OSCC receiving cisplatin-based IC followed by CCRT from January 1, 2006, through January 1, 2012. Immunohistochemistry was used to assess OPN expression in OSCC patients’ biopsy specimens from paraffin blocks before treatment. In addition, MTT/colony formation assay was used to estimate the influence of OPN in an oral cancer cell line treated with cisplatin. Results. Of the 121 patients, 94 had positive OPN findings and 52 responded to IC followed by CCRT. Positive osteopontin immunostaining also correlated significantly with positive N status/TNM stage/male gender and smoking. Univariate analyses showed that patients whose tumors had a low expression of OPN were more likely to respond to chemotherapy and have a significantly better OS than those whose tumors had a high expression of OPN. Multivariate analysis revealed that prolonged survival was independently predicted for patients with stage IVA disease, negative lymph nodes, and negative expressions of OPN and for those who received chemotherapy with Docetaxel/cisplatin/fluorouracil (TPF. An oral cancer line stimulated with OPN exhibited a dose-dependent resistance to cisplatin treatment. Conversely, endogenous OPN depletion by OPN-mediated shRNA increased sensitivity to cisplatin. Conclusions. A positive expression of OPN predicts a poor response and survival in patients with locally advanced stage IVA/B OSCC treated with cisplatin-based IC followed by CCRT.

  10. Reduced membrane protein associated with resistance of human squamous carcinoma cells to methotrexate and cis-platinum.

    Science.gov (United States)

    Bernal, S D; Speak, J A; Boeheim, K; Dreyfuss, A I; Wright, J E; Teicher, B A; Rosowsky, A; Tsao, S W; Wong, Y C

    1990-06-01

    A membrane protein recognized by monoclonal antibody SQM1 was identified in human squamous carcinomas, including those originating in the head and neck (SqCHN), lung and cervix. Cell lines derived from SqCHN of previously untreated patients expressed high amounts of this protein. In contrast, many cell lines established from SqCHN of patients previously treated with chemotherapy and/or radiation showed diminished amounts of this SQM1 protein. The expression of SQM1 antigen was determined in several SqCHN cell lines made resistant by exposure to methotrexate (MTX) in vitro. The parent cell lines all exhibited strong binding to SQM1 antibody. The MTX-resistant sublines showed much lower membrane binding of SQM1. The lowest SQM1 reactivity was found in cell lines with high resistance to MTX and with diminished rate of MTX transport. Some highly MTX-resistant cell lines which had high levels of dihydrofolate reductase, but which retained a high rate of MTX transport, also retained high levels of SQM1 binding. Reduced SQM1 protein was also found in SqCHN cells which developed resistance to the alkylating drug cis-latinum (CDDP) and which showed reduced membrane transport of CDDP. Cell growth kinetics and non-specific antigenic shifts were not responsible for the differences in SQM1 binding between the parent cell lines and their drug-resistant sublines. The finding of a novel protein which is reduced in cells resistant to MTX and CDDP could contribute to our understanding of the basic mechanisms of drug resistance. By detecting SQM1 protein in clinical specimens, it may be possible to monitor the development of drug resistance in tumors. PMID:2195318

  11. Cervical squamous carcinoma cells are resistant to the combined action of tumor necrosis factor-α and histamine whereas normal keratinocytes undergo cytolysis

    International Nuclear Information System (INIS)

    Previous reports showed that mast cells can typically be found in the peritumoral stroma of cervix carcinomas as well as in many other cancers. Both histamine and TNF-α are potent preformed mast cell mediators and they can act simultaneously after release from mast cells. Thus, the effect of TNF-α and histamine on cervical carcinoma cell lines was studied. TNF-α alone induced slight growth inhibition and cell cycle arrest at G0/G1 phase in SiHa cells, but increased their migration. Histamine alone had no effect on cells. In addition, TNF-α and histamine in combination showed no additional effect over that by TNF-α alone, although SiHa cells were even pretreated with a protein synthesis inhibitor. Furthermore, TNF-α-sensitive ME-180 carcinoma cells were also resistant to the combination effect of TNF-α and histamine. In comparison, TNF-α or histamine alone induced growth inhibition in a non-cytolytic manner in normal keratinocytes, an effect that was further enhanced to cell cytolysis when both mediators acted in combination. Keratinocytes displayed strong TNF receptor (TNFR) I and II immunoreactivity, whereas SiHa and ME-180 cells did not. Furthermore, cervix carcinoma specimens revealed TNF-α immunoreactivity in peritumoral cells and carcinoma cells. However, the immunoreactivity of both TNFRs was less intense in carcinoma cells than that in epithelial cells in cervical specimens with non-specific inflammatory changes. SiHa and ME-180 cells are resistant to the cytolytic effect of TNF-α and histamine whereas normal keratinocytes undergo cytolysis, possibly due to the smaller amount of TNFRs in SiHa and ME-180 cells. In the cervix carcinoma, the malignant cells may resist this endogenous cytolytic action and TNF-α could even enhance carcinoma cell migration

  12. Apoptosis of drug-resistant human ovarian carcinoma cell line COC1/DDP induced by survivin antisense oligonucleotides

    Institute of Scientific and Technical Information of China (English)

    ZHENG Fei; RUAN Fei; XIE Xian-kuan; LIU Shao-yang

    2006-01-01

    @@ Currently, surgery-oriented treatment plays a major role in the treatment of ovarian cancer patients. But 5-year survival rate of patients is still around 30%. One of the main reasons for the Iow survival rate is the drug resistance of tumor cells against chemotherapy.1,2 The function of antiapoptosis in the course of initiation and progress of cancer has a close relationship with drug resistance of tumor cells. Survivin is a new discovered anti-apoptosis gene, its expression levels correlating with more aggressive disease and poor clinical outcome in many of these tumors. It has been reported that survivin is expressed during fetal development and in cancer tissues.3 Furthermore,survivin overexpression, by disrupting the balance between cell proliferation/differentiation and apoptosis, may relate with the resistance to a variety of apoptotic stimuli, including chemotherapy.4,5 We designed antisense oligonucleotides of survivin to treat the drug-resistant human ovarian carcinoma cell line COC1/DDP, and studied its effects on inducing COC1/DDP apoptosis. The purpose of this study was to find a novel approach to improve the sensitivity of ovarian carcinoma chemotherapy.

  13. The Enhanced metastatic potential of hepatocellular carcinoma (HCC cells with sorafenib resistance.

    Directory of Open Access Journals (Sweden)

    Ariel Ka-Man Chow

    Full Text Available Acquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3 were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs in SorR cells. Control (CTL and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44(+ and CD44(+CD133(+ cells were also observed in SorR cells. All (8/8 mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib.

  14. RNA interference-mediated hTERT inhibition enhances TRAIL-induced apoptosis in resistant hepatocellular carcinoma cells.

    Science.gov (United States)

    Zhang, Ru-Gang; Zhao, Jing-Jing; Yang, Liu-Qin; Yang, Shi-Ming; Wang, Rong-Quan; Chen, Wen-Sheng; Peng, Gui-Yong; Fang, Dian-Chun

    2010-04-01

    TRAIL has been reported to induce apoptosis in a variety of tumor cell types including hepato-cellular carcinoma (HCC) cell lines. However, considerable numbers of HCC cells, especially some highly malignant tumors, show resistance to TRAIL-induced apoptosis. The molecular mechanisms that regulate sensitivity versus resistance of tumor cells to TRAIL-induced apoptosis remain poorly defined. It has been shown that human telomerase catalytic subunit (hTERT) is overexpressed in human HCCs. In this study, we investigated the effects and the mechanisms of hTERT RNAi on the TRAIL-induced apoptosis of HCC cells that exhibit resistance to TRAIL. Our results indicate that hTERT RNAi sensitizes TRAIL-resistant HCC cells to TRAIL-induced apoptosis. hTERT RNAi-mediated sensitization to TRAIL-induced apoptosis is accompanied up-regulation of procaspases-8 and -9, inhibition of telomerase activity and loss of telomere length. Our results suggest that hTERT RNAi overcame the resistance of the HCC cells against TRAIL, at least in part, via the mitochondrial type II apoptosis pathway and telomerase-dependent pathway. PMID:20204286

  15. Proteomic analysis of docetaxel resistance in human nasopharyngeal carcinoma cells using the two-dimensional gel electrophoresis method.

    Science.gov (United States)

    Peng, Xingchen; Gong, Fengming M; Ren, Min; Ai, Ping; Wu, ShaoYong; Tang, Jie; Hu, XiaoLin

    2016-09-01

    Docetaxel-based chemotherapy has been recommended for advanced nasopharyngeal carcinoma (NPC). However, treatment failure often occurs because of acquired drug resistance. In this study, a docetaxel-resistant NPC cell line CNE-2R was established with increasing doses of docetaxel for more than 6 months. Two-dimensional gel electrophoresis and ESI-Q-TOF-MS were used to compare the differential expression of docetaxel-resistance-associated proteins between human NPC CNE-2 cells and docetaxel-resistant CNE-2R cells. As a result, 24 differentially expressed proteins were identified, including 11 proteins with increased expression and 13 proteins with decreased expression. These proteins function in diverse biological processes such as metabolism, signal transduction, calcium ion binding, immune response, proteolysis, and so on. Among these, α-enolase (ENO1), significantly upregulated in CNE-2R, was selected for detailed analysis. Inhibition of ENO1 by shRNA restored CNE-2R cells' sensitivity to docetaxel. Moreover, overexpression of ENO1 could facilitate the development of acquired resistance of docetaxel in CNE-2 cells. Western blot and reverse-transcription PCR data of clinical samples confirmed that α-enolase was upregulated in docetaxel-resistant human NPC tissues. Finding such proteins might improve interpretation of the molecular mechanisms leading to the acquisition of docetaxel chemoresistance. PMID:27333594

  16. High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.

    Directory of Open Access Journals (Sweden)

    Michael Boettcher

    Full Text Available Acquired drug resistance represents a frequent obstacle which hampers efficient chemotherapy of cancers. The contribution of aberrant DNA methylation to the development of drug resistant tumor cells has gained increasing attention over the past decades. Hence, the objective of the presented study was to characterize DNA methylation changes which arise from treatment of tumor cells with the chemotherapeutic drug doxorubicin. DNA methylation levels from CpG islands (CGIs linked to twenty-eight genes, whose expression levels had previously been shown to contribute to resistance against DNA double strand break inducing drugs or tumor progression in different cancer types were analyzed. High-definition DNA methylation profiles which consisted of methylation levels from 800 CpG sites mapping to CGIs around the transcription start sites of the selected genes were determined. In order to investigate the influence of CGI methylation on the expression of associated genes, their mRNA levels were investigated via qRT-PCR. It was shown that the employed method is suitable for providing highly accurate methylation profiles, comparable to those obtained via clone sequencing, the gold standard for high-definition DNA methylation studies. In breast carcinoma cells with acquired resistance against the double strand break inducing drug doxorubicin, changes in methylation of specific cytosines from CGIs linked to thirteen genes were detected. Moreover, similarities between methylation profiles obtained from breast and ovarian carcinoma cell lines with acquired doxorubicin resistance were found. The expression levels of a subset of analyzed genes were shown to be linked to the methylation levels of the analyzed CGIs. Our results provide detailed DNA methylation information from two separate model systems for acquired doxorubicin resistance and suggest the occurrence of similar methylation changes in both systems upon exposure to the drug.

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

    OpenAIRE

    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 ...

  18. The effect of ephrin-A1 on resistance to Photofrin-mediated photodynamic therapy in esophageal squamous cell carcinoma cells.

    Science.gov (United States)

    Yang, Pei-Wen; Chiang, Tzu-Hsuan; Hsieh, Ching-Yueh; Huang, Ya-Chuan; Wong, Li-Fan; Hung, Mien-Chie; Tsai, Jui-Chang; Lee, Jang-Ming

    2015-12-01

    Esophageal squamous cell carcinoma (ESCC), the most prevalent cell type of esophageal cancer, remains a dismal disease with poor prognosis. Photodynamic therapy (PDT) is a minimally invasive treatment option for early esophageal cancer. To explore possible factors involved in resistance to PDT in esophageal cancer cells, we selected PDT-resistant subcell lines by repeated treatment of CE48T/VGH (CE48T) ESCC cells with Photofrin-PDT and then analyzed the global gene modulations in the PDT-resistant cells by whole-genome microarray. More than 700 genes reached a fold change greater than 1.5 in each of the PDT-resistant cells compared to parental cells. Among these genes, both tumor necrosis factor (TNF) and EFNA1 genes were significantly upregulated in resistant cell lines. However, they were significantly downregulated in Photofrin-PDT-treated cells compared to untreated cells. The observations made in the microarray analysis were further confirmed by quantitative PCR. We observed that recombinant tumor necrosis factor alpha (TNF-α) activated the gene expression of EFNA1 at both the messenger RNA (mRNA) level and the protein level in CE48T cells. Functional analysis showed that when incubated with oligomeric and monomeric ephrin-A1 simultaneously, ESCC cells became significantly resistant to Photofrin-PDT. Functional analysis further suggested that transmembrane and soluble ephrin-A1 may cooperate to enhance resistance to Photofrin-PDT in ESCC cells.

  19. Resistance of renal cell carcinoma to sorafenib is mediated by potentially reversible gene expression.

    Directory of Open Access Journals (Sweden)

    Liang Zhang

    Full Text Available PURPOSE: Resistance to antiangiogenic therapy is an important clinical problem. We examined whether resistance occurs at least in part via reversible, physiologic changes in the tumor, or results solely from stable genetic changes in resistant tumor cells. EXPERIMENTAL DESIGN: Mice bearing two human RCC xenografts were treated with sorafenib until they acquired resistance. Resistant 786-O cells were harvested and reimplanted into naïve mice. Mice bearing resistant A498 cells were subjected to a 1 week treatment break. Sorafenib was then again administered to both sets of mice. Tumor growth patterns, gene expression, viability, blood vessel density, and perfusion were serially assessed in treated vs control mice. RESULTS: Despite prior resistance, reimplanted 786-O tumors maintained their ability to stabilize on sorafenib in sequential reimplantation steps. A transcriptome profile of the tumors revealed that the gene expression profile of tumors upon reimplantation reapproximated that of the untreated tumors and was distinct from tumors exhibiting resistance to sorafenib. In A498 tumors, revascularization was noted with resistance and cessation of sorafenib therapy and tumor perfusion was reduced and tumor cell necrosis enhanced with re-exposure to sorafenib. CONCLUSIONS: In two RCC cell lines, resistance to sorafenib appears to be reversible. These results support the hypothesis that resistance to VEGF pathway therapy is not solely the result of a permanent genetic change in the tumor or selection of resistant clones, but rather is due to a great extent to reversible changes that likely occur in the tumor and/or its microenvironment.

  20. Technetium-99m sestamibi uptake in human breast carcinoma cell lines displaying glutathione-associated drug-resistance

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, L. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Oezker, K. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Hayward, M. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Akansel, G. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Griffith, O. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Isitman, A.T. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Hellman, R. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Collier, D. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States)

    1996-05-01

    An in vitro study was designed to evaluate the uptake of sestamibi (MIBI) in P-glycoprotein (Pgp) and glutathione-associated (GSH) multidrug-resistant (MDR) cell lines. MIBI uptake was studied in various human breast carcinoma cell lines, i.e. in wild-type (MCF7/wt) cells, in adriamycin-resistant (MCF7/adr) cells which express Pgp and in melphalan-resistant (MCF7/mph) cells with increased levels of GSH. The effects of buthiomine sulphoximine (BSO) and verapamil on MIBI uptake were also studied in the MCF7/mph and MCF7/adr cells respectively. The cells were incubated for 1 h with a dose of 0.1 MBq thallium-201 and technetium-99m MIBI. Both BIBI and {sup 201}Tl uptakes were higher for MCF7/mph cells than for the other cells studied. The mean MIBI uptake in MCF7/adr cells was significantly lower than that in MCF7/wt cells (1.9%{+-}0.5% vs 3.1%.0.6%; P<0.01). Verapamil treatment increased the MIBI uptake in MCF7/adr cells (to 2.6%.0.3%; P<0.05). Treatment of MCF7/mph cells with BSO resulted in a significant reduction in GSH content (from 243.2{+-}81.1 nmol/mg protein to 17.6{+-}4.4 nmol/mg protein; P<0.001). However, MIBI uptake in BSO-treated and untreated MCF7/mph cells was similar (4.43%{+-}0.5% and 5.93%{+-}1.7%, respectively; P>0.1). This study suggests that the uptake of MIBI is not diminished by glutathione-associated drug resistance and that MIBI uptake in a tumour sample does not necessarly indicate that a cancer is sensitive to drugs. (orig.)

  1. Wild type p53 increased chemosensitivity of drug-resistant human hepatocellular carcinoma Be17402 / 5-FU cells

    Institute of Scientific and Technical Information of China (English)

    Yu-xiuLI; Zhi-binLIN; Huan-ranTAN

    2004-01-01

    AIM: To study the effect of wild type (wt) p53 gene transfection on drug resistant human hepatocellular carcinoma(HCC) cells induced by 5-Fluorouracil (5-FU). METHODS: The cytotoxicity of anticancer drugs on Be17402 and Be17402/5-FU cells was assessed using SRB assay, p53 expression was detected at its mRNA level by RT-PCR assay and at its protein level Western blot or immunocytochemistry assay in Be17402/5-FU cells transfected with either control vector or wt p53. AnnexinV-FITC/PI double labeled assay was performed to detect apoptosis. The chemosensitivity of Be17402/5-FU cells transfected with wt p53 was assessed using SRB assay. RESULTS: Be17402/5-FU cells exhibited cross-resistance to vincristine, doxorubicin, paclitaxel, and so on. wt p53 gene transfection upregulated the expression of p53 in Be17402/5-FU cells, wt p53 was able to greatly inhibit cell proliferation and significantly induce apoptosis in Be17402/5-FU cells. Moreover, wt p53 gene transfection increased the chemosensitivity of Be17402/5-FU cells to some anticancer drugs. CONCLUSION: These results indicated that the wt p53 gene transfection not only induced suppression of cell growth, but also increased the sensitivity of Be17402/5-FU cells to 5-FU, vincristine, and doxorubicin.

  2. Targeting SHP2 for EGFR inhibitor resistant non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Highlights: •SHP2 is required for EGFR inhibitor resistant NSCLC H1975 cell proliferation. •SHP2 inhibitor blocks EGF-stimulated ERK1/2 activation and proliferation. •SHP2 inhibitor exhibits marked anti-tumor activity in H1975 xenograft mice. •SHP2 inhibitor synergizes with PI3K inhibitor in suppressing cell growth. •Targeting SHP2 represents a novel strategy for EGFR inhibitor resistant NSCLCs. -- Abstract: Targeted therapy with inhibitors of epidermal growth factor receptor (EGFR) has produced a noticeable benefit to non-small cell lung cancer (NSCLC) patients whose tumors carry activating mutations (e.g. L858R) in EGFR. Unfortunately, these patients develop drug resistance after treatment, due to acquired secondary gatekeeper mutations in EGFR (e.g. T790M). Given the critical role of SHP2 in growth factor receptor signaling, we sought to determine whether targeting SHP2 could have therapeutic value for EGFR inhibitor resistant NSCLC. We show that SHP2 is required for EGF-stimulated ERK1/2 phosphorylation and proliferation in EGFR inhibitor resistant NSCLC cell line H1975, which harbors the EGFR T790M/L858R double-mutant. We demonstrate that treatment of H1975 cells with II-B08, a specific SHP2 inhibitor, phenocopies the observed growth inhibition and reduced ERK1/2 activation seen in cells treated with SHP2 siRNA. Importantly, we also find that II-B08 exhibits marked anti-tumor activity in H1975 xenograft mice. Finally, we observe that combined inhibition of SHP2 and PI3K impairs both the ERK1/2 and PI3K/AKT signaling axes and produces significantly greater effects on repressing H1975 cell growth than inhibition of either protein individually. Collectively, these results suggest that targeting SHP2 may represent an effective strategy for treatment of EGFR inhibitor resistant NSCLCs

  3. Targeting SHP2 for EGFR inhibitor resistant non-small cell lung carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jie; Zeng, Li-Fan; Shen, Weihua [Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (United States); Turchi, John J. [Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (United States); Department of Medicine, Indiana University School of Medicine, Indianapolis (United States); Zhang, Zhong-Yin, E-mail: zyzhang@iu.edu [Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (United States)

    2013-10-04

    Highlights: •SHP2 is required for EGFR inhibitor resistant NSCLC H1975 cell proliferation. •SHP2 inhibitor blocks EGF-stimulated ERK1/2 activation and proliferation. •SHP2 inhibitor exhibits marked anti-tumor activity in H1975 xenograft mice. •SHP2 inhibitor synergizes with PI3K inhibitor in suppressing cell growth. •Targeting SHP2 represents a novel strategy for EGFR inhibitor resistant NSCLCs. -- Abstract: Targeted therapy with inhibitors of epidermal growth factor receptor (EGFR) has produced a noticeable benefit to non-small cell lung cancer (NSCLC) patients whose tumors carry activating mutations (e.g. L858R) in EGFR. Unfortunately, these patients develop drug resistance after treatment, due to acquired secondary gatekeeper mutations in EGFR (e.g. T790M). Given the critical role of SHP2 in growth factor receptor signaling, we sought to determine whether targeting SHP2 could have therapeutic value for EGFR inhibitor resistant NSCLC. We show that SHP2 is required for EGF-stimulated ERK1/2 phosphorylation and proliferation in EGFR inhibitor resistant NSCLC cell line H1975, which harbors the EGFR T790M/L858R double-mutant. We demonstrate that treatment of H1975 cells with II-B08, a specific SHP2 inhibitor, phenocopies the observed growth inhibition and reduced ERK1/2 activation seen in cells treated with SHP2 siRNA. Importantly, we also find that II-B08 exhibits marked anti-tumor activity in H1975 xenograft mice. Finally, we observe that combined inhibition of SHP2 and PI3K impairs both the ERK1/2 and PI3K/AKT signaling axes and produces significantly greater effects on repressing H1975 cell growth than inhibition of either protein individually. Collectively, these results suggest that targeting SHP2 may represent an effective strategy for treatment of EGFR inhibitor resistant NSCLCs.

  4. Nuclear multidrug-resistance related protein 1 contributes to multidrug-resistance of mucoepidermoid carcinoma mainly via regulating multidrug-resistance protein 1: a human mucoepidermoid carcinoma cells model and Spearman's rank correlation analysis.

    Directory of Open Access Journals (Sweden)

    Bolei Cai

    Full Text Available BACKGROUND: Multidrug resistance-related protein 1 (MRP1/ABCC1 and multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1 are both membrane-bound drug transporters. In contrast to MDR1, MRP1 also transports glutathione (GSH and drugs conjugated to GSH. Due to its extraordinary transport properties, MRP1/ABCC1 contributes to several physiological functions and pathophysiological incidents. We previously found that nuclear translocation of MRP1 contributes to multidrug-resistance (MDR of mucoepidermoid carcinoma (MEC. The present study investigated how MRP1 contributes to MDR in the nuclei of MEC cells. METHODS: Western blot and RT-PCR was carried out to investigate the change of multidrug-resistance protein 1 (MDR1 in MC3/5FU cells after MRP1 was downregulated through RNA interference (RNAi. Immunohistochemistry (IHC staining of 127 cases of MEC tissues was scored with the expression index (EI. The EI of MDR1 and MRP1 (or nuclear MRP1 was analyzed with Spearman's rank correlation analysis. Using multiple tumor tissue assays, the location of MRP1 in other tissues was checked by HIC. Luciferase reporter assays of MDR1 promoter was carried out to check the connection between MRP1 and MDR1 promoter. RESULTS: MRP1 downregulation led to a decreased MDR1 expression in MC3/5FU cells which was caused by decreased activity of MDR1 promoter. IHC study of 127 cases of MEC tissues demonstrated a strong positive correlation between nuclear MRP1 expression and MDR1 expression. Furthermore, IHC study of multiple tumor tissue array sections showed that although nuclear MRP1 widely existed in MEC tissues, it was not found in normal tissues or other tumor tissues. CONCLUSIONS: Our findings indicate that nuclear MRP1 contributes to MDR mainly through regulating MDR1 expression in MEC. And the unique location of MRP1 made it an available target in identifying MEC from other tumors.

  5. Modulation of TRAIL resistance in colon carcinoma cells : Different contributions of DR4 and DR5

    NARCIS (Netherlands)

    van Geelen, Caroline M. M.; Pennarun, Bodvael; Le, Phuong T. K.; de Vries, Elisabeth G. E.; de Jong, Steven

    2011-01-01

    Background: rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether

  6. Embryonic carcinoma cells show specific dielectric resistance profiles during induced differentiation.

    Directory of Open Access Journals (Sweden)

    Simin Öz

    Full Text Available Induction of differentiation in cancer stem cells by drug treatment represents an important approach for cancer therapy. The understanding of the mechanisms that regulate such a forced exit from malignant pluripotency is fundamental to enhance our knowledge of tumour stability. Certain nucleoside analogues, such as 2'-deoxy-5-azacytidine and 1β-arabinofuranosylcytosine, can induce the differentiation of the embryonic cancer stem cell line NTERA 2 D1 (NT2. Such induced differentiation is associated with drug-dependent DNA-damage, cellular stress and the proteolytic depletion of stem cell factors. In order to further elucidate the mode of action of these nucleoside drugs, we monitored differentiation-specific changes of the dielectric properties of growing NT2 cultures using electric cell-substrate impedance sensing (ECIS. We measured resistance values of untreated and retinoic acid treated NT2 cells in real-time and compared their impedance profiles to those of cell populations triggered to differentiate with several established substances, including nucleoside drugs. Here we show that treatment with retinoic acid and differentiation-inducing drugs can trigger specific, concentration-dependent changes in dielectric resistance of NT2 cultures, which can be observed as early as 24 hours after treatment. Further, low concentrations of nucleoside drugs induce differentiation-dependent impedance values comparable to those obtained after retinoic acid treatment, whereas higher concentrations induce proliferation defects. Finally, we show that impedance profiles of substance-induced NT2 cells and those triggered to differentiate by depletion of the stem cell factor OCT4 are very similar, suggesting that reduction of OCT4 levels has a dominant function for differentiation induced by nucleoside drugs and retinoic acid. The data presented show that NT2 cells have specific dielectric properties, which allow the early identification of differentiating

  7. NMR spectroscopy analysis of phosphorus metabolites and the effect of adriamycin on these metabolite levels in an adriamycin-sensitive and -resistant human small cell lung carcinoma cell line

    NARCIS (Netherlands)

    de Jong, Steven; Mulder, N H; de Vries, Liesbeth; Robillard, G T

    1991-01-01

    P-31 nuclear magnetic resonance (NMR) spectra of cells and of cell extracts revealed high levels of phosphorylcholine (PC) and phosphocreatine (PCr) in an adriamycin-resistant human small cell lung carcinoma cell line (GLC4/ADR) and the adriamycin-sensitive parental cell line (GLC4). PCr levels in e

  8. Merkel Cell Carcinoma

    Science.gov (United States)

    ... of the Year Award Arnold P. Gold Foundation Humanism in Medicine Award Diversity Mentorship Program Eugene Van ... 300 PUVA treatments. What causes Merkel cell carcinoma? Scientists are still studying what causes this skin cancer. ...

  9. Endoplasmic reticulum stress is involved in the response of human laryngeal carcinoma cells to Carboplatin but is absent in Carboplatin-resistant cells.

    Directory of Open Access Journals (Sweden)

    Anamaria Brozovic

    Full Text Available The major obstacle of successful tumor treatment with carboplatin (CBP is the development of drug resistance. In the present study, we found that following treatment with CBP the amount of platinum which enters the human laryngeal carcinoma (HEp2-derived CBP-resistant (7T cells is reduced relative to the parental HEp2. As a consequence, the formation of reactive oxidative species (ROS is reduced, the induction of endoplasmic reticulum (ER stress is diminished, the amount of inter- and intrastrand cross-links is lower, and the induction of apoptosis is depressed. In HEp2 cells, ROS scavenger tempol, inhibitor of ER stress salubrinal, as well as gene silencing of ER stress marker CCAAT/enhancer-binding protein (CHOP increases their survival and renders them as resistant to CBP as 7T cell subline but did not influence the survival of 7T cells. Our results suggest that in HEp2 cells CBP-induced ROS is a stimulus for ER stress. To the contrary, despite the ability of CBP to induce formation of ROS and activate ER stress in 7T cells, the cell death mechanism in 7T cells is independent of ROS induction and activation of ER stress. The novel signaling pathway of CBP-driven toxicity that was found in the HEp2 cell line, i.e. increased ROS formation and induction of ER stress, may be predictive for therapeutic response of epithelial cancer cells to CBP-based therapy.

  10. [Merkel cell skin carcinoma].

    Science.gov (United States)

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

    2010-01-01

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

  11. Case of pure ovarian squamous cell carcinoma resistant to combination chemotherapy with paclitaxel and carboplatin but responsive to monotherapy with weekly irinotecan.

    Science.gov (United States)

    Nakamura, Yasuhiko; Kamei, Toshiaki; Shinagawa, Masahiro; Sakamoto, Yuka; Miwa, Ichiro

    2015-05-01

    Primary ovarian squamous cell carcinoma is uncommon, and the optimal treatment strategy for this disease has not yet been established. A 71-year-old woman diagnosed with FIGO stage IIb pure ovarian squamous cell carcinoma underwent cytoreductive surgery followed by combination chemotherapy with paclitaxel and carboplatin. After the second treatment course, a recurrent mass grew rapidly, and serum tumor maker levels increased. Monotherapy with weekly irinotecan was then instituted. This second-line chemotherapy was remarkably effective, and the patient subsequently underwent complete interval debulking surgery with a pathological complete response after the third treatment course. Weekly irinotecan is an effective choice for primary ovarian squamous cell carcinoma resistant to combination chemotherapy with paclitaxel and carboplatin. PMID:25511544

  12. Downregulation of δ opioid receptor by RNA interference enhances the sensitivity of BEL/FU drug-resistant human hepatocellular carcinoma cells to 5-FU

    OpenAIRE

    Tang, Bo; Hu, Zhigao; Li, Yang; YUAN, SHENGGUANG; Wang, Zhenran; Yu, Shuiping; He, Songqing

    2015-01-01

    δ opioid receptor (DOR) was the first opioid receptor of the G protein-coupled receptor family to be cloned. Our previous studies demonstrated that DOR is involved in regulating the development and progression of human hepatocellular carcinoma (HCC), and is involved in the regulation of the processes of invasion and metastasis of HCC cells. However, whether DOR is involved in the development and progression of drug resistance in HCC has not been reported and requires further elucidation. The ...

  13. Activating transcription factor 4 mediates a multidrug resistance phenotype of esophageal squamous cell carcinoma cells through transactivation of STAT3 expression.

    Science.gov (United States)

    Zhu, Hongwu; Chen, Xiong; Chen, Bin; Chen, Bei; Fan, Jianyong; Song, Weibing; Xie, Ziying; Jiang, Dan; Li, Qiuqiong; Zhou, Meihua; Sun, Dayong; Zhao, Yagang

    2014-11-01

    Multidrug resistance (MDR) is a major challenge to the clinical treatment of esophageal cancer. The stress response gene activating transcription factor 4 (ATF4) is involved in homeostasis and cellular protection. However, relatively little is known about the expression and function of ATF4 in esophageal squamous cell carcinoma (ESCC) MDR. In this study, we investigate the potential role and mechanisms of ATF4 in ESCC MDR. We demonstrated that overexpression of ATF4 promotes the MDR phenotype in ESCC cells, while depletion of ATF4 in the MDR ESCC cell line induces drug re-sensitization. We also demonstrated that ATF4 transactivates STAT3 expression by directly binding to the signal transducers and activators of transcription 3 (STAT3) promoter, resulting in MDR in ESCC cells. Significantly, inhibition of STAT3 by small interfering RNA (siRNA) or a selective inhibitor (JSI-124) reintroduces therapeutic sensitivity. In addition, increased Bcl-2, survivin, and MRP1 expression levels were observed in ATF4-overexpressing cells. In conclusion, ATF4 may promote MDR in ESCC cells through the up-regulation of STAT3 expression, and thus is an attractive therapeutic target to combat therapeutic resistance in ESCC.

  14. Extensive disease small cell carcinoma of the lung; trial of non-cross resistant chemotherapy and consolidation radiotherapy

    International Nuclear Information System (INIS)

    Twenty-nine patients with extensive disease, small-cell carcinoma of the lung, were treated with two cycles of intensive combination chemotherapy: HexaVAC (hexamethylmelamine, vincristine, Adriamycin, cyclophosphamide). Responders received prophylactic cranial radiation (2000 rad/10 fractions) and non cross resistant chemotherapy via a schedule of alternating cycles of CMV (cyclophosphamide, methotrexate, VP-16-213) and AMV (Adriamycin, methotrexate, VP-16-213). Whenever a complete response was achieved, consolidation radiotherapy was given to the lung primary (4000 rad/20 fractions, split dose) and abdominal metastases (2000 rad/10 fractions) synchronous with CMV therapy. The complete response rate was 14% with HexaVAC, but increased to 38% during CMV/AMV. Total response rate (complete and partial) was 59% and median survival was 42 weeks. Prophylactic brain radiation prevented clinical relapse in the brain in all 14 patients who received it. However, consolidation radiotherapy failed to prevent clinical relapse in the lung and/or liver, and therapeutic brain radiation (3000 rad) failed to prevent relapse in that site. The simultaneous administration of radiotherapy and chemotherapy was well-tolerated although two patients with poor performance status died of infectious complications while leukopenic. In spite of the high response rate, durable remissions with prolonged disease free survival were rare. Further evaluation of induction, consolidation, and maintenance modes of therapy are indicated

  15. Basal Cell Carcinoma

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... cell carcinoma public SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

  16. Squamous Cell Carcinoma

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... cell carcinoma public SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

  17. Targeting of p38 Mitogen-activated Protein Kinases to Early Growth Response gene 1 (EGR-1) in the Human Paclitaxel-resistance Ovarian Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    Meisong LU; Lan XIAO; Jianli HU; Suo DENG; Yan XU

    2008-01-01

    To investigate the relationship between the expression of early growth response gene 1(EGR-1) and p38MAPK pathway in the paclitaxel resistance of ovarian carcinoma cells, the effect of p38MAPK inhibitor SB203580 on cell apoptosis was examined by using Hoechst 33258 staining.The intracellular Rh123 (Rhodamine 123) accumulation was detected by the flow cytometry (FCM).The 50% inhibition concentration (IC50) of paclitaxel for A2780/Taxol cells was determined by MTT method. Electrophoretic motility shift assay (EMSA) was employed to examine the EGR-1DNA binding activity. MDR1 and EGR-1 mRNA were assessed by RT-PCR. The expressed of p-gp, phosphorylated p53 and p38 were detected by Western blotting. SB203580 could remarkably promote the apoptosis of A2780/Taxol cells, and the cell apoptosis was in a time-dependent manner. Cellular Rh123 accumulation was increased, and the IC50 of paclitaxel for A2780/Taxol cells was decreased significantly. A2780/Taxol cell line after SB203580 treatment was shown to have a significantly higher level of EGR-1 DNA binding activity. SB203580 down-regulated the activity of p38MAPK pathway, but up-regulated EGR-1 expression. SB203580 significantly increased the level of cellular phosphorylated p53 protein, but decreased the p-gp protein level and MDR1 mRNA level in A2780/Taxol cells. There existed a close relationship between p38MAPK pathway and the paclitaxel resistance of ovarian carcinoma cells. The expression of EGR-1 mediated by p38MAPK pathway plays a critical role in paclitaxel resistance of ovarian carcinoma cells.

  18. Regulation of Mucin 1 and multidrug resistance protein 1 by honokiol enhances the efficacy of doxorubicin-mediated growth suppression in mammary carcinoma cells.

    Science.gov (United States)

    Thulasiraman, Padmamalini; Johnson, Andrea Butts

    2016-08-01

    Understanding the link between chemoresistance and cancer progression may identify future targeted therapy for breast cancer. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of multidrug resistance proteins (MRPs). Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for the progression of the disease. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1) which has been implicated in reduced survival rate. The objective of this study was to understand the relationship between MUC1 and MRP1 using natural phenolic compound isolated from Magnolia grandiflora, honokiol, in mammary carcinoma cells. We provide evidence that honokiol suppresses the expression level of MUC1 and MRP1 in mammary carcinoma cells. In a time-dependent manner, honokiol-mediated reduction of MUC1 is followed by a reduction of MRP1 expression in the breast cancer cells. Additionally, silencing MUC1 suppresses the expression level of MRP1 and enhances the efficacy of doxorubicin, an MRP1 substrate. Taken together, these findings suggest MUC1 regulates the expression of MRP1 and provides a direct link between cancer progression and chemoresistance in mammary carcinoma cells. PMID:27221150

  19. Comparision of the Cytotoxic Effects of Birch Bark Extract, Betulin and Betulinic Acid Towards Human Gastric Carcinoma and Pancreatic Carcinoma Drug-sensitive and Drug-Resistant Cell Lines

    Directory of Open Access Journals (Sweden)

    Hermann Lage

    2009-04-01

    Full Text Available Betulin and betulinic acid are naturally occurring pentacyclic triterpenes showing cytotoxicity towards a number of cancer cell lines. These compounds can be found in the bark of the many plants. In this report we have compared the cytotoxic activity of crude birch bark extract and purified betulin and betulinic acid towards human gastric carcinoma (EPG85-257 and human pancreatic carcinoma (EPP85-181 drug-sensitive and drug-resistant (daunorubicin and mitoxantrone cell lines. Our results show significant differences in sensitivity between cell lines depending on the compound used, and suggest that both betulin and betulinic acid can be considered as a promising leads in the treatment of cancer.

  20. Penis squamous cell carcinoma

    OpenAIRE

    Leonor Hernández Piñero; José Luis Rodríguez López; María de Lourdes Menéndez Villa

    2015-01-01

    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 diagn...

  1. Lack of cross-resistance to fostriecin in a human small-cell lung carcinoma cell line showing topoisomerase II-related drug resistance

    NARCIS (Netherlands)

    de Jong, Steven; Zijlstra, J G; Mulder, Nanno; de Vries, Liesbeth

    1991-01-01

    Cells exhibiting decreased topoisomerase II (Topo II) activity are resistant to several drugs that require Topo II as an intermediate. These drugs are cytotoxic due to the formation of a cleavable complex between the drug, Topo II and DNA. Fostriecin belongs to a new class of drugs that inhibit Topo

  2. Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug resistance (study of TP as a MDR reversal agent)

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Aizhi E-mail: zhuaizhi@263.net; Wang Xiangyun; Guo Zhenquan

    2001-08-01

    The aim of this study was to examine MDR1 expression product P-glycoprotein (Pgp) and study the effect and mechanism of tea polyphenol (TP) in reversion of multidrug resistance (MDR) in carcinoma cell lines. Immunocytochemical method was used for qualitative detection of Pgp. A comparative study of cytotoxicity and multidrug resistance reversion effect was made by MTT assay for tea polyphenol and quinidine in MCF-7 and MCF-7/Adr cell lines. The multidrug resistance reversion effect and mechanism were studied by measuring the uptake of {sup 99m}Tc-tetrofosmin in the carcinoma cell lines. (1) The Pgp overexpression in MCF-7/Adr cells was found to be strong positive, while the Pgp expression of MCF-7 was negative. (2) Although both tea polyphenol and quinidine could not remarkably change the toxicity of adriamycin to MCF-7, they could improve the sensitivity of MCF-7/Adr to adriamycin. The reversion index of tea polyphenol and quinidine was 3 and 10 respectively. (3) The cellular uptake of {sup 99m}Tc-tetrofosmin was remarkably lower in MCF-7/Adr than in MCF-7. The uptake of {sup 99m}Tc-tetrofosmin in MCF-7/Adr exhibited a 4, 13, 16 fold increase in the presence of 200, 400 and 500 {mu}g/ml of tea polyphenol respectively. The uptake of {sup 99m}Tc-tetrofosmin in MCF-7/Adr exhibited only a 4-fold increase in the presence of 200 {mu}M of quinidine. Immunocytochemistry can detect P-glycoprotein expression level qualitatively. Tea polyphenol is not only an anti-tumor agent, but also a multidrug resistant modulator similar to quinidine. The multidrug resistance reversion mechanism of tea polyphenol seems to be its inhibition of the activity of P-glycoprotein. Tea polyphenol has the advantage of very low toxicity in tumor treatment.

