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Sample records for cell carcinoma hnscc

  1. Pretreatment oral hygiene habits and survival of head and neck squamous cell carcinoma (HNSCC) patients

    OpenAIRE

    Friemel, Juliane; Foraita, Ronja; Günther, Kathrin; Heibeck, Mathias; Günther, Frauke; Pflueger, Maren; Pohlabeln, Hermann; Behrens, Thomas; Bullerdiek, Jörn; Nimzyk, Rolf; Ahrens, Wolfgang

    2016-01-01

    Background The survival time of patients with head and neck squamous cell carcinoma (HNSCC) is related to health behavior, such as tobacco smoking and alcohol consumption. Poor oral health (OH), dental care (DC) and the frequent use of mouthwash have been shown to represent independent risk factors for head and neck cancerogenesis, but their impact on the survival of HNSCC patients has not been systematically investigated. Methods Two hundred seventy-six incident HNSCC cases recruited for the...

  2. Establishment and Molecular Cytogenetic Characterization of a Cell Culture Model of Head and Neck Squamous Cell Carcinoma (HNSCC)

    OpenAIRE

    Horst Zitzelsberger; Axel Walch; Johannes Weber; Herbert Braselmann; Reinhard Huber; Ludwig Hieber; Quirin Schaeffner; Bauer, Verena L.

    2010-01-01

    Cytogenetic analysis of head and neck squamous cell carcinoma (HNSCC) established several biomarkers that have been correlated to clinical parameters during the past years. Adequate cell culture model systems are required for functional studies investigating those potential prognostic markers in HNSCC. We have used a cell line, CAL 33, for the establishment of a cell culture model in order to perform functional analyses of interesting candidate genes and proteins. The cell line was cytogeneti...

  3. Establishment and Molecular Cytogenetic Characterization of a Cell Culture Model of Head and Neck Squamous Cell Carcinoma (HNSCC

    Directory of Open Access Journals (Sweden)

    Horst Zitzelsberger

    2010-11-01

    Full Text Available Cytogenetic analysis of head and neck squamous cell carcinoma (HNSCC established several biomarkers that have been correlated to clinical parameters during the past years. Adequate cell culture model systems are required for functional studies investigating those potential prognostic markers in HNSCC. We have used a cell line, CAL 33, for the establishment of a cell culture model in order to perform functional analyses of interesting candidate genes and proteins. The cell line was cytogenetically characterized using array CGH, spectral karyotyping (SKY and fluorescence in situ hybridization (FISH. As a starting point for the investigation of genetic markers predicting radiosensitivity in tumor cells, irradiation experiments were carried out and radiation responses of CAL 33 have been determined. Radiosensitivity of CAL 33 cells was intermediate when compared to published data on tumor cell lines.

  4. Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC)

    Science.gov (United States)

    Pectasides, Eirini; Rampias, Theodoros; Sasaki, Clarence; Perisanidis, Christos; Kouloulias, Vassilis; Burtness, Barbara; Zaramboukas, Thomas; Rimm, David; Fountzilas, George; Psyrri, Amanda

    2014-01-01

    Background Elucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT) phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC) prognosis. Methods Protein expression analysis of EGFR, β-catenin and E-cadherin was performed on a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using automated quantitative protein analysis (AQUA). We evaluated associations with clinicopathological parameters and prognosis. Results There were 67 patients with primary squamous cell carcinoma of the head and neck in this cohort who met inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR expression data. High E-cadherin expressers had longer 5-year progression-free survival (PFS) compared to those with low E-cadherin (59.7% versus 40.6%, p = 0.04) and overall survival (OS) (69.6% versus 44.3%, p  = 0.05). Kaplan-Meier analysis showed that patients with low beta-catenin-expressing tumors trended toward worse 5-year PFS (p = 0.057). High EGFR expressers had inferior OS compared to low EGFR expressers (27.7% vs. 54%, p = 0.029). In the multivariable analysis context, E-cadherin remained an independent predictor of improved OS (HR = 0.204, 95% CI 0.043 to 0.972, p = 0.046) while EGFR trended towards significance for OS. Conclusions The putative markers of EMT defined within a panel of HNSCC using AQUA are associated with tumors of poor prognosis. PMID:24722213

  5. Markers of epithelial to mesenchymal transition in association with survival in head and neck squamous cell carcinoma (HNSCC.

    Directory of Open Access Journals (Sweden)

    Eirini Pectasides

    Full Text Available BACKGROUND: Elucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC prognosis. METHODS: Protein expression analysis of EGFR, β-catenin and E-cadherin was performed on a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using automated quantitative protein analysis (AQUA. We evaluated associations with clinicopathological parameters and prognosis. RESULTS: There were 67 patients with primary squamous cell carcinoma of the head and neck in this cohort who met inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR expression data. High E-cadherin expressers had longer 5-year progression-free survival (PFS compared to those with low E-cadherin (59.7% versus 40.6%, p = 0.04 and overall survival (OS (69.6% versus 44.3%, p  = 0.05. Kaplan-Meier analysis showed that patients with low beta-catenin-expressing tumors trended toward worse 5-year PFS (p = 0.057. High EGFR expressers had inferior OS compared to low EGFR expressers (27.7% vs. 54%, p = 0.029. In the multivariable analysis context, E-cadherin remained an independent predictor of improved OS (HR = 0.204, 95% CI 0.043 to 0.972, p = 0.046 while EGFR trended towards significance for OS. CONCLUSIONS: The putative markers of EMT defined within a panel of HNSCC using AQUA are associated with tumors of poor prognosis.

  6. Head and neck squamous cell carcinoma (HNSCC) - detection of synchronous primaries with {sup 18}F-FDG-PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Strobel, Klaus; Schrank, Madeleine; Soyka, Jan D.; Veit-Haibach, Patrick; Hany, Thomas F. [University Hospital Zurich, Division of Nuclear Medicine, Department of Medical Radiology, Zurich (Switzerland); Haerle, Stephan K.; Stoeckli, Sandro J. [University Hospital Zurich, Department of Otorhinolaryngology, Head and Neck Surgery, Zurich (Switzerland)

    2009-06-15

    The aim of the study was to evaluate {sup 18}F-FDG-PET/CT for the detection of synchronous primaries at initial staging of patients with head and neck squamous cell carcinoma (HNSCC). FDG-PET/CT images acquired between March 2001 and October 2007 in 589 consecutive patients (147 women, 442 men; mean age 61.5 years, age range 32-97 years) with proven HNSCC were reviewed for the presence of synchronous primaries. Cytology, histology and/or clinical and imaging follow-up served as reference standard. FDG-PET/CT showed 69 suspected synchronous primaries in 62 patients of which 56 were finally confirmed in 44 patients. Of the 56 second cancers, 46 (82%) were found in the aerodigestive tract in the following locations: lung (26, 46%), head and neck (15, 17%), oesophagus (5, 9%). Ten second cancers (18%) were located outside the aerodigestive tract (colon, five; stomach, lymphoma, breast, thymus and kidney, one each). Six patients had three synchronous primaries and three patients had four synchronous cancers. Nine synchronous cancers were not detected by PET/CT (four head and neck, two lung, two oesophageal, one gastric). False-positive PET/CT findings were mainly related to benign FDG uptake in the intestine due to benign or precancerous polyps or physiological FDG uptake in other head and neck regions. Overall the prevalence of synchronous second primaries according to the reference standard was 9.5%, of which 84% were detected with FDG-PET/CT. In 80% of the patients, therapy was changed because of the detection of a synchronous primary. FDG-PET/CT detects a considerable number of synchronous primaries (8.0% prevalence) at initial staging of patients with HNSCC. Synchronous cancers were predominantly located in the aerodigestive tract, primarily in the lung, head and neck and oesophagus. Detection of second primaries has an important impact on therapy. PET/CT should be performed before panendoscopy. (orig.)

  7. Genomic Alteration in Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines Inferred from Karyotyping, Molecular Cytogenetics, and Array Comparative Genomic Hybridization.

    Science.gov (United States)

    Singchat, Worapong; Hitakomate, Ekarat; Rerkarmnuaychoke, Budsaba; Suntronpong, Aorarat; Fu, Beiyuan; Bodhisuwan, Winai; Peyachoknagul, Surin; Yang, Fengtang; Koontongkaew, Sittichai; Srikulnath, Kornsorn

    2016-01-01

    Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding, multiplex fluorescence in situ hybridization (M-FISH), and array comparative genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived from lymph-node metastatic lesions belonging to the same patients. Gain of chromosome 1, 7, and 11 were shared in almost all cell lines. Hierarchical clustering revealed that HN31 was closely related to HN4, which shared eight chromosome alteration cases. Large C-positive heterochromatins were found in the centromeric region of chromosome 9 in HN31 and HN4, which suggests complex structural amplification of the repetitive sequence. Array CGH revealed amplification of 7p22.3p11.2, 8q11.23q12.1, and 14q32.33 in all cell lines involved with tumorigenesis and inflammation genes. The amplification of 2p21 (SIX3), 11p15.5 (H19), and 11q21q22.3 (MAML2, PGR, TRPC6, and MMP family) regions, and deletion of 9p23 (PTPRD) and 16q23.1 (WWOX) regions were identified in HN31 and HN12. Interestingly, partial loss of PTPRD (9p23) and WWOX (16q23.1) genes was identified in HN31 and HN12, and the level of gene expression tended to be the down-regulation of PTPRD, with no detectable expression of the WWOX gene. This suggests that the scarcity of PTPRD and WWOX genes might have played an important role in progression of HNSCC, and could be considered as a target for cancer therapy or a biomarker in molecular pathology. PMID:27501229

  8. Genomic Alteration in Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines Inferred from Karyotyping, Molecular Cytogenetics, and Array Comparative Genomic Hybridization

    Science.gov (United States)

    Rerkarmnuaychoke, Budsaba; Suntronpong, Aorarat; Fu, Beiyuan; Bodhisuwan, Winai; Peyachoknagul, Surin; Yang, Fengtang; Koontongkaew, Sittichai; Srikulnath, Kornsorn

    2016-01-01

    Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding, multiplex fluorescence in situ hybridization (M-FISH), and array comparative genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived from lymph-node metastatic lesions belonging to the same patients. Gain of chromosome 1, 7, and 11 were shared in almost all cell lines. Hierarchical clustering revealed that HN31 was closely related to HN4, which shared eight chromosome alteration cases. Large C-positive heterochromatins were found in the centromeric region of chromosome 9 in HN31 and HN4, which suggests complex structural amplification of the repetitive sequence. Array CGH revealed amplification of 7p22.3p11.2, 8q11.23q12.1, and 14q32.33 in all cell lines involved with tumorigenesis and inflammation genes. The amplification of 2p21 (SIX3), 11p15.5 (H19), and 11q21q22.3 (MAML2, PGR, TRPC6, and MMP family) regions, and deletion of 9p23 (PTPRD) and 16q23.1 (WWOX) regions were identified in HN31 and HN12. Interestingly, partial loss of PTPRD (9p23) and WWOX (16q23.1) genes was identified in HN31 and HN12, and the level of gene expression tended to be the down-regulation of PTPRD, with no detectable expression of the WWOX gene. This suggests that the scarcity of PTPRD and WWOX genes might have played an important role in progression of HNSCC, and could be considered as a target for cancer therapy or a biomarker in molecular pathology. PMID:27501229

  9. The possible role of TP53 mutation status in the treatment of squamous cell carcinomas of the head and neck (HNSCC) with radiotherapy with different overall treatment times

    DEFF Research Database (Denmark)

    Eriksen, Jesper Grau; Alsner, Jan; Steiniche, Torben;

    2005-01-01

    for the outcome of radiotherapy. PATIENTS AND METHODS: DNA extracted from 180 paraffin-embedded formalin-fixed pretreatment biopsies of HNSCC was screened for mutations in exon 4C-10 by denaturing high-pressure liquid chromatography (DHPLC) followed by sequencing. Treatment was 66-68Gy, 2Gy/fx with overall...

  10. Post-operative chemo-radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC): first reported Australian experience

    International Nuclear Information System (INIS)

    In 1999, the Head and Neck Unit at Peter MacCallum Cancer Centre adopted a policy of treating high-risk, post-operative SCC patients with concurrent weekly platinum-based chemotherapy and radiotherapy. Patients were required to be medically fit to receive either cisplatin or carboplatin. Between July 1999 and January 2003, 59 patients were treated with post-operative chemo-radiotherapy. Median age was 59 (21 - 78) years, 76% were male and 83% had Stage III-IV disease at initial presentation. The predominant primary site was the oral cavity (37%). Thirty-five patients had nodal disease with extracapsular extension, and there were 37 cases with positive or close margins (<5mm) at the primary site. Thirteen patients received combined treatment due to recurrent disease. The majority of patients (54%) were treated with cisplatin, while the remaining 46% received carboplatin due to contraindications to cisplatin. The median radiation therapy dose was 60 (50-66) Gy. Fifty-seven (97%) patients completed at least 4 of the 6 planned courses of chemotherapy, 57 (97%) completed the planned course of radiotherapy. Twenty-seven (46%) patients had a grade 3/4 acute radiation reaction. Febrile neutropenia occurred in 2 (3%) patients. There were no treatment-related deaths. Median potential follow-up at the close-out date was 17 (4 - 45) months. The estimated 2-year local-regional control, progression free and overall survival was 69%, 53%, 61%, respectively. There have been 9 grade 3-4 late treatment sequelae. This series represents the largest reported Australian experience with post-operative chemo-radiotherapy in high-risk HNSCC. Treatment with concurrent platinum-based chemotherapy and radiotherapy is reasonably tolerated, and acute and late toxicity appears acceptable. The results we have achieved are comparable to those reported in the recent randomized trials of EORTC and RTOG

  11. Targeting FAK Radiosensitizes 3-Dimensional Grown Human HNSCC Cells Through Reduced Akt1 and MEK1/2 Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Hehlgans, Stephanie [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt am Main (Germany); Institute of Radiopharmacy, Helmholtz Center Dresden-Rossendorf, Dresden (Germany); Eke, Iris [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Cordes, Nils, E-mail: Nils.Cordes@OncoRay.de [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Institute of Radiopharmacy, Helmholtz Center Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany)

    2012-08-01

    Purpose: Focal adhesion kinase (FAK), a main regulator of integrin signaling and cell migration, is frequently overexpressed and hyperphosphorylated in human head-and-neck squamous cell carcinoma (HNSCC). We have previously shown that pharmacologic FAK inhibition leads to radiosensitization of 3-dimensionally grown HNSCC cell lines. To further evaluate the role of FAK in radioresistance and as a potential cancer target, we examined FAK and FAK downstream signaling in HNSCC cell lines grown in more physiologic extracellular matrix-based 3-dimensional cell cultures. Methods and Materials: Seven HNSCC cell lines were grown in 3-dimensional extracellular matrix and the clonogenic radiation survival, expression, and phosphorylation of FAK, paxillin, Akt1, extracellular signal-regulated kinase (ERK)1/2, and MEK1/2 were analyzed after siRNA-mediated knockdown of FAK, Akt1, MEK1, FAK+Akt1, or FAK+MEK1 compared with controls or stable overexpression of FAK. The role of MEK1/2 for clonogenic survival and signaling was investigated using the MEK inhibitor U0126 with or without irradiation. Results: FAK knockdown moderately or significantly enhanced the cellular radiosensitivity of 3-dimensionally grown HNSCC cells. The FAK downstream targets paxillin, Akt1, and ERK1/2 were substantially dephosphorylated under FAK depletion. FAK overexpression, in contrast, increased radiation survival and paxillin, Akt1, and ERK1/2 phosphorylation. The degree of radiosensitization upon Akt1, ERK1/2, or MEK1 depletion or U0126 was superimposable to FAK knockdown. Combination knockdown conditions (ie, Akt1/FAK, MEK1/FAK, or U0126/FAK) failed to provide additional radiosensitization. Conclusions: Our data provide further evidence for FAK as important determinant of radiation survival, which acts in the same signaling axis as Akt1 and ERK1/2. These data strongly support our hypothesis that FAK is a relevant molecular target for HNSCC radiotherapy.

  12. Lactate Dehydrogenase B Is Associated with the Response to Neoadjuvant Chemotherapy in Oral Squamous Cell Carcinoma

    OpenAIRE

    Wenyi Sun; Xiaomin Zhang; Xu Ding; Huaiqi Li; Meiyu Geng; Zuoquan Xie; Heming Wu; Min Huang

    2015-01-01

    Oral squamous cell carcinoma (OSCC) comprises a subset of head and neck squamous cell carcinoma (HNSCC) with poor therapeutic outcomes and high glycolytic dependency. Neoadjuvant chemotherapy regimens of docetaxel, cisplatin and 5-fluorouracil (TPF) are currently accepted as standard regimens for HNSCC patients with a high risk of distant metastatic spread. However, the antitumor outcomes of TPF neoadjuvant chemotherapy in HNSCC remain controversial. This study investigated the role of lactat...

  13. Hypoxia induces TFE3 expression in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Sun, Zhi-Jun; Yu, Guang-Tao; Huang, Cong-Fa; Bu, Lin-Lin; Liu, Jian-Feng; Ma, Si-Rui; Zhang, Wen-Feng; Liu, Bing; Zhang, Lu

    2016-03-01

    To assess the role of transcription factor μE3 (TFE3) in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC), human HNSCC tissue arrays were investigated for TFE3 expression. Human HNSCC tissues with neoadjuvant inductive chemotherapey (docetaxel, cisplatin and fluorouracil, TPF) and mice HNSCC tissues from transgenic mice model were evaluated for TFE3 expression and the hypoxia pathway. The roles of EGF/EGFR mediated hypoxia in TFE3 nuclear expression were analyzed in vitro and in vivo. TFE3 expression was higher in human HNSCC tissues compared with that in normal oral mucosa. Moreover, high TFE3 expression was related to HIF-1α, PAI-1, and EGFR, which demonstrated the activation of the hypoxia pathway in HNSCC tissues. Furthermore, elevated TFE3 expression was observed in HNSCC after cisplatin-based chemotherapy, and high TFE3 expression may indicate poor response to TPF inductive chemotherapy. Furthermore, similar changes with increased TFE3 were observed in HNSCC of the transgenic mouse HNSCC model. Hypoxic culture in the human HNSCC cell line increased TFE3 expression, which promoted cell survival under hypoxia. EGFR inhibiton by cetuximab could attenuate hypoxia-induced TFE3 in the HNSCC cell line and transgenic mouse HNSCC model. These findings indicated that TFE3 was an important hypoxia-induced transcriptional factor in HNSCC. TFE3 could be regarded as a durgable therapeutic oncotarget by EGFR inhibition. PMID:26872381

  14. Efficacy of gemcitabine and cetuximab combination treatment in head and neck squamous cell carcinoma

    OpenAIRE

    MASEKI, SHINICHIRO; IJICHI, KEI; NAKANISHI, HAYAO; Hasegawa, Yasuhisa; OGAWA, TETSUYA; Murakami, Shingo

    2013-01-01

    Head and neck squamous cell carcinoma (HNSCC) may be curable with surgery, radiation and chemotherapy in its early stages. However, recurrence and metastasis often prevail following primary treatment in advanced stage cases and are associated with significant morbidity and mortality. In this study we investigated the combination therapy of gemcitabine and cetuximab for HNSCC. The UM-SCC-6 and UM-SCC-23 HNSCC cell lines were analyzed following treatment with gemcitabine and cetuximab. To deter...

  15. HPV-positive HNSCC cell lines but not primary human fibroblasts are radiosensitized by the inhibition of Chk1

    International Nuclear Information System (INIS)

    Purpose: Despite the comparably high cure rates observed for HPV-positive HNSCC, there is still a great need for specific tumor radiosensitization due to the often severe side effects resulting from intense radiochemotherapy. We recently demonstrated that HPV-positive HNSCC cell lines are characterized by a defect in DNA double-strand break repair associated with a pronounced G2-arrest. Here we tested whether abrogation of this radiation-induced G2-arrest by the inhibition of Chk1 results in specific radiosensitization of HPV-positive HNSCC cells. Materials and methods: Experiments were performed with five HPV and p16-positive (93-VU-147T, UM-SCC-47, UT-SCC-45, UD-SCC-2, UPCI-SCC-154) and two HPV and p16-negative HNSCC cell lines, as well as two normal human fibroblast strains. Chk1 was inhibited by the selective inhibitor PF-00477736. Cell cycle distribution was determined by flow cytometry, Chk1-activity via Western blot and cell survival by colony formation assay. Results: With the exception of UPCI-SCC-154, the inhibition of Chk1 was found to abolish the pronounced radiation-induced G2-arrest in all HPV-positive cells utilized. All tumor cell lines that demonstrated the abrogation of G2-arrest also demonstrated radiosensitization. Notably, in G1-arrest-proficient normal human fibroblasts no radiosensitization was induced. Conclusion: Abrogation of the G2 checkpoint through the inhibition of Chk1 may be used to selectively increase the cellular radiosensitivity of HPV-positive HNSCC without affecting the surrounding normal tissue

  16. Novel insight into mutational landscape of head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Daria A Gaykalova

    Full Text Available Development of head and neck squamous cell carcinoma (HNSCC is characterized by accumulation of mutations in several oncogenes and tumor suppressor genes. We have formerly described the mutation pattern of HNSCC and described NOTCH signaling pathway alterations. Given the complexity of the HNSCC, here we extend the previous study to understand the overall HNSCC mutation context and to discover additional genetic alterations. We performed high depth targeted exon sequencing of 51 highly actionable cancer-related genes with a high frequency of mutation across many cancer types, including head and neck. DNA from primary tumor tissues and matched normal tissues was analyzed for 37 HNSCC patients. We identified 26 non-synonymous or stop-gained mutations targeting 11 of 51 selected genes. These genes were mutated in 17 out of 37 (46% studied HNSCC patients. Smokers harbored 3.2-fold more mutations than non-smokers. Importantly, TP53 was mutated in 30%, NOTCH1 in 8% and FGFR3 in 5% of HNSCC. HPV negative patients harbored 4-fold more TP53 mutations than HPV positive patients. These data confirm prior reports of the HNSCC mutational profile. Additionally, we detected mutations in two new genes, CEBPA and FES, which have not been previously reported in HNSCC. These data extend the spectrum of HNSCC mutations and define novel mutation targets in HNSCC carcinogenesis, especially for smokers and HNSCC without HPV infection.

  17. STAT3 as a chemoprevention target in carcinogen-induced head and neck squamous cell carcinoma.

    OpenAIRE

    Peyser, ND; Wang, L.; Zeng, Y.; Acquafondata, M.; Freilino, ML; Li, H.; M. Sen; Gooding, WE; Satake, M; Wang, Z.; Johnson; Grandis, JR

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal disease due in large part to a high rate of second primary tumor (SPT) formation. The 4-nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis provides a robust system in which to study chemopreventive agents in the context of chemically-induced HNSCC tumors. Signal transducer and activator of transcription 3 (STAT3) is a potent oncogene that is hyperactivated by tyrosine phosphorylation early in HNSCC carcinogenes...

  18. Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lacko, Martin [Department of Otorhinolaryngology—Head and Neck Surgery, Maastricht University Medical Center, Maastricht (Netherlands); Braakhuis, Boudewijn J.M. [Department of Otolaryngology—Head and Neck Surgery, VU University Medical Center, Amsterdam (Netherlands); Sturgis, Erich M. [Department of Head and Neck Surgery and Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Boedeker, Carsten C. [Department of Otorhinolaryngology—Head and Neck Surgery, Albert-Ludwigs-University, Freiburg, Germany and Department of Otorhinolaryngology - Head and Neck Surgery, HELIOS Hanseklinikum Stralsund, Stralsund (Germany); Suárez, Carlos [Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo (Spain); Instituto Universitario de Oncología del Principado de Asturias, Oviedo (Spain); Rinaldo, Alessandra; Ferlito, Alfio [ENT Clinic, University of Udine, Udine (Italy); Takes, Robert P., E-mail: robert.takes@radboudumc.nl [Department of Otolaryngology—Head and Neck Surgery, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)

    2014-05-01

    Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives of research on genetic susceptibility in HNSCC are discussed.

  19. Use of next generation sequencing in head and neck squamous cell carcinomas

    DEFF Research Database (Denmark)

    Tabatabaeifar, Siavosh; Kruse, Torben A; Thomassen, Mads;

    2014-01-01

    Head and neck squamous cell carcinoma (HNSCC) can primarily be attributed to alcohol consumption, tobacco use and infection with human papilloma virus. The heterogeneous nature of HNSCC has exposed a lack of tools for clinicians to provide more accurate prognosis. There is a need for biomarkers...

  20. Gene expression analysis for assessment of lymph node metastasis in head and neck squamous cell carcinoma

    NARCIS (Netherlands)

    Roepman, P.

    2006-01-01

    Head and neck squamous cell carcinoma (HNSCC) consists of a group of neoplasms that arise in the mucosal lining of the upper aero digestive tract. Treatment of HNSCC depends largely on assessment whether the patient has already developed lymph node metastases. However, due to difficulties in detecti

  1. Distant metastases from head and neck squamous cell carcinoma. Part III. Treatment

    NARCIS (Netherlands)

    Haigentz, Missak; Hartl, Dana M.; Silver, Carl E.; Langendijk, Johannes A.; Strojan, Primoz; Paleri, Vinidh; de Bree, Remco; Machiels, Jean-Pascal; Hamoir, Marc; Rinaldo, Alessandra; Paccagnella, Daniela; Shaha, Ashok R.; Takes, Robert P.; Ferlito, Alfio

    2012-01-01

    Distant metastases from head and neck squamous cell carcinoma (HNSCC), though rare at initial presentation, remain an important manifestation of cancer recurrence and mortality. Although generally considered incurable with a dismal prognosis despite palliative therapy, highly selected patients with

  2. Bimodal ex vivo expansion of T cells from patients with head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Junker, Niels; Andersen, Mads Hald; Wenandy, Lynn;

    2011-01-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has proven effective in metastatic melanoma and should therefore be explored in other types of cancer. The aim of this study was to examine the feasibility of potentially expanding clinically relevant quantities of tumor-specific T-cell cu......-cell cultures from TIL from patients with head and neck squamous cell carcinoma (HNSCC) using a more rapid expansion procedure compared with previous HNSCC studies....

  3. Prediction of Lymph Node Metastasis by Tumor Dimension Versus Tumor Biological Properties in Head and Neck Squamous Cell Carcinomas

    OpenAIRE

    Jang, Jeon Yeob; Kim, Min Ji; Ryu, Gwanghui; Choi, Nayeon; Ko, Young-Hyeh; Jeong, Han-Sin

    2015-01-01

    Purpose Lymph node metastasis (LNM) is a strong prognostic factor in many solid cancers, including head and neck squamous cell carcinomas (HNSCC), and LNM can be dependent upon primary tumor biology, as well as tumor dimension. Here, we investigate the relative risk of LNM in accordance to tumor dimension and biology in HNSCC subsites. Materials and Methods Medical data of 295 HNSCC patients who had undergone the initial curative surgery (oral tongue 174, oropharynx 75, hypopharynx 46) were a...

  4. ADAM17-mediated CD44 cleavage promotes orasphere formation or stemness and tumorigenesis in HNSCC

    International Nuclear Information System (INIS)

    CD44, an extracellular matrix (ECM) receptor, has been described as a cancer stem cell marker in multiple cancers, including head and neck squamous cell carcinoma (HNSCC). HNSCC orasphere formation or stemness was characterized by cleavage of CD44, and thus we hypothesized that this proteolytic processing may be critical to stemness and tumorigenesis. We tested this hypothesis by examining the mechanisms that regulate this process in vitro and in vivo, and by exploring its clinical relevance in human specimens. Sphere assays have been used to evaluate stemness in vitro. Spheres comprised of HNSCC cells or oraspheres and an oral cancer mouse model were used to examine the significance of CD44 cleavage using stable suppression and inhibition approaches. These mechanisms were also examined in HNSCC specimens. Oraspheres exhibited increased levels of CD44 cleavage compared to their adherent counterparts. Given that disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) is a major matrix metalloproteinase known to cleave CD44, we chemically inhibited and stably suppressed ADAM17 expression in HNSCC cells and found that these treatments blocked CD44 cleavage and abrogated orasphere formation. Furthermore, stable suppression of ADAM17 in HNSCC cells also diminished tumorigenesis in an oral cancer mouse model. Consistently, stable suppression of CD44 in HNSCC cells abrogated orasphere formation and inhibited tumorigenesis in vivo. The clinical relevance of these findings was confirmed in matched primary and metastatic human HNSCC specimens, which exhibited increased levels of ADAM17 expression and concomitant CD44 cleavage compared to controls. CD44 cleavage by ADAM17 is critical to orasphere formation or stemness and HNSCC tumorigenesis

  5. Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1.

    Science.gov (United States)

    Joo, Nam E; Ritchie, Kathryn; Kamarajan, Pachiyappan; Miao, Di; Kapila, Yvonne L

    2012-12-01

    Nisin, a bacteriocin and commonly used food preservative, may serve as a novel potential therapeutic for treating head and neck squamous cell carcinoma (HNSCC), as it induces preferential apoptosis, cell cycle arrest, and reduces cell proliferation in HNSCC cells, compared with primary keratinocytes. Nisin also reduces HNSCC tumorigenesis in vivo. Mechanistically, nisin exerts these effects on HNSCC, in part, through CHAC1, a proapoptotic cation transport regulator, and through a concomitant CHAC1-independent influx of extracellular calcium. In addition, although CHAC1 is known as an apoptotic mediator, its effects on cancer cell apoptosis have not been examined. Our studies are the first to report CHAC1's new role in promoting cancer cell apoptosis under nisin treatment. These data support the concept that nisin decreases HNSCC tumorigenesis in vitro and in vivo by inducing increased cell apoptosis and decreased cell proliferation; effects that are mediated by activation of CHAC1, increased calcium influxes, and induction of cell cycle arrest. These findings support the use of nisin as a potentially novel therapeutic for HNSCC, and as nisin is safe for human consumption and currently used in food preservation, its translation into a clinical setting may be facilitated.

  6. 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.

  7. 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

  8. Novel Immunotherapeutic Approaches for Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Darrin V. Bann

    2016-09-01

    Full Text Available The immune system plays a key role in preventing tumor formation by recognizing and destroying malignant cells. For over a century, researchers have attempted to harness the immune response as a cancer treatment, although this approach has only recently achieved clinical success. Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer worldwide and is associated with cigarette smoking, alcohol consumption, betel nut use, and human papillomavirus infection. Unfortunately, worldwide mortality from HNSCC remains high, partially due to limits on therapy secondary to the significant morbidity associated with current treatments. Therefore, immunotherapeutic approaches to HNSCC treatment are attractive for their potential to reduce morbidity while improving survival. However, the application of immunotherapies to this disease has been challenging because HNSCC is profoundly immunosuppressive, resulting in decreased absolute lymphocyte counts, impaired natural killer cell function, reduced antigen-presenting cell function, and a tumor-permissive cytokine profile. Despite these challenges, numerous clinical trials testing the safety and efficacy of immunotherapeutic approaches to HNSCC treatment are currently underway, many of which have produced promising results. This review will summarize immunotherapeutic approaches to HNSCC that are currently undergoing clinical trials.

  9. Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: Normal tissue complication probability modeling with latent time correction

    DEFF Research Database (Denmark)

    Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren;

    2013-01-01

    To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors.......To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors....

  10. HIF-α/MIF and NF-κB/IL-6 axes contribute to the recruitment of CD11b+Gr-1+ myeloid cells in hypoxic microenvironment of HNSCC.

    Science.gov (United States)

    Zhu, Guiquan; Tang, Yaling; Geng, Ning; Zheng, Min; Jiang, Jian; Li, Ling; Li, Kaide; Lei, Zhengge; Chen, Wei; Fan, Yunlong; Ma, Xiangrui; Li, Longjiang; Wang, Xiaoyi; Liang, Xinhua

    2014-02-01

    CD11b+Gr-1+ myeloid cells have gained much attention due to their roles in tumor immunity suppression as well as promotion of angiogenesis, invasion, and metastases. However, the mechanisms by which CD11b+Gr-1+ myeloid cells recruit to the tumor site have not been well clarified. In the present study, we showed that hypoxia could stimulate the migration of CD11b+Gr-1+ myeloid cells through increased production of macrophage migration inhibitory factor (MIF) and interleukin-6 (IL-6) by head and neck squamous cell carcinoma (HNSCC) cells. Hypoxia-inducible factor-1α (HIF-1α)- and HIF-2α-dependent MIF regulated chemotaxis, differentiation, and pro-angiogenic function of CD11b+Gr-1+ myeloid cells through binding to CD74/CXCR2, and CD74/CXCR4 complexes, and then activating p38/mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinases (PI3K)/AKT signaling pathways. Knockdown (KD) of HIF-1α and HIF-2α in HNSCC cells decreased MIF level but failed to inhibit the CD11b+Gr-1+ myeloid cell migration, because HIF-1α/2α KD enhanced nuclear factor κB (NF-κB) activity that increased IL-6 secretion. Simultaneously blocking NF-κB and HIF-1α/HIF-2α had better inhibitory effect on CD11b+Gr-1+ myeloid cell recruitment in the hypoxic zone than individually silencing HIF-1α/2α or NF-κB. In conclusion, the interaction between HIF-α/MIF and NF-κB/IL-6 axes plays an important role in the hypoxia-induced accumulation of CD11b+Gr-1+ myeloid cells and tumor growth in HNSCC. PMID:24709424

  11. HIF-α/MIF and NF-κB/IL-6 Axes Contribute to the Recruitment of CD11b+Gr-1+ Myeloid Cells in Hypoxic Microenvironment of HNSCC

    Directory of Open Access Journals (Sweden)

    Guiquan Zhu

    2014-02-01

    Full Text Available CD11b+Gr-1+ myeloid cells have gained much attention due to their roles in tumor immunity suppression as well as promotion of angiogenesis, invasion, and metastases. However, the mechanisms by which CD11b+Gr-1+ myeloid cells recruit to the tumor site have not been well clarified. In the present study, we showed that hypoxia could stimulate the migration of CD11b+Gr-1+ myeloid cells through increased production of macrophage migration inhibitory factor (MIF and interleukin-6 (IL-6 by head and neck squamous cell carcinoma (HNSCC cells. Hypoxia-inducible factor-1α (HIF-1α- and HIF-2α-dependent MIF regulated chemotaxis, differentiation, and pro-angiogenic function of CD11b+Gr-1+ myeloid cells through binding to CD74/CXCR2, and CD74/CXCR4 complexes, and then activating p38/mitogen-activated protein kinase (MAPK and phosphatidylinositide 3-kinases (PI3K/AKT signaling pathways. Knockdown (KD of HIF-1α and HIF-2α in HNSCC cells decreased MIF level but failed to inhibit the CD11b+Gr-1+ myeloid cell migration, because HIF-1α/2α KD enhanced nuclear factor κB (NF-κB activity that increased IL-6 secretion. Simultaneously blocking NF-κB and HIF-1α/HIF-2α had better inhibitory effect on CD11b+Gr-1+ myeloid cell recruitment in the hypoxic zone than individually silencing HIF-1α/2α or NF-κB. In conclusion, the interaction between HIF-α/MIF and NF-κB/IL-6 axes plays an important role in the hypoxia-induced accumulation of CD11b+Gr-1+ myeloid cells and tumor growth in HNSCC.