  3. Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Renal cell carcinoma patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease. METHODS: In this retrospective study the expression of two of these transporter efflux pumps, namely MDR-1 P-gp (ABCB1) and MRP-1 (ABCC1) were studied by immunohistochemistry in archival material from 95 renal cell carcinoma patients. RESULTS: In the first study investigating MDR-1 P-gp and MRP-1 protein expression patterns in renal cell carcinoma patients, high levels of expression of both efflux pumps are observed with 100% of tumours studied showing MDR-1 P-gp and MRP-1 positivity. CONCLUSION: Although these findings do not prove a causal role, the high frequency of tumours expressing these efflux pumps suggests that they may be important contributors to the chemoresistance of this tumour type.

  4. Development of TRAIL Resistance by Radiation-Induced Hypermethylation of DR4 CpG Island in Recurrent Laryngeal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Cheol [Department of Otorhinolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Department of Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Lee, Won Hyeok [Department of Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Min, Young Joo [Department of Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Cha, Hee Jeong [Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Han, Myung Woul [Department of Otorhinolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Chang, Hyo Won [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sun-A [Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Seung-Ho [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Seong Who, E-mail: swhokim@gmail.com [Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sang Yoon, E-mail: sykim3715@gmail.com [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Biomedical Research Institute, Korea Institute of Science and Technology, Seoul (Korea, Republic of)

    2014-04-01

    Purpose: There are limited therapeutic options for patients with recurrent head and neck cancer after radiation therapy failure. To assess the use of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) as a salvage chemotherapeutic agent for recurrent cancer after radiation failure, we investigated the effect of clinically relevant cumulative irradiation on TRAIL-induced apoptosis. Methods and Materials: Using a previously established HN3 cell line from a laryngeal carcinoma patient, we generated a chronically irradiated HN3R isogenic cell line. Viability and apoptosis in HN3 and HN3R cells treated with TRAIL were analyzed with MTS and PI/annexin V-FITC assays. Western blotting and flow cytometry were used to determine the underlying mechanism of TRAIL resistance. DR4 expression was semiquantitatively scored in a tissue microarray with 107 laryngeal cancer specimens. Methylation-specific polymerase chain reaction and bisulfite sequencing for DR4 were performed for genomic DNA isolated from each cell line. Results: HN3R cells were more resistant than HN3 cells to TRAIL-induced apoptosis because of significantly reduced levels of the DR4 receptor. The DR4 staining score in 37 salvage surgical specimens after radiation failure was lower in 70 surgical specimens without radiation treatment (3.03 ± 2.75 vs 5.46 ± 3.30, respectively; P<.001). HN3R cells had a methylated DR4 CpG island that was partially demethylated by the DNA demethylating agent 5-aza-2′-deoxycytidine. Conclusion: Epigenetic silencing of the TRAIL receptor by hypermethylation of a DR4 CpG island might be an underlying mechanism for TRAIL resistance in recurrent laryngeal carcinoma treated with radiation.

  5. Development of TRAIL Resistance by Radiation-Induced Hypermethylation of DR4 CpG Island in Recurrent Laryngeal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Purpose: There are limited therapeutic options for patients with recurrent head and neck cancer after radiation therapy failure. To assess the use of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) as a salvage chemotherapeutic agent for recurrent cancer after radiation failure, we investigated the effect of clinically relevant cumulative irradiation on TRAIL-induced apoptosis. Methods and Materials: Using a previously established HN3 cell line from a laryngeal carcinoma patient, we generated a chronically irradiated HN3R isogenic cell line. Viability and apoptosis in HN3 and HN3R cells treated with TRAIL were analyzed with MTS and PI/annexin V-FITC assays. Western blotting and flow cytometry were used to determine the underlying mechanism of TRAIL resistance. DR4 expression was semiquantitatively scored in a tissue microarray with 107 laryngeal cancer specimens. Methylation-specific polymerase chain reaction and bisulfite sequencing for DR4 were performed for genomic DNA isolated from each cell line. Results: HN3R cells were more resistant than HN3 cells to TRAIL-induced apoptosis because of significantly reduced levels of the DR4 receptor. The DR4 staining score in 37 salvage surgical specimens after radiation failure was lower in 70 surgical specimens without radiation treatment (3.03 ± 2.75 vs 5.46 ± 3.30, respectively; P<.001). HN3R cells had a methylated DR4 CpG island that was partially demethylated by the DNA demethylating agent 5-aza-2′-deoxycytidine. Conclusion: Epigenetic silencing of the TRAIL receptor by hypermethylation of a DR4 CpG island might be an underlying mechanism for TRAIL resistance in recurrent laryngeal carcinoma treated with radiation

  6. 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.

  7. Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance.

    Science.gov (United States)

    Schneider, E; Horton, J K; Yang, C H; Nakagawa, M; Cowan, K H

    1994-01-01

    A human breast cancer cell line (MCF7/WT) was selected for resistance to etoposide (VP-16) by stepwise exposure to 2-fold increasing concentrations of this agent. The resulting cell line (MCF7/VP) was 28-, 21-, and 9-fold resistant to VP-16, VM-26, and doxorubicin, respectively. MCF7/VP cells also exhibited low-level cross-resistance to 4'-(9-acridinylamino)-methanesulfon-m-anisidide, mitoxantrone, and vincristine and no cross-resistance to genistein and camptothecin. Furthermore, these cells were collaterally sensitive to the alkylating agents melphalan and chlorambucil. DNA topoisomerase II levels were similar in both wild-type MCF7/WT and drug-resistant MCF7/VP cells. In contrast, topoisomerase II from MCF7/VP cells appeared to be 7-fold less sensitive to drug-induced cleavable complex formation in whole cells and 3-fold less sensitive in nuclear extracts than topoisomerase II from MCF7/WT cells. Although this suggested that the resistant cells may contain a qualitatively altered topoisomerase II, no mutations were detected in either the ATP-binding nor the putative breakage/resealing regions of either DNA topoisomerase II alpha or II beta. In addition, the steady-state intracellular VP-16 concentration was reduced by 2-fold in the resistant cells, in the absence of detectable mdr1/P-gp expression and without any change in drug efflux. In contrast, expression of the gene encoding the MRP was increased at least 10-fold in resistant MCF7/VP cells as compared to sensitive MCF7/WT cells. These results suggest that resistance to epipodophyllotoxins in MCF7/VP cells is multifactorial, involving a reduction in intracellular drug concentration, possibly as a consequence of MRP overexpression, and an altered DNA topoisomerase II drug sensitivity. PMID:7903202

  8. Quercetin as a Potential Modulator of P-Glycoprotein Expression and Function in Cells of Human Pancreatic Carcinoma Line Resistant to Daunorubicin

    Directory of Open Access Journals (Sweden)

    Piotr Dziegiel

    2010-02-01

    Full Text Available P-glycoprotein (P-gp is one of the ABC transporters responsible for the resistance of several tumours to successful chemotherapy. Numerous agents are capable of interfering with the P-gp-mediated export of drugs but unfortunately most of them produce serious side effects. Some plant polyphenols, including the flavonol quercetin (Q, manifest anti-neoplastic activity mainly due to their influence on cell cycle control and apoptosis. Reports are also available which show that Q may intensify action of cytostatic drugs and suppress the multidrug resistance (MDR phenomenon. The study aimed at determination if Q sensitizes cells resistant to daunorubicin (DB through its effect on P-gp expression and action. The experiments were conducted on two cell lines of human pancreatic carcinoma, resistant to DB EPP85-181RDB and sensitive EPP85-181P as a comparison. Cells of both lines were exposed to selected concentrations of Q and DB, and then membranous expression of P-gp and its transport function were examined. The influence on expression of gene for P-gp (ABCB1 was also investigated. Results of the studies confirmed that Q affects expression and function of P-gp in a concentration-dependent manner. Moreover it decreased expression of ABCB1. Thus, Q may be considered as a potential modulator of P-gp.

  9. Establishment of L-OHP-resistant colon carcinoma cell line and its drug resistance mechanism%结肠癌耐药细胞株LoVo/L-OHP的建立及其耐药机制

    Institute of Scientific and Technical Information of China (English)

    李敏; 方明治

    2011-01-01

    Objective :To estahlish a human drug resistance colon carcinoma cell line Lovo/L - OHP. and to explore its potential drug resistant mechanism. Methods : LoVo/L - OHP of a human drug - resistance colon carcinoma cell line was induced by continuously exposing human colon carcinoma cells to gradually increasing concentrations of L - OHP. The growth curve was observed. The drug resistance of LoVo/L - OHP was measured hy MTT assay and the drug resistant index ( RI ) was calculated. Several genes selected associated drug resistance genes were confirmed by reverse transcription - polymerase chain reaction ( RT - PCR ). Results : Compared with parental cells , the resistance cell line had a slower growth rate and larger morphology. RT - PCR results of LoVo/L - OHP cell line showed up - regulated P - gp, bcl - 2 , ERCC - 1genes, and p53 gene down - regulated. Conclusion : The altered biological properties of LoVo/L - OHP may he related to its drug resistance phenotype. Several genes, such as P - gp,bcl - 2, ERCC - 1 genes up - regulated and p53 gene down - regulated were possibly mechanism of drug resistance.%目的:建立获得性奥沙利铂(L-OHP)耐药的结肠癌细胞模型LoVo/L-OHP,并初步研究其耐药机制.方法:采用L-OHP浓度递增法建立人结肠癌细胞耐药模型LoVo/L-OHP,观察其生长规律并绘制细胞生长曲线;用MTT法鉴定耐药细胞株耐药性并计算耐药指数(RI);用半定量RT-PCR方法对部分耐药相关基因在耐药细胞及其亲本细胞中的表达情况进行分析.结果:成功建立了耐药的结肠癌细胞模型LoVo/L-OHP,LoVo/L-OHP细胞与LoVo细胞相比,生长缓慢,触角增多.通过RT-PCR半定量分析,P-gp、bcl-2、ERCC-1在LoVo/L-OHP中的表达上调,而p53基因表达下调.结论:LoVo/L-OHP细胞株耐药性稳定,耐药机制可能与P-gp、bcl-2、ERCC-1基因上调、p53基因下调多因素有关.

  10. Photodynamic action of LED-activated pyropheophorbide-α methyl ester in cisplatin-resistant human ovarian carcinoma cells

    International Nuclear Information System (INIS)

    Cisplatin-resistance is a major obstacle for the successful therapy to ovarian cancer, and exploring novel approach to deactivate cisplatin-resistant ovarian cells will improve the clinical outcomes. Our present study showed that there was no dark cytotoxicity of MPPa in the COC1/DDP cells at the dose of 0.25 – 4 μM, and LED-activated MPPa resulted in drug dose- and light-dependent cytotoxicity. Apoptotic rate 6 h after LED-activated MPPa (2 μM) increased to 16.71% under the light energy of 1 J/cm2. Confocal laser scanning microscopy showed that MPPa mainly localized in the intracellular membrane system, namely the endoplasmic reticulum, Golgi apparatus, lysosomes and mitochondria in the COC1/DDP cells. Mitochondrial membrane potential (ΔΨm) was collapsed when COC1/DDP cells were exposed to 2 μM MPPa for 20 h and then 1 J/cm2 irradiation of LED source. These data demonstrated that LED-activated MPPa significantly deactivated cisplatin-resistant ovarian cell line COC1/DDP cells and enhanced apoptosis and decreased ΔΨm, which suggests LED is an efficient light source for PDT and LED-activated MPPa can be developed as new modality for treating cisplatin-resistant ovarian

  11. Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells

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    Reedijk Jan

    2008-06-01

    Full Text Available Abstract Background Copper homeostasis proteins ATP7A and ATP7B are assumed to be involved in the intracellular transport of cisplatin. The aim of the present study was to assess the relevance of sub cellular localisation of these transporters for acquired cisplatin resistance in vitro. For this purpose, localisation of ATP7A and ATP7B in A2780 human ovarian carcinoma cells and their cisplatin-resistant variant, A2780cis, was investigated. Methods Sub cellular localisation of ATP7A and ATP7B in sensitive and resistant cells was investigated using confocal fluorescence microscopy after immunohistochemical staining. Co-localisation experiments with a cisplatin analogue modified with a carboxyfluorescein-diacetate residue were performed. Cytotoxicity of the fluorescent cisplatin analogue in A2780 and A2780cis cells was determined using an MTT-based assay. The significance of differences was analysed using Student's t test or Mann-Whitney test as appropriate, p values of Results In the sensitive cells, both transporters are mainly localised in the trans-Golgi network, whereas they are sequestrated in more peripherally located vesicles in the resistant cells. Altered localisation of ATP7A and ATP7B in A2780cis cells is likely to be a consequence of major abnormalities in intracellular protein trafficking related to a reduced lysosomal compartment in this cell line. Changes in sub cellular localisation of ATP7A and ATP7B may facilitate sequestration of cisplatin in the vesicular structures of A2780cis cells, which may prevent drug binding to genomic DNA and thereby contribute to cisplatin resistance. Conclusion Our results indicate that alterations in sub cellular localisation of transport proteins may contribute to cisplatin resistance in vitro. Investigation of intracellular protein localisation in primary tumour cell cultures and tumour tissues may help to develop markers of clinically relevant cisplatin resistance. Detection of resistant tumours

  12. Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells

    International Nuclear Information System (INIS)

    Copper homeostasis proteins ATP7A and ATP7B are assumed to be involved in the intracellular transport of cisplatin. The aim of the present study was to assess the relevance of sub cellular localisation of these transporters for acquired cisplatin resistance in vitro. For this purpose, localisation of ATP7A and ATP7B in A2780 human ovarian carcinoma cells and their cisplatin-resistant variant, A2780cis, was investigated. Sub cellular localisation of ATP7A and ATP7B in sensitive and resistant cells was investigated using confocal fluorescence microscopy after immunohistochemical staining. Co-localisation experiments with a cisplatin analogue modified with a carboxyfluorescein-diacetate residue were performed. Cytotoxicity of the fluorescent cisplatin analogue in A2780 and A2780cis cells was determined using an MTT-based assay. The significance of differences was analysed using Student's t test or Mann-Whitney test as appropriate, p values of < 0.05 were considered significant. In the sensitive cells, both transporters are mainly localised in the trans-Golgi network, whereas they are sequestrated in more peripherally located vesicles in the resistant cells. Altered localisation of ATP7A and ATP7B in A2780cis cells is likely to be a consequence of major abnormalities in intracellular protein trafficking related to a reduced lysosomal compartment in this cell line. Changes in sub cellular localisation of ATP7A and ATP7B may facilitate sequestration of cisplatin in the vesicular structures of A2780cis cells, which may prevent drug binding to genomic DNA and thereby contribute to cisplatin resistance. Our results indicate that alterations in sub cellular localisation of transport proteins may contribute to cisplatin resistance in vitro. Investigation of intracellular protein localisation in primary tumour cell cultures and tumour tissues may help to develop markers of clinically relevant cisplatin resistance. Detection of resistant tumours in patients may in turn

  13. Development of a Resistance-like Phenotype to Sorafenib by Human Hepatocellular Carcinoma Cells Is Reversible and Can Be Delayed by Metronomic UFT Chemotherapy

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    Terence C. Tang

    2010-11-01

    Full Text Available Acquired resistance to antiangiogenic drugs, such as sorafenib, is a major clinical problem. We studied development of a resistance to sorafenib in new preclinical models of human hepatocellular carcinoma (HCC along with a strategy to delay such resistance—combination with metronomic chemotherapy. Three different xenograft models were studied using human Hep3B HCC cells, which are highly responsive to sorafenib, namely, orthotopic and subcutaneous transplant in severe combined immunodeficient mice, and an orthotopic transplant in nude mice. The complementary DNA for the β-subunit of human choriogonadotropin was transfected into HCC cells, and urine levels of the protein were monitored as a surrogate of tumor burden. Extended daily treatments, sometimes interrupted by a break period of 3 to 7 days to allow recovery from toxicity at sorafenib doses of 30 to 60 mg/kg, were maintained until and after evidence of tumor relapse. Initially responsive tumors seemed to develop a resistance-like phenotype after long-term daily treatment (e.g., >42 days at doses of 30 to 60 mg/kg. Transplantation of cell lines established from progressing tumors into new hosts showed that the resistant phenotype was not propagated. Furthermore, a regimen of daily metronomic uracil + tegafur (UFT, an oral 5-fluorouracil prodrug chemotherapy with a less toxic regimen of sorafenib (15 mg/kg per day significantly delayed the onset of resistance (>91 days. In conclusion, development of a resistance-like phenotype to sorafenib is reversible, and metronomic UFT plus sorafenib may be a promising and well-tolerated treatment for increasing efficacy by delaying emergence of such resistance.

  14. Merkel cell carcinoma.

    Science.gov (United States)

    Minokadeh, Ardalan; Wulkan, Adam J; Beer, Kenneth; Waibel, Jill S

    2014-01-01

    A 92-year-old man presented for evaluation with a 1-month history of a rapidly growing asymptomatic pink nodule on his forearm. Biopsy results of the lesion demonstrated pathology consistent with Merkel cell carcinoma (MCC). Immunohistochemical studies displayed positive cytoplasmic staining for cytokeratin AE1/AE3, positive dot-like perinuclear staining for cytokeratin-20, diffuse cytoplasmic staining for neuron specific enolase, and no significant staining for S-100. Subsequent positron emission tomography did not reveal evidence of metastatic disease. Wide excision of the lesion was performed along with a sentinel node biopsy of his left axilla. The sentinel nodes were negative for MCC. Adjuvant radiation treatment of the tumor site was provided because the pathologist noted MCC within 2 mm of the deep margin. PMID:24933855

  15. Breast Cancer Anti-Estrogen Resistance 4 (BCAR4 Drives Proliferation of IPH-926 lobular Carcinoma Cells.

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    Ton van Agthoven

    Full Text Available Most breast cancers depend on estrogenic growth stimulation. Functional genetic screenings in in vitro cell models have identified genes, which override growth suppression induced by anti-estrogenic drugs like tamoxifen. Using that approach, we have previously identified Breast Cancer Anti-Estrogen Resistance 4 (BCAR4 as a mediator of cell proliferation and tamoxifen-resistance. Here, we show high level of expression and function of BCAR4 in human breast cancer.BCAR4 mRNA expression was evaluated by (qRT-PCR in a panel of human normal tissues, primary breast cancers and cell lines. A new antibody raised against C78-I97 of the putative BCAR4 protein and used for western blot and immunoprecipitation assays. Furthermore, siRNA-mediated gene silencing was implemented to study the function of BCAR4 and its downstream targets ERBB2/3.Except for placenta, all human normal tissues tested were BCAR4-negative. In primary breast cancers, BCAR4 expression was comparatively rare (10%, but associated with enhanced proliferation. Relative high BCAR4 mRNA expression was identified in IPH-926, a cell line derived from an endocrine-resistant lobular breast cancer. Moderate BCAR4 expression was evident in MDA-MB-134 and MDA-MB-453 breast cancer cells. BCAR4 protein was detected in breast cancer cells with ectopic (ZR-75-1-BCAR4 and endogenous (IPH-926, MDA-MB-453 BCAR4 mRNA expression. Knockdown of BCAR4 inhibited cell proliferation. A similar effect was observed upon knockdown of ERBB2/3 and exposure to lapatinib, implying that BCAR4 acts in an ERBB2/3-dependent manner.BCAR4 encodes a functional protein, which drives proliferation of endocrine-resistant breast cancer cells. Lapatinib, a clinically approved EGFR/ERBB2 inhibitor, counteracts BCAR4-driven tumor cell growth, a clinical relevant observation.

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

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

    2006-12-15

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

  17. Hexabromocyclododecane and polychlorinated biphenyls increase resistance of hepatocellular carcinoma cells to cisplatin through the phosphatidylinositol 3-kinase/protein kinase B pathway.

    Science.gov (United States)

    An, Jing; Wang, Xiu; Guo, Panpan; Zhong, Yufang; Zhang, Xinyu; Yu, Zhiqiang

    2014-08-17

    Hepatocellular carcinoma (HCC) is one of the most common cancers in China with high mortality, high chemotherapy resistance incidence, and poor prognosis. This study aimed to investigate the influence of polychlorinated biphenyls (PCBs) and hexabromocyclododecane (HBCD) on chemoresistance of HCC cells (HepG2, MHCC97H, and MHCC97L) to cisplatin and to explore the potential molecular mechanism. Cell viability, DNA damage, the expression level and activity of nuclear factor-κB (NF-κB), p53/Mdm4, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were measured. The results showed that HBCD and PCBs could significantly reduce the chemosensitivity of HCC cells to cisplatin, increasing the cell viability and decreasing DNA damage. Moreover, HBCD and PCBs could induce the transcriptional activity of NF-κb and suppress the p53 expression in HepG2 and MHCC97H cells. In MHCC97L cells, however, opposite changes for NF-κB protein expression, NF-κB transcriptional activity, and p53/Mdm4 expression were observed after HBCD and PCBs exposure. Further investigation revealed that HBCD and PCBs exposure significantly increased the expression level of p-Akt and mammalian target of rapamycin (mTOR) in HepG2 and MHCC97H cells, but reduced that in MHCC97L cells. PI3K inhibitor LY294002 could relieve the influence of HBCD and PCBs on chemoresistance in HepG2 and MHCC97H cells. Taken together, HBCD and PCBs at low concentrations could increase the resistance of HCC cells to cisplatin through modulation on NF-κB pathway activation and p53 function, which is associated with the activity of PI3K/Akt pathway.

  18. Elimination of Enhanced Thermal Resistance of Spheroid Culture Model of Prostate Carcinoma Cell Line by Inhibitors of Hsp70 Induction

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    Samideh Khoei

    2010-01-01

    Full Text Available AbstractObjective: The purpose of this study was to investigate the enhanced thermal resistancemechanism of the DU145 tumor spheroid cultures as compared to the prostate carcinomacell line's monolayer cultures.Materials and Methods: DU145 cells were cultured either as spheroids or monolayers.Cultures were treated with hyperthermia in a precision water bath (at 43°C for 60 minutesand/or quercetin (50 and 500 μM for monolayer and spheroid cultures respectively. Afterhyperthermic treatment, the cell viability colony forming ability, and the expression of heatshock protein 70 (Hsp70 were examined in both culture systems. Hsp70 expression wasstudied using the western blot method.Results: Our results showed that the DU145 monolayer and spheroid cell culture treatmentwith hyperthermia alone resulted in a marked survival inhibition. Furthermore, thespheroids showed a more significant resistance to hyperthermia compared to the monolayercultures (p = 0.01. They also produced more Hsp70 than the monolayer cultures.Treatment of cells with quercetin reduced the Hsp70 level in both culture systems. However,with the reduced Hsp70 levels, thermal resistance of the spheroids showed a greaterdecrease in relation to that of the monolayers.Conclusion: The results suggest that the enhanced hyperthermia resistance mechanismof the spheroid cultures compared to that of the monolayer cultures can be attributed tospheroids' Hsp70 production.

  19. Pulmonary Metastasis of Basal Cell Carcinoma

    OpenAIRE

    Seo, Sang-Hee; Shim, Woo-Haing; SHIN, DONG-HOON; Kim, Yun-Seong; Sung, Hyun-Woo

    2011-01-01

    Although basal cell carcinoma is the most common skin cancer, it rarely metastasizes. Metastatic basal cell carcinoma may, therefore, initially elude diagnosis and management. We describe the case of a patient with a metastatic basal cell carcinoma present in the lungs. The differential diagnosis of suspected metastatic lesions should include metastases from a cutaneous basal cell carcinoma, in addition to those from more commonly metastasizing carcinomas, especially in patients with a histor...

  20. Targeting cancer stem cells in hepatocellular carcinoma

    OpenAIRE

    MISHRA, LOPA

    2014-01-01

    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 fun...

  1. The HIF-2α-MALAT1-miR-216b axis regulates multi-drug resistance of hepatocellular carcinoma cells via modulating autophagy.

    Science.gov (United States)

    Yuan, Peng; Cao, Weibin; Zang, Quanling; Li, Guixin; Guo, Xiangfei; Fan, Jianghe

    2016-09-23

    In this study, we firstly investigated the association among lncRNA MALAT1, HIF-1α and HIF-2α in hepatocellular carcinoma (HCC) cells. Then, we investigated the regulative effect of MALAT1 on multi-drug resistance (MDR) in HCC cells and the underlying mechanism. The results showed that MALAT1 was over two times higher in BEL-7402/5-FU cells than in BEL-7402 cells. It was HIF-2α, but not HIF-1α induced MALAT1 upregulation in HCC cells. Dual luciferase assay demonstrated that there were at least two binding sites of miR-26b in MALAT1. Therefore, we infer that there is a HIF-2α-MALAT1-miR-216b axis in HCC cells. Cell viability assay showed that both MALAT1 siRNA and miR-216b mimics reduced IC50 of 5-FU, ADR and MMC in BEL-7402/5-FU cells. MALAT1 siRNA and miR-216b mimics showed similar effect as 3-MA on reducing LC3-II levels, inhibiting p62 degradation and suppressing GFP-LC3 puncta formation in BEL-7402/5-FU cells. Flow cytometric analysis showed that 3-MA treatment, MALAT1 siRNA and miR-216b mimics all promoted 5-FU induced apoptosis in BEL-7402/5-FU cells. Therefore, this study firstly revealed that there is a HIF-2α-MALAT1-miR-216b axis regulating MDR of HCC cells via modulating autophagy. PMID:27524242

  2. Simultaneous Laryngeal Squamous Cell Carcinoma and Papillary Thyroid Carcinoma

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    Bighan Khademi

    2011-04-01

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

  3. Integrative transcriptomics-based identification of cryptic drivers of taxol-resistance genes in ovarian carcinoma cells: Analysis of the androgen receptor.

    Science.gov (United States)

    Sun, Nian-Kang; Huang, Shang-Lang; Lu, Hsing-Pang; Chang, Ting-Chang; Chao, Chuck C-K

    2015-09-29

    A systematic analysis of the genes involved in taxol resistance (txr) has never been performed. In the present study, we created txr ovarian carcinoma cell lines to identify the genes involved in chemoresistance. Transcriptome analysis revealed 1,194 overexpressed genes in txr cells. Among the upregulated genes, more than 12 cryptic transcription factors were identified using MetaCore analysis (including AR, C/EBPβ, ERα, HNF4α, c-Jun/AP-1, c-Myc, and SP-1). Notably, individual silencing of these transcription factors (except HNF4`)sensitized txr cells to taxol. The androgen receptor (AR) and its target genes were selected for further analysis. Silencing AR using RNA interference produced a 3-fold sensitization to taxol in txr cells, a response similar to that produced by silencing abcb1. AR silencing also downregulated the expression of prominent txr gene candidates (including abcb1, abcb6, abcg2, bmp5, fat3, fgfr2, h1f0, srcrb4d, and tmprss15). In contrast, AR activation using the agonist DHT upregulated expression of the target genes. Individually silencing seven out of nine (78%) AR-regulated txr genes sensitized txr cells to taxol. Inhibition of AKT and JNK cellular kinases using chemical inhibitors caused a dramatic suppression of AR expression. These results indicate that the AR represents a critical driver of gene expression involved in txr.

  4. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma

    Science.gov (United States)

    Lyford-Pike, Sofia; Peng, Shiwen; Young, Geoffrey D.; Taube, Janis M.; Westra, William H.; Akpeng, Belinda; Bruno, Tullia C.; Richmon, Jeremy D.; Wang, Hao; Bishop, Justin A.; Chen, Lieping; Drake, Charles G.; Topalian, Suzanne L.; Pardoll, Drew M.; Pai, Sara I.

    2013-01-01

    Human papillomavirus-associated head and neck squamous cell carcinomas (HPV-HNSCC) originate in the tonsils, the major lymphoid organ that orchestrates immunity to oral infections. Despite its location, the virus escapes immune elimination during malignant transformation and progression. Here, we provide evidence for the role of the PD-1:PD-L1 pathway in HPV-HNSCC immune resistance. We demonstrate membranous expression of PD-L1 in the tonsillar crypts, the site of initial HPV infection. In HPV-HNSCCs that are highly infiltrated with lymphocytes, PD-L1 expression on both tumor cells and CD68+ tumor associated macrophages (TAMs) is geographically localized to sites of lymphocyte fronts, while the majority of CD8+ tumor infiltrating lymphocytes (TILs) express high levels of PD-1, the inhibitory PD-L1 receptor. Significant levels of mRNA for interferon-γ (IFN-γ), a major cytokine inducer of PD-L1 expression, were found in HPV+ PD-L1(+) tumors. Our findings support the role of the PD-1:PD-L1 interaction in creating an “immune-privileged” site for initial viral infection and subsequent adaptive immune resistance once tumors are established and suggest a rationale for therapeutic blockade of this pathway in patients with HPV-HNSCC. PMID:23288508

  5. A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo

    International Nuclear Information System (INIS)

    In search of a suitable GSH-depleting agent, a novel copper complex viz., copper N-(2-hydroxyacetophenone) glycinate (CuNG) has been synthesized, which was initially found to be a potential resistance modifying agent and later found to be an immunomodulator in mice model in different doses. The objective of the present work was to decipher the effect of CuNG on reactive oxygen species (ROS) generation and antioxidant enzymes in normal and doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)-bearing Swiss albino mice. The effect of CuNG has been studied on ROS generation, multidrug resistance-associated protein1 (MRP1) expression and on activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). CuNG increased ROS generation and reduced MRP1 expression in EAC/Dox cells while only temporarily depleted glutathione (GSH) within 2 h in heart, kidney, liver and lung of EAC/Dox bearing mice, which were restored within 24 h. The level of liver Cu was observed to be inversely proportional to the level of GSH. Moreover, CuNG modulated SOD, CAT and GPx in different organs and thereby reduced oxidative stress. Thus nontoxic dose of CuNG may be utilized to reduce MRP1 expression and thus sensitize EAC/Dox cells to standard chemotherapy. Moreover, CuNG modulated SOD, CAT and and GPx activities to reduce oxidative stress in some vital organs of EAC/Dox bearing mice. CuNG treatment also helped to recover liver and renal function in EAC/Dox bearing mice. Based on our studies, we conclude that CuNG may be a promising candidate to sensitize drug resistant cancers in the clinic

  6. A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo

    Directory of Open Access Journals (Sweden)

    Efferth Thomas

    2006-11-01

    Full Text Available Abstract Background In search of a suitable GSH-depleting agent, a novel copper complex viz., copper N-(2-hydroxyacetophenone glycinate (CuNG has been synthesized, which was initially found to be a potential resistance modifying agent and later found to be an immunomodulator in mice model in different doses. The objective of the present work was to decipher the effect of CuNG on reactive oxygen species (ROS generation and antioxidant enzymes in normal and doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox-bearing Swiss albino mice. Methods The effect of CuNG has been studied on ROS generation, multidrug resistance-associated protein1 (MRP1 expression and on activities of superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GPx. Results CuNG increased ROS generation and reduced MRP1 expression in EAC/Dox cells while only temporarily depleted glutathione (GSH within 2 h in heart, kidney, liver and lung of EAC/Dox bearing mice, which were restored within 24 h. The level of liver Cu was observed to be inversely proportional to the level of GSH. Moreover, CuNG modulated SOD, CAT and GPx in different organs and thereby reduced oxidative stress. Thus nontoxic dose of CuNG may be utilized to reduce MRP1 expression and thus sensitize EAC/Dox cells to standard chemotherapy. Moreover, CuNG modulated SOD, CAT and and GPx activities to reduce oxidative stress in some vital organs of EAC/Dox bearing mice. CuNG treatment also helped to recover liver and renal function in EAC/Dox bearing mice. Conclusion Based on our studies, we conclude that CuNG may be a promising candidate to sensitize drug resistant cancers in the clinic.

  7. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

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    Divvya

    2014-05-01

    Full Text Available Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differentiation is practically very rare.

  8. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

    OpenAIRE

    Divvya; Rehana; Viswanathan; Krishnaswamy; Anvar Ali

    2014-01-01

    Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differen...

  9. Nuclear Multidrug-Resistance Related Protein 1 Contributes to Multidrug-Resistance of Mucoepidermoid Carcinoma Mainly via Regulating Multidrug-Resistance Protein 1: A Human Mucoepidermoid Carcinoma Cells Model and Spearman's Rank Correlation Analysis

    OpenAIRE

    Bolei Cai; Ye Miao; Yuan Liu; Xiaofang Xu; Sumin Guan; Junzheng Wu; Yanpu Liu

    2013-01-01

    BACKGROUND: Multidrug resistance-related protein 1 (MRP1/ABCC1) and multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1) are both membrane-bound drug transporters. In contrast to MDR1, MRP1 also transports glutathione (GSH) and drugs conjugated to GSH. Due to its extraordinary transport properties, MRP1/ABCC1 contributes to several physiological functions and pathophysiological incidents. We previously found that nuclear translocation of MRP1 contributes to multidrug-resistance (MDR) of...

  10. Sulindac enhances arsenic trioxide induced apoptotic potential mediated by reactive oxygen species production in arsenic trioxide-resistant A549 lung carcinoma cells

    International Nuclear Information System (INIS)

    Full text: Recent reports indicate a broad spectrum of antitumor activity for arsenic trioxide (As2 O3) due to its ability to induce apoptosis via intracellular production of reactive oxygen species (ROS). Sulindac and nonsteroidal anti-inflammatory drugs induce apoptosis in a variety of cancer cells, including those of colon, prostate, breast, and leukemia. Therefore, we examined the effects of sulindac on As2O3-induced apoptosis in As2 O3-resistant A549 lung carcinoma cells in clinically available concentrations. Sulindac produced hydrogen peroxide (H 2 O 2 ) and nitric oxide (NO) in a dose-dependent manner and greatly sensitized the cells to As2O3-induced apoptosis. Apoptotic cell death was preceded by collapse of the mitochondrial membrane potential, release of cytochrome c/apoptosis inducing factor(AIF) and activation of caspase-3, -8, -9 activation. Importantly, the combined effect of As2O3 and sulindac was associated with an increased production of intracellular H2O3/reactive nitrogen species(RNS) and was completely suppressed by the reduced glutathione. In conclusion, intracellular ROS/RNS products most likely constitute the key mediators contributing to the combined effect of As2O3 and sulindac. Our data provide evidence for the first time that sulindac may help to extend the therapeutic spectrum of As2O3 and suggest that the combination of As2O3 and sulindac could be more broadly applied in cancer therapy

  11. JAK2 inhibitor TG101348 overcomes erlotinib-resistance in non-small cell lung carcinoma cells with mutated EGF receptor.

    Science.gov (United States)

    Zhang, Fu-quan; Yang, Wen-tao; Duan, Shan-zhou; Xia, Ying-chen; Zhu, Rong-ying; Chen, Yong-bing

    2015-06-10

    Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are responsive to EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, NSCLC patients with secondary somatic EGFR mutations are resistant to EGFR-TKI treatment. In this study, we investigated the effect of TG101348 (a JAK2 inhibitor) on the tumor growth of erlotinib-resistant NSCLC cells. Cell proliferation, apoptosis, gene expression and tumor growth were evaluated by diphenyltetrazolium bromide (MTT) assay, flow cytometry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, Western Blot and a xenograft mouse model, respectively. Results showed that erlotinib had a stronger impact on the induction of apoptosis in erlotinib-sensitive PC-9 cells but had a weaker effect on erlotinib-resistant H1975 and H1650 cells than TG101348. TG101348 significantly enhanced the cytotoxicity of erlotinib to erlotinib-resistant NSCLC cells, stimulated erlotinib-induced apoptosis and downregulated the expressions of EGFR, p-EGFR, p-STAT3, Bcl-xL and survivin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of TG101348 and erlotinib induced apoptosis, inhibited the activation of p-EGFR and p-STAT3, and inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo. Our results indicate that TG101348 is a potential adjuvant for NSCLC patients during erlotinib treatment.

  12. p21-activated kinase 1 determines stem-like phenotype and sunitinib resistance via NF-κB/IL-6 activation in renal cell carcinoma.

    Science.gov (United States)

    Zhu, Y; Liu, H; Xu, L; An, H; Liu, W; Liu, Y; Lin, Z; Xu, J

    2015-02-12

    The p21-activated kinase 1 (PAK1), a serine/threonine kinase that orchestrates cytoskeletal remodeling and cell motility, has been shown to function as downstream node for various oncogenic signaling pathways to promote cell proliferation, regulate apoptosis and accelerate mitotic abnormalities, resulting in tumor formation and invasiveness. Although alterations in PAK1 expression and activity have been detected in various human malignancies, its potential biological and clinical significance in renal cell carcinoma (RCC) remains obscure. In this study, we found increased PAK1 and phosphorylated PAK1 levels in tumor tissues according to TNM stage progression. Elevated phosphorylated PAK1 levels associated with progressive features and indicated unfavorable overall survival (OS) as an independent adverse prognosticator for patients with RCC. Moreover, PAK1 kinase activation with constitutive active PAK1 mutant T423E promoted growth, colony formation, migration, invasion and stem-like phenotype of RCC cells, and vice versa, in PAK1 inhibition by PAK1 kinase inactivation with specific PAK1 shRNA, dead kinase PAK1 mutant K299R or allosteric inhibitor IPA3. Stem-like phenotype due to sunitinib administration via increased PAK1 kinase activation could be ameliorated by PAK1 shRNA, PAK1 mutant K299R and IPA3. Furthermore, nuclear factor-κB (NF-κB)/interleukin-6 (IL-6) activation was found to be responsible for PAK1-mediated stem-like phenotype following sunitinib treatment. Both IL-6 neutralizing antibody and IPA3 administration enhanced tumor growth inhibition effect of sunitinib treatment on RCC cells in vitro and in vivo. Our results unraveled that oncogenic activation of PAK1 defines an important mechanism for maintaining stem-like phenotype and sunitinib resistance through NF-κB/IL-6 activation in RCC, lending PAK1-mediated NF-κB/IL-6 activation considerable appeal as novel pharmacological therapeutic targets against sunitinib resistance.

  13. Prognostic significance of multidrug-resistance protein (MDR-1) in renal clear cell carcinomas: A five year follow-up analysis

    International Nuclear Information System (INIS)

    A large number of renal cancer patients shows poor or partial response to chemotherapy and the mechanisms have not been still understood. Multi-drug resistance is the principal mechanism by which many cancers develop resistance to chemotherapic drugs. The role of the multi-drug resistant transporter (MDR-1/P-glycoprotein), the gene product of MDR-1, and that one of the so-called multi-drug resistance associated protein (MRP), two energy-dependent efflux pumps, are commonly known to confer drug resistance. We studied MDR-1 expression in selected cases of renal cell carcinoma (RCC), clear cell type, with long-term follow-up, in order to establish its prognostic role and its possible contribution in the choice of post-surgical therapy. MDR-1 has been studied by standard LSAB-HRP immunohistochemical technique, in paraffin embedded RCC samples. Protein expression has been compared to clinical and histopathological data and to disease specific survival of RCC patients, by Kaplan-Meier curve and Cox multivariate regression analyses. Two groups of RCCs were obtained by esteeming MDR-1 expression and disease specific survival (obtained with Kaplan-Meier curve and Cox multivariate regression analyses): the first one presents low or absent MDR-1 expression and good survival; the second one is characterized by high MDR-1 expression and significant poor outcome (p < 0.05). Afterwards, we have found disease specific survival, adjusted for stages and independent of therapy: this difference of survival rates was statistically significant (p < 0.05). Stage adjusted disease specific survival rate, according to MDR-1 expression and therapy in patients affected by RCC in early stage (stage I), has revealed that the group of patients with high MDR-1 expression and without adjuvant therapy showed poor survival (p < 0.05). Cox multivariate regression analysis has confirmed that, in our cohort of RCC (clear cell type) patients, the strong association between MDR-1 and worse outcome is

  14. 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

  15. Basal cell carcinoma of penis: case report.

    OpenAIRE

    Sulaiman, M Z; Polacarz, S V; Partington, P E

    1988-01-01

    Basal cell carcinoma of the penis is rare. A patient who presented with a penile and scrotal ulcer due to basal cell carcinoma is reported. Wide local excision and split skin grafting were performed to excise the lesion completely.

  16. Potential mechanisms involved in resistant phenotype of MCF-7 breast carcinoma cells to ionizing radiation induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yanling [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China); Zhang Hong [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China)], E-mail: zhangh@impcas.ac.cn; Li Ning [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China); Wang Xiaohu [Department of Radiotherapy, Gansu Tumor Hospital, Lanzhou 730050 (China); Hao Jifang [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Zhao Weiping [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China)

    2009-03-15

    In the present study, we investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest in IR-induced apoptosis in MCF-7 cells. X-irradiation, in particular at low dose (1 Gy), but not carbon ion irradiation, had a significant antiproliferative effect on the growth of MCF-7 cells. 1 Gy X-irradiation resulted in G1 and G2 phase arrest, but 4 Gy induced a significant G1 block. In contrast, carbon ion irradiation resulted in a significant accumulation in the G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage, carbon ion irradiation resulted in an approximately 1.9-2.8-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected for X-irradiation. Carbon ion irradiation caused a dramatic increase in p21 expression and drastic decrease in Bax expression compared with X-irradiation. The data implicated that phosphorylation of BRCA1 on serine residue 1524 might, at least partially, induce p21 expression but repress Bax expression. Together, our results suggested that the phosphorylation of BRCA1 at Ser-1524 might contribute to the G2 phase arrest and might be an upstream signal involved in preventing apoptosis signal via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio.