  12. [Present status of concurrent chemoreadiotherapy in squamous cell carcinoma of head and neck].

    Science.gov (United States)

    Li, X M; Song, Q

    2016-07-01

    Head neck squamous cell carcinoma (HNSCC) is a common kind of malignancies in human body. For HNSCC in early stage, either surgical operation or radiotherapy can acquire satisfactory treatment results. However, any single treatment modality such as surgery alone or single radiation is insufficient to gain satisfactory tumor control. Multidisciplinary treatment (MDT) has become a mainstay and important therapeutic strategy in the management of HNSCC. Among various approaches in the MDT, concurrent chemoradiotheraqpy (CCR) constitutes a major progress, which implicates a lot in improving outcomes and organ preservations in managing HNSCC. In the present review, the history, mechanisms, indications along with side effects and drawbacks, and perspectives of CCR are to be described and discussed, in the hope of providing effective guidance for the domestic MDT, especially CCR in the management of HNSCC. PMID:27480307

  13. Involvement of calprotectin (S100A8/A9) in molecular pathways associated with HNSCC.

    Science.gov (United States)

    Khammanivong, Ali; Sorenson, Brent S; Ross, Karen F; Dickerson, Erin B; Hasina, Rifat; Lingen, Mark W; Herzberg, Mark C

    2016-03-22

    Calprotectin (S100A8/A9), a heterodimeric protein complex of calcium-binding proteins S100A8 and S100A9, plays key roles in cell cycle regulation and inflammation, with potential functions in squamous cell differentiation. While upregulated in many cancers, S100A8/A9 is downregulated in squamous cell carcinomas of the cervix, esophagus, and the head and neck (HNSCC). We previously reported that ectopic S100A8/A9 expression inhibits cell cycle progression in carcinoma cells. Here, we show that declining expression of S100A8/A9 in patients with HNSCC is associated with increased DNA methylation, less differentiated tumors, and reduced overall survival. Upon ectopic over-expression of S100A8/A9, the cancer phenotype of S100A8/A9-negative carcinoma cells was suppressed in vitro and tumor growth in vivo was significantly decreased. MMP1, INHBA, FST, LAMC2, CCL3, SULF1, and SLC16A1 were significantly upregulated in HNSCC but were downregulated by S100A8/A9 expression. Our findings strongly suggest that downregulation of S100A8/A9 through epigenetic mechanisms may contribute to increased proliferation, malignant transformation, and disease progression in HNSCC. PMID:26883112

  14. Combined paclitaxel, cisplatin and fluorouracil therapy enhances ionizing radiation effects, inhibits migration and induces G0/G1 cell cycle arrest and apoptosis in oral carcinoma cell lines

    OpenAIRE

    Elias, Silvia Taveira; BORGES, GABRIEL ALVARES; RÊGO, DANIELA FORTUNATO; E SILVA, LUIS FELIPE OLIVEIRA; AVELINO, SAMUEL; DE MATOS NETO, JOÃO NUNES; Simeoni, Luiz Alberto; GUERRA, ELIETE NEVES SILVA

    2015-01-01

    Although taxels (in particular paclitaxel), cisplatin and fluorouracil (TPF) chemotherapy has been approved for use in the treatment of head and neck squamous cell carcinoma (HNSCC), little is known with regard to the cellular mechanisms of this novel drug association. In order to investigate the reaction of cells to this novel treatment, the present study aimed to examine the cytotoxic effect of TPF in HNSCC cell lines in combination with irradiation, to analyze its effect on cell cycle prog...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

    Science.gov (United States)

    Radhakrishnan, Aneesha; Nanjappa, Vishalakshi; Raja, Remya; Sathe, Gajanan; Puttamallesh, Vinuth N.; Jain, Ankit P.; Pinto, Sneha M.; Balaji, Sai A.; Chavan, Sandip; Sahasrabuddhe, Nandini A.; Mathur, Premendu P.; Kumar, Mahesh M.; Prasad, T. S. Keshava; Santosh, Vani; Sukumar, Geethanjali; Califano, Joseph A.; Rangarajan, Annapoorni; Sidransky, David; Pandey, Akhilesh; Gowda, Harsha; Chatterjee, Aditi

    2016-01-01

    Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC. PMID:27796319

  17. JAK Kinase Inhibition Abrogates STAT3 Activation and Head and Neck Squamous Cell Carcinoma Tumor Growth

    Directory of Open Access Journals (Sweden)

    Malabika Sen

    2015-03-01

    Full Text Available Aberrant activation of the Janus kinase (JAK/signal transducer and activator of transcription (STAT 3 has been implicated in cell proliferation and survival of many cancers including head and neck squamous cell carcinoma (HNSCC. AZD1480, an orally active pharmacologic inhibitor of JAK1/JAK2, has been tested in several cancer models. In the present study, the in vitro and in vivo effects of AZD1480 were evaluated in HNSCC preclinical models to test the potential use of JAK kinase inhibition for HNSCC therapy. AZD1480 treatment decreased HNSCC proliferation in HNSCC cell lines with half maximal effective concentration (EC50 values ranging from 0.9 to 4 μM in conjunction with reduction of pSTAT3Tyr705 expression. In vivo antitumor efficacy of AZD1480 was demonstrated in patient-derived xenograft (PDX models derived from two independent HNSCC tumors. Oral administration of AZD1480 reduced tumor growth in conjunction with decreased pSTAT3Tyr705 expression that was observed in both PDX models. These findings suggest that the JAK1/2 inhibitors abrogate STAT3 signaling and may be effective in HNSCC treatment approaches.

  18. Effector memory T-cell frequencies in relation to tumour stage, location and HPV status in HNSCC patients

    NARCIS (Netherlands)

    A.W. Turksma; H.J. Bontkes; H. van den Heuvel; T.D. de Gruijl; B.M.E. von Blomberg; B.J.M. Braakhuis; C.R. Leemans; E. Bloemena; C.J.L.M. Meijer; E. Hooijberg

    2013-01-01

    Background The immune system plays an important role in tumour immune surveillance. Head and neck squamous cell carcinoma patients are often immune compromised. Objective To chart the baseline levels of T-cell subpopulation frequencies in patients with cancer prior to treatment. Subjects and methods

  19. TMEM16A/ANO1 is differentially expressed in HPV-negative versus HPV-positive head and neck squamous cell carcinoma through promoter methylation.

    Science.gov (United States)

    Dixit, Ronak; Kemp, Carolyn; Kulich, Scott; Seethala, Raja; Chiosea, Simion; Ling, Shizhang; Ha, Patrick K; Duvvuri, Umamaheswar

    2015-11-13

    Head and neck squamous cell carcinoma (HNSCC) has a variety of causes. Recently, the human papilloma virus (HPV) has been implicated in the rising incidence of oropharyngeal cancer and has led to variety of studies exploring the differences between HPV-positive and HPV-negative HNSCC. The calcium-activated chloride channel TMEM16A is overexpressed in a variety of cancers, including HNSCC, but whether or not it plays different roles in HPV-positive and HPV-negative HNSCC is unknown. Here, we demonstrate that TMEM16A is preferentially overexpressed in HPV-negative HNSCC and that this overexpression of TMEM16A is associated with decreased patient survival. We also show that TMEM16A expression is decreased in HPV-positive HNSCC at the DNA, RNA, and protein levels in patient samples as well as cell lines. We demonstrate that the lower levels of TMEM16A expression in HPV-positive tumors can be attributed to both a combination of copy number alteration and promoter methylation at the DNA level. Additionally, our cellular data show that HPV-negative cell lines are more dependent on TMEM16A for survival than HPV-positive cell lines. Therefore, we suspect that the down-regulation of TMEM16A in HPV-positive HNSCC makes TMEM16A a poor therapeutic target in HPV-positive HNSCC, but a potentially useful target in HPV-negative HNSCC.

  20. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Jan Chia-Ing

    2009-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhang Jun

    2010-11-01

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

  4. Receptor-type Protein Tyrosine Phosphatase β Regulates Met Phosphorylation and Function in Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yiru Xu

    2012-11-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer and has a high rate of mortality. Emerging evidence indicates that hepatocyte growth factor receptor (or Met pathway plays a pivotal role in HNSCC metastasis and resistance to chemotherapy. Met function is dependent on tyrosine phosphorylation that is under direct control by receptor-type protein tyrosine phosphatase β (RPTP-β. We report here that RPTP-β expression is significantly downregulated in HNSCC cells derived from metastatic tumors compared to subject-matched cells from primary tumors. Knockdown of endogenous RPTP-β in HNSCC cells from primary tumor potentiated Met tyrosine phosphorylation, downstream mitogen-activated protein (MAP kinase pathway activation, cell migration, and invasion. Conversely, restoration of RPTP-β expression in cells from matched metastatic tumor decreased Met tyrosine phosphorylation and downstream functions. Furthermore, we observed that six of eight HNSCC tumors had reduced levels of RPTP-β protein in comparison with normal oral tissues. Collectively, the results demonstrate the importance of RPTP-β in tumor biology of HNSCC through direct dephosphorylation of Met and regulation of downstream signal transduction pathways. Reduced RPTP-β levels, with or without Met overexpression, could promote Met activation in HNSCC tumors.

  5. Clusterin is a Gene Specific Target of MicroRNA-21 in Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    Mydlarz, Wojciech; Uemura, Mamoru; Ahn, Sun; Hennessey, Patrick; Chang, Steven; Demokan, Semra; Sun, Wenyue; Shao, Chunbo; Bishop, Justin; Krosting, Julie; Mambo, Elizabeth; Westra, William; Ha, Patrick; Sidransky, David; Califano, Joseph

    2014-01-01

    Purpose: MicroRNA-21 (miRNA-21) has proto-oncogenic properties, though no miRNA-21 specific targets have been found in head and neck squamous cell carcinoma (HNSCC). Further study of miRNA-21 and its specific targets is essential to understanding HNSCC biology. Experimental Design: miRNA expression profiles of 10 HNSCC and 10 normal mucosa samples were investigated using a custom miRNA microarray. 13 HNSCC and 5 normal mucosa primary tissue specimens underwent mRNA expression microarray analysis. To identify miRNA-21 downstream targets, oral keratinocyte cells were subjected to microarray analysis after miRNA-21 transient transfection. miRNA and mRNA expression were validated by RT-qPCR in a separate cohort of 16 HNSCC and 15 normal mucosal samples. Microarray and bioinformatics analyses were integrated to identify potential gene targets. In vitro assays looked at the function and interaction of miRNA-21 and its specific gene targets. Results: miRNA-21 was upregulated in HNSCC and stimulated cell growth. Integrated analyses identified Clusterin (CLU) as a potential miRNA-21 gene target. CLU was downregulated after forced expression of miRNA-21 in normal and HNSCC cell lines. The activity of a luciferase construct containing the 3’UTR of CLU was repressed by the ectopic expression of miRNA-21. CLU was also downregulated in primary HNSCC and correlated with miRNA-21 over-expression. CLU variant 1 (CLU-1) was the predominant splice variant in HNSCC, and showed growth suppression function that was reversed by miRNA-21 over-expression. Conclusions: CLU is a specific, functional target of oncogenic miRNA-21 in HNSCC. CLU-1 isoform is the predominant growth suppressive variant targeted by miRNA-21. PMID:24327270

  6. Elevated ZNF703 Protein Expression Is an Independent Unfavorable Prognostic Factor for Survival of the Patients with Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Hang Yang

    2015-01-01

    Full Text Available Aim. Data from The Cancer Genome Atlas (TCGA show that the ZNF703 gene amplifies and overexpresses in head and neck squamous cell carcinomas (HNSCC. However, the clinical relevance of this observation in HNSCC is unclear. The purpose of this study was to clarify the expression of ZNF703 protein and its prognostic effect on HNSCC. Methods. Two hundred ten HNSCC patients from Sun Yat-Sen University Cancer Center with complete survival follow-up were included in this study. Tumor samples from primary sites were collected. The expression of the ZNF703 protein was tested by immunohistochemistry (IHC. Results. The high expression of ZNF703 in HNSCC tumor tissues was significantly higher than that of the matched noncancerous tissues (48.6% versus 11.6%, P<0.001. ZNF703 overexpression was correlated with tumor position (laryngeal carcinoma and recurrence (all P<0.05. Multivariate analysis revealed that ZNF703 protein overexpression was an independent prognostic factor (P=0.022, hazard ratio = 1.635, 95% CI 1.073–2.493 in HNSCC patients. Conclusion. ZNF703 overexpression is associated with adverse prognosis in HNSCC, which might be a novel biomarker of HNSCC.

  7. Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

    NARCIS (Netherlands)

    van Kempen, Pauline M. W.; Noorlag, Rob; Braunius, Weibel W.; Moelans, Cathy B.; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; van Es, RJJ; Willems, Stefan M.

    2015-01-01

    Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer tr

  8. Illness cognitions in head and neck squamous cell carcinoma: Predicting quality of life outcome

    NARCIS (Netherlands)

    M. Scharloo (Margreet); R.J.B. de Jong; T.P.M. Langeveld (ton); E. van Velzen-Verkaik (Els); M.M. den Doorn-op den Akker (Margreet); A.A. Kaptein (Adrian)

    2010-01-01

    textabstractGoals of work: This paper presents an observational study of the longitudinal effects of cancer treatment on quality of life (QoL) in patients treated for head and neck squamous cell carcinoma (HNSCC), and evaluated the contribution of patients' baseline illness cognitions to the predict

  9. Head and Neck Squamous Cell Carcinomas Do Not Express EGFRvIII

    NARCIS (Netherlands)

    Melchers, Lieuwe J; Clausen, Martijn J A M; Mastik, Mirjam F; Slagter-Menkema, Lorian; Langendijk, Johannes A; van der Laan, Bernard F A M; van der Wal, Jacqueline E; van der Vegt, Bert; Roodenburg, Jan L N; Schuuring, Ed

    2014-01-01

    Purpose: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was opt

  10. The rotamase Pin1 is up-regulated, hypophosphorylated and required for cell cycle progression in head and neck squamous cell carcinomas.

    Science.gov (United States)

    Wiegand, Susanne; Dakic, Branka; Rath, Ariane F E; Makarova, Galina; Sterz, Carolina; Meissner, Wolfgang; Bette, Michael; Adamkiewicz, Jürgen; Müller-Brüsselbach, Sabine; Müller, Rolf; Werner, Jochen A; Mandic, Robert

    2009-10-01

    The peptidyl-prolyl cis/trans isomerase Pin1 has been implicated in malignant transformation in multiple studies, however, little is known about its potential impact in head and neck cancer. This study evaluates the role of Pin1 in head and neck squamous cell carcinomas (HNSCCs). Pin1 expression and level of phosphorylation was evaluated by Western blot analysis and 2D-gel-electrophoresis. Pin1 was inhibited with juglone (5-hydroxy-1,4-naphthalenedione) or Pin1 specific siRNA and its influence on cell cycle checkpoint distribution was assessed by FACS analysis. Pin1 overexpression was found in HNSCC tissues and cell lines. 2D-gel-electrophoresis data pointed to Pin1 being hypophosphorylated in HNSCC cells which is consistent with overactivation of this rotamase. Inhibition of HNSCC cells with juglone or Pin1 siRNA induced the cell cycle inhibitor p21(WAF1/Cip1) with a concomitant reduction of cells in G2/M and an increased fraction of cells with fragmented DNA. Cell death did not correlate with significant levels of apoptosis in Pin1 depleted HNSCC cells. In summary, the data shows that Pin1 is overexpressed and hypophosphorylated in HNSCC, and that inhibition of Pin1 blocks cell cycle progression and triggers tumor cell death. Pin1 therefore could represent a new target for the development of improved HNSCC targeting drugs.

  11. HIV Protease Inhibitors Sensitize Human Head and Neck Squamous Carcinoma Cells to Radiation by Activating Endoplasmic Reticulum Stress.

    Directory of Open Access Journals (Sweden)

    Runping Liu

    Full Text Available Human head and neck squamous cell carcinoma (HNSCC is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that HIV PIs induce cell apoptosis via activation of endoplasmic reticulum (ER stress. The aim of this study was to examine the role of ER stress in HIV PI-induced radiosensitivity in human HNSCC.HNSCC cell lines, SQ20B and FaDu, and the most commonly used HIV PIs, lopinavir and ritonavir (L/R, were used in this study. Clonogenic assay was used to assess the radiosensitivity. Cell viability, apoptosis and cell cycle were analyzed using Cellometer Vision CBA. The mRNA and protein levels of ER stress-related genes (eIF2α, CHOP, ATF-4, and XBP-1, as well as cell cycle related protein, cyclin D1, were detected by real time RT-PCR and Western blot analysis, respectively. The results demonstrated that L/R dose-dependently sensitized HNSCC cells to irradiation and inhibited cell growth. L/R-induced activation of ER stress was correlated to down-regulation of cyclin D1 expression and cell cycle arrest under G0/G1 phase.HIV PIs sensitize HNSCC cells to radiotherapy by activation of ER stress and induction of cell cycle arrest. Our results provided evidence that HIV PIs can be potentially used in combination with radiation in the treatment of HNSCC.

  12. 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 ...

  13. Functional imaging of head and neck squamous cell carcinoma with diffusion-weighted MRI and FDG PET/CT: quantitative analysis of ADC and SUV

    OpenAIRE

    Varoquaux, Arthur; Rager, Olivier; Lovblad, Karl-Olof; Masterson, Karen; Dulguerov, Pavel; Ratib, Osman; Becker, Christoph D.; Becker, Minerva

    2013-01-01

    Purpose Head and neck squamous cell carcinoma (HNSCC) may cause a decreased apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging (DW MRI) and an increased standardized uptake value (SUV) on fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). We analysed the reproducibility of ADC and SUV measurements in HNSCC and evaluated whether these biomarkers are correlated or independent. Methods This retrospective analysis of DW MRI and FDG PET/CT data serie...

  14. OX40 signaling in head and neck squamous cell carcinoma: Overcoming immunosuppression in the tumor microenvironment.

    Science.gov (United States)

    Bell, R Bryan; Leidner, Rom S; Crittenden, Marka R; Curti, Brendan D; Feng, Zipei; Montler, Ryan; Gough, Michael J; Fox, Bernard A; Weinberg, Andrew D; Urba, Walter J

    2016-01-01

    OX40 is a member of the tumor necrosis factor (TNF) receptor family and a potent co-stimulatory pathway that when triggered can enhance T-cell memory, proliferation and anti-tumor activity in patients with metastatic cancer. Ongoing investigations at our institution have demonstrated that OX40 expressing T cells are found in abundance in the tumors of patients with advanced stage head and neck squamous cell carcinoma (HNSCC). This has led to the initiation of human clinical trials investigating OX40-directed therapy for patients with HNSCC in both the metastatic and curative setting. The purpose of this review is to explore what is known about OX40 signaling and discuss how this pathway potentially can be modulated to improve outcome for patients with HNSCC. PMID:26614363

  15. The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell carcinoma cell growth in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qiang; Song, Xin-mao; Ji, Yang-yang; Jiang, Hui; Xu, Lin-gen, E-mail: drlingenxu@126.com

    2013-11-01

    Highlights: •AZD8055 induces significant cytotoxic effects in cultured HNSCC cells. •AZD8055 blocks mTORC1 and mTORC2 activation in cultured HNSCC cells. •JNK activation is required for AZD8055-induced HNSCC cell death. •AZD8055 inhibits Hep-2 cell growth in vivo, and was more efficient than rapamycin. -- Abstract: The serine/threonine kinase mammalian target of rapamycin (mTOR) promotes cell survival and proliferation, and is constitutively activated in head and neck squamous cell carcinoma (HNSCC). Thus mTOR is an important target for drug development in this disease. Here we tested the anti-tumor ability of AZD8055, the novel mTOR inhibitor, in HNSCC cells. AZD8055 induced dramatic cell death of HNSCC lines (Hep-2 and SCC-9) through autophagy. AZD8055 blocked both mTOR complex (mTORC) 1 and mTORC2 activation without affecting Erk in cultured HNSCC cells. Meanwhile, AZD8055 induced significant c-Jun N-terminal kinase (JNK) activation, which was also required for cancer cell death. JNK inhibition by its inhibitors (SP 600125 and JNK-IN-8), or by RNA interference (RNAi) alleviated AZD8055-induced cell death. Finally, AZD8055 markedly increased the survival of Hep-2 transplanted mice through a significant reduction of tumor growth, without apparent toxicity, and its anti-tumor ability was more potent than rapamycin. Meanwhile, AZD8055 administration activated JNK while blocking mTORC1/2 in Hep-2 tumor engrafts. Our current results strongly suggest that AZD8055 may be further investigated for HNSCC treatment in clinical trials.

  16. MAGEB2 is activated by promoter demethylation in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Kavita M Pattani

    Full Text Available PURPOSE: Although promoter hypermethylation has been an accepted means of tumor suppressor gene inactivation, activation of otherwise normally repressed proto-oncogenes by promoter demethylation has been infrequently documented. EXPERIMENTAL DESIGN: In this study we performed an integrative, whole-genome analysis for discovery of epigenetically activated proto-oncogenes in head and neck cancer tumors. We used the 47K GeneChip U133 Plus 2.0 Affymetrix expression microarray platform to obtain re-expression data from 5-aza treated normal cell line and expression data from primary head and neck squamous cell carcinoma (HNSCC tumor tissues and normal mucosa tissues. We then investigated candidate genes by screening promoter regions for CpG islands and bisulfite sequencing followed by QUMSP and RT PCR for the best candidate genes. Finally, functional studies were performed on the top candidate gene. RESULTS: From the top 178 screened candidates 96 had CpG islands in their promoter region. Seven candidate genes showed promoter region methylation in normal mucosa samples and promoter demethylation in a small cohort of primary HNSCC tissues. We then studied the demethylation of the top 3 candidate genes in an expanded cohort of 76 HNSCC tissue samples and 17 normal mucosa samples. We identified MAGEB2 as having significant promoter demethylation in primary head and neck squamous cell carcinoma tissues. We then found significantly higher expression of MAGEB2 in tumors in a separate cohort of 73 primary HNSCC tissues and 31 normal tissues. Finally, we found that MAGEB2 has growth promoting effects on minimally transformed oral keratinocyte cell lines but not a definite effect on HNSCC cell lines. CONCLUSION: In conclusion, we identified MAGEB2 as activated by promoter demethylation in HNSCCand demonstrates growth promoting effects in a minimally transformed oral keratinocyte cell line. More studies are needed to evaluate MAGBE2's exact role in HNSCC.

  17. Cold atmospheric plasma treatment selectively targets head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Guerrero-Preston, Rafael; Ogawa, Takenori; Uemura, Mamoru; Shumulinsky, Gary; Valle, Blanca L; Pirini, Francesca; Ravi, Rajani; Sidransky, David; Keidar, Michael; Trink, Barry

    2014-10-01

    The treatment of locoregional recurrence (LRR) of head and neck squamous cell carcinoma (HNSCC) often requires a combination of surgery, radiation therapy and/or chemotherapy. Survival outcomes are poor and the treatment outcomes are morbid. Cold atmospheric plasma (CAP) is an ionized gas produced at room temperature under laboratory conditions. We have previously demonstrated that treatment with a CAP jet device selectively targets cancer cells using in vitro melanoma and in vivo bladder cancer models. In the present study, we wished to examine CAP selectivity in HNSCC in vitro models, and to explore its potential for use as a minimally invasive surgical approach that allows for specific cancer cell or tumor tissue ablation without affecting the surrounding healthy cells and tissues. Four HNSCC cell lines (JHU-022, JHU-028, JHU-029, SCC25) and 2 normal oral cavity epithelial cell lines (OKF6 and NOKsi) were subjected to cold plasma treatment for durations of 10, 30 and 45 sec, and a helium flow of 20 l/min-1 for 10 sec was used as a positive treatment control. We showed that cold plasma selectively diminished HNSCC cell viability in a dose-response manner, as evidenced by MTT assays; the viability of the OKF6 cells was not affected by the cold plasma. The results of colony formation assays also revealed a cell-specific response to cold plasma application. Western blot analysis did not provide evidence that the cleavage of PARP occurred following cold plasma treatment. In conclusion, our results suggest that cold plasma application selectively impairs HNSCC cell lines through non-apoptotic mechanisms, while having a minimal effect on normal oral cavity epithelial cell lines.

  18. Molecular Cross-Talk between the NFκB and STAT3 Signaling Pathways in Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Cristiane H. Squarize

    2006-09-01

    Full Text Available The development of head and neck squamous cell carcinoma (HNSCC involves the accumulation of genetic and epigenetic alterations in tumor-suppressor proteins, together with the persistent activation of growth-promoting signaling pathways. The activation of epidermal growth factor receptor (EGFR is a frequent event in HNSCC. However, EGFR-independent mechanisms also contribute to the activation of key intracellular signaling routes, including signal transducer and activator of transcription-3 (STAT3, nuclear factor κB (NFκB, and Akt. Indeed, the autocrine activation of the gp130 cytokine receptor in HNSCC cells by tumor-released cytokines, such as IL-6, can result in the EGFR-independent activation of STAT3. In this study, we explored the nature of the molecular mechanism underlying enhanced IL-6 secretion in HNSCC cells. We found that HNSCC cells display an increased activity of the IL-6 promoter, which is dependent on the presence of an intact NFκB site. Furthermore, NFκB inhibition downregulated IL-6 gene and protein expression, and decreased the release of multiple cytokines. Interestingly, interfering with NFκB function also prevented the autocrine/paracrine activation of STAT3 in HNSCC cells. These findings demonstrate a cross-talk between the NFκB and the STAT3 signaling systems, and support the emerging notion that HNSCC results from the aberrant activity of a signaling network.

  19. 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 ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-27

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

  1. Radionuclides detected in lime samples that consumed with tobacco and betel nuts by people of Northeast India where head and neck squamous cells cancer (HNSCC) is prevalent

    International Nuclear Information System (INIS)

    Complete text of publication follows. Head and neck squamous cell cancer (HNSCC) is a very predominant type of cancer amongst the population of northeastern states of India than the rest of the world. Epidemiological and other data suggest consumption of betel nuts with/without tobacco and lime or tobacco alone with lime is a probable cause of high cancer incidence. The fundamental question arises that why this particular cancer is induced more in this region while people follow the similar habits elsewhere. Here we report the results on analysis of lime samples, collected from 12 different locations spectrophotometrically by high-purity germanium detector. The calculated activity of radionuclides showed to an average of 2.68, 0.10 and 0.83 Bq/gm for 238U, 235U and 232Th series respectively for ten samples which are about 8 times higher than the normal background level of 0.37, 0.02 and 0.02 Bq/gm for 238U, 235U and 232Th series found in control samples, collected from outside of northeast. The results conclusively showed for the first time that the lime samples almost throughout the northeastern India contain high proportion of radionuclides of uranium, thorium and actinides series. Further, annual effective dose of gamma radiation calculations from these results of earth's crust in northeast showed that gamma rays emitted at an average dose of up to 2.5 mSv/year/consumer approximately. This dose calculation in the oral cavity is underestimated as short range radiations by decay of alpha, beta and electron-capture etc are not considered in the present study. Continuous exposure of such low dose radiations emitting from different radionuclides to the sensitive squamous cells of the oral cavity for a long twenty years or more amounting to a total minimum dose of at least 50 mSv evidently contributes towards excessive HNSCC to the people of northeast than other parts of India.

  2. CT120A Acts as an Oncogene in Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    Baltaci, Elif; Ekizoglu, Seda; Sari, Elif; Karaman, Emin; Ulutin, Turgut; Buyru, Nur

    2015-01-01

    Squamous cell carcinoma of the head and neck (HNSCC) is among the most frequent cancers worldwide. The etiology and pathogenesis of HNSCC are influenced by multiple genetic factors in addition to environmental and lifestyle-related factors. However, the mechanism underlying the HNSCC is still far from clear. The membrane associated gene CT120 was previously identified from chromosome 17p13.3 as a lung cancer-associated gene. Its function as an activator of the Erk and Akt signaling pathways in human lung cancer cell lines suggested that CT120 has an oncogenic function. However, there is no data in the literature on the role of CT120 in any other cancer type. Therefore, the aim of this study was to determine the expression rate and probable function of CT120 in HNSCC. Tumor tissues from 50 patients were analyzed by real-time quantitative RT-PCR to investigate the expression rate and by direct sequencing to differentiate the CT120A and CT120B variants. CT120 overexpression was observed in 58% of tumors compared to non-cancerous tissue samples and this up-regulation was directly associated with the upregulation of the CT120A variant and with the stage of the disease (p=0.001). Our results indicate that the CT120 gene may function in the development of HNSCC. PMID:26535067

  3. Expression and prognostic significance of a panel of tissue hypoxia markers in head-and-neck squamous cell carcinomas

    DEFF Research Database (Denmark)

    Le, Quynh-Thu; Kong, Christina; Lavori, Phillip W;

    2007-01-01

    PURPOSE: To investigate the expression pattern of hypoxia-induced proteins identified as being involved in malignant progression of head-and-neck squamous cell carcinoma (HNSCC) and to determine their relationship to tumor pO(2) and prognosis. METHODS AND MATERIALS: We performed immunohistochemic...... their utility in identifying patients for hypoxia-targeted therapy....

  4. Non-smoking and non-drinking patients with head and neck squamous cell carcinoma: a distinct population.

    NARCIS (Netherlands)

    Farshadpour, F.; Hordijk, G.J.; Koole, R.; Slootweg, P.J.

    2007-01-01

    OBJECTIVE: To recognize specific clinicopathological characteristics of non-smoking and non-drinking (NSND) head and neck squamous cell carcinoma (HNSCC) patients. This can increase our knowledge regarding a potentially different carcinogenesis in these patients. STUDY DESIGN/METHODS: Retrospective

  5. Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status.

    Science.gov (United States)

    Coordes, Annekatrin; Lenz, Klaus; Qian, Xu; Lenarz, Minoo; Kaufmann, Andreas M; Albers, Andreas E

    2016-08-01

    Data indicate a better prognosis for human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). HPV and p16 detection are established markers for HPV-related HNSCC. Both are accepted as survival-independent predictors. Previous studies investigating the survival in HNSCC patients depending on HPV(+/-) and p16(+/-) status consistently found discordant results with p16(-)/HPV(+) and p16(+)/HPV(-). However, no meta-analysis regarding the survival according to combined HPV/p16 status has been performed yet. The objective of this study was to discriminate the impact of combined HPV(+/-) and p16(+/-) status on survival. Data sources were identification and review of publications assessing survival of the distinct subgroups with both p16 and HPV investigated in HNSCC until February, 2015. A meta-analysis was performed to classify survival and clinical outcomes. 18 out of 397 articles (4424 patients) were eligible for the meta-analysis. The percent proportion of the subgroups was 25 % for HPV(+)/p16(+), 61.2 % for HPV(-)/p16(-), 7.1 % for HPV(-)/p16(+) and 6.8 % for HPV(+)/P16(-). The meta-analysis showed a significantly improved 5-year overall survival (OS), 5-year disease-free survival and their corresponding hazard ratio for HPV(+)/p16(+) HNSCC in comparison to HPV(-)/p16(-), HPV(+)/p16(-) and HPV(-)/p16(+). The 5-year OS of the HPV(-)/p16(+) subgroup was intermediate while HPV(+)/p16(-) and HPV(-)/p16(-) HNSCC had the shortest survival. With current therapeutic strategies, survival of patients with HNSCC is better if associated with HPV(+)/p16(+) or HPV(-)/p16(+). Clinical trials are needed to confirm the distinct survival pattern and to investigate possible differences in survival for HPV(+)/p16(-) and HPV(-)/p16(+) HNSCC. To further differentiate p16(+) HNSCC, HPV testing may be advisable. PMID:26227616

  6. Polymorphisms in human DNA repair genes and head and neck squamous cell carcinoma

    Indian Academy of Sciences (India)

    Rim Khlifi; Ahmed Rebai; Amel Hamza-Chaffai

    2012-12-01

    Genetic polymorphisms in some DNA repair proteins are associated with a number of malignant transformations like head and neck squamous cell carcinoma (HNSCC). Xeroderma pigmentosum group D (XPD) and X-ray repair cross-complementing proteins 1 (XRCC1) and 3 (XRCC3) genes are involved in DNA repair and were found to be associated with HNSCC in numerous studies. To establish our overall understanding of possible relationships between DNA repair gene polymorphisms and development of HNSCC, we surveyed the literature on epidemiological studies that assessed potential associations with HNSCC risk in terms of gene–environment interactions, genotype-induced functional defects in enzyme activity and/or protein expression, and the influence of ethnic origin on these associations.We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of HNSCC when DNA repair capacity is reduced.