  17. Potential mechanisms involved in resistant phenotype of MCF-7 breast carcinoma cells to ionizing radiation induced apoptosis

    Science.gov (United States)

    Wang, Yan-ling; Zhang, Hong; Li, Ning; Wang, Xiao-hu; Hao, Ji-fang; Zhao, Wei-ping

    2009-03-01

    In the present study, we investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest in IR-induced apoptosis in MCF-7 cells. X-irradiation, in particular at low dose (1 Gy), but not carbon ion irradiation, had a significant antiproliferative effect on the growth of MCF-7 cells. 1 Gy X-irradiation resulted in G1 and G2 phase arrest, but 4 Gy induced a significant G1 block. In contrast, carbon ion irradiation resulted in a significant accumulation in the G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage, carbon ion irradiation resulted in an approximately 1.9-2.8-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected for X-irradiation. Carbon ion irradiation caused a dramatic increase in p21 expression and drastic decrease in Bax expression compared with X-irradiation. The data implicated that phosphorylation of BRCA1 on serine residue 1524 might, at least partially, induce p21 expression but repress Bax expression. Together, our results suggested that the phosphorylation of BRCA1 at Ser-1524 might contribute to the G2 phase arrest and might be an upstream signal involved in preventing apoptosis signal via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio.

  18. Evaluation of airway resistance in primary small cell carcinoma of the trachea by MostGraph: a case study.

    Science.gov (United States)

    Hagiwara, Eri; Gon, Yasuhiro; Hayashi, Kentaro; Takahashi, Mai; Iida, Yuko; Hiranuma, Hisato; Nakagawa, Yoshiko; Hataoka, Tsukasa; Mizumura, Kenji; Maruoka, Shuichiro; Shimizu, Tetsuo; Takahashi, Noriaki; Hashimoto, Shu

    2016-08-01

    The case subject was a 58-year-old woman who presented to our hospital with a chief complaint of respiratory discomfort. Wheezing could be heard in both lungs; treatment was initiated with inhaled steroids for suspected bronchial asthma. However, 1 week later, the respiratory discomfort had not improved and the wheezing sound had progressed to the neck area. Upper airway obstruction was suspected; therefore, chest computed tomography (CT) was performed, revealing tracheal stenosis caused by a tumor in the upper airway. Because of the high risk of airway obstruction, tracheotomy and tracheal tumor resection were performed. Histopathological examination of the resected tumor revealed small cell lung cancer (SCLC); the stage was determined to be clinical stage IIIB (cT4N2M0), for which chemotherapy with two cycles of cisplatin plus etoposide followed by radiation therapy were administered. Pulmonary function testing revealed no change in the forced expiratory volume in 1 sec and flow volume (FV) curve before and after tumor resection, whereas airway resistance measured by MostGraph-01 showed a marked decrease following treatment. We believe that MostGraph-01 may be useful for measuring airway resistance and evaluating a tracheal tumor, and report a case using MostGraph-01. PMID:27621904

  19. [The Dutch guideline 'Renal cell carcinoma'].

    NARCIS (Netherlands)

    Osanto, S.; Bex, A.; Hulsbergen- van de Kaa, C.A.; Soetekouw, P.M.M.B.; Stemkens, D.

    2012-01-01

    The Dutch guideline 'Renal Cell Carcinoma' has been revised on the basis of new literature. With the assistance of the Netherlands Cancer Registry an assessment was made of the current care for patients with renal cell carcinoma. Renal cell carcinoma is a type of cancer for which knowledge of the ge

  20. 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.

  1. Basal cell carcinoma-treatment with cryosurgery

    OpenAIRE

    Kaur S; Thami G; Kanwar A

    2003-01-01

    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.

  2. 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.

  3. 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.

  4. Small cell undifferentiated carcinoma in the epididymis

    Institute of Scientific and Technical Information of China (English)

    CHEN Jia-wei; YUAN Lin; Hu Hong-hui

    2005-01-01

    @@ Small cell undifferentiated carcinoma is a special type of tumor which is usually found in the lungs. However, it is very rare in extra pulmonary tissues, especially in epididymis. One case of small cell undifferentiated carcinoma in the right epididymis, with partial differentiation to adenocarcinoma and neuroendocrine carcinoma is reported as follows.

  5. Reversal of taxol resistance by cisplatin in human nasopharyngeal carcinoma cell lines%顺铂逆转鼻咽癌紫杉醇耐药细胞的耐药性

    Institute of Scientific and Technical Information of China (English)

    彭小伟; 李维; 谭国林

    2011-01-01

    目的:观察顺铂是否能够逆转鼻咽癌紫杉醇耐药细胞HNE-2/taxol和5-8F/taxol的耐药性.方法:运用集落形成实验观察不同浓度顺铂对鼻咽癌亲本细胞(HNE-2及5-8F)和紫杉醇耐药细胞(HNE-2/taxol及5-8F/taxol)的生长抑制率,并且判断经低浓度顺铂预处理后,耐药细胞耐药指数的改变.通过等效剂量和联用指数分析,评价紫杉醇和顺铂联合用药的效果.运用FCM法检测不同浓度顺铂处理后鼻咽癌亲本细胞和耐药细胞的凋亡率变化.结果:两种鼻咽癌紫杉醇耐药细胞株对顺铂的敏感性均显著高于其亲本细胞(P<0.05).顺铂与紫杉醇合用时,对鼻咽癌亲本细胞的增殖抑制能够产生相加作用,而对耐药细胞的增殖抑制则能够产生协同作用.经过低浓度顺铂预处理后,耐药细胞的耐药指数明显降低.在顺铂作用下,鼻咽癌紫杉醇耐药细胞的早期凋亡率显著高于亲本细胞(P<0.05).结论:顺铂可以逆转鼻咽癌细胞的紫杉醇耐药性.顺铂和紫杉醇联舍作用于鼻咽癌紫杉醇耐药细胞,能够产生协同效应.%Objective: To observe whether cisplatin (DDP) can reverse taxol-resistant phenotype of human nasopharyngeal carcinoma cell lines HNE-2/taxol and 5-8F/taxol. Methods: The inhibitory effects of DDP on the proliferation of parental cell lines (HNE-2 and 5-8F) and taxol-resistant cell lines (HNE-2/taxol and 5-8F/taxol) were detected by colony formation assay. The influence of a low dose of DDP on drug resistance index of taxol-resistant nasopharyngeal carcinoma cells was estimated by colony formation assay. The combined effect of taxol with DDP was measured by isobologram and combination index (Cl) analyses. The effects of DDP at different concentrations on the apoptotic rates of taxol-resistant cells and their parental cells were detected by flow cytometry. Results: The taxolresistant nasopharyngeal carcinoma cells showed more sensitive to DDP than their parental cells (P<0

  6. The many faces of basal cell carcinoma

    OpenAIRE

    Jackson, Robert

    1982-01-01

    Basal cell carcinoma is the most easily cured carcinoma, but because of the many forms it can take, and because it grows so slowly, it can be misdiagnosed or neglected. The author discusses its more common forms and etiologic considerations.

  7. Interaction of Stellate Cells with Pancreatic Carcinoma Cells

    International Nuclear Information System (INIS)

    Pancreatic cancer is characterized by its late detection, aggressive growth, intense infiltration into adjacent tissue, early metastasis, resistance to chemo- and radiotherapy and a strong “desmoplastic reaction”. The dense stroma surrounding carcinoma cells is composed of fibroblasts, activated stellate cells (myofibroblast-like cells), various inflammatory cells, proliferating vascular structures, collagens and fibronectin. In particular the cellular components of the stroma produce the tumor microenvironment, which plays a critical role in tumor growth, invasion, spreading, metastasis, angiogenesis, inhibition of anoikis, and chemoresistance. Fibroblasts, myofibroblasts and activated stellate cells produce the extracellular matrix components and are thought to interact actively with tumor cells, thereby promoting cancer progression. In this review, we discuss our current understanding of the role of pancreatic stellate cells (PSC) in the desmoplastic response of pancreas cancer and the effects of PSC on tumor progression, metastasis and drug resistance. Finally we present some novel ideas for tumor therapy by interfering with the cancer cell-host interaction

  8. Intradural squamous cell carcinoma in the sacrum

    Directory of Open Access Journals (Sweden)

    Fujisawa Kozo

    2009-02-01

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

  9. Effects of an inducible anti-sense c-myc gene transfer in a drug-resistant human small-cell-lung-carcinoma cell line

    NARCIS (Netherlands)

    Van Waardenburg, R C; Meijer, C; Burger, H; Nooter, K; De Vries, E G; Mulder, N H; de Jong, Steven

    1997-01-01

    Small-cell-lung-cancer (SCLC) is characterized by rapid development of resistance to cytotoxic agents, such as cisplatin (cDDP) and anthracyclines. c-myc over-expression is one of the reported genetic alterations in this tumor. Amplification of the c-myc gene in this and other cancers is often corre

  10. Immunotherapy in renal cell carcinoma.

    Science.gov (United States)

    Bukowski, R M

    1999-06-01

    Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy include the observations of spontaneous tumor regression, the presence of a T-cell-mediated immune response, and the tumor responses observed in patients receiving cytokine therapy. Analysis of prognostic factors in these patients demonstrates that clinical responses occur most frequently in individuals with good performance status. The cytokines interleukin-2 (IL-2, aldesleukin [Proleukin], interferon-alfa (Intron A, Roferon-A), or the combination produce responses in 15% to 20% of patients. Randomized trials suggest that administration of interferon-alfa may result in a modest improvement in median survival. Investigation of the molecular genetics of renal cell carcinoma and the presence of T-lymphocyte immune dysregulation have suggested new therapeutic strategies. Further preclinical and clinical studies investigating inhibitors of angiogenesis or pharmacologic methods to reverse immune dysregulation are ongoing. Therapeutic results in patients with renal cell carcinoma remain limited, and investigational approaches are warranted. PMID:10378218

  11. Gastric Large Cell Neuroendocrine Carcinoma

    Science.gov (United States)

    Rustagi, Tarun; Alekshun, Todd J.

    2010-01-01

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

  12. Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma.

    Science.gov (United States)

    Kannan, Nagarajan; Kang, Jian; Kong, Xiangjun; Tang, Jianzhong; Perry, Jo K; Mohankumar, Kumarasamypet M; Miller, Lance D; Liu, Edison T; Mertani, Hichem C; Zhu, Tao; Grandison, Prudence M; Liu, Dong-Xu; Lobie, Peter E

    2010-12-01

    We report herein that trefoil factor 3 (TFF3) is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Forced expression of TFF3 in mammary carcinoma cells increased cell proliferation and survival, enhanced anchorage-independent growth, and promoted migration and invasion. Moreover, forced expression of TFF3 increased tumor size in xenograft models. Conversely, depletion of endogenous TFF3 with small interfering RNA (siRNA) decreased the oncogenicity and invasiveness of mammary carcinoma cells. Neutralization of secreted TFF3 by antibody promoted apoptosis, decreased cell growth in vitro, and arrested mammary carcinoma xenograft growth. TFF3 expression was significantly correlated to decreased survival of estrogen receptor (ER)-positive breast cancer patients treated with tamoxifen. Forced expression of TFF3 in mammary carcinoma cells increased ER transcriptional activity, promoted estrogen-independent growth, and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. siRNA-mediated depletion or antibody inhibition of TFF3 significantly enhanced the efficacy of antiestrogens. Increased TFF3 expression was observed in tamoxifen-resistant (TAMR) cells and antibody inhibition of TFF3 in TAMR cells improved tamoxifen sensitivity. Functional antagonism of TFF3 therefore warrants consideration as a novel therapeutic strategy for mammary carcinoma.

  13. Targeting PCDH20 gene by microRNA-122 confers 5-FU resistance in hepatic carcinoma.

    Science.gov (United States)

    Wang, Wei; Liu, Wen Bin; Huang, Da Bing; Jia, Wei; Ji, Chu Shu; Hu, Bing

    2016-01-01

    Drug resistance is one of the main hurdles for the successful treatment of hepatic carcinoma. However, the detailed mechanisms underlying resistance remain largely unknown and therapeutic approaches are limited. In the present study, we show that miR-122 confers resistance to 5-fluorouracil induced hepatocellular carcinoma cell apoptosis in vitro and reduces the potency of 5-fluorouracil in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-122 modulates drug resistance through down-regulation of expression of PCDH20, which belongs to the protocadherin gene family and negatively regulates Akt activation. Knockdown of PCDH20 expression increases Akt phosphorylation, which leads to elevated mTOR activity and enhanced 5-fluorouracil resistance; whereas rescue of PCDH20 expression in miR-122-expressing cells decreases Akt and mTOR phosphorylation, re-sensitizing hepatocellular carcinoma cell to 5-fluorouracil induced apoptosis. Moreover, a specific and potent Akt inhibitor reverses miR-122-conferred 5-fluorouracil resistance. These findings indicate that the miR-122/PCDH20/Akt/mTOR signaling axis has an important role in mediating response to chemotherapy in human hepatocellular carcinoma. A major implication of our study is that inhibition of miR-122 or restoration of PCDH20 expression may have significant therapeutic potential to overcome drug resistance in hepatocellular carcinoma and that the combined use of an Akt inhibitor with 5-fluorouracil may increase efficacy in liver cancer treatment. PMID:27648358

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  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. Scalp squamous cell carcinoma in xeroderma pigmentosum

    OpenAIRE

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

    2014-01-01

    Context: 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. Case Report: 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...

  18. Synchronous Squamous Cell Carcinoma in Multiple Digits

    OpenAIRE

    Abner, Sabra; Redstone, Jeremiah; Chowdhry, Saeed; Kasdan, Morton L.; Wilhelmi, Bradon J.

    2011-01-01

    Cancers of the perionychium are relatively rare occurrences and are often related to chronic inflammation associated with trauma, infection, exposure to ultraviolet radiation, or other carcinogens. Squamous cell carcinoma is the most common tumor reported of the nail bed. Synchronous squamous cell carcinomas of the perionychium have been rarely reported. We present a case of a 46-year-old woman with synchronous squamous cell carcinomas involving both hands and multiple digits. Treatment modal...

  19. Merkel Cell Carcinoma Concurrent with Bowen's Disease

    OpenAIRE

    Park, Hyun Chul; Kang, Ho Song; Park, Kyoung Tae; Oh, Young Ha; Yu, Hee Joon; Kim, Joung Soo

    2012-01-01

    Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy of the elderly and immunocompromised patients. It is occasionally found coexisting with other diseases, such as squamous cell carcinoma, basal cell carcinoma, actinic keratosis, miscellaneous adnexal tumors, and rarely Bowen disease. A 75-year-old woman presented with a 6-month history of an irregularly shaped erythematous patch on the left mandibular angle. Three months later, a 1.5×1.0 cm sized painless and rapidly growi...

  20. Neglected Giant Scalp Basal Cell Carcinoma

    OpenAIRE

    Anne Kristine Larsen, MD; Waseem-Asim Ghulam El-Charnoubi, MD; Julie Gehl, MD, PhD; Christen Krag, MD, PhD

    2014-01-01

    Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstruct...

  1. 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.

  2. Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2

    Institute of Scientific and Technical Information of China (English)

    Bin Liut; Edgar Staren; Takeshi Iwamura; Hubert Appert; John Howard

    2001-01-01

    @@ INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].

  3. Merkel cell carcinoma versus metastatic small cell primary bronchogenic carcinoma

    Directory of Open Access Journals (Sweden)

    Katya Lisette Velasquez Cantillo

    2013-01-01

    Full Text Available Merkel cell carcinoma (MCC of the skin is a rare, aggressive, malignant neuroendocrine neoplasm. The tumor classically demonstrates positive immunohistochemistry (IHC staining for chromogranin A(ChrA, cytokeratin 20 (CK20, neuron specific enolase (NSE and/or achaete-acute complex-like 1 (MASH1. The newly identified Merkel cell polyomavirus (MCPyV has been found to be associated with most MCC cases. The primary histologic differential diagnoses of cutaneous MCC is small cell primary bronchogenic carcinoma (SCLC; moreover, both are of neuroendocrine origin. SCLC accounts for approximately 10-15% of all primary lung cancer cases; this histologic subtype is a distinct entity with biological and oncological features distinct from non-small cell lung cancer (NSCLC. In contradistinction to MCC, SCLC is classically IHC positive for cytokeratin 7 (CK7 and transcription factor (TTF-1. Similar to SCLC, MCC cell lines may be classified into two different biochemical subgroups designated as Classic and Variant. In our review and case report, we aim to emphasize the importance of a multidisciplinary approach to the approach to this difficult differential diagnosis. We also aim to comment about features of the cells of origin of MCC and SCLC; to summarize the microscopic features of both tumors; and to review their respective epidemiologic, clinical, prognostic and treatment features. We want to emphasize the initial workup study of the differential diagnosis patient, including evaluating clinical lymph nodes, a clinical history of any respiratory abnormality, and chest radiogram. If a diagnosis of primary cutaneous MCC is confirmed, classic treatment includes excision of the primary tumor with wide margins, excision of a sentinel lymph node, and computed tomography, positron emission tomography and/or Fluorine-18-fluorodeoxyglucose positron emission tomography scan studies

  4. 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 Filho, Carlos D'Apparecida Santos

    2016-01-01

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

  5. Chemoresistance of CD133+ cancer stem cells in laryngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    YANG Jing-pu; LIU Yan; ZHONG Wei; YU Dan; WEN Lian-ji; JIN Chun-shun

    2011-01-01

    Background Mounting evidence suggests that tumors are histologically heterogeneous and are maintained by a small population of tumor cells termed cancer stem cells. CD133 has been identified as a candidate marker of cancer stem cells in laryngeal carcinoma. This study aimed to analyze the chemoresistance of CD133+ cancer stem cells.Methods The response of Hep-2 cells to different chemotherapeutic agents was investigated and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133,and the CD133+ subset of cells was separated and analyzed in colony formation assays,cell invasion assays,chemotherapy resistance studies,and analyzed for the expression of the drug resistance gene ABCG2.Results About 1%-2% of Hep-2 cells were CD133+ cells,and the CD133+ proportion was enriched by chemotherapy.CD133+ cancer stem cells exhibited higher potential for clonogenicity and invasion,and were more resistant to chemotherapy. This resistance was correlated with higher expression of ABCG2.Conclusions This study suggested that CD133+ cancer stem cells are more resistant to chemotherapy. The expression of ABCG2 could be partially responsible for this. Targeting this small population of CD133+ cancer stem cells could be a strategy to develop more effective treatments for laryngeal carcinoma.

  6. Breast cancer anti-estrogen resistance 4 (BCAR4) drives proliferation of IPH-926 lobular carcinoma cells

    NARCIS (Netherlands)

    T.L.A. van Agthoven (Thecla); L.C.J. Dorssers (Lambert); U. Lehmann (Ulrich); H. Kreipe (Hans); L.H.J. Looijenga (Leendert); M. Christgen (Matthias)

    2015-01-01

    textabstractBackground: Most breast cancers depend on estrogenic growth stimulation. Functional genetic screenings in in vitro cell models have identified genes, which override growth suppression induced by anti-estrogenic drugs like tamoxifen. Using that approach, we have previously identified Brea

  7. Squamous Cell Carcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Andre Luiz De Souza

    2014-11-01

    Full Text Available We previously published our and Johns Hopkins data titled: "Platinum-based therapy in adenosquamous pancreatic cancer: experience at two institutions” [1]. We will here like to submit a related case report as a letter to the editor to JOP in reference to the above paper. Squamous cell carcinoma of the pancreas has various reported incidence rates, ranging from 0.5% to as high as 5% of pancreatic ductal carcinomas [2, 3]. Of the 1300 cases of pancreatic cancers observed at autopsy in a survey in Japan in 1992, 0.7% were squamous cell carcinoma [4]. A Mayo clinic review of very rare exocrine tumors showed an even rarer incidence of squamous cell carcinoma when compared to acinar and small cell carcinoma of the pancreas [5]. This discrepancy in the reported incidence rates related to the fact that some of the cases represent adenosquamous carcinoma rather than pure squamous cell carcinoma of pancreas. In an analysis of 25 patients, mean age at diagnosis of pancreatic squamous cell carcinoma was 62 years (range: 33–80 years and there was no gender difference [6]. There is no study about the molecular profile of squamous carcinoma of the pancreas. There are no retrospective or prospective studies about the best therapy for these tumors

  8. The Expression of p53 and Cox-2 in Basal Cell Carcinoma, Squamous Cell Carcinoma and Actinic Keratosis Cases

    OpenAIRE

    Ülker KARAGECE YALÇIN; Selda SEÇKİN

    2012-01-01

    Objective: The aim of this study was to investigate p53 and COX-2 expressions in basal cell carcinoma, squamous cell carcinoma and actinic keratoses, and to determine a possible relationship.Material and Method: 50 basal cell carcinoma, 45 squamous cell carcinoma and 45 actinic keratosis cases were evaluated. The type of tumor in basal cell carcinoma and tumor differentiation in squamous cell carcinoma were noted and the paraffin block that best represented the tumor was chosen. Immunostainin...

  9. Acinar Cell Carcinoma of the Pancreas

    Institute of Scientific and Technical Information of China (English)

    Hua Li; Qiang Li

    2008-01-01

    Acinar cell carcinoma of the pancreas is a rare tumor which is defined as a carcinoma that exhibits pancreatic enzyme production by neoplastic cells. This review includes re-cent developments in our understanding of the epidemiology and pathogenesis of ACC, imaging and pathological diagnosis and ap-proaches to treatment with reference to the literature.

  10. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

  12. Inhibition of p70S6K1 Activation by Pdcd4 Overcomes the Resistance to an IGF-1R/IR Inhibitor in Colon Carcinoma Cells.

    Science.gov (United States)

    Zhang, Yan; Wang, Qing; Chen, Li; Yang, Hsin-Sheng

    2015-03-01

    Agents targeting insulin-like growth factor 1 receptor (IGF-1R) are being actively examined in clinical trials. Although there has been some initial success of single-agent targeting IGF-1R, attempts in later studies failed because of resistance. This study aimed to understand the effects of programmed cell death 4 (Pdcd4) on the chemosensitivity of the IGF-1R inhibitor OSI-906 in colorectal cancer cells and the mechanism underlying this impact. Using OSI-906-resistant and -sensitive colorectal cancer cells, we found that the Pdcd4 level directly correlates with cell chemosensitivity to OSI-906. In addition, tumors derived from Pdcd4 knockdown cells resist the growth inhibitory effect of OSI-906 in a colorectal cancer xenograft mouse model. Moreover, Pdcd4 enhances the antiproliferative effect of OSI-906 in resistant cells through suppression of p70S6K1 activation. Knockdown of p70S6K1, but not p70S6K2, significantly increases the chemosensitivity of OSI-906 in cultured colorectal cancer cells. Furthermore, the combination of OSI-906 and PF-4708671, a p70S6K1 inhibitor, efficiently suppresses the growth of OSI-906-resistant colon tumor cells in vitro and in vivo. Taken together, activation of p70S6K1 that is inhibited by Pdcd4 is essential for resistance to the IGF-1R inhibitor in colon tumor cells, and the combinational treatment of OSI-906 and PF-4708671 results in enhanced antiproliferation effects in colorectal cancer cells in vitro and in vivo, providing a novel venue to overcome the resistance to the IGF-1R inhibitor in treating colorectal cancer. PMID:25573956

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

    Directory of Open Access Journals (Sweden)

    Mahesh Deshmukh

    2011-01-01

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

  14. Long-term cultivation of colorectal carcinoma cells with anti-cancer drugs induces drug resistance and telomere elongation: an in vitro study

    Directory of Open Access Journals (Sweden)

    Mochizuki Hidetaka

    2001-08-01

    Full Text Available Abstract Background The role of telomerase activation in the expression and/or maintenance of drug resistance is not clearly understood. Therefore, we investigated the relationships, among the telomerase activity, telomere length and the expression of multidrug resistance genes in colorectal cancer cell lines cultivated with anti-cancer drugs. Methods LoVo and DLD-1 cells were continuously grown in the presence of both CDDP and 5-FU for up to 100 days. Cell proliferation, telomerase activity, telomere length and the expression of multidrug resistance genes were serially monitored as the PDL increased. Results The expression of multidrug resistance genes tended to increase as the PDL increased. However, an abnormal aneuploid clone was not detected as far as the cells were monitored by a DNA histogram analysis. Tumor cells showing resistance to anti-cancer drugs revealed a higher cell proliferation rate. The telomere length gradually increased with a progressive PDL. The telomerase activity reached a maximum level at 15 PDL in LoVo cells and at 27 PDL in DLD-1 cells. An increase in the mRNA expression of the telomerase components, especially in hTERT and in hTR, was observed at the same PDLs. Conclusions These results suggest that a high telomerase activity and an elongation of telomeres both appear to help maintain and/or increase drug resistance in colorectal cancer cells. Cancer cells with long telomeres and a high proliferative activity may thus be able to better survive exposure to anti-cancer drugs. This is presumably due to an increased chromosome stability and a strong expression of both mdr-1 and MRP genes.

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

    Science.gov (United States)

    2016-05-16

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

  16. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    OpenAIRE

    Yeliz Bilir; Erkan Gokce; Banu Ozturk; Faik Alev Deresoy; Ruken Yuksekkaya; Emel Yaman

    2014-01-01

    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...

  17. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  18. 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.

  19. Basal cell carcinoma in oculo-cutaneous albinism

    OpenAIRE

    Ajay Kumar; Ashish Chauhan; Subhash Kashyap

    2016-01-01

    The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition ...

  20. Paraneoplastic Cough and Renal Cell Carcinoma.

    Science.gov (United States)

    Sullivan, Stephen

    2016-01-01

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

  1. Sunitinib benefits patients with renal cell carcinoma

    Science.gov (United States)

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

  2. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    Science.gov (United States)

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    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.

  3. Squamous cell carcinoma arising in an odontogenic cyst

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jae Jung; Hwang, Eui Hwan; Lee, Sang Rae [Kyunghee University College of Medicine, Seoul (Korea, Republic of); Choi, Jeong Hee [Chonnam National University College of Medicine, Kwangju (Korea, Republic of)

    2003-12-15

    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.

  4. Using 99mTc-MIBI to Evaluate the Effects of Chemosensitizer on P-glycoprotein in Multidrug-resistant Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANGZhenwei; ZHANGXuemei; WUHua; ZHAOMing; XIANYUZhiqun; ZHOUJian; LAIShiying

    2005-01-01

    Objective: To establish a method to evaluate the effects of chemosensitizer on P-glycoprotein using 99mTc-MIBI, and observe the changes of 99mTc-MIBI uptake kinetics and P-glycoprotein levels after using verapamil in MDR human breast cells MCF-7/Adr. Methods: MDR breast carcinoma cells, MCF-7/Adr, were incubated and different protocols were performed. Protocol I: a chemosensitizer, verapamil (10μmol/L), was added into cell culture medium, while in control group, the same volume of DMEM was given. Cells were harvested after 2 h incubation with 99mTc-MIBI. Protocol Ⅱ: Verapamil (10μmol/L) was added into cell culture medium and incubated for 20 min, 40 min, 60 rain, 80 min, 8 h, 24 h, 48 h and 72 h respectively. Cells were harvested after 2 h incubation with 99mTc-MIBI. The radioactivity of the cells was measured and P-glycoprotein expression levels were determined with immunohistochemical stain. Results: Protocol I: After 2h incubation with verapamil the cellular uptake of 99mTc-MIBI was remarkably higher than control group (t=2.33, P0.05). Protocol

  5. Hurthle cell carcinoma of the thyroid

    OpenAIRE

    Sandoval, Mark Anthony S; Paz-Pacheco, Elizabeth

    2011-01-01

    A 63-year-old man consulted for a non-toxic thyroid nodule of 2 years’ duration. Fine needle aspiration revealed cell findings consistent with papillary thyroid carcinoma. He eventually underwent total thyroidectomy. Microscopic examination revealed histologic features of Hurthle cell carcinoma of the thyroid. He received radioactive iodine therapy and suppressive levothyroxine treatment. Post-therapy whole body iodine-131 scan revealed thyroid tissue remnants limited to the anterior neck. Fo...

  6. Renal Cell Carcinoma Metastasized to Pagetic Bone.

    Science.gov (United States)

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

    2016-01-01

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

  7. MRP3 as a novel resistance factor for sorafenib in hepatocellular carcinoma.

    Science.gov (United States)

    Tomonari, Tetsu; Takeishi, Shunsaku; Taniguchi, Tatsuya; Tanaka, Takahiro; Tanaka, Hironori; Fujimoto, Shota; Kimura, Tetsuo; Okamoto, Koichi; Miyamoto, Hiroshi; Muguruma, Naoki; Takayama, Tetsuji

    2016-02-01

    The mechanism of resistance of hepatocellular carcinoma (HCC) to sorafenib is unknown and no useful predictive biomarker for sorafenib treatment has been reported. Accordingly, we established sorafenib-resistant HCC cells and investigated the underlying mechanism of resistance to sorafenib. Sorafenib-resistant cell lines were established from the HCC cell line PLC/PRF5 by cultivation under continuous exposure to increasing concentration of sorafenib. The IC50 values of the 2 resistant clones PLC/PRF5-R1 and PLC-PRF5-R2 were 9.2±0.47 μM (1.8-fold) and 25±5.1 μM (4.6-fold) respectively, which were significantly higher than that of parental PLC/PRF5 cells (5.4±0.17 μM) (p BSEP, MDR1, MRP2, BCRP, MRP4 and OCT1 between resistant clones and parent cells. However, the expression levels of MRP3 in the 2 resistant clones were significantly higher than that of parent cells. When MRP3 gene was knocked down by siRNA in PLC-PRF5-R2 cells, the sensitivity of the cells to sorafenib was restored. In the analysis of gene mutation, there was no mutation in the activation segment of Raf1 kinase in the resistant clones. Our data clearly demonstrate that the efflux transporter MRP3 plays an important role in resistance to sorafenib in HCC cells. PMID:26769852

  8. 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

  9. Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability

    NARCIS (Netherlands)

    den Bakker, Michael A.; Willemsen, Sten; Gruenberg, Katrien; Noorduijn, L. Arnold; van Oosterhout, Matthijs F. M.; van Suylen, Robert J.; Timens, Wim; Vrugt, Bart; Wiersma-van Tilburg, Anne; Thunnissen, Frederik B. J. M.

    2010-01-01

    Aims: To test the hypothesis that the published morphological criteria permit reliable segregation of small cell carcinoma of the lung (SCLC) and large cell neuroendocrine carcinoma (LCNEC) cases by determining the interobserver variation. Methods and results: One hundred and seventy cases of SCLC,

  10. Cost-effectiveness and budget impact analysis of vinflunine used in the treatment of patients with urothelial transitional cell carcinoma resistant to platinum-based regimens

    Directory of Open Access Journals (Sweden)

    A. Yu. Kulikov

    2015-01-01

    Full Text Available As of now, vinflunine is the only second-line chemotherapy drug showing an advantage over the best maintenance therapy in a Phase IIIrandomized study treating patients with urothelial transitional cell carcinoma. Due to the advent of this drug, it was relevant to make a pharmacoeconomic analysis comparing therapy with vinflunine in combination with the best maintenance therapy and the latter only. A budget impact analysis showed that the use of the new drug required additional expenditures. The ICER reflecting the cost of one additional year of life and estimating vinflunine therapy as cost-effective was determined by the results of a cost-effectiveness analysis.

  11. Curcumin Promoted the Apoptosis of Cisplain-resistant Human Lung Carcinoma Cells A549/DDP through Down-regulating miR-186*

    Directory of Open Access Journals (Sweden)

    Jian ZHANG

    2010-04-01

    Full Text Available Background and objective Curcumin, a natural compound, is derived from the rthizom of Curcuma longa. In vitro and in vivo preclinical studies have shown its anti-inflammatory, antioxidant, anticancer activities and so on. miR-186*, which was found by microarray technology, was highly expressed in lung carcinoma cells A549/DDP. The aim of this study is to illustrate whether Curcumin could promote the apoptosis of A549/DDP cells through regulating the expression of miR-186*. Methods An oligonucleotide microarray chip was used to profile microRNA (miRNA expressions in A549/DDP cells treated with and without Curcumin. The significantly differentially expressed miRNA, which was selected from microarray chip, validated by quantitative real-time PCR. Ultimately, the remarkably expressed miRNA modulated the apoptosis assaying by flow cytometry expriments and the survival rate was measured by MTT method. Results The microarray chip results demonstrated: Curcumin altered the expression level of miRNAs compared with untreated control in A549/DDP cell line, miR-186* was significantly down-regulated after Curcumin treatment, which confirmed by quantitative real-time PCR. Downregulation of miR-186* expression by curcumin elevated the apoptosis, and the survival rate of A549/DDP cells decreased; but up-regulation of miR-186* expression by transfection its mimics restrained the apoptosis, the survival rate of A549/DDP cells increased, which were assayed by flow cytometry expriments and MTT method. Conclusion Modulation of miRNAs expression may be an important mechanism underlying the biological roles of Curcumin.

  12. Reversing the Multidrug Resistance of Human Carcinoma of Colon Cell of SchB%五味子乙素逆转人结肠癌细胞多药耐药性

    Institute of Scientific and Technical Information of China (English)

    徐秋玲; 金秀东; 郭冉; 张绪东; 刘桂莲

    2011-01-01

    【Objective】The research of multidrug-resistance of SchB on resistance to human carcinoma of colon cell line(THC-8307/OXA).【Method】The cytotoxic effect of OXA and SchB was evaluated by MTT assay.The effect of SchB on BCRP of THC-8307/OXA was evaluated by Western Blot.【Result】MTT assay showed that SchB at the concentration of 12.5,25,50μg/mL had no cytotoxicity to human carcinoma cell line of colon(THC-8307) and THC-8307/OXA.The IC50 value of OXA to THC-8307 cell line was 3.50μg/mL and that of to THC-8307/OXA cell line was 12.21μg/mL,which indicated THC-8307/OXA cell line were 3.49 times more resistant to OXA in comparison with the THC-8307 cell line,SchB at the concentration of 12.5-50μg/mL could decrease the IC50 value of OXA to THC-8307/OXA cell line to 5.94,4.47,3.15μg/mL,reverse multiple was 2.06,2.73,3.88 respectively.BCRP of THC-8307/OXA cell line was significantly decreased through Western Blot after treated with SchB(25μg/mL)and OXA(20μg/mL) for 48 h.【Conclusion】SchB could reverse MDR in multidrug-resistant human carcinoma THC-8307/OXA cell line of colon.Its mechanism might be associated with down-regulation of expression of BCRP.%目的:研究五味子乙素(SchisandrinB,SchB)抑制逆转耐奥沙利铂人结肠癌细胞(THC-8307/OXA)多药耐药性(MDR)。方法:采用噻唑蓝(MTT)比色法检测奥沙利铂(OXA)和五味子乙素的细胞毒性;Western Blot检测SchB对耐奥沙利铂人结肠癌细胞THC-8307/OXA细胞BCRP蛋白水平的影响。结果:SchB(12.5、25、50μg/mL)对人结肠癌细胞(THC-8307)和THC-8307/OXA无显著毒性作用(P〉0.05,)OXA对THC-8307的IC50为3.50μg/mL,而对THC-8307/OXA的IC50为12.21μg/mL,THC-8307/OXA较THC-8307对OXA耐药3.49倍,SchB(12.5、25、50μg/mL)能使OXA对THC-8307/OXA细胞的IC50从12.21μg/mL依次下降至5.94、4.47、3.15μg/mL,逆转倍数分别为2.06、2.73、3.88倍。Western Blot检测SchB(25

  13. Epidemiologia do carcinoma basocelular Epidemiology of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Valquiria Pessoa Chinem

    2011-04-01

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

  14. Large Cell Neuroendocrine Carcinoma of the Lung

    Directory of Open Access Journals (Sweden)

    Yusuf Aydemir

    2015-11-01

    Full Text Available Large-cell neuroendocrine carcinomas of the lung are extremely rare. There are difficulties related to the diagnosis and treatment and there are no consensus because of the small number of studies. 65-year-old male patient presented with hemoptysis. Chest X-ray and thoracic computorized tomography scan showed a mass lesion and it could not be diagnosed by bronchoscopic biopsy and lavage. Lobectomy was performed due to the high value of standardized uptake value in positron emission tomography. Large cell neuroendocrine carcinoma was diagnosed with pathological evaluation and immunohistochemical study and after 20-month follow-up there was no recurrence. The diagnosis, treatment, and prognosis of large cell neuroendocrine carcinoma in the light of the literature is presented.

  15. THE RELATIONSHIP BETWEEN mdrl GENE EXPRESSION AND DRUG-RESISTANCE IN OVARIAN CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    朱玲; 郎景和; 沈铿; 冷金花

    1998-01-01

    Objective. To investigate the relationship between mdrl gene expression and multidrug resistance in ovarian Carcinoma. Design. We established tumor-bearing mice model of ovarian carcinoma,compared the anticancer drug sensitivity of OC/mdr cell and OC/mdr4 cell in vitro, investigated the effect of cyclosporin A on reversing the multidrug resistance both in vitro and in the tumor bearing mice model,detected the mdrl gene expresion in human ovarian carcinoma specimens. Main outcome measures. Anticancer drug sensitivity of both OC/mdr-cell and OC/mdr+ cell is measured by the methods of MTT assays. mdrl gene expression is detected by the methods of RT-PCR. Results. Using MTT assay,OC/mdr+ cell is 4.1~15.5 times more resistant to VP-16,VCR,DNR,and DOX than OC/mdr- cell in vitro 2μg/ml cyclosporice A(CsA)reducod the resistance of OC/mdr+ cell to DOX,from 0. 324±0. 072μg/ml to 0. 088±0. 024μg/ml. To OC/mdr- cell,CsA did not significandy increase its sensitivity to DOX. Tumor-hearing mice with positive mdrl gene expression showed non-responsiveness to DOX chemotherapy. When combined with intraperitonesl injection of CsA, the growth rate of tumor cells decreased significantly (P<0. 01). Only 4 of 23(17.39%)tumors from patients who had not received chemotherapy exhibited pcsitive mdrl gene expreession,while 6 of 9 (66.67%)treated patients showed positive mdrl gene expression (Fisher exact test= P<0. 05). After cytoreductive surgery and chemotherapy, 14 of 19 untreated patients with negative mdrl gene expression had partial or complete response, while in patients with positive rndrl gene expression, 8 of 10 showed poor prognosis(Fisher exact test: P<0. 05). Conclusion. The expression of nadrl gene is associated with previous chemotherapy. CsA can reverse the resistance of mdr+ cells to indr-associated drs both in vitro and in vivo. For the patients with ovarian Carcinomas, the percentage of nonresponsiveness to the chemotherapy was found to he significantly higher among

  16. MET Inhibition in Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

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

    2016-01-01

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

  17. Steroid metabolism in the hormone dependent MCF-7 human breast carcinoma cell line and its two hormone resistant subpopulations MCF-7/LCC1 and MCF-7/LCC2

    DEFF Research Database (Denmark)

    Jørgensen, L; Brünner, N; Spang-Thomsen, M;

    1998-01-01

    and 17beta-hydroxysteroid oxidoreductase were investigated isolating the following steroids: estriol (E3), estradiol (E2), estrone (E1), 3alpha/beta-androstanediol (A-diol), testosterone (T), dihydrotestosterone (DHT), androsterone (AND), androstenedion (4-AD) and androstanedione (A-dion). For all......, and preincubation with cortisol had no effect on the enzyme activity. With [14C]T as the substrate, the metabolized level of DHT was very similar in the three cell lines, though MCF-7/LCC1 and MCF-7/LCC2 utilized the substrate to a much lesser extent. The amount of DHT and 4-AD produced were comparable in the two...... to the parent MCF-7. However, since treatment with DHT and T inhibited cell growth equally well in all three tumor cell lines, it is unlikely that the found differences in steroid metabolism was involved in the acquisition of the endocrine resistance of the two MCF-7 sublines....

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

    Science.gov (United States)

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

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

  19. 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...