  7. Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine.

    Science.gov (United States)

    Michmerhuizen, Nicole L; Birkeland, Andrew C; Bradford, Carol R; Brenner, J Chad

    2016-05-01

    While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events. PMID:27551333

  8. Epidermal growth factor receptor inhibition reduces angiogenesis via hypoxia-inducible factor-1α and Notch1 in head neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Wei-Ming Wang

    Full Text Available Angiogenesis, a marker of cancer development, affects response to radiotherapy sensibility. This preclinical study aims to understand the receptor tyrosine kinase-mediated angiogenesis in head neck squamous cell carcinoma (HNSCC. The receptor tyrosine kinase activity in a transgenic mouse model of HNSCC was assessed. The anti-tumorigenetic and anti-angiogenetic effects of cetuximab-induced epidermal growth factor receptor (EGFR inhibition were investigated in xenograft and transgenic mouse models of HNSCC. The signaling transduction of Notch1 and hypoxia-inducible factor-1α (HIF-1α was also analyzed. EGFR was overexpressed and activated in the Tgfbr1/Pten deletion (2cKO mouse model of HNSCC. Cetuximab significantly delayed tumor onset by reducing tumor angiogenesis. This drug exerted similar effects on heterotopic xenograft tumors. In the human HNSCC tissue array, increased EGFR expression correlated with increased HIF-1α and micro vessel density. Cetuximab inhibited tumor-induced angiogenesis in vitro and in vivo by significantly downregulating HIF-1α and Notch1. EGFR is involved in the tumor angiogenesis of HNSCC via the HIF-1α and Notch1 pathways. Therefore, targeting EGFR by suppressing hypoxia- and Notch-induced angiogenesis may benefit HNSCC therapy.

  9. Microarray and Biochemical Analysis of Lovastatin-induced Apoptosis of Squamous Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Jim Dimitroulakos

    2002-01-01

    Full Text Available We recently identified 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, as a potential therapeutic target of the head and neck squamous cell carcinomas (HNSCC and cervical carcinomas (CC. The products of this complex biochemical pathway, including de novo cholesterol, are vital for a variety of key cellular functions affecting membrane integrity, cell signaling, protein synthesis, and cell cycle progression. Lovastatin, a specific inhibitor of HMG-CoA reductase, induces a pronounced apoptotic response in a specific subset of tumor types, including HNSCC and CC. The mediators of this response are not well established. Identification of differentially expressed genes represents a feasible approach to delineate these mediators as lovastatin has the potential to modulate transcription indirectly by perturbing levels of sterols and other mevalonate metabolites. Expression analysis following treatment of the HNSCC cell lines SCC9 or SCC25 with 10 μM lovastatin for 1 day showed that less than 2% (9 cDNAs of the 588 cDNAs on this microarray were affected in both cell lines. These included diazepam-binding inhibitor/acyl-CoA-binding protein, the activated transcription factor 4 and rhoA. Because the biosynthesis of mevalonate leads to its incorporation into more than a dozen classes of end products, their role in lovastatin-induced apoptosis was also evaluated. Addition of the metabolites of all the major branches of the mevalonate pathway indicated that only the nonsterol moiety, geranylgeranyl pyrophosphate (GGPP, significantly inhibited the apoptotic effects of lovastatin in HNSCC and CC cells. Because rhoA requires GGPP for its function, this links the microarray and biochemical data and identifies rhoA as a potential mediator of the anticancer properties of lovastatin. Our data suggest that the depletion of nonsterol mevalonate metabolites, particularly GGPP, can be potential mediators of

  10. The Role of 3 Tesla Diffusion-Weighted Imaging in the Differential Diagnosis of Benign versus Malignant Cervical Lymph Nodes in Patients with Head and Neck Squamous Cell Carcinoma

    OpenAIRE

    Flavio Barchetti; Nicola Pranno; Guglielmo Giraldi; Alessandro Sartori; Silvia Gigli; Giovanni Barchetti; Luigi Lo Mele; Luigi Tonino Marsella

    2014-01-01

    Objective. The aim of this study was to validate the role of diffusion-weighted imaging (DWI) at 3 Tesla in the differential diagnosis between benign and malignant laterocervical lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). Materials and Methods. Before undergoing surgery, 80 patients, with biopsy proven HNSCC, underwent a magnetic resonance exam. Sensitivity (Se) and specificity (Spe) of conventional criteria and DWI in detecting laterocervical lymph node metas...

  11. Expression of p27Kip1 and E-cadherin in Head and Neck Squamous Cell Carcinoma of Indonesian Patients.

    Science.gov (United States)

    E I, Auerkari; V, Joewono; D R, Handjari; A T, Sarwono; A W, Suhartono; K, Eto; M A, Ikeda

    2014-01-01

    Cancer cells exhibit characteristic damage of DNA and its expression. The expression of the tumor suppressors E-cadherin and p27(Kip1) has been tested on 57 head and neck squamous cell carcinomas (HNSCC) of Indonesian subjects. HNSCC tumor samples including both primary and (unrelated) nodal cases were obtained from the archives of Indonesian hospitals, in accordance with acknowledged ethical requirements. Only modest correlation was found between reduced expression of E-cadherin or p27(Kip1) with increased malignancy of primary and nodal growth. The observed strong correlation regardless of malignancy between the expressed levels of E-cadherin and p27(Kip1) suggests that also in combination these would not help to better predict the outcome of HNSCC.

  12. Rewiring of an Epithelial Differentiation Factor, miR-203, to Inhibit Human Squamous Cell Carcinoma Metastasis

    Directory of Open Access Journals (Sweden)

    Nathan Benaich

    2014-10-01

    Full Text Available Metastatic colonization of distant organs underpins the majority of human-cancer-related deaths, including deaths from head and neck squamous cell carcinoma (HNSCC. We report that miR-203, a miRNA that triggers differentiation in multilayered epithelia, inhibits multiple postextravasation events during HNSCC lung metastasis. Inducible reactivation of miR-203 in already established lung metastases reduces the overall metastatic burden. Using an integrated approach, we reveal that miR-203 inhibits metastasis independently of its effects on differentiation. In vivo genetic reconstitution experiments show that miR-203 inhibits lung metastasis by suppressing the prometastatic activities of three factors involved in cytoskeletal dynamics (LASP1, extracellular matrix remodeling (SPARC, and cell metabolism (NUAK1. Expression of miR-203 and its downstream effectors correlates with HNSCC overall survival outcomes, indicating the therapeutic potential of targeting this signaling axis.

  13. Targeting Antiapoptotic Bcl-2 Family Members with Cell-Permeable BH3 Peptides Induces Apoptosis Signaling, Death in Head, Neck Squamous Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Rongxiu Li

    2007-10-01

    Full Text Available Head, neck squamous cell carcinomas (HNSCCs are frequently characterized by chemotherapy, radiation resistance, by overexpression of Bcl-XL, an antiapoptotic member of the Bcl-2 protein family. In this report, we examined whether cell-permeable peptides derived from the BH3 domains of proapoptotic Bax, Bad, or Bak could be used to target Bcl-XL and/or Bcl-2 in HNSCC cells, induce apoptotic death in these cells. To render the peptides cell-permeable, Antennapedia (Ant or polyarginine (R8 peptide transduction domain was fused to the amino termini. Fluorescence microscopy of peptide-treated HNSCC cells revealed that the BH3 peptides colocalized with mitochondria, the site of Bcl-XL, Bcl-2 expression. By contrast, a mutant peptide (BaxE BH3 that cannot bind Bcl-XL or Bcl-2 was diffusely localized throughout the cytoplasm. Treatment of three HNSCC cell lines (1483, UM-22A, UM-22B with the wild-type BH3 peptides resulted in loss of viability, induction of apoptosis, as assessed by 3-(4,5-dimethythiazol-2yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS assays, annexin V staining. In general, Ant-conjugated peptides were more potent than R8-conjugated peptides, Bad BH3 peptide was typically more potent than Bax BH3 or Bak BH3. Treatment of purified HNSCC mitochondria with BH3 peptides resulted in robust release of cytochrome c. Thus, the relative apoptosis resistance of HNSCC cells is not due to a deficit in this step of the intrinsic, mitochondrialmediated apoptosis pathway. We conclude that cellpermeable BH3 peptides can be used to target Bcl-XL and/or Bcl-2 in HNSCC, that targeting of these proteins may have therapeutic value in the treatment of this disease.

  14. Growth Inhibition of Head and Neck Squamous Cell Carcinoma Cells by sgRNA Targeting the Cyclin D1 mRNA Based on TRUE Gene Silencing

    OpenAIRE

    Iizuka, Satoshi; Oridate, Nobuhiko; Nashimoto, Masayuki; Fukuda, Satoshi; Tamura, Masato

    2014-01-01

    Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any...

  15. 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. ...

  16. Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Yu-Chin Lin

    2012-06-01

    Full Text Available Epidermal growth factor receptor (EGFR is an important oncoprotein that promotes cell growth and proliferation. Dasatinib, a bcr-abl inhibitor, has been approved clinically for the treatment of chronic myeloid leukemia and demonstrated to be effective against solid tumors in vitro through Src inhibition. Here, we disclose that EGFR degradation mediated dasatinib-induced apoptosis in head and neck squamous cell carcinoma (HNSCC cells. HNSCC cells, including Ca9-22, FaDu, HSC3, SAS, SCC-25, and UMSCC1, were treated with dasatinib, and cell viability, apoptosis, and underlying signal transduction were evaluated. Dasatinib exhibited differential sensitivities against HNSCC cells. Growth inhibition and apoptosis were correlated with its inhibition on Akt, Erk, and Bcl-2, irrespective of Src inhibition. Accordingly, we found that down-regulation of EGFR was a determinant of dasatinib sensitivity. Lysosome inhibitor reversed dasatinib-induced EGFR down-regulation, and c-cbl activity was increased by dasatinib, indicating that dasatinib-induced EGFR down-regulation might be through c-cbl-mediated lysosome degradation. Increased EGFR activation by ligand administration rescued cells from dasatinib-induced apoptosis, whereas inhibition of EGFR enhanced its apoptotic effect. Estrogen receptor α (ERα was demonstrated to play a role in Bcl-2 expression, and dasatinib inhibited ERα at the pretranslational level. ERα was associated with EGFR in dasatinib-treated HNSCC cells. Furthermore, the xenograft model showed that dasatinib inhibited HSC3 tumor growth through in vivo down-regulation of EGFR and ERα. In conclusion, degradation of EGFR is a novel mechanism responsible for dasatinib-induced apoptosis in HNSCC cells.

  17. [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

  18. Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt

    International Nuclear Information System (INIS)

    Cancer stem cells (CSC) are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. MTS and TUNEL assays were used to study cell proliferation and apoptosis as a function of salinomycin exposure in JLO-1, a putative HNSCC stem cell culture. MTS and trypan blue dye exclusion assays were performed to investigate potential drug interactions between salinomycin and cisplatin or paclitaxel. Stem cell-like phenotype was measured by mRNA expression of stem cell markers, sphere-forming capacity, and matrigel invasion assays. Immunoblotting was also used to determine expression of epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation. Arrays by Illumina, Inc. were used to profile microRNA expression as a function of salinomycin dose. In putative HNSCC stem cells, salinomycin was found to significantly inhibit cell viability, induce a 71.5% increase in levels of apoptosis, elevate the Bax/Bcl-2 ratio, and work synergistically with cisplatin and paclitaxel in inducing cell death. It was observed that salinomycin significantly inhibited sphere forming-capability and repressed the expression of CD44 and BMI-1 by 3.2-fold and 6.2-fold, respectively. Furthermore, salinomycin reduced invasion of HNSCC stem cells by 2.1 fold. Contrary to expectations, salinomycin induced the expression of EMT markers Snail, vimentin, and Zeb-1, decreased expression of E-cadherin, and also induced phosphorylation of Akt and its downstream targets GSK3-β and mTOR. These results demonstrate that in HNSCC cancer stem cells, salinomycin can cause cell death and decrease stem cell properties despite activation of both EMT and

  19. Lactate dehydrogenase B is associated with the response to neoadjuvant chemotherapy in oral squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Wenyi Sun

    Full Text Available Oral squamous cell carcinoma (OSCC comprises a subset of head and neck squamous cell carcinoma (HNSCC with poor therapeutic outcomes and high glycolytic dependency. Neoadjuvant chemotherapy regimens of docetaxel, cisplatin and 5-fluorouracil (TPF are currently accepted as standard regimens for HNSCC patients with a high risk of distant metastatic spread. However, the antitumor outcomes of TPF neoadjuvant chemotherapy in HNSCC remain controversial. This study investigated the role of lactate dehydrogenase B (LDHB, a key glycolytic enzyme catalyzing the inter-conversion between pyruvate and lactate, in determining chemotherapy response and prognosis in OSCC patients. We discovered that a high protein level of LDHB in OSCC patients was associated with a poor response to TPF regimen chemotherapy as well as poor overall survival and disease-free survival. Our in-depth study revealed that high LDHB expression conferred resistance to taxol but not 5-fluorouracil or cisplatin. LDHB deletion sensitized OSCC cell lines to taxol, whereas the introduction of LDHB decreased sensitivity to taxol treatment. Taxol induced a pronounced impact on LDHB-down-regulated OSCC cells in terms of apoptosis, G2/M phase cell cycle arrest and energy metabolism. In conclusion, our study highlighted the critical role of LDHB in OSCC and proposed that LDHB could be used as a biomarker for the stratification of patients for TPF neoadjuvant chemotherapy and the determination of prognosis in OSCC patients.

  20. Current prognosis and quality of life following surgical treatment for head and neck squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cristina Hernández-Vila

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world with a close relation with some risk factor like, tobacco, alcohol consumption and more recently, with human papilloma virus infection. A review of the literature about actual prognosis and quality of life in HNSCC has been done analysing the results of surgical treatment and their impact on the quality of life of patients. Despite the elevated incidence of HNSCC, the survival rate has increased considerably over the last years thanks to the development of new surgical techniques, such as, microvascular reconstruction or transoral robotic surgery and the most accurate adjuvant radiochemotherapy. Even in bad prognosis cases, there are many options to take into account not only with curative expectation, even, keeping in mind the preservation of the quality of life of patients. Due to the improvement of the prognosis, the interest of surgeons has been focused on preserve the aesthetics, functional and psychosocial aspect of patients without a worsening of the main objective which is the curative result. Although prognosis of HNSCC has improved, further studies are necessary to understand the behaviour in every case and determine how the impact on the quality of life can be a useful tool to individualize the therapies.

  1. Overexpression of neuromedin U is correlated with regional metastasis of head and neck squamous cell carcinoma.

    Science.gov (United States)

    Wang, Lei; Chen, Chen; Li, Fen; Hua, Qing-Quan; Chen, Shiming; Xiao, Bokui; Dai, Mengyuan; Li, Man; Zheng, Anyuan; Yu, Di; Hu, Zhang Wei; Tao, Zezhang

    2016-08-01

    Regional metastasis is an important prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). Neuromedin U (Nmu) is a secreted neuropeptide, named due to its potent uterine contraction‑inducing activity. The aim of the present study was to analyze the significance of Nmu in the regional metastasis of HNSCC. The characteristics of 240 patients recruited from the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University (Wuhan, China) were summarized retrospectively. The positive rate of neck dissection was analyzed according to the material. The expression levels of Nmu in human tumor samples were analyzed using immunohistochemistry. Subsequently, the expression of Nmu was investigated using a tissue microassay to analyze the association between Nmu protein expression and Tumor Node Metastasis (TNM) status. The positive rate of neck dissection was 51.4% in the study sample. The expression levels of Nmu in primary tumors with regional metastasis were higher, compared with those without metastasis. There was increased protein expression of Nmu in the advanced tumor tissues. The data obtained in the present study demonstrated that the expression of Nmu was correlated with regional metastasis and TNM status. Overexpression of Nmu may be involved in the process of regional metastasis of HNSCC, and may serve as a novel and valuable biomarker for predicting regional metastasis in patients with HNSCC. PMID:27279246

  2. Reference gene selection for head and neck squamous cell carcinoma gene expression studies

    Directory of Open Access Journals (Sweden)

    Raynal Caroline

    2009-08-01

    Full Text Available Abstract Background It is no longer adequate to choose reference genes blindly. We present the first study that defines the suitability of 12 reference genes commonly used in cancer studies (ACT, ALAS, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPL27, RPS29, SHAD and TBP for the normalization of quantitative expression data in the field of head and neck squamous cell carcinoma (HNSCC. Results Raw expression levels were measured by RT-qPCR in HNSCC and normal matched mucosa of 46 patients. We analyzed the expression stability using geNorm and NormFinder and compared the expression levels between subgroups. In HNSCC and/or normal mucosa, the four best normalization genes were ALAS, GAPDH, RPS18 and SHAD and the most stable combination of two genes was GAPDH-SHAD. We recommend using KALPHA-TBP for the study of T1-T2 tumors, RPL27-SHAD for T3-T4 tumors, KALPHA-SHAD for N0 tumors, and ALAS-TBP for N+ tumors. ACT, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPS29, SHAD and TBP were slightly misregulated ( Conclusion In the field of HNSCC, this study will guide researchers in selecting the most appropriate reference genes from among 12 potentially suitable reference genes, depending on the specific setting of their experiments.

  3. EGFR kinase promotes acquisition of stem cell-like properties: a potential therapeutic target in head and neck squamous cell carcinoma stem cells.

    Directory of Open Access Journals (Sweden)

    Eric L Abhold

    Full Text Available Members of the EGFR/ErbB family of tyrosine kinases are found to be highly expressed and deregulated in many cancers, including head and neck squamous cell carcinoma (HNSCC. The ErbB family, including EGFR, has been demonstrated to play key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these characteristics have been linked to a small subpopulation of cells classified as cancer stem cells (CSCs which are believed to be responsible for tumor initiation and maintenance. In this study, we investigated the possible role of EGFR as a regulator of "stemness" in HNSCC cells. Activation of EGFR by the addition of EGF ligand or ectopic expression of EGFR in two established HNSCC cell lines (UMSCC-22B and HN-1 resulted in the induction of CD44, BMI-1, Oct-4, NANOG, CXCR4, and SDF-1. Activation of EGFR also resulted in increased tumorsphere formation, a characteristic ability of cancer stem cells. Conversely, treatment with the EGFR kinase inhibitor, Gefinitib (Iressa, resulted in decreased expression of the aforementioned genes, and loss of tumorsphere-forming ability. Similar trends were observed in a 99.9% CD44 positive stem cell culture derived from a fresh HNSCC tumor, confirming our findings for the cell lines. Additionally, we found that these putative cancer stem cells, when treated with Gefitinib, possessed a lower capacity to invade and became more sensitive to cisplatin-induced death in vitro. These results suggest that EGFR plays critical roles in the survival, maintenance, and function of cancer stem cells. Drugs that target EGFR, perhaps administered in combination with conventional chemotherapy, might be an effective treatment for HNSCC.

  4. Tinospora crispa extract inhibits MMP-13 and migration of head and neck squamous cell carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Hataipan Phienwej; Ih-si Swasdichira; Surattana Amnuoypol; Prasit Pavasant; Piyamas Sumrejkanchanakij

    2015-01-01

    To investigate the effect of Tinospora crispa (T. crispa) extract on matrix metalloproteinase 13 (MMP-13) expression and cell migration. Methods: The cytotoxicity of T. crispa extract was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on head and neck squamous cell carcinoma (HNSCC) cell lines. The effect on expression of MMP-13 was analysed by RT-PCR and ELISA. The migration was assessed by wound healing assay. Results: MMP-13 mRNA was highly expressed in the metastatic human HNSCC cell lines, HN22 and HSC-3. T. crispa extract at a concentration of 100.0 µg/mL caused about 50% reduction of cell survival. T. crispa extract at a non-toxic concentration of 12.5, 25.0 and 50.0 µg/mL significantly suppressed MMP-13 mRNA expression and secreted MMP-13 in both HN22 and HSC-3. The expression of tissue inhibitors of metalloprotease by HSC-3 cells was attenuated by 25.0 and 50.0 µg/mL of T. crispa extract. Addition of the extract to cells in a wound healing assay showed inhibition of cell migration by HN22 cells. Conclusions: These data suggest that T. crispa could be considered as a potential therapeutic drug to prevent metastasis of HNSCC.

  5. Tinospora crispa extract inhibits MMP-13 and migration of head and neck squamous cell carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Hataipan; Phienwej; Ih-si; Swasdichira; Surattana; Amnuoypol; Prasit; Pavasant; Piyamas; Sumrejkanchanakij

    2015-01-01

    Objective: To investigate the effect of Tinospora crispa(T. crispa) extract on matrix metalloproteinase 13(MMP-13) expression and cell migration. Methods: The cytotoxicity of T. crispa extract was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on head and neck squamous cell carcinoma(HNSCC) cell lines. The effect on expression of MMP-13 was analysed by RT-PCR and ELISA. The migration was assessed by wound healing assay. Results: MMP-13 m RNA was highly expressed in the metastatic human HNSCC cell lines, HN22 and HSC-3. T. crispa extract at a concentration of 100.0 μg/m L caused about 50% reduction of cell survival. T. crispa extract at a non-toxic concentration of 12.5, 25.0 and 50.0 μg/m L signii cantly suppressed MMP-13 m RNA expression and secreted MMP-13 in both HN22 and HSC-3. The expression of tissue inhibitors of metalloprotease by HSC-3 cells was attenuated by 25.0 and 50.0 μg/m L of T. crispa extract. Addition of the extract to cells in a wound healing assay showed inhibition of cell migration by HN22 cells. Conclusions: These data suggest that T. crispa could be considered as a potential therapeutic drug to prevent metastasis of HNSCC.

  6. 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 ...

  7. 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 ...

  8. The cyclic GMP/protein kinase G pathway as a therapeutic target in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Tuttle, Traci R; Mierzwa, Michelle L; Wells, Susanne I; Fox, Sejal R; Ben-Jonathan, Nira

    2016-01-28

    Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with high mortality. Treatments, which can result in significant morbidity, have not substantially changed in three decades. The second messenger cyclic GMP (cGMP), which targets protein kinase G (PKG), is generated by guanylate cyclases (GCs), and is rapidly hydrolyzed by phosphodiesterases (PDEs). Activation of the cGMP/PKG pathway is antineoplastic in several cancer types, but its impact on HNSCC has not been fully exploited. We found differential expression of critical components of this pathway in four HNSCC cell lines. Several activators of soluble GC (sGC), as well as inhibitors of PDE5, increased intracellular cGMP, reduced cell viability, and induced apoptosis in HNSCC cells. The apoptotic effects of the sGC activator BAY 41-2272 and the PDE5 inhibitor Tadalafil (Cialis) were mediated by PKG. Furthermore, Tadalafil substantially reduced the growth of CAL27-derived tumors in athymic mice. Several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer.

  9. miRNA array analysis determines miR-205 is overexpressed in head and neck squamous cell carcinoma and enhances cellular proliferation

    Directory of Open Access Journals (Sweden)

    Howard JD

    2013-08-01

    Full Text Available MicroRNAs (miRNAs play a critical role in cell cycle and pro-survival signal regulation. Consequently, their deregulation can enhance tumorigenesis and cancer progression. In the current investigation, we determined whether cancer- or human papillomavirus (HPV-specific miRNA deregulation could further elucidate signal transduction events unique to head and neck squamous cell carcinoma (HNSCC. Twenty-nine newly diagnosed HNSCC tumors (HPV-positive: 14, HPV-negative: 15 and four normal mucosa samples were analyzed for global miRNA expression. Differential miRNA expression analysis concluded HNSCC is characterized by a general upregulation of miRNAs compared to normal mucosa. Additionally, miR-449a and miR-129-3p were statistically significant miRNAs differentially expressed between HPV-positive and HPV-negative HNSCC. The upregulation of miR-449a was also validated within an independent dataset obtained from TCGA containing 279 HNSCCs and 39 normal adjacent mucosa samples. To gain a better understanding of miRNA-mediated cell cycle deregulation in HNSCC, we functionally evaluated miR-205, a transcript upregulated in our cancer-specific analysis and a putative regulator of E2F1. Modulation of miR-205 with a miRNA mimic and inhibitor revealed miR-205 is capable of regulating E2F1 expression in HNSCC and overexpression of this transcript enhances proliferation. This study demonstrates miRNA expression is highly deregulated in HNSCC and functional evaluations of these miRNAs may reveal novel HPV context dependent mechanisms in this disease.

  10. Advancements in the Management of HPV-Associated Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ross Zeitlin

    2015-04-01

    Full Text Available Head and neck carcinomas have long been linked to alcohol and tobacco abuse; however, within the last two decades, the human papillomavirus (HPV has emerged as a third etiology and is specifically associated with head and neck squamous cell carcinomas (HNSCC. In this anatomical region, the oncogenic HPV-16 mediates transformation and immortalization of epithelium, most commonly in the oropharynx. Nevertheless, the recent identification of novel HPV mechanisms thought to be specific to oropharyngeal carcinogenesis has coincided with observations that HPV-associated HNSCC has differing clinical behavior—in terms of natural history, therapeutic response, and prognosis—than HPV-negative head and neck tumors. Taken together with the growing incidence of HPV transmission in younger populations, these discoveries have sparked a rapid expansion in both laboratory and clinical studies on the infection and disease. Herein, we review the clinical characteristics of HPV-associated HNSCC, with particular emphasis on recent advancements in our understanding of the management of this infectious malignancy.

  11. The Effects of GLUT1 on the Survival of Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Shengjiao Li

    2013-09-01

    Full Text Available Background/Aims: Cancer cells require increased nutrient uptake to support a high rate of proliferation, and the overexpression of glucose transporters, in particular GLUT1, is a common characteristic of human malignancies. Here, we investigated the relationship between the expression of GLUT1 and cell viability, colony forming ability and apoptosis of head and neck squamous cell carcinoma (HNSCC in vitro and in a xenograft mouse model in vivo. Methods: Lentiviral mediated overexpression and knock-down of GLUT1 was performed in two oral cancer cell lines (CAL27 and SCC25. QRT-PCR and Western blot analysis were used to detect the mRNA and protein expression of GLUT1 and nuclear factor-kappa B (NFκB p65 subunit. Cell viability and apoptosis were assessed by MTT and flow cytometry analyses, respectively. Colony formation assays were performed by staining with 0.5% crystal violet. The role of GLUT1 in HNSCC was examined in vivo through the generation of a CAL27 (or CAL27 with different transfections nude mice xenograft model of HNSCC. Results: GLUT1 overexpression promoted cell viability and colony formation whereas GLUT1 silencing had the opposite effect. GLUT1 knock-down significantly increased the number of Annexin V positive cells in both cell lines and GLUT1 overexpression had the opposite effect, indicating that GLUT1 modulates apoptosis. Xenograft mouse models of GLUT1 knockdown and overexpression showed that GLUT1 expression was associated with poor survival and increased tumor growth. GLUT1 overexpression significantly upregulated the expression of NFκB-p65, and this effect was reversed by inhibition of GLUT1 expression. Conclusions: GLUT1 expression plays an important role in the survival of HNSCC, and its effects may be associated with the activation of the NFκB pathway.

  12. Afatinib down-regulates MCL-1 expression through the PERK-eIF2α-ATF4 axis and leads to apoptosis in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Liu, Xianfang; Lv, Zhenghua; Zou, Jidong; Liu, Xiuxiu; Ma, Juke; Wang, Jinhua; Sa, Na; Jing, Peihang; Xu, Wei

    2016-01-01

    Afatinib is the second generation of irreversible inhibitor of EGFR, HER2 and HER4, which has shown encouraging phase II and III clinical outcomes in the treatment of head and neck squamous cell carcinoma (HNSCC). However, the molecular mechanism of afatinib-induced apoptosis in HNSCC is poorly understood. In the present investigation, we discovered that down-regulation of MCL-1, an anti-apoptotic member of BCL-2 family, was responsible for afatinib-triggered apoptosis. And the inactivation of AKT-mTOR signaling caused by afatinib lead to translational inhibition of MCL-1 expression. As a crucial branch of ER stress, PERK-eIF2α-ATF4 axis was also stimulated in HNSCC cells after afatinib incubation. Silencing either eIF2α or ATF4 by siRNA transfection relieved afatinib-caused suppression of AKT-mTOR activity, attenuating MCL-1 down-regulation as well as subsequent apoptosis. Collectively, the results show that afatinib hampers AKT-mTOR activation by stimulating PERK-eIF2α-ATF4 signaling pathway, giving rise to MCL-1 down-regulation mediated apoptosis in HNSCC cells. Therefore, our findings reveal the elaborate molecular network of afatinib-induced apoptosis in HNSCC, which would provide substantial theoretical underpinnings for afatinib clinical application and highlight its promising prospect in HNSCC treatment. PMID:27648360

  13. Triggering of Toll-like Receptor 4 Expressed on Human Head and Neck Squamous Cell Carcinoma Promotes Tumor Development and Protects the Tumor from Immune Attack

    OpenAIRE

    Szczepanski, Miroslaw J.; Czystowska, Malgorzata; Szajnik, Marta; Harasymczuk, Malgorzata; Boyiadzis, Michael; Kruk-Zagajewska, Aleksandra; Szyfter, Witold; Zeromski, Jan; Whiteside, Theresa L.

    2009-01-01

    Toll-like receptors (TLR) expressed on inflammatory cells play a key role in host defense against pathogens, benefiting the host. TLR are also expressed on tumor cells. To evaluate the role of TLR in tumor cells, we investigated TLR4 signaling effects on human head and neck squamous cell carcinoma (HNSCC). Tumor tissues were obtained from 27 patients with laryngeal and 12 with oral cavity cancers. Normal mucosa was obtained from 10 patients with nonneoplastic disorders. Smears for bacteria we...

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

    Directory of Open Access Journals (Sweden)

    Satoshi Iizuka

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

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

    Science.gov (United States)

    Iizuka, Satoshi; Oridate, Nobuhiko; Nashimoto, Masayuki; Fukuda, Satoshi; Tamura, Masato

    2014-01-01

    Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial small guide RNA (sgRNA). In this study, we designed several sgRNAs targeting human cyclin D1 mRNA to examine growth inhibition of HNSCC cells. Transfection of certain sgRNAs decreased levels of cyclin D1 mRNA and protein in HSC-2 and HSC-3 cells, and also inhibited their proliferation. The combination of these sgRNAs and cisplatin showed more than additive inhibition of cancer cell growth. These findings demonstrate that TRUE gene silencing of cyclin D1 leads to inhibition of the growth of HNSCC cells and suggest that these sgRNAs alone or combined with cisplatin may be a useful new therapy for HNSCCs. PMID:25437003

  16. 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...

  17. Detection of High Risk Human Papillomavirus DNA Sequences in Head and Neck Squamous Cell Carcinoma in Iranian Fanconi Anemia Patients

    Directory of Open Access Journals (Sweden)

    Anahita Mohseni Meybodi

    2010-01-01

    Full Text Available Objective: Fanconi anemia (FA is an autosomal recessive disorder characterizedby congenital malformations, bone marrow failure, development of squamous cellcarcinoma (SCC, and other cancers. Human papillomavirus (HPV in the oral cavityor oropharynx has been associated with an increased risk of laryngeal papillomatosis,invasive squamous cell carcinoma of the head and neck (HNSCC and cervicaland other genital cancers. The prevalence of HPV DNA in the oral cavity/oropharynxin FA patients and controls was compared.Materials and Methods: A risk factor questionnaire and oral exfoliated cells werecollected from FA patients. The study group consisted of 22 FA patients with HNSCC(case subjects and 24 patients with HNSCC without FA (control subjects. HPVDNA was detected using polymerase chain reaction (PCR and specific primers thatcovered high risk types of HPV. Moreover, special serological assays were used forthe detection of specific antibodies against HPV in patient’s sera.Results: HPV DNA was detected in 82% of the SCC specimens from the case subjectswhich was statistically higher (p< 0.05 than the SCC specimens from the controlsubjects (62.5%. In all cases, the presence of HPV antibodies in patient’s serahas been shown. Among the case subject specimens, 14 cases, and in the controlsubjects, 11 cases were infected by high risk HPV (hr-HPV.Conclusion: These data confirm that HPV infection, especially with high risk types(16,18, could be one of several risk factors for HNSCC particularly in FA patients.

  18. CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients

    DEFF Research Database (Denmark)

    Olivieri, Eloisa Helena Ribeiro; da Silva, Sabrina Daniela; Mendonça, Fernando Fernandes;

    2009-01-01

    Head and neck squamous cell carcinoma (HNSCC) is associated with environmental factors, especially tobacco and alcohol consumption. Most of the carcinogens present in tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYPs) enzymes and detoxification of these substances...