  20. Basal Cell Carcinoma in a Child

    OpenAIRE

    Samet Vasfi Kuvat; Zuhal Gücin; Barış Keklik; Gülzade Özyalvaçlı; Karaca Başaran

    2011-01-01

    Basal cell carcinoma is the most commonly seen nonmelanoma skin cancer which is rarely encountered in the childhood period. An 11-year old child was admitted to our clinic due to an erythematous and a slightly pigmented lesion with a 3 × 4 cm diameter on his posterior scalp. Macroscopically, the lesion was excised with a 10 mm safety margin. Pathologic examination revealed a basal cell carcinoma. No symptoms or signs of a syndrome were observed both in the patient and his family.

  1. Basal Cell Carcinoma Arising in a Tattooed Eyebrow

    OpenAIRE

    Lee, Jong-Sun; Park, Jin; Kim, Seong-min; Yun, Seok-Kweon; 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.

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

    Science.gov (United States)

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

    2013-07-01

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

  3. High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

    Directory of Open Access Journals (Sweden)

    Chien Chih-Yen

    2011-03-01

    Full Text Available Abstract Background This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1 expression on response to cisplatin-based induction chemotherapy (IC followed by concurrent chemoradiation (CCRT in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC patients. Methods Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records. Results The 12-month progression-free survival (PFS and 2-year overall survival (OS rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p Conclusions Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.

  4. Basaloid squamous cell carcinoma involving floor of the mouth

    Directory of Open Access Journals (Sweden)

    Sah Kunal

    2008-01-01

    Full Text Available Basaloid squamous cell carcinomas of oral mucosa are uncommon. Majority of them can be differentiated from squamous cell carcinoma by their aggressive clinical course and their histopathological features. This case report presents a case of 70-year-old male with basaloid squamous cell carcinoma involving the floor of the mouth.

  5. Stem cell research in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chengyi SUN; Shi ZUO

    2008-01-01

    The traditional view that adult human liver tumors, mainly hepatocellular carcinoma (HCC), arise from mature cell types has been challenged in recent dec-ades. The results of several studies suggest that HCC can be derived from liver stem cells. There are four levels of cells in the liver stem cell lineage: hepatocytes, hepatic stem cells/oval cells, bone marrow stem cells and hepato-pancreas stem cells. However, whether HCC is resulted from the differentiation block of stem cells and, moreover, which liver stem cell lineage is the source cell of hepatocarcinogenesis remain controversial. In this review, we focus on the current status of liver stem cell research and their roles in carcinogenesis of HCC, in order to explore new approaches for stem cell therapy of HCC.

  6. Ipsilateral synchronous renal pelvic transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    韩平; 魏强; 石明; 杨宇如

    2004-01-01

    @@ Reports of multiple synchronous primary renal neoplasms in the literature are rare. Although primary renal tumors of 2 distinctively dissimilar origins have been sporadically described,1-6 to our knowledge there have been no reported cases of triple primary renal neoplasms in the same kidney. Here we report a very rare case of ipsilateral synchronous renal pelvic transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma with marked hydronephrosis and multiple stones in the same kidney.

  7. Morphometric characteristics of basal cell carcinoma peritumoral stroma varies among basal cell carcinoma subtypes

    OpenAIRE

    Lesack Kyle; Naugler Christopher

    2012-01-01

    Abstract Background The role that the peritumoral stroma plays in the growth of tumours is currently poorly understood. In this manuscript the morphometric characteristics of basal cell carcinoma subtypes and their associated peritumoral stromas are presented. Methods Ninety eight digitized basal cell carcinoma histology slides were categorized as infiltrative, nodular, or superficial subtypes, and were analysed using a combination of manual and computer-assisted approaches. The morphometric ...

  8. Oesophageal squamous cell carcinoma in two cats

    International Nuclear Information System (INIS)

    Two cases of feline oesophageal squamous cell carcinoma are described. In both cases, diagnosis was achieved by radiography, endoscopy and cytology, and later confirmed by histology. One cat underwent oesophagectomy followed by end-to-end anastomosis, but died three days postsurgery; the second cat was euthanased after diagnosis

  9. The epidemiology of renal cell carcinoma

    NARCIS (Netherlands)

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

    2011-01-01

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

  10. Pancreatic Stellate Cells and Pancreatic Carcinoma: An Unholy Alliance

    Directory of Open Access Journals (Sweden)

    Johannes-Matthias Löhr

    2009-07-01

    Full Text Available The importance of the stromal compartment in the development, proliferation, invasion, metastasis and resistance of epithelial cancers has increasingly been recognized in recent decades [1, 2]. This stromal reaction is found in many carcinomas, e.g. in breast, prostate, colon, ovarian and pancreatic cancer. It is made up of stromal cells, endothelial cells, immune cells and extracellular matrix proteins. Moreover, the ECM proteins in the stroma act as a reservoir for growth factors released either by tumor or stromal cells, thus enabling autocrine and paracrine stimulation of the cells within the tumor mass. In this respect, groundbreaking work in solid tumors was done by Mina Bissell with breast carcinoma as her model system [3]. Recently, Vonlaufen et al. have contributed a review on the relationship between activated pancreatic stellate cells (PSCs and pancreatic ductal adenocarcinoma cells which is worth reading [4]. Vonlaufen et al., with their own study [5] and those of some other groups (see their review, convincingly demonstrate a reciprocal influence of both nonepithelial and epithelial constituents of pancreatic carcinoma which works to their mutual benefit. Thus, the coinjection of PSC and pancreatic tumor cells enhances tumor growth and metastasis. In In vitro and animal models, PSCs increase tumor cell proliferation and decrease basal and induced apoptosis of pancreatic tumor cells. On the other hand, pancreatic tumor cells activate PSCs, recruit them to their vicinity and stimulate their proliferation. This review clearly exemplifies the specialized milieu in which both cell types grow to their mutual benefit, thus forming one of the deadliest tumors we know.

  11. Basal cell carcinoma in oculo-cutaneous albinism

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2016-06-01

    Full Text Available The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition and diagnosis of suspected lesions by performing histopathological examination in unusual circumstances. [Int J Res Med Sci 2016; 4(6.000: 2452-2454

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

    Energy Technology Data Exchange (ETDEWEB)

    Felthaus, O. [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany); Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Ettl, T.; Gosau, M.; Driemel, O. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Brockhoff, G. [Department of Gynecology and Obstetrics, University of Regensburg (Germany); Reck, A. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Zeitler, K. [Institute of Pathology, University of Regensburg (Germany); Hautmann, M. [Department of Radiotherapy, University of Regensburg (Germany); Reichert, T.E. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Schmalz, G. [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany); Morsczeck, C., E-mail: christian.morsczeck@klinik.uni-regensburg.de [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany)

    2011-04-01

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

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

    International Nuclear Information System (INIS)

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

  14. Bilateral acrometastasis in a case renal cell carcinoma

    Science.gov (United States)

    Vaishya, Raju; Vijay, Vipul; Vaish, Abhishek

    2014-01-01

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

  15. Tnhibitory effect of Fuzheng Yiliuyin in combination with chemotherapeutics on human gastric carcinoma cell strain

    Institute of Scientific and Technical Information of China (English)

    Yi Liu; Rui Wang; Gen-Quan Qiu; Ke-Jun Nan; Xi-Cai Sun

    2006-01-01

    AIM: To study the inhibitory effects of Fuzheng Yiliuyin (Decoction for Suppressing Tumors by Strengthening the Body Resistance) in combination with chemotherapeutics on human gastric carcinoma cell strain.METHODS: Fuzheng Yiliuyin (ZY) combined with various kinds of chemotherapeutics was put into two kinds of cultivated human gastric carcinoma cell strains,then its inhibitory effects on human gastric carcinoma cell strains were determind by the MTT method. Flow cytometer was used to assay the apoptosis rate, and the ultrastructure of gastric carcinoma cells was observed under transmission electron microscope.RESULTS: Obvious apoptosis was seen in gastric carcinoma cells after treatment with ZY for 72 h. ZY and chemical drugs had synergistic inhibition effects on the cultivated gastric carcinoma cells, but the effects were different on various cell strains. The inhibitory effects of ZY could be strengthened by cytotoxic action and apoptosis. ZY combined with fluorouracil, etoposide and cisplatin (EFP) chemotherapeutics had better inhibitory effects on SGC-7901, while ZY combined with EFP or with DDP chemotherapeutics had better inhibitory effects than other drugs on MGC-803.CONCLUSION: ZY induces apoptosis and inhibits the growth of gastric carcinoma cells. ZY has the synergistic function of chemotherapeutics.

  16. Primary Small Cell Carcinoma of the Vagina

    Directory of Open Access Journals (Sweden)

    Rafael Oliveira

    2013-01-01

    Full Text Available The primary small cell carcinoma of the vagina is rare, and it is a highly aggressive malignancy with no consensus regarding the treatment of this tumor. The survival rate for patients treated in the early stages is around two years. We related the case report of a patient of 41 years with a vegetative and necrotic lesion in left vaginal wall, in middle and upper third, and involvement of parametrium in its proximal third and medium third. A biopsy showed a small cell undifferentiated carcinoma composed of epithelial cells with round nuclei, oval or elongated, hyperchromatic nuclei, with little distinct nucleoli, and scarce cytoplasm. Immunohistochemistry showed positivity for AE1/AE3, CD57, and chromogranin A. The patient received 6 cycles of chemotherapy with cisplatin and etoposide and radiotherapy, achieving complete response, with complete regression of the lesion. The patient had no sign of tumor recurrence and locoregional or distant metastases after 5 months of followup.

  17. The Expression of p53 and Cox-2 in Basal Cell Carcinoma, Squamous Cell Carcinoma and Actinic Keratosis Cases

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    Ülker KARAGECE YALÇIN

    2012-05-01

    Full Text Available Objective: The aim of this study was to investigate p53 and COX-2 expressions in basal cell carcinoma, squamous cell carcinoma and actinic keratoses, and to determine a possible relationship.Material and Method: 50 basal cell carcinoma, 45 squamous cell carcinoma and 45 actinic keratosis cases were evaluated. The type of tumor in basal cell carcinoma and tumor differentiation in squamous cell carcinoma were noted and the paraffin block that best represented the tumor was chosen. Immunostaining by p53 and COX-2 was performed on sections of the paraffin blocks.Results: p53 expression was observed in 98% of basal cell carcinoma, 88.9% of squamous cell carcinoma and all actinic keratosis cases. p53 expression was also noted in non-dysplastic appearing epithelium in actinic keratosis cases. COX-2 expression was seen in 90, 100 and 88.9% of the basal cell carcinoma, squamous cell carcinoma and actinic keratosis groups, respectively. Skin appendages, inflammatory cells and vascular structures were also stained by COX-2 besides tumor tissue. COX-2 expression increased by the p53 expression increase in basal cell carcinoma and squamous cell carcinoma. p53 and COX-2 expressions were not related in terms of tumor type in the BCC and were not related in terms of differentiation in SCC.Conclusion: The existence of p53 expression in actinic keratosis cases has supported the idea that p53 plays a role in the early steps of carcinogenesis in skin cancers. The fact that the expression of COX-2 increases in line with the increase of p53 expression in basal cell carcinoma and squamous cell carcinoma cases indicates that COX-2 expression may be affected by p53

  18. Effects of Hydroxyapatite Nanoparticles on Apoptosis and Invasion of Human Renal Cell Carcinoma 786-0 Cells

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-xin; KONG Xiang-bo; ZHAO Xu; ZHANG Ling; HOU Yi; HAN Wei; WANG Kai-chen; GUO Bao-feng; LIU Ying; CHANG Xi-hua; WANG Wei-hua; NA Wan-li

    2011-01-01

    Renal cell carcinoma is the most common cancer of the kidney, and resistant to traditional therapies. The aim of this study is to investigate the effects of hydroxyapatite nanoparticles on human renal cell carcinoma 786-0 cells. Cell proliferation was assessed with an 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide(MTT)staining kit. The apoptosis assay was assessed with an FITC Annexin V Apoptosis Detection Kit. Caspase-3 and caspase-12 were detected by immunocytochemical staining and semi-quantitative RT-PCR. Cell wound healing assay was used to ensure cell motility. Matrigel invasion assay was analysed via transwell chambers. Our results showed that hydroxyapatite nanoparticles significantly reduced cell proliferation, invasion and induced apoptosis of 786-0 cells. The inhibiting action may have relation with up-regulated caspase-12, leading the cells to apoptosis. This study suggests that hydroxyapatite nanoparticles may be an effective and delivery system for renal cell carcinoma therapy.

  19. Cell survival curve for primary hepatic carcinoma cells and relationship between SF2 of hepatic carcinoma cells and radiosensitivity

    Institute of Scientific and Technical Information of China (English)

    Zhi-Zhong Liu; Wen-Ying Huang; Ju-Sheng Lin; Xiao-Sheng Li; Xiao Lan; Xiao-Kun Cai; Kuo-Huan Liang; Hai-Jun Zhou

    2005-01-01

    AIM: To establish the cell survival curve for primary hepatic carcinoma cells and to study the relationship between SF2 of primary hepatic carcinoma cells and radiosensitivity.METHODS: Hepatic carcinoma cells were cultured in vitro using 39 samples of hepatic carcinoma at stagesⅡ-Ⅳ. Twenty-nine samples were cultured successfully in the fifth generation cells. After these cells were radiated with different dosages, the cell survival ratio and SF2were calculated by clonogenic assay and SF2 model respectively. The relationship between SF2 and the clinical pathological feature was analyzed.RESULTS: Twenty-nine of thirty-nine samples were successfully cultured. After X-ray radiation of the fifth generation cells with 0, 2, 4, 6, 8 Gy, the cell survival rate was 41%, 36.5%, 31.0%, 26.8%, and 19%,respectively. There was a negative correlation between cell survival and irradiation dosage (r = -0.973, P<0.05).SF2 ranged 0.28-0.78 and correlated with the clinical stage and pathological grade of hepatic carcinoma(P<0.05). There was a positive correlation between SF2and D0.5 (r = 0.773, P<0.05).CONCLUSION: SF2 correlates with the clinical stage and pathological grade of hepatic carcinoma and is a marker for predicting the radiosensitivity of hepatic carcinomas.

  20. Delayed Diagnosis: Giant Basal Cell Carcinoma of Scalp

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    Didem Didar Balcı,

    2008-07-01

    Full Text Available Although basal cell carcinoma (BCC is the most common form of skin cancer, the scalp lesions of BCC have been rarely reported. Giant BCC is defined as a tumor larger than 5 cm in diameter and only 0.5-1 % of all BCCs achieve this size. We report a case of giant BCC on the scalp that was treated with topical coticosteroids and antifungal shampoo for five years. BCC should be considered in the differential diagnosis in erythematous plaque type lesions resistant to therapy with long duration localized on the scalp.

  1. Reversal Effect of γ-Schisandrin Compound on Multidrug Resistance of Human Carcinoma of Colon Cell THC-8307%复方五味子素B逆转多药耐药性人结肠癌细胞THC-8307

    Institute of Scientific and Technical Information of China (English)

    金秀东; 徐秋玲; 郑学芝; 张绪东; 刘桂莲; 孙卫

    2011-01-01

    Objective To investigate the reversal effect and mechanism of γ-Schisandrin compound (γSC )against multidrug resistance(MDR )of human carcinoma of colon cell THC-8307/OXA. Methods The cytotoxic effect of the therapeutic agents on cells was determined hy MTT assay. The expression of P-gp in THC-8307 cells was examined by Westernblot method. Results γSC was nontoxic to THC-8307 cells and THC -8307/OXA when its concentration was less than 12. 5 mg/L. However,it obviously reversed the multidrug resistance of THC-8307/OXA. P-gp was highly expressed in THC-8307/OXA while no expression in THC-8307. γSC could decrease the expression of P-gp in THC-8307/OXA. Conclusion γSC reversed the multidrug resistance of tumor THC -8307/OXA cells by the way of decreasing the expression of P-gp.%目的 探讨复方五味子素B(Γsc)逆转人结肠癌细胞THC -8307/OXA多药耐药的作用机制.方法 采用四甲基偶氮唑蓝(MTT)法测定药物对细胞的毒性作用;通过Western blot法分析药物对THC-8307细胞P糖蛋白(P-gp)多药耐药相关蛋白表达的影响.结果 Γsc在浓度<12.5 mg/L时对THC -8307和THC -8307/OXA无毒性作用,12.5 mg/L的Γsc可明显逆转THC -8307/OXA耐药细胞的耐药性.THC -8307细胞不表达P-gp,THC -8307/OXA细胞P-gp高表达.加入Γsc后THC -8307/OXA细胞P-gp蛋白的表达明显下降.结论 Γsc具有逆转THC -8307/OXA的作用,主要通过下调肿瘤多药耐药细胞内P-gp的表达逆转耐药.

  2. An Unusual Presentation of Merkel Cell Carcinoma

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    Kamuran İbiş

    2012-03-01

    Full Text Available We describe a 71-year-old male patient admitted to the hospital with posterior chest pain. Following the detection of a paravetebral mass at the level of the 2nd thoracic vertebra, the patient underwent a surgical en bloc resection of the mass. The histopathologic examination revealed a Merkel cell carcinoma. One month after the operation, magnetic resonance imaging showed an inoperable mass in the same location, which indicated a rapid progression of the tumor. The patient died of progressive respiratory failure due to pneumonia on the 6th day after the onset of radiochemotherapy. Although this appears to be an isolated case, Merkel cell carcinoma must be included in the differential diagnosis of intrathoracic masses.

  3. Oral Cavity Clear Cell Odontogenic Carcinoma.

    Science.gov (United States)

    Ginat, Daniel Thomas; Villaflor, Victoria; Cipriani, Nicole A

    2016-06-01

    A case of clear cell odontogenic carcinoma of the oral cavity is described in this sine qua non radiology-pathology correlation article. CT demonstrated a solid and cystic mass arising from the mandible. Histology demonstrated variably-sized nests of clear to pale eosinophilic cells with occasional central necrosis embedded in a hyalinized to fibrocellular stroma. The specimen was also positive for the characteristic rearrangement of the EWSR1 (22q12) locus in 93.5 % of interphase cells. PMID:25994920

  4. Management of the Patient with Aggressive and Resistant Papillary Thyroid Carcinoma

    Science.gov (United States)

    Miftari, Rame; Topçiu, Valdete; Nura, Adem; Haxhibeqiri, Valdete

    2016-01-01

    Purpose: Papillary carcinoma is the most frequent type of thyroid cancer and was considered the most benign of all thyroid carcinomas, with a low risk of distant metastases. However, there are some variants of papillary thyroid carcinoma that have affinity to spread in many organs, such as: lymph nodes, lungs and bones. Aim: The aim of this study was presentation of a case with papillary carcinoma of the thyroid gland, very persistent and resistant in treatment with I 131. Material and results: A man 56 years old were diagnosed with papillary carcinoma of thyroid gland. He underwent a surgical removal of the tumor and right lobe of thyroid gland. With histopathology examination, were confirmed follicular variant of papillary carcinoma pT4. Two weeks later he underwent total thyroidectomy and was treated with 100 mCi of J 131. Six months later, the value of thyroglobulin was found elevated above upper measured limits (more than 500 ng/ml). Patient underwent surgical removal of 10 metastatic lymph nodes in the left side of the neck and has been treated with 145 mCi of radioiodine I 131. The examination after 5 months shows elevation of thyroglobulin, more than 20000 ng/ml and focally uptake of J 131 in the left lung. Patient was treated once again with 150 mCi radioiodine J 131. Whole body scintigraphy was registered focal uptake of radioiodine in the middle of the left collarbone. After a month, patient refers the enlargement of the lymph node in the right side of the neck. Currently patient is being treated with kinase inhibitor drug sorafenib and ibandronate. We have identified first positive response in treatment. Enlarged lymph node in the neck was reduced and the patient began feeling better. Conclusion: This study suggests that some subtypes of papillary thyroid carcinoma appear to have more aggressive biological course. Subtypes of papillary thyroid carcinoma such as diffuse sclerosing carcinoma, tall cell or columnar cell and insular variants, appears to

  5. Renal Preservation Therapy for Renal Cell Carcinoma

    OpenAIRE

    Yichun Chiu; Allen W. Chiu

    2012-01-01

    Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC) for 20 years. Nowadays partial nephrectomy (PN) is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN). Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN) and robot assisted laparoscopic partial nephrectomy...

  6. Targeted therapy for metastatic renal cell carcinoma

    OpenAIRE

    Patel, P H; Chaganti, R.S.K.; Motzer, R J

    2006-01-01

    Metastatic renal cell carcinoma (RCC) has historically been refractory to cytotoxic and hormonal agents; only interleukin 2 and interferon alpha provide response in a minority of patients. We reviewed RCC biology and explored the ways in which this understanding led to development of novel, effective targeted therapies. Small molecule tyrosine kinase inhibitors, monoclonal antibodies and novel agents are all being studied, and phase II studies show promising activity of sunitinib, sorafenib a...

  7. Papillocystic Variant of Acinar Cell Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Jasim Radhi

    2010-01-01

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

  8. Basal cell carcinoma of the perineum

    OpenAIRE

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

    2014-01-01

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

  9. Linear Basal Cell Carcinoma: A Case Report

    OpenAIRE

    Ichinokawa, Yuko; Ohtuki, Akiko; Hattori, Mariko; Sadamasa, Hiroko; Hiruma, Masataro; Matumoto, Toshiharu

    2011-01-01

    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.

  10. Systemic adjuvant therapies in renal cell carcinoma

    OpenAIRE

    Sebastiano Buti; Melissa Bersanelli; Maddalena Donini; Andrea Ardizzoni

    2012-01-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to d...

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

    Science.gov (United States)

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

    2012-11-01

    Basaloid squamous cell carcinoma of the esophagus is a rare variant of squamous cell carcinoma. We reviewed 878 cases of esophageal squamous cell carcinoma and detected 22 cases (3%) of basaloid squamous cell carcinoma. These tumors and stage-matched paired conventional squamous cell carcinomas were investigated for clinicopathologic features and immunoreactivity of cytokeratin subtypes, p53, B-cell lymphoma 2 (bcl-2), β-catenin, and epidermal growth factor receptor. Molecular aberrations in p53, CTNNB1 (the gene encoding β-catenin), and epidermal growth factor receptor (EGFR) were also determined. Patients with basaloid squamous cell carcinomas demonstrated a 5-year survival rate of 42%, significantly worse than those with well-differentiated squamous cell carcinoma (Pcarcinomas, the basaloid squamous cell carcinomas were less immunoreactive for cytokeratin 14, cytokeratin 903, and membranous β-catenin (Pcarcinomas, low-level expression of cytokeratin 14/cytokeratin 903 and mutations of p53 and EGFR had a significant influence on worse survival (Pcarcinoma, a neoplasm with particularly aggressive biologic behavior, should be differentiated from conventional squamous cell carcinomas. In this context, immunohistochemical assessment of several markers might provide a useful adjunct diagnostic tool. Aberrations of p53 and epidermal growth factor receptor genes are possibly involved in progression of esophageal basaloid squamous cell carcinoma.

  12. Dimethyl sulfoxide induces chemotherapeutic resistance in the treatment of testicular embryonal carcinomas

    OpenAIRE

    Kita, Hiroko; Okamoto, Keisei; Kushima, Ryoji; KAWAUCHI, AKIHIRO; Chano, Tokuhiro

    2015-01-01

    Dimethyl sulfoxide (DMSO) is an amphipathic molecule that is used as a solvent in biological studies and as a vehicle for drug therapy. The present study was designed to evaluate the potential effects of DMSO as a solvent in the treatment of testicular embryonal carcinomas (ECs). DMSO was applied to two human EC cell lines (NEC8 and NEC14), with the treated cells evaluated in relation to cisplatin (CDDP) resistance, differentiation (using Vimentin, Fibronectin, TRA-1-60, and SSEA-1 and -3 as ...

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

    Science.gov (United States)

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

    2010-06-01

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

  14. 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.

  15. Genistein sensitizes ovarian carcinoma cells to chemotherapy by switching the cell cycle progression in vitro

    Institute of Scientific and Technical Information of China (English)

    Huang Yanhong; Yuan Peng; Zhang Qinghong; Xin Xiaoyan

    2009-01-01

    Objective: To address how genistein sensitizes the chemotherapy-resistant ovarian carcinoma cells and promotes apoptosis in the respect of cell cycle and the regulation of survivin expression in the process. Methods: Ovarian SKOV-3 carcinoma cell line was treated with genistein or cisplatin either alone or in combination. Cell viability was showed by MTT method. Cell cycle and apoptosis were detected by flow cytometry. Survivin mRNA and protein were revealed by RT-PCR and immunocytochemistry, respectively. Results: Genistein could reduce the cell viability in a dose-dependent manner, while cisplatin did so at a much higher level. In contrast, if the two agents were treated in combination, half growth inhibition (IC50) value for cisplatin was reduced remarkably and the effect was synergistic as analyzed by isobologram. In particular, the reduced cell viability was exhibited by a switch in cell cycle progression, as the cells were arrested in G2/M phase and the G0/G1 phase-fraction was significantly decreased. The reduced cell viability appeared to involve apoptosis, based on our results from flow cytometry and Hoechst 33258 staining. In the meanwhile, genistein performed the inhibitory effect on cisplatin-induced survivin expression. Conclusion: Genistein can sensitize ovarian carcinoma cells to cisplatin therapy with the inhibition of survivin expression as the potential mechanism.

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

    Directory of Open Access Journals (Sweden)

    Arash Akhavein

    2014-05-01

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

  17. Preliminary Study on Identification of Drug Resistant and Non-drug Resistant Oral Squamous Carcinoma Cell line Tca8113 Using Metabolomics%耐药和非耐药口腔鳞癌Tca8113代谢组学方法鉴定的初步研究

    Institute of Scientific and Technical Information of China (English)

    王辉; 孟雅; 张平

    2015-01-01

    Objective:To identify the drug resistant and non-drug resistant of oral squamous carcinoma Tca8113.Methods:Cell growth curve was drafted and drug sensitivity were detected by the MTT assay.The immunohistochemistry was applied to detect the expression of P-gp which was related to multidrug resistance phenomenon in drug resistant cells.Extracellular metabolites of all cell lines was collected and was detected by nuclear magnetic resonance (NMR).Data analysis used principal component analysis(PCA).Results:The principal component analysis showed the obvious clustering relations in the data of drug resistant and non-drug resistant cells,indicating 1H NMR-based metabolomics method could distinguish between drug resistant and non-drug resistant Tca8113.Conclusion:The metabolomics is expected to be favorable application prospect in rapid identification of oral cancer cells with resistance,and it is expected to become a new testing method in future.%目的:初步将基于氢谱核磁共振(1H-NMR)的代谢组学方法应用于口腔耐药和非耐药口腔鳞癌Tca8113的鉴定.方法:MTT法绘制细胞生长曲线并检测药物敏感性,免疫组织化学检测与多药耐药现象相关蛋白P-gp的表达情况;收集胞外代谢产物进行核磁共振检测,用主成分分析法进行数据分析.结果:主成分分析法显示耐药细胞和非耐药细胞数据内部有集中的聚类关系,基于氢谱核磁共振的代谢组学方法可以区分耐药和非耐药的Tca8113.结论:代谢组学方法在产生耐药性的口腔癌细胞的快速鉴定中具有良好的应用前景,有望成为一种新的检测手段.

  18. Obstructive jaundice in small cell lung carcinoma.

    Science.gov (United States)

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

    2015-08-01

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

  19. Transitional cell carcinoma of the sinonasal tract: A rare entity

    Directory of Open Access Journals (Sweden)

    Madhumita Mondal

    2015-01-01

    Full Text Available Malignant sinonasal carcinomas are a rare entity comprising less than 1% of all cancers and around 3% of all head and neck malignancies seen in humans. Among these 15-20% are transitional cell carcinoma also known as non keratinizing carcinoma of sinonasal tract. We are reporting the case of a 45 years female with history of nasal obstruction and epistaxis. A contrast enhanced computed tomography (CECT was done which showed mucosal thickening in the right nasal cavity. Endoscopy assisted biopsy was taken which revealed non keratinizing carcinoma (transitional type. Very few reported cases of this type of malignancy was found. A possible reason could be multiple synonyms like cylindrical cell carcinoma, Schneiderian carcinoma and transitional cell carcinoma.

  20. Renal cell carcinoma in a setting of chronic lithium toxicity

    OpenAIRE

    Zardawi, Ibrahim; Nagonkar, Santoshi; Patel, Purvish

    2013-01-01

    Patient: Female, 72 Final Diagnosis: Renal cell carcinoma Symptoms: — Medication: — Clinical Procedure: — Specialty: Oncology Objective: Challenging differential diagnosis Background: Lithium salts are widely used in the treatment of affective disorders of the bipolar type. Lithium is a nephrotoxic substance which can cause both acute and chronic renal disease, including cyst formation. Cysts appear to predispose the kidney to renal cell carcinoma. Case Report: A case of renal cell carcinoma ...

  1. PIGMENTED BASAL CELL CARCINOMA: A RARE CLINICAL AND HISTOPATHOLOGICAL VARIANT

    OpenAIRE

    Chandralekha; Vijaya Bhaskar; Bhagyalakshmi; Sudhakar; Sumanlatha

    2015-01-01

    Basal cell carcinoma is a common malignant tumour of skin , commonly referred to as „rodent ulcer‟. It is common in the head and neck region. Exposure to ultraviolet radiation is an important risk factor. Pigmented basal cell carcinoma is a clinical and histological variant of basal cell carcinoma that exhibits inc reased pigmentation. It is a rare variant that can clinically mimic malignant melanoma. It is more common in males than females. Herein , we are...

  2. 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

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

    Science.gov (United States)

    2016-09-15

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid. PMID:26589365

  6. Transitional cell carcinoma express vitamin D receptors

    DEFF Research Database (Denmark)

    Hermann, G G; Andersen, C B

    1997-01-01

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

  7. Spindle cell carcinoma of the nasal cavity

    Directory of Open Access Journals (Sweden)

    Mark D DeLacure

    2013-02-01

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

  8. Acanthosis Nigricans associated with clear-cell renal cell carcinoma.

    Science.gov (United States)

    Ferraz de Campos, Fernando Peixoto; Narvaez, Margarita Rosa Aveiga; Reis, Paola Vasconcellos Soares; Gomes, Augusto Cesar Marins; Paraskevopoulos, Daniela Kallíope de Sá; Santana, Frederico; Fugita, Oscar Eduardo Hidetoshi

    2016-01-01

    Acanthosis nigricans (AN), an entity recognized since the 19th century, is a dermatopathy associated with insulin-resistant conditions, endocrinopathies, drugs, chromosome abnormalities and neoplasia. The latter, also known as malignant AN, is mostly related to abdominal neoplasms. Malignant AN occurs frequently among elderly patients. In these cases, the onset is subtle, and spreading involves the flexural regions of the body, particularly the axillae, palms, soles, and mucosa. Gastric adenocarcinoma is the most frequent associated neoplasia, but many others have been reported. Renal cell carcinoma (RCC), although already reported, is rarely associated with malignant AN. The authors report the case of a woman who was being treated for depression but presented a long-standing and marked weight loss, followed by darkening of the neck and the axillary regions. Physical examination disclosed a tumoral mass in the left flank and symmetrical, pigmented, velvety, verrucous plaques on both axillae, which is classical for AN. The diagnostic work-up disclosed a huge renal mass, which was resected and further diagnosed as a RCC. The post-operative period was uneventful and the skin alteration was evanescent at the first follow-up consultation. The authors call attention to the association of AN with RCC. PMID:27284539

  9. 苦参碱及其衍生物对人鼻咽癌细胞的耐药逆转作用%Reversal Effect of Matrine on Drug Resistance of Human Nasopharyngeal Carcinoma Cell Line

    Institute of Scientific and Technical Information of China (English)

    张俊; 唐安洲

    2012-01-01

    目的:探讨中药苦参碱(matrine,MAT)及其衍生物对鼻咽癌耐药细胞HONE1/DDP的耐药逆转作用.方法:采用逐渐增加剂量的方法,诱导建立人鼻咽癌细胞HONE1耐顺铂细胞株HONE1/DDP;将不同浓度苦参碱及其衍生物按倍比稀释浓度分别加入到HONE1/DDP中,测定其细胞毒性;MTr法测定非细胞毒性浓度苦参碱及其衍生物对HONE1/DDP细胞株的逆转作用,流式细胞仪检测细胞周期分布情况,并以Western blot测定MRP1、BAX、BCL-2蛋白表达.结果:HONE1/DDP细胞系对顺铂耐药;经苦参碱、苦参碱衍生物作用24h后,HONE1/DDP细胞株对顺铂的耐药性下降,逆转指数分别为1.45、1.77;与HONE1/DDP比较,经非细胞毒性浓度苦参碱处理的HONE1/DDP细胞周期Go/G1明显增加(P<0.05),经非细胞毒性浓度苦参碱衍生物处理的HONE1/DDP细胞周期S期减少(P<0.05);HONE1/DDP细胞的MRP1表达显著高于HONE1 (P <0.05),而经苦参碱、苦参碱衍生物作用后MRP1表达显著降低(P<0.05),且二者作用后BAX表达水平降低,BCL-2表达水平升高,BAX/BCL-2比值降低(P<0.05).结论:人鼻咽癌细胞株HONE1对顺铂耐药,其耐药机制可能与增加MRP1的表达有关;苦参碱及其衍生物可以逆转HONE1/DDP对顺铂的耐药性,其机制可能与其改变细胞周期分布及下调MRP1的表达、降低BAX/BCL-2比值有关.%Objective:To study the reversal effect of matrine and its derivatives on drug resistance of human nasopharyngeal carcinoma cell line HONE1/DDP. Methods; The drug-resistant cell line was established by the human nasopharyngeal carcinoma cells HONE1 with gradually increasing concentration of cisplatin. The matrine and its derivatives were added into the HONE1/DDP according to different concentrations to measure their cytotoxicity. MTT assay was used to measure the reversal effect on the drug resistance of the non-toxic doses of matrine and its derivatives. Cell cycle was measured by flow cytomety

  10. Primary Endometrial Squamous Cell Carcinoma In Situ

    Science.gov (United States)

    Jetley, Sujata; Jairajpuri, Zeeba S.; Hassan, Mohammad J.; Madaan, Garima; Jain, Reena

    2015-01-01

    Squamous cell carcinoma (SCC) of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year’s duration. A total abdominal hysterectomy with a bilateral salpingooophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up. PMID:26629388

  11. 叶酸受体1在鼻咽癌细胞抵抗紫杉醇化疗药物中的作用%Role of folate receptor 1 in paclitaxol-resistance of nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    李维; 谭国林; 马艳红; 彭小伟; 贺广湘

    2010-01-01

    Objective To provide experimental evidence for the folate receptor 1 (FOLR1)mediated targeted cancer therapy and resistance reversal, the FOLR1 expression differences in nasopharyngeal carcinoma cells (CNE-1) and immortalized normal nasopharyngeal cells (NP69) and the correlation between FOLR1 expression and paclitaxel resistance index in nasopharyngeal carcinoma were investigated. Methods The expressions of FOLR1 in CNE-1, CNE-1/Taxol (paclitaxel-resistance cells)and NP69 was detected by cDNA microarray, reverse transcriptase-polymerase chain reaction(RT-PCR),Western blot and immunocytochemistry. Proliferation inhibition rates of CNE-1 and CNE-1/Taxol cells were measured by colony formation assay after treated by short interfering RNA (siRNA) of FOLR1. Results The expressions of FOLR1 gene in CNE-1/Taxol cells and CNE-1 cells were 2636.0 and 176. 0,respectively. The expression of FOLR1 was not detected in the NP69 by semi-quantative RT-PCR and Western blot. The high expression of FOLR1 in CNE-1/Taxol was verified by semi-quantative RT-PCR, and its expression level was positively correlated to the degree of drug-resistance(r2 =0. 8719). The results were also validated by Western blot and immunocytochemistry. The sensitivity of CNE-1/Taxol to paclitaxel significantly increased after inhibition of FOLR1 gene expression by siRNA, and its IC50 value was decreased by 59. 6% (t = 6. 92, P < 0. 01). Conclusions The expression of FOLR1 is closely related to the occurrence of NPC and Taxol resistance. FOLR1 gene may be one of the important target molecules in NPC treatment and reversion of the paclitaxel-resistance in NPC.%目的 研究叶酸受体1(folate receptor 1,FOLR1)在鼻咽癌细胞和永生化正常鼻咽细胞(NP69)中表达的差异,及FOLR1的表达与鼻咽癌紫杉醇耐药的相关性,为FOLR1介导的肿瘤靶向治疗及耐药逆转提供实验依据.方法 利用基因芯片技术,反转录聚合酶链反应(RT-PCR),Western blot和免

  12. Selective stimulation of prostatic carcinoma cell proliferation by transferrin.

    OpenAIRE

    M.C. Rossi; Zetter, B R

    1992-01-01

    Aggressive prostatic carcinomas most frequently metastasize to the skeletal system. We have previously shown that cultured human prostatic carcinoma cells are highly responsive to growth factors found in human bone marrow. To identify the factor(s) responsible for the increased prostatic carcinoma cell proliferation, we fractionated crude bone marrow preparations by using hydroxylapatite HPLC. The major activity peak contained two high molecular weight bands (M(r) = 80,000 and 69,000) that cr...

  13. 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.

  14. The Effect of Sortilin Silencing on Ovarian Carcinoma Cells

    OpenAIRE

    Ghaemimanesh, Fatemeh; Ahmadian, Gholamreza; Talebi, Saeed; Zarnani, Amir-Hassan; Behmanesh, Mehrdad; Hemmati, Shayda; Hadavi, Reza; Jeddi-Tehrani, Mahmood; Farzi, Maryam; Akhondi, Mohammad mehdi; Rabbani, Hodjattallah

    2014-01-01

    Background Our preliminary data on the protein expression of SORT1 in ovarian carcinoma tissues showed that sortilin was overexpressed in ovarian carcinoma patients and cell lines, while non-malignant ovaries expressed comparably lower amount of this protein. In spite of diverse ligands and also different putative functions of sortilin (NTR3), the function of overexpressed sortilin in ovarian carcinoma cells is an intriguing subject of inquiry. The aim of this study was, therefore, to investi...

  15. Management of tonsillar squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    吴雪溪; 唐平章; 祁永发; 徐震纲

    2003-01-01

    Objective To discuss treatment options for tonsillar squamous cell carcinoma.Methods A total of 108 patients with biopsy-proven tonsillar squamous cell carcinoma, treated between 1984 and 2000, were reviewed, including 82 men and 26 women, with ages ranging from 19 to 70 years. Treatments consisted of either radiotherapy and surgery reserved as salvage treatment (Salvage Surgery, 83 patients), or planned surgery with preoperative radiation (Planned Surgery, 25 patients). Radiotherapy was delivered primarily in a dosage of 60-70 Gy for Salvage Surgery patients and 40-50 Gy for Planned Surgery patients. Both salvage and planned surgeries were radical, with resection of the lateral oropharyngeal wall, segmental resection of the mandible and neck dissection. The pectoralis major myocutaneous flaps were used to repair surgical defects. Results The percentages of radical surgery used in the Salvage Surgery and Planned Surgery groups were 24.1% (20/83) and 88.0% (22/25), respectively (P=0.000). The local recurrence rates were 28.9% (24/83) and 20.0% (5/25) in the Salvage Surgery and Planned Surgery groups, respectively (P= 0.378). The neck recurrence rates were 9.6% (8/83) and 8.0% (2/25) in the Salvage Surgery and Planned Surgery groups respeatively (P= 0.804). The 5-year survival rates were 59.3% and 55.3% in the Salvage Surgery and Planned Surgery groups, respeatively (P= 0.7056).Conclusions Although the two treatments had a similar survival rate, Salvage Surgery avoided 60% commando operations compared with the Planned Surgery group, which benefits to recovery of oral functions. Primary radiotherapy is recommended as the treatment of choice for tonsillar squamous cell carcinoma. After radical radiotherapy, salvage surgery should be undertaken in the case of tumor remnants or recurrences.

  16. Early Onset Basal Cell Carcinoma: Surgical Approach

    OpenAIRE

    Betekhtin M.; Ananiev J.; Tchernev G.; Zisova L.; Philipov S.; Hristova R.

    2014-01-01

    Basal cell carcinoma (BCC) is the most frequent non-melanoma skin cancer. Only 5-15% of BCC cases can be found in patients aged 20-40 years (so-called early onset). The early onset BCC is characterized by active and aggressive tumour growth, clinically presenting in most of the cases as a morpheaform, locally infiltrating or recurrent BCC. Despite the advances in the study of the pathogenesis of this tumour, surgery remains the most used, most effective and most suitable treatment modality. W...

  17. Nonsurgical Treatment Options for Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Mary H. Lien

    2011-01-01

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

  18. Percutaneous Cryoablation for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Tsitskari Maria

    2015-06-01

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

  19. Aldesleukin in advanced renal cell carcinoma.

    Science.gov (United States)

    Schmidinger, Manuela; Hejna, Michael; Zielinski, Christoph C

    2004-12-01

    Renal cell carcinoma accounts for 2-3% of all malignancies. The most common subtype [85%] is the clear cell variant. A total of 30% of patients present with metastatic disease at diagnosis and another 30-40% will develop metastases during the course of the disease. Conventional cancer treatment is not effective, but cytokines including recombinant interleukin-2 (aldesleukin) have demonstrated clinical activity of various degrees. This drug profile provides a review of the literature on studies using aldesleukin in patients with metastatic renal cell carcinoma. Aldesleukin has been used in different dose schedules applying various administration routes, as either monotherapy or in combination with other cytokines, chemotherapy, endocrine treatment and adoptive cellular immunotherapy. Although a large number of randomized trials have been performed with different treatment strategies, it still remains uncertain whether the dose or combination of aldesleukin with other agents substantially influence treatment outcome. It appears that factors other than those that are treatment related are responsible for the course of the disease. PMID:15606326

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

    Directory of Open Access Journals (Sweden)

    Samapika Routray

    2014-01-01

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

  1. siRNA抑制人Tca8113/CDDP细胞多药耐药相关蛋白表达的研究%A Study on MRP siRNA Reversing Multidrug Resistance of Human Tongue Squamous Cell Carcinoma Cell Line Tca8113/CDDP

    Institute of Scientific and Technical Information of China (English)

    蒋磊; 王代友; 陆新萍

    2011-01-01

    目的:利用小干扰RNA(small interfering RNA,siRNA)抑制人舌癌耐药细胞多药耐药相关蛋白(muhidrug resistance associated protein,MRP)的表达,观察其对培养细胞耐药性的干扰情况.方法:设计针对MRP基因的siRNA,转染人舌癌多药耐药细胞Tca8113/CDDP,用RT-PCR分析MRP mRNA的表达;免疫细胞化学技术检测MRP蛋白表达量;MTT法检测MRP siRNA的细胞毒作用.结果:Tca8113/CDDP细胞转染MRP siRNA后,MRP mRNA表达较对照组明显降低,降低率为61.3%;转染36 h后MRP siRNA组的MRP蛋白表达阳性率较对照组明显减低;MRP siRNA组中顺铂对Tca8113/CDDP细胞生长的抑制作用明显强于对照组.且抑制作用随时问的延长而增强.结论:MRP siRNA可以明显抑制口腔癌耐药细胞的多药耐药.%Objective: To investigate the inhibitive effect of MRP-siRNA on human tongue squamous cell carcinoma multidrug resistance. Methods: One siRNA-MRP was designed, synthesized and transfected into human tongue squamous cell carcinoma cell line Tca8113/CDDP. Expression level of MRP mRNA was detected through RT-PCR. MRP protein expression was assayed with immunocytochemistry. MTT was assayed for cytotoxic effects of MRP-siRNA. Results: After MRP-siRNA transfected to Tca8113/CDDP cell,expression intensity of MRP mRNA obviously decreased, the expression level of MRP mRNA decreased 61.3%. Trough 36 h after transfection, positive rate of MRP protein expression in MRP siRNA group was obviously decreased compared with the control group. The inhibition of Cisplatin (CDDP) on Tca8ll3/CDDP cell growth in MRP siRNA group was obviously increased compared with the control group. Conclusions: MRPsiRNA can obviously inhibit the multidrug resistance of human tongue squamous cell carcinoma cell line Tca8ll3/CDDP.

  2. Mechanisms for high methoxymorpholino doxorubicin cytotoxicity in doxorubicin-resistant tumor cell lines

    NARCIS (Netherlands)

    Bakker, M; Renes, J; Groenhuijzen, A; Visser, P; TimmerBosscha, H; Muller, M; Groen, HJM; Smit, EF; deVries, EGE

    1997-01-01

    Methoxymorpholino doxorubicin (MMRDX) is an anthracycline analogue that is able to overcome tumor cell resistance to classical anthracyclines. Mechanisms for increased MMRDX cytotoxicity were analyzed in a small cell lung carcinoma cell line (GLC(4)), its 300-fold doxorubicin-resistant and multidrug

  3. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    Directory of Open Access Journals (Sweden)

    Laila Ziko

    2015-01-01

    Full Text Available Cisplatin (CisPt is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2 cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death. Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death.

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

    Science.gov (United States)

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

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

  5. Percutaneous and laparoscopic assisted cryoablation of small renal cell carcinomas

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Borre, Michael;

    Aim: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Materials and methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made...

  6. PRL-3 expression in nasal sinus squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zi-Hui Chen; Min-Ying Li

    2016-01-01

    Objective:To investigate the relationship between liver regeneration phosphatase-3 (PRL-3) with differentiation extent of nasal sinus squamous cell carcinoma, and molecular biological effects on the pathogenesis of nasal sinus squamous cell carcinoma to comprehend its relevance, so as to make early diagnosis of patients, and to give guidance to the prognosis. Methods:Immunohistochemistry was used to detect PRL-3 in 30 cases of different degrees of sinus nasal squamous cell carcinoma. 20 cases of normal nasal cavity of mucosa tissues were set as control. Results:The PRL-3 in all levels of sinonasal squamous cell carcinoma tissues, there was a significant difference compared with the normal nasal mucosa (P<0.05), squamous cell carcinoma and its expression increased with the grade with enhanced trend. Conclusions:PRL-3 expression increased significantly in sinonasal squamous cell carcinoma than in nasal polyp tissue, showed that it may be associated with squamous cell carcinoma of nasal sinus squamous cell carcinoma, may be the early event.

  7. Assessment of pancreatic carcinoma cell chemosensitivity using a three-dimensional culture system

    Institute of Scientific and Technical Information of China (English)

    LIAO Quan; HU Ya; ZHAO Yu-pei; ZHOU Tao; ZHANG Qiang

    2010-01-01

    Background Monolayer cell culture models are the traditional culture models used for in vitro research of pancreatic carcinoma chemosensitivity. However, these models neglect the interactions between tumor cells and the impact of the tumor microenvironment. Such tumor cell monolayers poorly mimic the solid tumor microenvironment. The present study aimed to investigate the chemosensitivity characteristics of pancreatic cancer cells in a three-dimensional culture system by analyzing the differences in drug sensitivity between a scattered cell culture model and a multicellular spheroid culture model.Methods Three pancreatic cancer cell lines (SW1990, ASPC-1 and PCT-3) were cultured in three-dimensional collagen gels as well as in traditional two-dimensional monolayers. The chemosensitivities of the pancreatic carcinoma cells to 5-fluorouracil (5-FU), gemcitabine, and oxaliplatin in vitro were detected by both the Cell Counting Kit-8 test and the collagen gel droplet-embedded culture drug-sensitivity test.Results In the two-dimensional culture model, differences in the chemosensitivities of the cloned pancreatic carcinoma cells and scattered cells existed for some concentrations of 5-FU, gemcitabine and oxaliplatin. In the three-dimensional culture model, there were significant differences in the chemosensitivities of the pancreatic cancer cells between the scattered cells and multicellular spheroids (P <0.05).Conclusion Pancreatic carcinoma cells exhibit multicellular resistance in three-dimensional cultures.

  8. Renal cell carcinoma: links and risks

    Directory of Open Access Journals (Sweden)

    Kabaria R

    2016-03-01

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

  9. HLA expression in hepatocellular carcinoma cell lines.

    Science.gov (United States)

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

    1994-08-01

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

  10. Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Kyriakopoulos, Christos E; Chittoria, Namita; Choueiri, Toni K;

    2015-01-01

    BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology...... of sRCC is needed to develop alternative therapeutics....

  11. SIS3逆转多药耐药肝癌细胞的干性作用%Reversal of stemness in multidrug-resistant hepatocellular carcinoma cells by SIS3

    Institute of Scientific and Technical Information of China (English)

    严威; 文霆; 林素琼; 刘中财; 杨文超; 吴国洋

    2015-01-01

    ) hepatocellular carcinoma cells. Methods MDR HCC Huh7. 5. 1/ADM cell lines were developed by exposing parental cells to stepwise increasing concentrations of ADM. CCK⁃8 assay was used to determine the cellular sensitivity of various anticancer drugs. Flow cytometry ( FCM) was used to analyze the expression level of cancer stem cell marker CD133. Clone formation assay and mouse subcutaneous xenograft tumors were used to investigate the tumorigenicity in vitro and in vivo. Western blotting ( WB) was used to analyze the changes of expressions of CD133, Smad3, Bcl⁃2, Bax and p⁃Smad3 in different conditions. Results ADM treatment of HCC cells in vitro resulted in a development of subline, Huh7. 5. 1/ADM cells, with CSC phenotypes: stable MDR phenotype ( besides ADMc Huh7.5.1/ADM cells were also more resistant to some other anticancer drugs including VCR, MMC and CTX ) (IC50:0.215±0.018 vs. 0.123± 0.004, 0.145±0.009 vs. 0.014±0.002, 1.021± 0.119 vs. 0.071± 0.006, 27.007±1.606 vs. 1.919±0.032)(unit: μg/ml)(P multidrug resistant hepatocellular carcinoma cells.

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

    Science.gov (United States)

    Fadare, Oluwole; Liang, Sharon X

    2012-12-01

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

  13. Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

    Science.gov (United States)

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

    2016-01-01

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

  14. A case report of renal cell carcinoma in a dog

    Directory of Open Access Journals (Sweden)

    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.

  15. Phenylpropanoid glycosides reversing effect on multidrug resistance of colon carcinoma LoVo/Adr cells%苯丙素甙化合物逆转大肠癌LoVo/Adr细胞多药耐药性

    Institute of Scientific and Technical Information of China (English)

    马强; 张方信; 吕志诚

    2009-01-01

    目的:以大肠癌LoVo/Adr耐药株为实验对象,观察苯丙素甙(PPG)化合物逆转多药耐药(MDR)作用及可能机制.方法:采用M1Tr法检测PPG对LoVo细胞和l~Vo/Adr细胞增殖的影响.用PPG小于ICl0(存活率>90%)的剂量进行耐药逆转试验,确定半数抑制浓度(IC50)并计算逆转倍数.流式细胞术检测PIG对LoVo/Adr细胞阿无系霉素(ADR)的摄入影响;荧光显微镜观察PPG对ADR在细胞中分布的影响.结果:当PPG浓度为80,160 ms/L时,LoVo细胞存活率分别为(69.34±3.48)%,(30.15±1.86)%;LoVo/Adr细胞分别为(67.89±2.87)%,(34.96±2.14)%,提示PPG具有抑制细胞增殖作用且具有一定的量效关系(P<0.05).当PPG浓度小于加40mg/L时,LoVo/Adr,LoVo细胞存活率均大于90%;PPG浓度为20,40 ms/L时,逆转倍数分别为5.24,9.78.ADR 主要分布在LoVo/Adr细胞胞质区,加用PPG后,胞质区荧光强度从2.04±0.70升至2.35±0.87,摄入能力显著增强(P<0.05).结论:PPG具有抗肿瘤、逆转耐药作用,PPG通过增加LoVo/Adr细胞对ADR的摄入及细胞胞质区积聚是其逆转耐药机制之一.%AIM: To investigate the effect of phenylpropanoid glycosides ( PPG) on reversing multidrug resistance ( MDR) of colon carcinoma LoVo/Adr cells and its possible mechanism. METHODS: The effects of PPG on proliferation of LoVo and LoVo/ Adr cells were examined by MTT. The reversing test of PPG on MDR was identified when its IC10 was < 10% ; its IC_50, and rever sal fold was subsequently calculated. Flow cytometry technique was applied to determine the influence of PPG on the uptake of ad riamycin( ADR). The subcellular distribution of ADR in the cells was observed by fluorescence microscopy. RESULTS: At a con centration of 80 and 160 mg/L of PPG, the survival rate of LoVo cells was(69.34 ±3.48)% and(30. 15 ± 1. 86)% , respectively; while the survival rate of LoVo/Adr cells was (67. 89 ±2. 87) % and(34.96 ±2. 14)% , respectively. Therefore, PPG significantly inhibited proliferation of

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

    Science.gov (United States)

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

    2014-01-01

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

  17. Giant Basal Cell Carcinoma of the Forehead: A Case Report

    OpenAIRE

    Rudić, Milan; Kranjčec, Zoran; Lisica-Šikić, Nataša; Kovačić, Marijan

    2012-01-01

    Giant basal cell carcinoma (GBCC) is defined as a tumor 5cm or greater in diameter. They present less than 1% of all basal cell carcinomas. We present a case of an 85-year-old male patient with a giant ulcerating tumor of the left forehead (measuring 7x6cm). Under local anesthesia tumor was surgically excised. No involvement of the underlying periostal or bone structure was noted. Pathohystological exam revealed the giant basal cell carcinoma, with free surgical margins. Giant basal cell carc...

  18. Measuring The Contact Resistances Of Photovoltaic Cells

    Science.gov (United States)

    Burger, D. R.

    1985-01-01

    Simple method devised to measure contact resistances of photovoltaic solar cells. Method uses readily available equipment and applicable at any time during life of cell. Enables evaluation of cell contact resistance, contact-end resistance, contact resistivity, sheet resistivity, and sheet resistivity under contact.

  19. Knockdown of asparagine synthetase by RNAi suppresses cell growth in human melanoma cells and epidermoid carcinoma cells.

    Science.gov (United States)

    Li, Hui; Zhou, Fusheng; Du, Wenhui; Dou, Jinfa; Xu, Yu; Gao, Wanwan; Chen, Gang; Zuo, Xianbo; Sun, Liangdan; Zhang, Xuejun; Yang, Sen

    2016-05-01

    Melanoma, the most aggressive form of skin cancer, causes more than 40,000 deaths each year worldwide. And epidermoid carcinoma is another major form of skin cancer, which could be studied together with melanoma in several aspects. Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine, and its expression is associated with the chemotherapy resistance and prognosis in several human cancers. The present study aims to explore the potential role of ASNS in melanoma cells A375 and human epidermoid carcinoma cell line A431. We applied a lentivirus-mediated RNA interference (RNAi) system to study its function in cell growth of both cells. The results revealed that inhibition of ASNS expression by RNAi significantly suppressed the growth of melanoma cells and epidermoid carcinoma cells, and induced a G0/G1 cell cycle arrest in melanoma cells. Knockdown of ASNS in A375 cells remarkably downregulated the expression levels of CDK4, CDK6, and Cyclin D1, and upregulated the expression of p21. Therefore, our study provides evidence that ASNS may represent a potential therapeutic target for the treatment of melanoma. PMID:25858017

  20. Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-06

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

  1. Management of primary small cell carcinoma of the esophagus

    Institute of Scientific and Technical Information of China (English)

    SUN Ke-lin; HE Jie; CHENG Gui-yu; CHAI Li-xun

    2007-01-01

    Background Primary small cell carcinoma of the esophagus is rare. Although surgery is successful in eradicating local tumor, the five-year survival rate of patients with primary small cell carcinoma of the esophagus after resection is lower than that of patients with primary squamous cell carcinoma of the esophagus. The purpose of this study was to analyze the clinical manifestations, pathological features and treatment of primary small cell carcinoma of the esophagus.Methods A total of 73 patients with primary small cell carcinoma of the esophagus who had been treated by surgery from 1984 to 2003 were analyzed retrospectively.Results In this series, the overall resection rate was 94.5% (69/73), the radical resection rate 89.0% (65/73) and the operative mortality 1.4% (1/73). The 1-, 3- and 5-year survival rates of patients were 50.7%, 13.7% and 8.2%,respectively.Conclusions Primary small cell carcinoma of the esophagus is rare with a poor prognosis. Surgical resection is the leading method for patients with stage Ⅰ or Ⅱ primary small cell carcinoma of the esophagus. Postoperative chemotherapy is beneficial to these patients. The patients of stage Ⅲ or Ⅳ should be given chemotherapy and radiation therapy.

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

    Science.gov (United States)

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

    2012-04-01

    Most Merkel cell carcinomas display pure neuroendocrine differentiation (pure Merkel cell carcinoma), whereas a minority show combined neuroendocrine and nonneuroendocrine elements (combined Merkel cell carcinoma). Recent identification of Merkel cell polyomavirus DNA and Merkel cell polyomavirus large T antigen expression in a proportion of Merkel cell carcinomas has suggested viral-induced oncogenesis. To date, Merkel cell polyomavirus immunohistochemistry has shown an absence of viral large T antigen expression in combined Merkel cell carcinoma as well as select non-Merkel cell carcinoma cutaneous lesions and visceral neuroendocrine tumors. In our series, we aimed to further characterize the frequency and pattern of Merkel cell polyomavirus large T antigen expression by CM2B4 immunohistochemistry in primary and metastatic Merkel cell carcinoma (pure Merkel cell carcinoma and combined Merkel cell carcinoma) and various non-Merkel cell carcinoma lesions from patients with Merkel cell carcinoma, patients without Merkel cell carcinoma, and individuals with altered immune function. Merkel cell polyomavirus large T antigen was detected in 17 (63%) of 27 pure Merkel cell carcinomas and absent in all 15 (0%) combined Merkel cell carcinomas. Furthermore, complete concordance (100%) of Merkel cell polyomavirus large T antigen expression was observed in 10 cases of primary Merkel cell carcinoma and subsequent tumor metastases. We also evaluated 70 non-Merkel cell carcinoma lesions including 15 cases each of pulmonary and gastrointestinal neuroendocrine tumors. All 70 non-Merkel cell carcinoma lesions were negative for Merkel cell polyomavirus by CM2B4 immunohistochemistry, irrespective of any known Merkel cell carcinoma diagnosis and immune status. In summary, our identification of Merkel cell polyomavirus large T antigen expression in a subset of Merkel cell carcinoma and lack of findings in combined Merkel cell carcinomas and non-Merkel cell carcinoma lesions concur with

  3. [Functional surgery for head and neck squamous cell carcinoma].

    Science.gov (United States)

    Janot, François; Julieron, Morbize

    2002-12-01

    Surgery for head and neck squamous cell carcinoma can alter speech, swallowing, and cosmoses. Recent tendency is to avoid mutilating surgery unless the tumour is aggressive or resistant to chemotherapy and or radiotherapy. Functional surgery is being widely employed, and for example it may vary between conventional partial surgery and endoscopic laser surgery for small sized vocal cord cancers. Various new reconstructive procedures have been developed to help early functional restoration. Loco-regional flaps can be used to replace gums and avoid dental extractions. Free flaps with micro-vascular anastomosis can be employed for immediate reconstruction of extensive surgical defects involving pharyngeal wall, tongue, mandible and mid-face to restore better function and cosmoses. Few recently developed techniques can be also employed in selected cases of laryngo-pharyngeal cancers to avoid permanent laryngeal mutilation. Another goal of functional surgery is to decrease the postoperative radiotherapy or chemo-radiotherapy sequelae, and obtain successful postoperative functional rehabilitation.

  4. 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.

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

    International Nuclear Information System (INIS)

    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.

  6. 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.

  7. Renal cell carcinoma: links and risks

    Science.gov (United States)

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

    2016-01-01

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

  8. Lupus vulgaris with squamous cell carcinoma.

    Science.gov (United States)

    Motswaledi, Mojakgomo Hendrick; Doman, Chantal

    2007-12-01

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

  9. Duodenal Bleeding from Metastatic Renal Cell Carcinoma

    Science.gov (United States)

    Rustagi, Tarun; Rangasamy, Priya; Versland, Mark

    2011-01-01

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

  10. Duodenal Bleeding from Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Tarun Rustagi

    2011-04-01

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

  11. Metabolic alterations in renal cell carcinoma.

    Science.gov (United States)

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

    2015-11-01

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

  12. Early Onset Basal Cell Carcinoma: Surgical Approach

    Directory of Open Access Journals (Sweden)

    Betekhtin M.

    2014-06-01

    Full Text Available Basal cell carcinoma (BCC is the most frequent non-melanoma skin cancer. Only 5-15% of BCC cases can be found in patients aged 20-40 years (so-called early onset. The early onset BCC is characterized by active and aggressive tumour growth, clinically presenting in most of the cases as a morpheaform, locally infiltrating or recurrent BCC. Despite the advances in the study of the pathogenesis of this tumour, surgery remains the most used, most effective and most suitable treatment modality. We describe a case of a 39-year-old woman who developed an early onset BCC of the nasolabial fold. After the subsequent surgical excision an excellent cosmetic result was achieved.

  13. Emerging surgical treatments for renal cell carcinoma.

    Science.gov (United States)

    Husain, Fatima Z; Badani, Ketan K; Sfakianos, John P; Mehrazin, Reza

    2016-04-01

    Treatment of renal cell carcinoma has evolved considerably over the last few years. While total nephrectomy is necessary at times, nephron-sparing surgery, with a goal of renal function preservation, should always be considered. Although open partial nephrectomy is considered the gold standard approach for nephron-sparing surgery, laparoscopic- or robotic-assisted techniques allow urologists to perform renal surgery less invasively, with excellent long-term oncological outcomes. Cryotherapy and radiofrequency ablation are less invasive management approaches for carefully selected patients with small renal masses. Active surveillance should be considered in elderly or patients who are unfit for surgery. Ultimately, the method chosen for management of a renal mass is an informed decision made by the physician and patient. PMID:26892144

  14. Duodenal bleeding from metastatic renal cell carcinoma.

    Science.gov (United States)

    Rustagi, Tarun; Rangasamy, Priya; Versland, Mark

    2011-04-20

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

  15. Renal cell carcinoma: links and risks.

    Science.gov (United States)

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

    2016-01-01

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

  16. [Outlook: Future therapy of renal cell carcinoma].

    Science.gov (United States)

    Bergmann, Lothar; Miller, Kurt

    2010-01-01

    Targeted therapies have fundamentally altered the therapy of metastatic renal cell carcinoma (mRCC). Sunitinib today is an internationally recommended reference standard in first-line therapy; other drugs such as Temsirolimus, Everolimus, Bevacizumab (in combination with Interferon-alpha) and Sorafenib are part of the therapeutic arsenal. Practitioners thus have now more and better therapeutic options at hand, leading to a significantly improved prognosis for mRCC patients. Numerous ongoing research activities aim at the improvement of the benefits of the new compounds in the metastatic situation or application earlier in the course of the disease. Key aspects of future development in RCC are the optimization of the current therapy options by developing new targeted therapies, the search for the best combinations and sequences including the role of nephrectomy and the assessment in the adjuvant or neo-adjuvant setting. The following contribution provides an overview of ongoing studies, thus giving insight into the future therapy of RCC. PMID:20164673

  17. Corrosion resistant PEM fuel cell

    Science.gov (United States)

    Fronk, Matthew Howard; Borup, Rodney Lynn; Hulett, Jay S.; Brady, Brian K.; Cunningham, Kevin M.

    2002-01-01

    A PEM fuel cell having electrical contact elements comprising a corrosion-susceptible substrate metal coated with an electrically conductive, corrosion-resistant polymer containing a plurality of electrically conductive, corrosion-resistant filler particles. The substrate may have an oxidizable metal first layer (e.g., stainless steel) underlying the polymer coating.

  18. 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.

  19. Breast carcinoma with osteoclast-like giant cells

    DEFF Research Database (Denmark)

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

    2001-01-01

    Primary carcinoma with osteoclast-like giant cells is a very rare tumour of the female breast. The clinical course, histological, immunohistochemical and ultrastructural features of 61 cases of invasive duct carcinoma with osteoclast-like multinucleated giant cells (OMGCs) are reviewed and a new...... stroma. Immunohistochemical and ultrastructural studies have claimed a benign histiocytic nature of the OMGCs; they may represent a special type of polykaryon, distinct from both osteoclasts and inflammatory giant cells....

  20. 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.

  1. An Unusual Location of Basal Cell Carcinoma: Two Case Reports

    OpenAIRE

    Birgül Tepe

    2012-01-01

    Basal cell carcinoma is the most common malignant skin tumour. Chronic sun exposure is considered as the main etiologic factor in its development. Although it mainly occurs on sun-exposed areas as the face and neck, it rarely develops on the forearms and/or arms. The etiologic factors which affect the anatomic distribution of basal cell carcinoma are not well-known. Here we report two patients who developed basal cell carcinoma on the forearm. None of the patients had a specific etiologic fac...

  2. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids.

    Directory of Open Access Journals (Sweden)

    Cynthia A Batchelder

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

  3. Tamoxifen can reverse multidrug resistance of colorectal carcinoma in vivo

    Institute of Scientific and Technical Information of China (English)

    Li-Zong Shen; Yi-Bing Hua; Xue-Ming Yu; Qing Xu; Tao Chen; Jian-Hua Wang; Wen-Xi Wu

    2005-01-01

    AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER).METHODS: Multidrug resistance was determined by means of semi-quantitative retro-transcription polymerase chain reaction (RT-PCR) to test mdr1 gene mRNA and ER expression was studied by immunohistochemistry. Tumor tissues from three cases of human colon carcinoma, which had mdr1( + )/ER(+ ), mdr1( + )/ER(-), mdr1(-) expressions,were planted subcutaneously in the neck of nude mice to establish three xenograft models. These models were subdivided into four subgroups randomly: Doxorubicin(DOX)-treated group, TAN-treated group, DOX and TAM group and control group. The dimensions of these xenografts were measured after each course of treatment and the xenografts were removed at the end of the experiments for measurements of weight and the variation of mdr1 mRNA level with RT-PCR. In each course, TAM[15 mg/(kg/d)] was administrated orally per day in the first seven days and DOX (3.6 mg/kg) was injected peritoneally on the first day. Data was evaluated by q and ttests.RESULTS: In the animal models with mdr1(-) tumor, the weights and volumes of the planted tumor in DOX group[(39.1±2.29) mg, (31.44±1.61) mm3] and TAM and DOX group [(38.72±2.56) mg, (31.31±1.74) mm3], which were lesser than that of control group [(45.48±3.92) mg,(36.42±2.77) mm3, P = 0.037, P = 0.016 respectively]significantly. In the animal models with mdr1(+)/ER(+)tumor, the weights and volumes of planted tumor were not affected by DOX or TAM treatment; however, in TAM and DOX group [(425.5±28.58) mg, (340.35±22.28) mm3],they were significantly less than that of control group[(634.23±119.41) mg, (507.45±93.34) mm3, P = 0.022,P = 0.045 respectively], which are similar to that in the models with mdr1(+)/ER(-) tumor. No significant changes were found in the expressive level of mdr1 mRNA following these treatments.CONCLUSION: The expression

  4. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Motzer, Robert J; Escudier, Bernard; McDermott, David F;

    2015-01-01

    in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg......BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus...... patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.)....

  5. Detection of squamous carcinoma cells using gold nanoparticles

    Science.gov (United States)

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

    2015-03-01

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

  6. The use of Ber-EP4 antigen in the differential diagnosis of basosquamous carcinoma from squamous and basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Nermin KARAHAN

    2006-05-01

    Full Text Available Basal cell and squamous cell carcinoma of skin are common tumors which can be easily distinguished on hematoxylin and eosin stained sections, but basosquamous carcinoma is a controversial entity. The aim of our study was to distinguish basal cell carcinoma and basosquamous carcinoma using Ber-EP4, immunohistochemically in 52 skin tumors. Twenty basal cell carcinomas, 20 squamous cell carcinomas, 10 basosquamous carcinomas and 2 collision tumors of the skin were stained with Ber-EP4 immunohistochemically. All basal cell carcinomas were stained strongly and diffusely with Ber-EP4, whereas squamous cell carcinomas were not, and basosquamous carcinomas were partially stained. Our results suggest that, distinction of basal cell carcinoma and basosquamous carcinoma can be achieved with routine immunohistochemical Ber-EP4 staining.

  7. Bone Metastasis from Renal Cell Carcinoma

    Science.gov (United States)

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

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

  8. Epidemiologia do carcinoma basocelular Epidemiology of basal cell carcinoma

    OpenAIRE

    Valquiria Pessoa Chinem; Hélio Amante Miot

    2011-01-01

    O carcinoma basocelular é a neoplasia maligna mais comum em humanos e sua incidência vem aumentando nas últimas décadas. Sua grande frequência gera significativo ônus ao sistema de saúde, configurando problema de saúde pública. Apesar das baixas taxas de mortalidade e de rara ocorrência de metástases, o tumor pode apresentar comportamento invasivo local e recidivas após o tratamento, provocando importante morbidade. Exposição à radiação ultravioleta representa o principal fator de risco ambie...

  9. Biological characteristics of breast carcinomas with neuroendocrine cell differentiation

    Institute of Scientific and Technical Information of China (English)

    姚根有; 周吉林; 赵仲生; 阮俊

    2004-01-01

    Background The aim of this study was to investigate DNA content and expression of c-erbB-2, PS2, and prostate-specific antigen (PSA) proteins in breast carcinomas with neuroendocrine (NE) cell differentiation.Methods Chromogranin, c-erbB-2, PS2, and PSA in 131 samples of breast cancer were detected immunohistochemically. Classic Feulgen staining image analysis techniques were used to quantify DNA content in 81 of the breast cancer samples.Results The c-erbB-2 positive rate in breast carcinoma samples containing neuroendocrine cells was 37.5% and the rate of high expression of c-erbB-2 (++ or +++) was 33.3%, both significantly lower than that in breast carcinomas without neuroendocrine cells (62.6% and 68.7%, respectively, P 5c aneuploidy cells, and rate of aneuploidy among cells were all lower than that in NE (-) breast carcinomas (P<0.01). In NE (+) grade I or II breast carcinomas, these indices were also all lower than that in the NE (-) breast carcinoma samples (P<0.01).Conclusion Breast carcinomas with neuroendocrine differentiation have a lower rate of malignancy. Neuroendocrine differentiation could serve as a prognostic marker in clinical practice.

  10. Basal cell carcinoma with progression to metastatic neuroendocrine carcinoma: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Volkan Adsay

    2010-03-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Merkel cell carcinoma (MCC or primary cutaneous neuroendocrine carcinoma is a malignant tumor considered to demonstrate differentiation towards Merkel cells that are present at the base of the epidermis or around the apical end of some hair follicles and are thought to play an yet uncertain role in sensory transduction. Here we present the case of a 54-year-old female with a basal cell carcinoma (BCC of the skin with neuroendocrine features (positivity for chromogranin that has evolved during multiple recurrences and radiotherapy into a high-grade neuroendocrine carcinoma with morphologic and immunohistochemical features of MCC (trabecular and nesting arrangement, positivity for chromogranin, cytokeratin 20, neuron specific enolase, and also neurosecretory granules on electron microscopy. The progression from a chromogranin positive basal cell carcinoma of the skin, to a high grade neuroendocrine carcinoma demonstrates the potential for cross differentiation among skin tumors.

  11. Mechanical properties of hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Gang Zhang; Mian Long; Zhe-Zhi Wu; Wei-Qun Yu

    2002-01-01

    AIM: To study the viscoelastic properties of humanhepatocytss and helatocellulsr carcinoma (HCC) cellsunder cytoslelstal perturbation, and to further to study theviscoelastic properties and the adhesive properties of mousehepatorna cells (HTC) in different cell cycls.METHODS: Micropipette aspiration technique was adopted tomeasure viscoelastic coefficients and adhesion force tocollagen coated surface ofthe cells. Three kinds ofcytoskeleton perturbing agents, colchiclnes (Col),cytochalssin D (CD) and vinblastine (VBL), were used totreat HCC cells and hepatocytes and the effects of thesetreatent on cell viscoelastic coefficients were investigated.The experimental results were analyzed with a thres-elsmentstandard linear solid. Further, the viscoelastic properties ofHTC cells and the adhesion force of different cycle HTC cellswere also investigated. The synchronous G1 and S phasecells were achieved through thymine-2-desoryriboside andcolchicines sequential blockage method and thymine-2-desoryriboside blockage method respectively.RESULTS: The elastic coefficients, but not viscouscoefficient of HCC cells (k1 = 103.6± 12.6N.m-2, k2 =42.5±10.4N. m-2, μ = 4.5 ± 1.9Pa. s), were significantly higherthan the corresponding value for hepatocytes (K1 = 87.5 ±12.1N.m-2, k2 =33.3± 10.3N.m-2, μ=5.9±3.0Pa. s, P<0.01). Upon treatment with CD, the viscoelastic coefficients ofboth hepotocytes and HCC cells decreased consistently,with magnitudes for the decrease in elastic coefficients ofHCC cells (k1: 68.7 N.m-2 to 81.7N.m-2, 66.3 % to 78.9 %;k2: 34.5 N.m-2 to37.1N.m-2, 81.2% to 87.3 %, P<0.001)larger than those for normal hepatocytes (k1: 42.6N. m-2 to49.8N.nt-2, 48.7% to56.9 %; k2: 17.2N.m-2 to 20.4N.m-2,51.7 % to 61.3 %, P< 0.001). There was a little decrease inthe vlscous coefficient of HCC cells (2.0 to 3.4Pa. s, 44.4 to75.6 %, P<0.001) than that for hepatocytes (3.0 to 3.gPa.s, 50.8to 66.1% P<0.001). Upon trastment with Col andVBL, the elastic coefficients

  12. Pigmented Basal Cell Carcinoma: A Clinical Variant, Report of Two Cases

    OpenAIRE

    K., Deepadarshan; M., Mallikarjun; N. Abdu, Noshin

    2013-01-01

    Basal cell carcinoma is the most common malignant tumour of skin, comprising 80% of non-melanoma cancers. Intermittent exposure to ultraviolet radiation is an important risk factor. Pigmented basal cell carcinoma is a clinical and histological variant of basal cell carcinoma that exhibits increased pigmentation. It is a very rare variant, although its frequency can reach upto 6% of total basal cell carcinomas in Hispanics. Herein, we are reporting 2 cases of pigmented basal cell carcinoma.

  13. Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Zou, Xue; Zhang, Mengxiao; Sun, Yiming; Zhao, Surong; Wei, Yingmei; Zhang, Xudong; Jiang, Chenchen; Liu, Hao

    2015-10-01

    Tumor cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, which is therefore targeted by therapeutic agents. The compound 3-bromopyruvate (3-BrPA), a strong alkylating agent and hexokinase inhibitor, inhibits tumor cell glycolysis and the production of ATP, causing apoptosis. 3-BrPA induces apoptosis of nasopharyngeal carcinoma (NPC) cell lines HNE1 and CNE-2Z, which may be related to its molecular mechanisms. In the present study, we investigated the effects of 3-BrPA on the viability, reactive oxygen species (ROS), apoptosis and other types of programmed cell death in NPC cells in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers. PMID:26239511

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

    Directory of Open Access Journals (Sweden)

    Ronald M. Bukowski

    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. Treatment of early glassy cell carcinoma of uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Bae; Kim, Jin Hee; Choi, Tae Jin [Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2006-06-15

    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.

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

    NARCIS (Netherlands)

    H.S. van Monsjou; A.J.M. Balm; M.M. van den Brekel; V.B. Wreesmann

    2010-01-01

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

  17. 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.

  18. Basal cell carcinoma arising in a smallpox vaccination site.

    OpenAIRE

    Rich, J D; Shesol, B F; Horne, D W

    1980-01-01

    A case of pigmented basal cell carcinoma developing in a smallpox revaccination site is presented. Any progressive change within a smallpox vaccination scar should be thoroughly evaluated and treated appropriately after tissue diagnosis.

  19. 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

  20. Squamous cell carcinoma of the pancreas with liver metastasis: a case report

    Institute of Scientific and Technical Information of China (English)

    CHEN Qiang-pu; OU Kun; GUAN Qing-hai; ZHANG Fan

    2008-01-01

    @@ Squamous cell carcinoma of the pancreas is an unusual cancer of ductal cell origin. In a review of 6668 cases of exocrine pancreatic cancer from various registries reported from 1950 through 1985, the incidence of squamous carcinoma and adenosquamous carcinoma was 0.005% and 0.01%, respectively.1 We report a case of squamous cell carcinoma of the pancreas with liver metastasis.

  1. Digital necrosis with squamous cell carcinoma of the tonsil

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    2016-03-11

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

  3. Mast cells and human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Fabio Grizzi; Barbara Franceschini; Maurizio Chiriva-Internati; Young Liu; Paul L. Hermonat; Nicola Dioguardi

    2003-01-01

    AIM: To investigate the density of mast cells (MCs) in human hepatocellular carcinoma (HCC), and to determine whether the MCs density has any correlations with histopathological grading, staging or some baseline patient characteristics.METHODS: Tissue sections of 22 primary HCCs were histochemically stained with toluidine blue, in order to be able to quantify the MCs in and around the neoplasm using a computer-assisted image analysis system. HCC was staged and graded by two independent pathologists. To identify the sinusoidal capillarisation of each specimen 3μm thick sections were histochemically stained with sirius red, and semi-quantitatively evaluated by two independent observers. The data were statistically analysed using Spearman′s correlation and Student′s t-test when appropriate.RESULTS: MCs density did not correlate with the age or sex of the patients, the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, or the stage or grade of the HCC. No significant differences were found between the MCs density of the patients with and without hepatitis C virus infection, but they were significantly higher in the specimens showing marked sinusoidal capillarisation.CONCLUSION: The lack of any significant correlation between MCs density and the stage or grade of the neoplastic lesions suggests that there is no causal relationship between MCs recruitment and HCC. However, as capillarisation proceeds concurrently with arterial blood supply during hepatocarcinogenesis, MCs may be considered of primary importance in the transition from sinusoidal to capillary-type endothelial cells and the HCC growth.

  4. 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.

  5. Merkel Cell Carcinoma in Immunosuppressed Patients

    International Nuclear Information System (INIS)

    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

    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.

  7. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

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

    2015-01-01

    to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. METHODS: We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily......-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.)....

  8. Translocation Renal Cell Carcinomas in Adults: A Single Institution Experience

    OpenAIRE

    Zhong, Minghao; De Angelo, Patricia; Osborne, Lisa; Mondolfi, Paniz; Geller, Matthew; Yang, Youfeng; Linehan, W. Marston; Merino, Maria J.; Cordon-Cardo, Carlos; Cai, Dongming

    2012-01-01

    Translocation renal cell carcinoma is a newly recognized subtype of renal cell carcinoma (RCC) with chromosomal translocations involving TFE3 (Xp11.2) or, less frequently, TFEB (6p21). Xp11 translocation RCC was originally described as a pediatric neoplasm representing 20–40% of pediatric RCCs with a much lower frequency in the adult population. TFEB translocation RCC is very rare, with approximately 10 cases reported in the literature. Here, we describe the clinicopathological features of ad...

  9. 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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

  12. Corneal squamous cell carcinoma in a Border Collie.

    Science.gov (United States)

    Busse, Claudia; Sansom, Jane; Dubielzig, R R; Hayes, Alison

    2008-01-01

    A 6-year-old, female, spayed Border Collie was presented to the Unit of Comparative Ophthalmology at the Animal Health Trust with a 6-month history of a progressive nonpainful opacity of the left cornea. A keratectomy was performed and the tissue submitted for histopathology. The diagnosis was squamous cell carcinoma. There has been no recurrence of the neoplasm to date (5 months). Canine corneal squamous cell carcinoma (SCC) has not been reported previously in the UK. PMID:18190354

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

    Science.gov (United States)

    Beirne, Gilbert A.; Beirne, Clinton G.

    1956-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-07-01

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

  15. 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.