  19. Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

    International Nuclear Information System (INIS)

    This study was performed to identify the potential role of Alpha-2 Heremans Schmid Glycoprotein (AHSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) tumorigenesis using an HNSCC cell line model. HNSCC cell lines are unique among cancer cell lines, in that they produce endogenous AHSG and do not rely, solely, on AHSG derived from serum. To produce our model, we performed a stable transfection to down-regulate AHSG in the HNSCC cell line SQ20B, resulting in three SQ20B sublines, AH50 with 50% AHSG production, AH20 with 20% AHSG production and EV which is the empty vector control expressing wild-type levels of AHSG. Utilizing these sublines, we examined the effect of AHSG depletion on cellular adhesion, proliferation, migration and invasion in a serum-free environment. We demonstrated that sublines EV and AH50 adhered to plastic and laminin significantly faster than the AH20 cell line, supporting the previously reported role of exogenous AHSG in cell adhesion. As for proliferative potential, EV had the greatest amount of proliferation with AH50 proliferation significantly diminished. AH20 cells did not proliferate at all. Depletion of AHSG also diminished cellular migration and invasion. TGF-β was examined to determine whether levels of the TGF-β binding AHSG influenced the effect of TGF-β on cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-β influenced SMAD and ERK signaling, it did not clearly affect proliferation, suggesting that AHSG influences on adhesion, proliferation, invasion and migration are primarily due to its role in adhesion and cell spreading. The previously reported role of AHSG in potentiating metastasis via protecting MMP-9 from autolysis was also supported in this cell line based model system of endogenous AHSG production in HNSCC. Together, these data show that endogenously produced AHSG in an HNSCC cell line, promotes in vitro cellular properties identified as having a role in tumorigenesis. Highlights: • Head

  20. Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Pamela D.; Sakwe, Amos [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Koumangoye, Rainelli [Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Yarbrough, Wendell G. [Division of Otolaryngology, Departments of Surgery and Pathology and Yale Cancer Center, Yale University, New Haven, CT 06520 (United States); Ochieng, Josiah [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Marshall, Dana R., E-mail: dmarshall@mmc.edu [Department of Pathology, Anatomy and Cell Biology, Meharry Medical College, Nashville, TN 37208 (United States)

    2014-02-15

    This study was performed to identify the potential role of Alpha-2 Heremans Schmid Glycoprotein (AHSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) tumorigenesis using an HNSCC cell line model. HNSCC cell lines are unique among cancer cell lines, in that they produce endogenous AHSG and do not rely, solely, on AHSG derived from serum. To produce our model, we performed a stable transfection to down-regulate AHSG in the HNSCC cell line SQ20B, resulting in three SQ20B sublines, AH50 with 50% AHSG production, AH20 with 20% AHSG production and EV which is the empty vector control expressing wild-type levels of AHSG. Utilizing these sublines, we examined the effect of AHSG depletion on cellular adhesion, proliferation, migration and invasion in a serum-free environment. We demonstrated that sublines EV and AH50 adhered to plastic and laminin significantly faster than the AH20 cell line, supporting the previously reported role of exogenous AHSG in cell adhesion. As for proliferative potential, EV had the greatest amount of proliferation with AH50 proliferation significantly diminished. AH20 cells did not proliferate at all. Depletion of AHSG also diminished cellular migration and invasion. TGF-β was examined to determine whether levels of the TGF-β binding AHSG influenced the effect of TGF-β on cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-β influenced SMAD and ERK signaling, it did not clearly affect proliferation, suggesting that AHSG influences on adhesion, proliferation, invasion and migration are primarily due to its role in adhesion and cell spreading. The previously reported role of AHSG in potentiating metastasis via protecting MMP-9 from autolysis was also supported in this cell line based model system of endogenous AHSG production in HNSCC. Together, these data show that endogenously produced AHSG in an HNSCC cell line, promotes in vitro cellular properties identified as having a role in tumorigenesis. Highlights: • Head

  1. Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Kinoshita, Takashi; Hanazawa, Toyoyuki; Nohata, Nijiro; Kikkawa, Naoko; Enokida, Hideki; Yoshino, Hirofumi; Yamasaki, Takeshi; Hidaka, Hideo; Nakagawa, Masayuki; Okamoto, Yoshitaka; Seki, Naohiko

    2012-11-01

    Recent our microRNA (miRNA) expression signature revealed that expression of microRNA-218 (miR-218) was reduced in cancer tissues, suggesting a candidate of tumor suppressor in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the functional significance of miR-218 and its mediated moleculer pathways in HNSCC. Restoration of miR-218 in cancer cells led to significant inhibition of cell migration and invasion activities in HNSCC cell lines (FaDu and SAS). Genome-wide gene expression analysis of miR-218 transfectants and in silico database analysis showed that focal adhesion pathway was a promising candidate of miR-218 target pathways. The laminins are an important and biologically active part of the basal lamina, the function of that are various such as influencing cell differentiation, migration and adhesion as well as proliferation and cell survival. Interestingly, all components of laminin-332 (LAMA3, LAMB3 and LAMC2) are listed on the candidate genes in focal adhesion pathway. Furthermore, we focused on LAMB3 which has a miR-218 target site and gene expression studies and luciferase reporter assays showed that LAMB3 was directly regulated by miR-218. Silencing study of LAMB3 demonstrated significant inhibition of cell migration and invasion. In clinical specimens with HNSCC, the expression levels of laminin-332 were significantly upregulated in cancer tissues compared to adjacent non-cancerous tissues. Our analysis data showed that tumor suppressive miR-218 contributes to cancer cell migration and invasion through regulating focal adhesion pathway, especially laminin-332. Tumor suppressive miRNA-mediated novel cancer pathways provide new insights into the potential mechanisms of HNSCC oncogenesis. PMID:23159910

  2. p27Kip1 expression as a prognostic marker for squamous cell carcinoma of the head and neck

    Science.gov (United States)

    DE ALMEIDA, MIGUEL REIS; PÉREZ-SAYÁNS, MARIO; SUÁREZ-PEÑARANDA, JOSÉ MANUEL; SOMOZA-MARTÍN, JOSÉ MANUEL; GARCÍA-GARCÍA, ABEL

    2015-01-01

    Regulation of the cell cycle is essential for carcinogenesis. The cell cycle is controlled by cyclin-dependent kinases (CDKs), which are upregulated by cyclins and downregulated by CDK inhibitors (CDKIs). Decreased p27Kip1 expression has been associated with survival rate, tumor size, histological differentiation and the presence of lymph node metastasis in patients with various types of cancer. The aim of the current study is to provide a literature review on the association between p27Kip1 expression and the clinical and pathological aspects of head and neck squamous cell carcinoma (HNSCC), and the expression of other CDKIs of the Cip/Kip family and cyclins. Throughout the literature, different methodologies were used to determine the immunohistochemical expression of p27Kip1; thus, results concerning p27Kip1 expression in HNSCC vary widely. However, it has now been confirmed that p27Kip1 is underexpressed in SCC cells. p27 may be a promising marker for determining the prognosis of HNSCC, despite the marked variability of the results obtained. An association between p27 expression and survival rate, time to recurrence and tumor stage has been observed. Based on the information currently available, it is premature to recommend the analysis of p27Kip1 expression in guiding HNSCC treatment planning. However, although relatively unstudied, the correlation between p27Kip1 expression and other tumor suppressor genes may turn out to be important in determining the prognosis of HNSCC. Further prospective studies utilizing standardized laboratory methodologies and statistics that facilitate meta-analyses are required to confirm this proposal. PMID:26722226

  3. MART-10, a newly synthesized vitamin D analog, represses metastatic potential of head and neck squamous carcinoma cells

    Science.gov (United States)

    Yang, Shih-Wei; Tsai, Chi-Ying; Pan, Yi-Chun; Yeh, Chun-Nan; Pang, Jong-Hwei S; Takano, Masashi; Kittaka, Atsushi; Juang, Horng-Heng; Chen, Tai C; Chiang, Kun-Chun

    2016-01-01

    Even with multidisciplinary treatment, the prognosis and quality of life of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) are still not satisfactory. Previously, 19-Nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3 (MART-10), the new brand 1α,25(OH)2D3 analog, has been demonstrated to be an effective drug to inhibit HNSCC growth in vitro. Since most cancer patients die of metastasis, in this study, the antimetastatic effect of MART-10 on HNSCC was investigated. Our results reveal that both 1α,25(OH)2D3 and MART-10 effectively repressed the migration and invasion of HNSCC cells, with MART-10 being much more potent than 1α,25(OH)2D3. The antimetastatic effect of 1α,25(OH)2D3 and MART-10 was mediated by attenuation of epithelial–mesenchymal transition (EMT), which was supported by the finding that the expression of EMT-inducing transcriptional factors, Sail and Twist, was inhibited by 1α,25(OH)2D3 and MART-10. The upregulation of E-cadherin and downregulation of N-cadherin in FaDu cells induced by both drugs further confirmed the repression of EMT. In addition, 1α,25(OH)2D3 and MART-10 treatment inhibited intracellular MMP-9 expression and extracellular MMP activity in FaDu cells. Collectively, our results suggest that the less-calcemia 1α,25(OH)2D3 analog, MART-10, is a promising drug for HNSCC treatment. Further clinical studies are warranted.

  4. Expression of the T cell receptor αβ on a CD123+ BDCA2+ HLA-DR+ subpopulation in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Annette Thiel

    Full Text Available Human Plasmacytoid Dendritic Cells (PDCs infiltrating solid tumor tissues and draining lymph nodes of Head and Neck Squamous Cell Carcinoma (HNSCC show an impaired immune response. In addition to an attenuated secretion of IFN-α little is known about other HNSCC-induced functional alterations in PDCs. Particular objectives in this project were to gain new insights regarding tumor-induced phenotypical and functional alterations in the PDC population. We showed by FACS analysis and RT-PCR that HNSCC orchestrates an as yet unknown subpopulation exhibiting functional autonomy in-vitro and in-vivo besides bearing phenotypical resemblance to PDCs and T cells. A subset, positive for the PDC markers CD123, BDCA-2, HLA-DR and the T cell receptor αβ (TCR-αβ was significantly induced subsequent to stimulation with HNSCC in-vitro (p = 0.009 and also present in metastatic lymph nodes in-vivo. This subgroup could be functionally distinguished due to an enhanced production of IL-2 (p = 0.02, IL-6 (p = 0.0007 and TGF-β (not significant. Furthermore, after exposure to HNSCC cells, mRNA levels revealed a D-J-beta rearrangement of the TCR-beta chain besides a strong enhancement of the CD3ε chain in the PDC population. Our data indicate an interface between the PDC and T cell lineage. These findings will improve our understanding of phenotypical and functional intricacies concerning the very heterogeneous PDC population in-vivo.

  5. 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.

  6. Head and Neck Squamous Cell Carcinomas Do Not Express EGFRvIII

    International Nuclear Information System (INIS)

    Purpose: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was optimized on formalin-fixed, paraffin-embedded tissue using glioblastoma tissue. It was compared with EGFR and EGFRvIII RNA expression using a specific reverse transcription–polymerase chain reaction also optimized for formalin-fixed, paraffin-embedded tissue. Tissue microarrays including 531 HNSCCs of various stages with complete clinicopathologic and follow-up data were tested for the presence of EGFRvIII. Results: None of the 531 cases showed EGFRvIII protein expression. Using an immunohistochemistry protocol reported by others revealed cytoplasmic staining in 8% of cases. Reverse transcription–polymerase chain reaction for the EGFRvIII transcript of the 28 highest cytoplasmic staining cases, as well as 69 negative cases, did not show expression in any of the tested cases, suggesting aspecific staining by a nonoptimal protocol. Conclusions: The EGFRvIII mutation is not present in HNSCC. Therefore, EGFRvIII does not influence treatment response in HNSCC and is not a usable clinical prognostic marker

  7. Head and Neck Squamous Cell Carcinomas Do Not Express EGFRvIII

    Energy Technology Data Exchange (ETDEWEB)

    Melchers, Lieuwe J., E-mail: l.j.melchers@umcg.nl [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Clausen, Martijn J.A.M. [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Mastik, Mirjam F. [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Slagter-Menkema, Lorian [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Laan, Bernard F.A.M. van der [Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Wal, Jacqueline E. van der; Vegt, Bert van der [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Roodenburg, Jan L.N. [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Schuuring, Ed [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

    2014-10-01

    Purpose: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was optimized on formalin-fixed, paraffin-embedded tissue using glioblastoma tissue. It was compared with EGFR and EGFRvIII RNA expression using a specific reverse transcription–polymerase chain reaction also optimized for formalin-fixed, paraffin-embedded tissue. Tissue microarrays including 531 HNSCCs of various stages with complete clinicopathologic and follow-up data were tested for the presence of EGFRvIII. Results: None of the 531 cases showed EGFRvIII protein expression. Using an immunohistochemistry protocol reported by others revealed cytoplasmic staining in 8% of cases. Reverse transcription–polymerase chain reaction for the EGFRvIII transcript of the 28 highest cytoplasmic staining cases, as well as 69 negative cases, did not show expression in any of the tested cases, suggesting aspecific staining by a nonoptimal protocol. Conclusions: The EGFRvIII mutation is not present in HNSCC. Therefore, EGFRvIII does not influence treatment response in HNSCC and is not a usable clinical prognostic marker.

  8. Occupational dust exposure and head and neck squamous cell carcinoma risk in a population-based case–control study conducted in the greater Boston area

    International Nuclear Information System (INIS)

    Head and neck cancers account for an estimated 549,000 global cancer diagnoses each year. While tobacco use, alcohol consumption, and HPV16 infection are considered to be the major risk factors for this disease, occupational risk factors, including exposure to asbestos, have also been described, although dust exposures other than asbestos have been historically understudied. We have investigated the relationship between occupational exposures to five types of dusts, including sawdust, concrete dust, leather dust, metal dust, and chimney soot, and head and neck squamous cell carcinomas (HNSCC) in the greater Boston area. We report findings from a population-based case–control study involving 951 incident HNSCC cases and 1193 controls, frequency matched on age (±3 years), sex, and town/neighborhood of residence. Multivariable logistic regression was used to assess the association between occupational exposure to each type of dust and HNSCC, overall and by primary tumor site. After adjusting for age, sex, race, smoking, alcohol consumption, education, and HPV16 serology, laryngeal carcinoma risk increased for each decade of occupational exposure to sawdust (OR = 1.2, 95% CI: 1.0, 1.3) and metal dust (OR = 1.2, 95% CI: 1.0, 1.4); and HNSCC risk increased for each decade of occupational leather dust exposure (OR = 1.5, 95% CI: 1.2, 1.9). We have provided evidence for an association between occupational sawdust and metal dust and laryngeal squamous cell carcinoma, and leather dust and HNSCC, with increasing risk with longer duration at the exposed occupation

  9. Triggering of Toll-like receptor 4 expressed on human head and neck squamous cell carcinoma promotes tumor development and protects the tumor from immune attack.

    Science.gov (United States)

    Szczepanski, Miroslaw J; Czystowska, Malgorzata; Szajnik, Marta; Harasymczuk, Malgorzata; Boyiadzis, Michael; Kruk-Zagajewska, Aleksandra; Szyfter, Witold; Zeromski, Jan; Whiteside, Theresa L

    2009-04-01

    Toll-like receptors (TLR) expressed on inflammatory cells play a key role in host defense against pathogens, benefiting the host. TLR are also expressed on tumor cells. To evaluate the role of TLR in tumor cells, we investigated TLR4 signaling effects on human head and neck squamous cell carcinoma (HNSCC). Tumor tissues were obtained from 27 patients with laryngeal and 12 with oral cavity cancers. Normal mucosa was obtained from 10 patients with nonneoplastic disorders. Smears for bacteria were taken from all patients during surgery. TLR4 expression in tumors and HNSCC cell lines (PCI-1, PCI-13, and PCI-30) was detected by reverse transcription-PCR and immunohistochemistry. Cell growth, apoptosis, nuclear factor-kappaB (NF-kappaB) translocation, and MyD88 and IRAK-4 expression, as well as Akt phosphorylation were measured following tumor cell exposure to the TLR4 ligand lipopolysaccharide (LPS). Tumor cell sensitivity to NK-92-mediated lysis was evaluated in 4-hour (51)Cr-release assays. Cytokine levels in HNSCC supernatants were measured in Luminex-based assays. TLR4 was expressed in all tumors, HNSCC cell lines, and normal mucosa. The TLR4 expression intensity correlated with tumor grade. LPS binding to TLR4 on tumor cells enhanced proliferation, activated phosphatidylinositol 3-kinase/Akt pathway, up-regulated IRAK-4 expression, induced nuclear NF-kappaB translocation, and increased production (P<0.05) of interleukin (IL)-6, IL-8, vascular endothelial growth factor, and granulocyte macrophage colony-stimulating factor. TLR4 triggering protected tumor cells from lysis mediated by NK-92 cells. TLR4 ligation on tumor cells supports HNSCC progression. PMID:19318560

  10. Head and neck squamous cell carcinoma in chronic areca nut chewing Indian women: Case series and review of literature

    Directory of Open Access Journals (Sweden)

    Sidramesh Shivanand Muttagi

    2012-01-01

    Full Text Available Background: Head and neck squamous cell carcinoma (HNSCC is an important public health problem in India. Several risk factors such as tobacco, human papilloma virus, alcohol, areca nut usage have been extensively studied as causative agents. Though Areca nut chewing is known cause of oral cancer, its association with hypopharynx cancer has not been previously reported. Since areca nut is mostly consumed along with tobacco, it is uncommon to find patients who consume the areca nut alone. Materials and Methods: This is a prospective case series of ten women who presented to us with HNSCC with history of chewing of areca nut alone for several years. We have excluded all those cases where areca nut was consumed along with tobacco in any form. The data were prospectively collected with regard to clinical parameters, duration and frequency of areca nut usage, the socio-economic status and education level. Results: All ten females had varying degree of submucous fibrosis and coexisting squamous cell carcinoma either in the oral cavity or hypopharynx. Submucous fibrosis was characterized by burning mouth, unhealthy oral mucosa, buried third molars, trismus, poor oral hygiene, etc. The disease presented in an advanced stage in majority of the cases. All patients were unaware of areca nut′s deleterious effects. Conclusion: Areca nut chewing is an important risk factor for HNSCC in females. Despite plethora of information, little importance is given to areca nut control in cancer prevention campaigns in India.

  11. Lack of prognostic and predictive value of CA IX in radiotherapy of squamous cell carcinoma of the head and neck with known modifiable hypoxia: An evaluation of the DAHANCA 5 study

    DEFF Research Database (Denmark)

    Eriksen, Jesper Grau; Overgaard, Jens

    2007-01-01

    BACKGROUND AND PURPOSE: CA IX is suggested to be an endogenous marker of hypoxia in tumours like squamous cell carcinomas of the head and neck (HNSCC). The aim of the present study was to investigate whether CA IX served as a prognostic factor for outcome in a large population of HNSCC and if CA IX......+/-the hypoxic radiosensitizer nimorazole. CA IX was measured using immunohistochemistry and results were divided into four groups of CA IX expression: 30% of the tumour area with positive membrane staining. Locoregional control and disease-specific survival were used as endpoints...... in the head and neck treated with conventional radiotherapy and concomitant nimorazole....

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

    Directory of Open Access Journals (Sweden)

    Ali Khammanivong

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

  13. 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

  14. Ligand-receptor dissociated expression explains high TSLP without prognostic impact in human primary head and neck squamous cell carcinoma.

    Science.gov (United States)

    Guillot-Delost, Maude; Guilleré, Lia; Berger, Frédérique; Ventre, Aurore; Michea, Paula; Sirven, Philémon; Pattarini, Lucia; Scholer-Dahirel, Alix; Kebir, Fatima-Zahra; Huerre, Michel; Chouchane-Mlik, Olfa; Lappartient, Emmanuelle; Rodriguez, José; Jouffroy, Thomas; Klijanienko, Jerzy; Nicolas, André; Sastre-Garau, Xavier; Honorio, Sofia; Mosseri, Véronique; Le Peltier, Nelly; Sablin, Marie-Paule; Le Tourneau, Christophe; Tartour, Éric; Badoual, Cécile; Soumelis, Vassili

    2016-07-01

    Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine expressed by epithelial cells during allergic inflammation, and activating dendritic cells (DC). Its expression and functional role in cancer remain controversial. We conducted retrospective (n = 89), and prospective studies including patients with untreated primary head and neck squamous cell carcinoma (HNSCC). We found that TSLP was overexpressed by HNSCC tumor cells, and associated with a highly differentiated status. However, no significant difference in overall and recurrence-free survival was found between patients bearing a tumor with high and low TSLP levels, respectively. Surprisingly, there was no significant association between the levels of TSLP expression, and the number of tumor-infiltrating mature DCLAMP(+) DC. In order to explain the apparent lack of TSLP-induced DC activation, we performed phenotypic and functional experiments on freshly resected tumors. Tumor-infiltrating immune cells, including DC, did not express the TSLP receptor heterodimer (TSLPR chain, IL-7Ralpha chain). Furthermore, freshly sorted blood CD11c(+) DC from healthy donors cultured with tumor-conditioned supernatant exhibited an activated profile, but this was not affected by an anti-TSLP blocking antibody, suggesting a DC activation pathway independent of tumor-derived TSLP. Overall, our results demonstrate that TSLP is overexpressed in HNSCC but its function is hampered by the lack of TSLPR-expressing cells in the tumor microenvironment. Such a dissociated ligand-receptor expression may impact intercellular communication in other immune activation pathways, and tumor types. PMID:27622034

  15. Initial Experience of 3-Tesla Apparent Diffusion Coefficient Values in Characterizing Squamous Cell Carcinomas of the Head and Neck

    International Nuclear Information System (INIS)

    Background: With the increased clinical use of 3-Tesla (3T) magnets, it becomes important to identify the potential applications of advanced magnetic resonance (MR) imaging techniques such as diffusion-weighted imaging in head and neck pathologies. Purpose: To establish the 3T apparent diffusion coefficient (ADC) values for normal neck structures, and to examine the utility of ADC values in distinguishing head and neck squamous cell carcinomas (HNSCC) from normal neck anatomy. Material and Methods: 3T diffusion-weighted imaging was performed on 10 normal volunteers and 10 patients with known HNSCC. In the volunteers, mean ADC was calculated in the parotid gland, submandibular gland, base of the tongue, pterygoid muscle, masseter muscle, paraspinal muscles, true vocal cord, thyroid gland, thyroid cartilage, cricoid cartilage, and lymph nodes. The mean tumor ADC value was calculated from the 10 patients with HNSCC and compared with the normal ADC values from various neck structures. Results: The mean ADC value measured in the HNSCC was 1.101 (±0.214)x10-3mm2/s. This was significantly lower than ADC values of paraspinal muscles, pterygoid muscle, masseter muscle, thyroid gland, and base of the tongue (P=0.0006, 0.0002, 0.0001, 0.001, and 0.002, respectively). The tumor ADC values were not significantly different from ADC values of parotid and submandibular glands (P=0.057 and 0.14, respectively). Conclusion: 3T ADC values show potential for distinguishing HNSCC from normal extracranial head and neck structures

  16. Expression microarray analysis reveals alternative splicing of LAMA3 and DST genes in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Ryan Li

    Full Text Available Prior studies have demonstrated tumor-specific alternative splicing events in various solid tumor types. The role of alternative splicing in the development and progression of head and neck squamous cell carcinoma (HNSCC is unclear. Our study queried exon-level expression to implicate splice variants in HNSCC tumors.We performed a comparative genome-wide analysis of 44 HNSCC tumors and 25 uvulopalatopharyngoplasty (UPPP tissue samples at an exon expression level. In our comparison we ranked genes based upon a novel score-the Maximum-Minimum Exon Score (MMES--designed to predict the likelihood of an alternative splicing event occurring. We validated predicted alternative splicing events using quantitative RT-PCR on an independent cohort.After MMES scoring of 17,422 genes, the top 900 genes with the highest scores underwent additional manual inspection of expression patterns in a graphical analysis. The genes LAMA3, DST, VEGFC, SDHA, RASIP1, and TP63 were selected for further validation studies because of a high frequency of alternative splicing suggested in our graphical analysis, and literature review showing their biological relevance and known splicing patterns. We confirmed TP63 as having dominant expression of the short DeltaNp63 isoform in HNSCC tumor samples, consistent with prior reports. Two of the six genes (LAMA3 and DST validated by quantitative RT-PCR for tumor-specific alternative splicing events (Student's t test, P<0.001.Alternative splicing events of oncologically relevant proteins occur in HNSCC. The number of genes expressing tumor-specific splice variants needs further elucidation, as does the functional significance of selective isoform expression.

  17. Predictors of IMRT and Conformal Radiotherapy Use in Head and Neck Squamous Cell Carcinoma: A SEER-Medicare Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: dsher@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Center for Outcomes and Policy Research, Dana Farber Cancer Institute, Boston, MA (United States); Neville, Bridget A. [Center for Outcomes and Policy Research, Dana Farber Cancer Institute, Boston, MA (United States); Chen, Aileen B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Center for Outcomes and Policy Research, Dana Farber Cancer Institute, Boston, MA (United States); Schrag, Deborah [Center for Outcomes and Policy Research, Dana Farber Cancer Institute, Boston, MA (United States)

    2011-11-15

    Purpose: The extent to which new techniques for the delivery of radiotherapy for head and neck squamous cell carcinoma (HNSCC) have diffused into clinical practice is unclear, including the use of 3-dimensional conformal RT (3D-RT) and intensity-modulated radiation therapy (IMRT). Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 2,495 Medicare patients with Stage I-IVB HNSCC diagnosed at age 65 years or older between 2000 and 2005 and treated with either definitive (80%) or adjuvant (20%) radiotherapy. Our primary aim was to analyze the trends and predictors of IMRT use over this time, and the secondary aim was a similar description of the trends and predictors of conformal radiotherapy (CRT) use, defined as treatment with either 3D-RT or IMRT. Results: Three hundred sixty-four (15%) patients were treated with IMRT, and 1,190 patients (48%) were treated with 3D-RT. Claims for IMRT and CRT rose from 0% to 33% and 39% to 86%, respectively, between 2000 and 2005. On multivariable analysis, IMRT use was associated with SEER region (West 18%; Northeast 11%; South 12%; Midwest 13%), advanced stage (advanced, 21%; early, 9%), non-larynx site (non-larynx, 23%; larynx, 7%), higher median census tract income (highest vs. lowest quartile, 18% vs. 10%), treatment year (2003-2005, 31%; 2000-2002, 6%), use of chemotherapy (26% with; 9% without), and higher radiation oncologist treatment volume (highest vs. lowest tertile, 23% vs. 8%). With CRT as the outcome, only SEER region, treatment year, use of chemotherapy, and increasing radiation oncologist HNSCC volume were significant on multivariable analysis. Conclusions: The use of IMRT and CRT by Medicare beneficiaries with HNSCC rose significantly between 2000 and 2005 and was associated with both clinical and non-clinical factors, with treatment era and radiation oncologist HNSCC treatment volume serving as the strongest predictors of IMRT use.

  18. Diagnostic performance of FDG PET/CT to detect subclinical HNSCC recurrence 6 months after the end of treatment

    Energy Technology Data Exchange (ETDEWEB)

    Robin, Philippe; Abgral, Ronan; Le Roux, Pierre-Yves; Keromnes, Nathalie; Palard, Xavier; Salaun, Pierre-Yves [University Hospital of Brest, Nuclear Medicine Department, Brest Cedex (France); Valette, Gerald; Potard, Gael; Marianowski, Remi [University Hospital of Brest, Department of Head and Neck Surgery, Brest (France); Rousset, Jean [Military Hospital of Brest, Department of Radiology, Brest (France)

    2015-01-15

    Posttreatment follow-up for the recurrence of head and neck squamous cell carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination or conventional imaging. Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is widely validated for the diagnosis of suspected recurrence. Moreover, we have shown in a previous prospective study the high effectiveness of FDG PET/CT in the assessment of subclinical recurrence 12 months after treatment. The aim of this prospective study was to evaluate the effectiveness of an earlier FDG PET/CT, at 6 months after the end of treatment. All patients treated for histologically proven HNSCC from April 2009 to May 2012 at the University Hospital of Brest who did not show any findings suggestive of recurrence at 6 months of their usual follow-up underwent an FDG PET/CT examination. FDG PET/CT findings were correlated with histopathology or imaging follow-up. The study included 116 patients. FDG PET/CT examinations were performed within a mean period ± SD of 5.6 ± 1.8 months after treatment. FDG PET/CT examinations exhibited abnormal FDG uptake in 34 patients and found no suspected recurrence in 82 cases. Of these 82 FDG PET/CT considered as negative, only 1 had a recurrence. Among the 34 positive FDG PET/CT, 22 relapsed whereas 12 did not show evidence of recurrence. The sensitivity and specificity of FDG PET/CT in this study for the diagnosis of occult HNSCC recurrence were 96 (22/23) and 87 % (81/93), respectively. The positive predictive value was 65 % (22/34). The negative predictive value was 99 % (81/82). The overall accuracy was 89 % (103/116). Of the 116 patients, FDG PET/CT highlighted 22 (19 %) subclinical recurrences. Our study showed the high effectiveness of FDG PET/CT in the assessment of subclinical HNSCC recurrence 6 months after completion of treatment. These results

  19. Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck

    OpenAIRE

    Schell, Amy; Ley, Jessica; Wu, Ningying; Trinkaus, Kathryn; Wildes, Tanya Marya; Michel, Loren; Thorstad, Wade; Gay, Hiram; Lewis, James; Rich, Jason; Diaz, Jason; Paniello, Randal C.; Nussenbaum, Brian; Adkins, Douglas R.

    2015-01-01

    We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally ...

  20. FEASIBILITY OF INDUCTION DOCETAXEL, CISPLATIN, 5-FLUOROURACIL, CETUXIMAB (TPF-C) FOLLOWED BY CONCURRENT CETUXIMAB RADIOTHERAPY FOR LOCALLY ADVANCED HEAD AND NECK SQUAMOUS CELL CARCINOMA

    OpenAIRE

    Nikolaos eCharalambakis; Vassilis eKouloulias; Helena eVaja; Dimitrios ePectasides; Theodoros eRampias; Theofanis eEconomopoulos; Panagiotis eKatsaounis; Spiros eSiolos; Valentina eBartzi; Christos ePerisanidis; Konstantinos eLaschos; Pavlos eMaragoudakis; Konstantinos ePrikas; Nikolaos ePapadimitriou; Nikolaos ePapadogeorgakis

    2013-01-01

    Purpose: To report our experience with a sequential regimen of induction TPF-C followed by radioimmunotherapy with cetuximab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Patients and Methods: Toxicity and outcome was retrospectively analyzed in 22 patients receiving sequential therapy with induction TPF-C followed by radioimmunotherapy between October 2008 and December 2011. Outcome was estimated using Kaplan-Meier analyses. In addition, we performed mutati...

  1. Akt activation synergizes with Trp53 loss in oral epithelium to produce a novel mouse model for head and neck squamous cell carcinoma

    OpenAIRE

    Moral, Marta; Segrelles, Carmen; Lara, M. Fernanda; Martinez-Cruz, Ana Belen; Lorz, Corina; Santos, Mirentxu; Garcia-Escudero, Ramon; Lu, Jerry; Kiguchi, Kaoru; Buitrago, Agueda; Costa, Clotilde; Saiz, Cristina; Rodriguez-Peralto, Jose L; Martinez-Tello, Francisco J; Rodriguez-Pinilla, Maria

    2009-01-01

    Head and neck squamous cell carcinoma is a common human neoplasia with poor prognosis and survival that frequently display Akt overactivation. Here we show that mice displaying constitutive Akt activity (myrAkt) in combination with Trp53 loss in stratified epithelia develop oral cavity tumors that phenocopy human HNSCC. The myrAkt mice develop oral lesions making it a possible model of human oral dysplasia. The malignant conversion of these lesions, which is hampered due to the induction of p...

  2. Moving towards personalised therapy in head and neck squamous cell carcinoma through analysis of next generation sequencing data

    DEFF Research Database (Denmark)

    Giefing, M; Wierzbicka, M; Szyfter, K;

    2016-01-01

    Personalised medicine tumour boards, which leverage genomic data to improve clinical management, are becoming standard for the treatment of many cancers. This paper is designed as a primer to assist clinicians treating head and neck squamous cell carcinoma (HNSCC) patients with an understanding...... of the discovery and functional impact of recurrent genetic lesions that are likely to influence the management of this disease in the near future. This manuscript integrates genetic data from publicly available array comparative genome hybridization (aCGH) and next-generation sequencing genetics databases...... to identify the most common molecular alterations in HNSCC. The importance of these genetic discoveries is reviewed and how they may be incorporated into clinical care decisions is discussed. Considerations for the role of genetic stratification in the clinical management of head and neck cancer are maturing...

  3. Analysis of death receptor 5 and caspase-8 expression in primary and metastatic head and neck squamous cell carcinoma and their prognostic impact.

    Directory of Open Access Journals (Sweden)

    Heath A Elrod

    Full Text Available Death receptor 5 (DR5 and caspase-8 are major components in the extrinsic apoptotic pathway. The alterations of the expression of these proteins during the metastasis of head and neck squamous cell carcinoma (HNSCC and their prognostic impact have not been reported. The present study analyzes the expression of DR5 and caspase-8 by immunohistochemistry (IHC in primary and metastatic HNSCCs and their impact on patient survival. Tumor samples in this study included 100 primary HNSCC with no evidence of metastasis, 100 primary HNSCC with lymph node metastasis (LNM and 100 matching LNM. IHC analysis revealed a significant loss or downregulation of DR5 expression in primary tumors with metastasis and their matching LNM compared to primary tumors with no evidence of metastasis. A similar trend was observed in caspase-8 expression although it was not statistically significant. Downregulation of caspase-8 and DR5 expression was significantly correlated with poorly differentiated tumors compared to moderately and well differentiated tumors. Univariate analysis indicates that, in HNSCC with no metastasis, higher expression of caspase-8 significantly correlated with better disease-free survival and overall survival. However, in HNSCC with LNM, higher caspase-8 expression significantly correlated with poorer disease-free survival and overall survival. Similar results were also generated when we combined both DR5 and caspase-8. Taken together, we suggest that both DR5 and caspase-8 are involved in regulation of HNSCC metastasis. Our findings warrant further investigation on the dual role of caspase-8 in cancer development.