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

    Science.gov (United States)

    Reifenberger, J

    2007-05-01

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

  17. RMP Plays Distinct Roles in the Proliferation of Hepatocellular Carcinoma Cells and Normal Hepatic Cells

    Science.gov (United States)

    Yang, Sijun; Wang, Hongmin; Guo, Yunlan; Chen, Shaomu; Zhang, Mei-Yin; Shen, Jian; Yu, Huijun; Miao, Jingcheng; Wang, Hui-Yun; Wei, Wenxiang

    2013-01-01

    RMP has been shown to function in the transcription regulation through association with RNA polymerase (RNAP) II subunit RPB5. It also has been shown to be required for the proliferation of hepatocellular carcinoma (HCC) cells with an antiapoptotic property. In this article, we further demonstrate that RMP displays distinct features in HCC cells compared with normal hepatic cells. RMP expression is remarkably increased in various cancer cell lines including HCC cells when compared with normal cells. Depletion of RMP could inhibit the proliferation of HCC cells, but not the normal hepatic cells. RMP significantly prevented apoptosis of HCC cells in SMMC-7721 and HepG2, but had little effect on apoptosis in the normal hepatic cells. The mechanisms of RMP's distinct features rely on different responsive expressions of apoptosis factors induced by RMP in HCC and hepatic cells. Either overexpression or depletion of RMP significantly affected the expression of apoptosis factors in HCC cells. However, normal hepatic cells showed a tendency to resist RMP for the regulation of apoptosis. In the clinical samples, the increased expression of RMP in HCCs was also observed when compared with the matched non-tumor tissues from 30 HCC patients. The different expression levels of and distinct responses to RMP between HCC and hepatic cells suggest that RMP might serve as not only a biomarker for the diagnosis of HCC, but also a potential target for the HCC therapy. PMID:23847445

  18. LATE PRESENTATION OF BASAL CELL CARCINOMA - A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Phani Kumar

    2013-12-01

    Full Text Available PURPOSE: To present a case of basal cell carcinoma with late presentation. METHODS: A 55year - old woman with gradual progressive, nodular, small brown lesion at the left lower eye lid for past 3 years was examined with, computed tomography (CT and then Excisional biopsy was done. RESULTS: The presenting symptom s of the patient were gradual progressive, nodular, sma ll brown lesion at the left lower eye lid . Excisional bi opsy with frozen section of the lesion was performed. Histopathologic evaluation of the eyelid lesion disclosed Trichoblastic (basal cell carcinoma of lower eye lid with large nodular and cribiform (a denoid patterns without any lymph - vascula r and perineural invasion. Post - operative period was uneventful. CONCLUSION: We are hereby reporting this case of eyelid BCC, with no history of skin cancer, or radiation treatment but exposure to sunlight. With earl y adequate treatment the prognosis is good KEYWORDS: B asal cell carcinoma, Excisional biopsy, Trichoblastic carcinoma .

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

    Science.gov (United States)

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

    1983-02-01

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

  20. Selective assembly of laminin variants by human carcinoma cells

    DEFF Research Database (Denmark)

    Wewer, U M; Wayner, E A; Hoffstrom, B G;

    1994-01-01

    in negligible amounts as detected by Northern blotting and PCR. The only exception was the HU-1 lung adenocarcinoma cell line which expressed significant quantities of laminin M chain mRNA and lower levels of laminin A chain mRNA. The presence in the HU-1 cells of translated polypeptides was demonstrated...... cell lines produced laminin chains B1, B2 and S, but no or little A or M. The only exception was the lung carcinoma cell line HU-1. Human HU-1 carcinoma cells in culture synthesize several homologous laminin chains and regulate the process of assembly, secretion and deposition of laminin variants...

  1. Cancer Stem Cell Markers in Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Aidan G. Major

    2013-01-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is one of the world’s top ten most common cancers. Current survival rates are poor with only 50% of patients expected to survive five years after diagnosis. The poor survival rate of HNSCC is partly attributable to the tendency for diagnosis at the late stage of the disease. One of the reasons for treatment failure is thought to be related to the presence of a subpopulation of cells within the tumour called cancer stem cells (CSCs. CSCs display stem cell-like characteristics that impart resistance to conventional treatment modalities and promote tumour initiation, progression, and metastasis. Specific markers for this population have been investigated in the hope of developing a deeper understanding of their role in the pathogenesis of HNSCC and elucidating novel therapeutic strategies.

  2. Microarray profile of human kidney from diabetes, renal cell carcinoma and renal cell carcinoma with diabetes

    OpenAIRE

    Kosti, Adam; Harry Chen, Hung-I; Mohan, Sumathy; Liang, Sitai; Chen, Yidong; Habib, Samy L

    2015-01-01

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have screened whole human DNA genome from healthy control, patients with diabetes or renal cell carcinoma (RCC) or RCC+diabetes. We found that 883 genes gain/163 genes loss of copy number in RCC+diabetes group, 669 genes gain/307 genes loss in RCC group and 458 genes gain/38 genes loss of copy number in diabetes group, after removing gain/loss genes ob...

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

    OpenAIRE

    Mehta, Karaninder S.; Mahajan, Vikram K.; Pushpinder S Chauhan; Anju Lath Sharma; Vikas Sharma; Abhinav, C.; Gayatri Khatri; Neel Prabha; Saurabh Sharma; Muninder Negi

    2012-01-01

    Basal cell carcinoma (BCC) accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide s...

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

    Directory of Open Access Journals (Sweden)

    Davis Paul

    2006-12-01

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

  5. Selective cytotoxicity of indirect nonequilibrium atmospheric pressure plasma against ovarian clear-cell carcinoma.

    Science.gov (United States)

    Utsumi, Fumi; Kajiyama, Hiroaki; Nakamura, Kae; Tanaka, Hiromasa; Hori, Masaru; Kikkawa, Fumitaka

    2014-01-01

    Ovarian clear cell carcinoma (CCC) is a histological type of epithelial ovarian cancer that is less responsive to chemotherapy and associated with a poorer prognosis than serous and endometrioid carcinoma. Non-thermal atmospheric pressure plasma which produces reactive species has recently led to an explosion of research in plasma medicine. Plasma treatment can be applied to cancer treatment to induce apoptosis and tumor growth arrest. Furthermore, recent studies have shown that a medium exposed to plasma also has an anti-proliferative effect against cancer in the absence of direct exposure to plasma. In this study, we confirmed whether this indirect plasma has an anti-tumor effect against CCC, and investigated whether this efficacy is selective for cancer cells. Non-thermal atmospheric pressure plasma induced apoptosis in CCC cells, while human peritoneal mesothelial cells remained viable. Non-thermal atmospheric pressure plasma exhibits selective cytotoxicity against CCC cells which are resistant to chemotherapy.

  6. TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells.

    Science.gov (United States)

    Palladino, Giuseppe; Notarangelo, Tiziana; Pannone, Giuseppe; Piscazzi, Annamaria; Lamacchia, Olga; Sisinni, Lorenza; Spagnoletti, Girolamo; Toti, Paolo; Santoro, Angela; Storto, Giovanni; Bufo, Pantaleo; Cignarelli, Mauro; Esposito, Franca; Landriscina, Matteo

    2016-09-01

    Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone upregulated in several human malignancies and involved in protection from apoptosis and drug resistance, cell cycle progression, cell metabolism and quality control of specific client proteins. TRAP1 role in thyroid carcinoma (TC), still unaddressed at present, was investigated by analyzing its expression in a cohort of 86 human TCs and evaluating its involvement in cancer cell survival and proliferation in vitro Indeed, TRAP1 levels progressively increased from normal peritumoral thyroid gland, to papillary TCs (PTCs), follicular variants of PTCs (FV-PTCs) and poorly differentiated TCs (PDTCs). By contrast, anaplastic thyroid tumors exhibited a dual pattern, the majority being characterized by high TRAP1 levels, while a small subgroup completely negative. Consistently with a potential involvement of TRAP1 in thyroid carcinogenesis, TRAP1 silencing resulted in increased sensitivity to paclitaxel-induced apoptosis, inhibition of cell cycle progression and attenuation of ERK signaling. Noteworthy, the inhibition of TRAP1 ATPase activity by pharmacological agents resulted in attenuation of cell proliferation, inhibition of ERK signaling and reversion of drug resistance. These data suggest that TRAP1 inhibition may be regarded as potential strategy to target specific features of human TCs, i.e., cell proliferation and resistance to apoptosis. PMID:27422900

  7. Renal Preservation Therapy for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yichun Chiu

    2012-01-01

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

  8. Temporal bone squamous cell carcinoma - Penang experience.

    Science.gov (United States)

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

    2015-12-01

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

  9. Perfusion computed tomography in renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  10. Systemic adjuvant therapies in renal cell carcinoma.

    Science.gov (United States)

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  11. Systemic adjuvant therapies in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sebastiano Buti

    2012-10-01

    Full Text Available Renal cell carcinoma (RCC is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC.

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

    Directory of Open Access Journals (Sweden)

    Nouf Hijazi, MD

    2014-12-01

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

  13. Interferon-Gamma-Induced Nitric Oxide Inhibits the Proliferation of Murine Renal Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    David J. Tate Jr., John R. Patterson, Cruz Velasco-Gonzalez, Emily N. Carroll, Janie Trinh, Daniel Edwards, Ashok Aiyar, Beatriz Finkel-Jimenez, Arnold H. Zea

    2012-01-01

    Full Text Available Renal cell carcinoma (RCC remains one of the most resistant tumors to systemic chemotherapy, radiotherapy, and immunotherapy. Despite great progress in understanding the basic biology of RCC, the rate of responses in animal models and clinical trials using interferons (IFNs has not improved significantly. It is likely that the lack of responses can be due to the tumor's ability to develop tumor escape strategies. Currently, the use of targeted therapies has improved the clinical outcomes of patients with RCC and is associated with an increase of Th1-cytokine responses (IFNγ, indicating the importance of IFNγ in inhibiting tumor proliferation. Thus, the present study was designed to investigate a new mechanism by which IFNγ mediates direct anti-proliferative effects against murine renal cell carcinoma cell lines. When cultured RCC cell lines were exposed to murine recombinant IFNγ, a dose dependent growth inhibition in CL-2 and CL-19 cells was observed; this effect was not observed in Renca cells. Growth inhibition in CL-2 and CL-19 cell lines was associated with the intracellular induction of nitric oxide synthase (iNOS protein, resulting in a sustained elevation of nitric oxide (NO and citrulline, and a decrease in arginase activity. The inhibition of cell proliferation appears to be due to an arrest in the cell cycle. The results indicate that in certain RCC cell lines, IFNγ modulates L-arginine metabolism by shifting from arginase to iNOS activity, thereby developing a potent inhibitory mechanism to encumber tumor cell proliferation and survival. Elucidating the cellular events triggered by IFNγ in murine RCC cell lines will permit anti-tumor effects to be exploited in the development of new combination therapies that interfere with L-arginine metabolism to effectively combat RCC in patients.

  14. Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression

    OpenAIRE

    Shi, Si; Zhang, Qicheng; Xia, Yunfei; You, Bo; Shan, Ying; Bao, Lili; Li, Li; You, Yiwen; Gu, Zhifeng

    2016-01-01

    Mesenchymal stem cells (MSCs), which are capable of differentiating into multiple cell types, are reported to exert multiple effects on tumor development. However, the relationship between MSCs and nasopharyngeal carcinoma (NPC) cells remains unclear. Exosomes are small membrane vesicles that can be released by several cell types, including MSCs. Exosomes, which can carry membrane and cytoplasmic constituents, have been described as participants in a novel mechanism of cell-to-cell communicat...

  15. Derived vascular endothelial cells induced by mucoepidermoid carcinoma cells: 3-dimensional collagen matrix model*

    OpenAIRE

    Yang, Sen; Guo, Li-Juan; Gao, Qing-hong; Xuan, Ming; Tan, Ke; Zhang, Qiang; Wen, Yu-ming; Wang, Chang-mei; Tang, Xiu-fa; Wang, Xiao-yi

    2010-01-01

    Mucoepidermoid carcinoma undergoes uniquely vigorous angiogenic and neovascularization processes, possibly due to proliferation of vascular endothelial cells (ECs) induced by mucoepidermoid carcinoma cells (MCCs) in their three-dimensional (3D) microenvironment. To date, no studies have dealt with tumor cells and vascular ECs from the same origin of mucoepidermoid carcinoma using the in vitro 3D microenvironment model. In this context, the current research aims to observe neovascularization w...

  16. Circulating tumor cells in oral squamous cell carcinoma: An insight

    Directory of Open Access Journals (Sweden)

    B V Prakruthi

    2015-01-01

    Full Text Available Circulating tumor cells (CTCs are those cells present in the blood and have antigenic and/or genetic characteristics of a specific tumor type. CTCs can be detected in the peripheral blood of cancer patients. Various techniques are available for detection of CTCs, which provide evidence for future metastasis. CTCs may provide new insight into the biology of cancer and process of metastasis in oral squamous cell carcinoma (OSCC. The detection of CTCs may represent a new diagnostic tool for predicting the occurrence of metastatic disease in OSCC and endow with the treatment strategies to efficiently treat and prevent cancer metastasis. This review gives an insight into the significance of CTCs and different techniques for detection of CTCs.

  17. Dexamethasone-induced enhancement of resistance to ionizing radiation and chemotherapeutic agents in human tumor cells

    International Nuclear Information System (INIS)

    Background: Dexamethasone-induced changes in radioresistance have previously been observed by several authors. Here, we examined effects of dexamethasone on resistance to ionizing radiation in 10 additional human cell lines and strains, and on resistance to carboplatin and paclitaxel in 13 fresh tumor samples. Material and Methods: Eight human carcinoma cell lines, a glioblastoma cell line and a strain of normal human diploid fibroblasts were arbitrarily chosen for these in-vitro studies. Effects on radiosensitivity were assessed using a conventional colony formation assay. Effects on resistance to the drugs were investigated prospectively (ATP cell viability assay) using 13 fresh tumor samples from consecutive patients operated for ovarian cancer within the context of a Swiss nation-wide randomized prospective clinical trial (SAKK 45/94). Results: Dexamethasone promoted proliferation of 1 of the cell lines without affecting radiosensitivity, while it completely inhibited proliferation of another cell line (effects on radiosensitivity could thus not be examined). Furthermore, dexamethasone induced enhanced radioresistance in 1 of the 8 carcinoma cell lines examined. In the glioblastoma cell line, there was no effect on growth or radioresistance, nor in the fibroblasts. Treatment with dexamethasone enhanced resistance of the malignant cells to carboplatin in 4 of the 13 fresh tumor samples examined, while no enhancement in resistance to paclitaxel was observed. Conclusions: In agreement with previous reports, we found that dexamethasone may induce radioresistance in human carcinoma cells. Including the published data from the literature, dexamethasone induced enhancement in radioresistance in 4 of 12 carcinoma cell lines (33%), but not in 3 glioblastoma cell lines, nor in 3 fibroblast strains. Dexamethasone also induced enhanced resistance to carboplatin with a similar probability in fresh samples of ovarian cancer evaluated prospectively (in 4 of 13 samples; 31

  18. Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC). However, CD44 is widely expressed in most cells in HNSCC tumor samples and several cell lines tested. We previously identified a small population of CD24+/CD44+ cells in HNSCC. In this study, we examined whether this population of cells may represent CSC in HNSCC. CD24+/CD44+ cells from HNSCC cell lines were sorted by flow cytometry, and their phenotype was confirmed by qRT-PCR. Their self-renewal and differentiation properties, clonogenicity in collagen gels, and response to anticancer drugs were tested in vitro. The tumorigenicity potential of CD24+/CD44+ cells was tested in athymic nude mice in vivo. Our results show that CD24+/CD44+ cells possessed stemness characteristics of self-renewal and differentiation. CD24+/CD44+ cells showed higher cell invasion in vitro and made higher number of colonies in collagen gels compared to CD24-/CD44+ HNSCC cells. In addition, the CD24+/CD44+ cells were more chemo-resistant to gemcitabine and cisplatin compared to CD24-/CD44+ cells. In vivo, CD24+/CD44+ cells showed a tendency to generate larger tumors in nude mice compared to CD24-/CD44+ cell population. Our study clearly demonstrates that a distinct small population of CD24+/CD44+ cells is present in HNSCC that shows stem cell-like properties. This distinct small population of cells should be further characterized and may provide an opportunity to target HNSCC CSC for therapy

  19. Establishment of a mdrl Multidrug Resistant Model of Orthotopic Transplantation of Liver Carcinoma on Nude Mice

    Institute of Scientific and Technical Information of China (English)

    HANYu; CHENXiaoping

    2005-01-01

    Objective: To develop a new method of inducing mdrl multidrug resistance by establishing a nude mice model of orthotopic transplantation of liver carcinoma by sporadic abdominal chemotherapy at intervals. Methods: Hepatocellular carcinoma HepG2 cell was cultured and injected subcutaneously to form the tumor-supplying mice. The tumor bits from the tumor-supplying mice were implanted under the envelope of the mice liver and induced by abdominal chemotherapy with Pharmorubicin. Physical examination, ultrasonography, spiral CT and operative inspection were used to examine tumor progression. RT-PCR and immunohistochemistry were adopted to detect the expression of mdrl-mRNA and its encoded protein P-gp protein (P-gp). Results: There was no operative dead, the rate of implanting tumor successfully was 88% (22/25), the rate of implanting secondly successfully was 100% (3/3), and the rate of inducing successfully was 80% (16/20). The expression of mdrl-mRNA and the P-gp in the inducing group was 23 folds and 13 folds in the control group respectively. Conclusion: We have established an in vivo model of mdr using nude mice transplanted with orthotopic liver neoplasm coupled to chemotherapy.

  20. RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis

    OpenAIRE

    Tsuta, K; Kohno, T.; Yoshida, A.; Shimada, Y.; Asamura, H.; Furuta, K; Kushima, R

    2014-01-01

    Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcriptio...

  1. (-)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma

    OpenAIRE

    Luo, Ting; Wang, Jiao; Yin, Yancun; Hua, Hui; Jing, Jing; Sun, Xiangming; Li, Minjing; Zhang, You; Jiang, Yangfu

    2010-01-01

    Introduction Paclitaxel (Taxol®) is a microtubule-targeted agent that is widely used for cancer treatment. However, resistance to paclitaxel is frequently encountered in the clinic. There is increasing interest in identifying compounds that may increase the sensitivity to conventional chemotherapeutic agents. In this study, we investigated whether green tea polyphenol (-)-epigallocatechin gallate (EGCG) could sensitize breast carcinoma to paclitaxel in vivo. Methods Breast cancer cells were t...

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

    International Nuclear Information System (INIS)

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

  3. MONOCLONAL-ANTIBODIES TO HUMAN EMBRYONAL CARCINOMA-CELLS - ANTIGENIC RELATIONSHIPS OF GERM-CELL TUMORS

    NARCIS (Netherlands)

    DEWIT, TFR; WILSON, L; VANDENELSEN, PJ; THIELEN, F; BREKHOFF, D; OOSTERHUIS, JW; PERA, MF; STERN, PL

    1991-01-01

    Fifteen monoclonal antibodies (mAb) that show specificity for human embryonal carcinoma cells are described. C57BL/6 mice were immunized with Tera-2 embryonal carcinoma cells, and hybridomas were isolated and tested versus a set of human developmental tumor cell lines. The antigens exhibit relativel

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

    Science.gov (United States)

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

    2012-04-01

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

  5. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  6. Properties of Lewis Lung Carcinoma Cells Surviving Curcumin Toxicity

    OpenAIRE

    Dejun Yan, Michael E. Geusz, Roudabeh J. Jamasbi

    2012-01-01

    The anti-inflammatory agent curcumin can selectively eliminate malignant rather than normal cells. The present study examined the effects of curcumin on the Lewis lung carcinoma (LLC) cell line and characterized a subpopulation surviving curcumin treatments. Cell density was measured after curcumin was applied at concentrations between 10 and 60 μM for 30 hours. Because of the high cell loss at 60 μM, this dose was chosen to select for surviving cells that were then used to establis...

  7. Upregulation of TrkB promotes epithelial-mesenchymal transition and anoikis resistance in endometrial carcinoma.

    Directory of Open Access Journals (Sweden)

    Wei Bao

    Full Text Available Mechanisms governing the metastasis of endometrial carcinoma (EC are poorly defined. Recent data support a role for the cell surface receptor tyrosine kinase TrkB in the progression of several human tumors. Here we present evidence for a direct role of TrkB in human EC. Immunohistochemical analysis revealed that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF, are more highly expressed in EC than in normal endometrium. High TrkB levels correlated with lymph node metastasis (p<0.05 and lymphovascular space involvement (p<0.05 in EC. Depletion of TrkB by stable shRNA-mediated knockdown decreased the migratory and invasive capacity of cancer cell lines in vitro and resulted in anoikis in suspended cells. Conversely, exogenous expression of TrkB increased cell migration and invasion and promoted anoikis resistance in suspension culture. Furthermore, over-expression of TrkB or stimulation by BDNF resulted in altered the expression of molecular mediators of the epithelial-to-mesenchymal transition (EMT. RNA interference (RNAi-mediated depletion of the downstream regulator, Twist, blocked TrkB-induced EMT-like transformation. The use of in vivo models revealed decreased peritoneal dissemination in TrkB-depleted EC cells. Additionally, TrkB-depleted EC cells underwent mesenchymal-to-epithelial transition and anoikis in vivo. Our data support a novel function for TrkB in promoting EMT and resistance to anoikis. Thus, TrkB may constitute a potential therapeutic target in human EC.

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

    Science.gov (United States)

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

    2015-08-01

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

  9. Expression of Uncoupling Protein 2 in Breast Cancer Tissue and Drug-resistant Cells

    Institute of Scientific and Technical Information of China (English)

    Sun Yan; Yuan Yuan; Zhang Lili; Zhu Hong; Hu Sainan

    2013-01-01

    Objective:To explore the expression of uncoupling protein-2 (UCP2) in clinical breast cancer tissue and drug-resistant cells. Methods:The expression of UCP2 in breast cancer tissue and normal tissue adjacent to carcinoma as well as breast cancer cell MCF-7 and paclitaxel-resistant cell MX-1/T were respectively detected by immunohistochemistry and Western blot. Results:The expression of UCP2 in breast cancer tissue was signiifcantly higher than in normal tissue adjacent to carcinoma, and that in paclitaxel-resistant cell MX-1/T obviously higher than in breast cancer cell MCF-7. Conclusion:UCP2 is highly expressed in breast cancer tissue and drug-resistant cells.

  10. Expression of Uncoupling Protein 2 in Breast Cancer Tissue and Drug-resistant Cells

    Directory of Open Access Journals (Sweden)

    Yan Sun

    2013-09-01

    Full Text Available Objective: To explore the expression of uncoupling protein-2 (UCP2 in clinical breast cancer tissue and drug-resistant cells. Methods: The expression of UCP2 in breast cancer tissue and normal tissue adjacent to carcinoma as well as breast cancer cell MCF-7 and paclitaxel-resistant cell MX-1/T were respectively detected by immunohistochemistry and Western blot. Results: The expression of UCP2 in breast cancer tissue was significantly higher than in normal tissue adjacent to carcinoma, and that in paclitaxel-resistant cell MX-1/T obviously higher than in breast cancer cell MCF-7. Conclusion: UCP2 is highly expressed in breast cancer tissue and drug-resistant cells.

  11. 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.

  12. A case of small cell carcinoma of the vagina

    Directory of Open Access Journals (Sweden)

    Ryosuke Tamura

    2013-12-01

    Full Text Available Primary small cell carcinoma of the vagina is quite rare, and a standard treatment has not been established yet. Herein, we report a case of an 81-year-old woman who was diagnosed with a vaginal tumor without continuity with the uterine cervix. Histopathological diagnosis indicated alveolar solid growth of nuclear chromatin-rich atypical cells with a high N/C ratio and a partially recognized rosette-like structure, suggesting a differentiated neuroendocrine system. Chromogranin A and synapto- physin were positive. Stage I vaginal small cell carcinoma localized to the vagina was diagnosed. The tumor disappeared by radiation monotherapy with external beam irradiation and endocavitary irradiation. The patient remains alive without any disease 1 year and 8 months after the treatment, suggesting the efficacy of radiotherapy in small cell carcinoma of the vagina.

  13. Spiclomazine induces apoptosis associated with the suppression of cell viability, migration and invasion in pancreatic carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Wenjing Zhao

    Full Text Available The effective treatment for pancreatic carcinoma remains critically needed. Herein, this current study showed that spiclomazine treatment caused a reduction in viability in pancreatic carcinoma cell lines CFPAC-1 and MIA PaCa-2 in vitro. It was notable in this regard that, compared with pancreatic carcinoma cells, normal human embryonic kidney (HEK-293 and liver (HL-7702 cells were more resistant to the antigrowth effect of spiclomazine. Biochemically, spiclomazine treatment regulated the expression of protein levels in the apoptosis related pathways. Consistent with this effect, spiclomazine reduced the mitochondria membrane potential, elevated reactive oxygen species, and activated caspase-3/9. In addition, a key finding from this study was that spiclomazine suppressed migration and invasion of cancer cells through down-regulation of MMP-2/9. Collectively, the proposed studies did shed light on the antiproliferation effect of spiclomazine on pancreatic carcinoma cell lines, and further clarified the mechanisms that spiclomazine induced apoptosis associated with the suppression of migration and invasion.

  14. c-Myc plays a key role in TADs-induced apoptosis and cell cycle arrest in human hepatocellular carcinoma cells

    OpenAIRE

    Zhang, Dongdong; QI, JUNPENG; Liu, Rui; Dai, Bingling; Ma, Weina; Zhan, Yingzhuan; Zhang, Yanmin

    2015-01-01

    Cancer cell growth is complicated progression which is regulated and controlled by multiple factors including cell cycle, migration and apoptosis. In present study, we report that TADs, a novel derivative of taspine, has an essential role in resisting hepatocellular carcinoma growth (including arrest cell cycle) and migration, and inducing cell apoptosis. Our findings demonstrated that the TADs showed good inhibition on the hepatoma cell growth and migration, and good action on apoptosis indu...

  15. A rare bladder cancer - small cell carcinoma: review and update

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Small cell carcinoma of the bladder (SCCB is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC. Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease ( or = cT4bN+M+ should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients. The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB.

  16. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    cells were stained by antisera to carcinoembryonic antigen, keratin and epithelial membrane antigen, but not by antisera to alpha-lactalbumin, desmin or vimentin. Ultrastructurally, the epithelial derivation of the tumour was confirmed. Only a few intracytoplasmic lumina were demonstrated. The tumour......The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumour...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  17. High dose etretinate and interferon-alpha--a phase I study in squamous cell carcinomas and transitional cell carcinomas

    OpenAIRE

    Roth, Arnaud; Morant, Rudolf Hans Joséf; Alberto, Pierre

    1999-01-01

    Simultaneous exposure to retinoids and interferons can result in enhanced antiproliferative and differentiating effects on malignant lesions. We studied the toxicity and the potential efficacy of an association of high dose etretinate and Interferon-alpha (IFN-alpha) in squamous cell carcinomas of the lung, head and neck, the esophagus, cervix and the penis, as well as in transitional carcinomas of the bladder. The treatment consisted of etretinate (Tigason) 4 mg/kg/d on 2, 3, 4 and finally 5...

  18. Expression of stromelysin 3 in basal cell carcinomas.

    Science.gov (United States)

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

    2001-01-01

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

  19. Epithelial mesenchymal transition is required for acquisition of anoikis resistance and metastatic potential in adenoid cystic carcinoma.

    Directory of Open Access Journals (Sweden)

    Jun Jia

    Full Text Available Human adenoid cystic carcinoma (ACC is characterized by diffused invasion of the tumor into adjacent organs and early distant metastasis. Anoikis resistance and epithelial mesenchymal transition (EMT are considered prerequisites for cancer cells to metastasize. Exploring the relationship between these processes and their underlying mechanism of action is a promising way to better understand ACC tumors. We initially established anoikis-resistant sublines of ACC cells; the variant cells revealed a mesenchymal phenotype through Slug-mediated EMT-like transformation and displayed enhanced metastatic potential both in vitro and in vivo. Suppression of EMT by knockdown of Slug significantly impaired anoikis resistance, migration, and invasion of the variant cells. With overexpression of Slug and Twist, we determined that induction of EMT in normal ACC cells could prevent anoikis, albeit partially. These findings strongly suggest that EMT is indispensable in anoikis resistance, at least in ACC cells. Furthermore, we found that the EGFR/PI3K/Akt pathway acts as the common regulator for EMT-like transformation and anoikis resistance, as confirmed by their specific inhibitors. Gefitinib and LY294003 restored the sensibilities of anoikis-resistant cells to anoikis and simultaneously impaired their metastatic potential. In addition, the results from our in vivo model of metastasis suggest that pretreatment with gefitinib promotes mouse survival by alleviating pulmonary metastasis. Most importantly, immunohistochemistry of human ACC specimens showed a correlation between the overexpression of Slug and EGFR staining. This study has demonstrated that Slug-mediated EMT-like transformation is required by human ACC cells to achieve anoikis resistance and their metastatic potential. Targeting the EGFR/PI3K/Akt pathway holds potential as a preventive strategy against distant metastasis of ACC.

  20. ICAM1 Is a Potential Cancer Stem Cell Marker of Esophageal Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Sheng-Ta Tsai

    Full Text Available Esophageal squamous cell carcinoma (ESCC accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1 was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC.

  1. (123)I-interleukin-2 uptake in squamous cell carcinoma of the head and neck carcinoma

    NARCIS (Netherlands)

    Loose, David; Signore, Alberto; Staelens, Ludovicus; Bulcke, Katia Vanden; Vermeersch, Hubert; Dierckx, Rudi Andre; Bonanno, Elena; de Wiele, Christophe Van

    2008-01-01

    Introduction Information obtained on the IL-2 receptor status of tumour infiltrating lymphocytes in patients suffering from squamous cell carcinoma of the head and neck (SSCHN) before and after IL-2 treatment may lead to a better understanding of the immunological changes and related kinetics induce

  2. Gene expression profile of renal cell carcinoma clear cell type

    Directory of Open Access Journals (Sweden)

    Marcos F. Dall’Oglio

    2010-08-01

    Full Text Available PURPOSE: The determination of prognosis in patients with renal cell carcinoma (RCC is based, classically, on stage and histopathological aspects. The metastatic disease develops in one third of patients after surgery, even in localized tumors. There are few options for treating those patients, and even the new target designed drugs have shown low rates of success in controlling disease progression. Few studies used high throughput genomic analysis in renal cell carcinoma for determination of prognosis. This study is focused on the identification of gene expression signatures in tissues of low-risk, high-risk and metastatic RCC clear cell type (RCC-CCT. MATERIALS AND METHODS: We analyzed the expression of approximately 55,000 distinct transcripts using the Whole Genome microarray platform hybridized with RNA extracted from 19 patients submitted to surgery to treat RCC-CCT with different clinical outcomes. They were divided into three groups (1 low risk, characterized by pT1, Fuhrman grade 1 or 2, no microvascular invasion RCC; (2 high risk, pT2-3, Fuhrman grade 3 or 4 with, necrosis and microvascular invasion present and (3 metastatic RCC-CCT. Normal renal tissue was used as control. RESULTS: After comparison of differentially expressed genes among low-risk, high-risk and metastatic groups, we identified a group of common genes characterizing metastatic disease. Among them Interleukin-8 and Heat shock protein 70 were over-expressed in metastasis and validated by real-time polymerase chain reaction. CONCLUSION: These findings can be used as a starting point to generate molecular markers of RCC-CCT as well as a target for the development of innovative therapies.

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

    Science.gov (United States)

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

    2008-04-01

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

  4. An Unusual Location of Basal Cell Carcinoma: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Birgül Tepe

    2012-06-01

    Full Text Available Basal cell carcinoma is the most common malignant skin tumour. Chronic sun exposure is considered as the main etiologic factor in its development. Although it mainly occurs on sun-exposed areas as the face and neck, it rarely develops on the forearms and/or arms. The etiologic factors which affect the anatomic distribution of basal cell carcinoma are not well-known. Here we report two patients who developed basal cell carcinoma on the forearm. None of the patients had a specific etiologic factor except for chronic sunlight exposure. The aim of our report is to show that this prevalant cutaneous malignancy can be encountered in rare/unusual areas. (Turk J Dermatol 2012; 6: 51-4

  5. Expression of cyclooxygenase-2 in human esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jian-Gang Jiang; Dao-Wen Wang; Jiang-Bo Tang; Chun-Lian Chen; Bao-Xing Liu; Xiang-Ning Fu; Zhi-Hui Zhu; Wei Qu; Katherine Cianflone; Michael P. Waalkes

    2004-01-01

    AIM: To determine whether cyclooxygenase-2 (COX-2) was expressed in human esophageal squamous cell carcinoma.METHODS: Quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, immunohistochemistry and immunofluorescence were used to assess the expression level of COX-2 in esophageal tissue.RESULTS: COX-2 mRNA levels were increased by >80-fold in esophageal squamous cell carcinoma when compared to adjacent noncancerous tissue. COX-2 protein was present in 21 of 30 cases of esophageal squamous cell carcinoma tissues, but was undetectable in noncancerous tissue. Immunohistochemistry was performed to directly show expression of COX-2 in tumor tissue.CONCLUSION: These results suggest that COX-2 may be an important factor for esophageal cancer and inhibition of COX-2 may be helpful for prevention and possibly treatment of this cancer.

  6. Focus on Merkel cell carcinoma: diagnosis and staging

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-01

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

  7. Expression of EpCAM Increases in the Hepatitis B Related and the Treatment-Resistant Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Osamu Kimura

    2014-01-01

    Full Text Available Increasing evidence supports the important role of cancer stem cells (CSCs. Many reports suggest that epithelial cell adhesion molecule (EpCAM is a useful marker for cancer stem cells in hepatocellular carcinoma (HCC. To elucidate the mechanisms of cancer stem cells, the development of specific molecular targeted drugs has become very important. In the present study, we examined the EpCAM expression pattern and its characteristic expression in resected HCC. We studied the drug resistance of EpCAM expression cells. EpCAM expression was detected significantly more frequently with hepatitis B virus (HBV than with other etiologies. In HCC resection patients who had received prior treatment (transcatheter arterial embolization or hepatic arterial infusion chemotherapy, EpCAM was strongly expressed. In particular, very strong expression was observed after hepatic arterial infusion chemotherapy. The PLC/PRF/5 human HCC cell line expressed bimodal EpCAM, and EpCAM-positive cells had CSC cell potency. The EpCAM expression in EpCAM-positive cells increased significantly by treatment with cisplatin. EpCAM-positive cells showed better viability than EpCAM-negative cells when treated with ciplatin. Collectively, our results suggest that cancer stem cells are highly expressed in hepatitis B and have potential anticancer drug resistance.

  8. Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Clara E. Jäkel

    2012-01-01

    Full Text Available Metastatic renal cell carcinoma (RCC seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells.

  9. The use of the CELLection kit in the isolation of carcinoma cells from mononuclear cell suspensions

    DEFF Research Database (Denmark)

    Werther, K; Normark, M; Hansen, B F;

    2000-01-01

    antibody Ber-EP4 was used as the primary capture antibody. In order to permit phenotyping of the isolated carcinoma cells the magnetic beads were removed from the carcinoma cells by DN'ase digestion of the DNA linker between the magnetic bead and the secondary antibody. In an ex vivo model system...

  10. Liver Label Retaining Cancer Cells Are Relatively Resistant to the Reported Anti-Cancer Stem Cell Drug Metformin

    OpenAIRE

    Xin, Hong-Wu; Ambe, Chenwi M.; Miller, Tyler C.; Chen, Jin-Qiu; Wiegand, Gordon W.; Anderson, Andrew J.; Ray, Satyajit; Mullinax, John E.; Hari, Danielle M; Koizumi, Tomotake; Godbout, Jessica D.; Goldsmith, Paul K.; Stojadinovic, Alexander; Rudloff, Udo; Thorgeirsson, Snorri S.

    2016-01-01

    Background & Aims: Recently, we reported that liver Label Retaining Cancer Cells (LRCC) can initiate tumors with only 10 cells and are relatively resistant to the targeted drug Sorafenib, a standard of practice in advanced hepatocellular carcinoma (HCC). LRCC are the only cancer stem cells (CSC) isolated alive according to a stem cell fundamental function, asymmetric cell division. Metformin has been reported to preferentially target many other types of CSC of different organs, including live...

  11. PRIMARY TRANSITIONAL CELL CARCINOMA OF THE OVARY: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Anju

    2016-05-01

    Full Text Available A 38-year-old female presented with a history of progressively enlarging abdominal mass. Abdominal computed tomography showed a pelvic mass involving both the ovaries and omentum. CA-125 was normal. Staging surgery was performed and the histopathological diagnosis of Transitional Cell Carcinoma was made and later confirmed by immuno-histochemistry. Transitional cell carcinoma of the ovary is a rare subtype of epithelial ovarian cancer. Surgical resection is the primary therapeutic approach, and patient’s outcomes after chemotherapy are better than for other types of ovarian cancers.

  12. Squamous cell carcinoma larynx presenting as idiopathic thrombocytopenic purpura

    Directory of Open Access Journals (Sweden)

    Bekur R

    2015-01-01

    Full Text Available Association of immune thrombocytpenic purpura with solid malignancy as paraneoplastic manifestation has been reported earlier mainly with lymphoma and breast cancer. We report the case of a patient with squamous cell carcinoma of the larynx presenting with idiopathic thombocytopenic purpura (ITP. A 67-year-old lady presented with multiple ecchymotic patches and petechiae all over the body and bleeding from oral cavity was found to have severe thrombocytopenia diagnosed as ITP with bone marrow evidence of peripheral destruction without infiltration of bone marrow. Five months later she was diagnosed to have squamous cell carcinoma of larynx. Platelet count improved after splenectomy.

  13. Cutaneous Squamous Cell Carcinoma with Invasion through Ear Cartilage

    Directory of Open Access Journals (Sweden)

    Julie Boisen

    2016-01-01

    Full Text Available Cutaneous squamous cell carcinoma of the ear represents a high-risk tumor location with an increased risk of metastasis and local tissue invasion. However, it is uncommon for these cancers to invade through nearby cartilage. Cartilage invasion is facilitated by matrix metalloproteases, specifically collagenase 3. We present the unusual case of a 76-year-old man with an auricular squamous cell carcinoma that exhibited full-thickness perforation of the scapha cartilage. Permanent sections through the eroded cartilage confirmed tumor invasion extending to the posterior ear skin.

  14. Metastatic transitional cell carcinoma of the tibia radiologically mimicking osteosarcoma.

    LENUS (Irish Health Repository)

    Cunningham, Laurence Patrick

    2013-01-01

    We report a case of a 73-year-old lady with transitional cell carcinoma and no evidence of metastatic disease presenting with gradual weight loss, pretibial swelling and painful weightbearing. Investigations revealed a lesion of the right tibial diaphysis. The radiological and clinical appearance was that of primary osteosarcoma. Biopsy results revealed metastatic transitional cell carcinoma of the tibia. Intramedullary nailing was performed which relieved pain on weightbearing. The patient declined radiotherapy and was started on a palliative care regimen. This case illustrates the importance of histological diagnosis in the treatment of diaphyseal lesions.

  15. Isolated pancreatic metastases from a bronchogenic small cell carcinoma.

    LENUS (Irish Health Repository)

    Walshe, T

    2012-01-31

    We describe the case of a 60 year old female smoker who presented with a three month history of weight loss (14 Kg), generalized abdominal discomfort and malaise. Chest radiography demonstrated a mass projected inferior to the hilum of the right lung. Computed Tomography of thorax confirmed a lobulated lesion in the right infrahilar region and subsequent staging abdominal CT demonstrated a low density lesion in the neck of the pancreas. Percutaneous Ultrasound guided pancreatic biopsy was performed, histology of which demonstrated pancreatic tissue containing a highly necrotic small cell undifferentiated carcinoma consistent with metastatic small cell carcinoma of the bronchus.

  16. Bilateral multiloculated cystic renal cell carcinoma (Case report)

    OpenAIRE

    Gümürdülü, D; Uğuz, A; Gökdemir, A.; Soyupak, B.

    2014-01-01

    Aim: Multiloculated cystic renal cell carcinoma is a rare variant of renal cell carcinoma. Incidence and biological behaviour of the tumor are unknown and bilateral cases are very rare. Case report: Fifty four-years- old male patient was admitted to the Urology policlinic with a left flank pain which was present during one month. On ultra sonographic examination solid hypoecoic mass 37x 32 mm in size and extending to the adrenal area were found at the upperpole of right kidney. Another mass 3...

  17. Acinic cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

    Science.gov (United States)

    Fukuzawa, Ryuji; Fukuzawa, Kazuhiro; Abe, Hitoshi; Nagai, Toshihiro; Kameyama, Kaori

    2004-01-01

    A male African pygmy hedgehog (Atelerix albiventris), estimated to be 3 years old, presented with exophthalmos and fixed abduction of the right eye. Radiographic examination revealed a retrobulbar tumor in the right orbital cavity. The mass was surgically resected but recurred 3 months later and the hedgehog died. There was no gross or microscopic evidence of salivary or lacrimal gland involvement of the tumor at surgery or at necropsy. The histopathologic, immunohistochemical, and ultrastructural findings were those of acinic cell carcinoma, the origin of which was unknown. This is the first known case of acinic cell carcinoma in an African hedgehog. PMID:15048626

  18. Renal cell carcinoma arising in ipsilateral duplex system.

    Science.gov (United States)

    Mohan, Harsh; Kundu, Reetu; Dalal, Usha

    2014-09-01

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

  19. Genetic mutations associated with metastatic clear cell renal cell carcinoma

    Science.gov (United States)

    Wu, Qingjian; Li, Fengjie; Zhao, Jiang; Wu, Kaijin; Qu, Cunye; Chen, Yibu; Li, Meng; Chen, Xuelian; Stucky, Andres; Zhong, Jiangjian; Li, Longkun; Zhong, Jiang F.