  4. Cross talk Initiated by Endothelial Cells Enhances Migration and Inhibits Anoikis of Squamous Cell Carcinoma Cells through STAT3/Akt/ERK Signaling

    Directory of Open Access Journals (Sweden)

    Kathleen G. Neiva

    2009-06-01

    Full Text Available It is well known that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effect of endothelial cell-secreted factors on the phenotype and behavior of tumor cells. The hypothesis underlying this study is that endothelial cells initiate signaling pathways that enhance tumor cell survival and migration. Here, we observed that soluble mediators from primary human dermal microvascular endothelial cells induce phosphorylation of signal transducer and activator of transcription 3 (STAT3, Akt, and extracellular signal-regulated kinase (ERK in a panel of head and neck squamous cell carcinoma (HNSCC cells (OSCC-3, UM-SCC-1, UM-SCC-17B, UM-SCC-74A. Gene expression analysis demonstrated that interleukin-6 (IL- 6, interleukin-8 (CXCL8, and epidermal growth factor (EGF are upregulated in endothelial cells cocultured with HNSCC. Blockade of endothelial cell-derived IL-6, CXCL8, or EGF by gene silencing or neutralizing antibodies inhibited phosphorylation of STAT3, Akt, and ERK in tumor cells, respectively. Notably, activation of STAT3, Akt, and ERK by endothelial cells enhanced migration and inhibited anoikis of tumor cells. We have previously demonstrated that Bcl-2 is upregulated in tumor microvessels in patients with HNSCC. Here, we observed that Bcl-2 signaling induces expression of IL-6, CXCL8, and EGF, providing a mechanism for the upregulation of these cytokines in tumor-associated endothelial cells. This study expands the contribution of endothelial cells to the pathobiology of tumor cells. It unveils a new mechanism in which endothelial cells function as initiators of molecular crosstalks that enhance survival and migration of tumor cells.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-12-15

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

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

    International Nuclear Information System (INIS)

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

  7. 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...

  8. Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions stimulates a protective immune response

    OpenAIRE

    De Costa, Anna-Maria A.; Justis, Danielle N.; Schuyler, Corinne A.; M. Rita I. Young

    2012-01-01

    The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by immune evasion tactics often employed by carcinomas such as head and neck squamous cell carcinoma (HNSCC). The present study aims to determine if an immune response can be elicited by administering a DC vaccine during the premalignant stages of HNSCC, prior to development of immune escape. Mice treated with the carcinogen 4-nitroquinoline 1-oxide (4NQO) in drinking water develop premalignant oral lesions tha...

  9. A Naturally Occurring Feline Model of Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Jackie M. Wypij

    2013-01-01

    Full Text Available Despite advances in understanding cancer at the molecular level, timely and effective translation to clinical application of novel therapeutics in human cancer patients is lacking. Cancer drug failure is often a result of toxicity or inefficacy not predicted by preclinical models, emphasizing the need for alternative animal tumor models with improved biologic relevancy. Companion animals (dogs and cats provide an opportunity to capitalize on an underutilized and biologically relevant translational research model which allows spontaneous disease modeling of human cancer. Head and neck squamous cell carcinoma (HNSCC is a common cancer with a poor prognosis and limited clinical advancements in recent years. One potential novel spontaneous animal tumor model is feline oral squamous cell carcinoma (FOSCC. FOSCC and HNSCC share similar etiopathogenesis (tobacco and papillomavirus exposure and molecular markers (EGFR, VEGF, and p53. Both human and feline SCCs share similar tumor biology, clinical outcome, treatment, and prognosis. Future clinical trials utilizing FOSCC as a tumor model may facilitate translation of preclinical cancer research for human cancer patients.

  10. 人类乳头状瘤病毒感染与头颈部鳞状细胞癌%Human papillomavirus related head and neck squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    张洁莉

    2010-01-01

    大量基础和临床研究的证据显示,人类乳头状瘤病毒(HPV)感染和头颈部鳞状细胞癌(HNSCC)的发生发展有关,但两者间确切发病机制尚不明确.HPV表达E6和E7导致被感染细胞发生恶性转化是其主要的致癌机制.HPV阳性HNSCC对放化疗更为敏感,预后更好.HPV疫苗可能成为预防和治疗HNSCC的重要手段.%Accumulating evidence shows that human papillomavirus (HPV) may play a significant role in head and neck squamous cell carcinomas (HNSCC) initiation and development, however, the detailed mechanism remains unclear. It is possible that the malicious transformation of infected cells by HPV E6 and E7might contribute to development of HPV positive HNSCC. In order to give a full description of HPV positive HNSCC, this review will focus on HPV infection epidemiology, carcinogenesis mechanism and feasibility of HPV vaccine in cancer prevention/treatment.

  11. Osteoactivin Promotes Migration of Oral Squamous Cell Carcinomas.

    Science.gov (United States)

    Arosarena, Oneida A; Dela Cadena, Raul A; Denny, Michael F; Bryant, Evan; Barr, Eric W; Thorpe, Ryan; Safadi, Fayez F

    2016-08-01

    Nearly 50% of patients with oral squamous cell carcinoma (OSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell adhesion, migration, and invasion. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies. The aims were to determine how integrin interactions modulate OA-induced OSCC cell migration; and to investigate OA effects on cell survival and proliferation. We confirmed OA mRNA and protein overexpression in OSCC cell lines. We assessed OA's interactions with integrins using adhesion inhibition assays, fluorescent immunocytochemistry and co-immunoprecipitation. We investigated OA-mediated activation of mitogen-activated protein kinases (MAPKs) and cell survival. Integrin inhibition effects on OA-mediated cell migration were determined. We assessed effects of OA knock-down on cell migration and proliferation. OA is overexpressed in OSCC cell lines, and serves as a migration-promoting adhesion molecule. OA co-localized with integrin subunits, and co-immunoprecipitated with the subunits. Integrin blocking antibodies, especially those directed against the β1 subunit, inhibited cell adhesion (P = 0.03 for SCC15 cells). Adhesion to OA activated MAPKs in UMSCC14a cells and OA treatment promoted survival of SCC15 cells. Integrin-neutralizing antibodies enhanced cell migration with OA in the extracellular matrix. OA knock-down resulted in decreased proliferation of SCC15 and SCC25 cells, but did not inhibit cell migration. OA in the extracellular matrix promotes OSCC cell adhesion and migration, and may be a novel target in the prevention of HNSCC spread. J. Cell. Physiol. 231: 1761-1770, 2016. © 2015 Wiley Periodicals, Inc.

  12. Simultaneous Laryngeal Squamous Cell Carcinoma and Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Bighan Khademi

    2011-04-01

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

  13. The anti-EGFR antibody cetuximab sensitizes human head and neck squamous cell carcinoma cells to radiation in part through inhibiting radiation-induced upregulation of HIF-1α

    OpenAIRE

    Lu, Haiquan; Liang, Ke; Lu, Yang; Fan, Zhen

    2012-01-01

    In this study, we investigated the mechanisms underlying cetuximab-mediated radiosensitization of HNSCC. Irradiation of HNSCC cells upregulated hypoxia-inducible factor-1 alpha (HIF-1α) via a mechanism involving de novo synthesis of HIF-1α protein. Radiation-induced upregulation of HIF-1α was completely abolished by concurrent treatment of HNSCC cells with cetuximab. Experimental elevation of constitutively expressed HIF-1α abolished cetuximab-mediated radiosensitization in HNSCC cells, where...

  14. Effect of the Premalignant and Tumor Microenvironment on Immune Cell Cytokine Production in Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Sara D. [Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425 (United States); De Costa, Anna-Maria A. [Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425 (United States); Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425 (United States); Young, M. Rita I., E-mail: rita.young@va.gov [Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425 (United States); Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425 (United States); Medical Research Service (151), Ralph H. Johnson Veterans Affairs Medical Center, 109 Bee Street, Charleston, SC 29401 (United States)

    2014-04-02

    Head and neck squamous cell carcinoma (HNSCC) is marked by immunosuppression, a state in which the established tumor escapes immune attack. However, the impact of the premalignant and tumor microenvironments on immune reactivity has yet to be elucidated. The purpose of this study was to determine how soluble mediators from cells established from carcinogen-induced oral premalignant lesions and HNSCC modulate immune cell cytokine production. It was found that premalignant cells secrete significantly increased levels of G-CSF, RANTES, MCP-1, and PGE{sub 2} compared to HNSCC cells. Splenocytes incubated with premalignant supernatant secreted significantly increased levels of Th1-, Th2-, and Th17-associated cytokines compared to splenocytes incubated with HNSCC supernatant. These studies demonstrate that whereas the premalignant microenvironment elicits proinflammatory cytokine production, the tumor microenvironment is significantly less immune stimulatory and may contribute to immunosuppression in established HNSCC.

  15. 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.

  16. Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Kotowski, Ulana; Heiduschka, Gregor; Eckl-Dorna, Julia; Kranebitter, Veronika; Stanisz, Isabella; Brunner, Markus; Lill, Claudia; Thurnher, Dietmar [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Seemann, Rudolf [Medical University of Vienna, Departement of Cranio-, Maxillofacial- and Oral Surgery, Vienna (Austria); Schmid, Rainer [Medical University of Vienna, Department of Radiotherapy, Vienna (Austria)

    2015-01-10

    Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation. (orig.) [German] Cafestol ist ein Diterpen, das in der Kaffeebohne vorkommt und antikanzerogene Eigenschaften besitzt. Ziel der Studie war, die Wirkung von Cafestol auf Kopf-Hals-Tumorzelllinien zu untersuchen. Drei Kopf-Hals-Tumorzelllinien (SCC25, CAL27 und FaDu) wurden mit steigenden Cafestol-Dosen behandelt. Anschliessend fanden Kombinationsexperimente mit Cisplatin und Bestrahlung statt. Die Wechselwirkung zwischen den Substanzen und moegliche synergistische Wirkungen wurden mit dem Combination-Index analysiert. Koloniebildungstests wurden nach Bestrahlung mit 2, 4, 6 und 8 Gy durchgefuehrt. Apoptose wurde mittels Durchflusszytometrie gemessen. Die Behandlung der Kopf-Hals-Tumorzelllinien mit Cafestol fuehrt zu einer dosisabhaengigen Abnahme des Zellueberlebens und zur Induktion von Apoptose. Die Kombination von Cafestol mit Bestrahlung zeigt eine geringere

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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...

  19. Endothelial Interleukin-6 defines the tumorigenic potential of primary human cancer stem cells

    OpenAIRE

    Krishnamurthy, Sudha; Warner, Kristy A.; Dong, Zhihong; Imai, Atsushi; Nör, Carolina; Ward, Brent B.; Helman, Joseph I.; Taichman, Russell S.; Bellile, Emily L.; McCauley, Laurie K.; Polverini, Peter J.; Prince, Mark E.; Wicha, Max S.; Jacques E Nör

    2014-01-01

    Head and neck squamous cell carcinomas (HNSCC) contain a small sub-population of stem cells endowed with unique capacity to generate tumors. These cancer stem cells (CSC) are localized in perivascular niches and rely on crosstalk with endothelial cells for survival and self-renewal, but the mechanisms involved are unknown. Here, we report that stromal interleukin (IL)-6 defines the tumorigenic capacity of CSC sorted from primary human HNSCC and transplanted into mice. In search for the cellul...

  20. 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

  1. 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.

  2. miRNAs Signature in Head and Neck Squamous Cell Carcinoma Metastasis: A Literature Review

    Directory of Open Access Journals (Sweden)

    Soussan Irani

    2016-06-01

    Full Text Available Statement of the Problem: Head and neck cancers include epithelial tumors arising in the oral cavity, pharynx, larynx, paranasal sinuses, and nasal cavity. Metastasis is a hallmark of cancer. MicroRNAs (miRNAs are endogenous small non-coding RNAs involved in cell proliferation, development, differentiation and metastasis. It is believed that miRNA alterations correlate with initiation and progression of cancer cell proliferation or inhibition of tumorigenesis. Moreover, miRNAs have different roles in development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC. Altered expression of miRNAs could be novel molecular biomarkers for the definite diagnosis of cancer, metastatic site, cancer stage, and its progression. Purpose: The purpose of this review was to provide a comprehensive literature review of the role of miRNAs in head and neck cancer metastasis. Search strategy: A relevant English literature search in PubMed, ScienceDirect, and Google Scholar was performed. The keywords ‘miRNA’, ‘head and neck’, and ‘cancer’ were searched in title and abstract of publications; limited from 1990 to 2015. The inclusion criterion was the role of miRNAs in cancer metastasis. The exclusion criterion was the other functions of miRNAs in cancers. Out of 15221 articles, the full texts of 442 articles were retrieved and only 133 articles met the inclusion criteria. Conclusion: Despite the advances in cancer treatment, the mortality rate of HNSCC is still high. The potential applica-tion of miRNAs for cancer therapy has been demonstrated in many studies; miRNAs function as either tumor suppres-sor or oncogene. The recognition of metastamir and their targets may lead to better understanding of HNSCC oncogen-esis, and consequently, development of new therapeutic strategies which is a necessity in cancer treatment. Develop-ment of therapeutic agents based on miRNAs is a promising target.

  3. miRNAs Signature in Head and Neck Squamous Cell Carcinoma Metastasis: A Literature Review

    Science.gov (United States)

    Irani, Soussan

    2016-01-01

    Statement of the Problem Head and neck cancers include epithelial tumors arising in the oral cavity, pharynx, larynx, paranasal sinuses, and nasal cavity. Metastasis is a hallmark of cancer. MicroRNAs (miRNAs) are endogenous small non-coding RNAs involved in cell proliferation, development, differentiation and metastasis. It is believed that miRNA alterations correlate with initiation and progression of cancer cell proliferation or inhibition of tumorigenesis. Moreover, miRNAs have different roles in development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC). Altered expression of miRNAs could be novel molecular biomarkers for the definite diagnosis of cancer, metastatic site, cancer stage, and its progression. Purpose The purpose of this review was to provide a comprehensive literature review of the role of miRNAs in head and neck cancer metastasis. Search strategy A relevant English literature search in PubMed, ScienceDirect, and Google Scholar was performed. The keywords ‘miRNA’, ‘head and neck’, and ‘cancer’ were searched in title and abstract of publications; limited from 1990 to 2015. The inclusion criterion was the role of miRNAs in cancer metastasis. The exclusion criterion was the other functions of miRNAs in cancers. Out of 15221 articles, the full texts of 442 articles were retrieved and only 133 articles met the inclusion criteria. Conclusion Despite the advances in cancer treatment, the mortality rate of HNSCC is still high. The potential application of miRNAs for cancer therapy has been demonstrated in many studies; miRNAs function as either tumor suppressor or oncogene. The recognition of metastamir and their targets may lead to better understanding of HNSCC oncogenesis, and consequently, development of new therapeutic strategies which is a necessity in cancer treatment. Development of therapeutic agents based on miRNAs is a promising target. PMID:27284551

  4. 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....

  5. Neoadjuvant chemotherapy of cisplatin and fluorouracil regimen in head and neck squamous cell carcinoma: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    SU Yu-xiong; ZHENG Jia-wei; ZHENG Guang-sen; LIAO Gui-qing; ZHANG Zhi-yuan

    2008-01-01

    Background The benefit of neoadjuvant chemotherapy in the management of head and neck squamous cell carcinomas (HNSCC) still remains controversial. The aim of this meta-analysis is to evaluate the role of the neoadjuvant chemotherapy with the cisplatin and fluororacil (PF) regimen in enhancing the overall survival of and decreasing locoregional relapse and distant metastasis in HNSCC patients.Methods Medline and manual searches were performed to identify all published randomized controlled trials (RCTs) investigating the efficacy of the neoadjuvant chemotherapy with the PF regimen. Outcomes assessed by meta-analysis included Iocoregional relapse, distant metastasis, and overall survival. The odds ratio was the principle measurement of effect, which was calculated as the treatment group (chemotherapy plus Iocoregional treatment) versus the control group (Iocoregional treatment alone) and was presented as a point estimate with 95% confidence intervals (Cl).Results Eight RCTs were adopted for analysis. The meta-analysis showed that the odds ratio for the Iocoregional relapse was 0.92 (0.70-1.22, 95%Cl), which was not statistically significant. The odds ratios for distant metastasis and overall survival were 0.47 (0.33-0.68, 95% Cl) and 1.28 (1.01-1.62, 95% Cl) respectively, which were both statistically significant.Conclusions Neoadjuvant chemotherapy with the PF regimen in HNSCC patients has no effect on Iocoregional relapse. However, it shows a small but significant benefit in reducing distant metastasis and improving the overall survival.

  6. LIMD1 is more frequently altered than RB1 in head and neck squamous cell carcinoma: clinical and prognostic implications

    Directory of Open Access Journals (Sweden)

    Roy Anup

    2010-03-01

    Full Text Available Abstract Introduction To understand the role of two interacting proteins LIMD1 and pRB in development of head and neck squamous cell carcinoma (HNSCC, alterations of these genes were analyzed in 25 dysplastic head and neck lesions, 58 primary HNSCC samples and two HNSCC cell lines. Methods Deletions of LIMD1 and RB1 were analyzed along with mutation and promoter methylation analysis of LIMD1. The genotyping of LIMD1 linked microsatellite marker, hmlimD1, was done to find out any risk allele. The mRNA expression of LIMD1 and RB1 were analyzed by Q-PCR. Immunohistochemical analysis of RB1 was performed. Alterations of these genes were correlated with different clinicopathological parameters. Results High frequency [94% (78/83] of LIMD1 alterations was observed in the samples studied. Compare to frequent deletion and methylation, mutation of LIMD1 was increased during tumor progression (P = 0.007. Six novel mutations in exon1 and one novel intron4/exon5 splice-junction mutation were detected in LIMD1 along with a susceptible hmlimD1 (CA20 allele. Some of these mutations [42% (14/33] produced non-functional proteins. RB1 deletion was infrequent (27%. Highly reduced mRNA expression of LIMD1 (25.1 ± 19.04 was seen than RB1 (3.8 ± 8.09, concordant to their molecular alterations. The pRB expression supported this data. Tumors with LIMD1 alterations in tobacco addicted patients without HPV infection showed poor prognosis. Co-alterations of these genes led the worse patients' outcome. Conclusions Our study suggests LIMD1 inactivation as primary event than inactivation of RB1 in HNSCC development.

  7. [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

  8. 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.

  9. 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.

  10. Genetic alterations in head and neck squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Nagai M.A.

    1999-01-01

    Full Text Available The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations and tumor suppressor gene inactivation (loss of function mutations, leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.

  11. 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.

  12. 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.

  13. Membranous expression of Her3 is associated with a decreased survival in head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hong Seung-Mo

    2011-07-01

    Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC still remains a lethal malignancy benefiting from the identification of the new target for early detection and/or development of new therapeutic regimens based on a better understanding of the biological mechanism for treatment. The overexpression of Her2 and Her3 receptors have been identified in various solid tumors, but its prognostic relevance in HNSCC remains controversial. Methods Three hundred eighty-seven primary HNSCCs, 20 matching metasis and 17 recurrent HNSCCs were arrayed into tissue microarrays. The relationships between Her2 and Her3 protein expression and clinicopathological parameters/survival of HNSCC patients were analyzed with immunohistochemistry. Results Her3 is detected as either a cytoplasmic or a membranous dominant expression pattern whereas Her2 expression showed uniform membranous form. In primary tumor tissues, high membranous Her2 expression level was found in 104 (26.9% cases while positive membranous and cytoplasmic Her3 expression was observed in 34 (8.8% and 300 (77.5% samples, respectively. Membranous Her2 expression was significantly associated with histological grade (P = 0.021, as grade 2 tumors showed the highest positive expression. Membranous Her3 over-expression was significantly prevalent in metastatic tissues compared to primary tumors (P = 0.003. Survival analysis indicates that membranous Her3 expression is significantly associated with worse overall survival (P = 0.027 and is an independent prognostic factor in multivariate analysis (hazard ratio, 1.51; 95% confidence interval, 1.01-2.23; P = 0.040. Conclusions These results suggest that membranous Her3 expression is strongly associated with poor prognosis of patients with HNSCC and is a potential candidate molecule for targeted therapy.

  14. The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Heiduschka, G. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Comprehensive Cancer Center, Vienna (Austria); Medical University of Vienna, Clinical Pharmacology, Vienna (Austria); Lill, C.; Schneider, S.; Kotowski, U.; Thurnher, D. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Comprehensive Cancer Center, Vienna (Austria); Seemann, R. [Medical University of Vienna, Craniomaxillofacial and Oral Surgery, Vienna (Austria); Kornek, G. [Medical University of Vienna, Internal Medicine, Vienna (Austria); Schmid, R. [Medical University of Vienna, Radiotherapy and Radiobiology, Vienna (Austria)

    2014-05-15

    Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity. (orig.) [German] Durch ihre Rolle bei der Angiogenese sind Integrine ein attraktives Ziel in der onkologischen Forschung. Der derzeit vielversprechendste Inhibitor dieser Molekuele ist Cilengitide, welches bereits in klinischen Studien getestet wird. Dennoch ist erst wenig ueber die zellulaeren Vorgaenge bekannt, welche durch Cilengitide in Kopf-Hals-Karzinomen (HNSCC) insbesondere in Kombination mit Strahlentherapie und

  15. 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.

  16. 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.

  17. The small molecule inhibitor QLT0267 Radiosensitizes squamous cell carcinoma cells of the head and neck.

    Directory of Open Access Journals (Sweden)

    Iris Eke

    Full Text Available BACKGROUND: The constant increase of cancer cell resistance to radio- and chemotherapy hampers improvement of patient survival and requires novel targeting approaches. Integrin-Linked Kinase (ILK has been postulated as potent druggable cancer target. On the basis of our previous findings clearly showing that ILK transduces antisurvival signals in cells exposed to ionizing radiation, this study evaluated the impact of the small molecule inhibitor QLT0267, reported as putative ILK inhibitor, on the cellular radiation survival response of human head and neck squamous cell carcinoma cells (hHNSCC. METHODOLOGY/PRINCIPAL FINDINGS: Parental FaDu cells and FaDu cells stably transfected with a constitutively active ILK mutant (FaDu-IH or empty vectors, UTSCC45 cells, ILK(floxed/floxed(fl/fl and ILK(-/- mouse fibroblasts were used. Cells grew either two-dimensionally (2D on or three-dimensionally (3D in laminin-rich extracellular matrix. Cells were treated with QLT0267 alone or in combination with irradiation (X-rays, 0-6 Gy single dose. ILK knockdown was achieved by small interfering RNA transfection. ILK kinase activity, clonogenic survival, number of residual DNA double strand breaks (rDSB; gammaH2AX/53BP1 foci assay, cell cycle distribution, protein expression and phosphorylation (e.g. Akt, p44/42 mitogen-activated protein kinase (MAPK were measured. Data on ILK kinase activity and phosphorylation of Akt and p44/42 MAPK revealed a broad inhibitory spectrum of QLT0267 without specificity for ILK. QLT0267 significantly reduced basal cell survival and enhanced the radiosensitivity of FaDu and UTSCC45 cells in a time- and concentration-dependent manner. QLT0267 exerted differential, cell culture model-dependent effects with regard to radiogenic rDSB and accumulation of cells in the G2 cell cycle phase. Relative to corresponding controls, FaDu-IH and ILK(fl/fl fibroblasts showed enhanced radiosensitivity, which failed to be antagonized by QLT0267. A

  18. 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

  19. 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

  20. Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma

    Science.gov (United States)

    Rohrbach, Daniel J.; Rigual, Nestor; Arshad, Hassan; Tracy, Erin C.; Cooper, Michelle T.; Shafirstein, Gal; Wilding, Gregory; Merzianu, Mihai; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

    2016-01-01

    This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

  1. Expression of IL-1α correlates with distant metastasis in patients with head and neck squamous cell carcinoma

    Science.gov (United States)

    León, Xavier; Bothe, Carolina; García, Jacinto; Parreño, Matilde; Alcolea, Sonia; Quer, Miquel

    2015-01-01

    The presence of IL-1 in human cancers is associated with aggressive tumor biology but its prognostic value is unknown. We studied whether IL-1α expression is a prognostic marker of distant metastasis in patients with head and neck squamous cell carcinoma (HNSCC). IL-1α mRNA and protein levels were determined in tumor samples and cancer cell lines using RT-PCR and ELISA. The effects of constitutive IL-1α expression by tumor lines were characterized. IL-1α mRNA and protein secretion were higher in tumor samples from patients who later developed distant metastasis than in patients who did not. By using distant metastasis as a dependent variable, patients were classified into two categories of IL-1α transcript-levels. The high-IL-1α group had a significantly lower five-year distant metastasis-free survival than the low-IL-1α group [70.0% (CI 95%: 55.9-84.1%) vs 94.7% (CI 95%:90.2-99.2%)]. When IL-1α transcript-levels were combined with clinical factors related to tumor metastasis, the predictive power of the model increased significantly. Additionally, transcript levels of IL-1α correlated significantly with those of the IL-1 family genes and genes related to the metastatic process. IL-1 treatment of microvascular endothelial cells increased adhesion of HNSCC cells but no differences were found based on constitutive IL-1α expression by tumor cells. Nevertheless, IL-1α produced by tumor cells effectively increased their transmigration across the endothelium. We found a significant relationship between IL-1α expression and development of distant metastasis in HNSCC patients. IL-1α expression could help to define a subset of patients at high risk of distant metastasis who could benefit from adjuvant treatment. PMID:26460957

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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.

  8. Secondary oesophageal or gastric cancer in patients treated for head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Anja Rosenlund; Bjerring, Ole Steen; Godballe, Christian;

    2016-01-01

    SPM. CONCLUSION: In this study, we confirm that there is an elevated risk of developing oesophageal and gastric cancer in the Danish population of patients with a cancer in the supraglottic or hypopharyngeal region. Therefore, we recommend close follow-up of these patients and a low threshold......INTRODUCTION: Patients with head and neck squamous cell carcinoma (HNSCC) are at an elevated risk of developing second primary malignancies (SPM). Our objectives were to estimate the excess risk of oesophageal and gastric SPMs in patients with malignancies of the pharynx or larynx and, additionally.......004) and hypopharyngeal (OR = 3.9; p cancer compared with 3.4 years (95% CI: 3.1-4.3; range: 0.04-13.7) for patients without...

  9. 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

  10. 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.

  11. The rational design of specific peptide inhibitor against p38α MAPK at allosteric-site: a therapeutic modality for HNSCC.

    Directory of Open Access Journals (Sweden)

    Kamaldeep Gill

    Full Text Available p38α is a significant target for drug designing against cancer. The overproduction of p38α MAPK promotes tumorigenesis in head and neck squamous cell carcinoma (HNSCC. The ATP binding and an allosteric site referred as DFG are the key sites of the p38α mitogen activated protein kinase (MAPK exploited for the design of inhibitors. This study demonstrated design of peptide inhibitor on the basis of allosteric site using Glide molecular docking software and the biochemical analysis of the best modeled peptide. The best fitted tetrapeptide (FWCS in the allosteric site inhibited the pure recombinant and serum p38α of HNSCC patients by 74 and 72%, respectively. The potency of the peptide was demonstrated by its IC50 (4.6 nM and KD (3.41×10-10 M values, determined by ELISA and by surface plasmon resonance (SPR technology, respectively. The cell viability of oral cancer i.e. KB cell line was reduced in dose dependent manner by 60 and 97% by the treatment of peptide and the IC50 was 600 and 210 µM after 24 and 72 h incubation, respectively. Our result provides an insight for the development of a proficient small peptide as a promising anticancer agent targeting DFG site of p38α kinase.

  12. 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

  13. 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

  14. 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.

  15. Prevention of tumor growth driven by PIK3CA and HPV oncogenes by targeting mTOR signaling with metformin in oral squamous carcinomas expressing OCT3.

    Science.gov (United States)

    Madera, Dmitri; Vitale-Cross, Lynn; Martin, Daniel; Schneider, Abraham; Molinolo, Alfredo A; Gangane, Nitin; Carey, Thomas E; McHugh, Jonathan B; Komarck, Christine M; Walline, Heather M; William, William N; Seethala, Raja R; Ferris, Robert L; Gutkind, J Silvio

    2015-03-01

    Most squamous cell carcinomas of the head and neck (HNSCC) exhibit a persistent activation of the PI3K-mTOR signaling pathway. We have recently shown that metformin, an oral antidiabetic drug that is also used to treat lipodystrophy in HIV-infected (HIV(+)) individuals, diminishes mTOR activity and prevents the progression of chemically induced experimental HNSCC premalignant lesions. Here, we explored the preclinical activity of metformin in HNSCCs harboring PIK3CA mutations and HPV oncogenes, both representing frequent HNSCC alterations, aimed at developing effective targeted preventive strategies. The biochemical and biologic effects of metformin were evaluated in representative HNSCC cells expressing mutated PIK3CA or HPV oncogenes (HPV(+)). The oral delivery of metformin was optimized to achieve clinical relevant blood levels. Molecular determinants of metformin sensitivity were also investigated, and their expression levels were examined in a large collection of HNSCC cases. We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter. Coexpression of OCT3 and the mTOR pathway activation marker pS6 were observed in most HNSCC cases, including those arising in HIV(+) patients. Activation of the PI3K-mTOR pathway is a widespread event in HNSCC, including HPV(-) and HPV(+) lesions arising in HIV(+) patients, all of which coexpress OCT3. These observations may provide a rationale for the clinical evaluation of metformin to halt HNSCC development from precancerous lesions, including in HIV(+) individuals at risk of developing HPV(-) associated cancers.

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

    Directory of Open Access Journals (Sweden)

    Soares Fernando A

    2011-04-01

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

  17. HPV vaccination to prevent oropharyngeal carcinoma: What can be learned from anogenital vaccination programs?

    NARCIS (Netherlands)

    Takes, R.P.; Wierzbicka, M.; D'Souza, G.; Jackowska, J.; Silver, C.E.; Rodrigo, J.P.; Dikkers, F.G.; Olsen, K.D.; Rinaldo, A.; Brakenhoff, R.H.; Ferlito, A.

    2015-01-01

    Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was

  18. HPV vaccination to prevent oropharyngeal carcinoma : What can be learned from anogenital vaccination programs?

    NARCIS (Netherlands)

    Takes, Robert P.; Wierzbicka, Malgorzata; D'Souza, Gypsyamber; Jackowska, Joanna; Silver, Carl E.; Rodrigo, Juan P.; Dikkers, Frederik G.; Olsen, Kerry D.; Rinaldo, Alessandra; Brakenhoff, Ruud H.; Ferlito, Alfio

    2015-01-01

    Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was

  19. 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

  20. 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...

  1. 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.

  2. 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

  3. Phase I Study of IMRT and Molecular-Image Guided Adaptive Radiation Therapy for Advanced HNSCC

    Science.gov (United States)

    2016-06-08

    Salivary Gland Squamous Cell Carcinoma; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Oral Cavity

  4. 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.

  5. Association between FAT1 mutation and overall survival in patients with human papillomavirus–negative head and neck squamous cell carcinoma

    Science.gov (United States)

    Kim, Ki Tae; Kim, Bo‐Sung

    2016-01-01

    Abstract Background The purpose of this study was to characterize the mutation profile of FAT atypical cadherin 1 (FAT1) and determine the prognostic significance of FAT1 mutation for overall survival in patients with human papillomavirus (HPV)‐negative head and neck squamous cell carcinoma (HNSCC). Methods Data were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) data portals and used as discovery and validation sets. FAT1 mutational status was determined in 234 and 37 patients with HPV‐negative HNSCC, respectively, and overall survival analysis was performed. For comparison, HPV‐positive patients were also analyzed for overall survival. Results Most of the identified nonsynonymous somatic FAT1 mutations were loss‐of‐function mutations. FAT1 mutation was significantly associated with better overall survival in HPV‐negative patients from both the TCGA cohort (p = .026) and the ICGC cohort (p = .047), but not in HPV‐positive patients. Conclusion FAT1 mutational status is a strong independent prognostic factor in patients with HPV‐negative HNSCC. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E2021–E2029, 2016 PMID:26876381

  6. A comparative study of survival rates after treatment with induction chemotherapy or concurrent chemoradiotherapy in locoregionally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Since 1989 our treatment approach for head and neck squamous cell carcinoma (HNSCC) has involved comprehensive treatment with chemotherapy, radiation followed by surgery, if needed. Between 1989 and 2005 chemotherapy using fluorouracil and carboplatin div was administered as induction chemotherapy (ICT), and concurrent chemoradiotherapy (CCRT) was administered more recently between 2006 and 2011. In this study we compared the statistical difference in 3-year survival rates between the ICT group and CCRT group. The number of target patients was 137, all of which were previously untreated and suffered from locoregionally advanced HNSCC: 52 with Stage III, 78 with Stage IVA, 7 with Stage IVB. In the ICT and CCRT groups, 3-year cause-specific survival rates were 68.2% and 76.3% respectively, both of which were statistically not recessive compared to those in the other issues. Furthermore, the rate between the two groups was identified as significant for Stage III and not significant for Stage IV. In conclusion, the addition of new modalities for the treatment of far-advanced HNSCC should be mandatory. (author)

  7. The apparent diffusion coefficient of a primary lesion correlates with local failure of head and neck squamous cell carcinoma treated with radiotherapy. President award proceedings

    International Nuclear Information System (INIS)

    We prospectively investigated whether the value of the apparent diffusion coefficient (ADC) of a primary lesion prior to treatment correlated with local failure of head and neck squamous cell carcinoma (HNSCC) following radiotherapy. In 17 patients who underwent radiotherapy for primary HNSCC, we compared variables considered to affect local failure, including parameters related to magnetic resonance (MR) imaging, such as ADC and its alteration ratio, between cases of local failure and controls and analyzed survival among those patients in whom the variables differed or demonstrated association with local failure. We also retrospectively analyzed variables in a validation study of 40 patients. In the prospective study, pretreatment values of ADChigh (calculated with b-values of 300, 500, 750, and 1000 s/mm2) alone showed significant association with local failure (P=0.0186). In the validation study, pretreatment values of tumor volume (P=0.0217) and ADChigh (P=0.0001) were significantly associated with local failure. Pretreatment ADChigh was superior to pretreatment tumor volume regarding association with local failure. These results suggest that pretreatment values of both ADC obtained using high b-values and tumor volume correlate with local failure of HNSCC treated with radiotherapy. (author)

  8. Correlation of Choline/Creatine and Apparent Diffusion Coefficient values with the prognostic parameters of Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Razek, Ahmed Abdel Khalek Abdel; Nada, Nadia

    2016-04-01

    The aim of this study was to measure choline/creatine (Ch/Cr) levels through (1)H-MRS and apparent diffusion coefficient (ADC) values through diffusion-weighted MRI, and to correlate these values with the prognostic parameters of head and neck squamous cell carcinoma (HNSCC). The institutional review board approved this study and informed written consent was obtained from all study participants. A prospective study of 43 patients (31 men and 12 women; mean age, 65 years) with HNSCC was conducted. Single-voxel (1)H-MRS was performed at the tumor or metastatic cervical lymph node with point-resolved spectroscopy (PRESS) at TE = 135 ms. Diffusion-weighted MR images with b values of 0, 500 and 1000 s/mm(2) and contrast MRI of the head and neck were performed. The Ch/Cr levels and ADC values of HNSCC were calculated. The gross tumor volume (GTV) was also calculated. The degree of tumor differentiation was determined through pathological examination. The HNSCC Ch/Cr level was negatively correlated with the ADC value (r = -0.662, p = 0.001). There was a significant difference in the Ch/Cr and ADC values at different degrees of tumor differentiation (p = 0.003 and p = 0.001) and with different GTVs (p = 0.122 and p = 0.001). The following prognostic parameter categories were used: (i) poorly differentiated and undifferentiated versus well differentiated to moderately differentiated; and (ii) HNSCC with GTV 30 cm(3). The cut-off values for Cho/Cr and ADC for each category were 1.83, 0.95 and 1.94, 0.99, respectively, and the areas under the curve were 0.771, 0.967 and 0.726, 0.795, respectively, for each category. We conclude that the Ch/Cr levels determined using (1)H-MRS and the ADC values are well correlated with several prognostic parameters of HNSCC.