    2016-01-01

    Metastasis is the major cause of death among cancer patients, yet early detection and intervention of metastasis could significantly improve their clinical outcomes. We have sequenced and analyzed RNA (Expression) and DNA (Mutations) from the primary tumor (PT), tumor extension (TE) and lymphatic metastatic (LM) sites of patients with clear cell renal cell carcinoma (CCRCC) before treatment. Here, we report a three-nucleotide deletion near the C-region of Plk5 that is specifically associated with the lymphatic metastasis. This mutation is un-detectable in the PT, becomes detectable in the TE and dominates the LM tissue. So while only a few primary cancer cells carry this mutation, the majority of metastatic cells have this mutation. The increasing frequency of this mutation in metastatic tissue suggests that this Plk5 deletion could be used as an early indicator of CCRCC metastasis, and be identified by low cost PCR assay. A large scale clinical trial could reveal whether a simple PCR assay for this mutation at the time of nephrectomy could identify and stratify high-risk CCRCC patients for treatments. PMID:26908440

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

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang, E-mail: wenfang64@hotmail.com; Zhang, Yi, E-mail: syzi960@yahoo.com

    2013-11-01

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

  1. Clinicopathologic Observations on Small Cell Carcinoma of the Esophagus

    Institute of Scientific and Technical Information of China (English)

    XiaolingWang; ShuongLiu; GuoxiangWu; XionliMeng; MingGuo; HuichaiYang

    2004-01-01

    OBJECTIVE To investigate the histogenesis and biological characteristics and factors influencing prognosis of small cell carcinoma of the esophagus(ESCC).METHODS The expression of CK, NSE, Syn, CHr-A and CD56 proteins were detected immunohistochemically in 63 cases of small cell carcinoma of the esophagus.RESULTS The ESCC cases were divided into two groups as follows: a puresmall cell group (28/63) and compound small cell group (35/63). Theimmunohistochemistry results were positive for: CK in 41.3%, NSE in 36.5%,Syn in 90.5%, CHr-A in 60.3% and CD56 in 50.8%. The difference betweenstaining of the pure small cell carcinoma and compound small cellcarcinoma was not statistically significant. The size and depth of tumorinvasion, the positive residual incision edge and lymph node metastasiswere the major factors influencing long-term survival.CONCLUSION Small cell carcinoma of the esophagus is a highly malignanttumor, which expresses neuroendocrine antigens. The histophathologicorigin is still unknown but the non-neuroepithelial origin was accepted in thisstudy.

  2. Evaluating hemorrhage in renal cell carcinoma using susceptibility weighted imaging.

    Directory of Open Access Journals (Sweden)

    Wei Xing

    Full Text Available BACKGROUND: Intratumoral hemorrhage is a frequent occurrence in renal cell carcinoma and is an indicator of tumor subtype. We hypothesize that susceptibility weighted imaging (SWI is sensitive to hemorrhage in renal cell carcinoma and can give a more diagnostic image when compared to conventional imaging techniques. MATERIALS AND METHODS: A retrospective review of 32 patients with clear cell renal cell carcinoma was evaluated. All patients underwent magnetic resonance imaging (MRI and 22 out of 32 patients also underwent a computed tomography (CT scan. Hemorrhage was classified into 3 different categories according to shape and distribution. Histopathology was obtained from all masses by radical nephrectomy. The ability to detect the presence of hemorrhage using CT, non-contrast conventional MRI and SWI was evaluated, and the patterns of hemorrhage were compared. RESULTS: Using pathologic results as the gold standard, the sensitivities of non-contrast conventional MRI, SWI and CT in detecting hemorrhage in clear cell renal cell carcinoma were 65.6%, 100% and 22.7%, respectively. Accuracy of non-contrast conventional MRI and SWI in evaluating hemorrhagic patterns were 31.3% and 100%, respectively. CONCLUSION: These results demonstrate that SWI can better reveal hemorrhage and characterize the pattern more accurately than either non-contrast conventional MRI or CT. This suggests that SWI is the technique of choice for detecting hemorrhagic lesions in patients with renal cancer.

  3. Cetuximab resistance in squamous carcinomas of the upper aerodigestive tract is driven by receptor tyrosine kinase plasticity

    DEFF Research Database (Denmark)

    Kjær, Ida; Lindsted, Trine; Fröhlich, Camilla;

    2016-01-01

    Squamous cell carcinomas (SCC) arising in upper parts of the aero-digestive tract (UAT) are among the leading causes of death worldwide. The epidermal growth factor receptor (EGFR) has been found to play an essential role in driving the malignancy of SCCUAT, but despite this, clinical results using...... a range of different EGFR- targeted agents have been disappointing. Cetuximab is currently the only EGFR-targeted agent approved by the FDA for treatment of SCCUAT. However, intrinsic and acquired cetuximab resistance is a major problem for effective therapy. Thus, a better understanding of the mechanisms...... by continuous selective pressure in vitro and in vivo. Our results show that resistant clones maintain partial dependency on EGFR and that RTK plasticity mediated by HER3 and IGF1R plays an essential role. A multi-target mAb mixture against EGFR, HER3, and IGF1R was able to overcome cetuximab resistance...

  4. Biology of Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Michele Milella, Alessandra Felici

    2011-01-01

    Full Text Available In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1 even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2 prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3 although we have successfully identified classes of drugs (or molecular mechanisms of action that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4 finally (and perhaps most importantly, even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer

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

    Directory of Open Access Journals (Sweden)

    Ravi Saini

    2015-01-01

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

  6. Octreotide inhibits proliferation and induces apoptosis of hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Hai-lin LIU; Li HUO; Lei WANG

    2004-01-01

    AIM: To study the effect of octreotide on cell proliferation and apoptosis in different hepatocellular carcinoma (HCC) cells and hepatocytes. METHODS: The proliferation of HCC cells (HepG2, SMMC-7721) and hepatocytes (L-02) was determined by MTT assay. Apoptosis was detected either by fluorescent staining, transmission electron microscopy or flow cytometry. The content of AFP in the supernatant of cultured HCC cells was determined by electrochemiluminescence immunoassay. The expression of SSTR subtypes was identified by RT-PCR.RESULTS: The proliferation of HCC cells and L-02 cells was inhibited significantly by octreotide (0.25, 0.5, 1.0,2.0 and 4.0 mg/L). However, the apoptosis of HCC cells markedly increased in a concentration-dependent manner.Both the apoptosis index and the percentage of apoptotic cells in L-02 cells were significantly lower than those of HepG2 and SMMC-7721 cells. The content of AFP in the supematant of cultured HepG2 cells treated with octreotide was also statistically reduced. Furthermore, SSTR2 and SSTR4 were positive in both the hepatocellular carcinoma cells and in the L-02 cells. SSTR3 was only expressed in the two heptatocellular carcinoma cells, and SSTR5 was found in the SMMC-7721 cells. No SSTR1 was detected either in HCC cells or L-02 cells. CONCLUSIONS:Apoptosis induction is a major mechanism of octreotide inhibition on hepatocellular cells. SSTR3 is expressed in the HCC cells, but not in the L-02 cells, which suggests a molecular basis for the HCC-selective effects of octreotide.

  7. File list: Pol.Bld.05.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  1. File list: DNS.Bld.10.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. Clear cell variant of intraosseous mucoepidermoid carcinoma: Report of a rare entity

    Directory of Open Access Journals (Sweden)

    Sujatha Varma

    2012-01-01

    Full Text Available Intraosseous mucoepidermoid carcinoma of jaw bones is a rare lesion. Abundance of clear cells in an intraosseous mucoepidermoid carcinoma may complicate its histopathologic diagnosis. It becomes extremely important to distinguish this lesion from other clear cell lesions of jaw region. Here, we report a case of clear cell variant of intraosseous mucoepidermoid carcinoma in the mandible.

  3. Renal cell carcinoma with metastasis to the submandibular and parotid glands A case report

    NARCIS (Netherlands)

    Smits, J.G.; Slootweg, P.J.

    1984-01-01

    Differential diagnosis between acinic cell carcinoma and renal cell carcinoma is an oft-quoted problem. A case is presented of a 60-year-old woman with metastatic lesions from a renal cell carcinoma to the parotid as well as the submandibular gland. Appropriate diagnosis was delayed due to lack of c

  4. File list: Oth.Bld.20.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

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    Lifescience Database Archive (English)

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  6. File list: Unc.Bld.05.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

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  7. File list: His.Bld.50.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

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  11. File list: Pol.Bld.10.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

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  12. File list: His.Bld.05.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

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  13. Effect of Celecoxib on Apoptosis of Endometrial Carcinoma Cell

    Institute of Scientific and Technical Information of China (English)

    SHENG Xiu-jie; FANG Zhao

    2007-01-01

    Objective: To investigate the effect of Celecoxib on proliferation and apoptosis of the endometrial carcinoma cell HEC-1B and the effect on the expression of Fas and Survivin mRNA. Methods: The inhibition on the growth of human endometrial carcinoma cell HEC-1B was investigated by cell culture and MTT experiment when treated with different concentrations of Celecoxib. The cell apoptosis was detected by flow cytometry and DNA Ladder Electrophoresis. The change of the expression of Fas and Survivin mRNA after the treatment of Celecoxib was detected With RT-PCR. Results: Celecoxib could effectively inhibit the growth of HEC-1B cells and induce apoptosis. Survivin mRNA expression was decreased and Fas mRNA expression was increased after treating with Celecoxib. Conclusion: Celecoxib could inhibit HEC-1B cell proliferation and induce its apoptosis.

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

    International Nuclear Information System (INIS)

    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.

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

    Science.gov (United States)

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

  16. Spindle cell carcinoma of the larynx: A rare case report

    Directory of Open Access Journals (Sweden)

    Binayak Baruah

    2016-01-01

    Full Text Available Spindle cell carcinoma (SpCC of the larynx, a subtype and a more aggressive variant of the commonly occurring squamous cell carcinoma, is a unique and rare neoplasm. It comprises of 0.6–1.5% of all laryngeal cancers. Macroscopically, it usually presents as a large pedunculated, polypoidal mass with surface ulceration. Microscopically, however, it is considered as a biphasic tumor that has surface epithelial changes (in situ to invasive carcinoma and an underlying mesenchymal spindle shaped neoplastic proliferation. If detected early, it has a very good prognosis. We present a case of SpCC in a 70-year-old male, who presented with progressive hoarseness since 1 year. The mass was removed under videolaryngoscopic guidance and thereafter, the patient underwent cobalt 60 radiotherapy. His symptoms gradually improved, and he regained good control of his voice.

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

    Science.gov (United States)

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

    2015-01-09

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

  18. Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus

    OpenAIRE

    Scott J Rodig; Cheng, Jingwei; Wardzala, Jacek; Dorosario, Andrew; Scanlon, Jessica J.; Laga, Alvaro C.; Martinez-Fernandez, Alejandro; Barletta, Justine A.; Bellizzi, Andrew M.; Sadasivam, Subhashini; Holloway, Dustin T.; Cooper, Dylan J.; Kupper, Thomas S.; Wang, Linda C; DeCaprio, James A.

    2012-01-01

    A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T...

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

    Science.gov (United States)

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

    2005-09-01

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

  20. Relationship between Cell Proliferation and Apoptosis in Cervical Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To study the relationship between cell proliferation and apoptosis in cervical carcinoma and its clinical significance.Methods The cell proliferation and apoptosis of cervical epithelial cells in archival formalin-fixed,paraffin-embedded tissue sections of normal cervix ,cervical intraepithelial neoplasms(CN) and cervical squamous carcinoma were tested by using immunohistochemistry assay and DNA nick end-labeling technigue.The proliferation index(PI) and apoptosis index(AI) were calculated and their correlation with clinical and pathological data was analyzed. Results PI was gradually increased,but the AI and AI/PI ratio decreased from normal cervical epithelium,CIN to cervical carcinoma. There was no significant relationship among cell proliferation,apoptosis,clinical stages and pathological grades.High AI was always asso-ciated with a poor prognosis of the patients. Conclusion Cell proliferation and apoptosis allow to distinguish among normal epithelium,CIN and cervical carcinoma and are useful for the assessment of the malignant potential of tumor tissues.

  1. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Paolo Aiello

    2014-01-01

    Full Text Available The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

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

    Directory of Open Access Journals (Sweden)

    Rombo, Roman

    2016-04-01

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

  3. Collision tumours, squamous cell carcinoma of larynx, papillary thyroid carcinoma, metastatic lymphatic node. Clinical Presentation

    International Nuclear Information System (INIS)

    the opening of the stoma. Papillary carcinoma compromises peritiroideo deep surgical limits and mucous upper right margin. Squamous cell carcinoma committed focally vocal cord left. Foci of vascular and perineural invasion papillary carcinoma. Two papillary carcinoma metastatic lymph nodes perilaringeos. Right middle yugulocarotidea 2-Chain: papillary carcinoma metastatic lymph node conglomerate (9.3 cm.) And tissue extension adipose periganglionar and metastatic squamous cell carcinoma of two lymph nodes (macro metastasis with capsule intact). 3-Chain yugulocarotidea middle and lower left: papillary carcinoma metastatic lymph node conglomerate in (7.2 cm.) And metastatic squamous cell carcinoma four lymph nodes (macro metastases with capsule intact). In two of said nodes simultaneously both tumor metastases is observed. Starts radiation therapy (65Gy) weekly concurrent CDDP, after which there is no evidence of tumor. Six months later, treatment is performed with ablative doses of iodine 131 scintigraphy showed that the remaining thyroid nodular captante in glandular bed. The patient progresses with lung and liver metastases died at 10 months after surgery. Although the literature we found other cases of tumors in collision, we have not found a case with two metastatic tumors in a single node with these histologist

  4. Effects of transforming growth interacting factor on biological behaviors of gastric carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Zhong-Liang Hu; Ji-Fang Wen; De-Sheng Xiao; Hui Zhen; Chun-Yan Fu

    2005-01-01

    AIM:Transforming growth interacting factor (TGIF) is an inhibitor of both transforming growth factor β (TGF-β) and retinoid signaling pathways. Moreover, the activation of MAPK pathway can prolong its half-life. However, its role in carcinogenesis is still unknown. Thus we attempted to investigate the effect of TGIF on biologic behaviors of gastric carcinoma cells.METHODS: Gastric carcinoma cell line, SGC-7901, was stably transfected with plasmid PcDNA3.1-TGIF. Western blotting and cell immunohistochemistry screening for the highly expressing clone of TGIF were employed. The growth of transfected cells was investigated by MTT and colonyformation assays, and apoptosis was measured by flow cytometry (FCM) and transmission electron microscopy.Tumorigenicity of the transfectant cells was also analyzed.RESULTS: TGIF had no effect on the proliferation, cell cycle and apoptosis of SGC-7901 cells, but cellular organelles of cells transfected with TGIF were richer than those of vector control or parental cells. Its clones were smaller than the control ones in plate efficiency, and its tumor tissues also had no obvious necrosis compared with the vector control or parental cells. Moreover, TGIF could resist TGF-β mediated growth inhibition.CONCLUSION: TGIF may induce differentiation of stomach neoplastic cells. In addition, TGIF can counteract the growth inhibition induced by TGF-β.

  5. 乳腺癌实施化疗后癌干细胞同P-糖蛋白及耐药蛋白在残存癌组织中表达的相关性%Breast cancer stem cells after chemotherapy with P - glycoprotein and resistant protein expression of correlation in the residual carcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    乔婉晴; 涂巍

    2014-01-01

    目的:研究乳腺癌实施化疗后癌干细胞、P-糖蛋白及耐药蛋白在残存癌组织中的表达情况。方法将本院2012年5月至2013年5月收治的53例乳腺癌患者作为研究对象,比较化疗前后癌组织中癌干细胞、P-糖蛋白及耐药蛋白表达情况。结果患者化疗后,残留癌细胞中的癌干细胞含量上升且形成的微球体直径增加,与化疗前相比差异具有显著性(t=6.3615,191.3086;P=0.0000);患者化疗后,残留癌细胞中癌干细胞内谷胱甘肽转移酶π、拓补异构酶Ⅱ的阳性表达率上升,与化疗前相比差异具有显著性(χ2=3.9775,4.4002;P=0.0461,0.0359);患者化疗后,残留癌组织中P-糖蛋白表达水平上升,而耐药蛋白表达水平上升极其明显;与化疗前相比差异极其显著(t=6.5045,11.2765;P=0.0000)。结论乳腺癌患者在化疗后,残存癌组织中的癌干细胞含量上升、P-糖蛋白及耐药蛋白的阳性表达率上升,产生一定的耐药性。%ObjectiveTo study the breast cancer stem cells after chemotherapy, P-glycoprotein and resistant protein expression in the residual carcinoma tissue.MethodsFrom May 2012 to May 2013 were 53 cases of breast cancer patients as the research object, compared before and after chemotherapy cancer stem cells in cancer tissue, P-glycoprotein and resistant protein expression.ResultsThe patients after chemotherapy, residual carcinoma cells in cancer stem cells content increased and the formation of the microsphere diameter increase, signiifcant difference compared with before treatment (t=6.3615, 191.3086;P=6.3615). Cancer stem cells in patients after chemotherapy, residual cancer cells within the glutathione transferase PI, the topology isomerase II the positive expression rate of rise, compared with before treatment with statistical signiifcance (χ2=3.9775, 3.9775;P=0.0461, 0.0359); after chemotherapy, patients with residual P

  6. Decreased Aquaporin Expression Leads to Increased Resistance to Apoptosis in Hepatocellular Carcinoma

    OpenAIRE

    Jablonski, Elizabeth M.; Mattocks, M. Adrian; Sokolov, Eugene; Koniaris, Leonidas G.; Hughes, Francis M; Fausto, Nelson; Pierce, Robert H.; Mckillop, Iain H.

    2006-01-01

    Cells undergoing apoptosis are characterized by decreased cell size due to changes in intracellular ion concentration and rapid, aquaporin (AQP)-dependent water movement out of the cell, events required for the activation of pro-apoptotic enzymes. The current study demonstrates AQP 8 and 9 expression is significantly decreased in hepatocellular carcinoma (HCC) versus normal liver. Isolation of hepatic tumor cells (H4IIE) and hepatocytes confirmed a lack of water movement across the H4IIE cell...

  7. Hepatocellular Carcinoma with Foamy Histiocyte-Like Appearance: A Deceptively Clear Cell Carcinoma Appearing Variant

    Directory of Open Access Journals (Sweden)

    Takuji Noro

    2010-08-01

    Full Text Available Hepatocellular carcinoma (HCC shows many pathological features, and it varies architecturally and cytologically. There have been many reports and discussions of the morphological features of HCC. A 63-year-old man was found to have a solitary tumor in liver segment 7 that was diagnosed as HCC. A partial resection of liver segment 7 was performed. Microscopically, the tumor lesion showed a moderately differentiated HCC. There was also a lesion with foamy histiocyte-like cells corresponding to the white lesion in the face of the cut tumor. Immunohistochemical staining showed that they were negative for CD68, S-100, vimentin, and HMB-45. The cytoplasm itself was negative on periodic acid Schiff (PAS and Sudan staining. Without immunohistological analysis, it is difficult to distinguish this HCC variant from clear cell carcinoma or metastases of renal cell carcinoma. It is important to recognize this type as a specific cytological variant of HCC that requires confirmation by immunohistochemistry. This report describes the case of a patient with a morphologically distinctive pattern of HCC with prominent cell cytoplasm that had a foamy histiocyte-like appearance. To the best of our knowledge, this is the first report of this HCC variant.

  8. Does a new polyomavirus contribute to Merkel cell carcinoma?

    Science.gov (United States)

    Garneski, Kelly M; DeCaprio, James A; Nghiem, Paul

    2008-01-01

    A new technique designed to hunt for non-human transcripts has identified a novel SV40-like virus present in the majority of Merkel cell carcinomas. Here we examine what it will take to determine whether or not this virus contributes to carcinogenesis. PMID:18598371

  9. Does a new polyomavirus contribute to Merkel cell carcinoma?

    OpenAIRE

    Garneski, Kelly M; Nghiem, Paul; DeCaprio, James A.

    2008-01-01

    A new technique designed to hunt for non-human transcripts has identified a novel SV40-like virus present in the majority of Merkel cell carcinomas. Here we examine what it will take to determine whether or not this virus contributes to carcinogenesis.

  10. Saudi Oncology Society clinical management guidelines for renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Shouki Bazarbashi

    2011-01-01

    Full Text Available In this report, guidelines for the evaluation, medical and surgical management of renal cell carcinoma is presented. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7th edition. The recommendations are presented with supporting evidence level.

  11. The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

    NARCIS (Netherlands)

    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

    2014-01-01

    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

  12. Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Todenhöfer Tilman

    2012-03-01

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

  13. Male Pelvic Squamous Cell Carcinoma of Unknown Primary Origin

    Directory of Open Access Journals (Sweden)

    Lauren Chiec

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  15. Large and small cells non-keratinizing epidermoid vaginal carcinoma

    International Nuclear Information System (INIS)

    Five case reports of patients who were assisted at the cervix Pathology Department from 'Mariana Grajales Coello' Provincial Gynecological Obstetrical Hospital in Santiago de Cuba due to vaginal bleeding, low abdominal pain, leukorrhea and vaginal injuries are presented. The pathological study confirmed the diagnosis of squamous or epidermoid cells carcinoma

  16. Merkel cell carcinoma and iodine-131 metaiodobenzylguanidine scan

    International Nuclear Information System (INIS)

    Two cases of Merkel cell carcinoma, a neuroendocrine neoplasia of the skin, investigated with iodine, 131 metaiodobenzylguanidine (131I-mIBG) scintigraphy, are reported. Uptake in the tumor was evident only in 1 case. The possible diagnostic and therapeutic role of 131I-mIBG in patients with this rare neoplasm is discussed. (orig.)

  17. Transitional Cell Carcinoma within a Portion of Inguinally Herniated Bladder

    Directory of Open Access Journals (Sweden)

    Matthew A. Uhlman

    2013-01-01

    Full Text Available Bladder herniation within the inguinal canal is a relatively uncommon finding. We report an even less-common occurrence of transitional cell carcinoma located within a portion of inguinally herniated bladder. Fewer than 20 reports exist in the literature describing this scenario.

  18. Merkel cell carcinoma and iodine-131 metaiodobenzylguanidine scan

    Energy Technology Data Exchange (ETDEWEB)

    Castagnoli, A.; Biti, G.; De Cristofaro, M.T.R.; Papi, M.G. (Florence Univ. (Italy). Dipt. di Fisiopatologia); Ferri, P. (Florence Univ. (Italy). U.O. Medicina Nuclear USL 10D); Magrini, S.M. (Florence Univ. (Italy). U.O. Radioterapia USL 10D); Bianchi, S. (Florence Univ. (Italy). Ist. di Anatomia Patologica)

    1992-10-01

    Two cases of Merkel cell carcinoma, a neuroendocrine neoplasia of the skin, investigated with iodine, 131 metaiodobenzylguanidine ({sup 131}I-mIBG) scintigraphy, are reported. Uptake in the tumor was evident only in 1 case. The possible diagnostic and therapeutic role of {sup 131}I-mIBG in patients with this rare neoplasm is discussed. (orig.).

  19. Oat cell carcinoma of the esophagus: Unusual radiological appearances

    Energy Technology Data Exchange (ETDEWEB)

    Bedi, D.G.; Shaw, M.T.

    1986-08-01

    Primary oat cell carcinoma of the esophagus is a very rare tumour. The radiographic appearance of the three cases described in this paper are unusual because they resemble benign lesions such as leiomyoma, fibrous polyp and candidiasis. It would be interesting to investigate whether such an unusual appearance is common for this neoplasm.

  20. Transitional cell carcinoma arising in a tailgut cyst.

    Science.gov (United States)

    Sheikh, Adnan A; Rotimi, Olorundi; Jacob, Deepa; Hyland, Racheal; Sagar, Peter M

    2015-01-01

    Malignant transformation in tailgut cysts (TGCs) is extremely rare, with no reports of transitional cell carcinoma arising in them in the UK literature. Here, we discuss a case of a patient with a malignant TGC encapsulating the rectum. This case report highlights the pathological and diagnostic considerations and discusses its management. PMID:26217002

  1. Transitional cell carcinoma arising in a tailgut cyst

    OpenAIRE

    Sheikh, Adnan A.; Rotimi, Olorundi; Jacob, Deepa; Hyland, Racheal; Sagar, Peter M.

    2015-01-01

    Malignant transformation in tailgut cysts (TGCs) is extremely rare, with no reports of transitional cell carcinoma arising in them in the UK literature. Here, we discuss a case of a patient with a malignant TGC encapsulating the rectum. This case report highlights the pathological and diagnostic considerations and discusses its management.

  2. New common variants affecting susceptibility to basal cell carcinoma.

    NARCIS (Netherlands)

    Stacey, S.N.; Sulem, P.; Masson, G.; Gudjonsson, S.A.; Thorleifsson, G.; Jakobsdottir, M.; Sigurdsson, A.; Gudbjartsson, D.F.; Sigurgeirsson, B.; Benediktsdottir, K.R.; Thorisdottir, K.; Ragnarsson, R.; Scherer, D.; Hemminki, K.; Rudnai, P.; Gurzau, E.; Koppova, K.; Botella-Estrada, R.; Soriano, V.; Juberias, P.; Saez, B.; Gilaberte, Y.; Fuentelsaz, V.; Corredera, C.; Grasa, M.; Hoiom, V.; Lindblom, A.; Bonenkamp, J.J.; Rossum, M.M. van; Aben, K.K.H.; Vries, E. de; Santinami, M.; Mauro, M.G. Di; Maurichi, A.; Wendt, J.; Hochleitner, P.; Pehamberger, H.; Gudmundsson, J.; Magnusdottir, D.N.; Gretarsdottir, S.; Holm, H.; Steinthorsdottir, V.; Frigge, M.L.; Blondal, T.; Saemundsdottir, J.; Bjarnason, H.; Kristjansson, K.; Bjornsdottir, G.; Okamoto, I.; Rivoltini, L.; Rodolfo, M.; Kiemeney, L.A.L.M.; Hansson, J.; Nagore, E.; Mayordomo, J.I.; Kumar, R.; Karagas, M.R.; Nelson, H.H.; Gulcher, J.R.; Rafnar, T.; Thorsteinsdottir, U.; Olafsson, J.H.; Kong, A.; Stefansson, K.

    2009-01-01

    In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A vari

  3. Vimentin positive acantholytic penile squamous cell carcinoma with rhabdoid features

    Directory of Open Access Journals (Sweden)

    Ramesh Y Chavan

    2014-01-01

    Full Text Available Acantholytic variant of penile squamous cell carcinoma (SCC is an exceedingly rare and associated with bad prognosis. Histologically it mimics angiosarcoma due to pseudovascular spaces. Vimentin immunopositivity in such cases represent epithelial to mesenchymal transition manifested by cellular discohesion. We describe a case of vimentin positive acantholytic penile SCC in a 55-year-old patient.

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

    Science.gov (United States)

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

    2012-07-01

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

  5. Oat cell carcinoma of the esophagus: Unusual radiological appearances

    International Nuclear Information System (INIS)

    Primary oat cell carcinoma of the esophagus is a very rare tumour. The radiographic appearance of the three cases described in this paper are unusual because they resemble benign lesions such as leiomyoma, fibrous polyp and candidiasis. It would be interesting to investigate whether such an unusual appearance is common for this neoplasm. (orig.)

  6. Squamous cell carcinoma of the lacrimal caruncle : case reports

    NARCIS (Netherlands)

    van de Put, Mathijs A. J.; Haeseker, Barbara I.; De Wolff-Rouendaal, Did; De Keizer, Robert J. W.

    2014-01-01

    Purpose: To report 2 cases of squamous cell carcinoma of the lacrimal caruncle. Methods: Two patients, a 38-year-old man and a 72-year-old woman, presented with a painful mass in the medial angle of the eyelid aperture, with signs of inflammation. Biopsy was performed in both cases. Results: Patholo

  7. Array comparative genomic hybridization of keratoacanthomas and squamous cell carcinomas

    DEFF Research Database (Denmark)

    Li, Jian; Wang, Kai; Gao, Fei;

    2012-01-01

    Keratoacanthoma (KA) is a benign keratinocytic neoplasm that spontaneously regresses after 3-6 months and shares features with squamous cell carcinomas (SCCs). Furthermore, there are reports of KAs that have metastasized, invoking the question of whether KA is a variant of SCC (Hodak et al., 1993...

  8. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia;

    2015-01-01

    INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing of...

  9. Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma

    Directory of Open Access Journals (Sweden)

    Bing Han

    2015-09-01

    Full Text Available During the chemotherapy of cancer, drug resistance is the first issue that chemotherapeutic drugs cannot be effectively used for the treatment of cancers repeatedly for a long term, and the main reason for this is that tumor cell detoxification is mediated by GSH (glutathione catalyzed by GST (glutathione-S-transferase. In this study, a GST inhibitor, ethacrynic acid (ECA, was designed to be coupled with methoxy poly(ethylene glycol-poly(lactide (MPEG–PLA by disulfide bonds to prepare methoxy poly(ethylene glycol-poly(lactide-disulphide bond-mthacrynic acid (MPEG–PLA–SS–ECA as a carrier material of the nanoparticles. Nanoparticles of pingyangmycin (PYM and carboplatin (CBP were prepared, respectively, and their physicochemical properties were investigated. The ECA at the disulfide could be released in the presence of GSH, the pingyangmycin, carboplatin and ECA were all uniformly released, and the nanoparticles could release all the drugs completely within 10 days. The half maximal inhibitory concentration (IC50 of the prepared MPEG–PLA–SS–ECA/CBP and MPEG–PLA–SS–ECA/PYM nanoparticles in drug-resistant oral squamous cell carcinoma cell lines SCC15/CBP and SCC15/PYM cells was 12.68 μg·mL−1 and 12.76 μg·mL−1, respectively; the resistant factor RF of them in the drug-resistant cells were 1.51 and 1.24, respectively, indicating that MPEG–PLA–SS–ECA nanoparticles can reverse the drug resistance of these two drug-resistant cells.

  10. Establishment of a human hepatoma multidrug resistant cell line in vitro

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To establish a multidrug-resistant hepatoma cell line(SK-Hep-1),and to investigate its biological characteristics.METHODS:A highly invasive SK-Hep-1 cell line of human hepatocellular carcinoma,also known as malignant hepatoma was incubated with a high concentration of cisplatin(CDDP) to establish a CDDP-resistant cell subline(SK-Hep-1/CDDP).The 50% inhibitory dose(IC50) values and the resistance indexes [(IC50 SK-Hep-1/CDDP)/(IC50 SK-Hep-1)] for other chemotherapeutic agents and the growth curve of cell...

  11. The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Highlights: •Spheroids were created from esophageal carcinoma cells using NanoCulture® Plates. •The proportion of strongly ALDH-positive cells increased in 3-D culture. •Expression of cancer stem cell-related genes was enhanced in 3-D culture. •CA-9 expression was enhanced, suggesting hypoxia had been induced in 3-D culture. •Drug resistance was increased. 3-D culture is useful for inducing cancer stem cells. -- Abstract: In recent years, research on resistance to chemotherapy and radiotherapy in cancer treatment has come under the spotlight, and researchers have also begun investigating the relationship between resistance and cancer stem cells. Cancer stem cells are assumed to be present in esophageal cancer, but experimental methods for identification and culture of these cells have not yet been established. To solve this problem, we created spheroids using a NanoCulture® Plate (NCP) for 3-dimensional (3-D) cell culture, which was designed as a means for experimentally reproducing the 3-D structures found in the body. We investigated the potential for induction of cancer stem cells from esophageal cancer cells. Using flow cytometry we analyzed the expression of surface antigen markers CD44, CD133, CD338 (ABCG2), CD318 (CDCP1), and CD326 (EpCAM), which are known cancer stem cell markers. None of these surface antigen markers showed enhanced expression in 3-D cultured cells. We then analyzed aldehyde dehydrogenase (ALDH) enzymatic activity using the ALDEFLUOR reagent, which can identify immature cells such as stem cells and precursor cells. 3-D-cultured cells were strongly positive for ALDH enzyme activity. We also analyzed the expression of the stem cell-related genes Sox-2, Nanog, Oct3/4, and Lin28 using RT-PCR. Expression of Sox-2, Nanog, and Lin28 was enhanced. Analysis of expression of the hypoxic surface antigen marker carbonic anhydrase-9 (CA-9), which is an indicator of cancer stem cell induction and maintenance, revealed that CA-9 expression

  12. The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Daisuke [Department of Esophageal and Gastroenterological Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Kato, Kazunori, E-mail: kzkatou@juntendo.ac.jp [Department of Biomedical Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585 (Japan); Department of Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Nohara, Shigeo; Iwanuma, Yoshimi; Kajiyama, Yoshiaki [Department of Esophageal and Gastroenterological Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2013-05-17

    Highlights: •Spheroids were created from esophageal carcinoma cells using NanoCulture® Plates. •The proportion of strongly ALDH-positive cells increased in 3-D culture. •Expression of cancer stem cell-related genes was enhanced in 3-D culture. •CA-9 expression was enhanced, suggesting hypoxia had been induced in 3-D culture. •Drug resistance was increased. 3-D culture is useful for inducing cancer stem cells. -- Abstract: In recent years, research on resistance to chemotherapy and radiotherapy in cancer treatment has come under the spotlight, and researchers have also begun investigating the relationship between resistance and cancer stem cells. Cancer stem cells are assumed to be present in esophageal cancer, but experimental methods for identification and culture of these cells have not yet been established. To solve this problem, we created spheroids using a NanoCulture® Plate (NCP) for 3-dimensional (3-D) cell culture, which was designed as a means for experimentally reproducing the 3-D structures found in the body. We investigated the potential for induction of cancer stem cells from esophageal cancer cells. Using flow cytometry we analyzed the expression of surface antigen markers CD44, CD133, CD338 (ABCG2), CD318 (CDCP1), and CD326 (EpCAM), which are known cancer stem cell markers. None of these surface antigen markers showed enhanced expression in 3-D cultured cells. We then analyzed aldehyde dehydrogenase (ALDH) enzymatic activity using the ALDEFLUOR reagent, which can identify immature cells such as stem cells and precursor cells. 3-D-cultured cells were strongly positive for ALDH enzyme activity. We also analyzed the expression of the stem cell-related genes Sox-2, Nanog, Oct3/4, and Lin28 using RT-PCR. Expression of Sox-2, Nanog, and Lin28 was enhanced. Analysis of expression of the hypoxic surface antigen marker carbonic anhydrase-9 (CA-9), which is an indicator of cancer stem cell induction and maintenance, revealed that CA-9 expression

  13. Tivozanib in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hepgur M

    2013-06-01

    Full Text Available Mehmet Hepgur, Sarmad Sadeghi, Tanya B Dorff, David I Quinn Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA Abstract: Renal cell carcinoma (RCC is an aggressive malignancy compared to other urological malignancies and has been associated with poor responses to conventional cytotoxic chemotherapy. Interferon-a and interleukin-2 were previously utilized in a limited number of patients with good performance status due to toxicity and safety issues. Over the last decade, through advances in the understanding of the biology and pathology of RCC, the important role of vascular endothelial growth factor (VEGF in RCC has been identified. Data from randomized trials have led to the approval of first-generation tyrosine kinase inhibitors (TKIs sorafenib, sunitinib, and pazopanib; however, these agents inhibit a wide variety of kinase targets and are associated with a range of adverse effects. More recently, a new generation TKI, axitinib, has been approved by the US Food and Drug Administration. Tivozanib is a novel TKI, which is a potent inhibitor of VEGF-1, VEGF-2, VEGF-3, c-kit, and PDGR kinases, with a more restricted target spectrum. Phase II and III studies have demonstrated significant activity and a favorable safety profile as an initial targeted treatment for advanced RCC. This review examines the emerging data with tivozanib for the treatment of advanced RCC. Preclinical investigations as well as Phase I, II, and III data are examined; data on the comparative benefits of tivozanib are reviewed. Finally, we discuss the future potential of tivozanib in combination, biomarkers associated with tivozanib response, and acquisition of resistance and nonkidney cancer indications. Keywords: targeted therapy, renal cell cancer, tyrosine kinase inhibitor, tivozanib

  14. Enterovesical fistula caused by a bladder squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chun-Hsiang Ou Yang; Keng-Hao Liu; Tse-Ching Chen; Phei-Lang Chang; Ta-Sen Yeh

    2009-01-01

    Enterovesical fistulas are not uncommon in patients with inflammatory or malignant colonic disease, however,fistulas secondary to primary bladder carcinomas are extremely rare. We herein reported a patient presenting with intractable urinary tract infection due to enterovesical fistula formation caused by a squamous cell carcinoma of the urinary bladder. This patient underwent en bloc resection of the bladder dome and involved ileum, and recovered uneventfully without urinary complaint. To the best of our knowledge, this is the first case reported in the literature.

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

    Science.gov (United States)

    Sellers, William; Fiorelli, Robert

    2015-11-01

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

  16. Synchronous Hurthle Cell Carcinoma and Papillary Carcinoma in a Patient with Hashimoto’s Thyroiditis: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Narayanan O. Navya

    2014-10-01

    Full Text Available Hashimoto’s thyroiditis, the most common autoimmune thyroid disease, is due to destruction of the thyroid gland by autoantibodies. Various types of thyroid malignancies may arise in Hashimoto’s thyroiditis. Follicular carcinomas, papillary carcinomas, lymphomas, medullary carcinomas and hurthle cell neoplasms may develop in Hashimoto’s thyroiditis. We present a rare case report of a 35-year-old female who presented with hypothyroidism of a two-year duration. A diagnosis of Hashimoto’s thyroiditis was made for which she was under treatment. Due to the recent increase in size of the thyroid, a fine needle aspiration cytology was done. A preoperative diagnosis of Hurthle cell neoplasm was made based on fine needle aspiration cytology findings. The total thyroidectomy specimen revealed Hashimoto’s thyroiditis with synchronous papillary carcinoma and Hurthle cell carcinoma, which is a very rare occurrence.

  17. Ruptured renal cell carcinoma in pregnancy: a rare case presentation

    Directory of Open Access Journals (Sweden)

    Prameela RC

    2016-05-01

    Full Text Available Malignancy in pregnancy is rare. Carcinomas in pregnancy are mostly kidney cell mass. Renal cell carcinoma (RCC is the commonest malignancy in pregnancy. Because of softness and increased vascularity, rupture of renal cell carcinoma is not uncommon. Here we are presenting a rare case of renal cell carcinoma in pregnancy with spontaneous rupture resulting in massive hemoperitoneum and serious outcome because of late presentation renal cell carcinoma seldom ruptures. A 26 year old woman G2P1L1 with term pregnancy was referred to hospital 80kms away from periphery with non-progression of labour. There was antenatal record suggesting hypertensive disorder of pregnancy in second trimester. On examination, patient was in hypovolemic shock with profuse distension of abdomen. Diagnosis of abruption grade 3 or rupture uterus was made and immediate laparotomy was done. On opening the abdomen, there was hemoperitoneum but uterus was intact. Emergency LSCS done extracted a stillborn baby. There were no retro placental clots also. There was lot of necrotic tissue in the abdomen and there was a tumour arising from lower pole of left kidney which had invaded the renal vessels and had ruptured. Peripartum hysterectomy and left nephrectomy was done. Women did not respond to treatment and died. The objective of presenting this case is the dilemmas faced by the obstetrician in case of shock in 2nd stage of labour. Simple diagnostic tool like renal ultrasound will help to detect at an early stage which could improve the outcome. All cases of hypertensive disorders of pregnancy should be investigated for secondary causes of hypertension. Abdominal USG must be done for all cases of hypertensive disorders of pregnancy in 2nd trimester. Prompt diagnosis and early treatment is the key in management of such condition in pregnancy. [Int J Reprod Contracept Obstet Gynecol 2016; 5(5.000: 1677-1679

  18. Squamous cell carcinoma and pilonidal cyst disease.

    Science.gov (United States)

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

    2015-02-20

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

  19. Epigenetic disruption of cell signaling in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li-Li Li; Xing-Sheng Shu; Zhao-Hui Wang; Ya Cao; Qian Tao

    2011-01-01

    Nasopharyngeal carcinoma (NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia. Alternative to genetic changes, aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/ or histone modifications. These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC. In this review, we summariye the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research. Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.