  9. 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.

  10. Association of drug transporter expression with mortality and progression-free survival in stage IV head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Rolf Warta

    Full Text Available Drug transporters such as P-glycoprotein (ABCB1 have been associated with chemotherapy resistance and are considered unfavorable prognostic factors for survival of cancer patients. Analyzing mRNA expression levels of a subset of drug transporters by quantitative reverse transcription polymerase chain reaction (qRT-PCR or protein expression by tissue microarray (TMA in tumor samples of therapy naïve stage IV head and neck squamous cell carcinoma (HNSCC (qRT-PCR, n = 40; TMA, n = 61, this in situ study re-examined the significance of transporter expression for progression-free survival (PFS and overall survival (OS. Data from The Cancer Genome Atlas database was used to externally validate the respective findings (n = 317. In general, HNSCC tended to lower expression of drug transporters compared to normal epithelium. High ABCB1 mRNA tumor expression was associated with both favorable progression-free survival (PFS, p = 0.0357 and overall survival (OS, p = 0.0535. Similar results were obtained for the mRNA of ABCC1 (MRP1, multidrug resistance-associated protein 1; PFS, p = 0.0183; OS, p = 0.038. In contrast, protein expression of ATP7b (copper transporter ATP7b, mRNA expression of ABCG2 (BCRP, breast cancer resistance protein, ABCC2 (MRP2, and SLC31A1 (hCTR1, human copper transporter 1 did not correlate with survival. Cluster analysis however revealed that simultaneous high expression of SLC31A1, ABCC2, and ABCG2 indicates poor survival of HNSCC patients. In conclusion, this study militates against the intuitive dogma where high expression of drug efflux transporters indicates poor survival, but demonstrates that expression of single drug transporters might indicate even improved survival. Prospectively, combined analysis of the 'transportome' should rather be performed as it likely unravels meaningful data on the impact of drug transporters on survival of patients with HNSCC.

  11. Prognostic Value of Metabolic Tumor Volume Measured by {sup 18F} FDG PET/CT in Locally Advanced Head and Neck Squamous Cell Carcinomas Treated by Surgery

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kyu Ho; Yoo, Ie Ryung; Han, Eun Ji; Kim, Yeon Sil; Kim, Gi Wom; Na, Sea Jung; Sun, Dong Il; Jung, So Lyung; Jung, Chan Kwon; Kim, Min Sik; Lee, So Yeon; Kim, Sung Hoon [The Cathholic Univ. of Korea, Seoul (Korea, Republic of)

    2011-03-15

    We assessed the prognostic value of metabolic tumor volume (MTV) measured using {sup 18F} fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) inpatients with locally advanced head and neck squamous cell carcinoma (HNSCC). We retrospectively reviewed 56 patients (51 men, five women; mean age 56.0{+-}8.8 years) who had locally advanced HNSCC and underwent FDG PET/CT for initial evaluation. All patients had surgical resection and radiotherapy with or without concurrent chemotherapy. The peak standardized uptake (SUV{sup peak)} and MTV of the target lesion, including primary HNSCC and metastatic cervical lymph nodes, were measured SUV{sup peak,} MTV, and clinico pathologic variables such as age, Eastern Cooperative Oncology Group (ECOG) performance status, pN stage, pT stage, TNM stage, histologic grade and treatment modality to disease free survival (DFS) and overall survival (OS). On the initial FDG PET/CT scans, the median SUV{sup peakw}as 7.8 (range, 1.8-19.0) and MTV was 17.0cm{sup 3(}range, 0.1-131.0cm{sup 3)}. The estimated 2 year DFS and OS rates were 67.2% and 81.8%. The cutoff points of SUV{sup peak6}.2 and MTV 20.7cm{sup 3w}ere the best discriminative values for predicting clinical outcome. MTV and ECOG performance status were significantly related to DFS and OS on univariate and multivariate analyses (P=0.05). The MTV obtained from initial FDG PET/CT scan is a significant prognostic factor for disease recurrence and mortality in locally advanced HNSCC treated with surgery and radiotherapy with or without chemotherapy.

  12. 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

  13. Activation of K(+) channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca(2+) ionophore-induced cell death.

    Science.gov (United States)

    Yin, Ming Zhe; Park, Seok-Woo; Kang, Tae Wook; Kim, Kyung Soo; Yoo, Hae Young; Lee, Junho; Hah, J Hun; Sung, Myung Hun; Kim, Sung Joon

    2016-01-01

    Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular Ca(2+) ([Ca(2+)]i)-dependent signaling affects the fate of cancer cells. Here we investigate the role of Ca(2+)-activated K(+) channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of different cell lines; SNU-1076, OSC-19 and HN5. Treatment with 1 µM ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of Ca(2+)-activated Cl(-) channels (Ano-1) and Ca(2+)-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward K(+) current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Consistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the Ca(2+) overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC. PMID:26807020

  14. 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...

  15. Paired-agent imaging for resection during surgery (PAIRS) of head and neck squamous cell carcinomas (Conference Presentation)

    Science.gov (United States)

    Samkoe, Kimberley S.; Tichauer, Kenneth M.; Chen, Eunice; Gunn, Jason R.; Hoopes, P. Jack; Wells, Wendy A.; Hasan, Tayyaba; Pogue, Brian W.

    2016-03-01

    Ninety percent of patients with head and neck squamous cell carcinomas (HNSCC) have overexpression of epidermal growth factor receptor (EGFR), which is correlated with poor prognosis. Complete surgical resection of HNSCC tumors has a large impact on patient survival, where detection of tumor at or close to surgical margins increases the risk of death at 5-years by 90%. In addition, large surgical margins can greatly increase the morbidity experienced by the patient due to functional and cosmetic damage of oral and facial structures. Single fluorescence targeting agents are often used for tumor detection in in vivo pre-clinical imaging; however, the arising signal is qualitative at best because it is a complex mixture of vascular perfusion, vascular leakage, inhibited lymphatic clearance, and receptor binding. In vivo ratiometric receptor concentration imaging (RCI) allows quantification of receptor expression (hence identification of cancerous tissue) by utilizing co-administered paired-agents consisting of a targeted agent and non-targeted perfusion agent to reference the plasma delivery and leakage. A panel of HNSCC tumors with varying levels of EGFR expression (SCC-15 >SCC-25 > SCC-09) have been imaged using ABY-029, a clinically relevant anti-EGFR affibody labeled with IRDye 800CW, and affibody control imaging agent labeled with IRDye 680RD. RCI maps of in vivo tissue have been created and are spatially correlated with EGFR and CD31 immunohistochemistry and basic H and E staining. The RCI threshold parameters for distinguishing tumor from normal tissues (skin and muscle) and the accuracy of margin detection in these tumors will be presented. RCI surgical resection will be further developed using a novel multi-channel, gated fluorescence-guided surgery (FGS) imaging system that is capable of performing RCI in normal room light.

  16. FDG-PET/CT in the Assessment of Treatment Response after Oncologic Treatment of Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    Keski-Säntti, Harri; Mustonen, Timo; Schildt, Jukka; Saarilahti, Kauko; Mäkitie, Antti A

    2014-01-01

    BACKGROUND In many centers, 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used to monitor treatment response after definitive (chemo)radiotherapy [(C)RT] for head and neck squamous cell carcinoma (HNSCC), but its usefulness remains somewhat controversial. We aimed at assessing the accuracy of FDG-PET/CT in detecting residual disease after (C)RT. METHOD All HNSCC patients with FDG-PET/CT performed to assess treatment response 10–18 weeks after definitive (C)RT at our institution during 2008–2010 were included. The patient charts were reviewed for FDG-PET/CT findings, histopathologic findings, and follow-up data. The median follow-up time for FDG-PET/CT negative patients was 26 months. RESULTS Eighty-eight eligible patients were identified. The stage distribution was as follows: I, n = 1; II, n = 15; III, n = 17; IV, n = 55. The negative predictive value, positive predictive value, specificity, sensitivity, and accuracy of FDG-PET/CT in detecting residual disease were 87%, 81%, 94%, 65%, and 85%, respectively. The corresponding specific figures for the primary tumor site were 91%, 71%, 94%, 59%, and 86% and for the neck 93%, 100%, 100%, 75%, and 94%, respectively. CONCLUSIONS In patients who have received definitive (C)RT for HNSCC, post-treatment FDG-PET/CT has good potential to guide clinical decision-making. Patients with negative scan can safely be followed up clinically only, while positive scan necessitates tissue biopsies or a neck dissection to rule out residual disease. PMID:25210484

  17. Impact of comorbidity on treatment outcome in head and neck squamous cell carcinoma – A systematic review

    International Nuclear Information System (INIS)

    The significant association with tobacco and alcohol combined with advanced age at time of diagnosis predispose head and neck squamous cell carcinoma (HNSCC) patients to increased risk of comorbidities. The presence of comorbidity affects treatment, treatment selection and subsequent outcome. Multiple studies have demonstrated comorbidity to be a strong prognostic factor for survival, and therefore comorbidity can be a major confounder in clinical trials. This review provides a summary of the current literature on comorbidity in head and neck cancer, measurements of comorbidity, the impact of comorbidity on treatment, treatment selection, and survival. A systematic search was performed in six electronic databases. In all, 31 papers were selected for this review. A meta-analysis on the prognostic impact of comorbidity was performed including 10 studies. Furthermore, 21 studies concerning comorbidity were reviewed. Several valid indices to classify comorbidity were described in the literature, none proven to be superior over the other. The prevalence of comorbidity increased with age and the presence of comorbidity influenced treatment and treatment selection. Furthermore, comorbidity was associated with lower socio economic status and increased the risk of early retirement after treatment. The meta-analysis on comorbidity as a prognostic factor, including 22,932 patients, showed that overall survival was significantly worsened among patients with comorbidity (HR = 1.38 (1.32–1.43)). Increasing comorbidity-score was associated with increased risk of death. Comorbidity is important in HNSCC and significantly impacts on overall survival. Trials concerning HNSCC should always include information on comorbidity and randomized trials should stratify patients according to comorbidity in order to avoid bias in the study

  18. 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...

  19. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

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

  20. Down regulation of E-Cadherin (ECAD - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx

    Directory of Open Access Journals (Sweden)

    Studer Gabriela

    2011-06-01

    Full Text Available Abstract Background Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. Objectives To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease. Methods E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue, 10 tumours in the oropharynx (8.3%. Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS. These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance. Results pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (p = 0.018 and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (p = 0.005 in univariate and multivariate analysis. Conclusion These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx. Level of evidence: 2b

  1. 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 ...

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. Anti EGFR therapy in the treatment of non-metastatic head and neck squamous cell carcinoma: The current evidence

    Directory of Open Access Journals (Sweden)

    Rony Benson

    2016-09-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC accounts for a large oncologic burden in the developing countries. In patients with locally advanced head and neck cancer multimodality treatment is warranted. Radiation therapy with concurrent chemotherapy has long been considered the standard for patients with disease involving the oropharynx, larynx and hypopharynx. However, addition of chemotherapy to radiotherapy increases treatment related toxicity by many folds and compliance rates decrease. In this context a systemic therapy, which when used concurrent with radiation with favorable toxicity profile is of great importance for improving disease control in locally advanced HNSCC. Anti-epithelial growth factor receptor targeted therapy emerged as a potential treatment option. In recent years many trials were conducted to find the optimum treatment option with the combination of these targeted agents. The initial trials showed excellent results with minimal morbidity and led to great enthusiasm across the globe to incorporate these regimens as a standard of care. However, subsequently many trials failed to maintain such results and now there is little agreement to the initial results achieved with these drugs. Based on the current evidence we cannot recommend the replacement of cisplatin with targeted therapy in concurrent setting. It may be considered in patients with altered renal parameters, hypersensitivity or intolerance to cisplatin. The addition of targeted therapy in addition to chemotherapy in the concurrent setting can’t also be recommended as the benefit is doubtful and is associated with a significant increase in toxicity.

  8. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells

    OpenAIRE

    Krishnamurthy, Sudha; Dong, Zhihong; Vodopyanov, Dmitry; Imai, Atsushi; Helman, Joseph I.; Prince, Mark E.; Wicha, Max S.; Jacques E Nör

    2010-01-01

    Recent studies have demonstrated that cancer stem cells play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). However, little is known about functional interactions between head and neck cancer stem-like cells (CSC) and surrounding stromal cells. Here, we used Aldehyde Dehydrogenase activity and CD44 expression to sort putative stem cells from primary human HNSCC. Implantation of 1,000 CSC (ALDH+CD44+Lin−) led to tumors in 13 (out of 15) mice, while 10,...

  9. 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.

  10. p16 (INK4a) has clinicopathological and prognostic impact on oropharynx and larynx squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Silva, S.D. [Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia, Hospital A.C. Camargo, São Paulo, SP (Brazil); Department of Oncology, Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Department of Otolaryngology-Head and Neck Surgery, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Nonogaki, S. [Departamento de Anatomia Patológica, Hospital A.C. Camargo, São Paulo, SP (Brazil); Soares, F.A. [Departamento de Anatomia Patológica, Hospital A.C. Camargo, São Paulo, SP (Brazil); Departamento de Estomatologia, Faculdade de Odontologia, Universidade de São Paulo, São Paulo, SP (Brazil); Kowalski, L.P. [Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia, Hospital A.C. Camargo, São Paulo, SP (Brazil)

    2012-09-07

    CDKN2A encodes proteins such as p16 (INK4a), which negatively regulate the cell-cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur frequently in cancer. Although p16 (INK4a) may be involved in tumor progression, the clinical impact and prognostic implications in head and neck squamous cell carcinoma (HNSCC) are controversial. The objective of this study was to evaluate the frequency of the immunohistochemical expression of p16 (INK4a) in 40 oropharynx and 35 larynx from HNSCC patients treated in a single institution and followed-up at least for 10 years in order to explore potential associations with clinicopathological outcomes and prognostic implications. Forty cases (53.3%) were positive for p16 (INK4a) and this expression was more intense in non-smoking patients (P = 0.050), whose tumors showed negative vascular embolization (P = 0.018), negative lymphatic permeation (P = 0.002), and clear surgical margins (P = 0.050). Importantly, on the basis of negative p16 (INK4a) expression, it was possible to predict a probability of lower survival (P = 0.055) as well as tumors presenting lymph node metastasis (P = 0.050) and capsular rupture (P = 0.0010). Furthermore, increased risk of recurrence was observed in tumors presenting capsular rupture (P = 0.0083). Taken together, the alteration in p16 (INK4a) appears to be a common event in patients with oropharynx and larynx squamous cell carcinoma and the negative expression of this protein correlated with poor prognosis.

  11. 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,

  12. 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

  13. Retrospective analysis of concurrent chemoradiotherapy for head and neck squamous-cell carcinoma: preliminary experience from ABC School of Medicine, Santo Andre, Sao Paulo State, Brazil; Avaliacao retrospectiva do tratamento quimiorradioterapico concomitante em carcinoma epidermoide de cabeca e pescoco: experiencia preliminar da Faculdade de Medicina do ABC, Santo Andre, SP

    Energy Technology Data Exchange (ETDEWEB)

    Borba Junior, Antonio Freitas [Faculdade de Medicina do ABC, Santo Andre, SP (Brazil). Dept. de Oncologia Clinica; Giglio, Auro del [Faculdade de Medicina do ABC, Santo Andre, SP (Brazil). Dept. de Hematologia e Oncologia]. E-mail: sandrabr@netpoint.com.br; Philbert, Paula Lajolo; Kaliks, Rafael [Faculdade de Medicina do ABC, Santo Andre, SP (Brazil). Hospital de Ensino

    2005-07-01

    Background: concurrent chemoradiotherapy constitutes an option for head and neck squamous-cell carcinoma (HNSCC) treatment. Although we found a high incidence of this tumor in our population, we do not have so far results reported for the Brazilian population. Methods: medical records from HNSCC patients who ere treated with concurrent chemoradiotherapy between January 2001 to June 2004 were systematically reviewed. Results: twenty-two HNSCC patients were treated with chemoradiotherapy. The median age was 56 years. The primary tumor site was located in the oropharynx in 11, the larynx in 9 and hypopharynx in 2 patients. Most of the patients (86%) presented with stage III or IV disease. 19 (86%) patients were treated with Cisplatin 100 mg/m{sup 2} D1-22-43, and 3 (14%) patients used Cisplatin 20 mg/m{sup 2} weekly, concurrent with radiotherapy. Hematological and renal toxicity grade 3 or higher was seen in 58% and 10% patients, respectively. Eleven patients achieved a complete response and 8 a partial response. Median disease-free survival was 10 months and median overall survival was 25 months. (author)

  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. [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

  16. 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...

  17. 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.

  18. Safety and efficacy of quadrapeutics versus chemoradiation in head and neck carcinoma xenograft model.

    Science.gov (United States)

    Lukianova-Hleb, Ekaterina Y; Kim, Yoo-Shin; Aryasomayajula, Bhawani; Boulikas, Teni; Phan, Jack; Hung, Mien-Chie; Torchilin, Vladimir P; O'Neill, Brian E; Lapotko, Dmitri O

    2015-01-01

    Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard chemoradiation and quadrapeutics using identical drug and radiation doses. We applied liposomal cisplatin or doxorubicin, colloidal gold, near-infrared laser pulses and radiation, all at low safe doses. The final evaluation used a xenograft model of HNSCC. Quadrapeutics enhanced standard chemoradiation in vitro by reducing head and neck cancer cell proliferation by 1000-fold, inhibiting tumor growth in vivo by 34-fold and improving animal survival by 5-fold, and reducing the side effects to a negligible level. In quadrapeutics, we observed an "inversion" of the drug efficacy of two standard drugs: doxorubicin, a low efficacy drug for the cancers studied, was two times more efficient than cisplatin, the first choice drug in clinic for HNSCC. The radical therapeutic gain of quadrapeutics resulted from the intracellular synergy of the four components employed which we administered in a specific sequence, while the reduction in the toxicity was due to the low doses of all four components. The biodistribution, safety and efficacy data for quadrapeutics in HNSCC ensure its high translational potential and justify the possibility of clinical trials. PMID:26885444

  19. 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.

  20. 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.

  1. Randomized phase III trial (GORTEC 98-03) comparing re-irradiation plus chemotherapy versus methotrexate in patients with recurrent or a second primary head and neck squamous cell carcinoma, treated with a palliative intent

    International Nuclear Information System (INIS)

    Purpose: This randomized phase III trial investigated the potential benefit of concurrent re-irradiation, fluorouracil and hydroxyurea versus methotrexate for patients treated with palliative intent for recurrent or second primary head and neck squamous cell carcinoma (HNSCC) in previously irradiated area. Patients and methods: Patients with recurrent HNSCC or a second primary not amenable to curative-intent treatment were randomized to the R-RT arm (concurrent re-irradiation, fluorouracil and hydroxyurea) or to the Ch-T arm (methotrexate). The primary endpoint was overall survival (OS). Due to a very slow accrual, the trial was closed after inclusion of 57 patients. Results: Fifty-seven patients were included. All patients died in the two arms with a maximal follow-up of 5 years. Although four complete responses were achieved in R-RT arm, (none in Ch-T arm) re-irradiation did not improve OS compared with methotrexate (23% versus 22% at 1 year, NS). Sixteen patients experienced clinical grade ≥3 late toxicities (>6 months), 11 in R-RT arm and five in Ch-T arm. Conclusions: Premature discontinuation of the trial did not allow us to draw firm conclusions. However, there was no suggestion that concurrent re-irradiation, fluorouracil and hydroxyurea improved OS compared to methotrexate alone in patients treated with palliative intent for a recurrent or second primary HNSCC.

  2. 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.

  3. The effect of red-allotrope selenium nanoparticles on head and neck squamous cell viability and growth.

    Science.gov (United States)

    Hassan, Christopher E; Webster, Thomas J

    2016-01-01

    Given their low toxicity and natural presence in the human diet, selenium nanoparticles have been established as potential candidates for the treatment of numerous cancers. Red-allotrope selenium nanoparticles (rSeNPs) were synthesized and characterized in this study. Head and neck squamous cell carcinoma (HNSCC) and human dermal fibroblast (HDF) cells were cultured and exposed to rSeNPs at concentrations ranging from 0.01 to 100 μg rSeNP/mL media for 1-3 days. The toxicity of rSeNP toward HNSCC and HDFs was analyzed. Results indicated that the particles were approximately four times as cytotoxic toward HNSCC compared to HDFs, with their respective IC50 values at 19.22 and 59.61 μg rSeNP/mL media. Using statistical analysis, an effective dosage range for killing HNSCC cells while simultaneously minimizing damage to HDFs over a 3-day incubation period was established at 20-55 μg rSeNP/mL media. Observations showed that doses of rSeNP lysosomes and mitochondria. Analysis of cell morphology showed that the rSeNPs primarily induced HNSCC apoptosis. Collectively, these results indicated that rSeNPs are a promising option for treating HNSCC without adversely affecting healthy cells and without resorting to the use of harmful chemotherapeutics. PMID:27536104

  4. 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.

  5. Antisense inhibition of ATM gene enhances the radiosensitivity of head and neck squamous cell carcinoma in mice

    Directory of Open Access Journals (Sweden)

    Zheng Xuelian

    2008-10-01

    Full Text Available Abstract Background Treatment failure after radiotherapy of head and neck squamous cell carcinoma (HNSCC could be a significant problem. Our objective is to sensitize SCCVII cells to ionizing radiation in vitro and in vivo through inhibiting ATM expression using antisense oligodeoxynucleotides (AS-ODNs, and investigate the potential mechanism of radiosensitization. Methods We designed and synthesized AS-ODNs that target ATM mRNA to reduce the ATM expression. The influence on the expression of ATM mRNA and protein in SCCVII cells were analysed by real-time quantitative PCR and western blotting respectively. Clonogenic survival assay was performed to detect the survival ability of SCCVII cells after irradiation, while flow cytometry used to analyse the cell cycle and apoptosis. The volume of solid tumors generated with SCCVII cells was measured, and cell apoptosis was analysed by TUNEL assay after irradiation. Results The relative ATM mRNA and protein expression in SCCVII cells treated with ATM AS-ODNs were decreased to 25.7 ± 3.1% and 24.1 ± 2.8% of that in untreated cells respectively (P P P P P Conclusion Inhibition of ATM expression sensitized SCCVII cells to ionizing radiation in vitro and in vivo. The potential mechanism should be the defective G2/M cell cycle checkpoint control and enhanced radiation-induced apoptosis.

  6. Tbx3 represses PTEN and is over-expressed in head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Burgucu Durmus

    2012-10-01

    Full Text Available Abstract Background Despite advances in diagnostic and treatment strategies, head and neck squamous cell cancer (HNSCC constitutes one of the worst cancer types in terms of prognosis. PTEN is one of the tumour suppressors whose expression and/or activity have been found to be reduced in HNSCC, with rather low rates of mutations within the PTEN gene (6-8%. We reasoned that low expression levels of PTEN might be due to a transcriptional repression governed by an oncogene. Tbx2 and Tbx3, both of which are transcriptional repressors, have been found to be amplified or over-expressed in various cancer types. Thus, we hypothesize that Tbx3 may be over expressed in HNSCC and may repress PTEN, thus leading to cancer formation and/or progression. Methods Using immunohistochemistry and quantitative PCR (qPCR, protein and mRNA levels of PTEN and Tbx3 were identified in samples excised from cancerous and adjacent normal tissues from 33 patients who were diagnosed with HNSCC. In addition, HeLa and HEK cell lines were transfected with a Tbx3 expressing plasmid and endogenous PTEN mRNA and protein levels were determined via qPCR and flow cytometry. Transcription assays were performed to demonstrate effects of Tbx3 on PTEN promoter activity. Mann–Whitney, Spearman’s Correlation and Wilcoxon signed-rank tests were used to analyze the data. Results We demonstrate that in HNSCC samples, Tbx3 mRNA levels are increased with respect to their normal tissue counterparts (p Conclusions We show that Tbx3 is up-regulated in tissue samples of HNSCC patients and that Tbx3 represses PTEN transcription. Thus, our data not only reveals a new mechanism that may be important in cancer formation, but also suggests that Tbx3 can be used as a potential biomarker in cancer.

  7. 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.

  8. 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 ...

  9. 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

  10. 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

  11. Head and Neck Cancer Stem Cells

    OpenAIRE

    Krishnamurthy, S.; Nör, J.E.

    2012-01-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signalin...

  12. 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

  13. 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

  14. Human papilloma virus (HPV) modulation of the HNSCC epigenome.

    Science.gov (United States)

    Stephen, Josena K; Worsham, Maria J

    2015-01-01

    Currently, the human papilloma virus (HPV), in addition to tobacco and alcohol, is considered another independent risk factor for oropharyngeal squamous head and neck cancer (OPSCC), where the prevalence of HPV-16 increases to 50-90 % for the oropharynx. Also, incidence and mortality in head and neck SCC (HNSCC) continue to be higher in African Americans (AA) than in Caucasian Americans (CA). A recent study found that poorer survival outcomes for AA versus CA with oropharyngeal tumors were attributable to racial differences in the prevalence of HPV positive (+) tumors; HPV negative (-) AA and CA patients had similar outcomes (Settle et al., Cancer Prev Res (Phila) 2:776-781, 2009). Evidence indicates that a HPV+ diagnosis has significant prognostic implications; these patients have at least half the risk of death when compared with the HPV- patient, due in part to a better response to chemoradiotherapy (Fakhry et al., J Natl Cancer Inst 100:261-269, 2008).Epigenetic events of promoter hypermethylation are emerging as promising molecular strategies for cancer detection, representing tumor-specific markers occurring early in tumor progression. HPV infection is now recognized to play a role in the pathogenesis of OPSCC, where HPV+ and HPV- patients appear to be clinically and biologically distinct with reported genome-wide hypomethylation and promoter hypermethylation in HPV+ HNSCC tumors. A recent study from our group applying pathway analysis to investigate the biological role of the differentially methylated genes in HPV+ and HPV- HNSCC reported 8 signal transduction pathways germane to HNSCC (Worsham et al., Otolaryngol Head Neck Surg 149:409-416, 2013).

  15. FEASIBILITY OF INDUCTION DOCETAXEL, CISPLATIN, 5-FLUOROURACIL, CETUXIMAB (TPF-C FOLLOWED BY CONCURRENT CETUXIMAB RADIOTHERAPY FOR LOCALLY ADVANCED HEAD AND NECK SQUAMOUS CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Nikolaos eCharalambakis

    2013-01-01

    Full Text Available Purpose: To report our experience with a sequential regimen of induction TPF-C followed by radioimmunotherapy with cetuximab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC. Patients and Methods: Toxicity and outcome was retrospectively analyzed in 22 patients receiving sequential therapy with induction TPF-C followed by radioimmunotherapy between October 2008 and December 2011. Outcome was estimated using Kaplan-Meier analyses. In addition, we performed mutation analysis for PIK3CA genes and high-risk HPV-DNA detection using PCR. Results: Median follow-up was 16 months. Six patients were TNM Stage III, 15 patients IV (IVA or IVB and 1 patient Stage II with bulky disease. During TPF-C, Grade 3 and 4 toxicities occurred in 8 patients (36.4%, dose modifications in 7 (31.8%, delays in 1 (4.5%, and unplanned admissions in 5 (22.7%. Clinical tumor response was documented in 18 of the 21 patients who completed at least 3 cycles of TPF-C (85.7% with 3 patients developing complete response and 15 partial responses. Grade 3/4 mucositis was observed in 6 (31.6% patients. At a median follow up of 19 months, 13 patients were alive and 9 (40.9% had died including 7 patients as a result of disease persistence or recurrence and two as a result of unrelated causes. PIK3CA mutations were not identified and our 2 oropharynx cases were HPV negative.Conclusions: The combination of induction TPF-C with concurrent cetuximab radioimmunotherapy in patients with locally advanced HNSCC is tolerable, with encouraging efficacy.Keywords: HNSCC, TPF-C, cetuximab radiotherapy, toxicity and outcome, mutation analysis, PIK3CA, HPV-DNA.

  16. A prospective clinical study of {sup 18}F-FAZA PET-CT hypoxia imaging in head and neck squamous cell carcinoma before and during radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Servagi-Vernat, Stephanie [Institut de Recherche Clinique (IREC), Universite catholique de Louvain, St-Luc University Hospital, Department of Radiation Oncology and Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Brussels (Belgium); University Hospital Jean Minjoz, Department of Radiation Oncology, Besancon (France); Differding, Sarah; Labar, Daniel; Bol, Anne; Lee, John A.; Gregoire, Vincent [Institut de Recherche Clinique (IREC), Universite catholique de Louvain, St-Luc University Hospital, Department of Radiation Oncology and Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Brussels (Belgium); Hanin, Francois-Xavier [Institut de Recherche Clinique (IREC), Universite catholique de Louvain, St-Luc University Hospital, Department of Nuclear Medicine and Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Brussels (Belgium)

    2014-08-15

    Hypoxia in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis and outcome. {sup 18}F-Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within tumor. The aim of this study was to evaluate the use of {sup 18}F-FAZA-PET for assessment of hypoxia before and during radiation therapy. Twelve patients with locally advanced HNSCC underwent {sup 18}F-FAZA-PET scans before and at fraction 7 and 17 of concomitant chemo-radiotherapy. A hypoxic voxel was defined as a voxel expressing a standardized uptake value (SUV) equal or above the SUV{sub mean} of the posterior contralateral neck muscles plus three standard deviations. The fractional hypoxic volume fraction (FHV) and the spatial move of hypoxic volumes during treatment were analyzed. A hypoxic volume could be identified in ten patients before treatment. FAZA-PET FHV varied from 0 to 54.3 % and from 0 to 41.4 % in the primary tumor and in the involved node, respectively. Six out of these ten patients completed all the FAZA-PET-computed tomography (CT) during the radiotherapy. In all patients, FHV and SUV{sub max} values decreased. All patient presented a spatial move of hypoxic volume, but only three patients had newborn hypoxic voxels after 17 fractions. This study indicated that {sup 18}F-FAZA-PET could be used to identify and quantify tumor hypoxia before and during concomitant radio-chemotherapy in patients with locally advanced HNSCC. In addition to the information on prognostic value, the use of {sup 18}F-FAZA-PET allowed the delineation of hypoxic volumes for dose escalation protocols. However, due to fluctuation of hypoxia during treatment, repeated scan will have to be performed (i.e. adaptive radiotherapy). (orig.)

  17. Activation of EGFR promotes squamous carcinoma SCC10A cell migration and invasion via inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin.

    Science.gov (United States)

    Zuo, Jian-Hong; Zhu, Wei; Li, Mao-Yu; Li, Xin-Hui; Yi, Hong; Zeng, Gu-Qing; Wan, Xun-Xun; He, Qiu-Yan; Li, Jian-Huang; Qu, Jia-Quan; Chen, Yu; Xiao, Zhi-Qiang

    2011-09-01

    EGFR is a potent stimulator of invasion and metastasis in head and neck squamous cell carcinomas (HNSCC). However, the mechanism by which EGFR may stimulate tumor cell invasion and metastasis still need to be elucidated. In this study, we showed that activation of EGFR by EGF in HNSCC cell line SCC10A enhanced cell migration and invasion, and induced loss of epitheloid phenotype in parallel with downregulation of E-cadherin and upregulation of N-cadherin and vimentin, indicating that EGFR promoted SCC10A cell migration and invasion possibly by an epithelial to mesenchymal transition (EMT)-like phenotype change. Interestingly, activation of EGFR by EGF induced production of matrix metalloproteinase-9 (MMP-9) and soluble E-cadherin (sE-cad), and knockdown of MMP-9 by siRNA inhibited sE-cad production induced by EGF in SCC10A. Moreover, both MMP-9 knockdown and E-cadherin overexpression inhibited cell migration and invasion induced by EGF in SCC10A. The results indicate that EGFR activation promoted cell migration and invasion through inducing MMP-9-mediated degradation of E-cadherin into sE-cad. Pharmacologic inhibition of EGFR, MEK, and PI3K kinase activity in SCC10A reduced phosphorylated levels of ERK-1/2 and AKT, production of MMP-9 and sE-cad, cell migration and invasion, and expressional changes of EMT markers (E-cadherin and N-cadherin) induced by EGF, indicating that EGFR activation promotes cell migration and invasion via ERK-1/2 and PI3K-regulated MMP-9/E-cadherin signaling pathways. Taken together, the data suggest that EGFR activation promotes HNSCC SCC10A cell migration and invasion by inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin into sE-cad related to activation of ERK-1/2 and PI3K signaling pathways.