  20. Properties of Lewis Lung Carcinoma Cells Surviving Curcumin Toxicity

    OpenAIRE

    Yan, Dejun; Geusz, Michael E; Jamasbi, Roudabeh J

    2011-01-01

    The anti-inflammatory agent curcumin can selectively eliminate malignant rather than normal cells. The present study examined the effects of curcumin on the Lewis lung carcinoma (LLC) cell line and characterized a subpopulation surviving curcumin treatments. Cell density was measured after curcumin was applied at concentrations between 10 and 60 μM for 30 hours. Because of the high cell loss at 60 μM, this dose was chosen to select for surviving cells that were then used to establish a new ce...

  1. Monoclonal antibodies for human non-small cell lung carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Hellstrom, I.; Hellstrom, K.E.; Linsley, P.; Brown, J.P.; Horn, D.

    1987-01-07

    The present invention is concerned with two novel monoclonal antibodies which define carbohydrate antigens associated with human non-small cell lung carcinomas (NSCLC) and certain other human carcinomas. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use in diagnostic methods such as the detection of malignant cells associated with NSCLC and therapeutic methods. The invention also comprises a method for determining the presence of a malignant condition in the lung of a subject. The method involves examining tissue from the subject for the presence of antigens which are Lesup(x) or Lesup(y) antigen or which have the characteristics of Lesup(y) and Lesup(x).

  2. Candida albicans infection in patients with oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Čanković Miloš

    2010-01-01

    Full Text Available Bacground/Aim. Systemic candidiasis in intensive care units remains an improtant problem due to antifungal resistance. Patients undergoing radiotherapy for head and neck cancer are at increased risk of developing oral candidiasis and they more frequent have prior fungi colonization. Due to identification of specific risk factors predisposing to fungal infection in order to threat such patients the aim of this study was to determine the presence of Candida species in patients with oral squamous cell carcinoma and compare it to the control subjects (patients with benign oral mucosal lesions. Methods. A total number of 30 consecutive oral cancer examined patients were included in this prospective study (24 men and 6 women with a mean age of 61.47 years, range 41-81 years. The control group consisted of 30 consecutive patients with histologically proven benign oral mucosal lesions (16 men and 14 women with a mean age of 54.53 years, range 16- 83 years. The samples for mycological examination were obtained by using sterile cotton swabs from the cancer lesion surface and in the patients of the control group from the benign mucosal lesion surface. Samples were inoculated in Sabouraud' dextrose agar. For identification purposes, Mackenzie germ tube test was performend on all isolates. Results. The prevalence of Candida was significantly higher in oral cancer patients than in control subjects (χ2 = 5.455, p = 0.020. Candida was found on nine of the 30 cancer surfaces; 5 (16.7% were identified as non-albicans Candida and 4 (13.3% as Candida albicans. In the control group, only Candida albicans was isolated from 2 (6.7% patients. In this study, no statistically significant differences in the presence of Candida species was found with respect to gender, age, smoking, alcohol consumption, wearing of dental protheses and the site of cancer lesion. Conclusion. The increased prevalence of yeasts on the surfaces of oral carcinoma indicates a need for their

  3. Oncogenic micro-RNAs and Renal Cell Carcinoma

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    Cristina eGrange

    2014-03-01

    Full Text Available Tumor formation is a complex process that occurs in different steps and involves many cell types, including tumor cells, endothelial cells, and inflammatory cells, which interact to promote growth of the tumor mass and metastasization. Epigenetic alterations occurring in transformed cells result in de-regulation of miRNA expression (a class of small non-coding RNA that regulates multiple functions which contributes to tumorigenesis. The specific miRNAs, which have an aberrant expression in tumors, are defined as oncomiRNAs, and may be either over- or under-expressed, but down-regulation is most commonly observed.Renal cell carcinoma is a frequent form of urologic tumor, associated with an alteration of multiple signaling pathways. Many molecules involved in the progression of renal cell carcinomas, such as HIF, VEGF or mTOR, are possible targets of deregulated miRNAs. Within tumor mass, the cancer stem cell population is a fundamental component that promotes tumor growth. The cancer stem cell hypothesis postulates that cancer stem cells have the unique ability to self-renew and to maintain tumor growth and metastasis. Cancer stem cells present in renal cell carcinoma were shown to express the mesenchymal stem cell marker CD105 and to exhibit self-renewal and clonogenic properties, as well as the ability to generate serially transplantable tumors. The phenotype of cancer stem cell has been related to the potential to undergo the epithelial-mesenchymal transition, which has been linked to the expression pattern of tumorigenic miRNAs or down-regulation of anti-tumor miRNAs. In addition, the pattern of circulating miRNAs may allow discrimination between healthy and tumor patients. Therefore, a miRNA signature may be used as a tumor biomarker for cancer diagnosis, as well as to classify the risk of relapse and metastasis, and for a guide for therapy.

  4. Fusobacterium nucleatum and T-cells in Colorectal Carcinoma

    Science.gov (United States)

    Mima, Kosuke; Sukawa, Yasutaka; Nishihara, Reiko; Qian, Zhi Rong; Yamauchi, Mai; Inamura, Kentaro; Kim, Sun A; Masuda, Atsuhiro; Nowak, Jonathan A.; Nosho, Katsuhiko; Kostic, Alecsandar D.; Giannakis, Marios; Watanabe, Hideo; Bullman, Susan; Milner, Danny A.; Harris, Curtis C.; Giovannucci, Edward; Garraway, Levi A.; Freeman, Gordon J.; Dranoff, Glenn; Chan, Andrew T.; Garrett, Wendy S.; Huttenhower, Curtis; Fuchs, Charles S.; Ogino, Shuji

    2015-01-01

    Importance Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by down-regulating antitumor T-cell-mediated adaptive immunity. Objective To test the hypothesis that higher amount of Fusobacterium nucleatum in colorectal carcinoma tissue is associated with lower density of T-cells in tumor tissue. Design A cross-sectional analysis was conducted on colorectal carcinoma cases in two U.S. nationwide prospective cohort studies. The amount of Fusobacterium nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high versus low). Multivariable ordinal logistic regression analysis was conducted to assess associations of the amount of Fusobacterium nucleatum with densities (quartiles) of T-cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted two-sided α level to 0.013 for multiple hypothesis testing. Setting The Nurses’ Health Study and the Health Professionals Follow-up Study. Participants 598 colon and rectal carcinoma cases. Main outcomes and measures Densities of CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ T-cells in tumor tissue, determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Results Fusobacterium nucleatum was detected in colorectal carcinoma tissue in 76 (13%) of 598 cases. Compared with Fusobacterium nucleatum-negative cases, Fusobacterium nucleatum-high cases were inversely associated with the density of CD3+ T-cells

  5. Poorly Differentiated Squamous Cell Carcinoma Arising in Tattooed Skin

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    Deba P. Sarma

    2010-01-01

    Full Text Available Introduction. Tattoos have increasingly become accepted by mainstream Western society. As a result, the incidence of tattoo-associated dermatoses is on the rise. The presence of a poorly differentiated squamous cell carcinoma in an old tattooed skin is of interest as it has not been previously documented. Case Presentation. A 79-year-old white homeless man of European descent presented to the dermatology clinic with a painless raised nodule on his left forearm arising in a tattooed area. A biopsy of the lesion revealed a poorly differentiated squamous cell carcinoma infiltrating into a tattoo. The lesion was completely excised and the patient remains disease-free one year later. Conclusion. All previous reports of squamous cell carcinomas arising in tattoos have been well-differentiated low-grade type or keratoacanthoma-type and are considered to be coincidental rather than related to any carcinogenic effect of the tattoo pigments. Tattoo-associated poorly differentiated invasive carcinoma appears to be extremely rare.

  6. Adenosquamous cell carcinoma of the cervix — clinical and prognostic characteristics of the disease

    Directory of Open Access Journals (Sweden)

    E. K. Tanriverdieva

    2012-01-01

    Full Text Available Adenosquamous cell carcinoma of the cervix is a rare form of cancer of the cervix. Because of the small number of observations adenosquamous cell carcinoma of the cervix remains poorly understood disease, although the first mention of it dates back to 1956, when A. Glucksmann, and C.D. Cherry first described of mixed carcinoma (adenoacanthoma of the uterine cervix.

  7. Synchronous Pulmonary Squamous Cell Carcinoma and Mantle Cell Lymphoma of the Lymph Node

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    Yu Sun

    2011-01-01

    Full Text Available Synchronous occurrence of pulmonary squamous cell carcinoma and malignant lymphoma of the lymph node is not reported in the literature. We report a case of pulmonary squamous cell carcinoma coexisting with a mantle cell lymphoma involving cervical and mediastinal lymph node. It is important to recognize this synchronous occurrence histopathologically and to be aware of the existence of “in situ” MCL.

  8. Euphorbia tirucalli modulates gene expression in larynx squamous cell carcinoma

    OpenAIRE

    Franco-Salla, Gabriela Bueno; Prates, Janesly; Cardin, Laila Toniol; dos Santos, Anemari Ramos Dinarte; Silva Jr, Wilson Araújo da; da Cunha, Bianca Rodrigues; Tajara, Eloiza Helena; Oliani, Sonia Maria; Rodrigues-Lisoni, Flávia Cristina

    2016-01-01

    Background Some plants had been used in the treatment of cancer and one of these has attracted scientific interest, the Euphorbia tirucalli (E. tirucalli), used in the treatment of asthma, ulcers, warts has active components with activities scientifically proven as antimutagenic, anti-inflammatory and anticancer. Methods We evaluate the influence of the antitumoral fraction of the E. tirucalli latex in the larynx squamous cell carcinoma (Hep-2), on the morphology, cell proliferation and gene ...

  9. Curcumin suppresses migration and invasion of human endometrial carcinoma cells

    OpenAIRE

    Chen, Qian; Gao, Qing; Chen, Kunlun; Wang, Yidong; Chen, Lijuan; Li, Xu

    2015-01-01

    Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, follo...

  10. Male Pelvic Squamous Cell Carcinoma of Unknown Primary Origin

    OpenAIRE

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

    2014-01-01

    Pelvic squamous cell carcinoma of unknown primary origin has been described in several case reports of female patients. However, there have been no published reports describing male patients with pelvic squamous cell cancer of unknown primary origin. Our case describes a 52-year-old man who presented with right buttock pain, rectal urgency, and constipation. His physical examination demonstrated tenderness to palpation around his gluteal folds. Computed tomography scan of his abdomen and pelv...

  11. Spindle-cell carcinoma of the prostate

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    Carlos Hirokatsu Watanabe Silva

    2012-03-01

    Full Text Available Sarcoma of the prostate and sarcomatoid carcinoma of the prostate are rareconditions, both characterized by a poor prognosis. Sarcomatoid carcinoma ofthe prostate typically arises from the evolution of an underlying adenocarcinoma,occasionally featuring heterologous elements, bulky disease being possiblebut rare. In contrast, sarcoma of the prostate derives from non-epithelialmesenchymal components of the prostatic stroma, shows rapid growth, andfrequently presents as massive pelvic tumors obstructing the urinary tractat the time of diagnosis. We report the case of a 55-year-old patient with atwo-month history of symptoms of urinary obstruction. The patient presentedwith an extremely enlarged heterogeneous prostate, although his prostatespecificantigen level was low. The lack of a history of prostatic neoplasia ledus to suspect sarcoma, and a transrectal prostate biopsy was carried out. Animmunohistochemical study of the biopsy specimen did not confirm the clinicalsuspicion. However, in view of the clinical features, we believe that sarcoma ofthe prostate was the most likely diagnosis. The patient received neoadjuvantchemotherapy followed by radiation therapy. At this writing, surgical resectionhad yet to be scheduled.

  12. BRCC3 acts as a prognostic marker in nasopharyngeal carcinoma patients treated with radiotherapy and mediates radiation resistance in vitro

    International Nuclear Information System (INIS)

    BRCC3 has been found to be aberrantly expressed in breast tumors and involved in DNA damage response. The contribution of BRCC3 to nasopharyngeal carcinoma prognosis and radiosensitivity is still unclear. Immunohistochemical analysis of BRCC3 was carried out in 100 nasopharyngeal carcinoma tissues, and the protein level was correlated to patient survival. BRCC3 expression of nasopharyngeal carcinoma cell lines was determined by Western-blotting and real-time PCR. Additionally, the effects of BRCC3 knockdown on nasopharyngeal carcinoma cell clongenic survival, DNA damage repair, and cell cycle distribution after irradiation was assessed. The BRCC3 protein level was inversely correlated with nasopharyngeal carcinoma patient overall survival (P < 0.001) and 3-year loco-regional relapse-free survival (P = 0.034). Multivariate analysis demonstrated that BRCC3 expression was an independent prognostic factor (P = 0.010). The expression of BRCC3 was much higher in radioresistant nasopharyngeal carcinoma cells than in radiosensitive cells. Knockdown of BRCC3 increased the cell survival fraction, attenuated DNA damage repair and resulted in G2/M cell cycle arrest in radioresistant NPC cells. High BRCC3 expression in nasopharyngeal carcinoma patients is associated with poor survival. BRCC3 knockdown could abate the radioresistance in nasopharyngeal carcinoma cells. These findings suggest the utility of BRCC3 as a prognostic biomarker and novel target for nasopharyngeal carcinoma

  13. Myoepithelial cells in lobular carcinoma in situ: distribution and immunophenotype.

    Science.gov (United States)

    Wang, Ying; Jindal, Sonali; Martel, Maritza; Wu, Yaping; Schedin, Pepper; Troxell, Megan

    2016-09-01

    Myoepithelial cells have important physical and paracrine roles in breast tissue development, maintenance, and tumor suppression. Recent molecular and immunohistochemical studies have demonstrated phenotypic alterations in ductal carcinoma in situ-associated myoepithelial cells. Although the relationship of lobular carcinoma in situ (LCIS) and myoepithelial cells was described in 1980, further characterization of LCIS-associated myoepithelial cells is lacking. We stained 27 breast specimens harboring abundant LCIS with antibodies to smooth muscle myosin heavy chain, smooth muscle actin, and calponin. Dual stains for E-cadherin/smooth muscle myosin heavy chain and CK7/p63 were also performed. In each case, the intensity and distribution of staining in LCIS-associated myoepithelial cells were compared with normal breast tissue on the same slide. In 78% of the cases, LCIS-associated myoepithelial cells demonstrated decreased staining intensity for one or more myoepithelial markers. The normal localization of myoepithelial cells (flat against the basement membrane, pattern N) was seen in 96% of LCIS, yet 85% of cases had areas with myoepithelial cell cytoplasm oriented perpendicular to the basement membrane (pattern P), and in 30% of cases, myoepithelial cells appeared focally admixed with LCIS cells (pattern C). This study characterizes detailed architectural and immunophenotypic alterations of LCIS-associated myoepithelial cells. The finding of variably diminished staining favors application of several myoepithelial immunostains in clinical practice. The interaction of LCIS with myoepithelial cells, especially in light of the perpendicular and central architectural arrangements, deserves further mechanistic investigation. PMID:27195907

  14. Pro-apoptotic effect of cecropin AD on nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    XIAO Ye-chen; HUANG Ya-dong; XU Pei-lin; ZHOU Zhen-qing; LI Xiao-kun

    2006-01-01

    @@ Nasopharyngeal carcinoma (NPC) is one of the highly prevalent malignancies in Southeast Asia.1 Chemotherapy and radiotherapy are commonly administrated to treat nasopharyngeal carcinoma, but these therapies can not prevent the recurrence and metastasis of tumor cells.

  15. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

    Directory of Open Access Journals (Sweden)

    Andreas Krieg

    Full Text Available Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN according to their proliferation index into G1- or G2-neuroendocrine tumors (NET and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC. Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1 or lymph node metastases (NEC-DUE2 from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

  16. Diagnosis and treatment in primary bladder small cell carcinoma: Literature review

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    Orcun Celik

    2016-03-01

    Full Text Available Small cell bladder carcinoma is a rare and frequently fatal disease. It can be distinguished from classical urothelial carcinoma microscopically and immunohistochemically. Small cell bladder carcinoma has histologically similar properties with other small cell carcinomas in other organs. It has a worse prognosis when compared to urothelial bladder cancer. Multimodal treatments are recommended although there is no widely accepted consensus regarding to the treatment algorithm because of its rarity. In this review, clinical properties and diagnosis of small cell bladder carcinoma, its histopathological and immunohistochemical properties and treatment modalities are examined.

  17. Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

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    Sonia Gon

    2013-01-01

    Full Text Available Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bladder represent a challenge both to the pathologist and urologists for its diagnosis and treatment, respectively.

  18. The von Hippel-Lindau protein sensitizes renal carcinoma cells to apoptotic stimuli through stabilization of BIMEL

    OpenAIRE

    Guo, Y; Schoell, MC; Freeman, RS

    2009-01-01

    von Hippel-Lindau (VHL) disease is caused by germ-line mutations in the VHL tumor suppressor gene and is the most common cause of inherited renal cell carcinoma (RCC). Mutations in the VHL gene also occur in a large majority of sporadic cases of clear-cell RCC, which have high intrinsic resistance to chemotherapy and radiotherapy. Here we show that VHL-deficient RCC cells express lower levels of the pro-apoptotic Bcl-2 family protein BIMEL and are more resistant to etoposide and UV radiation ...

  19. Galectin-1 induces hepatocellular carcinoma EMT and sorafenib resistance by activating FAK/PI3K/AKT signaling.

    Science.gov (United States)

    Zhang, P-F; Li, K-S; Shen, Y-H; Gao, P-T; Dong, Z-R; Cai, J-B; Zhang, C; Huang, X-Y; Tian, M-X; Hu, Z-Q; Gao, D-M; Fan, J; Ke, A-W; Shi, G-M

    2016-01-01

    Galectin-1 (Gal-1) is involved in several pathological activities associated with tumor progression and chemoresistance, however, the role and molecular mechanism of Gal-1 activity in hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT) and sorafenib resistance remain enigmatic. In the present study, forced Gal-1 expression promoted HCC progression and sorafenib resistance. Gal-1 elevated αvβ3-integrin expression, leading to AKT activation. Moreover, Gal-1 overexpression induced HCC cell EMT via PI3K/AKT cascade activation. Clinically, our data revealed that Gal-1 overexpression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that Gal-1 may be a potential therapeutic target for HCC and a biomarker for predicting response to sorafenib treatment. PMID:27100895

  20. Ovarian small cell carcinoma complicated by carcinomatous meningitis

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    Terukazu Ishii

    2012-04-01

    Full Text Available Meningeal metastasis is rare in the clinical course of ovarian carcinoma and its prognosis is extremely poor. We experienced a case of carcinomatous meningitis from metastatic ovarian small cell carcinoma. A 33-year-old woman with atypical genital bleeding, was diagnosed with a right ovarian tumor and referred to our department. She underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy. It was an optimal debulking surgery. She was diagnosed with ovarian carcinoma classified as Stage IIIc according to the Féderation Internationale de Gynécologie et d’Obstétrique classification system. Histological findings showed small cell carcinoma of the pulmonary type. The tumor was bilateral with paraaortic lymph node involvement. The patient was treated with irinotecan and cisplatin (CPT-P therapy. After 4 courses of CPTP therapy, multiple liver metastases and Virchow’s lymph node metastases were found. She was treated with amrubicin as a secondline chemotherapy, but the treatment was ineffective. Five months after surgery, the patient complained of severe headache and nausea. Lumbar puncture was performed and cytology was positive. Magnetic resonance brain imaging indicated meningeal thickening. The patient was diagnosed with meningeal metastasis and received 19-Gy whole cranial irradiation. In spite of these treatments, her disease progressed rapidly and she was often drowsy. She died of aspiration pneumonia 6 months after surgery.

  1. Trigeminal perineural spread of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hornik, Alejandro; Rosenblum, Jordan; Biller, Jose [Stritch School of Medicine, Loyola University Medical Center, Chicago (United States)

    2012-07-01

    A 55-year-old man had a five-day history of 'pins and needles' sensation on the left chin. Examination showed decreased pinprick sensation on the territory of the left mandibular branch of the trigeminal nerve. Brain magnetic resonance imaging (MRI) with gadolinium showed enhancement involving the left mandibular branch. Computed tomography (CT) of the chest, abdomen, and pelvis showed a left kidney mass diagnosed as renal carcinoma following nephrectomy. The 'numb-chin' syndrome heralds or accompanies systemic malignancies. Trigeminal perineural spread has been well-documented in head and neck neoplasms, however, to our knowledge, it has not been reported in renal neoplasms. (author)

  2. Using Molecular Biology to Develop Drugs for Renal Cell Carcinoma

    Science.gov (United States)

    Cowey, C. Lance; Rathmell, W. Kimryn

    2010-01-01

    Background Renal cell carcinoma is a disease marked by a unique biology which has governed it’s long history of poor response to conventional cancer treatments. The discovery of the signaling pathway activated as a result of inappropriate constitutive activation of the hypoxia inducible factors (HIF), transcription factors physiologically and transiently stabilized in response to low oxygen, has provided a primary opportunity to devise treatment strategies to target this oncogenic pathway. Objective A review of the molecular pathogenesis of renal cell cancer as well as molecularly targeted therapies, both those currently available and those in development, will be provided. In addition, trials involving combination or sequential targeted therapy are discussed. Methods A detailed review of the literature describing the molecular biology of renal cell cancer and novel therapies was performed and summarized. Results/Conclusion Therapeutics targeting angiogenesis have provided the first class of agents which provide clinical benefit in a large majority of patients and heralded renal cell carcinoma as a solid tumor paradigm for the development of novel therapeutics. Multiple strategies targeting this pathway and now other identified pathways in renal cell carcinoma provide numerous potential opportunities to make major improvements in treating this historically devastating cancer. PMID:20648240

  3. Long-term survival in uterine clear cell carcinoma and uterine papillary serous carcinoma.

    Science.gov (United States)

    Lindahl, Bengt; Persson, Jan; Ranstam, Jonas; Willén, Roger

    2010-09-01

    Uterine clear cell carcinoma (UCC) and uterine papillary serous carcinoma (UPSC) are rare entities that differ in clinical behavior from endometrial adenocarcinoma. Compared with endometrioid adenocarcinoma, they more often metastasize early and more commonly in the upper abdomen including the omentum. Treatment programs of UCC and UPSC at different stages vary and range from no adjuvant therapy in stage Ia to a wide variety of chemotherapies and radiotherapies in more advanced stages. This study presents the outcome of 109 patients with UCC or UPSC treated according to essentially the same treatment program from May 1993 to December 2004. Most patients were treated with a simple hysterectomy with no further adjuvant treatment. In stage Ia, 2/46 patients died of their disease and amongst all the stages, 30/109 patients died of their disease. These survival outcomes are comparable to or better than those presented previously. PMID:20944161

  4. Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC

    OpenAIRE

    Grimm, Martin; Cetindis, Marcel; Biegner, Thorsten; Lehman, Max; Munz, Adelheid; Teriete, Peter; Reinert, Siegmar

    2015-01-01

    Background: Resistance to programmed cell death (apoptosis) is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Vitamin D (calcitriol) may overcome apoptosis resistance in tumor cells of OSCC. Vitamin D receptor (VDR) expression in oral precancerous lesions of OSCC has not been analyzed and serum vitamin D level seems to be a predictor of cancer development. Material and Methods: Expression of VDR was analyzed in normal oral mucosa (n=5), oral precursor lesions ...

  5. Taxol and discodermolide represent a synergistic drug combination in human carcinoma cell lines.

    Science.gov (United States)

    Martello, L A; McDaid, H M; Regl, D L; Yang, C P; Meng, D; Pettus, T R; Kaufman, M D; Arimoto, H; Danishefsky, S J; Smith, A B; Horwitz, S B

    2000-05-01

    Recently, three natural products have been identified, the epothilones, eleutherobin, and discodermolide, whose mechanism of action is similar to that of Taxol in that they stabilize microtubules and block cells in the mitotic phase of the cell cycle. In this report, we have compared and contrasted the effects of these new agents in Taxol-sensitive and -resistant cell lines. We also have taken advantage of a human lung carcinoma cell line, A549-T12, that was isolated as a Taxol-resistant cell line and found to require low concentrations of Taxol (2-6 nM) for normal cell division. This study then examined the ability of these new compounds to substitute for Taxol in sustaining the growth of A549-T12 cells. Immunofluorescence and flow cytometry have both indicated that the epothilones and eleutherobin, but not discodermolide, can substitute for Taxol in this Taxol-dependent cell line. In A549-T12 cells, the presence of Taxol significantly amplified the cytotoxicity of discodermolide, and this phenomenon was not observed in combinations of Taxol with either the epothilones or eleutherobin. Median effect analysis using the combination index method revealed a schedule-independent synergistic interaction between Taxol and discodermolide in four human carcinoma cell lines, an effect that was not observed between Taxol and epothilone B. Flow cytometry revealed that concurrent exposure of A549 cells to Taxol and discodermolide at doses that do not induce mitotic arrest caused an increase in the hypodiploid population, thereby indicating that a possible mechanism for the observed synergy is the potentiation of apoptosis. Our results suggest that Taxol and discodermolide may constitute a promising chemotherapeutic combination.

  6. Identification of HRAS as cancer-promoting gene in gastric carcinoma cell aggressiveness

    Science.gov (United States)

    Wu, Xiao Yu; Liu, Wen Tao; Wu, Zhen Feng; Chen, Che; Liu, Jia Yun; Wu, Guan Nan; Yao, Xue Quan; Liu, Fu Kun; Li, Gang

    2016-01-01

    Gastric carcinoma is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that HRAS is markedly up-regulated in gastric carcinoma. Prognostic analysis indicated that HRAS expression might be a prognostic indicator for the survival of patients with gastric carcinoma. Ectopic expression of HRAS in gastric carcinoma cells accelerated proliferation, migration, invasion, angiogenesis, and clone formation ability of gastric carcinoma cells in vitro. Furthermore, HRAS over-expressing significantly promoted the tumorigenicity of gastric carcinoma cells in vivo whereas silencing endogenous HRAS caused opposite outcomes. Moreover, we demonstrated that HRAS enhanced gastric carcinoma aggressiveness by activating VEGFA/PI3K/AKT pathway and Raf-1 signaling. Together, our results provide new evidence that HRAS overexpression promotes the progression of gastric carcinoma and might represent a novel therapeutic target for its treatment. PMID:27725900

  7. Hepatic stellate cells secreted hepatocyte growth factor contributes to the chemoresistance of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Guofeng Yu

    Full Text Available As the main source of extracellular matrix proteins in tumor stroma, hepatic stellate cells (HSCs have a great impact on biological behaviors of hepatocellular carcinoma (HCC. In the present study, we have investigated a mechanism whereby HSCs modulate the chemoresistance of hepatoma cells. We used human HSC line lx-2 and chemotherapeutic agent cisplatin to investigate their effects on human HCC cell line Hep3B. The results showed that cisplatin resistance in Hep3B cells was enhanced with LX-2 CM (cultured medium exposure in vitro as well as co-injection with LX-2 cells in null mice. Meanwhile, in presence of LX-2 CM, Hep3B cells underwent epithelial to mesenchymal transition (EMT and upregulation of cancer stem cell (CSC -like properties. Besides, LX-2 cells synthesized and secreted hepatic growth factor (HGF into the CM. HGF receptor tyrosine kinase mesenchymal-epithelial transition factor (Met was activated in Hep3B cells after LX-2 CM exposure. The HGF level of LX-2 CM could be effectively reduced by using HGF neutralizing antibody. Furthermore, depletion of HGF in LX-2 CM abolished its effects on activation of Met as well as promotion of the EMT, CSC-like features and cisplatin resistance in Hep3B cells. Collectively, secreting HGF into tumor milieu, HSCs may decrease hepatoma cells sensitization to chemotherapeutic agents by promoting EMT and CSC-like features via HGF/Met signaling.

  8. Hypoxia-induced enhancement of cell invasiveness in SMMC7721 hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To explore the effects of hypoxia(1% O2)on the ability of cell invasiveness and expression of KAI1/CD82 in SMMC7721 hepatocellular carcinoma cells.Methods SMMC7721 hepatocellular carcinoma cells were cultured by hypoxia(1% O2)in vitro,and the ability of cell invasiveness was analyzed by cell invasion assay.Immunohistochemistry staining technique was used to evaluate the protein expression of KAI1/CD82.Results Cell invasion assay revealed that hypoxia enhanced the ability of invasiveness of hepatoc...

  9. ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma

    Science.gov (United States)

    Han, Ping; Wang, Hong-Bo; Liang, Fa-Ya; Feng, Guo-Kai; Zhou, Ai-Jun; Cai, Mu-Yan; Zhong, Qian; Zeng, Mu-Sheng; Huang, Xiao-Ming

    2016-01-01

    Interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, is known for its anti-viral capacity. However, its role in tumorigenesis remains controversial. Here, using RNA-seq profiling analysis, we identified ISG15 as a differentially expressed gene in nasopharyngeal carcinoma (NPC) and validated its overexpression in NPC samples and cells. High ISG15 levels in NPC tissues were correlated with more frequent local recurrence and shorter overall survival and disease-free survival. ISG15 overexpression promoted a cancer stem cell phenotype in NPC cells, including increased colony and tumorsphere formation abilities, pluripotency-associated genes expression, and in vivo tumorigenicity. By contrast, knockdown of ISG15 attenuated stemness characteristics in NPC cells. Furthermore, overexpression of ISG15 increased NPC cell resistance to radiation and cisplatin (DDP) treatment. Our study demonstrates a protumor role of ISG15, and suggests that ISG15 is a prognostic predictor and a potential therapeutic target for NPC. PMID:26919245

  10. Carcinoma de pequenas células na síndrome de Pancoast Small cell carcinoma in Pancoast syndrome

    Directory of Open Access Journals (Sweden)

    Jefferson Fontinele e Silva

    2009-02-01

    Full Text Available A síndrome de Pancoast consiste de sinais e sintomas decorrentes do acometimento do ápice pulmonar e estruturas adjacentes por um tumor. Na maioria das vezes, o processo causal é uma neoplasia. O carcinoma broncogênico é a principal neoplasia causadora da síndrome. Os subtipos histológicos mais encontrados são o adenocarcinoma e o carcinoma epidermoide. A ocorrência de carcinoma de pequenas células de pulmão como gênese da síndrome de Pancoast é rara, com poucos relatos na literatura. Descrevemos o caso de um doente com síndrome de Pancoast causado por um carcinoma de pequenas células de pulmão, discutindo aspectos referentes ao diagnóstico e à terapêutica.Pancoast syndrome consists of signs and symptoms resulting from a tumor affecting the pulmonary apex and adjacent structures. The process is typically caused by a neoplasm. The majority of cases of Pancoast syndrome are caused by bronchogenic carcinoma. The most commonly found histologic subtypes are adenocarcinoma and epidermoid carcinoma. There have been very few reports of small cell lung carcinoma in the genesis of Pancoast syndrome. We describe the case of a patient with Pancoast syndrome caused by small cell lung carcinoma and discuss the aspects related to the diagnosis and treatment.

  11. Smac mimetic and oleanolic acid synergize to induce cell death in human hepatocellular carcinoma cells.

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    Liese, Juliane; Abhari, Behnaz Ahangarian; Fulda, Simone

    2015-08-28

    Chemotherapy resistance of hepatocellular carcinoma (HCC) is still a major unsolved problem highlighting the need to develop novel therapeutic strategies. Here, we identify a novel synergistic induction of cell death by the combination of the Smac mimetic BV6, which antagonizes Inhibitor of apoptosis (IAP) proteins, and the triterpenoid oleanolic acid (OA) in human HCC cells. Importantly, BV6 and OA also cooperate to suppress long-term clonogenic survival as well as tumor growth in a preclinical in vivo model of HCC underscoring the clinical relevance of our findings. In contrast, BV6/OA cotreatment does not exert cytotoxic effects against normal primary hepatocytes, pointing to some tumor selectivity. Mechanistic studies show that BV6/OA cotreatment leads to DNA fragmentation and caspase-3 cleavage, while supply of the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) revealed a cell type-dependent requirement of caspases for BV6/OA-induced cell death. The receptor interacting protein (RIP)1 kinase Inhibitor Necrostatin-1 (Nec-1) or genetic knockdown of RIP1 fails to rescue BV6/OA-mediated cell death, indicating that BV6/OA cotreatment does not primarily engage necroptotic cell death. Notably, the addition of several reactive oxygen species (ROS) scavengers significantly decreases BV6/OA-triggered cell death, indicating that ROS production contributes to BV6/OA-induced cell death. In conclusion, cotreatment of Smac mimetic and OA represents a novel approach for the induction of cell death in HCC and implicates further studies.

  12. A RARE CASE REPORT OF SYNCHRONOUS MALIGNANCY – SQUAMOUS CELL CARCINOMA OF BASE OF TONGUE AND ADENO CARCINOMA OF STOMACH

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    Prakash

    2014-11-01

    Full Text Available The synchronous occurrence of primary squamous cell carcinoma of base of tongue with gastric adenocarcinoma is very rare. We report a case of 50 year old male patient presented to ENT OPD with complaints of throat pain, painful swallowing since 1month. Indirect laryngoscopy showed ulceroproliferative growth in Base of tongue, vallecula and epiglottis. Upper GI endoscopy showed ulceroproloferative lesion involving base of tongue, left epiglottis and vallecula. Endoscopic Biopsy from the growth revealed squamous cell carcinoma of the base of the tongue and adeno carcinoma of the stomach. We report this case to highlight a rare occurrence of synchronous malignancy of posterior tongue and stomach

  13. Targeted treatments in advanced renal cell carcinoma: focus on axitinib

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    Verzoni E

    2014-03-01

    Full Text Available Elena Verzoni, Paolo Grassi, Isabella Testa, Roberto Iacovelli, Pamela Biondani, Enrico Garanzini , Filippo De Braud, Giuseppe ProcopioDepartment of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyAbstract: Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials.Keywords: axitinib, renal cell carcinoma, vascular endothelial growth factor receptor, angiogenesis

  14. Reduced expression of Slit2 in renal cell carcinoma.

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    Ma, Wei-Jie; Zhou, Yu; Lu, Dan; Dong, Dong; Tian, Xiao-Jun; Wen, Jie-Xi; Zhang, Jun

    2014-01-01

    Slit2, initially identified as an important axon guidance molecule in the nervous system, was suggested to be involved in multiple cellular processes. Recently, Slit2 was reported to function as a potential tumor suppressor in diverse tumors. In this study, we systematically analyzed the expression level of Slit2 in renal cell carcinoma. Compared to paired adjacent non-malignant tissues, both Slit2 mRNA and protein expression were significantly down-regulated in renal cell carcinoma (RCC). Methylation-specific PCR showed that Slit2 promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation dramatically induced Slit2 expression in cancer cell lines with weak expression of Slit2. Besides, bisulfite genomic sequencing confirmed that dense methylation existed in Slit2 promoter. Furthermore, in paired RCC samples, Slit2 methylation was observed in 8 out of 38 patients (21.1 %), which was well correlated with the down-regulation of Slit2 in RCC. Therefore, Slit2 may also be a potential tumor suppressor in RCC, which is down-regulated in RCC partially due to promoter methylation.

  15. Palliative Radiation Therapy for Symptomatic Control of Inoperable Renal Cell Carcinoma

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    Anatoly Nikolaev

    2016-01-01

    Full Text Available Renal cell carcinoma (RCC is traditionally considered to be resistant to conventional low dose radiation therapy (RT. The emergence of image-guided stereotactic body radiation therapy (SBRT made it possible to deliver much higher doses of radiation. Recent clinical trials of SBRT for RCC showed improvement in local control rates and acceptable toxicity. Here we report a case of inoperable symptomatic RCC that was managed with SBRT. Strikingly, the presenting symptoms of gross hematuria and severe anemia were completely resolved following a course of SBRT. Thus, our case report highlights the potential benefit of this technique for patients with inoperable RCC.

  16. CD133 promotes gallbladder carcinoma cell migration through activating Akt phosphorylation

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    Zhen, Jiaojiao; Ai, Zhilong

    2016-01-01

    Gallbladder carcinoma (GBC) is the fifth most common malignancy of gastrointestinal tract. The prognosis of gallbladder carcinoma is extremely terrible partially due to metastasis. However, the mechanisms underlying gallbladder carcinoma metastasis remain largely unknown. CD133 is a widely used cancer stem cell marker including in gallbladder carcinoma. Here, we found that CD133 was highly expressed in gallbladder carcinoma as compared to normal tissues. CD133 was located in the invasive areas in gallbladder carcinoma. Down-regulation expression of CD133 inhibited migration and invasion of gallbladder carcinoma cell without obviously reducing cell proliferation. Mechanism analysis revealed that down-regulation expression of CD133 inhibited Akt phosphorylation and increased PTEN protein level. The inhibitory effect of CD133 down-regulation on gallbladder carcinoma cell migration could be rescued by Akt activation. Consistent with this, addition of Akt inhibitor Wortmannin markedly inhibited the migration ability of CD133-overexpressing cells. Thus, down-regulation of CD133 inhibits migration of gallbladder carcinoma cells through reducing Akt phosphorylation. These findings explore the fundamental biological aspect of CD133 in gallbladder carcinoma progression, providing insights into gallbladder carcinoma cell migration. PMID:26910892

  17. Single metastatic renal cell carcinoma in gallbladder: A case report

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    Kim, Eun Young; Cho, Bum Sang; Kang, Min Ho; Lee, Seung Young; Yi, Kyung Sik; Park, Kil Sun; Sung, Ro Hyun [Chungbuk National Univ. Hospital, Cheongju (Korea, Republic of)

    2012-07-15

    Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancy. 25% to 57% of RCC patients exhibit overt evidence of metastatic disease at initial presentation. Metastases to the gallbladder is uncommon and usually detected in only 0.4-0.6% of autopsies. We report the case of a 58 year old man who presented with a metastasis in the gallbladder from RCC. He had undergone went a right nephrectomy four years ago. There was no evidence of metastasis. A follow up abdomen CT scan taken three years after operation showed a polypoid lesion within the gallbladder. The size of the polypoid lesion had increased at the follow up CT and the enhancement pattern of lesion became similar to that of RCC. A Cholecystectomy was performed. Histopathological examination revealed the polyp was clear cell carcinoma of metastatic origin from kidney.

  18. All delays before radiotherapy risk progression of Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Prolonged waiting times for radiotherapy have resulted in many centres assigning priorities to various patient or diagnostic groups. A high risk of progression on a waiting list is one factor that would reasonably influence the priority. The present descriptive study of 27 patients with Merkel cell carcinoma (MCC) found that a median wait of 24 days for radiotherapy is associated with a high risk of progression. Eleven (41%) of 27 patients developed progressive disease, including five (45%) of 11 patients waiting for adjuvant radiotherapy. Patients treated adjuvantly also had longer waiting times prior to their initial radiotherapy consultation (median 41 days), which may have contributed to the rate of progression. Merkel cell carcinoma is an aggressive but curable malignancy and appropriate management should include efforts to minimize all potential delays prior to the commencement of radiotherapy. Copyright (2004) Blackwell Science Pty Ltd

  19. A Unique Presentation of an Undiagnosed Renal Cell Carcinoma

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    Georgios Kravvas

    2014-01-01

    Full Text Available We describe a 58-year-old lady who presented initially to her general practitioner with a palpable warty urethral nodule. She was subsequently referred to the urology department for further investigations. She underwent flexible cystoscopy and imaging, followed by rigid cystoscopy and excision of the nodule. Histological analysis was consistent with renal cell carcinoma (RCC. CT imaging confirmed the presence of an invading metastatic left renal cell carcinoma with bilateral metastatic deposits to the lungs and adrenal glands. The patient was enlisted on the Panther Trial and received a course of Pazopanib before undergoing radical nephrectomy. Two years later she is still alive with metastases remaining reduced in size and numbers. During this study we have performed a literature review of similar cases with this unusual presentation of RCC.

  20. ORAL MYIASIS CONVERTING TO ORAL SQUAMOUS CELL CARCINOMA

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    Akshay

    2015-10-01

    Full Text Available INTRODUCTION: Oral Myiasis, a condition of infestation of the body by fly larvae (maggots is a rare pathology in humans. It is associated with poor oral hygiene, alcoholism, senility, suppurating lesions, severe halitosis. It is seen frequently in tropical countries and hot climatic regions. The reported cases in literature of oral Myiasis associated with oral cancer are few. The treatment is a mechanical removal of the maggots but a systemic treatment with Ivermectin, a semi - synthetic macrolide antibiotic, has been used successfully for treatment for oral m yiasis. We present a case of 55 yr old male alcoholic patient with oral myiasis with extensive proliferative growth of oral cavity. Our patient was managed with manual debridement and administration of systemic ivermect in along with antibiotic coverage. Incisional biopsy of the proliferative lesion showed well differentiated squamous cell carcinoma. Thus our patient showed presence of oral myiasis in association with oral squamous cell carcinoma.