  18. Head and Neck Cancer Stem Cells: From Identification to Tumor Immune Network.

    Science.gov (United States)

    Dionne, L K; Driver, E R; Wang, X J

    2015-11-01

    Head and neck squamous cell carcinoma (HNSCC) is the most common form of head and neck cancer. Annually, more than half a million individuals are diagnosed with this devastating disease, with increasing incidence in Europe and Southeast Asia. The diagnosis of HNSCC often occurs in late stages of the disease and is characterized by manifestation of a high-grade primary tumor and/or lymph node metastasis, precluding timely management of this deadly cancer. Recently, HNSCC cancer stem cells have emerged as an important factor for cancer initiation and maintenance of tumor bulk. Like normal stem cells, cancer stem cells can undergo self-renewal and differentiation. This unique trait allows for maintenance of the cancer stem cell pool and facilitates differentiation into heterogeneous neoplastic progeny when necessary. Recent studies have suggested coexistence of different cancer stem cell populations within a tumor mass, where the tumor initiation and metastasis properties of these cancer stem cells can be uncoupled. Cancer stem cells also possess resistant phenotypes that evade standard chemotherapy and radiotherapy, resulting in tumor relapse. Therefore, understanding distinctive pathways relating to cancer stem cells will provide insight into early diagnosis and treatment of HNSCC. In this review, we highlight current advances in identifying cancer stem cells, detail the interactions of these cells with the immune system within the tumor niche, and discuss the potential use of immunotherapy in managing HNSCC.

  19. Activity of the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid against Human Head and Neck Carcinoma Xenografts

    Directory of Open Access Journals (Sweden)

    Mukund Seshadri

    2006-07-01

    Full Text Available Head and neck squamous cell carcinomas (HNSCC constitute a majority of the tumors of the upper aerodigestive tract and continue to present a significant therapeutic challenge. To explore the potential of vascular-targeted therapy in HNSCC, we investigated the antivascular, antitumor activity of the potent vascular-disrupting agent (VDA 5,6-dimethylxanthenone-4-acetic acid (DMXAA against two HNSCC xenografts with markedly different morphologic and vascular characteristics. Athymic nude mice bearing subcutaneous FaDu (human pharyngeal squamous cell carcinoma and A253 (human submaxillary gland epidermoid carcinoma tumors were administered a single dose of DMXAA (30 mg/kg, i.p. Changes in vascular function were evaluated 24 hours after treatment using contrast-enhanced magnetic resonance imaging (MRI and immunohistochemistry (CD31. Signal enhancement (E and change in longitudinal relaxation rates (ΔR1 were calculated to measure alterations in vascular perfusion. MRI showed a 78% and 49% reduction in vascular perfusion in FaDu and A253 xenografts, respectively. CD31-immunostaining of tumor sections revealed three-fold (FaDu and two-fold (A253 reductions in microvessel density (MVD 24 hours after treatment. DMXAA was equally effective against both xenograffs, with significant tumor growth inhibition observed 30 days after treatment. These results indicate that DMXAA may be beneficial in the management of HNSCC, alone or in combination with other treatments.

  20. FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation.

    Directory of Open Access Journals (Sweden)

    Emilios Gemenetzidis

    Full Text Available BACKGROUND: Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC. METHODOLOGY/PRINCIPAL FINDINGS: FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR, expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23, were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression. CONCLUSIONS/SIGNIFICANCE: This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  3. Microarray gene expression analysis of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Meng Lian

    Full Text Available BACKGROUND: Laryngeal squamous cell carcinoma (LSCC is the most common type in head and neck squamous cell carcinoma (HNSCC, and the development and progression of LSCC are multistep processes accompanied by changes of molecular biology. OBJECTIVE: The purpose of this study was to investigate the molecular basis of tumorigenesis and regional lymph node metastasis in LSCC, and provide a set of genes that may be useful for the development of novel diagnostic markers and/or more effective therapeutic strategies. METHODS: A total number of 10 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for microarray analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by Illumina mRNA microarrays, and LSCC tissues with regional lymph node metastasis and LSCC tissues without regional lymph node metastasis were analyzed in the same manner. The most frequently differently expressed genes screened by microarrays were also validated by qRT-PCR in another 42 patients diagnosed for LSCC. RESULTS: Analysed by Illumina mRNA microarrays, there were 361 genes significantly related to tumorigenesis while 246 genes significantly related to regional lymph node metastasis in LSCC. We found that the six genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4 were most frequently differently expressed functional genes related to tumorigenesis while eIF3a and RPN2 were most frequently differently expressed functional genes related to regional lymph node metastasis in LSCC. The expressions of these genes were also validated by qRT-PCR. CONCLUSIONS: The research revealed a gene expression signature of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma. Of the total, the deregulation of several genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4, EIF3a and RPN2 were potentially associated with disease development and progression. The result will contribute to the understanding of the

  4. Co-targeting ALK and EGFR parallel signaling in oral squamous cell carcinoma.

    Science.gov (United States)

    Gonzales, Cara B; De La Chapa, Jorge J; Saikumar, Pothana; Singha, Prajjal K; Dybdal-Hargreaves, Nicholas F; Chavez, Jeffery; Horning, Aaron M; Parra, Jamie; Kirma, Nameer B

    2016-08-01

    Squamous cell carcinoma (SCC) comprises 90% of all head and neck cancers and has a poor survival rate due to late-stage disease that is refractive to traditional therapies. Epidermal growth factor receptor (EGFR) is over-expressed in greater than 80% of head and neck SCC (HNSCC). However, EGFR targeted therapies yielded little to no efficacy in clinical trials. This study investigated the efficacy of co-targeting EGFR and the anaplastic lymphoma kinase (ALK) whose promoter is hypomethylated in late-stage oral SCC (OSCC). We observed increased ALK activity in late-stage human OSCC tumors and invasive OSCC cell lines. We also found that while ALK inhibition alone had little effect on proliferation, co-targeting ALK and EGFR significantly reduced OSCC cell proliferation in vitro. Further analysis showed significant efficacy of combined treatment in HSC3-derived xenografts resulting in a 30% decrease in tumor volumes by 14days (panalysis showed that co-targeting ALK and EGFR significantly reduced EGFR phosphorylation (Y1148) in HSC3 cells but not Cal27 cells. ALK and EGFR downstream signaling interactions are also demonstrated by Western blot analysis in which lone EGFR and ALK inhibitors attenuated AKT activity whereas co-targeting ALK and EGFR completely abolished AKT activation. No effects were observed on ERK1/2 activation. STAT3 activity was significantly induced by lone ALK inhibition in HSC3 cells and to a lower extent in Cal27 cells. Together, these data illustrate that ALK inhibitors enhance anti-tumor activity of EGFR inhibitors in susceptible tumors that display increased ALK expression, most likely through abolition of AKT activation. PMID:27424178

  5. 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.

  6. Phase I trial of oral etoposide in combination with radiotherapy in head and neck squamous cell carcinoma - GORTEC 2004–02

    International Nuclear Information System (INIS)

    This study sought to determine the maximum tolerated dose (MTD) of oral etoposide in combination with radiotherapy in head and neck squamous cell carcinoma (HNSCC). Phase I, multicenter, open-labelled, non-comparative and dose escalating trial. Patients with locally advanced HNSCC were enrolled onto cohorts of escalating dose of etoposide. Oral etoposide was administered on five consecutive days every week for 7 weeks (7 treatment cycles) in combination with daily radiotherapy (70 Gy /35 fractions). Two dose levels (25 mg/day and 50 mg/day) of etoposide were planned and three to six patients were to be enrolled at each level according to the potential DLTs. Fourteen patients were allocated to two dose levels: 25 mg/day (3) and 50 mg/day (11). Cisplatin was contra-indicated in all the patients included. Only one patient (50 mg/day) presents a grade 4 neutropenia (DLT), no other DLTs were observed. The most frequently adverse events (AEs) were radiomucositis. Two deaths before 3 months of end of treatment were not related to treatment. Seven patients were still alive with a median follow-up of 30 months (12–58 months). Nine patients had a complete response (CR) at 3 months after the radiotherapy; Among the 9 patients, 3 patients had a local relapse; one patient with local and distant relapse. Due to only one DLT experienced, it is possible to a dose of 50 mg/day for phase II studies, however this should be considered with caution

  7. Stress associated gene expression in blood cells is related to outcome in radiotherapy treated head and neck cancer patients

    Directory of Open Access Journals (Sweden)

    Bøhn Siv K

    2012-09-01

    Full Text Available Abstract Background We previously observed that a radiotherapy-induced biochemical response in plasma was associated with favourable outcome in head and neck squamous carcinoma cancer (HNSCC patients. The aim of the present study was to compare stress associated blood cell gene expression between two sub-groups of HNSCC patients with different biochemical responses to radiotherapy. Methods Out of 87 patients (histologically verified, 10 biochemical ‘responders’ having a high relative increase in plasma oxidative damage and a concomitant decrease in plasma antioxidants during radiotherapy and 10 ‘poor-responders’ were selected for gene-expression analysis and compared using gene set enrichment analysis. Results There was a significant induction of stress-relevant gene-sets in the responders following radiotherapy compared to the poor-responders. The relevance of the involvement of similar stress associated gene expression for HNSCC cancer and radioresistance was verified using two publicly available data sets of 42 HNSCC cases and 14 controls (GEO GSE6791, and radiation resistant and radiation sensitive HNSCC xenografts (E-GEOD-9716. Conclusions Radiotherapy induces a systemic stress response, as revealed by induction of stress relevant gene expression in blood cells, which is associated to favourable outcome in a cohort of 87 HNSCC patients. Whether these changes in gene expression reflects a systemic effect or are biomarkers of the tumour micro-environmental status needs further study. Trial registration Raw data are available at ArrayExpress under accession number E-MEXP-2460.

  8. 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.

  9. 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

  10. 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...

  11. 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...

  12. Papillocystic Variant of Acinar Cell Pancreatic Carcinoma

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    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.

  13. 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...

  14. 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.

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. CT features of nonfunctioning islet cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-11-01

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

  20. 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.

  1. 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.

  2. Tumor associated antigen specific T-cell populations identified in ex vivo expanded TIL cultures

    DEFF Research Database (Denmark)

    Junker, Niels; Kvistborg, Pia; Køllgaard, Tania;

    2012-01-01

    Ex vivo expanded tumor infiltrating lymphocytes (TILs) from malignant melanoma (MM) and head & neck squamous cell carcinoma (HNSCC) share a similar oligoclonal composition of T effector memory cells, with HLA class I restricted lysis of tumor cell lines. In this study we show that ex vivo expanded...... TILs from MM and HNSCC demonstrate a heterogeneous composition in frequency and magnitude of tumor associated antigen specific populations by Elispot IFN¿ quantitation. TILs from MM and HNSCC shared reactivity towards NY ESO-1, cyclin B1 and Bcl-x derived peptides. Additionally we show that dominating...... the heterogeneous tumors upon adoptive transfer; increasing the probability of tumor control by minimizing immune evasion by tumor cell escape variants....

  3. 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

  4. 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.

  5. 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 ...

  6. 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...

  7. Tumor cells with low proteasome subunit expression predict overall survival in head and neck cancer patients

    International Nuclear Information System (INIS)

    Experimental and clinical data suggest that solid cancers contain treatment-resistant cancer stem cells that will impair treatment efficacy. The objective of this study was to investigate if head and neck squamous cell carcinoma (HNSCC) also contain cancer stem cells that can be identified by low 26S proteasome activity and if their presence correlates to clinical outcome. Human HNSCC cells, engineered to report lack of proteasome activity based on accumulation of a fluorescent fusion protein, were separated based on high (ZsGreen-cODCneg) or low (ZsGreen-cODCpos) proteasome activity. Self-renewal capacity, tumorigenicity and radioresistance were assessed. Proteasome subunit expression was analyzed in tissue microarrays and correlated to survival and locoregional cancer control of 174 patients with HNSCC. HNSCC cells with low proteasome activity showed a significantly higher self-renewal capacity and increased tumorigenicity. Irradiation enriched for ZsGreen-cODCpos cells. The survival probability of 82 patients treated with definitive radio- or chemo-radiotherapy exhibiting weak, intermediate, or strong proteasome subunit expression were 21.2, 28.8 and 43.8 months (p = 0.05), respectively. Locoregional cancer control was comparably affected. Subpopulations of HNSCC display stem cell features that affect patients’ tumor control and survival. Evaluating cancer tissue for expression of the proteasome subunit PSMD1 may help identify patients at risk for relapse

  8. 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

  9. Cell surface markers for T and B lymphocytes activation and adhesion as putative prognostic biomarkers for head and neck squamous cell carcinoma.

    Science.gov (United States)

    Andrade, Mariléia Chaves; Ferreira, Shirlene Barbosa Pimentel; Gonçalves, Luciana C; De-Paula, Alfredo Maurício Batista; de Faria, Elaine Speziali; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis

    2013-12-01

    The study population comprised HNSCC patients, risk-positive controls (tabagism and alcoholism habits), and risk-negative controls (without risk factors). Significant increases in the activation status of CD4(+)and CD8(+) T-cells, and higher migration potentials of lymphocytes were observed in HNSCC patients compared with control groups. Although decreased frequency of CD19(+)-B lymphocytes was observed in HSNCC patients, a higher percentage of HLA-DR(+)CD19(+)-B lymphocytes was detected in these individuals as compared with other evaluated groups. Metastasis and tumor grading were the major pathological parameters associated with significant alterations in the expression of activation molecules on circulating CD4(+) and CD8(+) T-cells. A reduced frequency of CD38-expressing CD8(+) T-cells was the most relevant biomarker associated with HNSCC aggressiveness. Performance analysis suggested a cut-off point for the CD8(+)CD38(+)/CD8(+) T-cell ratio of 7.0 for segregating patients according to tumor grading. In contrast, a higher proportion of CD8(+)CD54(+)/CD8(+) T-cells could represent a relevant biomarker associated with metastasis in HNSCC patients, and performance analysis suggested a cut-off point for the CD8(+)CD54(+)/CD8(+) T-cell ratio of 30 for segregating patients according to absence or presence of metastasis. The results obtained can increment immunological aspects of HNSCC and provide tools for the determination of cut-off scores of clinically relevant immunophenotypic prognostic biomarkers. PMID:23994583

  10. 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

  11. 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.

  12. 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

  13. 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...

  14. 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.

  15. Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head-and-Neck Squamous Cell Carcinoma Patients With Nodal Metastases

    International Nuclear Information System (INIS)

    Purpose: Dynamic contrast-enhanced MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of this study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery. Methods and Materials: Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using the Tofts model. DCE-MRI parameters were related to treatment outcome (progression-free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD), or dead of other causes (DOC). Prognostic significance was assessed using the log-rank test for single variables and Cox proportional hazards regression for combinations of variables. Results: At last clinical follow-up, for Stage III, all 12 patients were NED. For Stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. Ktrans is volume transfer constant. In a stepwise Cox regression, skewness of Ktrans (volume transfer constant) was the strongest predictor for Stage IV patients (PFS and OS: p trans was the strongest predictor of PFS and OS in Stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter Ktrans as a predictor of outcome in these patients.

  16. 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.

  17. 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.

  18. 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

  19. 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...

  20. 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.

  1. 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...

  2. 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.

  3. Clinical values for abnormal {sup 18}F-FDG uptake in the head and neck region of patients with head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hwan Seo [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jae Seung [Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Roh, Jong-Lyel, E-mail: rohjl@amc.seoul.kr [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Seung-Ho; Nam, Soon Yuhl [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sang Yoon [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)

    2014-08-15

    Highlights: • Abnormal {sup 18}F-FDG uptakes in the head and neck (HN) region can be carefully interpreted as being index primary, second primary cancer (SP) or benign. • {sup 18}F-FDG PET/CT identified 91.9% primary HN squamous cell carcinomas (HNSCC). • The specificity and negative predictive value of {sup 18}F-FDG PET/CT for identification of SP were as high as 98.7% and 99.3%, respectively. • Proper detection of primary tumors and SP in the HN region may promote appropriate therapeutic planning of HNSCC patients. - Abstract: Purpose: Fluorine 18-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/computed tomography (CT) is used to identify index or second primary cancer (SP) of the head and neck (HN) through changes in {sup 18}F-FDG uptake. However, both physiologic and abnormal lesions increase {sup 18}F-FDG uptake. Therefore, we evaluated {sup 18}F-FDG uptake in the HN region to determine clinical values of abnormal tracer uptake. Methods: A prospective study approved by the institutional review board was conducted in 314 patients with newly diagnosed HN squamous cell carcinoma (HNSCC) and informed consent was obtained from all enrolled patients. The patients received initial staging workups including {sup 18}F-FDG PET/CT and biopsies. All lesions with abnormal HN {sup 18}F-FDG uptake were recorded and most of those were confirmed by biopsies. Diagnostic values for abnormal {sup 18}F-FDG uptake were calculated. Results: Abnormal {sup 18}F-FDG uptake was identified in primary tumors from 285 (91.9%) patients. False-negative results were obtained for 22.3% (23/103) T1 tumors and 2.2% (2/93) T2 tumors (P < 0.001). Thirty-eight regions of abnormal {sup 18}F-FDG uptake were identified in 36 (11.5%) patients: the thyroid (n = 13), maxillary sinus (n = 7), palatine tonsil (n = 6), nasopharynx (n = 5), parotid gland (n = 2) and others (n = 5). Synchronous SP of the HN was identified in eight (2.5%) patients: the thyroid (n = 5), palatine

  4. 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...

  5. 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.

  6. 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.

  7. 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

  8. The Morphologic Profile of HPV-Related Head and Neck Squamous Carcinoma: Implications for Diagnosis, Prognosis, and Clinical Management

    OpenAIRE

    Westra, William H.

    2012-01-01

    Much recent attention has highlighted a subset of head and neck squamous cell carcinomas (HNSCCs) related to the human papillomavirus (HPV) that is characterized by an epidemiologic, demographic, and clinical profile that deviates from the profile of conventional non-HPV-related HNSCC. Lost in the dash to develop and implement diagnostic assays to detect the presence of HPV in HNSCCs is the unpretentious observation that these HPV-HNSCCs are also distinctive with respect to their microscopic ...

  9. HIF-α/MIF and NF-κB/IL-6 Axes Contribute to the Recruitment of CD11b+Gr-1+ Myeloid Cells in Hypoxic Microenvironment of HNSCC

    OpenAIRE

    Guiquan Zhu; Yaling Tang; Ning Geng; Min Zheng; Jian Jiang; Ling Li; Kaide Li; Zhengge Lei; Wei Chen; Yunlong Fan; Xiangrui Ma; Longjiang Li; Xiaoyi Wang; Xinhua Liang

    2014-01-01

    CD11b+Gr-1+ myeloid cells have gained much attention due to their roles in tumor immunity suppression as well as promotion of angiogenesis, invasion, and metastases. However, the mechanisms by which CD11b+Gr-1+ myeloid cells recruit to the tumor site have not been well clarified. In the present study, we showed that hypoxia could stimulate the migration of CD11b+Gr-1+ myeloid cells through increased production of macrophage migration inhibitory factor (MIF) and interleukin-6 (IL-6) by head an...

  10. Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck

    Directory of Open Access Journals (Sweden)

    Ohlsson Tomas

    2009-02-01

    Full Text Available Abstract Background The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24–35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC are valuable models for identifying such markers. The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status. Methods Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf. The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test (crystal violet, and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP with DNA sequencing and, for cyclin D1, by immunohistochemistry. Results Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake. Conclusion In vitro growth of HNSCC

  11. 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.

  12. 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...

  13. 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.

  14. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer12

    OpenAIRE

    Nör, Carolina; Zhang, Zhaocheng; Warner, Kristy A.; Bernardi, Lisiane; Visioli, Fernanda; Helman, Joseph I.; Roesler, Rafael; Jacques E Nör

    2014-01-01

    Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs). These unique cells, named here cancer stem cells (CSCs), proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6)] for their survival and self-renewal in HNSCC. Here, we...

  15. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

    OpenAIRE

    Carolina Nör; Zhaocheng Zhang; Warner, Kristy A.; Lisiane Bernardi; Fernanda Visioli; Helman, Joseph I.; Rafael Roesler; Jacques E Nör

    2014-01-01

    Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs). These unique cells, named here cancer stem cells (CSCs), proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6)] for their survival and self-renewal in HNSCC. Here, we...

  16. Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Antonin; Blanchard, Pierre; Bellefqih, Sara; Brahimi, Nacera; Deutsch, Eric; Daly-Schveitzer, Nicolas; Tao, Yungan [Gustave Roussy, Department of Radiation Oncology, Villejuif (France); Guigay, Joel [Gustave Roussy, Department of Medical Oncology, Villejuif (France); Janot, Francois; Temam, Stephane [Gustave Roussy, Department of Head and Neck Surgery, Villejuif (France); Bourhis, Jean [Gustave Roussy, Department of Radiation Oncology, Villejuif (France); University Hospital Lausanne, Department of Radiation Oncology, Lausanne (Switzerland)

    2014-09-15

    The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m{sup 2}, every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS. (orig.) [German] Die Therapieeffektivitaet mit Platin

  17. 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

  18. 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.

  19. 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....

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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...

  5. 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

  6. Spheroid Culture of Head and Neck Cancer Cells Reveals an Important Role of EGFR Signalling in Anchorage Independent Survival.

    Science.gov (United States)

    Braunholz, Diana; Saki, Mohammad; Niehr, Franziska; Öztürk, Merve; Borràs Puértolas, Berta; Konschak, Robert; Budach, Volker; Tinhofer, Ingeborg

    2016-01-01

    In solid tumours millions of cells are shed into the blood circulation each day. Only a subset of these circulating tumour cells (CTCs) survive, many of them presumable because of their potential to form multi-cellular clusters also named spheroids. Tumour cells within these spheroids are protected from anoikis, which allows them to metastasize to distant organs or re-seed at the primary site. We used spheroid cultures of head and neck squamous cell carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining the role of the epidermal growth factor receptor (EGFR) in cluster formation ability and cell survival after detachment from the extra-cellular matrix. The HNSCC cell lines FaDu, SCC-9 and UT-SCC-9 (UT-SCC-9P) as well as its cetuximab (CTX)-resistant sub-clone (UT-SCC-9R) were forced to grow in an anchorage-independent manner by coating culture dishes with the anti-adhesive polymer poly-2-hydroxyethylmethacrylate (poly-HEMA). The extent of apoptosis, clonogenic survival and EGFR signalling under such culture conditions was evaluated. The potential of spheroid formation in suspension culture was found to be positively correlated with the proliferation rate of HNSCC cell lines as well as their basal EGFR expression levels. CTX and gefitinib blocked, whereas the addition of EGFR ligands promoted anchorage-independent cell survival and spheroid formation. Increased spheroid formation and growth were associated with persistent activation of EGFR and its downstream signalling component (MAPK/ERK). Importantly, HNSCC cells derived from spheroid cultures retained their clonogenic potential in the absence of cell-matrix contact. Addition of CTX under these conditions strongly inhibited colony formation in CTX-sensitive cell lines but not their resistant subclones. Altogether, EGFR activation was identified as crucial factor for anchorage-independent survival of HNSCC cells. Targeting EGFR in CTC cluster formation might represent an attractive anti

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. [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

  3. 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.

  4. 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....

  5. 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

  6. FDG-PET/contrast-enhanced CT as a post-treatment tool in head and neck squamous cell carcinoma: comparison with FDG-PET/non-contrast-enhanced CT and contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Suenaga, Yuko; Kitajima, Kazuhiro; Sugimura, Kazuro [Kobe University Graduate School of Medicine, Department of Radiology, Kobe (Japan); Ishihara, Takeaki; Sasaki, Ryohei [Kobe University Graduate, School of Medicine, Department of Radiology, Division of Radiation Oncology, Kobe (Japan); Otsuki, Naoki; Nibu, Ken-ichi [Kobe University Graduate, School of Medicine, Department of Otolaryngology-Head and Neck Surgery, Kobe (Japan); Minamikawa, Tsutomu [Kobe University Graduate School of Medicine, Department of Oral and Maxillofacial Surgery, Kobe (Japan); Kiyota, Naomi [Kobe University Hospital, Department of Medical Oncology and Hematology, Kobe (Japan)

    2016-04-15

    To evaluate the accuracy of PET/CT using {sup 18}F-fluorodeoxyglucose (FDG) with IV contrast for suspected recurrent head and neck squamous cell carcinoma (HNSCC). One hundred and seventy patients previously treated for HNSCC underwent PET/CT, consisting of non-contrast-enhanced and contrast-enhanced CT, to investigate suspected recurrence. Diagnostic performance of PET/contrast-enhanced CT (PET/ceCT), PET/non-contrast-enhanced CT (PET/ncCT) and contrast-enhanced CT (ceCT) for local or regional recurrence, distant metastasis, overall recurrence and second primary cancer was evaluated. The reference standard included histopathology, treatment change and imaging follow-up. The patient-based areas under the receiver operating characteristic curves (AUC) for ceCT, PET/ncCT and PET/ceCT were 0.82, 0.96 and 0.98 for local recurrence, 0.73, 0.86 and 0.86 for regional recurrence, 0.86, 0.91 and 0.92 for distant metastasis, 0.72, 0.86 and 0.87 for overall recurrence, and 0.86, 0.89 and 0.91 for a second primary cancer. Both PET/ceCT and PET/ncCT statistically showed larger AUC than ceCT for recurrence, and the difference between PET/ceCT and PET/ncCT for local recurrence reached a significant level (p = 0.039). The accuracy of PET/ceCT for diagnosing overall recurrence was high, irrespective of the time interval after the last treatment (83.3-94.1 %). FDG-PET/CT was a more accurate HNSCC restaging tool than ceCT. The added value of ceCT at FDG-PET/CT is minimal. (orig.)

  7. 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.

  8. 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...

  9. 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.

  10. 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.)....

  11. 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.

  12. 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.

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. 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

  18. Optical imaging of head and neck squamous cell carcinoma in vivo using arginine-glycine- aspartic acid peptide conjugated near-infrared quantum dots

    Directory of Open Access Journals (Sweden)

    Huang H

    2013-12-01

    Full Text Available Hao Huang, Yun-Long Bai, Kai Yang, Hong Tang, You-Wei WangDepartment of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of ChinaAbstract: Molecular imaging plays a key role in personalized medicine and tumor diagnosis. Quantum dots with near-infrared emission spectra demonstrate excellent tissue penetration and photostability, and have recently emerged as important tools for in vivo tumor imaging. Integrin αvβ3 has been shown to be highly and specifically expressed in endothelial cells of tumor angiogenic vessels in almost all types of tumors, and specifically binds to the peptide containing arginine-glycine-aspartic acid (RGD. In this study, we conjugated RGD with quantum dots with emission wavelength of 800 nm (QD800 to generate QD800-RGD, and used it via intravenous injection as a probe to image tumors in nude mice bearing head and neck squamous cell carcinoma (HNSCC. Twelve hours after the injection, the mice were still alive and were sacrificed to isolate tumors and ten major organs for ex vivo analysis to localize the probe in these tissues. The results showed that QD800-RGD was specifically targeted to integrin αvβ3 in vitro and in vivo, producing clear tumor fluorescence images after the intravenous injection. The tumor-to-background ratio and size of tumor image were highest within 6 hours of the injection and declined significantly at 9 hours after the injection, but there was still a clearly visible tumor image at 12 hours. The greatest amount of QD800-RGD was found in liver and spleen, followed by tumor and lung, and a weak fluorescence signal was seen in tibia. No detectable signal of QD800-RGD was found in brain, heart, kidney, testis, stomach, or intestine. Our study demonstrated that using integrin αvβ3 as target, it is possible to use intravenously injected QD800-RGD to generate high quality images of HNSCC, and the technique offers great potential

  19. 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.

  20. 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.

  1. 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.

  2. MicroRNA expression profile in head and neck cancer: HOX-cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation

    International Nuclear Information System (INIS)

    Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC. MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression. Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of micro

  3. 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 (

  4. 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.

  5. 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.

  6. 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

  7. Association between GSTM1 and GSTT1 allelic variants and head and neck squamous cell cancinoma.

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    Full Text Available BACKGROUNDS: GSTM1 and GSTT1 are involved in the detoxification of carcinogens such as smoking by-products, and polymorphisms in these two genes with a result of loss of enzyme activity may increase risk of carcinogenesis. Although many epidemiological studies have investigated the association between GSTM1 or GSTT1 null genotype and head and neck squamous cell carcinoma (HNSCC, the results remain conflicting. To elucidate the overall association of GSTM1, GSTT1 and HNSCC, we included all available studies and performed this meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: A dataset including 42 articles for GSTM1, 32 articles for GSTT1, and 15 articles for GSTM1 and GSTT1 in combination were identified by a search in PubMed. Associations beween HNSCC and polymorphisms of GSTM1 and GSTT1 alone and in combination were analysed by software RevMan 5.1. Stratification analysis on ethnicity and smoking status, sensitivity analysis, heterogeneity among studies and their publication bias were also tested. Association was found in overall analysis between HNSCC and GSTM1 and GSTT1 null genotype. Stratified by ethnicity, we found increased risks of HNSCC in carriers with GSTM1 null genotype in Asian, GSTT1 null genotype in South American, and dual null genotype in European and Asian. When stratified by smoking, a more significant association of GSTM1 null genotype with HNSCC risk was observed in smokers. CONCLUSIONS/SIGNIFICANCE: This meta-analysis presented additional evidence of the association between GSTM1 and GSTT1 polymorphisms and HNSCC risk.

  8. 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.

  9. NOX4 mediates cytoprotective autophagy induced by the EGFR inhibitor erlotinib in head and neck cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sobhakumari, Arya [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Pathology, The University of Iowa, Iowa City, IA (United States); Schickling, Brandon M. [Department of Internal Medicine, The University of Iowa, Iowa City, IA (United States); Love-Homan, Laurie; Raeburn, Ayanna [Department of Pathology, The University of Iowa, Iowa City, IA (United States); Fletcher, Elise V.M. [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Pathology, The University of Iowa, Iowa City, IA (United States); Case, Adam J. [Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Domann, Frederick E. [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Pathology, The University of Iowa, Iowa City, IA (United States); Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics (UIHC), Iowa City, IA (United States); Miller, Francis J. [Department of Internal Medicine, The University of Iowa, Iowa City, IA (United States); Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics (UIHC), Iowa City, IA (United States); and others

    2013-11-01

    Most head and neck squamous cell carcinomas (HNSCCs) overexpress epidermal growth factor receptor (EGFR) and EGFR inhibitors are routinely used in the treatment of HNSCC. However, many HNSCC tumors do not respond or become refractory to EGFR inhibitors. Autophagy, which is a stress-induced cellular self-degradation process, has been reported to reduce the efficacy of chemotherapy in various disease models. The purpose of this study is to determine if the efficacy of the EGFR inhibitor erlotinib is reduced by activation of autophagy via NOX4-mediated oxidative stress in HNSCC cells. Erlotinib induced the expression of the autophagy marker LC3B-II and autophagosome formation in FaDu and Cal-27 cells. Inhibition of autophagy by chloroquine and knockdown of autophagy pathway genes Beclin-1 and Atg5 sensitized both cell lines to erlotinib-induced cytotoxicity, suggesting that autophagy may serve as a protective mechanism. Treatment with catalase (CAT) and diphenylene iodonium (DPI) in the presence of erlotinib suppressed the increase in LC3B-II expression in FaDu and Cal-27 cells. Erlotinib increased NOX4 mRNA and protein expression by increasing its promoter activity and mRNA stability in FaDu cells. Knockdown of NOX4 using adenoviral siNOX4 partially suppressed erlotinib-induced LC3B-II expression, while overexpression of NOX4 increased expression of LC3B-II. These studies suggest that erlotinib may activate autophagy in HNSCC cells as a pro-survival mechanism, and NOX4 may play a role in mediating this effect. - Highlights: • Erlotinib increased LC3B-II and autophagosome formation in HNSCC cells. • Inhibition of autophagy sensitized HNSCC cells to erlotinib. • Erlotinib increased NOX4 promoter and 3′UTR luciferase activity. • Manipulating NOX4 decreases or increases autophagy.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.)....

  17. 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...

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.)

  4. The Role of 3 Tesla Diffusion-Weighted Imaging in the Differential Diagnosis of Benign versus Malignant Cervical Lymph Nodes in Patients with Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    Pranno, Nicola; Sartori, Alessandro; Gigli, Silvia; Lo Mele, Luigi; Marsella, Luigi Tonino

    2014-01-01

    Objective. The aim of this study was to validate the role of diffusion-weighted imaging (DWI) at 3 Tesla in the differential diagnosis between benign and malignant laterocervical lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). Materials and Methods. Before undergoing surgery, 80 patients, with biopsy proven HNSCC, underwent a magnetic resonance exam. Sensitivity (Se) and specificity (Spe) of conventional criteria and DWI in detecting laterocervical lymph node metastases were calculated. Histological results from neck dissection were used as standard of reference. Results. In the 239 histologically proven metastatic lymphadenopathies, the mean apparent diffusion coefficient (ADC) value was 0.903 × 10−3 mm2/sec. In the 412 pathologically confirmed benign lymph nodes, an average ADC value of 1.650 × 10−3 mm2/sec was found. For differentiating between benign versus metastatic lymph nodes, DWI showed Se of 97% and Spe of 93%, whereas morphological criteria displayed Se of 61% and Spe of 98%. DWI showed an area under the ROC curve (AUC) of 0.964, while morphological criteria displayed an AUC of 0.715. Conclusions. In a DWI negative neck for malignant lymph nodes, the planned dissection could be converted to a wait-and-scan policy, whereas DWI positive neck would support the decision to perform a neck dissection. PMID:25003115

  5. The Role of 3 Tesla Diffusion-Weighted Imaging in the Differential Diagnosis of Benign versus Malignant Cervical Lymph Nodes in Patients with Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Flavio Barchetti

    2014-01-01

    Full Text Available Objective. The aim of this study was to validate the role of diffusion-weighted imaging (DWI at 3 Tesla in the differential diagnosis between benign and malignant laterocervical lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC. Materials and Methods. Before undergoing surgery, 80 patients, with biopsy proven HNSCC, underwent a magnetic resonance exam. Sensitivity (Se and specificity (Spe of conventional criteria and DWI in detecting laterocervical lymph node metastases were calculated. Histological results from neck dissection were used as standard of reference. Results. In the 239 histologically proven metastatic lymphadenopathies, the mean apparent diffusion coefficient (ADC value was 0.903 × 10−3 mm2/sec. In the 412 pathologically confirmed benign lymph nodes, an average ADC value of 1.650 × 10−3 mm2/sec was found. For differentiating between benign versus metastatic lymph nodes, DWI showed Se of 97% and Spe of 93%, whereas morphological criteria displayed Se of 61% and Spe of 98%. DWI showed an area under the ROC curve (AUC of 0.964, while morphological criteria displayed an AUC of 0.715. Conclusions. In a DWI negative neck for malignant lymph nodes, the planned dissection could be converted to a wait-and-scan policy, whereas DWI positive neck would support the decision to perform a neck dissection.

  6. 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.

  7. [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

  8. Should PET/CT be implemented in the routine imaging work-up of locally advanced head and neck squamous cell carcinoma? A prospective analysis

    International Nuclear Information System (INIS)

    The objective of this study was to determine the incremental staging information provided by positron emission tomography/computed tomography (PET/CT) and its impact on management plans in patients with untreated stage III-IV head and neck squamous cell carcinoma (HNSCC). We prospectively studied, between September 2011 and February 2013, 84 consecutive patients [median age 63.5 years (39-84); 73 men] with histologically confirmed HNSCC. First, based on a conventional work-up (physical examination, CT imaging of the head, neck and chest), the multidisciplinary Head and Neck Tumour Board documented the TNM stage and a management plan for each patient, outlining the modalities to be used, including surgery, radiation therapy (RT), chemotherapy or a combination. After release of the PET/CT results, new TNM staging and management plans were agreed on by the multidisciplinary Tumour Board. Any changes in stage or intended management due to the PET/CT findings were then analysed. The impact on patient management was classified as: low (treatment modality, delivery and intent unchanged), moderate (change within the same treatment modality: type of surgery, radiation technique/dose) or high (change in treatment intent and/or treatment modality → curative to palliative, or surgery to chemoradiation or detection of unknown primary tumour or a synchronous second primary tumour). TNM stage was validated by histopathological analysis, additional imaging or follow-up. Accuracy of the conventional and PET/CT-based staging was compared using McNemar's test. Conventional and PET/CT stages were discordant in 32/84 (38 %) cases: the T stage in 2/32 (6.2 %), the N stage in 21/32 (65.7 %) and the M stage 9/32 (28.1 %). Patient management was altered in 22/84 (26 %) patients, with a moderate impact in 8 (9.5 %) patients and high impact in 14 (16.6 %) patients. PET/CT TNM classification was significantly more accurate (92.5 vs 73.7 %) than conventional staging with a p value < 0

  9. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Nyflot, Matthew J., E-mail: nyflot@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Kruser, Tim J. [Department of Radiation Oncology, Cadence Cancer Center at Delnor Hospital, Geneva, Illinois (United States); Traynor, Anne M. [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Khuntia, Deepak [Varian Medical Systems, Palo Alto, California (United States); Yang, David T. [Departments of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hartig, Gregory K.; McCulloch, Timothy M. [Department of Surgery-Otolaryngology, H& N Surgery Division, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Wiederholt, Peggy A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Gentry, Lindell R. [Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hoang, Tien [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Jeraj, Robert [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Medical Physics, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); and others

    2015-04-01

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging

  10. Should PET/CT be implemented in the routine imaging work-up of locally advanced head and neck squamous cell carcinoma? A prospective analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cacicedo, Jon; Bilbao, Pedro [Cruces University Hospital, Radiation Oncology Department, Barakaldo, Bizkaia (Basque Country) (Spain); BioCruces Health Research Institute, Bizkaia, Basque Country (Spain); Fernandez, Iratxe [Cruces University Hospital, Nuclear Medicine Department, Barakaldo (Spain); Hoyo, Olga del; Hortelano, Eduardo [Cruces University Hospital, Radiation Oncology Department, Barakaldo, Bizkaia (Basque Country) (Spain); Dolado, Ainara [Cruces University Hospital, Radiodiagnostic and Medical Imaging Department, Barakaldo (Spain); Gomez-Suarez, Javier [Cruces University Hospital, Otolaryngology Department, Barakaldo (Spain); Sancho, Aintzane [Cruces University Hospital, Medical Oncology Department, Barakaldo (Spain); Pijoan, Jose I. [BioCruces Health Research Institute, Bizkaia, Basque Country (Spain); Cruces University Hospital, Clinical Epidemiology Unit, Barakaldo (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Madrid (Spain); Alvarez, Julio [Cruces University Hospital, Oral and Maxillofacial Surgery Department, Barakaldo (Spain); Espinosa, Jose M. [Cruces University Hospital, Medical Physics Department, Barakaldo (Spain); Gaafar, Ayman [Cruces University Hospital, Department of Pathology, Barakaldo (Spain)

    2015-08-15

    The objective of this study was to determine the incremental staging information provided by positron emission tomography/computed tomography (PET/CT) and its impact on management plans in patients with untreated stage III-IV head and neck squamous cell carcinoma (HNSCC). We prospectively studied, between September 2011 and February 2013, 84 consecutive patients [median age 63.5 years (39-84); 73 men] with histologically confirmed HNSCC. First, based on a conventional work-up (physical examination, CT imaging of the head, neck and chest), the multidisciplinary Head and Neck Tumour Board documented the TNM stage and a management plan for each patient, outlining the modalities to be used, including surgery, radiation therapy (RT), chemotherapy or a combination. After release of the PET/CT results, new TNM staging and management plans were agreed on by the multidisciplinary Tumour Board. Any changes in stage or intended management due to the PET/CT findings were then analysed. The impact on patient management was classified as: low (treatment modality, delivery and intent unchanged), moderate (change within the same treatment modality: type of surgery, radiation technique/dose) or high (change in treatment intent and/or treatment modality → curative to palliative, or surgery to chemoradiation or detection of unknown primary tumour or a synchronous second primary tumour). TNM stage was validated by histopathological analysis, additional imaging or follow-up. Accuracy of the conventional and PET/CT-based staging was compared using McNemar's test. Conventional and PET/CT stages were discordant in 32/84 (38 %) cases: the T stage in 2/32 (6.2 %), the N stage in 21/32 (65.7 %) and the M stage 9/32 (28.1 %). Patient management was altered in 22/84 (26 %) patients, with a moderate impact in 8 (9.5 %) patients and high impact in 14 (16.6 %) patients. PET/CT TNM classification was significantly more accurate (92.5 vs 73.7 %) than conventional staging with a p value < 0

  11. c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Baschnagel, Andrew M. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Williams, Lindsay [Department of Pathology, William Beaumont Hospital, Royal Oak, Michigan (United States); Hanna, Alaa; Chen, Peter Y.; Krauss, Daniel J. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Pruetz, Barbara L. [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Akervall, Jan [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Department of Otolaryngology, William Beaumont Hospital, Royal Oak, Michigan (United States); Wilson, George D., E-mail: George.Wilson@Beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States)

    2014-03-01

    Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16

  12. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    International Nuclear Information System (INIS)

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m2 and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [18F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [61Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates measureable

  13. Reproducibility of 18F-FDG PET uptake measurements in head and neck squamous cell carcinoma on both PET/CT and PET/MR

    Science.gov (United States)

    Fischer, B M; Aznar, M C; Hansen, A E; Vogelius, I R; Löfgren, J; Andersen, F L; Loft, A; Kjaer, A; Højgaard, L; Specht, L

    2015-01-01

    Objective: To investigate reproducibility of fluorine-18 fludeoxyglucose (18F-FDG) uptake on 18F-FDG positron emission tomography (PET)/CT and 18F-FDG PET/MR scans in patients with head and neck squamous cell carcinoma (HNSCC). Methods: 30 patients with HNSCC were included in this prospective study. The patients were scanned twice before radiotherapy treatment with both PET/CT and PET/MR. Patients were scanned on the same scanners, 3 days apart and according to the same protocol. Metabolic tumour activity was measured by the maximum and peak standardized uptake value (SUVmax and SUVpeak, respectively), and total lesion glycolysis from the metabolic tumour volume defined from ≥50% SUVmax. Bland–Altman analysis with limits of agreement, coefficient of variation (CV) from the two modalities were performed in order to test the reproducibility. Furthermore, CVs from SUVmax and SUVpeak were compared. The area under the curve from cumulative SUV–volume histograms were measured and tested for reproducibility of the distribution of 18F-FDG uptake. Results: 24 patients had two pre-treatment PET/CT scans and 21 patients had two pre-treatment PET/MR scans available for further analyses. Mean difference for SUVmax, peak and mean was approximately 4% for PET/CT and 3% for PET/MR, with 95% limits of agreement less than ±20%. CV was small (5–7%) for both modalities. There was no significant difference in CVs between PET/CT and PET/MR (p = 0.31). SUVmax was not more reproducible than SUVpeak (p = 0.09). Conclusion: 18F-FDG uptake in PET/CT and PET/MR is highly reproducible and we found no difference in reproducibility between PET/CT and PET/MR. Advances in knowledge: This is the first report to test reproducibility of PET/CT and PET/MR. PMID:25634069

  14. SU-E-T-275: Radiobiological Evaluation of Intensity Modulated Radiotherapy Treatment for Locally Advanced Head and Neck Squamous Cell Carcinomas

    International Nuclear Information System (INIS)

    Purpose: To evaluate the radiobiological outcome of Intensity Modulated Radiotherapy Treatment (IMRT) for locally advanced head and neck squamous cell carcinomas using HART (Histogram Analysis in Radiation Therapy; J Appl Clin Med Phys 11(1): 137–157, 2010) program and compare with the clinical outcomes. Methods: We have treated 20 patients of stage III and IV HNSCC Oropharynx and hypopharynx with accelerated IMRT technique and concurrent chemotherapy. Delineation of tumor and normal tissues were done using Danish Head and Neck Cancer Group (DAHANCA) contouring guidelines and radiotherapy was delivered to a dose of 70Gy in 35 fractions to the primary and involved lymph nodes, 63Gy to intermediate risk areas and 56 Gy to lower risk areas, Monday to Saturday, 6 Days/week using 6 MV Photons with an expected overall treatment time of 6 weeks. The TCP and NTCP's were calculated from the dose-volume histogram (DVH) statistics using the Poisson Statistics (PS) and JT Lyman models respectively and the Resultwas correlated with clinical outcomes of the patients with mean follow up of 24 months. Results: Using HART program, the TCP (0.89± 0.01) of primary tumor and the NTCP for parotids (0.20±0.12), spinal cord (0.05±0.01), esophagus (0.30±0.2), mandible (0.35±0.21), Oral cavity (0.37±0.18), Larynx (0.30±0.15) were estimated and correlated with clinical outcome of the patients. Conclusion: Accelerated IMRT with Chemotherapy is a clinical feasible option in the treatment of locally advanced HNSCC with encouraging initial tumour response and acceptable acute toxicities. The correlation between the clinical outcomes and radiobiological model estimated parameters using HART programs are found to be satisfactory

  15. SU-E-T-275: Radiobiological Evaluation of Intensity Modulated Radiotherapy Treatment for Locally Advanced Head and Neck Squamous Cell Carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Rekha Reddy, B.; Ravikumar, M.; Tanvir Pasha, C.R; Anil Kumar, M.R; Varatharaj, C. [Kidwai Memorial Institute of Oncology Bangalore, Karnataka (India); Pyakuryal, A [University Illinois at Chicago, Chicago, IL (United States); Narayanasamy, Ganesh [UTHSCSA, San Antonio, TX (United States)

    2014-06-01

    Purpose: To evaluate the radiobiological outcome of Intensity Modulated Radiotherapy Treatment (IMRT) for locally advanced head and neck squamous cell carcinomas using HART (Histogram Analysis in Radiation Therapy; J Appl Clin Med Phys 11(1): 137–157, 2010) program and compare with the clinical outcomes. Methods: We have treated 20 patients of stage III and IV HNSCC Oropharynx and hypopharynx with accelerated IMRT technique and concurrent chemotherapy. Delineation of tumor and normal tissues were done using Danish Head and Neck Cancer Group (DAHANCA) contouring guidelines and radiotherapy was delivered to a dose of 70Gy in 35 fractions to the primary and involved lymph nodes, 63Gy to intermediate risk areas and 56 Gy to lower risk areas, Monday to Saturday, 6 Days/week using 6 MV Photons with an expected overall treatment time of 6 weeks. The TCP and NTCP's were calculated from the dose-volume histogram (DVH) statistics using the Poisson Statistics (PS) and JT Lyman models respectively and the Resultwas correlated with clinical outcomes of the patients with mean follow up of 24 months. Results: Using HART program, the TCP (0.89± 0.01) of primary tumor and the NTCP for parotids (0.20±0.12), spinal cord (0.05±0.01), esophagus (0.30±0.2), mandible (0.35±0.21), Oral cavity (0.37±0.18), Larynx (0.30±0.15) were estimated and correlated with clinical outcome of the patients. Conclusion: Accelerated IMRT with Chemotherapy is a clinical feasible option in the treatment of locally advanced HNSCC with encouraging initial tumour response and acceptable acute toxicities. The correlation between the clinical outcomes and radiobiological model estimated parameters using HART programs are found to be satisfactory.

  16. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma.

    Science.gov (United States)

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-12-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93-7.62, P Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann-Whitney U, P patients with a high probability of survival after genotoxic treatment. PMID:24403269

  17. 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 .

  18. 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.

  19. 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...

  20. 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...

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Early prediction of survival following induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) using FDG PET/CT imaging in patients with locally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Locally advanced head and neck squamous cell carcinoma (HNSCC) has a high rate of recurrence. Induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) before chemoradiotherapy could lead to the best disease control of inoperable stage III/IV HNSCC but with an increased risk of acute toxicity. Early assessment of therapeutic efficacy is a key issue in considering the benefit of escalation in a poor prognosis population. Patients with stage III/IV HNSCC, in whom DCF induction chemotherapy followed by concurrent chemoradiotherapy had been validated by a multidisciplinary team, were prospectively included in the study. FDG PET/CT scans were performed in all patients before and after two of the three cycles of DCF. EORTC99 criteria were used to evaluate PET responses as follows: group 1 (metabolic responders) showing a complete response (CR) or partial response (PR), and subgroup 0 (metabolic nonresponders) showing stable disease (SD) or progressive disease (PD). The primary endpoint for monitoring patients was event-free survival (EFS). EFS probabilities between the two groups were estimated by the Kaplan-Meier method and statistically compared using the log-rank test. Fifteen consecutive patients (14 men, 1 woman; age 57.5 ± 6.2 years, mean ± SD) were analysed. Therapeutic assessment by PET/CT demonstrated CR in four patients, PR in six, SD in four and PD in one. Among the ten patients with a metabolic response (group 1), none had relapsed at the time of this report, while four of five patients with no metabolic response (group 0) showed recurrence within an average of 9.0 ± 1.6 months. Median EFS was, respectively, 18.9 months (3.8-25.3 months) and 10.2 months (7.5-12.7 months) in group 1 and group 0. The corresponding 1-year EFS rates were 100 % and 20 %, respectively. The difference in EFS between the two groups was statistically significant (p = 0.0014). Early therapeutic response demonstrated on FDG PET/CT after two cycles of induction

  10. 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...

  11. In vitro chemosensitivity of head and neck cancer cell lines

    Directory of Open Access Journals (Sweden)

    Schuler PJ

    2010-08-01

    Full Text Available Abstract Background Systemic treatment of head and neck squamous cell carcinoma (HNSCC includes a variety of antineoplastic drugs. However, drug-resistance interferes with the effectiveness of chemotherapy. Preclinical testing models are needed in order to develop approaches to overcome chemoresistance. Methods Ten human cell lines were obtained from HNSCC, including one with experimentally-induced cisplatin resistance. Inhibition of cell growth by seven chemotherapeutic agents (cisplatin, carboplatin, 5- fluorouracil, methotrexate, bleomycin, vincristin, and paclitaxel was measured using metabolic MTT-uptake assay and correlated to clinically-achievable plasma concentrations. Results All drugs inhibited cell growth in a concentration-dependent manner with an IC50 comparable to that achievable in vivo. However, response curves for methotrexate were unsatisfactory and for paclitaxel, the solubilizer cremophor EL was toxic. Cross-resistance was observed between cisplatin and carboplatin. Conclusion Chemosensitivity of HNSCC cell lines can be determined using the MTT-uptake assay. For DNA-interfering cytostatics and vinca alkaloids this is a simple and reproducible procedure. Determined in vitro chemosensitivity serves as a baseline for further experimental approaches aiming to modulate chemoresistance in HNSCC with potential clinical significance.

  12. 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...

  13. 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.

  14. 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...

  15. Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients

    OpenAIRE

    Jie, H-B; Gildener-Leapman, N; Li, J.; Srivastava, R. M.; Gibson, S P; Whiteside, T L; Ferris, R. L.

    2013-01-01

    Background: Although regulatory T cells (Treg) are highly enriched in human tumours compared with peripheral blood, expression of the immune-checkpoint receptors, immunosuppressive molecules and function of Treg in these two sites remains undefined. Methods: Tumour-infiltrating lymphocytes and peripheral blood lymphocytes were isolated from a cohort of head and neck squamous cell carcinoma (HNSCC) patients. The immunosuppressive phenotypes and function of intratumoral Treg were compared with ...

  16. 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

  17. 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.

  18. 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...

  19. 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.

  20. 头颈部鳞状细胞癌血清SCC、CYFRA21-1、NSE、CEA联合检测的临床意义%Clinical value of combined detection of tumor markers for nasopharyngeal carcinoma and squamous cell carcinoma in head and neck

    Institute of Scientific and Technical Information of China (English)

    王继生; 孙艳

    2009-01-01

    Objective To study the clinical value of serum SCC,CYFRA21-1,NSE and CEA for patients with nasopharyngeal carcinoma (NPC) and squamous cell carcinoma of head and neck (NHSCC). Methods From Aug 2004 to Sep 2007, the serum levels of SCC, CYFRA21-1, NSE and CEA were detected in 79 NPC and 51 HNSCC before and after radiotherapy. The clinical related factors were analyzed. Results Before treatment, the positive rates of serum SCC, CYFRA21-1, NSE and CEA for patients with NPC were 10.53 %, 46.75 %, 17.5 % and 2.04 %, respectively. The sensitivity of combined detection was 78.95 %. The positive rates for patients with HNSCC were 22 %, 19.75 %, 11.11% and 0, respectively. The sensitivity of combined detection was 36.17 %. The level of SCC was related to staging in HNSCC group. CYFRA21-1 was related to the rote of treatment response in NPC group. Conclusion The sensitivity of combined detection of tumor markers were significantly increased. CYFRA21-1 associated with NPC and SCC with HNSCC were noted in this study.%目的 探讨血清鳞状细胞癌相关抗原(SCC)、细胞角蛋白19血清片段21-1(CYFRA21-1)、神经元特异性烯醇化酶(NSE)、癌胚抗原(CEA)在鼻咽癌(NPC)和头其他颈部鳞癌(HNSCC)患者临床诊疗中的价值.方法 在2004年8月至2007年9月接受放疗的患者中,79例NPC和51例HNSCC治疗前后进行了血清SCC、CYFRA21-1、NSE和CEA水平的检测,对其结果与临床相关因素的关系进行分析.结果 治疗前NPC患者血清SCC、CYFRA21-1、NSE和CEA阳性率分别为10.53%、46.75%、17.50%和2.04%,联合检测阳性率是78.95%;HNSCC分别为22.00%、19.75%、11.11%、0,联合检测是36.17%,联合检测阳性率均明显增高(P<0.01).NPC治疗后血清CYFRA 21-1和NSE水平明显下降(P<0.0001),CYFRA 21-1与近期疗效相关(P=0.0339);HNSCC组中SCC与分期有相关趋势(P=0.0597).结论 联合检测的敏感性较单项检查高,可以提高HNSCC的阳性检出率,有较高的临床诊断价值.CYFRA 21-1

  1. 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.

  2. 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.

  3. 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.

  4. 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....

  5. 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...

  6. 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.

  7. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Marilene B

    2011-02-01

    Full Text Available Abstract Curcumin (diferuloylmethane is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-κB and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-α, interleukins and MMP-9. In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent.

  8. (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

  9. FDG-PET AS A ROUTINE SURVEILLANCE TOOL IN HEAD AND NECK CARCINOMA SIX MONTHS AFTER TREATMENT

    Institute of Scientific and Technical Information of China (English)

    XU Ya-nan; Sophie Périé; WANG Jia-dong

    2009-01-01

    Objective To evaluate prospectively the impact of fluorodeoxyglucose-fluorine-18 positron emission tomography (FDG-PET) in the detection of recurrence, second primary cancers, and distant metastases in head and neck squamous cell carcinoma (HNSCC) 6 months after treatment. Methods A total of 41 patients without any clinical element for recurrence, second primary cancer, or distant metastases received a whole-body FDG-PET as a routine surveillance tool 6 months after initial combined curative therapy for HNSCC. Results There were 35 negative PET results and 6 positive. One patient with abnormal FDG-PET did not have recurrent HNSCC (false positive). Five had true positive results: proven recurrence in 2 patients, second primary cancer in 2, and distant metastasis in 1. The sensitivity and specificity of FDG-PET for the diagnosis of HNSCC recurrence, second tumor, and distant metastases were 100% (5/5) and 97.2% (35/36), respectively. The positive predictive value was 83.3% (5/6). The negative predictive value was 100% (35/35). The overall accuracy was 97.6% (40/41). FDG-PET had a therapeutic impact in 5 of 41 patients (12.2%). There was no impact of FDG-PET on management in other 36 patients. Conclusion FDG-PET is useful as primary method for detecting nodal recurrence and distant metastases in HNSCC as well as second cancer in subclinical patients as it had a high effectiveness. But systematic FDG-PET performed at 6 months in patients without any clinical suspicion of local recurrence was scarcely useful.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.)

  15. 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...

  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. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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

  4. 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

  5. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Correlation between egfr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Pedicini Piernicola

    2012-08-01

    Full Text Available Abstract Purpose To investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr and the reduction of the effective doubling time (TD during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC. Methods A survey of the published papers comparing 3-years of local regional control rate (LCR for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of TD were obtained by a model incorporating the overall time corrected biologically effective dose (BED and a 3-year clinical LCR for high and low EGFr groups of patients (HEGFr and LEGFr, respectively. By obtaining the TD from the above analysis and the sub-sites’ potential doubling time (Tpot from flow cytometry and immunohistochemical methods, we were able to estimate the average TD for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (Dprolif, was estimated. Results The averages of TD were 77 (27-9095% days in LEGFr and 8.8 (7.3-11.095% days in HEGFr, if an onset of accelerated proliferation TK at day 21 was assumed. The correspondent HEGFr sub-sites’ TD were 5.9 (6.6, 5.9 (6.6, 4.6 (6.1, 14.3 (12.9 days, with respect to literature immunohistochemical (flow cytometry data of Tpot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The Dprolif for the HEGFr groups were 0.33 (0.29, 0.33 (0.29, 0.42 (0.31, 0.14 (0.15 Gy/day if α = 0.3 Gy-1 and α/β = 10 Gy were assumed. Conclusions A higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced TD and Dprolif for each head and neck

  12. Correlation between egfr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    To investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr) and the reduction of the effective doubling time (TD) during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC). A survey of the published papers comparing 3-years of local regional control rate (LCR) for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of TD were obtained by a model incorporating the overall time corrected biologically effective dose (BED) and a 3-year clinical LCR for high and low EGFr groups of patients (HEGFr and LEGFr), respectively. By obtaining the TD from the above analysis and the sub-sites’ potential doubling time (Tpot) from flow cytometry and immunohistochemical methods, we were able to estimate the average TD for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (Dprolif), was estimated. The averages of TD were 77 (27-90)95% days in LEGFr and 8.8 (7.3-11.0)95% days in HEGFr, if an onset of accelerated proliferation TK at day 21 was assumed. The correspondent HEGFr sub-sites’ TD were 5.9 (6.6), 5.9 (6.6), 4.6 (6.1), 14.3 (12.9) days, with respect to literature immunohistochemical (flow cytometry) data of Tpot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The Dprolif for the HEGFr groups were 0.33 (0.29), 0.33 (0.29), 0.42 (0.31), 0.14 (0.15) Gy/day if α = 0.3 Gy-1 and α/β = 10 Gy were assumed. A higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced TD and Dprolif for each head and neck sub-site

  13. 头颈鳞癌根治性手术后辅助治疗%Adjuvant treatment for squamous cell carcinoma of head and neck after definitive surgery

    Institute of Scientific and Technical Information of China (English)

    温江妹; 林少俊

    2013-01-01

    头颈部鳞癌根治术后的辅助治疗在整个治疗中占有重要地位。早期N+患者可接受根治手术后的辅助放疗;同步放化疗则是局部晚期头颈鳞癌患者术后辅助的标准治疗模式。联合治疗能有效提高肿瘤的局部控制率和患者的无病生存率及总生存率,但联合治疗所导致的急慢性不良反应亦不容忽视。调强放射治疗(intensity modulated radiation therapy,IMRT)较三维适型放疗更为精确和适形,但是否可能增加治疗后局部区域复发风险仍需进一步研究。分子靶向治疗(如西妥昔单抗、尼妥珠单抗)联合放射治疗虽可提高局部晚期头颈部鳞癌根治后的疗效,但其联合放疗的治疗策略在术后辅助治疗上的应用,尚无设计良好的临床研究结果的支持。人乳头状瘤病毒(human papillomavirus,HPV)与头颈部鳞癌的预后及治疗的相关性,及其对治疗选择的指导作用,则有待进一步研究。%Adjuvant treatment after deifnitive surgery is an integral part of the management of locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC). Earlier stage HNSCC with N+disease may require adjuvant radiotherapy, while locoregionally advanced disease requires postoperative chemoradiation therapy for eradicating subclinical residual disease. Tri-modality with surgery followed by concurrent chemoradiation can improve the local control, disease free survival, and overall survival rates in patients with advanced HNSCC as compare to surgery or surgery plus radiation. However, treatment induced adverse-effects should be addressed when deciding on the treatment options. Molecular targeted therapy is a new treatment modality and its efifcacy when used in concurrent with radiation as a deifnitive treatment has been suggested. However, adjuvant use of radiation and targeted therapy requires further investigation before it can be recommended routinely in clinical practice. The

  14. Molecular characterization of oropharyngeal and oral squamous cell carcinomas

    NARCIS (Netherlands)

    Kempen, P.M.W. van

    2016-01-01

    Despite improvements in conventional therapy, the five-year survival rate has not significantly changed over the past decades and remains approximately 50%. In addition, the impact on the quality of life remains a major consideration in selecting appropriate treatment for HNSCC. Nowadays, all patien

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  10. 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.

  11. 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

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  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Potential effect of matrix stiffness on the enrichment of tumor initiating cells under three-dimensional culture conditions.

    Science.gov (United States)

    Liu, Chang; Liu, Yang; Xu, Xiao-xi; Wu, Hao; Xie, Hong-guo; Chen, Li; Lu, Ting; Yang, Li; Guo, Xin; Sun, Guang-wei; Wang, Wei; Ma, Xiao-jun; He, Xin

    2015-01-01

    Cancer stem cell (CSC) or tumor initiating cell (TIC) plays an important role in tumor progression and metastasis. Biophysical forces in tumor microenvironment have an important effect on tumor formation and development. In this study, the potential effect of matrix stiffness on the biological characteristics of human head and neck squamous cell carcinoma (HNSCC) TICs, especially the enrichment of HNSCC TICs, was investigated under three-dimensional (3D) culture conditions by means of alginate gel (ALG) beads with different matrix stiffnesses. ALG beads with soft (21 kPa), moderate (70 kPa) and hard (105 kPa) stiffness were generated by changing alginate concentration. It was found that significant HNSCC TIC enrichment was achieved in the ALG beads with moderate matrix stiffness (70 kPa). The gene expression of stemness markers Oct3/4 and Nanog, TIC markers CD44 and ABCG2 was enhanced in cells under this moderate (70 kPa) stiffness. HNSCC TIC proportion was also highly enriched under moderate matrix stiffness, accompanying with higher tumorigenicity, metastatic ability and drug resistance. And it was also found that the possible molecular mechanism underlying the regulated TIC properties by matrix stiffness under 3D culture conditions was significantly different from 2D culture condition. Therefore, the results achieved in this study indicated that 3D biophysical microenvironment had an important effect on TIC characteristics and alginate-based biomimetic scaffolds could be utilized as a proper platform to investigate the interaction between tumor cells and 3D microenvironment.

  12. The effect of red-allotrope selenium nanoparticles on head and neck squamous cell viability and growth

    Directory of Open Access Journals (Sweden)

    Hassan CE

    2016-08-01

    Full Text Available Christopher E Hassan,1 Thomas J Webster1,2 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Given their low toxicity and natural presence in the human diet, selenium nanoparticles have been established as potential candidates for the treatment of numerous cancers. Red-allotrope selenium nanoparticles (rSeNPs were synthesized and characterized in this study. Head and neck squamous cell carcinoma (HNSCC and human dermal fibroblast (HDF cells were cultured and exposed to rSeNPs at concentrations ranging from 0.01 to 100 µg rSeNP/mL media for 1–3 days. The toxicity of rSeNP toward HNSCC and HDFs was analyzed. Results indicated that the particles were approximately four times as cytotoxic toward HNSCC compared to HDFs, with their respective IC50 values at 19.22 and 59.61 µg rSeNP/mL media. Using statistical analysis, an effective dosage range for killing HNSCC cells while simultaneously minimizing damage to HDFs over a 3-day incubation period was established at 20–55 µg rSeNP/mL media. Observations showed that doses of rSeNP <5 µg rSeNP/mL media resulted in cell proliferation. Transmission electron microscopy images of HNSCC and HDF cells, both treated with rSeNPs, revealed that the rSeNPs became localized in the cytoplasm near the lysosomes and mitochondria. Analysis of cell morphology showed that the rSeNPs primarily induced HNSCC apoptosis. Collectively, these results indicated that rSeNPs are a promising option for treating HNSCC without adversely affecting healthy cells and without resorting to the use of harmful chemotherapeutics. Keywords: selenium, nanotechnology, biomaterials, head and neck squamous cell carcinoma, human dermal fibroblasts, cancer 

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.)

  3. 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.

  4. 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.).

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.)

  12. 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

  13. 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...

  14. 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...

  15. Combined cetuximab and reirradiation for locoregional recurrent and inoperable squamous cell carcinoma of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Balermpas, Panagiotis; Roedel, Claus; Weiss, Christian [Dept. of Radiation Therapy and Oncology, Goethe Univ., Frankfurt/Main (Germany); Hambek, Markus [Dept. of Otorhinolaryngology, Goethe Univ., Frankfurt/Main (Germany); Seitz, Oliver [Dept. of Oral Maxillofacial and Plastic Facial Surgery, Goethe Univ., Frankfurt/Main (Germany)

    2009-12-15

    Purpose: to investigate the feasibility, toxicity, and efficacy of external-beam reirradiation (Re-RT) combined with cetuximab for patients with inoperable and recurrent squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: seven patients with inoperable recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were treated between August and December 2008 with Re-RT (1.8 Gy/fraction to 50.4 Gy) and cetuximab (400 mg/m{sup 2} initial dose in the 1st week, and then 250 mg/m{sup 2} once weekly). Recurrence had to be located at least {>=} 50% in the preirradiated field. Long term toxicity from previous treatment was recorded before Re-RT as a baseline value. Acute and late toxicity derived from the experimental regimen were recorded every week during RT, and then every 3 months. Efficacy was assessed with repeated imaging using response evaluation criteria in solid tumors (RECIST) and clinical examinations 8-12 weeks after end of the treatment and every 3 months thereafter (Tables 1 and 2). Results: only mild localized mucositis occurred in all patients. Two patients developed a grade 3 acneiform rash related to cetuximab. After treatment one patient developed a grade 2 trismus, another showed grade 3 abacterial salivary gland inflammation with severe pain requiring opioid medication. Two patients achieved a complete response after 7 months, one remained stable, three progressed, and one died from pneumonia without having restaging magnetic resonance imaging. Conclusion: A second course of RT combined with cetuximab in patients with inoperable, recurrent HNSCC proved to be feasible with mild or moderate toxicity and encouraging response to treatment. (orig.)

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Nör

    2014-02-01

    Full Text Available Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs. These unique cells, named here cancer stem cells (CSCs, proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B cells and observed that cisplatin treatment increased (P = .0013 the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDHhighCD44high]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1 and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDHhighCD44high immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3 phosphorylation (indicative of stemness was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK phosphorylation (indicative of differentiation processes was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs