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Sample records for adenocarcinoma squamous cell

  1. Atypical squamous cells in the urine revealing endometrioid adenocarcinoma of the endometrium with squamous cell differentiation: a case report.

    PubMed

    Wang, Yinong; Otis, Christopher N; Florence, Roxanne R

    2015-01-01

    Urine cytology is mainly used to detect urothelial carcinoma (UC), especially for high-grade lesions including urothelial carcinoma in situ. Benign squamous cells are often seen in the urine specimens of women, they are either exfoliated from the trigone area of the bladder, the urethra, or the cervicovaginal region. However, abnormal squamous cells in the urine raise concerns of abnormalities of the urinary tract and cervicovaginal area which range from squamous metaplasia of the urothelium, a cervicovaginal squamous intraepithelial lesion, condyloma acuminatum of the bladder, UC with squamous differentiation, and squamous cell carcinoma. We present here a unique case of atypical squamous cells (ASCs) in the urine subsequently leading to the diagnosis of endometrioid adenocarcinoma of the endometrium with squamous differentiation. The presence of ASCs in voided urine is a rare finding that may indicate an underlying malignancy. Careful evaluation of squamous cells in the urine is an important part of our daily cytopathology practice.

  2. Absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissues

    NASA Astrophysics Data System (ADS)

    Ivashko, Pavlo; Peresunko, Olexander; Zelinska, Natalia; Alonova, Marina

    2014-08-01

    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  3. Pulmonary mixed squamous cell and glandular papilloma mimicking adenocarcinoma: a case study and literature review.

    PubMed

    Lin, Dongliang; Jiang, Yanxia; Wang, Jigang; Ding, Li; Xin, Fangjie; Zhao, Han; Li, Yujun

    2013-08-01

    Mixed squamous cell and glandular papilloma of the lung is an extremely rare benign neoplasm. Here we present another case of mixed squamous cell and glandular papilloma in a 64-year-old female nonsmoker. Histologically, the tumor was composed of mainly papillary structures covered with squamous, glandular and transitional epithelium. Some glandular structures extending into adjacent bronchiolar and alveolar spaces with mucus were similar to adenocarcinoma. Immunohistochemical analysis showed the different kinds of epithelia had similar immunophenotype. The different components were positive for cytokeratin (CK)7, CK19, CAM5.2, CK5/6, CK34βE12, and TTF-1, but negative for CK20. The transitional morphology and immunohistochemistry indicate the different components likely come from a same kind of progenitor in the bronchiolar wall.

  4. The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma

    PubMed Central

    Fu, Pin; Chen, Fuchun; Pan, Qi; Zhao, Xianda; Zhao, Chen; Cho, William Chi-Shing; Chen, Honglei

    2017-01-01

    Caveolin-1 (Cav-1), a major structural protein of caveolae, is an integral membrane protein which plays an important role in the progression of carcinoma. However, whether Cav-1 acts as a tumor promoter or a tumor suppressor still remains controversial. For example, the tumor-promoting function of Cav-1 has been found in renal cancer, prostate cancer, tongue squamous cell carcinoma (SCC), lung SCC and bladder SCC. In contrast, Cav-1 also plays an inhibitory role in esophagus adenocarcinoma, lung adenocarcinoma and cutaneous SCC. The role of Cav-1 is still controversial in thyroid cancer, hepatocellular carcinoma, gastric adenocarcinoma, colon adenocarcinoma, breast cancer, pancreas cancer, oral SCC, laryngeal SCC, head and neck SCC, esophageal SCC and cervical SCC. Besides, it has been reported that the loss of stromal Cav-1 might predict poor prognosis in breast cancer, gastric cancer, pancreas cancer, prostate cancer, oral SCC and esophageal SCC. However, the accumulation of stromal Cav-1 has been found to be promoted by the progression of tongue SCC. Taken together, Cav-1 seems playing a different role in different cancer subtypes even of the same organ, as well as acting differently in the same cancer subtype of different organs. Thus, we hereby explore the functions of Cav-1 in human adenocarcinoma and SCC from the perspective of clinical significances and pathogenesis. We envision that novel targets may come with the further investigation of Cav-1 in carcinogenesis. PMID:28243118

  5. MiR-205 functions as a tumor suppressor in adenocarcinoma and an oncogene in squamous cell carcinoma of esophagus.

    PubMed

    Hezova, Renata; Kovarikova, Alena; Srovnal, Josef; Zemanova, Milada; Harustiak, Tomas; Ehrmann, Jiri; Hajduch, Marian; Sachlova, Milana; Svoboda, Marek; Slaby, Ondrej

    2016-06-01

    Esophageal cancer is a malignant disease with poor prognosis, increasing incidence, and ineffective treatment options. MicroRNAs are post-transcriptional regulators of gene expression involved in many biological processes including carcinogenesis. We determined miR-205 expression levels in tumor/non-tumor tissues of 45 esophageal cancer patients using qPCR and found that decreased level of miR-205 in tumor tissue correlates with poor overall survival in esophageal adenocarcinoma patients. Further, we observed significantly higher levels of miR-205 in tumor tissue of esophageal squamous cell carcinoma. Ectopic overexpression of miR-205 in adenocarcinoma cell line SK-GT-4 led to decreased cell proliferation, cell cycle arrest in G1, and decreased migration ability. Conversely, in squamous cell line KYSE-150, same effects like inhibition of proliferation, migration, and colony-forming potential and cell cycle arrest in G2 were observed after silencing of miR-205. We performed global gene expression profiling and revealed that suppressive functioning of miR-205 in adenocarcinoma could be realized through regulation of epithelial-mesenchymal transition (EMT), whereas oncogenic in squamous cell carcinoma by regulation of metalloproteinase 10. Our results suggest that miR-205 could serve as biomarker in esophageal cancer and acts as a tumor suppressor in esophageal adenocarcinoma and oncogene in esophageal squamous cell carcinoma.

  6. Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma

    PubMed Central

    Han, Xiangkun; Li, Fuming; Fang, Zhaoyuan; Gao, Yijun; Li, Fei; Fang, Rong; Yao, Shun; Sun, Yihua; Li, Li; Zhang, Wenjing; Ma, Huimin; Xiao, Qian; Ge, Gaoxiang; Fang, Jing; Wang, Hongda; Zhang, Lei; Wong, Kwok-kin; Chen, Haiquan; Hou, Yingyong; Ji, Hongbin

    2014-01-01

    Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment. PMID:24531128

  7. Comparison of absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissue

    NASA Astrophysics Data System (ADS)

    Peresunko, O. P.; Zelinska, N. V.; Prydij, O. G.; Zymnyakov, D. A.; Ushakova, O. V.

    2013-12-01

    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  8. Evidence, Mechanism, and Clinical Relevance of the Transdifferentiation from Lung Adenocarcinoma to Squamous Cell Carcinoma.

    PubMed

    Hou, Shenda; Zhou, Shiyu; Qin, Zhen; Yang, Liu; Han, Xiangkun; Yao, Shun; Ji, Hongbin

    2017-03-08

    Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct subtypes of non-small-cell lung carcinoma. Interestingly, approximately 4% to 9% of human non-small-cell lung carcinoma tumors contain mixed adenomatous and squamous pathologies in a single lesion, clinically termed adenosquamous cell carcinoma. More important, these two different pathological components frequently share identical oncogenic mutations, indicative of a potential transition. Indeed, recent data have provided convincing evidence in supporting the ADC to SCC transdifferentiation in lungs. In the liver kinase B1 (official name STK11)-deficient mouse model, lung ADC can progressively transdifferentiate to SCC through pathologically mixed adenosquamous cell carcinoma as the intermediate status. Mechanistic studies further identify essential roles of extracellular matrix remodeling and metabolic reprogramming during this phenotypic transition. Small molecular compounds, including lysyl oxidase inhibitors and reactive oxygen species-inducing reagents such as phenformin, significantly accelerate the transition from lung ADC to SCC and thus confer lung tumors with drug resistance. Consistent with these findings, recent clinical studies have shown that epidermal growth factor receptor-mutant lung ADC can transdifferentiate to SCC in relapsed cancer patients. Together, these data support that this phenotypic transition from lung ADC to SCC might represent a novel mechanism for drug resistance. This review will summarize our current understanding of the transdifferentiation from lung ADC to SCC.

  9. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas.

    PubMed

    Campbell, Joshua D; Alexandrov, Anton; Kim, Jaegil; Wala, Jeremiah; Berger, Alice H; Pedamallu, Chandra Sekhar; Shukla, Sachet A; Guo, Guangwu; Brooks, Angela N; Murray, Bradley A; Imielinski, Marcin; Hu, Xin; Ling, Shiyun; Akbani, Rehan; Rosenberg, Mara; Cibulskis, Carrie; Ramachandran, Aruna; Collisson, Eric A; Kwiatkowski, David J; Lawrence, Michael S; Weinstein, John N; Verhaak, Roel G W; Wu, Catherine J; Hammerman, Peter S; Cherniack, Andrew D; Getz, Gad; Artyomov, Maxim N; Schreiber, Robert; Govindan, Ramaswamy; Meyerson, Matthew

    2016-06-01

    To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. New amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase-Ras-Raf pathway alterations had mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least five predicted neoepitopes. Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes.

  10. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas

    PubMed Central

    Campbell, Joshua D.; Alexandrov, Anton; Kim, Jaegil; Wala, Jeremiah; Berger, Alice H.; Pedamallu, Chandra Sekhar; Shukla, Sachet A.; Guo, Guangwu; Brooks, Angela N.; Murray, Bradley A.; Imielinski, Marcin; Hu, Xin; Ling, Shiyun; Akbani, Rehan; Rosenberg, Mara; Cibulskis, Carrie; Ramachandran, Aruna; Collisson, Eric A.; Kwiatkowski, David J.; Lawrence, Michael S.; Weinstein, John N.; Verhaak, Roel G. W.; Wu, Catherine J.; Hammerman, Peter S.; Cherniack, Andrew D.; Getz, Gad; Artyomov, Maxim N.; Schreiber, Robert; Govindan, Ramaswamy; Meyerson, Matthew

    2016-01-01

    To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor/normal pairs. Recurrent alterations in lung SqCCs were more similar to other squamous carcinomas than to lung ADCs. Novel significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. Novel amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase/Ras/Raf alterations revealed mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least 5 predicted neoepitopes. While targeted therapies for lung ADC and lung SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes. PMID:27158780

  11. Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma

    PubMed Central

    Vanni, Irene; Coco, Simona; Bonfiglio, Silvia; Cittaro, Davide; Genova, Carlo; Biello, Federica; Mora, Marco; Rossella, Valeria; Dal Bello, Maria Giovanna; Truini, Anna; Banelli, Barbara; Lazarevic, Dejan; Alama, Angela; Rijavec, Erika; Barletta, Giulia; Grossi, Francesco

    2016-01-01

    Abstract The presence of multiple primary tumors (MPT) in a single patient has been identified with an increasing frequency. A critical issue is to establish if the second tumor represents an independent primary cancer or a metastasis. Therefore, the assessment of MPT clonal origin might help understand the disease behavior and improve the management/prognosis of the patient. Herein, we report a 73-year-old male smoker who developed 2 primary lung cancers (adenocarcinoma and squamous cell carcinoma) and a malignant peritoneal mesothelioma (PM). Whole exome sequencing (WES) of the 3 tumors and of germline DNA was performed to determine the clonal origin and identify genetic cancer susceptibility. Both lung cancers were characterized by a high mutational rate with distinct mutational profiles and activation of tumor-specific pathways. Conversely, the PM harbored a relative low number of genetic variants and a novel mutation in the WT1 gene that might be involved in the carcinogenesis of nonasbestos-related mesothelioma. Finally, WES of the germinal DNA displayed several single nucleotide polymorphisms in DNA repair genes likely conferring higher cancer susceptibility. Overall, WES did not disclose any somatic genetic variant shared across the 3 tumors, suggesting their clonal independency; however, the carcinogenic effect of smoke combined with a deficiency in DNA repair genes and the patient advanced age might have been responsible for the MPT development. This case highlights the WES importance to define the clonal origin of MPT and susceptibility to cancer. PMID:27902597

  12. Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the human lung

    SciTech Connect

    Weston, A.; Willey, J.C.; Modali, R.; Sugimura, H.; McDowell, E.M.; Resau, J.; Light, B.; Haugen, A.; Mann, D.L.; Trump, B.F.; Harris, C.C. )

    1989-07-01

    Activation of protooncogens and inactivation of putative tumor suppressor genes are genetic lesions considered to be important in lung carcinogenesis. Fifty-four cases of non-small-cell lung cancer (23 adenocarcinomas, 23 squamous-cell carcinomas, and 8 large-cell carcinomas) were examined for loss of DNA sequences at 13 polymorphic genetic loci. Loss of heterozygosity was seen more frequently in squamous-cell carcinoma than in adenocarcinoma. The loss of DNA sequences from the short arm of chromosome 17 (D17S1 locus) was detected in 8 of 9 heterozygous cases of squamous-cell carcinoma and in only 2 of 11 heterozygous cases of adenocarcinomas. Loss of DNA sequences from chromosome 3 was seen in 16 of 31 cases where the constitutive DNA was heterozygous-i.e., informative. Loss of heterozygosity at the chromosome 13q locus, D13S3, was seen in 9 of 21 informative cases, and in 2 cases, both adenocarcinomas, duplication of the intact DNA sequences suggested the possibility that mitotic recombination had occurred. Frequent DNA sequence deletions, including those from chromosome 17, in squamous-cell carcinomas may reflect the extensive mutagenic and clastogenic effects of tobacco smoke that may lead to inactivation of putative tumor-suppressor genes.

  13. Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

    PubMed

    Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad

    2014-01-01

    Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (P<0.05). Avocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers.

  14. Differential HPV16 variant distribution in squamous cell carcinoma, adenocarcinoma and adenosquamous cell carcinoma.

    PubMed

    Nicolás-Párraga, S; Alemany, L; de Sanjosé, S; Bosch, F X; Bravo, I G

    2017-05-01

    Human Papillomavirus 16 (HPV16) causes 70% of invasive cervical cancers (ICC) worldwide. Interaction between HPV16 genetic diversity, host genetics and target tissue largely determine the chances to trigger carcinogenesis. We have analyzed the differential prevalence of viral variants in 233 HPV16-monoinfected squamous (SCC), glandular (ADC) and mixed (ADSC) ICCs from four continents, assessing the contribution of geographical origin and cancer histology. We have further quantified the contribution of viral variants and cancer histology to differences in age at tumor diagnosis. The model fitted to the data explained 97% of the total variance: the largest explanatory factors were differential abundance among HPV16 variants (78%) and their interaction with cancer histology (9.2%) and geography (10.1%). HPV16_A1-3 variants were more prevalent in SCC while HPV16_D variants were increased in glandular ICCs. We confirm further a non-random geographical structure of the viral variants distribution. ADCs were diagnosed at younger ages than SCCs, independently of the viral variant triggering carcinogenesis. HPV16 variants are differentially associated with histological ICCs types, and ADCs are systematically diagnosed in younger women. Our results have implications for the implementation of cervical cancer screening algorithms, to ensure proper early detection of elusive ADCs.

  15. Best immunohistochemical panel in distinguishing adenocarcinoma from squamous cell carcinoma of lung: tissue microarray assay in resected lung cancer specimens.

    PubMed

    Kim, Mi Jin; Shin, Hyeong Chan; Shin, Kyeong Cheol; Ro, Jae Y

    2013-02-01

    The emergence of the targeted therapies for non-small cell lung carcinoma (NSCLC) has generated a need for accurate histologic subtyping of NSCLC. In this study, we assessed the utility of immunohistochemical markers that could be helpful in distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We performed a battery of immunohistochemistry using tissue microarray for napsin-A, Thyroid transcription factor 1 (TTF-1), p63, cytokeratin (CK) 5/6, thrombomodulin (CD141), Epithelial-related antigen (MOC-31), carcinoembryonic antigen (CEA), Cyclooxygenase 2 (COX-2), high-molecular-weight CK (HMWCK), p27kip1 (p27), and Rb protein in 129 resected primary NSCLC with 81 ADCs and 48 SCCs and 10 metastatic ADC to the lung (primary in colon, 7 cases; stomach, 2 cases; vagina, 1 case). Cases of ADC and SCC were morphologically unequivocal and solid tumors with no definite squamous or glandular differentiation were excluded for this analysis. Napsin-A and TTF-1 were positive in 81% and 70% of ADC and in 0% and 2% of SCC, respectively, whereas P63 and CK5/6 were positive in 91% and 90% of SCC and in 9% and 4% of ADC, respectively (P < .001). CD141 stained significantly higher in SCC over ADC (positive in 2% of ADC and 46% of SCC. MOC-31, CEA, COX-2, HMWCK, p27, and Rb appeared to be not useful markers in distinction between ADC and SCC because of their low specificity. None of metastatic ADC to the lung showed positive for napsin-A and TTF-1. It was evident that combination of napsin-A, TTF-1, CK5/6, and p63 was the best immunohistochemical panel in differentiating ADC from SCC of the lung in this study. CD141 appeared to be a potential new marker for SCC with high specificity. Cyclooxygenase 2, MOC-31, CEA, HMWCK, p27, and Rb showed less specificity for differentiation ADC from SCC.

  16. EGFR mutation in squamous cell carcinoma of the lung: does it carry the same connotation as in adenocarcinomas?

    PubMed Central

    Joshi, Amit; Zanwar, Saurabh; Noronha, Vanita; Patil, Vijay M; Chougule, Anuradha; Kumar, Rajiv; Janu, Amit; Mahajan, Abhishek; Kapoor, Akhil; Prabhash, Kumar

    2017-01-01

    Background EGFR tyrosine kinase inhibitors (TKIs) have greatly improved the outcomes of EGFR mutation-positive adenocarcinomas of the lung. In contrast, the significance of EGFR mutation in metastatic squamous cell carcinoma (SCC) of the lung has been debated. Methods All patients with metastatic SCC who underwent EGFR mutation testing at our center from 2010 to 2015 were included for analysis. EGFR kinase domain mutations were tested using Taqman-based real-time polymerase chain reaction (PCR). Response assessment was done using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Kaplan–Meier method was used for calculating progression-free survival (PFS) and overall survival (OS). Results EGFR mutation was detected in 29 out of 639 patients with SCC. Furthermore, 19 out of the 29 patients received TKIs at some point during their treatment. TKI therapy led to a partial response in 5 out of 19 patients and stable disease in 4 out of 19 patients. The median PFS of patients treated with TKIs was 5.0 months. The median OS of the whole EGFR-positive SCC cohort was 6.6 months. On univariate analysis, patients having received TKI therapy was the only factor associated with a significantly better OS of 13.48 months versus 2.58 months (P=0.000). On multivariate analysis, patients receiving TKI therapy, Eastern Cooperative Oncology Group–Performance Scale (ECOG-PS) score <2, EGFR exon 19 mutation and nonsmoking status were associated with significantly better OS. Conclusion EGFR mutation in SCC of the lung predicts a better outcome if the patient is given TKI, but it may be inferior to the outcomes seen in EGFR-positive adenocarcinomas treated with TKI.

  17. Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix.

    PubMed

    Blanco-Luquin, Idoia; Guarch, Rosa; Ojer, Amaya; Pérez-Janices, Noemí; Martín-Sánchez, Esperanza; Maria-Ruiz, Sergio; Monreal-Santesteban, Iñaki; Blanco-Fernandez, Laura; Pernaut-Leza, Eduardo; Escors, David; Guerrero-Setas, David

    2015-09-01

    Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors.

  18. Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma: A case report.

    PubMed

    Vanni, Irene; Coco, Simona; Bonfiglio, Silvia; Cittaro, Davide; Genova, Carlo; Biello, Federica; Mora, Marco; Rossella, Valeria; Dal Bello, Maria Giovanna; Truini, Anna; Banelli, Barbara; Lazarevic, Dejan; Alama, Angela; Rijavec, Erika; Barletta, Giulia; Grossi, Francesco

    2016-11-01

    The presence of multiple primary tumors (MPT) in a single patient has been identified with an increasing frequency. A critical issue is to establish if the second tumor represents an independent primary cancer or a metastasis. Therefore, the assessment of MPT clonal origin might help understand the disease behavior and improve the management/prognosis of the patient.Herein, we report a 73-year-old male smoker who developed 2 primary lung cancers (adenocarcinoma and squamous cell carcinoma) and a malignant peritoneal mesothelioma (PM).Whole exome sequencing (WES) of the 3 tumors and of germline DNA was performed to determine the clonal origin and identify genetic cancer susceptibility.Both lung cancers were characterized by a high mutational rate with distinct mutational profiles and activation of tumor-specific pathways. Conversely, the PM harbored a relative low number of genetic variants and a novel mutation in the WT1 gene that might be involved in the carcinogenesis of nonasbestos-related mesothelioma. Finally, WES of the germinal DNA displayed several single nucleotide polymorphisms in DNA repair genes likely conferring higher cancer susceptibility.Overall, WES did not disclose any somatic genetic variant shared across the 3 tumors, suggesting their clonal independency; however, the carcinogenic effect of smoke combined with a deficiency in DNA repair genes and the patient advanced age might have been responsible for the MPT development. This case highlights the WES importance to define the clonal origin of MPT and susceptibility to cancer.

  19. MCM2 and TIP30 are prognostic markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of the gallbladder

    PubMed Central

    Liu, Ziru; Yang, Zhulin; Jiang, Song; Zou, Qiong; Yuan, Yuan; Li, Jinghe; Li, Daiqiang; Liang, Lufeng; Chen, Meigui; Chen, Senlin

    2016-01-01

    The clinicopathological and biological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder remain to be fully elucidated, due to the fact that it is a rare gallbladder cancer subtype. In the current study, the expression of minichromosome maintenance complex component 2 (MCM2) and HIV-1 tat interactive protein 2 (TIP30) was measured in 46 cases of SC/ASC and 80 adenocarcinomas (AC) using immunohistochemistry. Positive MCM2 and negative TIP30 expression were significantly associated with large tumor size, high TNM stage, invasion, lymph node metastasis and lack of surgical curability in SC/ASC and AC. Positive MCM2 and negative TIP30 expression were significantly associated with poor differentiation in AC, whereas only MCM2 was correlated with differentiation in SC/ASC. Univariate Kaplan-Meier analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and surgical curability were significantly associated with post-operative survival in patients with SC/ASC and AC. Multivariate Cox regression analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and lack of surgical curability were also independent predictors of poor prognosis in patients with SC/ASC and AC. These data suggest that positive MCM2 and negative TIP30 expression are closely correlated with the clinical, pathological and biological parameters, in addition to poor prognosis in patients with gallbladder cancer. PMID:27748889

  20. Synchronous occurrence of squamous-cell carcinoma "transformation" and EGFR exon 20 S768I mutation as a novel mechanism of resistance in EGFR-mutated lung adenocarcinoma.

    PubMed

    Longo, Lucia; Mengoli, Maria Cecilia; Bertolini, Federica; Bettelli, Stefania; Manfredini, Samantha; Rossi, Giulio

    2017-01-01

    The occurrence of secondary EGFR mutation T790M in exon 20 and histologic "transformation" are common mechanisms underlying resistance to EGFR first- or second-generation tyrosine kinase inhibitors (TKI). We describe here on a hitherto unreported mechanism of EGFR TKI resistance synchronously combining squamous-cell carcinoma change and occurrence of the EGFR exon 20 S768I secondary mutation in a 43 year-old woman with stage IV adenocarcinoma harbouring EGFR exon 21 L858R mutation. After 8 months of response to gefitinib, the patient experienced EGFR TKI resistance and died of leptomeningeal neoplastic dissemination.

  1. Increased expression of the Th17-IL-6R/pSTAT3/BATF/RorγT-axis in the tumoural region of adenocarcinoma as compared to squamous cell carcinoma of the lung.

    PubMed

    Balabko, Ljubov; Andreev, Katerina; Burmann, Nadine; Schubert, Melanie; Mathews, Martina; Trufa, Denis I; Reppert, Sarah; Rau, Tilmann; Schicht, Martin; Sirbu, Horia; Hartmann, Arndt; Finotto, Susetta

    2014-12-10

    Here we describe increased expression of IL6R in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to squamous cell lung carcinoma. Moreover, here we found increased IL6R in the tumour free part of the lung. By using a murine model of lung adenocarcinoma, we discovered that few lung tumour cells expressed IL-6R and CD4+CD25+Foxp-3+ T regulatory cells down-regulated IL-6R in the tumour bearing lungs. Downstream of IL-6R, the Th17 lineage-specification factors: Signal transducer and activator of transcription 3 (STAT3), Basic leucine zipper transcription factor, BATF and a protein encoded by the RORC in human (RAR-related orphan receptor C) (RORγT), were also found induced in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to those carrying squamous cell carcinoma. Moreover, pSTAT3 protein was found phosphorylated and auto-phosphorylated in the tumoural region of patients with adeno cell carcinoma of the lung as compared to the tumoural region of patients with squamous cell carcinoma of the lung. Intranasal application of anti-IL-6R antibodies in a murine model of lung adenocarcinoma, induced T regulatory cell markers such as Foxp3, Ctla4, Icos, Il10, Il21, Folr4 and Lag3 and inhibited Rorc in lung adenocarcinoma.

  2. Increased expression of the Th17-IL-6R/pSTAT3/BATF/RorγT-axis in the tumoural region of adenocarcinoma as compared to squamous cell carcinoma of the lung

    PubMed Central

    Balabko, Ljubov; Andreev, Katerina; Burmann, Nadine; Schubert, Melanie; Mathews, Martina; Trufa, Denis I.; Reppert, Sarah; Rau, Tilmann; Schicht, Martin; Sirbu, Horia; Hartmann, Arndt; Finotto, Susetta

    2014-01-01

    Here we describe increased expression of IL6R in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to squamous cell lung carcinoma. Moreover, here we found increased IL6R in the tumour free part of the lung. By using a murine model of lung adenocarcinoma, we discovered that few lung tumour cells expressed IL-6R and CD4+CD25+Foxp-3+ T regulatory cells down-regulated IL-6R in the tumour bearing lungs. Downstream of IL-6R, the Th17 lineage-specification factors: Signal transducer and activator of transcription 3 (STAT3), Basic leucine zipper transcription factor, BATF and a protein encoded by the RORC in human (RAR-related orphan receptor C) (RORγT), were also found induced in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to those carrying squamous cell carcinoma. Moreover, pSTAT3 protein was found phosphorylated and auto-phosphorylated in the tumoural region of patients with adeno cell carcinoma of the lung as compared to the tumoural region of patients with squamous cell carcinoma of the lung. Intranasal application of anti-IL-6R antibodies in a murine model of lung adenocarcinoma, induced T regulatory cell markers such as Foxp3, Ctla4, Icos, Il10, Il21, Folr4 and Lag3 and inhibited Rorc in lung adenocarcinoma. PMID:25491772

  3. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

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

  4. Invasive Squamous Carcinoma and Adenocarcinoma of an Unreconstructed Exstrophic Bladder with HPV Infection

    PubMed Central

    Altan, Mesut; Çıtamak, Burak; Haberal, Hakan Bahadır; Söğütdelen, Emrullah; Bozaci, Ali Cansu; Baydar, Dilek Ertoy; Doğan, Hasan Serkan; Tekgül, Serdar

    2016-01-01

    Bladder exstrophy is a complex abnormality and is traditionally treated within the early years of life. It is associated with an increased risk of bladder cancer, with 95% of the arising tumors being adenocarcinomas and 3 to 5% being squamous cell carcinomas. HPV infections are also associated with an increased risk of bladder cancer. This case represents a patient with bladder exstrophy that gave rise to coinciding squamous cell carcinoma and adenocarcinoma. Final pathology results showed an infection with HPV. We presented the management of the case and discussed the diagnosis and treatment methods for this patient. PMID:27390585

  5. Combination of external beam radiotherapy and Californium (Cf)-252 neutron intracavity brachytherapy is more effective in control of cervical squamous cell carcinoma than that of cervical adenocarcinoma.

    PubMed

    Xiong, Yanli; Liu, Jia; Chen, Shu; Zhou, Qian; Xu, Wenjing; Tang, Chen; Chen, Yonghong; Yang, Mei; Lei, Xin

    2015-09-01

    The objective of this study was to compare the effect of combined external beam radiotherapy (EBRT) and Californium (Cf)-252 neutron intracavity brachytherapy (ICBT) on cervical squamous versus adenocarcinoma. A total of 106 patients with stage IB-IIIB cervical cancer were accrued between January 2005 and May 2011 and divided into squamous cell carcinoma (SCC) and adenocarcinoma (AC) as a pair with 53 patients in each group according to tumor size, stage, age, and hemoglobin level using matched-pair design. The whole pelvic EBRT was performed with 2 Gy/fraction, 4 fractions/week. The total dose was 48-54 Gy (the center of whole pelvic field was blocked by 4 cm in width after 20-36 Gy). Cf-252 neutron ICBT was delivered with 11 and 12 Gy-eq/f with the total dose at point A of 44 and 48 Gy-eq for SCC and AC patients, respectively. The mean follow-up time was 43 months. The 5-year LC, OS, DFS, LAC rates, and mean survival time were 66.0, 56.6, 52.8.0, 17.0%, and 76.4 ± 6.2 months, respectively, for AC patients, whereas they were 81.1, 69.8, 67.9, 11.3%, and 93.3 ± 4.3 months, respectively, for SCC patients. Furthermore, the early treatment toxicity was mild in both groups, the late treatment complications were mainly radiation-induced proctitis and cystitis, and there were no grade 3 or higher complications. Although the combination of Cf-252 neutron ICBT and EBRT was effective in both histology types of cervical cancer, a more aggressive strategy is needed to control cervical AC.

  6. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma

    PubMed Central

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

    Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992

  7. MiRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus and associations with survival

    PubMed Central

    Mathé, Ewy A; Nguyen, Giang Huong; Bowman, Elise D; Zhao, Yiqiang; Budhu, Anuradha; Schetter, Aaron J; Braun, Rosemary; Reimers, Mark; Kumamoto, Kensuke; Hughes, Duncan; Altorki, Nasser K; Casson, Alan G; Liu, Chang-Gong; Wang, Xin Wei; Yanaihara, Nozomu; Hagiwara, Nobutoshi; Dannenberg, Andrew J; Miyashita, Masao; Croce, Carlo M; Harris, Curtis C

    2009-01-01

    Purpose The dismal outcome of esophageal cancer patients highlights the need for novel prognostic biomarkers, such as microRNAs (miRNAs). While recent studies have established the role of miRNAs in esophageal carcinoma, a comprehensive multi-center study investigating different histological types, including squamous cell carcinoma (SCC) and adenocarinoma (ADC) with or without Barrett's, is still lacking. Experimental Design MiRNA expression was measured in cancerous and adjacent non-cancerous tissue pairs collected from 100 ADC and 70 SCC patients enrolled at 4 clinical centers from the US, Canada, and Japan. Microarray-based expression was measured in a subset of samples in two cohorts and was validated in all available samples. Results In ADC patients, miR-21, miR-223, miR-192, and miR-194 expression was elevated, while miR-203 expression was reduced in cancerous compared to non-cancerous tissue. In SCC patients, we found elevated miR-21 and reduced mir-375 expression levels in cancerous compared to non-cancerous tissue. When comparing cancerous tissue expression between ADC and SCC patients, mir-194 and mir-375 were elevated in ADC patients. Significantly, elevated mir-21 expression in non-cancerous tissue of SCC patients and reduced levels of mir-375 in cancerous tissue of ADC patients with Barrett's were strongly associated with worse prognosis. Associations with prognosis were independent of tumor stage or nodal status, cohort type, and chemoradiation therapy. Conclusions Our multi-center-based results highlight miRNAs involved in major histological types of esophageal carcinoma and uncover significant associations with prognosis. Elucidating miRNAs relevant to esophageal carcinogenesis is potentially clinically useful for developing prognostic biomarkers and identifying novel drug targets and therapies. PMID:19789312

  8. The novel HSP90 inhibitor AT13387 potentiates radiation effects in squamous cell carcinoma and adenocarcinoma cells.

    PubMed

    Spiegelberg, Diana; Dascalu, Adrian; Mortensen, Anja C; Abramenkovs, Andris; Kuku, Gamze; Nestor, Marika; Stenerlöw, Bo

    2015-11-03

    Overexpression of heat shock protein 90 (HSP90) is associated with increased tumor cell survival and radioresistance. In this study we explored the efficacy of the novel HSP90 inhibitor AT13387 and examined its radiosensitizing effects in combination with gamma-radiation in 2D and 3D structures as well as mice-xenografts. AT13387 induced effective cytotoxic activity and radiosensitized cancer cells in monolayer and tumor spheroid models, where low drug doses triggered significant synergistic effects on cell survival together with radiation. Furthermore, AT13387 treatment resulted in G2/M-phase arrest and significantly reduced the migration capacity. The expression of selected client proteins involved in DNA repair, cell-signaling and cell growth was downregulated in vitro, though the expression of most investigated proteins recurred after 8-24 h. These results were confirmed in vivo where AT13387 treated tumors displayed effective downregulation of HSP90 and its oncogenic client proteins.In conclusion, our results demonstrate that AT13387 is a potent new cancer drug and effective radiosensitizer in vitro with an excellent in vivo efficacy. AT13387 treatment has the potential to improve external beam therapy and radionuclide therapy outcomes and restore treatment efficacy in cancers that are resistant to initial therapeutic regimes.

  9. A phase IIa study of rhLTα-Da in combination with cisplatin and fluorouracil for patients with metastatic esophageal squamous cell carcinoma or gastric adenocarcinoma.

    PubMed

    Wang, Feng-Hua; Wang, Yun; Chen, Zhen-Dong; Chen, Jian-Hua; Qin, Feng-Zhan; Jiang, Wen-Qi; Li, Yu-Hong

    2016-11-01

    Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative missing 27 N-terminal amino acid residues. This multicenter phase IIa trial was conducted to evaluate the safety, efficacy and pharmacokinetics of rhLTα-Da with cisplatin (DDP) and 5-fluorouracil (5-Fu) for metastatic esophageal squamous cell cancer (ESCC) and gastric adenocarcinoma (GC). Two different rhLTα-Da doses (10 µg/m(2)/d and 20 µg/m(2)/d) in combination with DDP and 5-Fu were evaluated in this study. The first 6 ESCC and 6 GC patients were given 10 µg/m(2)/d rhLTα-Da followed by DDP (15 mg/m(2)/d) and 5-Fu (750 mg/m(2)/d) on days 1-5. The next 6 ESCC and 6 GC patients were given 20 µg/m(2)/d rhLTα-Da after fewer than 2 of the 6 patients who received the 10 µg/m(2)/d dose exhibited dose-limiting rhLTα-Da-related toxicities. The treatment was 21 days a cycle until a maximum of 6. The rhLTα-Da pharmacokinetic analyses were performed. Twelve ESCC and 12 GC patients were enrolled. The toxicities were controllable and reversible. The most common adverse events related to rhLTα-Da were chills (37.5 %, 9/24) and fever (16.7 %, 4/24) (all grades 1-2). The overall response rates in the 10- and 20-µg/m(2)/d groups were 50 % (6/12) and 33.3 % (4/12), respectively, and the overall response rates of the ESCC and GC patients were 66.7 % (8/12) and 16.7 % (2/12), respectively. rhLTα-Da in combination with DDP and 5-Fu exhibited a tolerable toxicity profile. The addition of rhLTα-Da may enhance the anti-tumor efficacy of platinum-based chemotherapy in metastatic ESCC.

  10. Subungual squamous cell carcinoma*

    PubMed Central

    Padilha, Carolina Barbosa de Sousa; Balassiano, Laila Klotz de Almeida; Pinto, Julyana Calegari; de Souza, Flávia Crespo Schueler; Kac, Bernard Kawa; Treu, Curt Mafra

    2016-01-01

    Although subungual squamous cell carcinoma is rare, it is the most common primary malignant neoplasms in this location. The higher incidence occurs in the fingernails, but involvement of the toenails is also possible. Subungual squamous cell carcinoma often looks like other more common benign lesions, such as fungal infection, onychomycosis, or viral wart. These factors, together with a general lack of awareness of this disease among physicians, often result in delayed diagnosis. Therefore, it is underdiagnosed, with few reports in the literature. The authors present a case of a man with a diagnosis of subungual squamous cell carcinoma in the hallux, without bone involvement, which was submitted to the appropriate surgical treatment. PMID:28099608

  11. YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression.

    PubMed

    Gao, Yijun; Zhang, Wenjing; Han, Xiangkun; Li, Fuming; Wang, Xujun; Wang, Rui; Fang, Zhaoyuan; Tong, Xinyuan; Yao, Shun; Li, Fei; Feng, Yan; Sun, Yihua; Hou, Yingyong; Yang, Zhongzhou; Guan, Kunliang; Chen, Haiquan; Zhang, Lei; Ji, Hongbin

    2014-08-13

    Whether the Hippo pathway contributes to cell lineage transition under pathological conditions, especially tumorigenesis, remains largely unknown. Here we show that YAP, the major effector of the Hippo pathway, displays a distinct activation pattern in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC); YAP is initially activated by LKB1 loss in lung ADC, which upregulates ZEB2 expression and represses DNp63 transcription in a default manner. During transdifferentiation, YAP is inactivated, which in turn relieves ZEB2-mediated default repression of DNp63 and triggers squamous differentiation reprogramming. Disruption of the YAP barrier for phenotypic transition significantly accelerates squamous transdifferentiation, whereas constitutive YAP activation conversely inhibits this transition. More importantly, ectopic DNp63 expression rescues the inhibitory effect of YAP on squamous transdifferentiation. These findings have established YAP as an essential barrier for lung cancer cell fate conversion and provided a mechanism for regulating cancer plasticity, which might hold important implication for YAP-targeted therapies.

  12. Squamous cell carcinoma.

    PubMed

    Webb, Julie L; Burns, Rachel E; Brown, Holly M; LeRoy, Bruce E; Kosarek, Carrie E

    2009-03-01

    Squamous cell carcinoma (SCC) is a relatively common, malignant neoplasm of dogs and cats that can arise in a variety of locations. The gross appearance of SCC can be variable and nonspecific, so definitive diagnosis requires microscopic examination of the tissue (cytology or histology). Several treatment modalities exist, but surgical excision, if possible, is regarded as the best treatment option. Early diagnosis and treatment of SCC are key because small, early-stage tumors are the most amenable to treatment and carry the best prognosis.

  13. p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma.

    PubMed

    Bishop, Justin A; Teruya-Feldstein, Julie; Westra, William H; Pelosi, Giuseppe; Travis, William D; Rekhtman, Natasha

    2012-03-01

    Immunohistochemistry has recently emerged as a powerful ancillary tool for differentiating lung adenocarcinoma and squamous cell carcinoma-a distinction with important therapeutic implications. Although the most frequently recommended squamous marker p63 is extremely sensitive, it suffers from low specificity due to its reactivity in a substantial proportion of lung adenocarcinomas and other tumor types, particularly lymphomas. p40 is a relatively unknown antibody that recognizes ΔNp63-a p63 isoform suggested to be highly specific for squamous/basal cells. Here we compared the standard p63 antibody (4A4) and p40 in a series of 470 tumors from the archives of Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Hospital, which included lung squamous cell carcinomas (n=81), adenocarcinomas (n=237), and large cell lymphomas (n=152). The p63 was positive in 100% of squamous cell carcinomas, 31% of adenocarcinomas, and 54% of large cell lymphomas (sensitivity 100%, specificity 60%). In contrast, although p40 was also positive in 100% of squamous cell carcinomas, only 3% of adenocarcinomas, and none of large cell lymphomas had p40 labeling (sensitivity 100%, specificity 98%). The mean percentage of p63 versus p40-immunoreactive cells in squamous cell carcinomas was equivalent (97 vs 96%, respectively, P=0.73). Rare adenocarcinomas with p40 labeling had reactivity in no more than 5% of tumor cells, whereas the mean (range) of p63-positive cells in adenocarcinomas and lymphomas was 26% (1-90%) and 48% (2-100%), respectively. In summary, p40 is equivalent to p63 in sensitivity for squamous cell carcinoma, but it is markedly superior to p63 in specificity, which eliminates a potential pitfall of misinterpreting a p63-positive adenocarcinoma or unsuspected lymphoma as squamous cell carcinoma. These findings strongly support the routine use of p40 in place of p63 for the diagnosis of pulmonary squamous cell carcinoma.

  14. [Advances of molecular targeted therapy in squamous cell lung cancer].

    PubMed

    Ma, Li; Zhang, Shucai

    2013-12-01

    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  15. Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population.

    PubMed

    Li, Wen-Qing; Hu, Nan; Hyland, Paula L; Gao, Ying; Wang, Zhao-Ming; Yu, Kai; Su, Hua; Wang, Chao-Yu; Wang, Le-Min; Chanock, Stephen J; Burdett, Laurie; Ding, Ti; Qiao, You-Lin; Fan, Jin-Hu; Wang, Yuan; Xu, Yi; Shi, Jian-Xin; Gu, Fangyi; Wheeler, William; Xiong, Xiao-Qin; Giffen, Carol; Tucker, Margaret A; Dawsey, Sanford M; Freedman, Neal D; Abnet, Christian C; Goldstein, Alisa M; Taylor, Philip R

    2013-07-01

    The DNA repair pathways help to maintain genomic integrity and therefore genetic variation in the pathways could affect the propensity to develop cancer. Selected germline single nucleotide polymorphisms (SNPs) in the pathways have been associated with esophageal cancer and gastric cancer (GC) but few studies have comprehensively examined the pathway genes. We aimed to investigate associations between DNA repair pathway genes and risk of esophageal squamous cell carcinoma (ESCC) and GC, using data from a genome-wide association study in a Han Chinese population where ESCC and GC are the predominant cancers. In sum, 1942 ESCC cases, 1758 GC cases and 2111 controls from the Shanxi Upper Gastrointestinal Cancer Genetics Project (discovery set) and the Linxian Nutrition Intervention Trials (replication set) were genotyped for 1675 SNPs in 170 DNA repair-related genes. Logistic regression models were applied to evaluate SNP-level associations. Gene- and pathway-level associations were determined using the resampling-based adaptive rank-truncated product approach. The DNA repair pathways overall were significantly associated with risk of ESCC (P = 6.37 × 10(-4)), but not with GC (P = 0.20). The most significant gene in ESCC was CHEK2 (P = 2.00 × 10(-6)) and in GC was CLK2 (P = 3.02 × 10(-4)). We observed several other genes significantly associated with either ESCC (SMUG1, TDG, TP53, GTF2H3, FEN1, POLQ, HEL308, RAD54B, MPG, FANCE and BRCA1) or GC risk (MRE11A, RAD54L and POLE) (P < 0.05). We provide evidence for an association between specific genes in the DNA repair pathways and the risk of ESCC and GC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.

  16. [Comparative clinico-morphological characteristics of the variants of adeno-squamous carcinoma and adenocarcinoma of the endometrium].

    PubMed

    Smirnov, O A; Smirnova, O N

    1985-01-01

    A clinico-morphological analysis of the data available on cases of adeno-squamous carcinoma (72) and endometrial adenocarcinoma (102) pointed to a correlation between the decrease in the degree of cell differentiation in said neoplasms and the decline in the frequency of hyperestrimism and metabolic-endocrine disorders. As a result over 70% of well-differentiated cell tumors were referred to one pathogenetic pattern of endometrial carcinoma (after Bokhman) and more than 50% of poorly-differentiated cell tumors--to another one. These findings further support the rationale for distinguishing the well- and poorly-differentiated cell patterns of adeno-squamous carcinoma. They may be used in establishing individual prognosis as well as choosing optimal scheme of treatment.

  17. Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: unique spectra involving G to A transitions and G to T transversions in both histologic types.

    PubMed

    Gao, Wei-Min; Mady, Hussam H; Yu, Guo-Ying; Siegfried, Jill M; Luketich, James D; Melhem, Mona F; Keohavong, Phouthone

    2003-05-01

    The p53 gene is frequently mutated in lung tumors, and mutations may be caused by both polycyclic aromatic hydrocarbons (PAHs) and nitrosamines found in tobacco smoke. The two major forms of lung cancer, adenocarcinoma (AC) and squamous cell carcinoma (SCC), are known to differ in the proportion of tumors exhibiting p53 mutation, and may also differ in the mutational spectra produced. Previous studies comparing p53 mutational spectra between AC and SCC of the lung have been limited by small sample size. We examined p53 mutations in exons 5-8 in 202 cases of AC and 82 cases of SCC from smoking lung cancer patients in the Western Pennsylvania region. The percent of cases with p53 mutation was significantly lower in ACs (40/202, 20%) compared to SCCs (29/82, 35%, P=0.006). The proportion of mutations present that were G to T transversions was not significantly different between the two tumor types (52% of p53 mutations in AC compared to 32% in SCC). G to A transitions either did not differ in frequency in the two types of lung cancer (20% of mutations in AC and 24% of mutations in SCC). A distinct spectrum was observed, however, in the p53 mutation pattern in the two types of lung cancer. ACs showed a strong preference for a mutational hotspot at codons 248 and 249, while squamous cell tumors showed mutational events spread throughout exons 5-8, with a preference for codon 267. Mutations at codon 267 in SCC were all C to T transitions that occurred at CpG sites. Both tumor types demonstrated preferential mutation of the non-transcribed strand (100% of all G to T transversions and 55% of the G to A transitions). These results suggest that p53 mutations in both types of lung tumors may arise from adduction by both PAHs and nitrosamines. Mutations arising in ACs appear selectively in regions of p53 that produce more rigid proteins, suggesting a drastic change in p53 function is needed to result in ACs, while less constrained changes in p53 function can result in SCCs

  18. Potential targets for lung squamous cell carcinoma

    Cancer.gov

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

  19. [Primary orbital squamous cell carcinoma].

    PubMed

    Campos Arbulú, Ana L; Sadava, Emmanuel E; Sánchez Ruiz, Alejandro; Fernández Vila, Juan M; Dillon, Horacio S; Mezzadri, Norberto A

    2017-01-01

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

  20. Squamous cell carcinoma of the anal sac in five dogs.

    PubMed

    Esplin, D G; Wilson, S R; Hullinger, G A

    2003-05-01

    Tumors of the perianal area of dogs are common and include multiple tumor types. Whereas perianal adenomas occur often, adenocarcinomas of the apocrine glands of the anal sac occur less frequently. A review of the literature revealed no reports of squamous cell carcinomas arising from the epithelial lining of the anal sac. Squamous cell carcinomas originating from the lining of the anal sac were diagnosed in five dogs. Microscopically, the tumors consisted of variably sized invasive nests and cords of epithelial cells displaying squamous differentiation. Four of the five dogs were euthanatized because of problems associated with local infiltration by the tumors. In the fifth dog, there was no evidence of tumor 7 months after surgical removal, but further follow up was not available.

  1. Squamous cell carcinoma of rectum presenting in a man: a case report

    PubMed Central

    2010-01-01

    Background Primary squamous cell carcinomas of the colorectum are very uncommon. Until now, to the best of our knowledge, only 114 cases of squamous cell carcinoma in the colorectum exist in the reported literature. Here we report a case of squamous cell carcinoma of the rectum in the ethnic Kashmiri population in northern India. Case Presentation The case of a 60-year-old male patient (Asian) with a pure squamous cell carcinoma of the rectum is presented here. The patient underwent a curative surgery with concomitant chemotherapy. Two years after the initial curative resection of the tumor he is still alive. Conclusion The prognosis for squamous cell carcinoma of the colorectum is worse than for that of adenocarcinoma, because of the delayed diagnosis. The etiopathogenicity of squamous cell carcinoma of the colorectum is discussed. Surgical resection of the lesion seems to be the treatment of choice. Chemotherapy also helps in improvement of the prognosis. PMID:21118539

  2. Squamous cell cancer (image)

    MedlinePlus

    ... a malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It is more likely than basal cell cancer to spread (metastasize) to other locations, including internal ...

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

    MedlinePlus

    ... Health Conditions head and neck squamous cell carcinoma head and neck squamous cell carcinoma Enable Javascript to view the ... body cavities such as the airways and intestines. Head and neck squamous cell carcinoma (HNSCC) develops in the mucous ...

  4. Magnifying endoscopy with narrow-band imaging findings in the diagnosis of Barrett's esophageal adenocarcinoma spreading below squamous epithelium.

    PubMed

    Omae, Masami; Fujisaki, Junko; Shimizu, Tomoki; Igarashi, Masahiro; Yamamoto, Noriko

    2013-05-01

    It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations (AVF) by magnifying endoscopy with narrow-band imaging (ME-NBI), and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontal cross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 μm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected.

  5. Obstructive Jaundice from Metastatic Squamous Cell Carcinoma of the Lung.

    PubMed

    Seth, Abhishek; Palmer, Thomas R; Campbell, Jason

    2016-01-01

    Obstructive jaundice from metastatic lung cancer is extremely rare. Most reported cases have had small cell cancer of lung or adenocarcinoma of lung as primary malignancy metastasizing to the biliary system. We report the case of a patient presenting with symptoms of obstructive jaundice found to have metastatic involvement of hepatobiliary system from squamous cell cancer (SCC) of lung. ERCP (endoscopic retrograde cholangiopancreatography) with biliary stenting is the procedure of choice in such patients. Our case is made unique by the fact that technical difficulties made it difficult for the anesthesiologists to intubate the patient for an ERCP. As a result percutaneous transhepatic cholangiogram (PTC) with internal-external biliary drainage was performed.

  6. Bupropion Hydrochloride or Patient's Choice for Smoking Cessation in Patients With Squamous Cell Head and Neck Cancer Undergoing Radiation Therapy With or Without Chemotherapy

    ClinicalTrials.gov

    2017-03-13

    Current Smoker; Head and Neck Squamous Cell Carcinoma; Hypopharyngeal Squamous Cell Carcinoma; Laryngeal Squamous Cell Carcinoma; Nasopharyngeal Carcinoma; Oral Cavity Squamous Cell Carcinoma; Oropharyngeal Squamous Cell Carcinoma

  7. Resection of intraocular squamous cell carcinoma.

    PubMed Central

    Char, D H; Crawford, J B; Howes, E L; Weinstein, A J

    1992-01-01

    A patient with recurrent squamous cell carcinoma of the conjunctiva was referred with 20/20 vision in an eye with obvious intraocular extension. A modified iridocyclochoroidectomy was performed and the tumour was removed. Three and a half years later the patient's vision is 20/30 and there is no recurrence. This is the first case in which an eye has been successfully salvaged with documented intraocular squamous cell carcinoma of the conjunctiva. Images PMID:1739709

  8. Laryngeal Dysplasia, Squamous Cell Carcinoma, and Variants.

    PubMed

    Thompson, Lester D R

    2017-03-01

    Squamous cell carcinoma (SCC) is a malignant epithelial tumor showing evidence of squamous differentiation. It is the most common malignancy of the larynx, with several variants (verrucous, exophytic or papillary, spindle-cell, basaloid, acantholytic, adenosquamous) recognized, with well-established precursor lesions. Dysplasia is now separated into only low-grade and high-grade categories. Each SCC variant has unique cytomorphologic features and histologic differential diagnoses that are important to consider, as management and outcomes are different.

  9. Fibroblast growth factor signaling and inhibition in non-small cell lung cancer and their role in squamous cell tumors

    PubMed Central

    Salgia, Ravi

    2014-01-01

    With the introduction of targeted agents primarily applicable to non-small cell lung cancer (NSCLC) of adenocarcinoma histology, there is a heightened unmet need in the squamous cell carcinoma population. Targeting the angiogenic fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway is among the strategies being explored in squamous NSCLC; these efforts are supported by growth-promoting effects of FGF signaling in preclinical studies (including interactions with other pathways) and observations suggesting that FGF/FGFR-related aberrations may be more common in squamous versus adenocarcinoma and other histologies. A number of different anti-FGF/FGFR approaches have shown promise in preclinical studies. Clinical trials of two multitargeted tyrosine kinase inhibitors are restricting enrollment to patients with squamous NSCLC: a phase I/II trial of nintedanib added to first-line gemcitabine/cisplatin and a phase II trial of ponatinib for previously treated advanced disease, with the latter requiring not only squamous disease but also a confirmed FGFR kinase amplification or mutation. There are several ongoing clinical trials of multitargeted agents in general NSCLC populations, including but not limited to patients with squamous disease. Other FGF/FGFR-targeted agents are in earlier clinical development. While results are awaited from these clinical investigations in squamous NSCLC and other disease settings, additional research is needed to elucidate the role of FGF/FGFR signaling in the biology of NSCLC of different histologies. PMID:24711160

  10. S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2017-03-16

    Recurrent Large Cell Lung Carcinoma; Recurrent Lung Adenocarcinoma; Recurrent Squamous Cell Lung Carcinoma; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Squamous Cell Lung Carcinoma

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

    ClinicalTrials.gov

    2016-12-19

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

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

    ClinicalTrials.gov

    2015-04-29

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

  13. A Case of Acantholytic Squamous Cell Carcinoma

    PubMed Central

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

    2008-01-01

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

  14. Emerging challenges of advanced squamous cell lung cancer

    PubMed Central

    Zhang, Yi-Chen; Zhou, Qing

    2016-01-01

    Squamous cell lung cancer (SQCLC) is an aggressive type of lung cancer and most are diagnosed at advanced stage. Patients with advanced SQCLC tend to be older, current or former smoker, with central type tumour located near large blood vessels and seldom with druggable genetic alternations. Consequently, progress of targeted therapy and antivascular agents available in lung adenocarcinoma could not be duplicated in this subset of patients. The treatment paradigms have long been dominant by cytotoxic agents and posed many therapeutic challenges. Until recent years, immune checkpoint inhibitors, other monoclonal antibodies and afatinib have been approved for treatment of advanced SQCLC, presenting a novel treatment landscape and initiating the era of precision medicine in this subset of patients. This review will summarise the recent treatment progresses in advanced SQCLC with a focus on checkpoint inhibitors of programmed cell death-1 receptor or its ligand, and discuss the emerging challenges in this new era. PMID:28255454

  15. [Lichen sclerosus and squamous cell carcinoma].

    PubMed

    Gutiérrez-Pascual, M; Vicente-Martín, F J; López-Estebaranz, J L

    2012-01-01

    Lichen sclerosus is a chronic inflammatory disease that can progress to malignancy. The literature indicates an association with anogenital squamous cell carcinoma and verrucous carcinoma. Two pathogenic pathways, differentiated vulvar and penile intraepithelial neoplasias, which have recently been described in relation to squamous cell carcinoma, are both highly associated with genital lichen sclerosus independently of human papilloma virus (HPV) infection. Furthermore, tumor-promoting molecular changes unrelated to HPV infection have been demonstrated and may explain the malignant potential of lichen sclerosus. The possible relationship between HPV and genital lichen sclerosus currently remains open to discussion, and the prognostic importance of the overlapping of these 2 diseases is still unclear. This review considers the relationship between lichen sclerosus and squamous cell and verrucous carcinomas, the possible oncogenic mechanisms involved, and their possible association with HPV infection.

  16. Lichen sclerosus and squamous cell carcinoma.

    PubMed

    Gutiérrez-Pascual, M; Vicente-Martín, F J; López-Estebaranz, J L

    2012-01-01

    Lichen sclerosus is a chronic inflammatory disease that can progress to malignancy. The literature indicates an association with anogenital squamous cell carcinoma and verrucous carcinoma. Two pathogenic pathways, differentiated vulvar and penile intraepithelial neoplasias, which have recently been described in relation to squamous cell carcinoma, are both highly associated with genital lichen sclerosus independently of human papilloma virus (HPV) infection. Furthermore, tumor-promoting molecular changes unrelated to HPV infection have been demonstrated and may explain the malignant potential of lichen sclerosus. The possible relationship between HPV and genital lichen sclerosus currently remains open to discussion, and the prognostic importance of the overlapping of these 2 diseases is still unclear. This review considers the relationship between lichen sclerosus and squamous cell and verrucous carcinomas, the possible oncogenic mechanisms involved, and their possible association with HPV infection.

  17. Squamous Cell Carcinoma of Pancreas: Mystery and Facts.

    PubMed

    Raghavapuram, Saikiran; Vaid, Arjun; Rego, Rayburn F

    2015-08-01

    Squamous cell carcinoma of the pancreas is very rare as pancreas does not have any squamous cells. Only a few cases have been reported in the literature so far. We describe such a case where in the patient presented with painless jaundice. CT and EUS confirmed the pancreatic mass biopsy of which showed squamous cell cancer.

  18. Primary squamous cell carcinoma of the pancreas: a report of two cases and review of the literature.

    PubMed

    Ben Kridis, Wala; Khanfir, Afef; Toumi, Nabil; Ben Amar, Mohamed; Boudawara, Tahia; Frikha, Mounir

    2015-01-01

    Primary squamous cell carcinoma (SCC) of the pancreas is extremely rare. We herein report two such cases. Aside from various morphological characteristics, the clinical presentation of pancreatic SCC is the same as that of adenocarcinoma. The treatment is controversial, and the prognosis is poor.

  19. Acrokeratosis Paraneoplastica Associated with Cervical Squamous Cell Carcinoma

    PubMed Central

    Daveluy, Steven D.; Joiner, Michael C.; Hurst, Newton; Bishop, Michael; Miller, Steven R.

    2016-01-01

    Background. Acrokeratosis paraneoplastica, or Bazex syndrome, is a paraneoplastic syndrome characterized by cutaneous psoriasiform lesions with associated acral erythema and scale, as well as nail changes, including onycholysis and ungual dystrophy. Its most advanced, severe form involves the trunk, elbows, and knees. It is typically associated with upper aerodigestive tract malignancies in males. Rare cases associated with gynecological cancers have been reported, including uterine adenocarcinoma, as well as ovarian and vulvar squamous cell carcinomas. Cutaneous manifestations often precede cancer diagnosis. In most reported cases, skin changes resolve when the underlying malignancy is adequately treated. Main Observations. We present the case of a 56-year-old female diagnosed with acrokeratosis paraneoplastica following the discovery of FIGO stage IIB cervical squamous cell carcinoma (SCC). Scaling, hyperpigmentation, xerosis, and fissuring were noted on the patient's hands, feet, legs, arms, and lower back. Pitting was noted on her fingernails. Her cervical cancer was successfully treated with chemoradiotherapy, after which her cutaneous lesions persisted for two months before resolving. Conclusions. The presentation of acrokeratosis paraneoplastica in this context is atypical. Reports of associations with gynecological cancers, as in our patient's case, are exceedingly rare. PMID:28101384

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

    ClinicalTrials.gov

    2017-01-31

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

  1. Expression of HuR, COX-2, and survivin in lung cancers; cytoplasmic HuR stabilizes cyclooxygenase-2 in squamous cell carcinomas.

    PubMed

    Kim, Gou Young; Lim, Sung-Jig; Kim, Youn Wha

    2011-10-01

    Hu antigen R (HuR) is a member of the human family of embryonic-lethal, abnormal vision-like proteins, which serves as an mRNA-binding protein. In the cytoplasm, HuR can stabilize the mRNA of cyclooxygenase-2 (COX-2), an enzyme that catalyses the synthesis of prostaglandins and is associated with promotion of carcinogenesis and tumor cell resistance to apoptosis. Intracellular (cytoplasmic and nuclear) localization of survivin has a prognostic significance as an apoptosis inhibitor and a regulator of cell division in tumors. Patients with 151 squamous cell carcinomas and 93 adenocarcinomas underwent lobectomy or pneumonectomy with hilar and mediastinal lymph node sampling. Paraffin-embedded tumor sections were retrieved for evaluation of nuclear and cytoplasmic staining of survivin and HuR, and cytoplasmic staining of COX-2. In squamous cell carcinomas, COX-2 expression was correlated with a difference of survivin (cytoplasmic-nuclear; P=0.004), cytoplasmic HuR (P=0.018), total HuR (cytoplasmic+nuclear; P=0.009), and difference of HuR (P=0.020). COX-2 was inversely correlated with nuclear survivin (P=0.006). In a univariate analysis by log-rank test, survival was associated with cytoplasmic survivin (adenocarcinoma, P<0.001; squamous cell carcinoma, P=0.005), difference of survivin (adenocarcinoma, P<0.001; squamous cell carcinoma, P=0.014), and COX-2 (squamous cell carcinoma, P=0.001). Survival was inversely associated with nuclear survivin (adenocarcinoma, P=0.006, squamous cell carcinoma, P=0.014). In a multivariate survival analysis, cytoplasmic survivin (adenocarcinoma, P=0.002; squamous cell carcinoma, P=0.015) and COX-2 (squamous cell carcinoma, P=0.020) were determined as independent prognostic factors. Cytoplasmic HuR expression is associated with COX-2 expression in squamous cell carcinomas. The expression of COX-2 in squamous cell carcinomas, and cytoplasmic survivin in adenocarcinomas and squamous cell carcinomas could be useful independent prognostic

  2. Squamous cell carcinoma arising in a meningomyelocele.

    PubMed Central

    Saksun, J. M.; Fisher, B. K.

    1978-01-01

    Squamous cell carcinoma developed in the meningomyelocele of a 25-year-old man. This is the third such case reported. The possibility of malignant disease arising in this congenital defect must be taken into account when treatment is being considered. Images FIG. 1 FIG. 2 FIG. 3 PMID:709475

  3. Squamous cell carcinoma associated with lupus vulgaris.

    PubMed

    Gooptu, C; Marks, N; Thomas, J; James, M P

    1998-05-01

    Squamous cell carcinomas are known to arise in certain chronic, scarring dermatoses and also to be associated with exposure to ultraviolet radiation. We now report a case arising in a plaque of lupus vulgaris, the patient having received radiation from a Finsen lamp as a child for a tuberculous abscess in that region.

  4. Metaplastic squamous cell carcinoma of the breast: A case report and literature review.

    PubMed

    Graziano, Luciana; Graziano, Paschoal; Bitencourt, Almir Galvão Vieira; Soto, Daniel Bernal; Hiro, Alexandre; Nunes, Cíntia Camillo

    2016-10-01

    Metaplastic tumors are rare and represent a heterogeneous group of neoplasms showing dominant areas of non-glandular differentiation. Etiology and pathogenesis of this type of lesion in the breast is uncertain. The most common sources of metastatic squamous cell carcinoma of the breast are lung, esophagus, cervix, and urinary bladder. Squamous cell carcinomas may present clinically with inflammation and average size greater than breast adenocarcinoma. As for imaging studies, mammography shows no typical findings and ultrasound can show a complicated cyst or an inflammatory process, among the differential diagnoses. Therefore, knowing this pathological entity, its clinical course and imaging findings is important to safely treat such a rare and aggressive disease. We herein report a case of metaplastic carcinoma, squamous subtype, diagnosed by core needle biopsy.

  5. Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma

    PubMed Central

    Park, Eunhyang; Park, Soo Young; Sun, Ping-Li; Jin, Yan; Kim, Ji Eun; Jheon, Sanghoon; Kim, Kwhanmien; Lee, Choon Taek

    2016-01-01

    Cancer stem cells (CSCs) are a small subset of tumor cells that exhibit stem cell-like properties and contribute in treatment failure. To clarify the expression and prognostic significance of several CSC markers in non-small cell lung cancer, we retrospectively analyzed 368 patients with adenocarcinoma (n = 226) or squamous cell carcinoma (n = 142). We correlated the expression of six CSC markers – CD133, CD44, aldehyde dehydrogenase 1 (ALDH1), sex determining region Y-box 2 (SOX2), octamer binding transcription factor 4 (OCT4), and Nanog – with clinicopathologic and molecular variables and survival outcomes. In adenocarcinoma, CD133, ALDH1 and CD44 expression was associated with low pathologic stage and absence of lymphovascular invasion, while Nanog expression correlated with high histologic grade, lymphatic invasion and increased expression of Snail-1, a transcription factor associated with epithelial-mesenchymal transition. CSC marker expression was also associated with histologic subtypes in adenocarcinoma. Multivariate analysis showed that high Nanog expression was an independent factor associated with a poor prognosis in adenocarcinoma. CSC markers had no prognostic value in squamous cell carcinoma. These results suggest that Nanog is an independent negative prognostic factor that may be associated with epithelial-mesenchymal transition in lung adenocarcinoma. PMID:27285762

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

    ClinicalTrials.gov

    2017-03-30

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

  7. Capecitabine and Lapatinib Ditosylate in Treating Patients With Squamous Cell Cancer of the Head and Neck

    ClinicalTrials.gov

    2017-01-24

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

  8. Squamous cell carcinoma of the anal sacs in three dogs.

    PubMed

    Mellett, S; Verganti, S; Murphy, S; Bowlt, K

    2015-03-01

    Anal sac squamous cell carcinoma is rare in dogs. Five cases have been previously reported, treatment of which involved surgery alone. This report describes three further cases of canine anal sac squamous cell carcinoma which underwent medical (meloxicam) management alone, resulting in survival of up to seven months. No metastases were identified. Squamous cell carcinoma, although extremely uncommon, should be considered as a possible differential diagnosis when a dog is presented for investigation of an anal sac mass.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-09-01

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

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

    ClinicalTrials.gov

    2017-02-08

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

  12. Desmosomal defects in acantholytic squamous cell carcinomas

    PubMed Central

    O’Shea, Charlene; Fitzpatrick, James E.; Koch, Peter J.

    2014-01-01

    Background Acantholytic squamous cell carcinoma (Acantholytic SCC) are epithelial tumors characterized by a loss of cell adhesion between neoplastic keratinocytes. The mechanism underlying loss of cell-cell adhesion in these tumors is not understood. Methods A retrospective analysis of acantholytic SCC (n=17) and conventional SCC (n=16, controls not showing acantholysis) was conducted using a set of desmosomal and adherens junction protein antibodies. Immunofluorescence microscopy was used to identify tumors with loss of adhesion protein expression. Results The vast majority of acantholytic SCC (89%) showed focal loss of at least one desmosomal cell adhesion protein. Most interestingly, 65% of these tumors lost expression of two or more desmosomal proteins. Conclusions Loss of cell adhesion in acantholytic SCC is most likely linked to the focal loss of desmosomal protein expression, thus providing potential mechanistic insight into the patho-mechanism underlying this malignancy. PMID:25264142

  13. Recurrence of primary squamous cell carcinoma of the ileum diagnosed by elevation of serum SCC: report of a case.

    PubMed

    Mino, Kazuhiro; Kamii, Naoki; Kawanishi, Norio; Okada, Tadao; Todo, Satoru

    2012-06-01

    Primary squamous cell carcinoma of the intestine is extremely rare. This report describes a patient with primary squamous cell carcinoma of the small intestine. A 72-year-old Japanese woman was referred to our hospital because of a diagnosis of intestinal obstruction. She underwent laparotomy owing to the diagnosis of mechanical intestinal obstruction due to a pelvic mass after conservative treatment. The affected ileum was resected, and histopathological examination revealed proliferation of differentiated squamous cell carcinoma at the submucosal area with no adenocarcinoma component. At the 4th month after the operation, the level of serum squamous cell carcinoma (SCC) antigen was elevated. At 6 months after the operation, the serum SCC value was further elevated, and enhanced CT revealed two new pelvic tumors with enhancement at the mesentery and free space. A second laparotomy was performed 8 months after the operation. Histopathological examination showed differentiated squamous cell carcinoma as in the first operation. The level of serum SCC decreased at the 28th postoperative day. Chemotherapy including carboplatin and paclitaxel was performed as an adjuvant regimen. The patient has experienced no recurrence of squamous cell carcinoma for 55 months.

  14. Desmocollin-3: a new marker of squamous differentiation in undifferentiated large-cell carcinoma of the lung.

    PubMed

    Monica, Valentina; Ceppi, Paolo; Righi, Luisella; Tavaglione, Veronica; Volante, Marco; Pelosi, Giuseppe; Scagliotti, Giorgio V; Papotti, Mauro

    2009-05-01

    Lung cancer classification in small-cell and non-small-cell types was recently challenged by data on the differential efficacy of new cytotoxic agents in specific histotypes. An accurate histotype definition has therefore gained interest in both preoperative and surgical materials, but is a hard task especially in undifferentiated large-cell tumors lacking morphological signs of squamous or glandular differentiation. The responsiveness of these latter subtypes to new drugs apparently more selective for adenocarcinomas or squamous carcinomas is not fully understood, also due to the heterogeneity of diagnostic criteria for this tumor entity. Current immunohistochemical markers are not fully specific and new molecules are to be explored. On the basis of gene expression profiling data, reporting a remarkable differential expression of desmocollin-3 (a protein localized in desmosomal junctions of stratified epithelial) between adeno- and squamous cancers, we immunostained 62 cases of resected undifferentiated large-cell lung carcinomas for desmocollin-3 (and for TTF-1, p63 and mucin stain), to test its ability to identify a (residual) squamous phenotype, if present. Desmocollin-3 was expressed in almost half of the undifferentiated large-cell cancers and was mutually exclusive with TTF-1 (positive in 39%; the remaining 18 % of cases was double negative). Special large-cell carcinoma variants expressed desmocollin-3 in 6 of 6 basaloid, 7 of 12 clear-cell types, again mutually exclusive with TTF-1 expression. None of seven sarcomatoid carcinomas reacted for either marker. In 31 cytological samples diagnosed as 'non-small-cell lung carcinoma', desmocollin-3 was again mutually exclusive with TTF-1 and stained all squamous carcinomas, 1 of 19 adenocarcinoma only, and 50% of large-cell carcinoma (all histologically confirmed). This combined morphophenotypic approach may represent a valid adjunct (for both surgical and cytological samples) in the selection of patients with

  15. Anogenital squamous cell carcinoma in neglected patient.

    PubMed

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

    2012-01-01

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

  16. [Gastric signet ring cell adenocarcinoma: A distinct entity].

    PubMed

    Tabouret, Tessa; Dhooge, Marion; Rouquette, Alexandre; Brezault, Catherine; Beuvon, Frédéric; Chaussade, Stanislas; Coriat, Romain

    2014-04-01

    Gastric signet ring cell carcinoma (GSRC) is a distinct entity. Their incidence is increasing. The pathologist plays a central role in the identification of this entity. Diagnosis is based on an adenocarcinoma containing a majority of signet ring cells (above 50 %). The prognosis of GSRC is the same as gastric adenocarcinoma while GSRC appeared more aggressive. Signet ring cells present a low sensitivity to chemotherapy. This review aimed to discuss the histological, the prognostic and the therapeutic aspect of this entity.

  17. Primary Squamous Cell Carcinoma of the Pancreas as a Cause of Biliary Obstruction

    PubMed Central

    Mehta, Jeet; Nehme, Fredy; Salyers, William

    2016-01-01

    Primary squamous cell carcinoma of the pancreas (SCCP) is a rare neoplasm, given a lack of naturally occurring squamous cells within the pancreas, accounting for only 0.2% of all pancreatic cancers. The etiology is unknown. Symptomatology is non-specific and similar to other pancreatic neoplasms. No non-invasive testing can adequately rule in SCCP, and workup should proceed similarly to any pancreatic mass. Tissue sampling is required for diagnosis and guidance of further management, most commonly by endoscopic ultrasound with fine needle aspirate. SCCP is more aggressive than adenocarcinoma of the pancreas with a median survival of three and ten months for those treated with palliative and surgical intent, respectively. The optimal treatment regimen remains unknown, though the uses of radiation therapy, platinum-based regimens, gemcitabine, and 5-FU have all been reported with favorable results. We present a case of primary SCCP in an 81-year-old female who presented with jaundice. PMID:27909644

  18. Squamous cell lung cancer: from tumor genomics to cancer therapeutics.

    PubMed

    Gandara, David R; Hammerman, Peter S; Sos, Martin L; Lara, Primo N; Hirsch, Fred R

    2015-05-15

    Squamous cell lung cancer (SCC) represents an area of unmet need in lung cancer research. For the past several years, therapeutic progress in SCC has lagged behind the now more common non-small cell lung cancer histologic subtype of adenocarcinoma. However, recent efforts to define the complex biology underlying SCC have begun to bear fruit in a multitude of ways, including characterization of previously unknown genomic and signaling pathways, delineation of new, potentially actionable molecular targets, and subsequent development of a large number of agents directed against unique SCC-associated molecular abnormalities. For the first time, SCC-specific prognostic gene signatures and predictive biomarkers of new therapeutic agents are emerging. In addition, recent and ongoing clinical trials, including the Lung-MAP master protocol, have been designed to facilitate approval of targeted therapy-biomarker combinations. In this comprehensive review, we describe the current status of SCC therapeutics, recent advances in the understanding of SCC biology and prognostic gene signatures, and the development of innovative new clinical trials, all of which offer new hope for patients with advanced SCC.

  19. Paget cells in the esophagus: assessment of their histopathologic features and near-universal association with underlying esophageal adenocarcinoma.

    PubMed

    Abraham, Susan C; Wang, Huamin; Wang, Kenneth K; Wu, Tsung-Teh

    2008-07-01

    Pagetoid spread of primary esophageal melanomas and several cases of pagetoid esophageal squamous cell carcinoma are known. However, true esophageal Paget disease (intraepithelial growth of neoplastic cells with glandular differentiation) has only rarely been reported. We encountered 3 endoscopic biopsy specimens containing Paget cells in squamous epithelium associated with adenocarcinomas in Barrett esophagus (BE) and in the esophagogastric junction. To determine the prevalence of Paget cells in the esophagus, we studied 81 endoscopic mucosal resections and 27 esophagectomies from patients with invasive or intramucosal adenocarcinoma, and compared the findings to a control group of 47 endoscopic mucosal resections and 25 esophagectomies from patients with high-grade dysplasia in BE. Paget cells were present in squamous epithelium overlying 5 (4.9%) of 108 adenocarcinomas but in none (0%) of 72 BE with high-grade dysplasia (P=0.16). A computerized search for primary Paget disease using the terms "Paget's and esophagus" or "pagetoid and esophagus" from 1994 to 2007 did not yield any additional cases. Among the 8 patients with Paget cells (including the 2 index biopsies) there were no differences in either sex distribution (7M:1F) or age (mean 62.4 y) as compared with 103 adenocarcinomas without Paget cells (93M:10F, P=0.58; mean age 69.2 y, P=0.78). Morphologically, all adenocarcinomas with Paget cells contained at least a component of diffuse, poorly differentiated adenocarcinoma, and 1 was a signet ring cell carcinoma. Paget cells involved only squamous epithelium directly above the poorly differentiated tumor foci. Histochemistry for periodic acid-Schiff with diastase (PAS-D) and mucicarmine, and immunohistochemistry for CK7, CK20, p53, and E-cadherin, were performed on 7 Paget cases with the following results: PAS-D+ (7 of 7, 100%), mucicarmine+ (6 of 7, 86%), CK7+ (7 of 7, 100%), CK20+ (5 of 7, 71%), p53 overexpression (3 of 7, 43%), and E-cadherin loss

  20. Advances in the management of cutaneous squamous cell carcinoma

    PubMed Central

    Parikh, Sonal A.

    2014-01-01

    Cutaneous squamous cell carcinoma is one of the most common non-melanoma skin cancers worldwide. While most cutaneous squamous cell carcinomas are easily managed, there is a high-risk subset of tumors that can cause severe morbidity and mortality. Tumor characteristics as well as patient characteristics contribute to the classification of cutaneous squamous cell carcinomas as low-risk vs. high-risk. Advances in the treatment of cutaneous squamous cell carcinomas largely relate to the management of this high-risk subset. Surgical and non-surgical management options, including newer targeted molecular therapies, will be discussed here. Larger, multicenter studies are needed to determine the exact significance of individual risk factors with respect to aggressive clinical behavior and the risks of metastasis and death, as well as the role of surgical and adjuvant therapies in patients with high-risk cutaneous squamous cell carcinomas. PMID:25165569

  1. Immunohistochemical characterization of mammary squamous cell carcinoma of the dog.

    PubMed

    Sassi, Francesco; Sarli, Giuseppe; Brunetti, Barbara; Morandi, Federico; Benazzi, Cinzia

    2008-11-01

    Squamous cell carcinoma of the mammary gland is rare in both veterinary and human medicine. Whereas human metaplastic and squamous variants are known, the objectives of the current study were to ascertain the presence of such entities in canine mammary tumors and to distinguish them from other (epidermal, sweat gland) squamous tumors that may develop in the same area. A panel of antibodies (anti-cytokeratin [CK] 19, CK 14, CK 5/6, pancytokeratin, and vimentin) was used on 18 mammary gland malignancies with squamous features and 16 malignant skin tumors (11 squamous cell carcinomas of the skin and 5 sweat glands). Fifteen of the 18 mammary carcinomas were classified as metaplastic carcinomas, and the remaining 3 were classified as squamous cell carcinomas. The 2 most useful markers to establish the histogenesis of mammary tumors were pancytokeratin and CK 19. All other antibodies were equally expressed (CK 14 and 5/6) in all histotypes. The antibody panel discriminated primary epidermal squamous tumors (pancytokeratin positive and CK 19 negative) from gland-derived squamous neoplasms (pancytokeratin positive and CK 19 positive) but failed to distinguish primary mammary tumors from other squamous tumors of glandular origin.

  2. Squamous cell carcinoma of the extremities

    SciTech Connect

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

    1985-06-15

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

  3. A novel marker for basal (stem) cells of mammalian stratified squamous epithelia and squamous cell carcinomas.

    PubMed

    Samuel, J; Noujaim, A A; Willans, D J; Brzezinska, G S; Haines, D M; Longenecker, B M

    1989-05-01

    We have developed a monoclonal antibody (174H.64) which selectively recognizes antigens shared by the basal cells of mammalian stratified squamous epithelium and squamous cell carcinoma (SCC). Histopathological studies of the frozen tissue sections demonstrated selective binding of this antibody to SCCs of human, bovine, canine, feline, and murine origin. Tumors of other histological types did not show reactivity with the antibody. In well-differentiated SCCs the peripheral layer of the tumor showed preferential binding of the antibody, suggesting that the antigens are associated with the proliferative compartment of the tumor. Studies on normal human tissues showed selective binding of the antibody to the basal layer of stratified squamous epithelia, thymic epithelial cells, and myoepithelial cells around breast ducts, while no antibody binding was observed for the suprabasal layers of stratified epithelia, simple epithelia, or tissues of nonepithelial origin. A similar pattern of antibody binding was also observed for bovine and murine skin with staining of the basal layer. The antigens detected by monoclonal antibody 174H.64 were characterized from cytoskeletal protein extracts of normal human keratinocytes as well as human and bovine SCC tissues by using an immunoblotting technique. The antigens detected in normal human keratinocytes consisted of two major protein bands of approximate molecular weights of 48,000-50,000 and 57,000. In bovine SCC tumor the antigen detected was the Mr 48,000-50,000 band and in the human SCC tumor it was the Mr 57,000 band. A murine lung SCC model was developed with a murine SCC cell line KLN-205. The lung tumor obtained was reactive against the antibody and showed selective staining of the peripheral layer of the tumor containing the stem cell population. The antigens described by monoclonal antibody 174H.64 appear to be molecules associated with the stem cell populations of normal stratified epithelium and squamous cell carcinoma.

  4. Metachronous squamous-cell carcinoma of the colon and treatment of rectal squamous carcinoma with chemoradiotherapy.

    PubMed

    Brammer, R D; Taniere, P; Radley, S

    2009-02-01

    Rectal squamous-cell carcinoma is a rare tumour with an incidence of less than 1 per 1000 cases. We report such a case treated with chemoradiotherapy. The patient developed a metastasis in the spleen and a further squamous tumour in the right colon, both of which were successfully resected. No histological evidence of recurrent rectal tumour has been found. Two years following presentation, the patient remains disease-free although symptomatic from a radiotherapy-induced stricture of the rectum.

  5. Paracrine influence of human perivascular cells on the proliferation of adenocarcinoma alveolar epithelial cells

    PubMed Central

    Kim, Eunbi; Na, Sunghun; An, Borim; Yang, Se-Ran; Kim, Woo Jin; Ha, Kwon-Soo; Han, Eun-Taek; Park, Won Sun; Lee, Chang-Min; Lee, Ji Yoon

    2017-01-01

    Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-1α and K562) in vitro using Transwell® co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-1α and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer. PMID:28280409

  6. Cell division cycle 20 overexpression predicts poor prognosis for patients with lung adenocarcinoma.

    PubMed

    Shi, Run; Sun, Qi; Sun, Jing; Wang, Xin; Xia, Wenjie; Dong, Gaochao; Wang, Anpeng; Jiang, Feng; Xu, Lin

    2017-03-01

    The cell division cycle 20, a key component of spindle assembly checkpoint, is an essential activator of the anaphase-promoting complex. Aberrant expression of cell division cycle 20 has been detected in various human cancers. However, its clinical significance has never been deeply investigated in non-small-cell lung cancer. By analyzing The Cancer Genome Atlas database and using some certain online databases, we validated overexpression of cell division cycle 20 in both messenger RNA and protein levels, explored its clinical significance, and evaluated the prognostic role of cell division cycle 20 in non-small-cell lung cancer. Cell division cycle 20 expression was significantly correlated with sex (p = 0.003), histological classification (p < 0.0001), and tumor size (p = 0.0116) in non-small-cell lung cancer patients. In lung adenocarcinoma patients, overexpression of cell division cycle 20 was significantly associated with bigger primary tumor size (p = 0.0023), higher MKI67 level (r = 0.7618, p < 0.0001), higher DNA ploidy level (p < 0.0001), and poor prognosis (hazard ratio = 2.39, confidence interval: 1.87-3.05, p < 0.0001). However, in lung squamous cell carcinoma patients, no significant association of cell division cycle 20 expression was observed with any clinical parameter or prognosis. Overexpression of cell division cycle 20 is associated with poor prognosis in lung adenocarcinoma patients, and its overexpression can also be used to identify high-risk groups. In conclusion, cell division cycle 20 might serve as a potential biomarker for lung adenocarcinoma patients.

  7. Helicobacter Pylory infection in patients with esophageal squamous cell carcinoma

    PubMed Central

    Poyrazoglu, Omer Bilgehan; Dulger, Ahmet Cumhur; Gultepe, Bilge Sumbul

    2017-01-01

    OBJECTIVE: Esophageal squamous cell carcinoma is one of the most common esophageal diseases in the developing world, but the relationship between esophageal squamous cell carcinoma and Helicobacter pylori infection remains a neglected topic. The primary objective of this study was to determine the association between Helicobacter pylori infection and esophageal squamous cell carcinoma. A second purpose was to determine the incidence and factors associated with Helicobacter pylori infection following esophagectomy. METHOD: The microorganism was identified by testing the gastric biopsy materials from 95 esophageal squamous cell carcinoma patients (66 females; 39 were esophagectomized) for urease activity in a medium containing urea and a power of hydrogen detection reagent and comparing the results with those from a healthy population. Differences in patient characteristics were assessed with chi-square tests and t-tests for categorical and continuous factors, respectively. RESULTS: The patients with esophageal squamous cell carcinoma had a significantly lower prevalence of Helicobacter pylori compared with the healthy population (p<0.001). The naive and esophagectomized patients, in contrast, showed no significant differences in Helicobacter pylori infection (p>0.005). Patients with esophageal squamous cell carcinoma showed a significant association between leukocytosis and hypoglobulinemia and the presence of Helicobacter pylori infection (p=0.023 and p=0.045, respectively). CONCLUSION: These results suggest that Helicobacter pylori is not an etiological factor in patients with esophageal squamous cell carcinoma. We found a statistically significant negative correlation between esophageal squamous cell cancer and Helicobacter pylori infection. These findings may guide new strategies for esophageal squamous cell carcinoma therapy. PMID:28355360

  8. Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-04-03

    Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Lung Adenocarcinoma, Mixed Subtype; Squamous Cell Lung Carcinoma; Stage III Non-Small Cell Lung Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  9. Lupus vulgaris with squamous cell carcinoma.

    PubMed

    Motswaledi, Mojakgomo Hendrick; Doman, Chantal

    2007-12-01

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

  10. Squamous cell carcinoma arising from neglected meningocele

    PubMed Central

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

    2016-01-01

    Background: A neural tube defect (NTD) is a common congenital anomaly with an incidence of 6.57–8.21 per 1000 live births. Patients usually present early because of obvious swelling or due to neurological deficit. However, neglecting the obvious cystic swelling on the back till its transformation into malignant tumor is rare. Case Description: We describe a case of malignant transformation of meningocele in a 60-year-old man. Magnetic resonance imaging showed sacral meningocele. Neurological examination revealed intact motor and sensory examination with normal bladder and bowel function. There were no signs of meningitis and hydrocephalus. Excision was done and biopsy revealed it as squamous cell carcinoma. Conclusion: Meningocele should be treated early and possibility of malignant change should be kept in mind in neglected cases presenting in adulthood. PMID:28194302

  11. Genetic Testing in Screening Patients With Stage IB-IIIA Non-Small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)

    ClinicalTrials.gov

    2017-04-12

    Large Cell Lung Carcinoma; Lung Adenocarcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IB Squamous Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIA Squamous Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIB Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Squamous Cell Lung Carcinoma

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

    PubMed

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

    2016-03-01

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

  13. A Rare Collision Tumour of Uterus- Squamous Cell Carcinoma and Endometrial Stromal Sarcoma

    PubMed Central

    Gupta, Bindiya; Pathre, Abhishek; Rajaram, Shalini; Goyal, Neerja

    2017-01-01

    Collision tumours are defined by co-existence of two tumours in the same or adjacent organs which are topographically and histologically distinct with minimal or no histological admixture. Collision tumours have been described in many organs notably thyroid, brain, adrenal gland, stomach and rarely uterus. Most of the collision tumours reported in uterus have two components; an adenocarcinoma and a sarcoma. We report a case of a 60-year-old lady who presented with complaints of post-menopausal bleeding. A cervical biopsy was performed which showed a non-keratinizing squamous cell carcinoma of cervix. Intra-operatively the uterus was bulky with a 6 cm x 5 cm polypoidal mass in the endometrial canal along with a 2 cm friable cervical growth. The fleshy uterine cavity mass was a spindle cell tumour with moderate pleomorphism and frequent mitosis. It was immunopositive for CD10 and negative for smooth muscle actin and cytokeratin 5/6. The other growth showed non-keratinizing squamous cell carcinoma which was positive for cytokeratin 5/6. Based on the distinct topographical location and limited areas of tumour admixture of the two tumours, a diagnosis of collision tumour of uterus comprising of endometrial stromal sarcoma (high grade) uterus and squamous cell carcinoma cervix was made. PMID:28384878

  14. Detection of squamous carcinoma cells using gold nanoparticles

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    ClinicalTrials.gov

    2017-02-14

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

  16. Genomic characterization of esophageal squamous cell carcinoma: Insights from next-generation sequencing

    PubMed Central

    Sasaki, Yasushi; Tamura, Miyuki; Koyama, Ryota; Nakagaki, Takafumi; Adachi, Yasushi; Tokino, Takashi

    2016-01-01

    Two major types of cancer occur in the esophagus: squamous cell carcinoma, which is associated with chronic smoking and alcohol consumption, and adenocarcinoma, which typically arises in gastric reflux-associated Barrett’s esophagus. Although there is increasing incidence of esophageal adenocarcinoma in Western counties, esophageal squamous cell carcinoma (ESCC) accounts for most esophageal malignancies in East Asia, including China and Japan. Technological advances allowing for massively parallel, high-throughput next-generation sequencing (NGS) of DNA have enabled comprehensive characterization of somatic mutations in large numbers of tumor samples. Recently, several studies were published in which whole exome or whole genome sequencing was performed in ESCC tumors and compared with matched normal DNA. Mutations were validated in several genes, including in TP53, CDKN2A, FAT1, NOTCH1, PIK3CA, KMT2D and NFE2L2, which had been previously implicated in ESCC. Several new recurrent alterations have also been identified in ESCC. Combining the clinicopathological characteristics of patients with information obtained from NGS studies may lead to the development of effective diagnostic and therapeutic approaches for ESCC. As this research becomes more prominent, it is important that gastroenterologist become familiar with the various NGS technologies and the results generated using these methods. In the present study, we describe recent research approaches using NGS in ESCC. PMID:26900290

  17. How Are Squamous and Basal Cell Skin Cancers Diagnosed?

    MedlinePlus

    ... and Staging Tests for Basal and Squamous Cell Skin Cancers Most skin cancers are brought to a ... non-cancerous) without the need for a biopsy. Skin biopsy If the doctor thinks that a suspicious ...

  18. Squamous cell carcinoma of cervix metastatic to ileal loop

    SciTech Connect

    Hulecki, S.J.; Klein, F.A.; Davis, J.E.

    1985-12-01

    A case is presented of squamous cell carcinoma of the cervix with an isolated metastasis to an ileal loop six years after diversion and seven years after definitive treatment of the primary lesion with irradiation.

  19. Second-line afatinib administration in an elderly patient with squamous cell carcinoma

    PubMed Central

    Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul; Steinheimer, Michael; Benhassen, Naim; Sardeli, Chrysanthi; Stalikas, Nikos; Toitou, Melpomeni; Huang, Haidong

    2017-01-01

    Introduction The majority of cases of lung cancer are still diagnosed at a late stage. At this stage, palliative therapeutic options including nonspecific cytotoxic drugs, targeted therapy, or immunotherapy can be utilized. In 2016, immunotherapy was approved in Europe for squamous cell carcinoma and adenocarcinoma. Moreover, afatinib was also approved as second-line therapy for squamous cell carcinoma. Case report This article presents a case of a 76-year-old male with squamous cell carcinoma who received nab-paclitaxel as first-line therapy, and his treatment was switched to the tyrosine kinase inhibitor afatinib (40 mg) after disease progression with left lung atelectasis. After receiving afatinib for only 28 days, the atelectasis resolved. No adverse effects were observed from the afatinib therapy. Discussion In this case, afatinib 40 mg proved to be an effective alternative treatment for an elderly patient. Treatment choice should be based on the performance status of the patient, cost-effectiveness, and drug treatment guidelines. PMID:28356747

  20. Oral Squamous Cell Carcinoma in Three Related Kowari (Dasyuroides byrnei).

    PubMed

    Saunders, Richard; Killick, Rowena; Barrows, Michelle; Stidworthy, Mark

    2017-02-11

    We report three kowari (Dasyuroides byrnei) with squamous cell carcinoma affecting the gingiva. These cases occurred in rapid succession in a related group of individuals of similar age, suggesting a familial tendency to this condition and a typical age of presentation. Other conditions affecting the oral cavity can mimic the appearance of oral squamous cell carcinoma in this species, and so knowledge of this condition can assist the veterinarian in making rapid decisions regarding prognosis and improving the welfare of these animals.

  1. Corneal squamous cell carcinoma in a Border Collie.

    PubMed

    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.

  2. Entolimod in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer Receiving Cisplatin and Radiation Therapy

    ClinicalTrials.gov

    2013-12-10

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

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

    ClinicalTrials.gov

    2016-04-19

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

  4. [Squamous cell carcinoma in lupus vulgaris].

    PubMed

    Kimmritz, Jens; Hermes, Barbara; Schewe, Christiane; Haas, Norbert

    2004-02-01

    Lupus vulgaris and carcinoma in lupo have become rare events that take place in the developed countries only under special circumstances. A 53-year-old woman developed such a carcinoma. She suffered from alcoholism, a well known risk factor for tuberculosis. The diagnosis of lupus vulgaris was confirmed by biopsy when an erythematous lesion on her arm that had been present for 25 years enlarged and subsequently ulcerated. Chemotherapy was discontinued because of lack of compliance and the ulcer grew markedly over the following 16 months. Therefore the entire lesion was excised. Histology showed a squamous cell carcinoma within the ulcer. Neither further systemic manifestations of tuberculosis nor metastases of the carcinoma were found. Under continuous combined antituberculous therapy, the patient remained free of symptoms. This case underlines the problems associated with a disease that has been nearly forgotten in the western countries. It also shows that alcoholism is a risk factor for tuberculosis, along with debilitating diseases such as lymphoma and AIDS as well as immunosuppressive therapy.

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

    ClinicalTrials.gov

    2013-01-08

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

  6. What's New in Research and Treatment of Basal and Squamous Cell Skin Cancers?

    MedlinePlus

    ... About Basal and Squamous Cell Skin Cancer What’s New in Basal and Squamous Cell Skin Cancer Research? ... cancer cells. Researchers are working to apply this new information to strategies for preventing and treating skin ...

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

    PubMed Central

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

    2016-01-01

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

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

    ClinicalTrials.gov

    2017-03-01

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

  9. Signet cell adenocarcinoma of the rectum metastatic to the orbit.

    PubMed

    Charles, Norman C; Ng, Diana D; Zoumalan, Christopher I

    2012-01-01

    A 24-year-old man developed abdominal carcinomatosis from signet cell carcinoma of the rectum. His only distal metastasis involved the superior orbit. Orbital pathology showed signet cells with a characteristic immunopathologic pattern. No hereditary syndrome was found. The authors identified only 5 cases in the literature describing colorectal adenocarcinoma metastatic to the orbit, with 2 showing histopathology. The authors believe that this rare case represents the first illustrating bona fide signet cell colorectal cancer involving the orbit.

  10. Chemoprevention of esophageal squamous cell carcinoma

    SciTech Connect

    Stoner, Gary D. Wang Lishu; Chen Tong

    2007-11-01

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

  11. Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck

    ClinicalTrials.gov

    2012-10-30

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

  12. Inappropriate antidiuretic hormone secretion due to squamous cell lung cancer.

    PubMed

    Kotoulas, Christophoros; Panagiotou, Ioannis; Tsipas, Panteleimon; Koutoulakis, Emmanouil

    2015-06-01

    The syndrome of inappropriate secretion of antidiuretic hormone is a disorder of impaired water excretion caused by the inability to suppress secretion of antidiuretic hormone. It has been commonly associated with small cell carcinoma. The association of this syndrome with squamous cell lung carcinoma has rarely been reported, with only 4 cases over the past two decades in the English literature. We describe the case of a 75-year-old Caucasian male who developed the syndrome after a right pneumonectomy for down-staged squamous cell lung cancer previously treated with neoadjuvant platinum-based chemotherapy and radiotherapy.

  13. Close relation of large cell carcinoma to adenocarcinoma by hierarchical cluster analysis: implications for histologic typing of lung cancer on biopsies.

    PubMed

    Hammer, Stephan H; Prall, Friedrich

    2015-09-01

    Determining histologic types of lung cancer on biopsies can be difficult. This study addresses the role of immunohistochemistry in histologic typing, using a tissue microarray (TMA) as "model biopsies," and presents a classification generated by an unsupervised hierarchical cluster analysis. A TMA was made from resection specimens of a consecutive series of 165 lung tumors. In a "tissue-spot review" with hematoxylin and eosin sections all the large cell carcinomas (N=22) were assigned to the noncommittal class of non-small cell lung cancer (NSCLC), as were an additional 37 tumors of defined histologic types. Adenocarcinomas and squamous cell carcinomas included with these NSCLC could be diagnosed by immunohistochemistry with antibodies against TTF-1, Napsin A, cytokeratin (CK)7, p40, p63, and CK5/6 with moderate to good sensitivities and specificities. Unsupervised hierarchical clustering was done with these data and additional high-molecular-weight cytokeratins, CD56, synaptophysin, and chromogranin immunohistochemistry. This delineated separate clusters for adenocarcinomas, large cell carcinomas, neuroendocrine tumors, and squamous cell carcinomas. Notably, adenocarcinoma and large cell carcinoma clusters were closely related and clearly set off from the squamous cell carcinoma cluster. As would be expected for a clinically well-staged series CDX2, GATA3, estrogen, and progesterone receptor immunohistochemistry remained negative in the vast majority of the tumors and, if positive, were restricted to very few cells. These results, the clustering data in particular, underpin the pragmatic recommendation canvassed with the IASLC/ATS/ERS classification of lung cancers that adenocarcinoma-type molecular studies should include NSCLC with a nonsquamous cell carcinoma immunophenotype.

  14. Comprehensive genomic characterization of squamous cell lung cancers.

    PubMed

    2012-09-27

    Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

  15. Clinicopathologic features of oral squamous papilloma and papillary squamous cell carcinoma: a study of 197 patients from eastern China.

    PubMed

    Bao, Zhexuan; Yang, Xihu; Shi, Linjun; Feng, Jinqiu; Liu, Wei; Zhou, Zengtong

    2012-12-01

    Oral squamous papilloma and papillary squamous cell carcinoma are 2 clinicopathologically distinctive papillary epithelial tumors. The current study aims to compare the clinical and pathologic features of these oral papillary lesions in a patient population from eastern China. A retrospective review in a series of patients with clinical and pathologic diagnosis of oral squamous papilloma (n = 141) and papillary squamous cell carcinoma (n = 56) was conducted. The average age of oral squamous papilloma was 51.0 years (male-to-female ratio, 1.82), with the palate being the predominant site. The average age of oral papillary squamous cell carcinoma was 63.3 years (male-to-female ratio, 1.67), with the gingiva being the predominant site. Multivariate analysis revealed that the elderly patient with papillary lesion (≥60 years) was associated with 3.09-fold (95% confidence interval, 1.59-6.03) increased carcinoma risk compared with the nonelderly patient. The lesion located on the gingiva was associated with 4.98-fold (95% confidence interval, 1.96-12.63) increased carcinoma risk compared with other oral sites. Collectively, clinicopathologic features of oral squamous papilloma and papillary squamous cell carcinoma in eastern China were elucidated. Elderly patients with oral papillary lesions located on the gingiva correlate with higher carcinoma risk. It highlights the importance of using a histologic examination to confirm the clinical diagnosis for any suspicious papillary lesions.

  16. Pembrolizumab Combined With Cetuximab for Treatment of Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-03-28

    HNSCC; Lip SCC; Oral Cavity Cancer; Oropharynx Cancer; Larynx Cancer; Hypopharynx Cancer; Nasopharynx Cancer; Sinonasal Carcinoma; Cutaneous Squamous Cell Carcinoma; Head and Neck Neoplasms; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

  17. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    PubMed Central

    Martinez, Victor D.; Becker-Santos, Daiana D.; Vucic, Emily A.; Lam, Stephen; Lam, Wan L.

    2011-01-01

    Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epigenomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans. PMID:22175027

  18. Primary invasive ocular squamous cell carcinoma in a horse.

    PubMed

    Kaps, Simone; Richter, Marianne; Philipp, Martin; Bart, Madeleine; Eule, Corinna; Spiess, Bernhard M

    2005-01-01

    A 12-year-old Haflinger gelding was presented to the veterinary medical teaching hospital of the University of Zurich with a light-pink raised mass on the temporal limbus and conjunctiva of the left eye. Squamous cell carcinoma was confirmed histologically after keratectomy and cryotherapy. Seven months later, a smooth pink, progressively enlarging mass was observed within the cornea of the left eye. Ultrasonographically, the mass was not only infiltrating the corneal stroma but seemed to protrude into the anterior chamber. The globe was surgically removed and submitted for pathology. A histologic diagnosis of corneal ocular squamous cell carcinoma with deep stromal invasion, infiltration of the uveoscleral meshwork and iridocorneal angle and resulting intraocular extension was made. This is the first detailed description of a limbal squamous cell carcinoma with invasion into the cornea and uvea in the horse.

  19. Existence of a squamous cell carcinoma antigen-immunoglobulin complex causes a deviation between squamous cell carcinoma antigen concentrations determined using two different immunoassays: first report of squamous cell carcinoma antigen coupling with immunoglobulin A.

    PubMed

    Mori, Eriko; Kurano, Makoto; Tobita, Akiko; Shimosaka, Hironori; Yatomi, Yutaka

    2017-01-01

    Background Squamous cell carcinoma antigen is used as a tumour marker and is routinely measured in clinical laboratories. We validated two different immunoassays and found three cases in which the squamous cell carcinoma antigen concentrations deviated greatly between the two immunoassays. Here, we aimed to elucidate the mechanisms responsible for these deviations. Methods The squamous cell carcinoma antigen concentrations were determined using the ARCHITECT SCC (CLIA method) and the ST AIA-PACK SCC (FEIA method). We performed polyethylene glycol precipitation and size exclusion chromatography to assess the molecular weight and spike recovery and absorption tests to examine the presence of an autoantibody. Results Both methods exhibited good performances for the measurement of squamous cell carcinoma antigen, although a correlation test showed large differences in the squamous cell carcinoma antigen concentrations measured using the two methods in three cases. The results of polyethylene glycol treatment and size exclusion chromatography indicated the existence of a large molecular weight squamous cell carcinoma antigen in these three cases. The spike recovery tests suggested the possible presence of an autoantibody against squamous cell carcinoma antigen. Moreover, the absorption test revealed that large squamous cell carcinoma antigen complexes were formed by the association of squamous cell carcinoma antigen with IgG in two cases and with both IgG and IgA in one case. Conclusions This study describes the existence of large molecular weight squamous cell carcinoma antigen that has complexed with immunoglobulin in the serum samples. The reason for the deviations between the two immunoassays might be due to differences of their reactivities against the squamous cell carcinoma antigen immune complexes with their autoantibody. To our knowledge, this is the first report to describe the coupling of squamous cell carcinoma antigen with IgA.

  20. HPV-Related Head and Neck Squamous Cell Carcinomas.

    PubMed

    Marszałek, Andrzej; Szylberg, Łukasz

    Since more than 5 years, it becomes evident that there is a new group of patients with squamous cell carcinomas of the head and neck area, namely human papillomavirus (HPV)-related (caused) tumors. As clinical statistics indicate, those patients have better prognosis, even despite more advanced stage compared to those with HPV-negative tumors. In fact, as a surrogate of HPV infection for clinical studies, an immunohistochemical expression of p16 protein is used. In the following chapter, the spectrum of squamous cell carcinomas variants with indication of the percentage cases with proved HPV infection will be presented.

  1. Unexpected Anal Squamous Cells Carcinoma after Open Hemorrhoidectomy

    PubMed Central

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

    2015-01-01

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

  2. Squamous cell carcinoma arising in a multiple verrucous epidermal nevus*

    PubMed Central

    Yarak, Samira; Machado, Taila Yuri Siqueira; Ogawa, Marilia Marufuji; Almeida, Mirian Luzia da Silva; Enokihara, Milvia Maria Simões e Silva; Porro, Adriana Maria

    2016-01-01

    Verrucous epidermal nevi are hamartomatous lesions of the epidermis that, unlike other epidermal nevi (such as sebaceous nevus or nevus comedonicus), are rarely associated with malignant neoplasms. The majority of squamous cell carcinoma develop in linear or multiple epidermal nevus and rarely in solitary epidermal nevus. In general, the prognosis is favorable. We report a case of well-differentiated invasive squamous cell carcinoma arising from a multiple verrucous epidermal nevus. Although there is no consensus on prophylactic removal of epidermal nevus, its removal and biopsy should be considered if changes occur. PMID:28300931

  3. Rare tumors of esophageal squamous mucosa.

    PubMed

    Tripathi, Monika; Swanson, Paul E

    2016-10-01

    In spite of increasing incidence of esophageal adenocarcinoma in the last few decades, esophageal squamous cell carcinoma (SCC) still remains the dominant subtype of esophageal cancer worldwide. Apart from conventional SCC, some rare unconventional tumors of esophageal squamous mucosa are also well known. This study provides an introduction to these and presents a brief review of the literature, including the diagnostic and prognostic importance of each variant.

  4. Synchronous high-grade squamous intraepithelial lesion and adenocarcinoma in situ of cervix in a young woman presenting with hyperchromatic crowded groups in the cervical cytology specimen: report of a case.

    PubMed

    Zafar, Nadeem; Balazs, Louisa; Benstein, Barbara D

    2008-11-01

    We report a 29-year-old woman who underwent routine gynecologic evaluation at a community clinic and had a cervical sample drawn for liquid-based cytologic evaluation. At cytology, many hyperchromatic crowded groups (HCG) were present, but a consensus could not be established whether the abnormal cells were primarily glandular or squamous with secondary endocervical glandular involvement. An interpretation of atypical endocervical cells, favor neoplastic, was rendered and biopsy advised if clinically appropriate. At biopsy, the cervix contained synchronous squamous cell carcinoma in situ, secondarily involving endocervical glands, and neighboring adenocarcinoma in situ. Immunohistochemistry for Ki-67 and p16(INK4A) crisply and precisely stained both the lesions, clearly separating them from the adjacent uninvolved mucosa. This case re-emphasizes the challenge associated with accurate evaluation of HCG at cytology, the significance of ancillary testing for surrogate markers of high-risk HPV (HR-HPV) infection, the need for adjunct testing for HPV-DNA in the setting of HCG at cervical cytology, and a recommendation to set up studies to evaluate the role of surrogate markers of HR-HPV infection in cytologic samples with HCG.

  5. COPD and squamous cell lung cancer: aberrant inflammation and immunity is the common link.

    PubMed

    Bozinovski, Steven; Vlahos, Ross; Anthony, Desiree; McQualter, Jonathan; Anderson, Gary; Irving, Louis; Steinfort, Daniel

    2016-02-01

    Cigarette smoking has reached epidemic proportions within many regions of the world and remains the highest risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Squamous cell lung cancer is commonly detected in heavy smokers, where the risk of developing lung cancer is not solely defined by tobacco consumption. Although therapies that target common driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related squamous cell lung cancer. Since COPD is characterized by an excessive inflammatory and oxidative stress response, this review details how aberrant innate, adaptive and systemic inflammatory processes can contribute to lung cancer susceptibility in COPD. Activated leukocytes release increasing levels of proteases and free radicals as COPD progresses and tertiary lymphoid aggregates accumulate with increasing severity. Reactive oxygen species promote formation of reactive carbonyls that are not only tumourigenic through initiating DNA damage, but can directly alter the function of regulatory proteins involved in host immunity and tumour suppressor functions. Systemic inflammation is also markedly increased during infective exacerbations in COPD and the interplay between tumour-promoting serum amyloid A (SAA) and IL-17A is discussed. SAA is also an endogenous allosteric modifier of FPR2 expressed on immune and epithelial cells, and the therapeutic potential of targeting this receptor is proposed as a novel strategy for COPD-lung cancer overlap.

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

    ClinicalTrials.gov

    2016-10-04

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

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

    ClinicalTrials.gov

    2017-04-12

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Major Salivary Gland Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  8. Gynecologic Cancer InterGroup (GCIG) consensus review for cervical adenocarcinoma.

    PubMed

    Fujiwara, Hiroyuki; Yokota, Harushige; Monk, Bradley; Treilleux, Isabelle; Devouassoux-Shisheboran, Mojgan; Davis, Alison; Kim, Jae-Weon; Mahner, Sven; Stany, Michael; Pignata, Sandro; Ray-Coquard, Isabelle; Fujiwara, Keiichi

    2014-11-01

    Cervical adenocarcinoma is known to be less common than squamous cell carcinoma of the cervix comprising approximately 25% of all cervical carcinomas. Differences in associated human papillomavirus types, patterns of spread, and prognosis call for treatments that are not always like those for squamous cancers. In this review, we report a consensus developed by the Gynecologic Cancer InterGroup surrounding cervical adenocarcinoma for epidemiology, pathology, treatment, and unanswered questions. Prospective clinical trials are needed to help develop treatment guidelines.

  9. Isolation, cultivation and identification of human lung adenocarcinoma stem cells

    PubMed Central

    ZHANG, DE-GENG; JIANG, AI-GUI; LU, HUI-YU; ZHANG, LI-XIN; GAO, XIAO-YAN

    2015-01-01

    Recently, an increasing number of studies have demonstrated that lung cancer is a stem cell disease. However, ideal cell surface markers for isolating stem cells in lung cancer are yet to be identified. In the present study, a cell population with a cluster of differentiation (CD)133+ phenotype was successfully isolated from a single cell suspension of lung adenocarcinoma tissue using magnetic-activated cell sorting (MACS) and enriched in a serum-free culture. In comparison to CD133− cells, the CD133+ cells exhibited an enhanced capacity for self-renewal and differentiation, and a greater potential for in vivo tumor formation, in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Tumors could be induced in NOD/SCID mice by the transplantation of 102 stem-like cells per mouse. The results of the present study demonstrated that CD133 may serve as a specific cell surface marker for lung adenocarcinoma stem cells, and that MACS combined with serum-free culture is an effective method for isolating and enriching lung cancer stem cells. PMID:25435932

  10. Molecular Analysis of Motility in Metastatic Mammary Adenocarcinoma Cells

    DTIC Science & Technology

    1996-09-01

    Culture MTLn3 cells were clonally derived from a lung metastasis of the 13762NF rat mammary adenocarcinoma ( Neri et al., 1982) (kindly provided by Dr...MTLn3 cells were plated on collagen I coated MATTEK tissue culture dishes for 24 hours. Cells were plated at a density of 5000 cells/sq cm and...mM KOH; 4 mM MgC12 ; 10 mM EGTA pH 6.5 with 20 mM KOH; 5 1M phallacidin; 0.025 % saponin) was added to the culture well. After 15 seconds of extraction

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

    ClinicalTrials.gov

    2013-07-01

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

  12. Carboplatin, Paclitaxel, Cetuximab, and Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Head and Neck Squamous Cell Cancer

    ClinicalTrials.gov

    2017-01-24

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

  13. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

    PubMed

    Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

    2012-11-01

    Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

  14. Necrotizing sialometaplasia of the lip simulating squamous cell carcinoma.

    PubMed

    Gad, A; Willén, H; Willén, R; Thorstensson, S; Ekman, L

    1980-01-01

    A case of necrotizing sialometaplasia of the lip in an 68-year-old pipe smoker is described. Necrotizing sialometaplasia is a self-healing non-neoplastic disease probably of ischaemic nature. Thirty-nine cases of sialometaplasia are described in the literature up to early 1979. These cases appeared in the palate, nasal cavity, gingiva, lip, hypopharynx and maxillary sinus. Six cases have also been reported from major salivary glands. Histologically there is necrosis of mucous cells with partial replacement by squamous epithelium. This entity has often been mistaken for squamous or mucoepidermoid carcinoma. One has to be familiar with the existence of necrotizing sialometaplasia in ordeg surgery.

  15. Perineural Spread of Cutaneous Squamous Cell Carcinoma Manifesting as Ophthalmoplegia

    PubMed Central

    Koukkoulli, Antigoni; Koutroumanos, Nikolas; Kidd, Desmond

    2015-01-01

    ABSTRACT An 89-year-old female presented with horizontal diplopia and was diagnosed with VI nerve palsy attributed to a microvascular event. She subsequently progressed to develop an orbital apex syndrome, with neuroimaging demonstrating tumour invasion. Eighteen months earlier, she had squamous cell carcinoma of the forehead excised with clear margins. Intraneural and perineural spread of squamous carcinoma from the face to the cranial cavity is an important cause of delayed cranial nerve palsies after local excision of the skin tumour. PMID:27928347

  16. Occult esophageal squamous cell carcinoma with metastases to the spine and central nervous system

    PubMed Central

    Roballo, Carla Adriane; de Campos, Pompeu Tomé Ribeiro; Teixeira, Carlos Osvaldo; Teixeira, Maria Aparecida Barone

    2015-01-01

    Esophageal malignancy encompasses a group of diseases that are mostly represented by the squamous cell carcinoma and the adenocarcinoma. Quite frequently, these neoplasms present aggressive behavior; therefore, the diagnosis is often made when the condition is in advanced stages. Dysphagia is the typical clinical complaint, although it is present only when most of the lumen is obstructed. Therefore, quite often, the metastatic disease is first diagnosed, which contributes to the patient's poor survival expectancy. The authors report the case of a 58-year-old man who looked for medical care complaining of a long-term history of scapular pain. The diagnostic work-up disclosed a cervical spine lytic lesion surrounded by a tumoral mass shown by computed tomography. The cervical tumor was sampled by fine needle aspiration, revealing an undifferentiated carcinoma. The outcome was unfavorable and the patient died. The autopsy findings revealed metastatic disease to the spine and central nervous system, and the primary tumor was found to be an esophageal squamous cell carcinoma, which had progressed without typical dysphagia. PMID:26484322

  17. Cutaneous squamous cell carcinomas consistently show histologic evidence of in situ changes: a clinicopathologic correlation.

    PubMed

    Guenthner, S T; Hurwitz, R M; Buckel, L J; Gray, H R

    1999-09-01

    Squamous cell carcinoma on sun-damaged skin is a malignant neoplasm that evolves from its inception as squamous cell carcinoma in situ, which is commonly referred to as an actinic keratosis. In this study, we reviewed 1011 squamous cell carcinomas on sun-damaged skin and found that nearly 100% of these lesions contained histopathologic changes consistent with squamous cell carcinoma in situ at the periphery or within the confines of the squamous cell carcinoma. These malignant changes began in single layer areas of the lower epidermis and evolved into the epidermis and dermis.

  18. Squamous cell cancer of female urethra. Successful treatment with chemoradiotherapy

    SciTech Connect

    Shah, A.B.; Kalra, J.K.; Silber, L.; Molho, L.

    1985-03-01

    The case is reported of a seventy-four-year-old woman with advanced squamous cell carcinoma of the urethra who achieved complete biopsy-proved regression of the tumor for more than thirty months after therapy with 5-fluorouracil, mitomycin-C, and radiotherapy.

  19. Subungual Squamous Cell Carcinoma: The Diagnostic Challenge and Clinical Pearls

    PubMed Central

    Kok, Wai Leong; Lee, Joyce Siong See; Chio, Martin Tze-wei

    2016-01-01

    Subungual squamous cell carcinoma is a rare entity and difficult to diagnose as its clinical presentation may resemble benign conditions. This case report highlights the need to maintain a high clinical index of suspicion, and recommends a practical approach for subungual conditions. Dermoscopy and a biopsy for histology are important adjuncts to clinch the diagnosis. PMID:27920677

  20. A dog with squamous cell carcinoma in the middle ear.

    PubMed

    Yoshikawa, Hiroto; Mayer, Monique N; Linn, Kathleen A; Dickinson, Ryan M; Carr, Anthony P

    2008-09-01

    An 8-year-old, castrated male golden retriever was referred for lethargy and inappetance. Severe pain was elicited on palpation of the left temporomandibular joint region. Computed tomography revealed aggressive bone destruction of the left bulla. Squamous cell carcinoma was diagnosed. Malignant tumor in the canine middle ear is rare.

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

    SciTech Connect

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

    1989-05-12

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

  2. TLR8 Agonist VTX-2337 and Cetuximab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Squamous Cell Cancer of Head and Neck

    ClinicalTrials.gov

    2015-03-03

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

  3. Review of paraneoplastic syndromes associated with oropharyngeal squamous cell carcinoma

    PubMed Central

    Mathew, Deepu George; Rooban, T; Janani, V; Joshua, E; Rao, UK; Ranganathan, K

    2010-01-01

    Malignancies are usually preceded by the presence of various paraneoplastic syndromes (PNS), which could be the indirect and/or remote effects of the metabolites produced by neoplastic cells. PNS manifested by oropharyngeal squamous cell carcinomas, which is the most common head and neck malignancy, are highlighted in this review. Knowledge of the clinical spectrum of these syndromes will equip the oral physician for early diagnosis and management of these hidden malignancies, especially of the pharyngeal region. PMID:21731261

  4. 5-Fluorouracil-radiation interactions in human colon adenocarcinoma cells

    SciTech Connect

    Buchholz, D.J.; Lepek, K.J.; Rich, T.A.

    1995-07-15

    The purpose of this investigation was to determine the effect of cellular proliferation and cell cycle stage on the ability of postirradiation 5-fluorouracil (5-FU) to radiosensitize cultured human colon adenocarcinoma Clone A cells. Cell survival curves were generated for irradiated: (a) log- and plateau-phase Clone A cells; and (b) Clone A cells separated by centrifugal elutriation into the various phases of the cell cycle; with and without postirradiation treatment with 100 {mu}g/ml 5-FU. Postirradiation treatment with 5-FU sensitized proliferating cells to a greater degree than it sensitized cells growing in plateau phase. The {beta} component of cell kill in log-phase cells was increased by a factor of 1.5 with a sensitizer enhancement ratio of 1.21 at the 0.01 survival level. Plateau-phase cells showed less radiosensitization (sensitizer enhancement ratio of 1.13 at the 0.01 survival level); however, there was a mild increase in both {alpha} and {beta} kill in plateau-phase cells. Elutriated G{sub 1} cells were the most radiosensitive, independent of treatment with 5-FU. The phase of the cell cycle had little effect on the ability of fluorouracil to radiosensitize Clone A cells. Proliferating cells are more susceptible to radiosensitization with 5-FU than plateau-phase cells are, but this effect appears to be independent of the phase of the cell cycle. 18 refs., 4 figs., 3 tabs.

  5. Conjunctival squamous cell carcinoma in a reindeer (Rangifer tarandus tarandus).

    PubMed

    Gonzalez-Alonso-Alegre, Elisa M; Rodriguez-Alvaro, Alfonso; Martinez-Nevado, Eva; Martinez-de-Merlo, Elena M; Sanchez-Maldonado, Belen

    2013-07-01

    An 8-year-old female adult reindeer (Rangifer tarandus tarandus) was referred to the Veterinary Hospital of Madrid for evaluation of a conjunctival mass on the left eye which had been present for about 2 months. A surgical excision was performed and biopsy material submitted for light microscopic evaluation which confirmed the diagnosis of conjuctival squamous cell carcinoma. Nuclear p53 immunolabeling was found in 52% of the neoplastic cells. Follow-up examination at 12 months postsurgery did not reveal recurrence of this neoplasm. Conjunctival squamous cell carcinoma has not been reported previously in reindeer and seems to have similar characteristics to the one existing in bovine species.

  6. Collision tumor of the thyroid gland: primary squamous cell and papillary thyroid carcinoma.

    PubMed

    Warman, Meir; Lipschitz, Noga; Ikher, Sergey; Halperin, Doron

    2011-01-01

    Introduction. Collision tumor of the thyroid gland is defined when independent and histologically distinct tumors coexist within the gland. The presence of both papillary and squamous cell carcinoma in the thyroid gland is unusual. Suggested etiologies include embryonic remanents of squamous epithelium, chronic inflammation, or thyroid malignancies promoting squamous metaplasia. Case Presentation. An elderly patient presented with a rapid enlargement of a long-standing right thyroid nodule. The tumor was locally invasive and unresectable. Pathology revealed the diagnosis of papillary and squamous cell carcinoma of the thyroid gland. Possible primary sites for squamous cell carcinoma in upper aerodigestive tract were excluded. The patient outcome was fatal although palliative chemoradiotherapy. Discussion. Collision tumor of papillary and squamous cell carcinoma of the thyroid gland is a rare entity that may imply bad prognosis, as to the presence of the squamous portion. The best treatment includes resection of the tumor; unfortunately it is not possible in most cases.

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

    PubMed Central

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

    2016-01-01

    Background Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Methods Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). Results The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. Conclusion The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment. PMID:27828631

  8. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  9. Pure Primary Ovarian Squamous Cell Carcinoma Perforating the Rectum

    PubMed Central

    Okada, Aiko; Haraguchi, Naotsugu; Tomimatsu, Takuji; Kimura, Tadashi

    2017-01-01

    Rectal perforation is uncommon in ovarian cancer, even in advanced stages. Pure primary ovarian squamous cell carcinoma is a very rare subtype of ovarian cancer and has not been reported to cause rectal perforation. A 50-year-old woman presented with rectal bleeding. Rectosigmoidoscopy suggested perforation of a pelvic tumor into the rectum. Abdominopelvic magnetic resonance imaging revealed a 9 cm heterogeneous mass in the pouch of Douglas. We performed complete cytoreduction, including an en-bloc resection of the tumor and rectosigmoid colon. Histopathology showed squamous cell carcinoma of the left ovary penetrating the rectal wall. A common symptom of rectal bleeding was caused by a very rare entity of ovarian cancer penetrating the rectal wall, but thorough evaluation led to its accurate diagnosis and appropriate treatment. PMID:28316851

  10. Focal cutaneous squamous cell carcinoma following radium-223 extravasation

    PubMed Central

    Benjegerdes, Katie E.; Housewright, Chad D.

    2017-01-01

    Long-term sequelae due to extravasation of intravenous radioisotopes resulting in radiation injuries are rarely reported. As the use of radioactive isotopes for the treatment of osteoblastic metastases increases, information regarding the prevention, treatment, and long-term monitoring of suspected extravasation injury will become increasingly important. We present a patient with no previous history of skin cancer who developed an aggressive cutaneous squamous cell carcinoma at the site of prior radium-223 extravasation. We recommend that patients who experience extravasation of therapeutic radioisotopes be monitored by dermatologists for long-term sequelae. Cutaneous squamous cell carcinoma should be recognized as a rare but potential adverse event following cutaneous extravasation of radium-223 and is likely a side effect that is severely underreported. PMID:28127143

  11. Animal models of head and neck squamous cell carcinoma.

    PubMed

    Supsavhad, Wachiraphan; Dirksen, Wessel P; Martin, Chelsea K; Rosol, Thomas J

    2016-04-01

    Head and neck squamous cell carcinoma (HNSCC) is the most common oral cancer worldwide. Local bone invasion into the maxilla or mandible and metastasis to regional lymph nodes often result in a poor prognosis, decreased quality of life and shortened survival time for HNSCC patients. Poor response to treatment and clinical outcomes are the major concerns in this aggressive cancer. Multiple animal models have been developed to replicate spontaneous HNSCC and investigate genetic alterations and novel therapeutic targets. This review provides an overview of HNSCC as well as the traditional animal models used in HNSCC preclinical research. The value and challenges of each in vivo model are discussed. Similarity between HNSCC in humans and cats and the possibility of using spontaneous feline oral squamous cell carcinoma (FOSCC) as a model for HNSCC in translational research are highlighted.

  12. Talactoferrin in Treating Patients With Relapsed or Refractory Non-Small Cell Lung Cancer or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-07-30

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral

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

    PubMed

    Esfandiary, Ali; Ghafouri-Fard, Soudeh

    2015-01-01

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

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

    PubMed

    Kumar, Dhruv

    2017-01-01

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

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

    PubMed Central

    Kumar, Dhruv

    2017-01-01

    Glycolysis is highly upregulated in head and neck squamous cell carcinoma (HNSCC). HNSCC glycolysis is an important contributor to disease progression and decreases sensitivity to radiation or chemotherapy. Despite therapeutic advances, the survival rates for HNSCC patients remain low. Understanding glycolysis regulation in HNSCC will facilitate the development of effective therapeutic strategies for this disease. In this review, we will evaluate the regulation of altered HNSCC glycolysis and possible therapeutic approaches by targeting glycolytic pathways. PMID:28191478

  16. Verrucous carcinoma and squamous cell papilloma of the oral cavity: Report of two cases and review of literature

    PubMed Central

    Alan, Hilal; Agacayak, Serkan; Kavak, Gulten; Ozcan, Ayse

    2015-01-01

    Verrucous carcinoma (VC) of oral cavity is a rare variant of well-differentiated squamous cell carcinoma and squamous papilloma is a benign proliferation of the stratified squamous epithelium, which results in a papillary or verrucous exophytic mass. There is a certain clinical similarity between squamous cell papilloma and VC. We presented a report of two cases which are VC and squamous cell papilloma that are showed the same clinical appearance but different pathological appearance, with a review of the literature. PMID:26430380

  17. Oral squamous cell carcinoma in a 10 year old boy.

    PubMed

    Khan, M H; Naushad, Q N

    2011-01-01

    Squamous cell carcinoma of the oral cavity a type of Oral Cancer in young patients is a very rare occurrence particularly during the first decade of life. Oral cancer is predominantly an aggressive neoplasm of middle-aged people where 96% of the patients are more than 40 years of age and it occurs mainly due to the excessive consumption of tobacco and alcohol. In South-East Asia it has a higher rate of occurrence than the rest of the world, partly due to increased consumption of chewing tobacco and various harmful spices, areca nuts and betel quids. These rare varieties of aggressive neoplasm commonly affect tongue and lip. This report describes a case of squamous cell carcinoma in a 10 year old boy who had an exophytic type of granulomatous lesion with some indurated borders which diffusely involved the left side of the hard palate, alveolar mucosa, left maxillary antrum and aggressively emerged within the left orbit by engulfing the left inferior rectus muscle. The purpose of this case report is to provide information that younger group can suffer from oral squamous cell carcinoma though it is very rare and this younger group would appear to have a biologically more aggressive tumor and they require more complex treatment. The role of more aggressive initial therapy must be considered.

  18. The emerging epidemic of melanoma and squamous cell skin cancer

    SciTech Connect

    Glass, A.G. ); Hoover, R.N. )

    1989-10-20

    Squamous cell skin cancer, though common, remains largely unreported and unstudied, with little known about its incidence and time trends. The authors have used a unique resource--a continuous population-based registry of cases of squamous cell skin cancer within a single prepaid health plant--to describe basic epidemiologic features of this malignancy and compare it with the more widely studied melanoma. Both malignancies are considerably more common in this population than they expected based on previous reports from the general population. From the 1960s to the 1980s, the incidence of squamous cell skin cancer increased 2.6 times in men and 3.1 times in women, while incidence of melanoma rose 3.5-fold and 4.6-fold in men and women, respectively. Skin cancers of both types involving the head and neck or the extremities increased essentially in parallel over these 27 years. Melanomas of the trunk, however, appeared to increase at a faster rate in both sexes. These observations are consistent with the impression that the rising incidence of both malignancies may be attributable to increased voluntary exposure to the sun over an extended period.

  19. Diagnosis of primary squamous cell carcinoma of the pancreas using endoscopic ultrasound-guided core needle biopsy.

    PubMed

    Kashani, Amir; Kahn, Melissa; Jamil, Laith H

    2015-05-16

    Primary squamous cell carcinoma (SCC) of the pancreas is a particularly rare entity. Diagnosis of this tumor is tentatively made after ruling out metastatic SCC from another primary site and adenosquamous carcinoma (ASC) of the pancreas. Here we discuss the case of a 76-year-old woman who was found to have a solitary pancreatic lesion and multiple hepatic lesions. Results of computed tomography-guided biopsy of the liver lesions were consistent with a metastatic carcinoma displaying squamous differentiation; therefore, an endoscopic ultrasound (EUS)-guided core-needle biopsy (CNB) of the pancreatic mass was performed. Meticulous histopathological examination of the pancreatic specimen at multiple levels revealed moderately well-differentiated SCC with no glandular component. An extensive metastatic work-up did not reveal an extra-pancreatic origin for this SCC; hence, a diagnosis of primary SCC of the pancreas was established. To our knowledge, this is the first report of the diagnosis of a primary SCC of the pancreas using EUS-guided CNB. We believe that CNB has a diagnostic yield equivalent to that of fine-needle aspiration for recognizing pancreatic adenocarcinoma; however, when cytological examinations reveal atypical squamous epithelial cells suggestive of malignancy, CNB may provide a better tissue specimen, from which to determine the presence of a glandular component. Such an assessment will differentiate pancreatic SCC from ASC.

  20. Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma.

    PubMed

    Li, Yan; Wang, Kai; Yin, Shankai; Zheng, Hongliang; Min, Daliu

    2016-12-01

    Xanthohumol is a flavonoid compound that exhibits antioxidant and anticancer effects, and is used to treat atherosclerosis. The aim of the present study was to investigate the effect of xanthohumol on the cell proliferation of laryngeal squamous cell carcinoma and to understand the mechanism of its action. The effects of xanthohumol on the cell viability and apoptosis rate of laryngeal squamous cell carcinoma SCC4 cells were assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining. In addition, the expression levels of pro-apoptotic proteins, caspase-3, caspase-8, caspase-9, poly ADP ribose polymerase (PARP) p53 and apoptosis-inducing factor (AIF), as well as anti-apoptotic markers, B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1), were analyzed by western blotting. The results revealed that treatment with 40 µM xanthohumol significantly inhibited the proliferation of SCC4 cells. Furthermore, xanthohumol treatment (40 µM) induced SCC4 cell apoptosis, as indicated by the significant increase in activity and expression of caspase-3, caspase-8, caspase-9, PARP, p53 and AIF. By contrast, the protein expression of Bcl-2 and Mcl-1 was significantly decreased following treatment with 40 µM xanthohumol. Taken together, the results of the present study indicated that xanthohumol mediates growth suppression and apoptosis induction, which was mediated via the suppression of Bcl-2 and Mcl-1 and activation of PARP, p53 and AIF signaling pathways. Therefore, future studies that investigate xanthohumol as a potential therapeutic agent for laryngeal squamous cell carcinoma are required.

  1. Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

    PubMed Central

    Li, Yan; Wang, Kai; Yin, Shankai; Zheng, Hongliang; Min, Daliu

    2016-01-01

    Xanthohumol is a flavonoid compound that exhibits antioxidant and anticancer effects, and is used to treat atherosclerosis. The aim of the present study was to investigate the effect of xanthohumol on the cell proliferation of laryngeal squamous cell carcinoma and to understand the mechanism of its action. The effects of xanthohumol on the cell viability and apoptosis rate of laryngeal squamous cell carcinoma SCC4 cells were assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining. In addition, the expression levels of pro-apoptotic proteins, caspase-3, caspase-8, caspase-9, poly ADP ribose polymerase (PARP) p53 and apoptosis-inducing factor (AIF), as well as anti-apoptotic markers, B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1), were analyzed by western blotting. The results revealed that treatment with 40 µM xanthohumol significantly inhibited the proliferation of SCC4 cells. Furthermore, xanthohumol treatment (40 µM) induced SCC4 cell apoptosis, as indicated by the significant increase in activity and expression of caspase-3, caspase-8, caspase-9, PARP, p53 and AIF. By contrast, the protein expression of Bcl-2 and Mcl-1 was significantly decreased following treatment with 40 µM xanthohumol. Taken together, the results of the present study indicated that xanthohumol mediates growth suppression and apoptosis induction, which was mediated via the suppression of Bcl-2 and Mcl-1 and activation of PARP, p53 and AIF signaling pathways. Therefore, future studies that investigate xanthohumol as a potential therapeutic agent for laryngeal squamous cell carcinoma are required. PMID:28105237

  2. Effect of gyromagnetic fields on human prostatic adenocarcinoma cells

    PubMed Central

    Lei, Hongen; Xu, Yongde; Guan, Ruili; Li, Meng; Hui, Yu; Gao, Zhezhu; Yang, Bicheng; Xin, Zhongcheng

    2015-01-01

    Purpose To investigate the biological effect of gyromagnetic fields (GMFs) on cell proliferation and apoptosis of human prostatic adenocarcinoma cells and explore the underlying mechanisms. Methods PC-3 cells were grouped into normal control (NC) and GMF treatment groups. Cell proliferation was analyzed with kit-8 and Ki67 immunofluorescence staining, while cell apoptosis was analyzed with flow cytometry double staining of Annexin V-PE/7-AAD. The Akt and p38 MAPK/Caspase signaling pathways were analyzed by western blotting and immunofluorescence staining, and cell polarization was analyzed with PARD3. Results Cell proliferation and activity of the Akt pathway were significantly decreased by the GMF, while cell apoptosis, activity of p38 MAPK, and PARD3-positive cell number were significantly increased in the GMF group compared to the NC group. Conclusion GMFs inhibit cell proliferation, induce apoptosis, and regulate tumor cell polarity conditions, potentially through down-regulating Akt, activating the p38 MAPK/Caspase pathway, and promoting PARD3 expression in PC-3 cells. PMID:26648740

  3. Verrucoid Variant of Invasive Squamous Cell Carcinoma in Oral Submucous Fibrosis: A Clinicopathological Challenge

    PubMed Central

    Ramani, Priya; Krithika, C.; Ananthalakshmi, R.; Jagdish, Praveena; Janardhanan, Sunitha; Jeevakarunyam, Sathiyajeeva

    2016-01-01

    Verrucous carcinoma (VC) is an exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. It is described as a lesion appearing in the sixth or seventh decade of life that has minimal aggressive potential and, in long-standing cases, has been shown to transform into squamous cell carcinoma. Oral submucous fibrosis (OSMF) is a potentially malignant disorder, and about one-third of the affected population develop oral squamous cell carcinoma. The histopathological diagnosis of verrucous carcinoma is challenging, and the interpretation of early squamous cell carcinoma requires immense experience. Here we present a rare case of a 24-year-old male with OSMF transforming to verrucous carcinoma with invasive squamous cell carcinoma. Even though the case had a straightforward clinical diagnosis, the serial sectioning done for pathological diagnosis disclosed the squamous cell carcinoma.

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

    PubMed

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

    2016-04-01

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

  5. A Gene Encoding Antigenic Peptides of Human Squamous Cell Carcinoma Recognized by Cytotoxic T Lymphocytes

    PubMed Central

    Shichijo, Shigeki; Nakao, Masanobu; Imai, Yasuhisa; Takasu, Hideo; Kawamoto, Mayumi; Niiya, Fumihiko; Yang, Damu; Toh, Yuji; Yamana, Hideaki; Itoh, Kyogo

    1998-01-01

    Except for melanomas, tumor antigens recognized by cytotoxic T lymphocytes (CTLs) are yet unidentified. We have identified a gene encoding antigenic peptides of human squamous cell carcinomas (SCCs) recognized by human histocompatibility leukocyte antigens (HLA)- A2601–restricted CTLs. This gene showed no similarity to known sequences, and encoded two (125- and 43-kilodalton [kD]) proteins. The 125-kD protein with the leucine zipper motif was expressed in the nucleus of the majority of proliferating cells tested, including normal and malignant cells. The 43-kD protein was expressed in the cytosol of most SCCs from various organs and half of lung adenocarcinomas, but was not expressed in other cancers nor in a panel of normal tissues. The three nonapeptides shared by the two proteins were recognized by the KE4 CTLs, and one of the peptides induced in vitro from peripheral blood mononuclear cells (PBMCs) the CTLs restricted to the autologous tumor cells. The 43-kD protein and this nonapeptide (KGSGKMKTE) may be useful for the specific immunotherapy of HLA-A2601+ epithelial cancer patients. PMID:9449708

  6. Sulphamoylated 2-Methoxyestradiol Analogues Induce Apoptosis in Adenocarcinoma Cell Lines

    PubMed Central

    Visagie, Michelle; Theron, Anne; Mqoco, Thandi; Vieira, Warren; Prudent, Renaud; Martinez, Anne; Lafanechère, Laurence; Joubert, Annie

    2013-01-01

    2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1–25 μM) was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues. PMID:24039728

  7. Touch imprint cytology: a rapid diagnostic tool for oral squamous cell carcinoma.

    PubMed

    Geetha, L; Astekar, M; Ashok, K N; Sowmya, G V

    2015-07-01

    Techniques for intraoperative pathologic examination of oral squamous cell carcinoma are rare in the literature. We evaluated the advantages and limitations of touch imprint cytology for intraoperative diagnosis of oral squamous cell carcinoma. We used 30 incisional biopsies of clinically diagnosed oral squamous cell carcinoma and compared touch imprint cytology to histopathological sections. Touch imprint cytology showed 24 specimens positive for malignancy, two suspicious for malignancy and four inadequate specimens. The accuracy of the test was 93.2%. Touch imprint cytology is an accurate, simple, rapid and cost-effective method that aids diagnosis of oral squamous cell carcinoma during operation, but it does not replace incisional biopsy.

  8. Labeling index in squamous cell carcinoma of the larynx

    SciTech Connect

    Balzi, M.; Ninu, B.M.; Becciolini, A.; Scubla, E.; Boanini, P.; Gallina, E.; Gallo, O.; Fini-Storchi, O.; Bondi, R. )

    1991-07-01

    Two cell kinetic parameters, the 3H-thymidine labeling index (TLI) and the mitotic index (MI), were studied in vitro on fragments of squamous cell carcinoma tissue of the larynx. They were evaluated to identify those elements able to characterize the growth of these solid tumors. The values of these parameters were analyzed as a function of the clinical stage and the involvement of the regional lymph nodes. Results showed a statistically significant increase in the TLI from stage T1 to T3. No statistically significant differences in the TLI values were observed between the patients with positive and negative lymph nodes.

  9. Visualization of early prostatic adenocarcinoma as a stem cell disease

    PubMed Central

    Jiang, Maggie Y.; Lee, Tammy L.; Hao, Su-Shin; Mahooti, Sepi; Baird, Stephen M.; Donoghue, Daniel J.; Haas, Martin

    2016-01-01

    Prostate Cancer represents the second leading cause of cancer death among men in the United States, and the third leading cause of cancer death among men in Europe. We have previously shown that cells possessing Cancer Stem Cell (CSC) characteristics can be grown from human PrCa tissue harvested at the time of prostatectomy. However, the cellular origin of these CSCs was not previously known. In most cases, simple hematoxylin and eosin (H&E) stained sections are sufficient to make a definitive diagnosis of prostatic adenocarcinoma (PrCa) in needle biopsy samples. We utilized six different antibodies specific for stem cell antigens to examine paraffin sections of PrCa taken at the time of needle-biopsy diagnosis. These antisera were specific for CD44, CD133, ALDH7A1, LGR-5, Oct-4 and NANOG. We demonstrate specific staining of tumor cells with all six antisera specific for stem cell antigens. Some of these antibodies also react with cells of hyperplastic glands, but the patterns of reactivity differ from those of malignant glands. These findings demonstrate that at the time of diagnosis, PrCa consists of cells exhibiting properties of CSCs and consistent with the possibility that PrCa is a stem cell disease. PMID:27764770

  10. Visualization of early prostatic adenocarcinoma as a stem cell disease.

    PubMed

    Jiang, Maggie Y; Lee, Tammy L; Hao, Su-Shin; Mahooti, Sepi; Baird, Stephen M; Donoghue, Daniel J; Haas, Martin

    2016-11-15

    Prostate Cancer represents the second leading cause of cancer death among men in the United States, and the third leading cause of cancer death among men in Europe. We have previously shown that cells possessing Cancer Stem Cell (CSC) characteristics can be grown from human PrCa tissue harvested at the time of prostatectomy. However, the cellular origin of these CSCs was not previously known. In most cases, simple hematoxylin and eosin (H&E) stained sections are sufficient to make a definitive diagnosis of prostatic adenocarcinoma (PrCa) in needle biopsy samples. We utilized six different antibodies specific for stem cell antigens to examine paraffin sections of PrCa taken at the time of needle-biopsy diagnosis. These antisera were specific for CD44, CD133, ALDH7A1, LGR-5, Oct-4 and NANOG. We demonstrate specific staining of tumor cells with all six antisera specific for stem cell antigens. Some of these antibodies also react with cells of hyperplastic glands, but the patterns of reactivity differ from those of malignant glands. These findings demonstrate that at the time of diagnosis, PrCa consists of cells exhibiting properties of CSCs and consistent with the possibility that PrCa is a stem cell disease.

  11. Stem cells as the root of pancreatic ductal adenocarcinoma

    SciTech Connect

    Balic, Anamaria; Dorado, Jorge; Alonso-Gomez, Mercedes; Heeschen, Christopher

    2012-04-01

    Emerging evidence suggests that stem cells play a crucial role not only in the generation and maintenance of different tissues, but also in the development and progression of malignancies. For the many solid cancers, it has now been shown that they harbor a distinct subpopulation of cancer cells that bear stem cell features and therefore, these cells are termed cancer stem cells (CSC) or tumor-propagating cells. CSC are exclusively tumorigenic and essential drivers for tumor progression and metastasis. Moreover, it has been shown that pancreatic ductal adenocarcinoma does not only contain one homogeneous population of CSC rather than diverse subpopulations that may have evolved during tumor progression. One of these populations is called migrating CSC and can be characterized by CXCR4 co-expression. Only these cells are capable of evading the primary tumor and traveling to distant sites such as the liver as the preferred site of metastatic spread. Clinically even more important, however, is the observation that CSC are highly resistant to chemo- and radiotherapy resulting in their relative enrichment during treatment and rapid relapse of disease. Many laboratories are now working on the further in-depth characterization of these cells, which may eventually allow for the identification of their Achilles heal and lead to novel treatment modalities for fighting this deadly disease.

  12. Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells.

    PubMed

    Ikari, Akira; Watanabe, Ryo; Sato, Tomonari; Taga, Saeko; Shimobaba, Shun; Yamaguchi, Masahiko; Yamazaki, Yasuhiro; Endo, Satoshi; Matsunaga, Toshiyuki; Sugatani, Junko

    2014-09-01

    Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines, although it is absent in normal lung tissue. However, the role of claudin-2 in cell proliferation and the regulatory mechanism of intracellular distribution remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells. This knockdown decreased the expression levels of ZONAB and cell cycle regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma tissues and proliferating A549 cells. The nuclear distribution of ZONAB and percentage of S phase cells were higher in cells exogenously expressing claudin-2 with a nuclear localization signal than in cells expressing claudin-2 with a nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of claudin-2, was higher than that of wild type. We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells.

  13. Integrative radiogenomic profiling of squamous cell lung cancer

    PubMed Central

    Abazeed, Mohamed E.; Adams, Drew J.; Hurov, Kristen E.; Tamayo, Pablo; Creighton, Chad J.; Sonkin, Dmitriy; Giacomelli, Andrew O.; Du, Charles; Fries, Daniel F.; Wong, Kwok-Kin; Mesirov, Jill P.; Loeffler, Jay S.; Schreiber, Stuart L.; Hammerman, Peter S.; Meyerson, Matthew

    2013-01-01

    Radiation therapy is one of the mainstays of anti-cancer treatment, but the relationship between the radiosensitivity of cancer cells and their genomic characteristics is still not well-defined. Here we report the development of a high-throughput platform for measuring radiation survival in vitro and its validation by comparison to conventional clonogenic radiation survival analysis. We combined results from this high-throughput assay with genomic parameters in cell lines from squamous cell lung carcinoma, which is standardly treated by radiation therapy, to identify parameters that predict radiation sensitivity. We showed that activation of NFE2L2, a frequent event in lung squamous cancers, confers radiation resistance. An expression-based, in silico screen nominated inhibitors of PI3K as NFE2L2 antagonists. We showed that the selective PI3K inhibitor, NVP-BKM120, both decreased NRF2 protein levels and sensitized NFE2L2 or KEAP1 mutant cells to radiation. We then combined results from this high-throughput assay with single-sample gene set enrichment analysis (ssGSEA) of gene expression data. The resulting analysis identified pathways implicated in cell survival, genotoxic stress, detoxification, and innate and adaptive immunity as key correlates of radiation sensitivity. The integrative, high-throughput methods shown here for large-scale profiling of radiation survival and genomic features of solid-tumor derived cell lines should facilitate tumor radiogenomics and the discovery of genotype-selective radiation sensitizers and protective agents. PMID:23980093

  14. Cellular systems for studying human oral squamous cell carcinomas.

    PubMed

    Patel, Vyomesh; Iglesias-Bartolome, Ramiro; Siegele, Bradford; Marsh, Christina A; Leelahavanichkul, Kantima; Molinolo, Alfredo A; Gutkind, J Silvio

    2011-01-01

    The human oral squamous epithelium plays an important role in maintaining a barrier function against mechanical, physical, and pathological injury. However, the self-renewing cells residing on the basement membrane of the epithelium can give rise to oral squamous cell carcinomas (OSCC), now the sixth most common cancer in the developed world, which is still associated with poor prognosis. This is due, in part, to the limited availability of well-defined culture systems for studying oral epithelial cell biology, which could advance our understanding of the molecular basis of OSCC. Here, we describe methods to successfully isolate large cultures of human oral epithelial cells and fibroblasts from small pieces of donor tissues for use in techniques such as three-dimensional cultures and animal grafts to validate genes suspected of playing a role in OSCC development and progression. Finally, the use of isolated oral epithelial cells in generating iPS cells is discussed which holds promise in the field of oral regenerative medicine.

  15. Current Management of Esophageal Squamous-Cell Carcinoma in Japan and Other Countries

    PubMed Central

    Koizumi, Wasaburo; Tanabe, Satoshi; Sasaki, Tohru; Katada, Chikatoshi; Azuma, Mizutomo; Nakatani, Kento; Ishido, Kenji; Naruke, Akira; Ryu, Takahiro

    2009-01-01

    The incidence of adenocarcinoma of the distal esophagus or esophagogastric junction has increased considerably in Western countries during the past 3 decades, whereas the incidence of squamous-cell carcinoma has decreased slightly. In Japan, most esophageal cancers are squamous-cell carcinomas. Endoscopic examinations are more frequently performed in Japan for routine screening and diagnosis and treatment than in other countries, thereby increasing the detection rate of superficial esophageal carcinomas. In Europe and North America, many clinical trials have been conducted to assess the effectiveness of neoadjuvant chemoradiotherapy followed by surgery in patients with resectable, advanced esophageal cancer. In Japan, surgical resection had been the mainstay of treatment for esophageal cancer. Since the results of the Japan Clinical Oncology Group (JCOG) 9907 study were reported, neoadjuvant chemotherapy with cisplatin plus 5-fluorouracil followed by surgery has emerged as a new standard treatment. As for definitive chemoradiotherapy, cisplatin, 5-fluorouracil, and concurrent radiotherapy dosed to 50.4 Gy are used as standard treatment in a randomized clinical trial performed in North America. In patients who have T4 tumors and/or M1 lymph-node metastasis, chemoradiotherapy with cisplatin and 5-fluorouracil is considered standard treatment, but docetaxel, cisplatin, and 5-fluorouracil plus concurrent radiotherapy is also being studied. Controlled studies have not shown that palliative chemotherapy is superior to best supportive care, but cisplatin plus 5-fluorouracil is still considered standard therapy. Clinical trials of targeted agents are in progress. It is hoped that targeted agents will be effective for esophageal cancer. PMID:19742141

  16. The Use of P63 Immunohistochemistry for the Identification of Squamous Cell Carcinoma of the Lung

    PubMed Central

    Conde, Esther; Angulo, Bárbara; Redondo, Pilar; Toldos, Oscar; García-García, Elena; Suárez-Gauthier, Ana; Rubio-Viqueira, Belén; Marrón, Carmen; García-Luján, Ricardo; Sánchez-Céspedes, Montse; López-Encuentra, Angel; Paz-Ares, Luis; López-Ríos, Fernando

    2010-01-01

    Introduction While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of “carcinoma NOS (not otherwise specified)” in a prospective series of small tumor samples. Methods With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC. Results The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs. Conclusions P63 IHC is useful for the identification of lung SCCs. PMID:20808915

  17. Mixed squamous cell and glandular papilloma of the lung in a 64-year-old woman.

    PubMed

    Yun, Ju Sik; Kim, Do Wan; Choi, Yoo Duk; Na, Kook Joo; Song, Sang Yun

    2014-02-01

    Mixed squamous cell and glandular papilloma of the lung is an extremely rare benign epithelial tumor showing a mixture of squamous and glandular epithelium. Here, we report a case of mixed squamous cell and glandular papilloma that presented as a solitary nodule in the left lower lobe of a 64-year-old woman. Chest computed tomography demonstrated a lobulated mass in the basal segment of the left lower lobe. The patient underwent a lobectomy under the suspicion of lung malignancy. The histopathological diagnosis was mixed squamous cell and glandular papilloma.

  18. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

    SciTech Connect

    Guo, Kai; Jin, Faguang

    2015-09-25

    The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

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

    SciTech Connect

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

    2011-04-01

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

  20. NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

    PubMed

    Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

    2016-08-01

    Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

  1. Proton Pump Inhibitors Display Antitumor Effects in Barrett's Adenocarcinoma Cells

    PubMed Central

    Chueca, Eduardo; Apostolova, Nadezda; Esplugues, Juan V.; García-González, María A.; Lanas, Ángel; Piazuelo, Elena

    2016-01-01

    Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H+-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H+-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro. H+-VATPase expression was assessed by immunohistochemistry in paraffined-embedded samples or by immunofluorescence in cultured BE and EAC cell lines. Cells were treated with different concentrations of PPIs and parameters of citotoxicity, oxidative stress, and autophagy were evaluated. H+-VATPase expression was found in all biopsies and cell lines evaluated, showing differences in the location of the pump between the cell lines. Esomeprazole inhibited proliferation and cell invasion and induced apoptosis of EAC cells. Production of reactive oxygen species (ROS) seemed to be involved in the cytotoxic effects observed since the addition of N-acetylcysteine significantly reduced esomeprazole-induced apoptosis in EAC cells. Esomeprazole also reduced intracellular pH of tumor cells, whereas only disturbed the mitochondrial membrane potential in OE33 cells. Esomeprazole induced autophagy in both EAC cells, but also triggered a blockade in autophagic flux in the metastatic cell line. These data provide in vitro evidence supporting the potential use of PPIs as novel antineoplastic drugs for EAC and also shed some light on the mechanisms that trigger PPIs cytotoxic effects, which differ upon the cell line evaluated. PMID:27932981

  2. Colonic adenocarcinoma with metastasis to the gingiva.

    PubMed

    Alvarez-Alvarez, Carlos; Iglesias-Rodríguez, Begoña; Pazo-Irazu, Susana; Delgado-Sánchez-Gracián, Carlos

    2006-01-01

    Metastatic tumors involve the oral cavity, and the most common primary sites are the breast and lung. Most cases affect the mandible and maxilla in that order, although some of them can be located in the soft perioral tissues. We report the case of a 62-year-old male who had been diagnosed with sigmoid adenocarcinoma with nodal and liver metastasis, who presented 6 months later with a gingival polypoid tumor, at first considered as a primary neoplasm of gingiva, that was diagnosed in a biopsy as metastatic intestinal adenocarcinoma. The histological evaluation is essential to separate adenocarcinoma from the commoner in this site squamous cell carcinoma, and the immunohistochemical techniques are useful to distinguish metastatic tumor versus primary adenocarcinoma from the minor salivary glands of the area. The intraoral spread of a disseminated neoplasm is generally a sign of bad prognosis, although a longer survival can be expected if a radical surgical treatment of a solitary metastasis is carried out.

  3. Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma

    PubMed Central

    Zhang, Li; Wu, Yong-Dong; Li, Peng; Tu, Jun; Niu, Ying-Lin; Xu, Cai-Min; Zhang, Shu-Tian

    2011-01-01

    AIM: To study the relationship between the cyclooxygenase (COX)-2 gene and the proliferation and apoptosis of esophageal squamous carcinoma EC109 cells. METHODS: The techniques of RNA interference (RNAi) and cell transfection, as well as the levels of oncogenicity in nude mice, were used to study the role of COX-2 in the esophageal squamous carcinoma cell (ESCC) line EC109. Following RNAi and transfection, Western blotting analysis was used to determine the expression of the COX-2 protein. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction assay was used to evaluate cell growth, and flow cytometry was used to detect cell apoptosis. RESULTS: Western blotting analysis demonstrated that COX-2 expression was significantly reduced in EC109 cells treated with COX-2-specific short interfering RNA (siRNA) but was increased in EC109 cells transfected with COX-2. Furthermore, COX-2 siRNA treatment inhibited cell proliferation (P < 0.01) and induced apoptosis in EC109 cells, as determined by an MTT assay and by flow cytometry, respectively. In contrast, transfected COX-2 led to increased cell proliferation (P < 0.05) and decreased apoptosis in EC109 cells. In addition, combination treatment of cells with COX-2 siRNA and aspirin had a synergistic effect (P < 0.01). For experiments measuring tumorigenicity, xenograft tumors of a greater volume and weight were found in the COX-2 group compared with other groups (P < 0.05). A large dose of aspirin inhibited tumor growth in nude mice effectively (P < 0.05), and the rate of tumor suppression was 51.8% in the high-dose aspirin group. CONCLUSION: COX-2 plays a very critical role in ESCC carcinogenesis, and COX-2 siRNA combined with aspirin has the potential to be an anticancer therapy for the treatment of ESCC. PMID:22147962

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

    ClinicalTrials.gov

    2014-05-07

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

  5. Polystyrene nanoparticles internalization in human gastric adenocarcinoma cells.

    PubMed

    Forte, Maurizio; Iachetta, Giuseppina; Tussellino, Margherita; Carotenuto, Rosa; Prisco, Marina; De Falco, Maria; Laforgia, Vincenza; Valiante, Salvatore

    2016-03-01

    The increase in the use of nanoparticles, as a promising tool for drug delivery or as a food additive, raises questions about their interaction with biological systems, especially in terms of evoked responses. In this work, we evaluated the kinetics of uptake of 44 nm (NP44) and 100 nm (NP100) unmodified polystyrene nanoparticles (PS-NPs) in gastric adenocarcinoma (AGS) cells, as well as the endocytic mechanism involved, and the effect on cell viability and gene expression of genes involved in cell cycle regulation and inflammation processes. We showed that NP44 accumulate rapidly and more efficiently in the cytoplasm of AGS compared to NP100; both PS-NPs showed an energy dependent mechanism of internalization and a clathrin-mediated endocytosis pathway. Dose response treatments revealed a non-linear curve. PS-NPs also affected cell viability, inflammatory gene expression and cell morphology. NP44 strongly induced an up-regulation of IL-6 and IL-8 genes, two of the most important cytokines involved in gastric pathologies. Our study suggests that parameters such as time, size and concentration of NPs must be taken carefully into consideration during the development of drug delivery systems based on NPs and for the management of nanoparticles associated risk factors.

  6. Cytotoxicity of selected magnetic fluids on human adenocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Hilger, Ingrid; Frühauf, Sylvia; Linß, Werner; Hiergeist, Robert; Andrä, Wilfried; Hergt, Rudolf; Kaiser, Werner A.

    2003-04-01

    Based on the knowledge that the magnetite particles seem to be well tolerated by the human body, the cytotoxic potential of coated particles was investigated, which had been selected for potential applications regarding the minimal-invasive elimination of breast tumors by magnetic thermoablation. Human adenocarcinoma cells (BT-20) were exposed (24, 48 and 72 h) to different magnetite particles with diverging total size (8, 10 and 220 nm) and coating (cationic and anionic). One sample contained only non-coated magnetite particles. The magnetite concentration ranged between 0.2 and 20 ng/cell. Cytotoxicity was estimated by measuring the succinate dehydrogenase activity. The morphologic features resulting from the interaction of magnetic fluids with BT-20 cells was determined by transmission electron microscopy. As opposed to the non-coated magnetic particles, cationic particles induced the strongest decrease in cell survival rates depending on time and concentration. Morphologically, the cationic particle samples exerted a strong binding to cellular membranes. Changes in the subcellular structure were found in relation to the coated magnetic particles. In conclusion, our results show that the coated prototype magnetic particles, particularly those with a cationic surfactant, are cytotoxic to BT-20 cells. The cytotoxicity is attributed to electrostatic bindings with cellular membranes, influences of chemical components or non-physiologic pH. Considering the in vivo applications, adverse systemic effects are conceivable and more biocompatible coatings for the selected magnetic particles should be elaborated.

  7. Paraneoplastic cutaneous lupus secondary to esophageal squamous cell carcinoma

    PubMed Central

    Tworek, Joseph; Schapiro, Brian; Zolotarevsky, Eugene

    2015-01-01

    Sporadic subacute cutaneous lupus erythematosus (SCLE) in an elderly man does not fit a typical demographic for the disease process. Using the McLean’s criteria we were able to establish a temporal relationship between the patient’s diagnosis of esophageal squamous cell carcinoma (SCC) and his dermatosis, both of which responded to cytotoxic chemotherapy. The clinical presentation and progression of the clinical illness is supportive of a very unusual and not previously reported paraneoplastic SCLE secondary to esophageal SCC. PMID:26029469

  8. Immunocompromised and immunocompetent mouse models for head and neck squamous cell carcinoma

    PubMed Central

    Lei, Zhen-ge; Ren, Xiao-hua; Wang, Sha-sha; Liang, Xin-hua; Tang, Ya-ling

    2016-01-01

    Mouse models can closely mimic human oral squamous epithelial carcinogenesis, greatly expand the in vivo research possibilities, and play a critical role in the development of diagnosis, monitoring, and treatment of head and neck squamous cell carcinoma. With the development of the recent research on the contribution of immunity/inflammation to cancer initiation and progression, mouse models have been divided into two categories, namely, immunocompromised and immunocompetent mouse models. And thus, this paper will review these two kinds of models applied in head and neck squamous cell carcinoma to provide a platform to understand the complicated histological, molecular, and genetic changes of oral squamous epithelial tumorigenesis. PMID:26869799

  9. Esophageal Squamous Cell Carcinoma Patients Have an Increased Risk of Coexisting Colorectal Neoplasms

    PubMed Central

    Baeg, Myong Ki; Choi, Myung-Gyu; Jung, Yun Duk; Ko, Sun-Hye; Lim, Chul-Hyun; Kim, Hyung Hun; Kim, Jin Su; Cho, Yu Kyung; Park, Jae Myung; Lee, In Seok; Kim, Sang-Woo

    2016-01-01

    Background/Aims Esophageal squamous cell carcinoma (ESCC) and colorectal neoplasms (CRNs) share risk factors. We aimed to investigate whether the CRN risk is increased in ESCC patients. Methods ESCC patients who underwent a colonoscopy within 1 year of diagnosis were retrospectively analyzed. Patients were matched 1:3 by age, gender, and body mass index to asymptomatic controls. CRN was defined as the histological confirmation of adenoma or adenocarcinoma. Advanced CRN was defined as any of the following: ≥3 adenomas, high-grade dysplasia, villous features, tumor ≥1 cm, or adenocarcinoma. The risk factors for both CRN and advanced CRN were evaluated by univariate and multivariate analyses. Results Sixty ESCC patients were compared with 180 controls. The ESCC group had significantly higher numbers of CRNs (odds ratio [OR], 2.311; 95% confidence interval [CI], 1.265 to 4.220; p=0.006) and advanced CRNs (OR, 2.317; 95% CI, 1.185 to 4.530; p=0.013). Significant risk factors for both CRN and advanced CRN by multivariate analysis included ESCC (OR, 2.157, 95% CI, 1.106 to 4.070, p=0.024; and OR, 2.157, 95% CI, 1.045 to 4.454, p=0.038, respectively) and older age (OR, 1.068, 95% CI, 1.032 to 1.106, p<0.001; and OR, 1.065, 95% CI, 1.024 to 1.109, p=0.002, respectively). Conclusions The rates of CRN and advanced CRN are significantly increased in ESCC. Colonos-copy should be considered at ESCC diagnosis. PMID:25963088

  10. Cutaneous squamous cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

    PubMed

    Couture, Émilie L; Langlois, Isabelle; Santamaria-Bouvier, Ariane; Benoit-Biancamano, Marie-Odile

    2015-12-01

    A cutaneous mass was surgically excised in a 4-year-old African pygmy hedgehog (Atelerix albiventris). A squamous cell carcinoma was diagnosed based on histopathological examination and local recurrence following excision is strongly suspected. To the authors' knowledge, this is the first well-documented report of a cutaneous squamous cell carcinoma in this species.

  11. Primary frontal sinus squamous cell carcinoma in a dog treated with surgical excision.

    PubMed

    Grimes, Janet A; Pagano, Candace J; Boudreaux, Bonnie B

    2017-01-01

    An 8-year-old castrated male mixed breed dog was presented for a squamous cell carcinoma of the left frontal sinus. A partial craniectomy was performed and polytetrafluoroethylene mesh was placed over the craniectomy site. The dog recovered well with a good cosmetic outcome. Histopathology confirmed primary frontal sinus squamous cell carcinoma.

  12. Squamous cell carcinoma of the breast diagnosis by vacuum-assisted core biopsy.

    PubMed

    Guerriero, Gabriella; Zagami, Maria Giovanna; Montesano, Marilena; Primavera, Angelo; Carino, Rita; Battista, Cleonice; Rabitti, Carla; Altomare, Vittorio

    2005-01-01

    Squamous cell breast carcinoma is a rare occurrence. Often the tumor is metastatic from an extramammary primary tumor. In order to determine the nature of the lesion, extensive sampling is necessary. We report a case of primary squamous cell carcinoma of the breast diagnosed by vacuum-assisted core biopsy.

  13. Cutaneous squamous cell carcinoma in an African pygmy hedgehog (Atelerix albiventris)

    PubMed Central

    Couture, Émilie L.; Langlois, Isabelle; Santamaria-Bouvier, Ariane; Benoit-Biancamano, Marie-Odile

    2015-01-01

    A cutaneous mass was surgically excised in a 4-year-old African pygmy hedgehog (Atelerix albiventris). A squamous cell carcinoma was diagnosed based on histopathological examination and local recurrence following excision is strongly suspected. To the authors’ knowledge, this is the first well-documented report of a cutaneous squamous cell carcinoma in this species. PMID:26663924

  14. Unbalanced acetylcholinesterase activity in larynx squamous cell carcinoma.

    PubMed

    Castillo-González, Ana Cristina; Pelegrín-Hernández, Juan Pablo; Nieto-Cerón, Susana; Madrona, Antonio Piñero; Noguera, José Antonio; López-Moreno, María Fuensanta; Rodríguez-López, José Neptuno; Vidal, Cecilio J; Hellín-Meseguer, Diego; Cabezas-Herrera, Juan

    2015-11-01

    Previous reports have demonstrated that a non-neuronal cholinergic system is expressed aberrantly in airways. A proliferative effect is exerted directly by cholinergic agonists through the activation of nicotinic and muscarinic receptors. In cancer, particularly those related with smoking, the mechanism through which tumour cells respond to aberrantly activated cholinergic signalling is a key question. Fifty paired pieces of larynx squamous cell carcinoma and adjacent non-cancerous tissue were compared in terms of their acetylcholinesterase activity (AChE). The AChE activity in non-cancerous tissues (0.248 ± 0.030 milliunits per milligram of wet tissue; mU/mg) demonstrates that upper respiratory tissues express sufficient AChE activity for controlling the level of acetylcholine (ACh). In larynx carcinomas, the AChE activity decreased to 0.157 ± 0.024 mU/mg (p=0.009). Larynx cancer patients exhibiting low ACh-degrading enzymatic activity had a significantly shorter overall survival (p=0.031). Differences in the mRNA levels of alternatively spliced AChE isoforms and molecular compositions were noted between glottic and supraglottic cancers. Our results suggest that the low AChE activity observed in larynx squamous cell carcinoma may be useful for predicting the outcome of patients.

  15. GLUT-1 Expression in Cutaneous Basal and Squamous Cell Carcinomas.

    PubMed

    Abdou, Asmaa Gaber; Eldien, Marwa Mohammad Serag; Elsakka, Daliah

    2015-09-01

    Glucose uptake is a key regulating step in glucose metabolism and is mediated by facilitative glucose transporters (GLUTs), and GLUT-1 is the predominant glucose transporter in many types of human cells. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most common skin cancer in Egypt. The present study aimed at evaluation of the pattern and distribution of GLUT-1 in cutaneous BCC (16 cases) and SCC (16 cases) by means of immunohistochemistry. GLUT-1 was expressed in all SCC (100%) and in 62.5% of BCC. Membranous pattern of GLUT-1 was seen in 62.5% of SCC and 31.25% of BCC. Positivity (P = .02) and percentage (P = .000) of GLUT-1 expression were in favor of SCC in comparison to BCC. The high percentage of GLUT-1 expression was associated with high grade in SCC (P = .03). The immunoreactivity for GLUT-1 was more in the periphery of malignant nests of SCC while it was more in the center of BCC nests. GLUT-1 is overexpressed in cutaneous non-melanoma skin cancer. Its expression in SCC is related to differentiation status, and its expression in BCC is intimately associated with squamous metaplastic areas.

  16. Multiple mutations of lung squamous cell carcinoma shared common mechanisms

    PubMed Central

    Hu, Zhaoyan; Gu, Biao; Shi, Yan

    2016-01-01

    Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell lung cancers which is the cause of 80% of all lung cancer deaths. The genes that highly mutated in patients with LUSC and their roles played in the tumorigenesis remains unknown. Data of patients with Lung squamous cell carcinoma (LUSC) were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed genes were identified between control and cancer samples. Patients and controls can be separated by mRNA expression level showing that the between-group variance and totally 1265 genes were differentially expressed between controls and patients. Top genes whose mutations highly occurred in patients with LUSC were identified, most of these genes were shown to be related with tumorigenesis in previous studies. All of the genes mostly mutated were independently correlated with expression levels of all genes. These mutations did not show the trend of co-occurrence. However, the influenced gene of these mutations had overlaps. After studying the intersection of these genes, a group of shared genes were identified. The shared pathways enriched which played critical role in LUSC were identified based on these shared genes. Different mutations had contribution to the progression of LUSC. Though these genes involved different specific mechanisms, most of them may share a common mechanism which is critical for LUSC. The results may suggest a neglected mechanism and also indicate a potential target for therapies. PMID:27835590

  17. Whole-genome sequencing of nine esophageal adenocarcinoma cell lines

    PubMed Central

    Contino, Gianmarco; Eldridge, Matthew D.; Secrier, Maria; Bower, Lawrence; Fels Elliott, Rachael; Weaver, Jamie; Lynch, Andy G.; Edwards, Paul A.W.; Fitzgerald, Rebecca C.

    2016-01-01

    Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines—ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4—all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC. PMID:27594985

  18. 25-Hydroxycholesterol promotes migration and invasion of lung adenocarcinoma cells.

    PubMed

    Chen, Li; Zhang, Lishan; Xian, Guozhe; Lv, Yinping; Lin, Yanliang; Wang, Yibing

    2017-03-18

    25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase in various organs and is involved in many processes, including lipid metabolism, inflammation and the immune response. However, the role of 25-HC in the migration and invasion of lung adenocarcinoma (ADC) cells remains largely unknown. In this study, we demonstrated that 0.1 μM 25-HC promoted ADC cell migration and invasion without affecting cell proliferation, especially after coculture with THP1-derived macrophages. Further investigation showed that 0.1 μM 25-HC significantly stimulated interleukin-1β (IL-1β) secretion in a coculture system and increased the expression of LXR and Snail. IL-1β also mimicked the effect of 25-HC. LXR knockdown notably blocked the 25-HC-induced Snail expression, migration and invasion in both the monoculture system and the coculture system, but it did not impact the effect of IL-1β, which suggested that IL-1β functioned in an LXR-independent manner. These results suggested that 25-HC promoted ADC cell migration and invasion in an LXR-dependent manner in the monoculture system but that in the coculture system, the 25-HC-induced IL-1β secretion enhanced the effect of 25-HC in an LXR-independent manner.

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

    PubMed

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

    2016-02-05

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

  20. Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-11-01

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  1. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  2. AgNORs in hyperplasia, papilloma and oral squamous cell carcinoma.

    PubMed

    Fonseca, L M; do Carmo, M A

    2000-01-01

    Ten inflammatory fibrous hyperplasias, ten papillomas, and nineteen oral squamous cell carcinomas were analyzed by the AgNOR technique to determine if different disturbances of oral epithelia presented different AgNOR counts. The papilloma group showed higher mean AgNOR counts (3.15 +/- 0.58) than the hyperplasia group (1.98 +/- 0.24) and smaller than the well-differentiated oral squamous cell carcinoma group (6.56 +/- 1.25) and poorly differentiated oral squamous cell carcinoma group (7.07 +/- 1.60). The differences among the groups of lesions were statistically significant (P < 0.05) except between the well differentiated oral squamous cell carcinoma group and the poorly differentiated oral squamous cell carcinoma group. Our findings suggest that the cellular proliferation ratio in papillomas is greater than hyperplasias and smaller than carcinomas.

  3. Radiation Therapy With Cisplatin, Docetaxel, or Cetuximab After Surgery in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-03-14

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

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

    ClinicalTrials.gov

    2017-01-19

    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

  5. The HSP90 Inhibitor Ganetespib Radiosensitizes Human Lung Adenocarcinoma Cells

    PubMed Central

    Gomez-Casal, Roberto; Bhattacharya, Chitralekha; Epperly, Michael W.; Basse, Per H.; Wang, Hong; Wang, Xinhui; Proia, David A.; Greenberger, Joel S.; Socinski, Mark A.; Levina, Vera

    2015-01-01

    The molecular chaperone HSP90 is involved in stabilization and function of multiple client proteins, many of which represent important oncogenic drivers in NSCLC. Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC) cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. The cytotoxic effects of ganetespib included; G2/M cell cycle arrest, inhibition of DNA repair, apoptosis induction, and promotion of senescence. All of these antitumor effects were both concentration- and time-dependent. Both pretreatment and post-radiation treatment with ganetespib at low nanomolar concentrations induced radiosensitization in lung AC cells in vitro. Ganetespib may impart radiosensitization through multiple mechanisms: such as down regulation of the PI3K/Akt pathway; diminished DNA repair capacity and promotion of cellular senescence. In vivo, ganetespib reduced growth of T2821 tumor xenografts in mice and sensitized tumors to IR. Tumor irradiation led to dramatic upregulation of β-catenin expression in tumor tissues, an effect that was mitigated in T2821 xenografts when ganetespib was combined with IR treatments. These data highlight the promise of combining ganetespib with IR therapies in the treatment of AC lung tumors. PMID:26010604

  6. Metastasized squamous cell carcinoma developed on lupus vulgaris.

    PubMed

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

    2008-01-01

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

  7. Prognostic impact of metallothionein on oral squamous cell carcinoma.

    PubMed

    Cardoso, Sérgio V; Barbosa, Hugo M; Candellori, Ignez M; Loyola, Adriano M; Aguiar, Maria Cássia F

    2002-08-01

    Metallothionein (MT), a low-molecular-weight protein with high cysteine content, seems to be related to neoplastic resistance to oncologic treatment and therefore has been studied as a prognostic factor for a variety of human malignant tumors. MT overexpression in neoplasms of ectodermal origin is usually associated with a poor prognosis. MT expression was evaluated in 60 samples of oral squamous cell carcinoma by immunohistochemistry to study its prognostic influence on oral cancer. Possible associations of MT immunoexpression were also investigated with respect to clinical stage (TNM), histological grading, and proliferation index (Ki-67) of the lesions. No significant statistical correlation was observed among these variables. The impact on overall survival was assessed by uni and multivariate statistical tests. Mean MT labeling index was 60%. High MT labeling indexes (over 76%) predicted shorter survival in univariate statistical analysis. In multivariate analysis, MT labeling index and clinical stage were independent prognostic factors. MT overexpression in oral squamous cell carcinoma seems to be related to a worse prognosis for patients.

  8. Fluorescence detection of oral squamous cell carcinoma using Hyperflav

    NASA Astrophysics Data System (ADS)

    Melnik, Ivan S.; Dets, Sergiy M.; Rawicz, Andrew H.; Zhang, Lewei

    2000-05-01

    A novel hypericin-based drug HyperflavTM has been evaluated for light-induced fluorescence detection of oral cancer. Squamous cell carcinoma was induced with carcinogenic agent in right pouches of forty hamsters (20/20 males/females). Solution of HyperflavTM was sprinkled into stomach with a single dose 0.2 - 4 mg of pure hypericin per kg b.w. and 4 - 8 hours before fluorescence analysis. In two animal groups with cancer symptoms the autofluorescence and hypericin-induced fluorescence were taken under 442 nm excitation. The buccal mucosa and adjacent areas were measured fiberoptically in-vivo and in-vitro using orange/green ratio (610/540). The in-vivo fluorescence imaging of malignant areas was conducted to assist the biopsy guidance and to compare with white-light images. Histological and morphological analyses were performed from biopsies. Oral squamous cell carcinoma in its early stage demonstrated specific higher 610/540 ratio for 37 tested hamsters. Advanced state involved another higher fluorescence maximum around 640 nm that in our opinion caused by strong porphyrin-induced native fluorescence. Such deformation of fluorescence spectra may lead to inadequate perception of diseased tissue area. To avoid this problem the autofluorescence spectra & images were added. HyperflavTM application is promising for demarcation of early oral cancer when combined with autofluorescence measurements.

  9. Oral papillary squamous cell carcinoma in twelve dogs.

    PubMed

    Nemec, A; Murphy, B G; Jordan, R C; Kass, P H; Verstraete, F J M

    2014-01-01

    Papillary squamous cell carcinoma (PSCC) is a distinct histological subtype of oral squamous cell carcinoma (SCC), described in both dogs and man. In dogs, PSCC has long been considered a malignant oral tumour of very young animals, but it has recently been reported to occur in adult dogs as well. The aim of this study was to describe the major clinicopathological characteristics of canine oral PSCC (COPSCC). Twelve dogs diagnosed with COPSCC were included in this retrospective study (1990-2012). The majority (75%) of the dogs were >6 years of age (median age 9 years). All tumours were derived from the gingiva of dentate jaws, with 66.7% affecting the rostral aspects of the jaws. The gross appearance of the lesions varied, with one having an intraosseous component only. The majority (91.7%) of the tumours were advanced lesions (T2 and T3), but no local or distant metastases were noted. Microscopically, two patterns were seen: (1) invasion of bone forming a cup-shaped indentation in the bone or a deeply cavitating cyst within the bone (cavitating pattern), (2) histologically malignant growth, but lack of apparent bone invasion (non-cavitating pattern). The microscopical appearance corresponded to imaging findings in a majority of cases, with cavitating forms presenting with a cyst-like pattern of bone loss or an expansile mass on imaging and non-cavitating forms showing an infiltrative pattern of bone destruction on imaging. These features suggest two distinct biological behaviours of COPSCC.

  10. Glutaminolysis and carcinogenesis of oral squamous cell carcinoma.

    PubMed

    Cetindis, Marcel; Biegner, Thorsten; Munz, Adelheid; Teriete, Peter; Reinert, Siegmar; Grimm, Martin

    2016-02-01

    Glutaminolysis is a crucial factor for tumor metabolism in the carcinogenesis of several tumors but has not been clarified for oral squamous cell carcinoma (OSCC) yet. Expression of glutaminolysis-related solute carrier family 1, member 5 (SLC1A5)/neutral amino acid transporter (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLDH) was analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry. SLC1A5/ASCT2 and GLS were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue, while GLDH was weakly detected. Compared with SIN I-III SLC1A5/ASCT2 and GLS expression were significantly increased in OSCC. GLDH expression did not significantly differ from SIN I-III compared with OSCC. This study shows the first evidence of glutaminolysis-related SLC1A5/ASCT2, GLS, and GLDH expression in OSCC. The very weak GLDH expression indicates that glutamine metabolism is rather related to nucleotide or protein/hexosamine biosynthesis or to the function as an antioxidant (glutathione) than to energy production or generation of lactate through entering the tricarboxylic acid cycle. Overcoming glutaminolysis by targeting c-Myc oncogene (e.g. by natural compounds) and thereby cross-activation of mammalian target of rapamycin complex 1 or SLC1A5/ASCT2, GLS inhibitors may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.

  11. Multiple squamous cell carcinomas in a patient with mycosis fungoides.

    PubMed

    Le, Katie; Lim, Adrian; Samaraweera, Ushma; Morrow, Christine; See, Adrian

    2005-11-01

    A 51-year-old man with type IV skin presented for evaluation of a generalized rash associated with multiple ulcerated, nodular lesions on his legs. The nodular lesions occurred approximately 18 months after the initial onset of generalized rash, which had been diagnosed as plaque/patch stage mycosis fungoides. He continued to develop further nodular lesions on his trunk in the weeks following presentation. The nodular lesions were shown to be squamous-cell carcinoma on histopathology. He had received only topical hydrocortisone prior to the development of the second cutaneous malignancy and had no past exposure to carcinogens. His squamous cell carcinomas were treated with surgical excision and split-skin grafting. He received total skin electron-beam therapy to treat the mycosis fungoides. Second malignancy in mycosis fungoides is a recognized phenomenon and usually occurs after potentially carcinogenic therapy. This case demonstrates the occurrence of second malignancy in the absence of a precipitating factor, suggesting that there are innate, immune-mediated mechanisms in the development of cancer in patients with mycosis fungoides.

  12. Expression of Prostanoid EP3 Receptors in Oral Squamous Epithelium and Oral Squamous Cell Carcinoma

    PubMed Central

    Ishfaq, Muhammad; Nagi, A. H.

    2015-01-01

    Objectives. To carry out a descriptive analysis of the expression of the EP3 receptors of PGE2 in different histological grades of OSCC and adjacent normal epithelium. Material and Methods. A total of 46 patients presenting with various histological subtypes and grades of OSCC were recruited from Maxillofacial Surgery Department of Nishtar Institute of Dentistry Multan. Microscopically tumour subtyping and histological grading according to Anneroth's grading system were carried out. Immunohistochemical staining with rabbit polyclonal EP3 receptor antibody was performed and sections were scored for intensity and proportion of positive adjacent squamous epithelial and tumour cells. Results. Out of 46 patients n = 28 (60.9%) were well differentiated, n = 15 (32.6%) were moderately differentiated, and only n = 3 (6.5%) were poorly differentiated. All n = 46 cases of OSCC were positive for EP3 receptor antibody, n = 14 (30.4%) cases had strong intensity of anti EP3 antibody staining in tumour tissue, n = 17 (37%) cases showed moderate intensity, and n = 15 (32.6%) cases showed weak intensity. Conclusion. Prostanoid EP3 receptors are widely but variably expressed in OSCC. Most of well differentiated OSCC cases show a moderate to strong expression of EP3 receptors. However, insignificant statistical relation to histological grades of OSCC has been observed. This might be due to small sample size of the study. PMID:25741449

  13. Racial Differences in Esophageal Squamous Cell Carcinoma: Incidence and Molecular Features

    PubMed Central

    Zhou, Kai; Yang, Liguang

    2017-01-01

    The incidence and histological type of esophageal cancer are highly variable depending on geographic location and race/ethnicity. Here we want to determine if racial difference exists in the molecular features of esophageal cancer. We firstly confirmed that the incidence rate of esophagus adenocarcinoma (EA) was higher in Whites than in Asians and Blacks, while the incidence of esophageal squamous cell carcinoma (ESCC) was highest in Asians. Then we compared the genome-wide somatic mutations, methylation, and gene expression to identify differential genes by race. The mutation frequencies of some genes in the same pathway showed opposite difference between Asian and White patients, but their functional effects to the pathway may be consistent. The global patterns of methylation and expression were similar, which reflected the common characteristics of ESCC tumors from different populations. A small number of genes had significant differences between Asians and Whites. More interesting, the racial differences of COL11A1 were consistent across multiple molecular levels, with higher mutation frequency, higher methylation, and lower expression in White patients. This indicated that COL11A1 might play important roles in ESCC, especially in White population. Additional studies are needed to further explore their functions in esophageal cancer. PMID:28393072

  14. HPV type 16 in conjunctival and junctional papilloma, dysplasia, and squamous cell carcinoma.

    PubMed Central

    Saegusa, M; Takano, Y; Hashimura, M; Okayasu, I; Shiga, J

    1995-01-01

    AIMS--To clarify the role of human papillomavirus (HPV) infection in the development of papilloma, dysplasia, squamous cell carcinoma, and basal cell epithelioma arising from the eyelids, including the tunica conjunctiva palpebrum (conjunctiva), its junction to epidemis of eyelid skin (junction), and eyelid skin. METHODS--Sixteen cases of papilloma, four of dysplasia, four of squamous cell carcinoma, and 12 of basal cell epithelioma were examined using formalin fixed and paraffin embedded samples. Detection of HPV-DNA was performed by PCR-RFLP and in situ hybridisation (ISH) methods. RESULTS--HPV-16 was detected in 12/16 papillomas (75%), 2/4 dysplasias (50%), and 1/4 squamous cell carcinomas (25%) but in none of the basal cell epitheliomas. No other HPV subtypes were found. ISH assay showed positive signals in only two cases of dysplasia and squamous cell carcinoma. The mean age of HPV-16 positive dysplasia and squamous cell carcinoma cases (81.7 years) was significantly higher than that of HPV-16 positive papilloma cases (p < 0.01). CONCLUSIONS--Based on the presence of HPV-16 in both benign and malignant lesions and the age distribution, it seems likely that HPV-16 alone may be incapable of causing development of conjunctival and junctional dysplasia and squamous cell carcinoma, and that any correlation between the papilloma-squamous cell carcinoma sequence and HPV infection may be due to rare events. Images PMID:8567996

  15. Hypoxia induced CCL28 promotes angiogenesis in lung adenocarcinoma by targeting CCR3 on endothelial cells.

    PubMed

    Huang, Guichun; Tao, Leilei; Shen, Sunan; Chen, Longbang

    2016-06-02

    Tumor hypoxia is one of the important features of lung adenocarcinoma. Chemokines might mediate the effects caused by tumor hypoxia. As confirmed in tumor tissue and serum of patients, CC chemokine 28 (CCL28) was the only hypoxia induced chemokine in lung adenocarcinoma cells. CCL28 could promote tube formation, migration and proliferation of endothelial cells. In addition, angiogenesis was promoted by CCL28 in the chick chorioallantoic membrane and matrigel implanted in dorsal back of athymic nude mice (CByJ.Cg-Foxn1(nu)/J). Tumors formed by lung adenocarcinoma cells with high expression of CCL28 grew faster and had a higher vascular density, whereas tumor formation rate of lung adenocarcinoma cells with CCL28 expression knockdown was quite low and had a lower vascular density. CCR3, receptor of CCL28, was highly expressed in vascular endothelial cells in lung adenocarcinoma when examining by immunohistochemistry. Further signaling pathways in endothelial cells, modulated by CCL28, were analyzed by Phosphorylation Antibody Array. CCL28/CCR3 signaling pathway could bypass that of VEGF/VEGFR on the levels of PI3K-Akt, p38 MAPK and PLC gamma. The effects could be neutralized by antibody against CCR3. In conclusion, CCL28, as a chemokine induced by tumor hypoxia, could promote angiogenesis in lung adenocarcinoma through targeting CCR3 on microvascular endothelial cells.

  16. Cell-surface markers for colon adenoma and adenocarcinoma.

    PubMed

    Sewda, Kamini; Coppola, Domenico; Enkemann, Steven; Yue, Binglin; Kim, Jongphil; Lopez, Alexis S; Wojtkowiak, Jonathan W; Stark, Valerie E; Morse, Brian; Shibata, David; Vignesh, Shivakumar; Morse, David L

    2016-04-05

    Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.

  17. Comprehensive genomic characterization of squamous cell lung cancers

    PubMed Central

    2012-01-01

    Summary Lung squamous cell carcinoma (lung SqCC) is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in lung SqCC have not been comprehensively characterized and no molecularly targeted agents have been developed specifically for its treatment. As part of The Cancer Genome Atlas (TCGA), we profiled 178 lung SqCCs to provide a comprehensive landscape of genomic and epigenomic alterations. Lung SqCC is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumor. We found statistically recurrent mutations in 18 genes in including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations were seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2/KEAP1 in 34%, squamous differentiation genes in 44%, PI3K/AKT in 47%, and CDKN2A/RB1 in 72% of tumors. We identified a potential therapeutic target in the majority of tumors, offering new avenues of investigation for lung SqCC treatment. PMID:22960745

  18. Multimodal confocal mosaicing microscopy: an emphasis on squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Chen, Nathaniel W.; Sensibaugh, Jordan; Ardeshiri, Ardaland; Blanchard, Adam; Jacques, Steven; Gareau, Daniel

    2010-02-01

    Our previous study reported a sensitivity of 96.6% and a specificity of 89.2% in rapidly detecting Basal Cell Carcinomas (BCCs) when nuclei were stained with acridine orange. Squamous Cell Carcinomas (SCCs) and infiltrative BCCs remain difficult to detect. More complete screening can be achieved utilizing both acridine orange for nuclei staining and eosin for cytoplasmic contrast, using two lasers to excite the two stains independently. Nuclear fluorescence is achieved by staining with acridine orange (0.5mM, 60 s), and cytoplasmic fluorescence is achieved by staining with eosin working solution (30 s). This work shows good morphological contrast of SCC and infiltrative BCC with eosin, acridine orange, and reflectance, and presents a means for rapid SCC and infiltrative BCC detection in fresh skin excisions using multimodal confocal microscopy. In addition, digital staining is shown to effectively simulate hematoxylin and eosin (H&E) histology with confocal mosaics.

  19. Biology and patterns of response to EGFR-inhibition in squamous cell cancers of the lung and head & neck.

    PubMed

    Juergens, Rosalyn A; Bratman, Scott V; Tsao, Ming-Sound; Laurie, Scott A; Sara Kuruvilla, M; Razak, Albiruni R A; Hansen, Aaron R

    2017-03-01

    The identification of common molecular aberrations that drive cancer progression has led to targeted therapies that improve treatment efficacy in many tumor types. Epidermal growth factor receptor (EGFR) inhibitors have been used to treat both lung and head and neck cancers with squamous cell histology. These tumors often show high EGFR expression and/or increased gene copy number, but low incidence of the activating kinase domain mutations common to adenocarcinomas of the lung. In this manuscript, we review clinical trial data on EGFR-inhibitors in the treatment of squamous cell carcinoma (SqCC) of the lung and head and neck (SCCHN), including both efficacy and biomarker analyses. Although some efficacy with use of EGFR inhibitors is observed, the level of benefit varies within and across tumor types, and the predictive capacity of high EGFR protein expression and/or gene amplification, if any, is limited. Due to the lack of candidate biomarkers that consistently predict response to EGFR-inhibitor therapy across treatment setting and class of agent in SqCC of the lung and SCCHN, we explore the biology, genomics and patterns of response to EGFR-inhibitors to inform identification of potential biomarkers, highlighting several key molecules that have shown promise in preclinical studies and clinical trials across multiple cancer sites.

  20. Regulation of cholesterol synthesis in four colonic adenocarcinoma cell lines.

    PubMed

    Cerda, S R; Wilkinson, J; Broitman, S A

    1995-12-01

    Colon tumor cells, unlike normal human fibroblasts, exhibited an uncoupling of low density lipoprotein (LDL)-derived cholesterol from cellular growth, when endogenous cholesterol synthesis was inhibited by mevinolin, a hydroxymethylglutaryl-CoA reductase (HMG-CoAR) competitive inhibitor [Fabricant, M., and Broitman, S.A. (1990) Cancer Res. 50, 632-636]. Further evaluation of cholesterol metabolism was conducted in two undifferentiated (SW480, SW1417) and two differentiated (HT29, CACO2) colonic adenocarcinoma (adeno-CA) cell lines and an untransformed human fibroblast, AG1519A. Cells grown in monolayer culture to near subconfluency were used to assess endogenous cholesterol synthesis by 14C-acetate incorporation, in response to the following treatments in lipoprotein-deficient serum (LPDS)-supplemented minimum essential medium (MEM): LPDS alone, LDL, mevinolin, mevinolin with LDL, and 25-hydroxy-cholesterol (25-OH-CH). Complete fetal bovine serum (FBS)-supplemented MEM was used as control. All colon tumor lines exhibited similarly high endogenous cholesterol synthesis in both FBS and LPDS relative to the fibroblasts which demonstrated low basal levels in FBS and maximal synthesis in LPDS. LDL treatment did not inhibit cholesterol synthesis in colon tumor cells, but suppressed that in the fibroblast by 70%. Sterol repression of cholesterol synthesis mediated by 25-OH-CH occurred in all cells. Mevinolin caused a reduction in cholesterol synthesis in the colonic cancer cell lines, which was not further decreased by concurrent addition of LDL. In contrast, in mevinolin-treated fibroblasts, LDL further inhibited cholesterol synthesis. When the effect of cell density on cholesterol synthesis regulation was evaluated under conditions of sparse density in SW480 and SW147, results indicated that (i) basal rates of cholesterol synthesis were higher, (ii) LDL inhibited cholesterol synthesis more effectively, and (iii) mevinolin or 25-OH-CH had a more pronounced effect than in

  1. Role of EZH2 in oral squamous cell carcinoma carcinogenesis.

    PubMed

    Zhao, Lingbo; Yu, Yang; Wu, Jie; Bai, Jing; Zhao, Yuzhen; Li, Chunming; Sun, Wenjing; Wang, Xiumei

    2014-03-10

    Oral squamous cell carcinoma (OSCC) is a common human malignancy with high incidence rate and poor prognosis. Although the polycomb group protein enhancer of zeste homolog 2 (EZH2) plays a crucial role in cell proliferation and differentiation during the occurrence and development progress of several kinds of malignant tumors, the impact of EZH2 on the development and progression of OSCC is unclear. In this study, we demonstrate that EZH2 is overexpressed in OSCC cells and clinical tissue. With in vitro RNAi analysis, we generated stable EZH2 knocking down cell lines from two OSCC cell lines, with two sh-RNAs targeting to EZH2, respectively. We found that knocking down of EZH2 could decrease the proliferation ability and induce apoptosis of OSCC cells. Moreover, we demonstrated that of EZH2 inhibition decreased the migration and metastasis of OSCC cells. In conclusion, the results of the current study demonstrated an association between EZH2 expression and OSCC cell development. We recommend that EZH2 acts as an oncogene and plays an important role in OSCC carcinogenesis.

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

    PubMed

    Martano, M; Damiano, S; Restucci, B; Paciello, O; Russo, V; Maiolino, P

    2006-01-01

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

  3. Circulating Tumor Cells in the Adenocarcinoma of the Esophagus

    PubMed Central

    Gallerani, Giulia; Fabbri, Francesco

    2016-01-01

    Circulating tumor cells (CTCs) are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC) is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted. PMID:27527155

  4. A case of signet ring cell adenocarcinoma of the bladder with spontaneous urinary extravasation

    PubMed Central

    Shringarpure, Sanish S.; Thachil, Joseph V.; Raja, T. `; Mani, Rama

    2011-01-01

    Primary signet ring cell adenocarcinoma (PSRCC) of the bladder is a relatively rare variant of adenocarcinoma of the bladder with poor prognosis. Also PSRCC of the bladder presenting with spontaneous urinary extravasation is very rare. We present the case of a 48-year male who presented with spontaneous urinary extravasation and was diagnosed to have PSRCC of the urinary bladder on evaluation. He was treated with radical cystectomy and adjuvant chemotherapy. This report emphasizes the need to rule out other primary sites of adenocarcinoma in the body, which may metastasize to the urinary bladder. PMID:22022068

  5. Collision of desmoplastic-neurotropic melanoma and squamous cell carcinoma on the lip.

    PubMed

    Falanga, Vincent; Chartier, Molly; Butmarc, Janet; Tibbetts, Lance

    2008-05-01

    We report on a case of the collision of a desmoplastic-neurotropic melanoma and a squamous cell carcinoma on the lip. A 46-year-old male developed a multifocal infiltrative squamous cell carcinoma of the lower lip, which also showed sparse melanocyte atypia within the epidermis and an extensive spindle cell proliferation within the dermis, subcutaneous tissues and nerves. An immunohistochemical panel showed that the spindle cells were melanocytes, not derived from the squamous cell carcinoma. Double labeling with AE1/AE3 and S100 showed striking localized proximity of the spindle-cell melanocytic and keratinocyte components in some areas of this tumor. To our knowledge, this is the first report of the collision of a squamous cell carcinoma and desmoplastic-neurotropic melanoma.

  6. TERT promoter mutations are frequent in cutaneous basal cell carcinoma and squamous cell carcinoma.

    PubMed

    Griewank, Klaus G; Murali, Rajmohan; Schilling, Bastian; Schimming, Tobias; Möller, Inga; Moll, Iris; Schwamborn, Marion; Sucker, Antje; Zimmer, Lisa; Schadendorf, Dirk; Hillen, Uwe

    2013-01-01

    Activating mutations in the TERT promoter were recently identified in up to 71% of cutaneous melanoma. Subsequent studies found TERT promoter mutations in a wide array of other major human cancers. TERT promoter mutations lead to increased expression of telomerase, which maintains telomere length and genomic stability, thereby allowing cancer cells to continuously divide, avoiding senescence or apoptosis. TERT promoter mutations in cutaneous melanoma often show UV-signatures. Non-melanoma skin cancer, including basal cell carcinoma and squamous cell carcinoma, are very frequent malignancies in individuals of European descent. We investigated the presence of TERT promoter mutations in 32 basal cell carcinomas and 34 cutaneous squamous cell carcinomas using conventional Sanger sequencing. TERT promoter mutations were identified in 18 (56%) basal cell carcinomas and in 17 (50%) cutaneous squamous cell carcinomas. The recurrent mutations identified in our cohort were identical to those previously described in cutaneous melanoma, and showed a UV-signature (C>T or CC>TT) in line with a causative role for UV exposure in these common cutaneous malignancies. Our study shows that TERT promoter mutations with UV-signatures are frequent in non-melanoma skin cancer, being present in around 50% of basal and squamous cell carcinomas and suggests that increased expression of telomerase plays an important role in the pathogenesis of these tumors.

  7. Increased EGF receptors on human squamous carcinoma cell lines.

    PubMed Central

    Cowley, G. P.; Smith, J. A.; Gusterson, B. A.

    1986-01-01

    Characterisation and quantitation of epidermal growth factor receptors (EGFR) have been carried out on eight human squamous carcinoma cell lines and the results compared with those from simian virus transformed keratinocytes and normal keratinocytes grown under similar conditions. All cells tested possess both high and low affinity receptors with dissociation constants ranging from 2.4 X 10(-10) M to 5.4 X 10(-9) M. When epidermal growth factor (EGF) binds to its receptor it is internalised and degraded and the receptor is down regulated. Malignant cells and virally transformed cells possess 5-50 times more EGF receptors than normal keratinocytes and one cell line LICR-LON-HN-5 possesses up to 1.4 X 10(7) receptors per cell, which is the highest number yet reported for a cell line. These results are discussed in the context of recent data that suggest that the increased expression of EGF receptors in epidermoid malignancies may be an important component of the malignant phenotype in these tumours. PMID:2420349

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

    PubMed

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

    2013-10-01

    Basal cell carcinoma of the anal region is rare and morphologically difficult to distinguish from basaloid squamous cell carcinoma, particularly on biopsies. This distinction has therapeutic and prognostic implications. We reviewed morphological features of 9 basal cell carcinomas and 15 basaloid squamous cell carcinomas from the anal region diagnosed during 1993-2011 and determined the utility of Ber-EP4, BCL2, TP63, CK5/6, CDKN2A, and SOX2 as diagnostic tools. Immunostains were scored in a semi-quantitative manner (1+-1-10%, 2+-11-50%, 3+->50%). All basal cell carcinomas were located in the perianal region, while all basaloid squamous cell carcinomas originated in the anal canal/anorectum. Nodular subtype of basal cell carcinoma was the most common subtype. Retraction artifact was the only significant distinguishing histological feature of basal cell carcinoma compared with basaloid squamous cell carcinoma (88% vs 26%; P=0.04). Atypical mitoses were more common in basaloid squamous cell carcinomas (71% vs 11%; P=0.05). An in situ component was only present in basaloid squamous cell carcinomas, and was noted in 6/15 cases. Basal cell carcinomas had 2-3+ Ber-EP4 (basal cell carcinoma 100% vs basaloid squamous cell carcinoma 40%; P<0.001) and BCL2 immunoreactivity (basal cell carcinomas 100% vs basaloid squamous cell carcinoma 33%; P<0.001). Diffuse CDKN2A and SOX2 expression was seen only in basaloid squamous cell carcinomas (basal cell carcinoma 0% vs basaloid squamous cell carcinoma 93%; P<0.001). There was no difference in TP63 and CK5/6 expression. Perianal location, retraction artifact, and lack of atypical mitoses are histological features that help distinguish basal cell carcinoma from basaloid squamous cell carcinoma. An in situ component, when present, supports the diagnosis of basaloid squamous cell carcinoma. Immunostains are extremely helpful as diffuse Ber-EP4 and BCL2 expression is a feature of basal cell carcinoma and basaloid squamous cell carcinoma

  9. Identification and characterization of CD133+CD44+ cancer stem cells from human laryngeal squamous cell carcinoma cell lines

    PubMed Central

    Wang, Jue; Wu, Yongyan; Gao, Wei; Li, Fei; Bo, Yunfeng; Zhu, Meixia; Fu, Rong; Liu, Qingqing; Wen, Shuxin; Wang, Binquan

    2017-01-01

    Background: Laryngeal squamous cell carcinoma ranks second among head and neck squamous-cell carcinomas. Cancer stem cells can support cancer growth and malignant behavior. Therefore, cancer stem cells isolated from laryngeal squamous cell carcinoma tissue could be used to investigate the initiation, progression, and treatment strategies of this cancer. Methods: We isolated CD133-CD44-, CD133-CD44+, CD133+CD44- and CD133+CD44+ cell populations from laryngeal squamous-cell carcinoma cell lines Hep2 and TU-177 by magnetic-activated cell sorting. Sphere formation, cell proliferation, migration, invasion, colony formation, resistance to radio- and chemotherapy, and in vivo tumorigenicity of these populations were evaluated. Moreover, we investigated the expression of the stem-cell markers (sex determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (OCT4) in CD133-CD44-, CD133-CD44+, CD133+CD44-, CD133+CD44+ cell populations and parental Hep2 and TU-177 cells. Results: As compared with CD133-CD44-, CD133-CD44+, CD133+CD44- populations and parental cells, CD133+CD44+ cells showed higher cell viability, migration and invasive capability and colony formation ability as well as stronger resistance to cisplatin and irradiation. Moreover, levels of SOX2 and OCT4 and tumorigenicity in nude mice were greater in CD133+CD44+ Hep2 and TU-177 cells than other cell populations and parental cells. Conclusion: The CD133+CD44+ population of laryngeal squamous-cell carcinoma Hep2 and TU-177 cells have stem cell properties and showed more malignant features than CD133+CD44- and CD133-CD44+ cell populations. CD133+CD44+ cancer stem cells may be a promising target for developing anticancer drugs and treatment strategies for laryngeal squamous cell carcinoma. PMID:28261352

  10. Granuloma inguinale mimicking as squamous cell carcinoma of penis

    PubMed Central

    Pilani, Abhishek; Vora, Rita; Anjaneyan, Gopikrishnan

    2014-01-01

    Granuloma inguinale (GI) is an acquired chronic, slowly progressive, mildly contagious disease of venereal origin, characterized by granulomatous ulceration of the genitalia and neighboring sites, with little or no tendency to spontaneous healing caused by Klebsiella (Calymmatobacterium) granulomatis. A 55-year-old male presented with fissured, foul smelling, fungating growth over prepuce with phimosis mimicking squamous cell carcinoma (SCC) without lymphadenopathy. It started with painless papulonodular showed pseudoepitheliomatous hyperplasia, infiltration in dermis, acanthosis and vacuolated macrophages suggestive of GI and not showing any histopathological features of SCC. Patient was successfully treated by giving cotrimoxazole twice a day for 21 days. Here, we presented a case of GI mimicking SCC of penis, which was diagnosed on basis of histopathology and treated with excision followed by medical therapy with cotrimoxazole. PMID:24958990

  11. NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis

    PubMed Central

    South, Andrew P; Purdie, Karin J; Watt, Stephen A; Haldenby, Sam; den Breems, Nicoline; Dimon, Michelle; Arron, Sarah T; Kluk, Michael J; Aster, Jon C; McHugh, Angela; Xue, Dylan J; Dayal, Jasbani HS; Robinson, Kim S; Rizvi, SM Hasan

    2014-01-01

    Cutaneous SCC (cSCC) is the most frequent skin cancer with metastatic potential and can manifest rapidly as a common side effect in patients receiving systemic kinase inhibitors. Here we use massively parallel exome and targeted level sequencing 132 sporadic cSCC, 39 squamoproliferative lesions and cSCC arising in patients receiving the BRAF inhibitor vemurafenib, as well as 10 normal skin samples to identify significant NOTCH1 mutation as an early event in squamous cell carcinogenesis. Bisected vemurafenib induced lesions revealed surprising heterogeneity with different activating HRAS and NOTCH1 mutations identified in two halves of the same cSCC suggesting polyclonal origin. Immunohistochemical analysis using an antibody specific to nuclear NOTCH1 correlates with mutation status in sporadic cSCC and regions of NOTCH1 loss or down-regulation are frequently observed in normal looking skin. Our data indicate that NOTCH1 acts as a gatekeeper in human cSCC. PMID:24662767

  12. Developments in the pathology of penile squamous cell carcinomas.

    PubMed

    Chaux, Alcides; Velazquez, Elsa F; Algaba, Ferran; Ayala, Gustavo; Cubilla, Antonio L

    2010-08-01

    Most penile cancers are squamous cell carcinoma (SCC) originating in the epithelium covering glans, coronal sulcus, and foreskin. Several histologic subtypes have been described, each with distinctive clinicopathologic and outcome features. The most common subtype is the usual SCC, representing one half to two thirds of penile carcinomas. Penile verruciform tumors encompass verrucous, warty (condylomatous), and papillary, not otherwise specified, carcinomas. As a group, verruciform tumors are low grade, with low metastatic and mortality rates. In contrast, basaloid and sarcomatoid carcinomas are among the most aggressive penile tumors. Other SCC variants, such as carcinoma cuniculatum and pseudohyperplastic, adenosquamous and acantholytic carcinomas, are rare. The most relevant clinicopathologic and outcome features are outlined for each of these SCC subtypes, and an algorithm that might aid the pathologist in the histologic classification is presented. In addition, recommendations for handling penile cancer specimens, frozen section specimens, and pathology reports are provided.

  13. Descriptive epidemiology of cutaneous squamous cell carcinoma in Croatia.

    PubMed

    Celić, Dijana; Lipozencić, Jasna; Toncić, Ruzica Jurakić; Pasić, Aida; Rados, Jaka; Puizina-Ivić, Neira

    2012-03-01

    The aim of the study was to investigate the squamous cell carcinoma (SCC) incidence in Croatia in the 2003-2005 period. The cases of SCC were retrospectively studied. Data were collected from University Department of Dermatology and Venereology, Zagreb University Hospital Center and National Cancer Registry. In the study period, there were 1,860 cases of SCC (934 men and 926 women). The crude incidence rate for the Croatian population of 100,000 was 14.6 for men and 13.4 for women. The age-standardized incidence rate (adjusted for the world standard population) was 8.9 for men and 5.2 for women. The head was almost exclusive localization of SCC in both sexes. The highest SCC incidence was recorded in Zadar County. These results will serve for the SCC trend monitoring in Croatia and Europe in the forthcoming years.

  14. Current Management of Advanced Resectable Oral Cavity Squamous Cell Carcinoma

    PubMed Central

    Ow, Thomas J.

    2011-01-01

    The oral cavity is the most common site of head and neck squamous cell carcinoma, a disease which results in significant morbidity and mortality worldwide. Though the primary modality of treatment for patients with oral cavity cancer remains surgical resection, many patients present with advanced disease and are thus treated using a multi-disciplinary approach. Patients with extracapsular spread of lymphatic metastasis and surgical margins that remain positive have been found to be at high risk for local-regional recurrence and death from disease, and are most often recommended to receive both post-operative radiation as well as systemic chemotherapy. The basis for this approach, as well as scientific developments that underly future trials of novels treatments for patients with high-risk oral cavity cancer are reviewed. PMID:21461056

  15. Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

    SciTech Connect

    Lacko, Martin; Braakhuis, Boudewijn J.M.; Sturgis, Erich M.; Boedeker, Carsten C.; Suárez, Carlos; Rinaldo, Alessandra; Ferlito, Alfio; Takes, Robert P.

    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.

  16. Verrucous Squamous Cell Cancer in the Esophagus: An Obscure Diagnosis

    PubMed Central

    Egeland, Charlotte; Achiam, Michael P.; Federspiel, Birgitte; Svendsen, Lars Bo

    2016-01-01

    Verrucous carcinoma is a rare, slow-growing type of squamous cell cancer. Fewer than 50 patients with verrucous carcinoma in the esophagus have been described worldwide. In 2014, two male patients were diagnosed with verrucous carcinoma in the distal part of the esophagus. The endoscopic examinations showed a similar wart-like, white, irregular mucosa in both cases. The diagnosis was difficult to make since all biopsies taken from the affected area showed no malignancy. This cancer type has a relatively good prognosis when the diagnosis is finally obtained. Both our patients presented with dysphagia, weight loss, and an endoscopically malignant tumor, but surgery was not performed until after 9 and 10 months, respectively, and then in order to get a diagnosis. At the last follow-up, both patients were without any recurrence of the disease. PMID:27721734

  17. Donovanosis and squamous cell carcinoma: The relationship conundrum!

    PubMed

    Arora, Amanjot K; Kumaran, Muthu S; Narang, Tarun; Saikia, Uma N; Handa, Sanjeev

    2017-03-01

    Donovanosis is a rare, chronic and indolent sexually transmitted infection caused by Klebsiella granulomatis. The ulcers in donovanosis rarely undergo malignant transformation, which is usually seen in longstanding ulcers. We present a case of a 32-year-old male who presented with a two-month history of rapidly progressive, large, foul-smelling ulcers over the groin, distal penile shaft and scrotum. Crushed tissue smears from ulcers revealed basophilic intracellular and extracellular Donovan bodies. Fine needle aspiration cytology from inguinal lymph nodes and biopsy from the ulcers revealed well-differentiated squamous cell carcinoma. The current case aims to alert clinicians that donovanosis is a rare but possible cause of cutaneous malignancy. Nonetheless, the pathogenesis of malignant transformation in donovanosis needs further research.

  18. PD-1 blockage delays murine squamous cell carcinoma development.

    PubMed

    Belai, Eduardo Bertoli; de Oliveira, Carine Ervolino; Gasparoto, Thaís Helena; Ramos, Rodrigo Nalio; Torres, Sergio Aparecido; Garlet, Gustavo Pompermaier; Cavassani, Karen Angélica; Silva, João Santana; Campanelli, Ana Paula

    2014-02-01

    Engagement of programmed death-1 (PD-1) with its two ligands [programmed death ligand-1 (PD-L1) and PD-L2] has been associated with the suppression of tumor-reactive T cells; however, the underlying mechanism for this T-cell dysfunction is not clear. We hypothesized that PD-1 and PD-L1 signals are, in part, responsible for squamous cell carcinoma (SCC) escape from immune antitumor regulation by modulation of the tumor environment. In the present study, we used a multistage model of SCC to examine the role of PD-1/PD-L1 activation during tumor development. Tumor sites presented an increased percentage of CD4(+) and CD8(+) T cells expressing PD-1 when compared with non-tumorigenic control mice, whereas the expression of PD-L1 was particularly increased in F4/80(+) macrophages in tumor sites. Further, the systemic immune neutralization of PD-1 resulted in a decreased number and delayed incidence rate of papillomas followed by a differential expression of cytokeratins, suggesting that the PD-1-PD-L1 interaction contributes to the progression of SCC by downregulation of antitumor responses. In fact, blocking PD-1 increased the percentage of CD8(+) and CD4(+) T cells, and the levels of interferon-γ in the tumor sites. Our results indicated involvement of PD-1(+) T cells in SCC development and in the modulation of the inflammatory immune response.

  19. Impact of HPV infection on oral squamous cell carcinoma

    PubMed Central

    Götz, Carolin; Drecoll, Enken; Straub, Melanie; Bissinger, Oliver; Wolff, Klaus-Dietrich; Kolk, Andreas

    2016-01-01

    Background Head and neck squamous cell carcinomas (HNSCC) are often divided by their aetiology. Noxae associated collectives are compared with the human papilloma virus (HPV)-associated group, whereas different localisations of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas are mostly discussed as one single group. Our aim was to show that classification by aetiology is not appropriate for OSCC. Results HPV DNA was detected by PCR in 7 (3.47%) patients, and we identified 12 (5.94%) positive (+) cases by p16INK4a immunostaining. Only 4 (1.98%) of the p16INK4a+ cases were + for HPV using PCR. Our homogenous collective of OSCC allowed us to compare HPV+ and HPV negative (−) patients without creating bias for tumour localisation, age, gender or tumour stage. Materials and methods After testing OSCC samples for HPV positivity, we compared the results of two commonly used HPV detection methods, p16INK4a immunostaining and HPV DNA-related PCR, on 202 OSCC patients. HPV subtypes were determined with an HPV LCD Array Kit. Clinicopathological features of the patients were analysed, and the disease specific survival rates (DSS) for HPV+ and HPV− patients were obtained. Conclusions p16INK4a immunostaining is a not a reliable HPV detection method for OSCC. Positive p16INK4a immunostaining did not agree with + results from PCR of HPV DNA. Furthermore, the influence of HPV-related oncogenic transformation in OSCC is overestimated. The significance of HPV infection remains clinically unclear, and its influence on survival rates is not relevant to OSCC cases. PMID:27732948

  20. Modulation of prostaglandin biosynthesis in murine mammary adenocarcinoma tumor cells

    SciTech Connect

    Shalinsky, D.R.

    1988-01-01

    In efforts to exploit the differential oxygen levels within the subcompartments of solid neoplasms, this project has focused on modulating prostaglandin (PG) biosynthesis under aerobic and hypoxic conditions. Mammary adenocarcinoma tumor cells (Line 4526), either intact or sonicated, were incubated with either 2.0 uM {sup 14}C-arachidonic acid (AA) or 20.0 uM {sup 14}C-PGH{sub 2}, respectively. Following metabolism, products were extracted, separated by thin layer chromatography and analyzed by radiochromatographic scan. PGE{sub 2} was predominantly formed with minimal amounts of PGF{sub 2a} or PGD{sub 2}. Indomethacin and ibuprofen inhibited the PGE{sub 2} formation from AA with an IC{sub 50} value of 6.3 {times} 10{sup {minus}8} and 9.6 {times} 10{sup {minus}5}M, respectively. Suspended cells in glass vials were made hypoxic by flushing with N{sub 2} for varying time intervals to study AA metabolism. A time-dependent inhibition of PG biosynthesis was observed under hypoxia, and by 30 min, the PGE{sub 2} synthesis was reduced by 50% which was further inhibited by indomethacin. Misonidazole, a 2-nitroimidazole analogue, partially reversed the inhibition of PGE{sub 2} synthesis under hypoxia by 49% at 100 uM. However, misonidazole did not affect PG biosynthesis under aerobic conditions. The stimulation of PGE{sub 2} biosynthesis by misonidazole under hypoxia was blocked by indomethacin, suggesting that misonidazole can not act independently of the cyclooxygenase.

  1. Atypical squamous epithelium in cytologic specimens from the pancreas: cytological differential diagnosis and clinical implications.

    PubMed

    Layfield, L J; Cramer, H; Madden, J; Gopez, E V; Liu, K

    2001-07-01

    Atypical squamous epithelium is an uncommon finding in cytologic specimens obtained from pancreatic lesions. A variety of pathologic conditions can result in the presence of these cells, including primary or metastatic carcinomas, chronic pancreatitis, and squamous metaplasia related to pancreatic or biliary duct stent placement. Primary adenosquamous and squamous-cell carcinomas of the pancreas are rare, representing 3.4% and 1.4 % of pancreatic carcinomas, respectively. Cytologic separation of these malignancies from less ominous metaplasias has immense clinical importance. We reviewed Indiana University Hospital's and Duke University's experiences with atypical squamous epithelium occurring within pancreatic aspirates. Study cases were identified using a computer to search the cytology records of these two institutions. Nine cases with a diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or atypical squamous epithelium were retrieved from the two institutions' Department of Pathology files. One case of pure squamous-cell carcinoma occurred in a patient with a known pulmonary primary; a single case of adenosquamous carcinoma was diagnosed in a patient with a coexistent endometrial primary; a single sample of adenocarcinoma with squamous differentiation was diagnosed in a patient without other known disease; and four primary squamous-cell carcinomas of the pancreas were detected. In addition, a single case of atypical squamous metaplasia associated with a stent was identified, and one case of atypical squamous epithelium associated with chronic pancreatitis was diagnosed. Despite the reactive atypia present in the examples of metaplastic squamous epithelium, separation of these cases from true squamous-cell carcinoma and adenosquamous carcinoma was achievable by cytologic evaluation. No cytologic criteria aided in separating primary pancreatic carcinomas with squamous differentiation from metastatic lesions. In this study, we report our findings in a

  2. Primary squamous cell carcinoma of the thyroid arising in Hashimoto's thyroiditis in an adolescent.

    PubMed

    Sanchez-Sosa, Sergio; Rios-Luna, Nina Paola; Tamayo, Bricia del Rosario; Simpson, Karen; Albores-Saavedra, Jorge

    2006-01-01

    Squamous cell carcinoma is a rare thyroid neoplasm that has been described exclusively in adults. We report what appears to be the first example of a primary squamous cell carcinoma of the thyroid gland arising in a background of Hashimoto's thyroiditis in an adolescent female. The tumor was well demarcated, confined to the right thyroid lobe, and did not metastasize, although follow up has been limited. The squamous cell carcinoma was well to moderately differentiated, and the stroma contained an abundant inflammatory infiltrate rich in lymphocytes and eosinophils. The lack of goblet cells, extracellular mucin, and extensive stromal sclerosis excluded the diagnosis of sclerosing mucoepidermoid carcinoma with eosinophilia. Immunohistochemical staining revealed focal expression of cytokeratin 7 and diffuse labeling with cytokeratin AE1/AE3. The squamous cell carcinoma overexpressed p53 protein and showed increased proliferative activity, as evidenced by the high MIB-1 labeling index. In contrast, the tumor did not show immunoreactivity for thyroglobulin or thyroid transcription factor 1.

  3. Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma: Tumor-Infiltrating CD10+ Neutrophil/CD20+ Lymphocyte Ratio as an Independent Prognostic Factor

    PubMed Central

    Kadota, Kyuichi; Nitadori, Jun-ichi; Ujiie, Hideki; Buitrago, Daniel H.; Woo, Kaitlin M.; Sima, Camelia S.; Travis, William D.; Jones, David R.; Adusumilli, Prasad S.

    2015-01-01

    Introduction We previously reported the prognostic significance of the lung adenocarcinoma immune microenvironment. In this study, we preformed comprehensive analysis of immune markers and their associations with prognosis in patients with lung squamous cell carcinoma. Methods We reviewed surgically resected, solitary lung squamous cell carcinoma patients (n = 485; 1999 to 2009) that were randomly split into a training cohort (n = 331) and validation cohort (n = 154). We constructed tissue microarrays and performed immunostaining for CD3, CD45RO, CD8, CD4, FoxP3, CD20, CD68, CXCL12, CXCR4, CCR7, IL-7R, and IL-12Rβ2. Overall survival (OS) was analyzed using the log-rank test and the Cox proportional hazards model. Results Analysis of single immune cell infiltration revealed that high tumor-infiltrating CD10+ neutrophils were associated with worse prognoses in the training cohort (P = 0.021). Analysis of biologically relevant immune cell combinations identified that patients with high CD10+ neutrophil and low CD20+ lymphocyte had a significantly worse OS (5-year OS, 42%) than those with other combinations of CD10 and CD20 (5-year OS, 62%; P < 0.001); this was confirmed in the validation cohort (P = 0.032). For the multivariate analysis, high CD10/low CD20 immune cell infiltration was an independent predictor of OS in both the training cohort (HR = 1.61, P = 0.006) and validation cohort (HR = 1.75; P = 0.043). Conclusions High CD10+/low CD20+ immune cell infiltration ratio is a significant prognostic factor of lung squamous cell carcinoma. Immunomodulatory therapy of tumor-specific neutrophil and B lymphocyte responses may have applicability in the treatment of lung squamous cell carcinoma. PMID:26291010

  4. Dynamics of regulatory networks in gastrin-treated adenocarcinoma cells.

    PubMed

    Doni Jayavelu, Naresh; Bar, Nadav

    2014-01-01

    Understanding gene transcription regulatory networks is critical to deciphering the molecular mechanisms of different cellular states. Most studies focus on static transcriptional networks. In the current study, we used the gastrin-regulated system as a model to understand the dynamics of transcriptional networks composed of transcription factors (TFs) and target genes (TGs). The hormone gastrin activates and stimulates signaling pathways leading to various cellular states through transcriptional programs. Dysregulation of gastrin can result in cancerous tumors, for example. However, the regulatory networks involving gastrin are highly complex, and the roles of most of the components of these networks are unknown. We used time series microarray data of AR42J adenocarcinoma cells treated with gastrin combined with static TF-TG relationships integrated from different sources, and we reconstructed the dynamic activities of TFs using network component analysis (NCA). Based on the peak expression of TGs and activity of TFs, we created active sub-networks at four time ranges after gastrin treatment, namely immediate-early (IE), mid-early (ME), mid-late (ML) and very late (VL). Network analysis revealed that the active sub-networks were topologically different at the early and late time ranges. Gene ontology analysis unveiled that each active sub-network was highly enriched in a particular biological process. Interestingly, network motif patterns were also distinct between the sub-networks. This analysis can be applied to other time series microarray datasets, focusing on smaller sub-networks that are activated in a cascade, allowing better overview of the mechanisms involved at each time range.

  5. ASC contributes to metastasis of oral cavity squamous cell carcinoma

    PubMed Central

    OuYang, Chun-Nan; Kao, Huang-Kai; Hsueh, Chuen; Chen, Lih-Chyang; Cheng, Hsiao-Yun; Liang, Ying; Liou, Willisa; Liang, Chih-lung; Chang, Yu-Sun

    2016-01-01

    ASC (Apoptosis-associated Speck-like protein containing a CARD) acts as a platform protein in the inflammasome cascade of some cancer types. However, its potential involvement in OSCC (oral cavity squamous cell carcinoma) has not yet been determined. Here, we investigated the potential role of ASC in OSCC. RT-qPCR analysis of 20 paired tumor and adjacent normal tissue samples revealed that the mRNA levels of ASC, along with IL-1β, CASP1, and NLRP3 in ASC-associated NLRP3 inflammasome were significantly elevated in OSCC tissues. Immunohistochemical staining of these four proteins in 111 clinical specimens revealed that high-level expression of ASC was significantly associated with tumor stage, node stage (p=0.001), overall stage (p<0.001), extracapsular spread (p<0.001), perineural invasion (p=0.004) and tumor depth (p<0.001). Kaplan-Meier survival analysis further revealed that high-level ASC expression was correlated with poorer overall survival (p=0.001), disease-specific survival (p<0.001) and disease-free survival (p<0.001). Studies using OSCC cell lines indicated that high-level ASC expression enhanced cell migration and invasion, and experiments using an orthotropic nude mouse model confirmed that ASC overexpression induced metastasis of OSCC cells. This is the first report to show that ASC contributes to OSCC metastasis, and that high-level ASC expression is a marker for poor prognosis in OSCC patients. PMID:27367024

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

    PubMed Central

    Bann, Darrin V.; Deschler, Daniel G.; Goyal, Neerav

    2016-01-01

    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. PMID:27669306

  7. Tie2 Regulates Tumor Metastasis of Oral Squamous Cell Carcinomas

    PubMed Central

    Kitajima, Daisuke; Kasamatsu, Atsushi; Nakashima, Dai; Miyamoto, Isao; Kimura, Yasushi; Saito, Tomoaki; Suzuki, Takane; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2016-01-01

    The endothelial-specific receptor, tyrosine kinase with immunoglobulin-like loops and epidermal growth factor homology domains-2 (Tie2) is a member of the tyrosine kinase family and is ubiquitous in normal tissues; however, little is known about the mechanisms and roles of Tie2 in oral squamous cell carcinomas (OSCCs). In the current study, we investigated the expression status of Tie2 in OSCCs by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry and the functional mechanisms of Tie2 using its overexpressed OSCC (oeTie2) cells and Tie2 blocking by its antibody. We found that Tie2 expression was down-regulated significantly (p < 0.05) in OSCCs compared with normal counterparts in vitro and in vivo. Interestingly, oeTie2 cells showed higher cellular adhesion (p < 0.05) and lower cellular invasion (p < 0.05) compared with control cells; whereas there was similar cellular proliferation in both transfectants. Furthermore, cellular adhesion was inhibited and invasion was activated by Tie2 function-blocking antibody (p < 0.05), indicating that Tie2 directly regulates cellular adhesion and invasion. As expected, among the clinical variables analyzed, Tie2-positivity in patients with OSCC was correlated closely with negative lymph node metastasis. These results suggested for the first time that Tie2 plays an important role in tumor metastasis and may be a potential biomarker for OSCC metastasis. PMID:27053959

  8. Immunohistochemical Evaluation of Mast Cells in Leukoplakia and Oral Squamous Cell Carcinoma

    PubMed Central

    Narasimhan, Malathi

    2016-01-01

    Introduction More than 90% of oral cancers are squamous cell carcinomas with oral leukoplakia being the most common potentially malignant disorder. Among the cell types in the stroma, mast cells play an important role in tumourigenesis through various mechanisms. Aim The present study was aimed at comparing the mast cell count among normal oral mucosa, leukoplakia and Oral squamous cell carcinoma (OSSC) and to evaluate the possible role of mast cells in carcinogenesis. Materials and Methods Mast cell count was assessed immunohistochemically using anti-mast cell tryptase amongst 20 cases of leukoplakia and OSSC each and 10 normal gingival samples. Overall comparison was done using Kruskal Wallis test and intergroup comparison was done using Mann-Whitney U test. Results The results of the present study showed an increase in mast cell count from normal oral mucosa (Mean: 7.73) to leukoplakia (Mean: 15.11) to squamous cell carcinoma (Mean: 22.73). Comparison of mean number of mast cells amongst three groups (p-value: 0.001) and intergroup comparisons showed statistical significance. Conclusion Mast cells favour malignant transformation and can be used as indicators of disease progression. PMID:27656549

  9. Squamous cell carcinoma in an inverted papilloma of the buccal mucosa.

    PubMed

    Boesen, P V; Laszewski, M J; Robinson, R A; Dawson, D E

    1991-09-01

    Inverted papillomas of the oral cavity are rare lesions. Although in the seven oral cases previously reported the lesions were benign, approximately 10% to 15% of inverted papillomas of the nasal cavity and paranasal sinuses develop or are associated with squamous cell carcinoma. This report presents a case of squamous cell carcinoma arising in an inverted papilloma of the buccal mucosa. Histologically, this lesion demonstrated the morphologic features of inverted papilloma in the superficial portion, and squamous carcinoma in deeper sections. This case suggests that although rare, inverted papillomas of the oral cavity should be considered potentially malignant or capable of harboring a malignancy.

  10. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

    PubMed Central

    Che, Keying; Zhao, Yang; Qu, Xiao; Pang, Zhaofei; Ni, Yang; Zhang, Tiehong; Du, Jiajun; Shen, Hongchang

    2017-01-01

    Purpose Gastric carcinoma (GC) is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma. Materials and methods Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS) was statistically analyzed. Results Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145) of them. Single cell invasion and large cell invasion were observed in 62.8% (186) and 16.9% (50) of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0.001). Similarly, the OS of patients with single cell invasion and large cell invasion was reduced (single cell invasion, HR: 3.553, P<0.001; large cell invasion, HR: 2.466, P<0.001). Following multivariate analysis, tumor budding and single cell invasion were observed to be independent risk factors for gastric adenocarcinoma (P<0.05). According to the Lauren classification, patients with intestinal-type adenocarcinoma had better outcomes than those with diffuse-type adenocarcinoma (HR: 2.563, P<0.001). Conclusion Tumor budding and single cell invasion in gastric adenocarcinoma are associated with an unfavorable prognosis. PMID:28255247

  11. Two Canine Papillomaviruses Associated With Metastatic Squamous Cell Carcinoma in Two Related Basenji Dogs.

    PubMed

    Luff, J; Rowland, P; Mader, M; Orr, C; Yuan, H

    2016-11-01

    Papillomaviruses (PV) are associated with benign mucosal and cutaneous epithelial proliferations. In dogs, PV-associated pigmented plaques and papillomas can undergo malignant transformation, but this is rare, and most cases of canine squamous cell carcinoma do not arise from PV-induced precursor lesions. We describe herein the progression of pigmented plaques to invasive and metastatic squamous cell carcinoma associated with 2 canine papillomaviruses (CPV) in 2 related Basenji dogs. Immunohistochemistry for PV antigen revealed strong nuclear immunoreactivity within keratinocytes from pigmented plaques from both dogs, consistent with a productive viral infection. Polymerase chain reaction (PCR) using degenerate primers for the L1 gene revealed PV DNA sequences from 2 different CPVs. In situ hybridization for CPV revealed strong hybridization signals within the pigmented plaques and neoplastic squamous epithelial cells from both dogs. We report here progression of PV-associated pigmented plaques to metastatic squamous cell carcinoma within 2 Basenji dogs associated with 2 different CPVs.

  12. [Inveterate squamous cell carcinoma of the upper eyelid: a case report].

    PubMed

    Rinaldi, S; Marcasciano, M; Pacitti, F; Toscani, M; Tarallo, M; Fino, P; Scuderi, G L

    2013-01-01

    Squamous cell carcinoma (SCC) is a malignant tumor of epithelium that shows squamous cell differentiation. It is the second most common cancer of the skin and usually occurs in areas exposed to the sun but it can rarely arise within the conjunctival epithelium with a deep component. We describe a woman with a history of chronic blepharoconjunctivitis unresponsive to topical medications. Examination disclosed a hyperaemic translucent patch with blurred margins of the upper palpebral conjunctiva. Tarsoconjunctival biopsy revealed intraepithelial squamous cell carcinoma. Management consisted of complete tumor excision with removal of the entire posterior lamella of the left upper eyelid and reconstruction. Histopathologic analysis confirmed primary squamous cell carcinoma arising from conjunctival epithelium, involving the underlying tarsus. Patients with unexplained chronic unilateral blepharoconjunctivitis or papillary hypertrophy of the palpebral conjunctiva should be considered for biopsy to rule out neoplasia, even when there is no sign of an evident mass.

  13. CUTANEOUS SQUAMOUS CELL CARCINOMA IN A PANTHER CHAMELEON (FURCIFER PARDALIS) AND TREATMENT WITH CARBOPLATIN IMPLANTABLE BEADS.

    PubMed

    Johnson, James G; Naples, Lisa M; Chu, Caroline; Kinsel, Michael J; Flower, Jennifer E; Van Bonn, William G

    2016-09-01

    A 3-yr-old male panther chameleon (Furcifer pardalis) presented with bilateral raised crusted skin lesions along the lateral body wall that were found to be carcinoma in situ and squamous cell carcinoma. Similar lesions later developed on the caudal body wall and tail. A subcutaneous implantable carboplatin bead was placed in the first squamous cell carcinoma lesion identified. Additional new lesions sampled were also found to be squamous cell carcinomas, and viral polymerase chain reaction was negative for papillomaviruses and herpesviruses. Significant skin loss would have resulted from excision of all the lesions, so treatment with only carboplatin beads was used. No adverse effects were observed. Lesions not excised that were treated with beads decreased in size. This is the first description of cutaneous squamous cell carcinoma and treatment with carboplatin implantable beads in a panther chameleon.

  14. Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration

    PubMed Central

    Gatzka, Martina; Treiber, Nicolai; Schneider, Lars A.; Mulaw, Medhanie A.; Lucas, Tanja; Kochanek, Stefan; Dummer, Reinhard; Levesque, Mitchell P.; Wlaschek, Meinhard; Scharffetter-Kochanek, Karin

    2016-01-01

    Aging is associated with a rising incidence of cutaneous squamous cell carcinoma (cSCC), an aggressive skin cancer with the potential for local invasion and metastasis. Acquisition of a senescence-associated secretory phenotype (SASP) in dermal fibroblasts has been postulated to promote skin cancer progression in elderly individuals. The underlying molecular mechanisms are largely unexplored. We show that Chemerin, a previously unreported SASP factor released from senescent human dermal fibroblasts, promotes cSCC cell migration, a key feature driving tumor progression. Whereas the Chemerin abundance is downregulated in malignant cSCC cells, increased Chemerin transcripts and protein concentrations are detected in replicative senescent fibroblasts in vitro and in the fibroblast of skin sections from old donors, indicating that a Chemerin gradient is built up in the dermis of elderly. Using Transwell® migration assays, we show that Chemerin enhances the chemotaxis of different cSCC cell lines. Notably, the Chemerin receptor CCRL2 is remarkably upregulated in cSCC cell lines and human patient biopsies. Silencing Chemerin in senescent fibroblasts or the CCRL2 and GPR1 receptors in the SCL-1 cSCC cell line abrogates the Chemerin-mediated chemotaxis. Chemerin triggers the MAPK cascade via JNK and ERK1 activation, whereby the inhibition impairs the SASP- or Chemerin-mediated cSCC cell migration. Taken together, we uncover a key role for Chemerin, as a major factor in the secretome of senescent fibroblasts, promoting cSCC cell migration and possibly progression, relaying its signals through CCRL2 and GPR1 receptors with subsequent MAPK activation. These findings might have implications for targeted therapeutic interventions in elderly patients. PMID:27907906

  15. Combined double CK5/P63 stain: useful adjunct test for diagnosing pulmonary squamous cell carcinoma.

    PubMed

    Fatima, Nazneen; Cohen, Cynthia; Lawson, Diane; Siddiqui, Momin T

    2012-11-01

    Increasing demand for accurate differentiation of pulmonary squamous cell carcinoma (SQCC) from other subtypes can be challenging for pathologists. This is more so in fine-needle aspirations (FNA) since the sample is small and SQCC may show degenerative changes and necrosis that distort the cellular features. Immunohistochemistry (IHC) is a valuable adjunct, and CK5/6 and P63 immunoreactivity is found to be basically restricted to SQCC. In our study, we evaluated the efficiency of CK5/P63 double staining in the diagnosis of pulmonary SQCC in cell blocks (CB) of lung FNA. We used a cohort including 24 CB of lung SQCC and 34 CB of lung adenocarcinomas (ADC). IHC was performed for CK5/P63 double stain. Seventeen of 24 (70%) lung SQCC were positive for the double stain CK5/P63. Two (8%) were positive for CK5 alone and two (8%) were positive for P63 alone. Thus, a total 19 of 24(79%) SQCC of the lung were positive for CK5 and P63 each. In ADC, no immunoreactivity was detected for CK5 alone or combined CK5/P63. Three of 34(8%) ADC were positive for P63. This first study of double staining of CK5/P63 in FNA CB shows a sensitivity of 70% and specificity of 100% for SQCC of the lung. When each marker staining alone is included, the sensitivity for CK5 and P63 increases to 79% each. This double stain can help in the diagnosis of pulmonary SQCC with an accuracy of 88% and a positive predictive value of 100%.

  16. Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity

    PubMed Central

    Jeon, Ji Hoon; Kim, Dong Keon; Shin, Youngmi; Kim, Hee Yeon; Song, Bomin; Lee, Eun Young; Kim, Jong Kwang; You, Hye Jin; Cheong, Heesun; Shin, Dong Hoon; Kim, Seong-Tae; Cheong, Jae-Ho; Kim, Soo Youl; Jang, Hyonchol

    2016-01-01

    A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated. Cells with a higher MMP exhibited greater migration and invasion than those with a lower MMP. Cells that survived treatment with cisplatin, a standard chemotherapeutic drug for lung adenocarcinoma, exhibited increased MMP and enhanced migration and invasion compared with parental cells. Consistent with these findings, inhibition of mitochondrial activity significantly impeded the migration and invasion of cisplatin-resistant cells. RNA-sequencing analysis indicated that the expression of mitochondrial complex genes was upregulated in cisplatin-resistant cells. These results suggested that drug-resistant cells have a greater MMP and that inhibition of mitochondrial activity could be used to prevent metastasis of drug-resistant lung adenocarcinoma cells. PMID:27932791

  17. Histological and molecular aspects of oral squamous cell carcinoma (Review).

    PubMed

    Rivera, César; Venegas, Bernardo

    2014-07-01

    Oral squamous cell carcinoma (OSCC) represents 95% of all forms of head and neck cancer, and over the last decade its incidence has increased by 50%. Oral carcinogenesis is a multistage process, which simultaneously involves precancerous lesions, invasion and metastasis. Degradation of the cell cycle and the proliferation of malignant cells results in the loss of control mechanisms that ensure the normal function of tissues. The aim of the current review is to present the histopathological features of OSCC, including potentially malignant changes, the international classification of tumors, the tumor invasion front and tumor biomarkers (Ki-67, p53, homeobox genes and collagen type IV), as well as the tumor microenvironment and function of cancer-associated fibroblasts in the most common type of oral cancer that is encountered by dental surgeons. In OSCC, associations have been identified between the proliferation, basal lamina degradation and connective tissue modulation. Therefore, the comparison of these factors with the survival time of OSCC patients from the histopathological diagnosis is of interest.

  18. Role of Cks1 Overexpression in Oral Squamous Cell Carcinomas

    PubMed Central

    Kitajima, Shojiro; Kudo, Yasusei; Ogawa, Ikuko; Bashir, Tarig; Kitagawa, Masae; Miyauchi, Mutsumi; Pagano, Michele; Takata, Takashi

    2004-01-01

    Down-regulation of p27 is frequently observed in various cancers due to an enhancement of its degradation. Skp2 is required for the ubiquitination and consequent degradation of p27 protein. Another protein called Cks1 is also required for p27 ubiquitination in the SCFSkp2 ubiquitinating machinery. In the present study, we examined Cks1 expression and its correlation with p27 in oral squamous cell carcinoma (OSCC) derived from tongue and gingiva. By immunohistochemical analysis, high expression of Cks1 was present in 62% of OSCCs in comparison with 0% of normal mucosae. In addition, 65% of samples with low p27 expression displayed high Cks1 levels. Finally, Cks1 expression was well correlated with Skp2 expression and poor prognosis. To study the role of Cks1 overexpression in p27 down-regulation, we transfected Cks1 with or without Skp2 into OSCC cells. Cks1 transfection could not induce a p27 down-regulation by itself, but both Cks1 and Skp2 transfection strongly induced. Moreover, we inhibited Cks1 expression by small interference RNA (siRNA) in OSCC. Cks1 siRNA transfection induced p27 accumulation and inhibited the growth of OSCC cells. These findings suggest that Cks1 overexpression may play an important role for OSCC development through Skp2-mediated p27 degradation, and that Cks1 siRNA can be a novel modality of gene therapy. PMID:15579456

  19. Molecular profiling of head and neck squamous cell carcinoma

    PubMed Central

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

    2015-01-01

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

  20. Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect

    PubMed Central

    Nishat, Roquaiya; Ramachandra, Sujatha; Kumar, Harish; Bandyopadhyay, Alokenath

    2015-01-01

    Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID:26266234

  1. Primary squamous cell carcinoma of the prostate: a case report of a rare clinical entity

    PubMed Central

    Biswas, Tithi; Podder, Tarun; Lepera, Pamela A; Walker, Paul

    2015-01-01

    Primary squamous cell carcinoma of the prostate is a unique and rare clinicopathological entity with fewer than 100 cases reported in the literature. Because of its rarity, the optimal management is not well known. Here, we report a case of primary squamous cell carcinoma of the prostate which was treated with definitive concurrent chemo-radiotherapy with excellent outcome along with a brief review of the literature. PMID:28031893

  2. Kaempferol inhibits cell proliferation and glycolysis in esophagus squamous cell carcinoma via targeting EGFR signaling pathway.

    PubMed

    Yao, Shihua; Wang, Xiaowei; Li, Chunguang; Zhao, Tiejun; Jin, Hai; Fang, Wentao

    2016-08-01

    Antitumor activity of kaempferol has been studied in various tumor types, but its potency in esophagus squamous cell carcinoma is rarely known. Here, we reported the activity of kaempferol against esophagus squamous cell carcinoma as well as its antitumor mechanisms. Results of cell proliferation and colony formation assay showed that kaempferol substantially inhibited tumor cell proliferation and clone formation in vitro. Flow cytometric analysis demonstrated that tumor cells were induced G0/G1 phase arrest after kaempferol treatment, and the expression of protein involved in cell cycle regulation was dramatically changed. Except the potency on cell proliferation, we also discovered that kaempferol had a significant inhibitory effect against tumor glycolysis. With the downregulation of hexokinase-2, glucose uptake and lactate production in tumor cells were dramatically declined. Mechanism studies revealed kaempferol had a direct effect on epidermal growth factor receptor (EGFR) activity, and along with the inhibition of EGFR, its downstream signaling pathways were also markedly suppressed. Further investigations found that exogenous overexpression of EGFR in tumor cells substantially attenuated glycolysis suppression induced by kaempferol, which implied that EGFR also played an important role in kaempferol-mediated glycolysis inhibition. Finally, the antitumor activity of kaempferol was validated in xenograft model and kaempferol prominently restrained tumor growth in vivo. Meanwhile, dramatic decrease of EGFR activity and hexokinase-2 expression were observed in kaempferol-treated tumor tissue, which confirmed these findings in vitro. Briefly, these studies suggested that kaempferol, or its analogues, may serve as effective candidates for esophagus squamous cell carcinoma management.

  3. A Study to Isolate and Test Circulating Tumor Cells Using the ClearCell® FX EP+ System

    ClinicalTrials.gov

    2017-03-01

    Lung Cancer; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms; Carcinoma, Non-small-cell Lung; Adenocarcinoma; Squamous Cell Carcinoma

  4. Primary squamous cell carcinoma of the rectum: An update and implications for treatment

    PubMed Central

    Guerra, Glen R; Kong, Cherng H; Warrier, Satish K; Lynch, Andrew C; Heriot, Alexander G; Ngan, Samuel Y

    2016-01-01

    AIM: To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma (SCC). METHODS: A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert. RESULTS: The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC’s are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-node-metastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external site of primary SCC with metastasis to the rectum. While the

  5. Clear cell adenocarcinoma of the renal pelvis: an extremely rare neoplasm of the upper urinary tract.

    PubMed

    Liu, K-W; Lin, V C-H; Chang, I-W

    2013-12-01

    Clear cell adenocarcinoma (CCA) in the urinary tract is a rare neoplasm morphologically identical to the Müllerian counterpart. Clear cell adenocarcinoma is extremely rare in the upper urinary tract. We present a case with CCA of the renal pelvis. Microscopically, the tumor exhibited exophytic growth with predominantly tubulocystic structures, as well as solid and papillary patterns. The neoplastic cells were cuboidal with clear to pale eosinophilic cytoplasm and abundant intracellular and extracellular eosinophilic hyaline globules. By immunohistochemically, the tumor was labeled by cytokeratins and hepatocyte nuclear factor-1β. The patient was still alive without evidence of recurrence in the follow-up period of nineteen months after diagnosis.

  6. Comprehensive genomic characterization of head and neck squamous cell carcinomas.

    PubMed

    2015-01-29

    The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.

  7. Squamous cell carcinoma and ledderhose disease: a case report.

    PubMed

    Motolese, Alberico; Mola, Federica; Cherubino, Mario; Giaccone, Micol; Pellegatta, Igor; Valdatta, Luigi

    2013-12-01

    Ledderhose disease is disorder of the plantar aponeurosis. This disease is not so common and can be tackled with a surgical or conservative approach. A case of a 73-year-old man came to our attention who had a 26-year history of painless bilateral plantar nodules coalescing into an indurated mass. An ulcerative nodule had been noted in the last 16 months on the right foot, in the absence of trauma, not responsive to conservative treatment, so we decided to perform a biopsy. The histopatologic examination showed squamous cell carcinoma, with warty, well-differentiated, low-grade malignancy. Surgical treatment was suggested, so, in pneumoischemia, we made a surgical incision including the skin lesion. Then we proceeded to sculpture the anterolateral thigh fasciacutaneous flap to obtain adequate soft tissue coverage. The tumor was completely removed. Current reconstructive possibilities comprise a good anatomofunctional recovery even in the case of large demolition requests for the therapy of advanced cases of the disease described in this article. Correlation between Ledderhose disease and the formation of malignant tumors has not been made as yet, but perhaps an element that could unite these pathologies can be researched in the lively cell proliferation that characterizes both. It would be interesting to analyze the biological substrate, as well as the systemic and local levels, in patients where both diseases are manifested.

  8. Sonic hedgehog in oral squamous cell carcinoma: An immunohistochemical study

    PubMed Central

    Srinath, Sahana; Iyengar, Asha R; Mysorekar, Vijaya

    2016-01-01

    Background: Recent studies have revealed the involvement of hedgehog (Hh) signaling component in proliferation and invasive behavior of many carcinomas. Aim: This study aims to identify the expression of sonic Hh (SHH) protein of SHH pathway in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) using SHH (H-160) (Santa Cruz, sc-9042) which could have therapeutic implication in future. Materials and Methods: A total of 250 cases comprising 50 normal oral mucosa, 50 cases of oral epithelial dysplasia, 50 well, 50 moderate and 50 poorly differentiated OSCCs were included in the study. Immunohistochemical evaluation of SHH protein expression was conducted using monoclonal antibody. Interpretation of the expression was done by immunoreactive score of Remmele and Stegner (IRS) scoring method. Statistical Analysis: Chi-Square test was used to analyze the results. Results: The study showed that SHH signaling molecules are highly expressed in OSCC, and their expression was mainly in the cytoplasm of epithelial cells. Conclusion: The SHH signaling component is associated with the pathological parameter in OSCC and oral epithelial dysplasia. PMID:27721600

  9. Comprehensive genomic characterization of head and neck squamous cell carcinomas

    PubMed Central

    2014-01-01

    The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. We find that human papillomavirus-associated (HPV) tumors are dominated by helicase domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss of TP53 mutations and CDKN2A with frequent copy number alterations including a novel amplification of 11q22. A subgroup of oral cavity tumors with favorable clinical outcomes displayed infrequent CNAs in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and wild-type TP53. Other distinct subgroups harbored novel loss of function alterations of the chromatin modifier NSD1, Wnt pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumors. Therapeutic candidate alterations were identified in the majority of HNSCC's. PMID:25631445

  10. Squamous cell carcinoma resulting from chronic osteomyelitis: a retrospective study of 8 cases

    PubMed Central

    Li, Qinghu; Cui, Haomin; Dong, Jinlei; He, Yu; Zhou, Dongsheng; Zhang, Peng; Liu, Ping

    2015-01-01

    Background: Squamous cell carcinoma is a severe malignant tumor but was rare in the chronic osteomyelitis. The purpose of this study was to present the results from a retrospective study the cases of squamous cell carcinoma arising from chronic osteomyelitis. Material and methods: Between 1974 and 2010, eight cases of squamous cell carcinoma after chronic osteomyelitis were treated. The patients had an average age of 55 years (range 45 to 66 years), with a male predominance (6 men and 2 woman). We analyzed the time up to cancerization, localization and histopathological types of the carcinoma, and types and results of the treatment. Results: The mean delay between the initial injury and the diagnosis of malignant transformation was 28 years (range 8 to 50 years). The carcinoma resulted from tibia osteomyelitis in six cases, femur in one case and ankle in one case. The pathological examination showed two cases of a well-differentiated squamous cell carcinoma with bone invasion and six cases of invasive squamous cell carcinoma. Curative amputation was performed in all patients but one who refused. No recurrence or metastasis occurred during follow-up time. Conclusion: Amputation appears to be an effective treatment method in squamous carcinoma secondary to chronic osteomyelitis. PMID:26617726

  11. Slug inhibition increases radiosensitivity of oral squamous cell carcinoma cells by upregulating PUMA.

    PubMed

    Jiang, Fangfang; Zhou, Lijie; Wei, Changbo; Zhao, Wei; Yu, Dongsheng

    2016-08-01

    As a new strategy, radio-gene therapy was widely used for the treatment of cancer patients in recent few years. Slug was involved in the radioresistance of various cancers and has been found to have an anti-apoptotic effect. This study aims to investigate whether the modulation of Slug expression by siRNA affects oral squamous cell carcinoma sensitivity to X-ray irradiation through upregulating PUMA. Two oral squamous cell carcinoma cell lines (HSC3 and HSC6) were transfected with small interfering RNA (siRNA) targeting Slug and subjected to radiotherapy in vitro. After transfection with Slug siRNA, both HSC3 and HSC6 cells showed relatively lower expression of Slug and higher expression of PUMA. The Slug siRNA transfected cells showed decreased survival and proliferation rates, an increased apoptosis rate and enhanced radiosensitivity to X-ray irradiation. Our results revealed that Slug siRNA transfection in combination with radiation increased the expression of PUMA, which contributed to radiosensitivity of oral squamous cell carcinoma cells. Thus, controlling the expression of Slug might contribute to enhance sensitivity of HSC3 and HSC6 cells toward X-ray irradiation in vitro by upregulating PUMA.

  12. Human papillomavirus detection in head and neck squamous cell carcinoma

    PubMed Central

    Vietía, Dayahindara; Liuzzi, Juan; Ávila, Maira; De Guglielmo, Zoraya; Prado, Yrneh; Correnti, María

    2014-01-01

    Introduction Human Papillomavirus (HPV) has been associated with benign and malignant lesions in different epitheliums. The relationship between specific genotypes of high-risk HPV and some human cancers is well established. The aim of this work was to detect the HPV genotypes present in head and neck squamous cell carcinoma (HNSCC). Methods We evaluated 71 samples of patients with histopathological diagnosis of HNSCC. The DNA extraction was conducted with the QIAGEN commercial kit. HPV detection and genotyping were performed by reverse hybridisation (INNO-LiPA) following the commercial specifications. Results The mean age of the patients evaluated was 60.7 ± 13.11 years. The distribution of the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients, 78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity and the larynx were the highest HPV-positivity sites with 35.40% and 29.10% respectively. The most frequent genotype was 16 as single infection (18.70%), or in combination with another HPV types. In the oral cavity and larynx the genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%, respectively; and in the oropharynx the most frequent genotype was 16 in 22.50% of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We observed that tumours with most advanced size and stage presented greater HPV positivity. Conclusions This study shows a high percentage of HPV positivity in SCC is mainly associated with high-risk HPV. It is important to highlight that viral infection, especially HPV-16, could be a risk factor in HNSCC progression. PMID:25374623

  13. SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis

    PubMed Central

    Kim, Bo Ram; Van de Laar, Emily; Tarumi, Shintaro; Hasenoeder, Stefan; Wang, Dennis; Virtanen, Carl; Bandarchi, Bizhan; Pham, Nhu An; Lee, Sharon; Keshavjee, Shaf; Tsao, Ming-Sound; Moghal, Nadeem

    2016-01-01

    Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and

  14. Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma

    PubMed Central

    Hyland, Paula L.

    2013-01-01

    In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal adenocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag single-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpathways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations. PMID:23358850

  15. High Intrathoracic Anastomosis with Thoracoscopy Is Safe and Feasible for Treatment of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Jeon, Hyun Woo; Park, Jae Kil; Song, Kyo Young; Sung, Sook Whan

    2016-01-01

    Background Minimally invasive esophagectomy (MIE) has the potential to reduce the morbidity and mortality of esophageal cancer surgery. Esophageal squamous cell carcinoma (ESCC) has a high incidence of earlier lymphatic spread and is usually located more proximal to the incisor than esophageal adenocarcinoma; consequently, the anastomosis should be made more proximal in the thorax or in the neck. We adopted the proximal intrathoracic anastomotic technique using thoracoscopy for mid-to-lower ESCC. Methods From October 2010 to August 2014, fifty-eight consecutive patients underwent MIE for ESCC. After laparoscopic gastric tubing, thoracoscopic esophageal resection and reconstruction were performed using a 28-mm circular stapler following radical mediastinal lymph node dissection. We tried to make an anastomosis at the apex of the chest. Postoperative outcomes, including overall survival and recurrence, were assessed. Results The mean patient age was 64.3±9 years. The mean operative time was 371.8±51.6 minutes, and the duration of the thorax procedure was 254.8±38.3 minutes. The mean number of lymph nodes dissected was 31±11.7. The mean intensive care unit (ICU) stay and hospital stay were 3.5±8.2 hours and 13.6±7.4 days, respectively. The level of anastomosis was 22.3±1.8cm from the incisor. One patient died of uncontrolled sepsis due to necrosis of the gastric graft. Two patients developed small contained leakage. Nine patients exhibited distant metastasis during the follow-up period. Conclusion Thoracoscopic intrathoracic anastomosis at the proximal esophagus is feasible and safe. PMID:27011160

  16. Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

    PubMed Central

    WANG, HUA-YI; YANG, GUI-FANG; HUANG, YAN-HUA; HUANG, QI-WEN; GAO, JUN; ZHAO, XIAN-DA; HUANG, LI-MING; CHEN, HONG-LEI

    2014-01-01

    Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development. PMID:25202355

  17. Novel Midkine Inhibitor iMDK Inhibits Tumor Growth and Angiogenesis in Oral Squamous Cell Carcinoma.

    PubMed

    Masui, Masanori; Okui, Tatsuo; Shimo, Tsuyoshi; Takabatake, Kiyofumi; Fukazawa, Takuya; Matsumoto, Kenichi; Kurio, Naito; Ibaragi, Soichiro; Naomoto, Yoshio; Nagatsuka, Hitoshi; Sasaki, Akira

    2016-06-01

    Midkine is a heparin-binding growth factor highly expressed in various human malignant tumors. However, its role in the growth of oral squamous cell carcinoma is not well understood. In this study, we analyzed the antitumor effect of a novel midkine inhibitor (iMDK) against oral squamous cell carcinoma. Administration of iMDK induced a robust antitumor response and suppressed cluster of differentiation 31 (CD31) expression in oral squamous cell carcinoma HSC-2 cells and SAS cells xenograft models. iMDK inhibited the proliferation of these cells dose-dependently, as well as the expression of midkine and phospho-extracellular signal-regulated kinase in HSC-2 and SAS cells. Moreover, iMDK significantly inhibited vascular endothelial growth factor and induced tube growth of human umbilical vein endothelial cells in a dose-dependent fashion. These findings suggest that midkine is critically involved in oral squamous cell carcinoma and iMDK can be effectively used for the treatment of oral squamous cell carcinoma.

  18. Clear cell variant of squamous cell carcinoma of skin: A report of a case.

    PubMed

    Lawal, Ahmed Oluwatoyin; Adisa, Akinyele Olumuyiwa; Olajide, Mofoluwaso A; Olusanya, Adeola Adenike

    2013-01-01

    Clear cell squamous cell carcinoma (SCC) is a rare variant of SCC of skin in which ultraviolet radiation has been suggested as possible etiology. This case is that of a 62-year-old male concrete block maker/bricklayer who presented with a 6 months history of a non-healing ulcer on the left side of his face. Histology showed features of malignant epithelial neoplasm composed of islands of large oval to polyhedral malignant squamous cells with eosinophilic to amphophilic cytoplasm and vesicular nuclei and there were areas showing clear cell differentiation and isolated areas of keratin pearl formation. The lesion was also negative for periodic acid schiff, mucicarmine, and alcian blue stains but was strongly positive for AE1/AE3 (immuno-stain). This case showed an aggressive and bizarre clinical presentation but more report of cases are needed to have a better characterization of the clinical presentation and prognosis of this variant of SCC.

  19. ARNT2 Regulates Tumoral Growth in Oral Squamous Cell Carcinoma

    PubMed Central

    Kimura, Yasushi; Kasamatsu, Atsushi; Nakashima, Dai; Yamatoji, Masanobu; Minakawa, Yasuyuki; Koike, Kazuyuki; Fushimi, Kazuaki; Higo, Morihiro; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2016-01-01

    Aryl hydrocarbon receptor nuclear translocator (ARNT) 2 is a transcriptional factor related to adaptive responses against cellular stress from a xenobiotic substance. Recent evidence indicates ARNT is involved in carcinogenesis and cancer progression; however, little is known about the relevance of ARNT2 in the behavior of oral squamous cell carcinoma (OSCC). In the current study, we evaluated the ARNT2 mRNA and protein expression levels in OSCC in vitro and in vivo and the clinical relationship between ARNT2 expression levels in primary OSCCs and their clinicopathologic status by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry. Using ARNT2 overexpression models, we performed functional analyses to investigate the critical roles of ARNT2 in OSCC. ARNT2 mRNA and protein were down-regulated significantly (P < 0.05 for both comparisons) in nine OSCC-derived cells and primary OSCC (n=100 patients) compared with normal counterparts. In addition to the data from exogenous experiments that ARNT2-overexpressed cells showed decreased cellular proliferation, ARNT2-positive OSCC cases were correlated significantly (P < 0.05) with tumoral size. Since von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase, a negative regulator of hypoxia-inducible factor (HIF1)-α, is a downstream molecule of ARNT2, we speculated that HIF1-α and its downstream molecules would have key functions in cellular growth. Consistent with our hypothesis, overexpressed ARNT2 cells showed down-regulation of HIF1-α, which causes hypofunctioning of glucose transporter 1, leading to decreased cellular growth. Our results proposed for the first time that the ARNT2 level is an indicator of cellular proliferation in OSCCs. Therefore, ARNT2 may be a potential therapeutic target against progression of OSCCs. PMID:27076852

  20. Assessing the patient at risk for oral squamous cell carcinoma.

    PubMed

    Epstein, J B; Scully, C

    1997-01-01

    Patients and health care workers require continuing education to promote knowledge of the signs, symptoms, and risk factors for oral cancer. This paper reviews the literature assessing diagnostic tools that are currently available or being developed, in order to assist in the biopsy site selection and subsequent diagnosis of patients at risk for oral cancer. There is a general consensus that oral examination of patients at risk for oral squamous cell carcinoma (SCC) should be conducted on a routine basis. However, there can be false-positive and false-negative findings. Toluidine blue has been shown to be useful as an adjunct to the clinical examination when used by experienced clinicians. Exfoliative cytology is not currently used as a routine measure for the evaluation of lesions of the oral mucosa, but further development and the application of biologic markers to cytologic specimens may increase its value. Fluorescent imaging of malignant lesions of the oral mucosa has been shown to be sensitive and specific in animal models but thus far has been reported in only one human trial. The sensitivity and specificity of these techniques when used by general practitioners need to be assessed. Further, none of the above procedures has yet been shown to be a cost-effective public health measure in screening for oral cancer.

  1. [Primary squamous cell carcinoma of the breast: rare form carcinoma].

    PubMed

    Maksimović, Sinisa

    2009-01-01

    Primary squamous cell carcinoma (SCC) is a rare form of breast carcinoma. Incidence is reported to be 0.1-3.6%. We report a case of a young woman, 37-year-old, with history of a lump in the upper outer quadrant of the left breast with ulceration of the skin surface. Menarche occurred at age of 12. The patient was married, had two deliveries and had her first child at age of 26. She did not use contraceptive pills. Diagnosis of the tumour of the breast was made at the Department of surgery in General Hospital in Bijeljina in September 2007. Clinical examination, mammography and ultrasonography were performed. Physical examination revealed a circumscribed and firm mass measuring 60 x 60 x 80 mm. Mammogram showed a round, high-density mass with almost regular but partially irregular margin. Ultrasonogram of the left breast tumor identified an irregularly shaped hypoechoic lesion. After clinical staging of the disease, we performed incision biopsy of the skin and tumour of the left breast with histopathology examination (standard hematoxylin and eosin). Patient had estrogen and progesteron receptors negative and was HER2/neu negative. After histopathology, patient's case was presented to the working group for breast tumors which decided to start with the neoadjuvant chemotherapy using platinum. After six cycles of neoadjuvant chemotherapy, regression of breast tumor was confirmed. Working group decided that radical mastectomy of left breast should be performed.

  2. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

    PubMed Central

    Chockalingam, Ramya; Downing, Christopher; Tyring, Stephen K.

    2015-01-01

    Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV) of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed. PMID:26239556

  3. GSTM1 polymorphism and oral squamous cell carcinoma.

    PubMed

    Drummond, Sérgio Neves; De Marco, Luiz; Noronha, Júlio Carlos Motta; Gomez, Ricardo Santiago

    2004-01-01

    We investigated the frequency of the GSTM1 genotypes in 70 Brazilian patients with oral squamous cell carcinoma (OSCC) and 82 age-sex matched controls. The GSTM1 genotypes were studied by PCR-based methods. The frequency of male patients with OSCC and null for the GSTM1 (70.5%) was statistically different from the male patients from the control group (48.5%) (Odds Ratio, OR=2.53, 95% CI=1.22-5.24, P<0.05). The frequency of the GSTM1 null genotype (0/0) in the group with OSCC (65.7%) was statistically different from the controls (48.7%) (OR=2.01, 95% CI=1.04-3.88, P<0.05). The prevalence of GSTM1 deficiency (null) was significantly higher for patients with oral cancer of the floor of the mouth (OR=3.67, 95% CI=1.11-12.11, P<0.05). In conclusion, the GSTM1 null genotype may increase the risk for OSCC development.

  4. Squamous cell carcinoma of the nasal planum in 17 dogs.

    PubMed

    Lascelles, B D; Parry, A T; Stidworthy, M F; Dobson, J M; White, R A

    2000-10-21

    Squamous cell carcinoma of the nasal planum was diagnosed in 17 dogs over a period of 11 years. Ulceration, bleeding and sneezing were the most common clinical signs. One dog had cytological evidence of metastasis to the local lymph node. The dogs were treated by surgical resection, fractionated megavoltage irradiation, or a combination of the two. Surgical resection gave the most favourable results; four of six dogs were cured but a recurrence of the tumour was predicted in the other two on the basis of incomplete or marginal resection. Radiotherapy alone was not as effective; one of four dogs was cured, and the tumour recurred in the others within 24 weeks (median eight weeks). Combined surgical resection and radiotherapy did not produce a cure in any of the seven remaining dogs, and the tumour recurred within 12 weeks (median nine weeks). Three dogs had cytological evidence of lymph node metastasis when the tumour recurred. The dogs' prognosis was adversely affected by the interval between their initial examination and treatment, but there was no apparent association between the histological grade of the tumour and the clinical outcome.

  5. Suspected Pulmonary Metastasis of Actinic Cutaneous Squamous Cell Carcinoma.

    PubMed

    Meter, Monet E; Nye, David J; Galvez, Christian R

    2017-01-01

    Introduction. It is rare for actinic or squamous cell carcinoma (SCC) in situ to metastasize. Case Presentation. A 67-year-old male had a significant medical history including severe psoriatic arthritis treated with UVB, methotrexate, and rapamycin. He had twenty-five different skin excisions of actinic keratosis four of which were invasive SCC. Our patient developed shortness of breath necessitating a visit to the emergency department. A CT scan of his chest revealed a mass in the right lower lung. A subsequent biopsy of the mass revealed well-differentiated SCC. He underwent thoracoscopic surgery with wedge resection of the lung lesion. Discussion. Actinic keratosis (AK) is considered precancerous and associated with UV exposure. It exists as a continuum of progression with low potential for malignancy. The majority of invasive SCCs are associated with malignant progression of AK, but only 5-10% of AKs will progress to malignant potential. Conclusion. In this case, a new finding of lung SCC in the setting of multiple invasive actinic cutaneous SCC associated with a history of extensive UV light exposure and immunosuppression supports a metastatic explanation for lung cancer.

  6. Interstitial brachytherapy and early tongue squamous cell carcinoma management

    SciTech Connect

    Lefebvre, J.L.; Coche-Dequeant, B.; Castelain, B.; Prevost, B.; Buisset, E.; Ton Van, J. )

    1990-05-01

    The results of treatment of 341 previously untreated patients with early squamous cell carcinoma (SCC) of the anterior two thirds of the tongue using iridium 192 implants (January 1974-December 1983) are presented. Furthermore, 265 patients underwent neck dissection, followed, in 102 cases, by radiotherapy. Incidence of local treatment complications was 19% (66 patients); however, only 3% (11 patients) needed more than a single medical treatment. Two months after completion of overall treatment, 326 patients (96%) were free of disease. Local failures occurred in 18% of cases; however, after successful salvage surgery this rate was reduced to 11%. Neck failures occurred in 18% of cases, but after successful salvage were reduced to 12%. Distant metastases were rare (1.5%), whereas metachronous cancers were frequent (102 patients). Survival rates were 61% (56% to 66%) at 3 years, 46% (41% to 51%) at 5 years, and 26% (23% to 34%) at 10 years. Deaths due to tongue cancer evolution (20%) equalled those due to metachronous cancers (18.5%) and intercurrent diseases (21%).

  7. Feline Oral Squamous Cell Carcinoma: Clinical Manifestations and Literature Review.

    PubMed

    Bilgic, Ozgur; Duda, Lili; Sánchez, Melissa D; Lewis, John R

    2015-01-01

    Squamous cell carcinoma (SCC) is the most commonly encountered malignant oral tumor in cats. The etiology of this locally invasive tumor is likely multifactorial. Several risk factors have been identified, including the use of flea collars, and a history of feeding canned food and canned tuna. Clinical signs vary depending on tumor location. The tumor commonly arises from the gingiva and mucosa of the maxilla, mandible, tongue, sublingual area, or tonsillar region. Maxillary SCC commonly presents clinically as an ulcerative lesion, whereas mandibular SCC is commonly proliferative, expansile, and firm. Lingual/sublingual SCC may be ulcerative, necrotic, infiltrative, or proliferative. In general, feline oral SCC is an invasive and malignant neoplasm regardless of its location. Surgery, radiation therapy, chemotherapy and combinations thereof have been attempted with rarely a satisfactory response. Currently, cures are obtained only in a small subset of cats whose tumors are amenable to complete resection, or where resection with microscopic residual disease is followed by definitive radiation therapy. A multimodal treatment approach likely offers the best chance of success. For cats with advanced disease, palliative care may improve patients' quality of life, albeit transiently. Sequelae associated with tumor progression and local tissue destruction often result in euthanasia of feline patients with oral SCC.

  8. Surgical management for squamous cell carcinoma of vulva

    PubMed Central

    Amavi, Ayi Kossigan; Kouadio, Laurent; Adabra, Komlan; Tengue, Kodjo; Tijami, Fouad; Jalil, Abdelouahed

    2016-01-01

    To analyze our surgical management and the result of squamous cell carcinoma (SCC) of vulva. Retrospectively, we collected 38 cases of SCC; 17 cases of them were early SCC and 21 cases were locally advanced. The patients underwent primary surgery. The survival was estimated using Kaplan-Meier analysis and the log rank test. The mean age was 60.78 years. Total vulvectomy was performed in all patients. Superficial and deep incision of bilateral inguinal lymphadenectomy was performed by separates incisions for SCC infiltrating more than 1mm. The average tumor size was 53 mm (10 to 140mm). Morbidity was 42.1%. Lateral resection margin ≥8mm was obtained in 57.1%. Eighteen patients benefited from adjuvant radiotherapy. The follow-up median was 19.4 months (6 to 61.5 month) with 05 recurrences in 12 months. The survival using the Kaplan-Meyer analysis at 5 years, was 62.1% (71.2%N- vs 46.7%N+; p = 0.13). We identified two groups for locally advanced vulva cancer. Primary surgery keeps its place. Neo adjuvant radio chemotherapy followed by surgery is the alternative treatment for locally extensive lesions. PMID:27642483

  9. Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma

    PubMed Central

    Lafzi, Atefeh; Kazan, Hilal

    2016-01-01

    RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation of mRNAs. Dysregulations in RBP-mediated mechanisms have been found to be associated with many steps of cancer initiation and progression. Despite this, previous studies of gene expression in cancer have ignored the effect of RBPs. To this end, we developed a lasso regression model that predicts gene expression in cancer by incorporating RBP-mediated regulation as well as the effects of other well-studied factors such as copy-number variation, DNA methylation, TFs and miRNAs. As a case study, we applied our model to Lung squamous cell carcinoma (LUSC) data as we found that there are several RBPs differentially expressed in LUSC. Including RBP-mediated regulatory effects in addition to the other features significantly increased the Spearman rank correlation between predicted and measured expression of held-out genes. Using a feature selection procedure that accounts for the adaptive search employed by lasso regularization, we identified the candidate regulators in LUSC. Remarkably, several of these candidate regulators are RBPs. Furthermore, majority of the candidate regulators have been previously found to be associated with lung cancer. To investigate the mechanisms that are controlled by these regulators, we predicted their target gene sets based on our model. We validated the target gene sets by comparing against experimentally verified targets. Our results suggest that the future studies of gene expression in cancer must consider the effect of RBP-mediated regulation. PMID:27186987

  10. Suspected Pulmonary Metastasis of Actinic Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Meter, Monet E.; Galvez, Christian R.

    2017-01-01

    Introduction. It is rare for actinic or squamous cell carcinoma (SCC) in situ to metastasize. Case Presentation. A 67-year-old male had a significant medical history including severe psoriatic arthritis treated with UVB, methotrexate, and rapamycin. He had twenty-five different skin excisions of actinic keratosis four of which were invasive SCC. Our patient developed shortness of breath necessitating a visit to the emergency department. A CT scan of his chest revealed a mass in the right lower lung. A subsequent biopsy of the mass revealed well-differentiated SCC. He underwent thoracoscopic surgery with wedge resection of the lung lesion. Discussion. Actinic keratosis (AK) is considered precancerous and associated with UV exposure. It exists as a continuum of progression with low potential for malignancy. The majority of invasive SCCs are associated with malignant progression of AK, but only 5–10% of AKs will progress to malignant potential. Conclusion. In this case, a new finding of lung SCC in the setting of multiple invasive actinic cutaneous SCC associated with a history of extensive UV light exposure and immunosuppression supports a metastatic explanation for lung cancer. PMID:28386508

  11. Squamous cell carcinoma arising in previously burned or irradiated skin

    SciTech Connect

    Edwards, M.J.; Hirsch, R.M.; Broadwater, J.R.; Netscher, D.T.; Ames, F.C.

    1989-01-01

    Squamous cell carcinoma (SCC) arising in previously burned or irradiated skin was reviewed in 66 patients treated between 1944 and 1986. Healing of the initial injury was complicated in 70% of patients. Mean interval from initial injury to diagnosis of SCC was 37 years. The overwhelming majority of patients presented with a chronic intractable ulcer in previously injured skin. The regional relapse rate after surgical excision was very high, 58% of all patients. Predominant patterns of recurrence were in local skin and regional lymph nodes (93% of recurrences). Survival rates at 5, 10, and 20 years were 52%, 34%, and 23%, respectively. Five-year survival rates in previously burned and irradiated patients were not significantly different (53% and 50%, respectively). This review, one of the largest reported series, better defines SCC arising in previously burned or irradiated skin as a locally aggressive disease that is distinct from SCC arising in sunlight-damaged skin. An increased awareness of the significance of chronic ulceration in scar tissue may allow earlier diagnosis. Regional disease control and survival depend on surgical resection of all known disease and may require radical lymph node dissection or amputation.

  12. Head and Neck Squamous Cell Carcinoma in Pregnant Women

    PubMed Central

    Eliassen, Anna M.; Hauff, Samantha J.; Tang, Alice L.; Thomas, Dafydd H.; McHugh, Jonathan B.; Walline, Heather M.; Stoerker, Jay; Maxwell, Jessica H.; Worden, Francis P.; Eisbruch, Avraham; Czerwinski, Michael J.; Papagerakis, Silvana M.; Chepeha, Douglas B.; Bradford, Carol R.; Hanauer, David A.; Carey, Thomas E.; Prince, Mark E.

    2012-01-01

    Objective To investigate oral cancer in pregnant women, a rare but therapeutically challenging patient subset. Methods After IRB approval, an EMERSE search was used to identify all women treated at the University of Michigan from 1998–2010 with head and neck squamous cell carcinoma (HNSCC) during pregnancy. This identified four patients with tongue cancer. Biomarkers and HPV were assessed by immunohistochemistry and multiplex PCR/Mass spectrometry, respectively. Results Two patients responded well to therapy and are alive more than 10 years after diagnosis; two died of disease. All tumors overexpressed EGFR and Bcl-xL, three of four overexpressed c-Met, both tumors that progressed overexpressed p53. All tumors were negative for HPV, p16, ER, PR, and HER-2. Conclusions Biomarkers of aggressive tumors (high EGFR, Bcl-xL, c-Met; low p53) did not correlate with outcome. Additional studies are needed to determine whether perineural invasion, delay in diagnosis, and p53 overexpression are factors related to poorer survival. PMID:22422571

  13. Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

    PubMed Central

    Bansal, Pranshu; Osman, Diaa; Gan, Gregory N.; Simon, George R.; Boumber, Yanis

    2016-01-01

    Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC). With the discovery of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor 2 (VEGFR2), RET, and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding. PMID:27200298

  14. Osteopontin Facilitates Ultraviolet B-induced Squamous Cell Carcinoma Development

    PubMed Central

    Chang, Pi-Ling; Hsieh, Yu-Hua; Wang, Chao-Cheng; Juliana, M. Margaret; Tsuruta, Yuko; Timares, Laura; Elmets, Craig; Ho, Kang-Jey

    2014-01-01

    Background Osteopontin (OPN) is a matricellular glycoprotein that is markedly expressed in cutaneous squamous cell carcinomas (cSCCs) and in actinic keratoses implicating its role in photocarcinogenesis. Objective To determine whether OPN facilitates the development of cSCC and its function. Methods cSCCs development was compared between wild-type (WT) and OPN-null mice subjected to UVB irradiation for 43 weeks. UVB-induced OPN expression was determined by Western blot, immunoprecipitation, ELISA, and semi-quantitative RT-PCR. Epidermal layer and TUNEL analyses assessed if OPN mediates UVB-induced epidermal hyperplasia or suppresses UVB-induced apoptosis of basal keratinocytes, respectively. In vitro experiments determined whether OPN enhances cell survival of UVB-induced apoptosis and its potential mechanisms. Immunohistochemical analyses of epidermis assessed the expression of CD44 and focal adhesion kinase (FAK), molecules that mediate OPN survival function. Results Compared to female WT mice, OPN-null mice did not develop cSCCs. UVB irradiation stimulated OPN protein expression in the dorsal skin by 11 h and remains high at 24 to 48h.OPN did not mediate UVB-induced epidermal hyperplasia; instead, it protected basal keratinocytes from undergoing apoptosis upon UVB exposure. Likewise, the addition of OPN suppressed UVB-induced OPN-null cSCC cell apoptosis, the activation of caspase-9 activity, and increased phosphorylation of FAK at Y397. Furthermore, the expression of CD44 and FAK in WT mice epidermis was greater than that of OPN-null mice prior to and during early acute UVB exposure. Conclusion These data support the hypothesis that chronic UVB-induced OPN expression protects the survival of initiated basal keratinocytes and, consequently, facilitates cSCC develop. PMID:24888687

  15. Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress

    SciTech Connect

    Cheng, Ya-Hsin; Huang, Su-Chin; Lin, Chun-Ju; Cheng, Li-Chuan; Li, Lih-Ann

    2012-03-15

    Environmental cigarette smoke has been suggested to promote lung adenocarcinoma progression through aryl hydrocarbon receptor (AhR)-signaled metabolism. However, whether AhR facilitates metabolic activation or detoxification in exposed adenocarcinoma cells remains ambiguous. To address this question, we have modified the expression level of AhR in two human lung adenocarcinoma cell lines and examined their response to an extract of cigarette sidestream smoke particulates (CSSP). We found that overexpression of AhR in the CL1-5 cell line reduced CSSP-induced ROS production and oxidative DNA damage, whereas knockdown of AhR expression increased ROS level in CSSP-exposed H1355 cells. Oxidative stress sensor Nrf2 and its target gene NQO1 were insensitive to AhR expression level and CSSP treatment in human lung adenocarcinoma cells. In contrast, induction of AhR expression concurrently increased mRNA expression of xenobiotic-metabolizing genes CYP1B1, UGT1A8, and UGT1A10 in a ligand-independent manner. It appeared that AhR accelerated xenobiotic clearing and diminished associated oxidative stress by coordinate regulation of a set of phase I and II metabolizing genes. However, the AhR-signaled protection could not shield cells from constant oxidative stress. Prolonged exposure to high concentrations of CSSP induced G0/G1 cell cycle arrest via the p53–p21–Rb1 signaling pathway. Despite no effect on DNA repair rate, AhR facilitated the recovery of cells from growth arrest when CSSP exposure ended. AhR-overexpressing lung adenocarcinoma cells exhibited an increased anchorage-dependent and independent proliferation when recovery from exposure. In summary, our data demonstrated that AhR protected lung adenocarcinoma cells against CSSP-induced oxidative stress and promoted post-exposure clonogenicity. -- Highlights: ► AhR expression level influences cigarette sidestream smoke-induced ROS production. ► AhR reduces oxidative stress by coordinate regulation of

  16. Squamous cell cancer – 31-year epidemiological study in a city of south Brazil*

    PubMed Central

    Nasser, Nilton; Nasser Filho, Nilton; Lehmkuhl, Rafaela Ludvig

    2015-01-01

    BACKGROUND The incidence and morbidity of squamous cell cancers are increasing worldwide. Epidemiological studies with morbidity coefficients about this type of cancer are scarce in Brazil. OBJECTIVES To determine morbidity coefficients, analyze and classify the squamous cell cancers diagnosed in the city of Blumenau - SC from 1980 to 2011, according to clinical and histological features. METHODS The authors revised 4000 histopathological exams with respect to sex, age, anatomic site and histological type. The morbidity coefficients were calculated using the number of squamous cell cancers found and the annual population estimated by the Brazilian Institute of Geography and Statistics between 1980 and 2011. RESULTS A total of 4000 tumors were identified, 2249 (56.2%) in male and 1751 (43.8%) in female patients. The standard incidence rates varied from 40 cases in 1980 to 120 cases/100,000 inhabitants in 2011. The morbidity above 70 years of age reached 1484 cases/100,000 inhabitants in male and 975 in female patients. As to primary anatomic site, we found more tumors on the lips and ears in male and on the face and legs in female patients. As to the degree of involvement, the more frequent were Well Differentiated Squamous cell carcinomas (70%) and Moderate Squamous cell carcinomas (19,1%). The Low Differentiated Squamous cell carcinomas, which represented those with the worst prognosis, were found in 4.5% of the tumors. CONCLUSION Squamous cell cancers in Blumenau - SC have similar patterns of distribution regarding age, primary anatomic site and histological types as found in the international literature. The morbidity increased by 300% in the last 31 years, which indicates that we need to dedicate special attention to the older population. PMID:25672295

  17. α-Mangostin Induces Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma Cell

    PubMed Central

    Kwak, Hyun-Ho; Park, Bong-Soo

    2016-01-01

    Mangosteen has long been used as a traditional medicine and is known to have antibacterial, antioxidant, and anticancer effects. Although the effects of α-mangostin, a natural compound extracted from the pericarp of mangosteen, have been investigated in many studies, there is limited data on the effects of the compound in human oral squamous cell carcinoma (OSCC). In this study, α-mangostin was assessed as a potential anticancer agent against human OSCC cells. α-Mangostin inhibited cell proliferation and induced cell death in OSCC cells in a dose- and time-dependent manner with little to no effect on normal human PDLF cells. α-Mangostin treatment clearly showed apoptotic evidences such as nuclear fragmentation and accumulation of annexin V and PI-positive cells on OSCC cells. α-Mangostin treatment also caused the collapse of mitochondrial membrane potential and the translocation of cytochrome c from the mitochondria into the cytosol. The expressions of the mitochondria-related proteins were activated by α-mangostin. Treatment with α-mangostin also induced G1 phase arrest and downregulated cell cycle-related proteins (CDK/cyclin). Hence, α-mangostin specifically induces cell death and inhibits proliferation in OSCC cells via the intrinsic apoptosis pathway and cell cycle arrest at the G1 phase, suggesting that α-mangostin may be an effective agent for the treatment of OSCC. PMID:27478478

  18. Primary mucinous adenocarcinoma of the larynx in female patient: a rare entity.

    PubMed

    Ebru, Tastekin; Omer, Yalcin; Fulya, Oz Puyan; Ufuk, Usta; Kemal, Kutlu

    2012-10-01

    Laryngeal malignant tumors are mainly composed of squamous cell carcinomas. Glandular carcinomas of the larynx are rare tumors that constitute less than 1% of all laryngeal malignancies where "adenocarcinoma not otherwise specified" is the most common histologic subtype. Here we report a case of a 70-year-old female patient with primary laryngeal mucinous adenocarcinoma. The rarity of the tumor type and the differential diagnosis of this tumor before reporting it as a primary adenocarcinoma of the larynx are discussed here with literature findings.

  19. NR4A2 Is Regulated by Gastrin and Influences Cellular Responses of Gastric Adenocarcinoma Cells

    PubMed Central

    Misund, Kristine; Selvik, Linn-Karina Myrland; Rao, Shalini; Nørsett, Kristin; Bakke, Ingunn; Sandvik, Arne K.; Lægreid, Astrid; Bruland, Torunn; Prestvik, Wenche S.; Thommesen, Liv

    2013-01-01

    The peptide hormone gastrin is known to play a role in differentiation, growth and apoptosis of cells in the gastric mucosa. In this study we demonstrate that gastrin induces Nuclear Receptor 4A2 (NR4A2) expression in the adenocarcinoma cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more diffuse and variable expression in tumor cells. We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER) and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1), suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2 increases apoptosis and hampers gastrin induced invasion, indicating a tumor suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2 in gastric adenocarcinoma cells, and suggest that both the level and the localization of NR4A2 protein are of importance regarding the cellular responses of these cells. PMID:24086717

  20. NR4A2 is regulated by gastrin and influences cellular responses of gastric adenocarcinoma cells.

    PubMed

    Misund, Kristine; Selvik, Linn-Karina Myrland; Rao, Shalini; Nørsett, Kristin; Bakke, Ingunn; Sandvik, Arne K; Lægreid, Astrid; Bruland, Torunn; Prestvik, Wenche S; Thommesen, Liv

    2013-01-01

    The peptide hormone gastrin is known to play a role in differentiation, growth and apoptosis of cells in the gastric mucosa. In this study we demonstrate that gastrin induces Nuclear Receptor 4A2 (NR4A2) expression in the adenocarcinoma cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more diffuse and variable expression in tumor cells. We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER) and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1), suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2 increases apoptosis and hampers gastrin induced invasion, indicating a tumor suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2 in gastric adenocarcinoma cells, and suggest that both the level and the localization of NR4A2 protein are of importance regarding the cellular responses of these cells.

  1. Squamous cell carcinoma of the urinary bladder: a clinicopathologic and immunohistochemical study of 16 cases.

    PubMed

    Guo, Charles C; Gomez, Enrique; Tamboli, Pheroze; Bondaruk, Jolanta E; Kamat, Ashish; Bassett, Roland; Dinney, Colin P; Czerniak, Bogdan A

    2009-10-01

    Squamous cell carcinoma is an uncommon histologic type in the urinary bladder. We searched our surgical pathology files and identified 16 cases of squamous cell carcinoma of the urinary bladder. The mean age of patients was 65.4 years (range, 41-77 years). All patients received transurethral resection of the bladder, which demonstrated pure squamous cell carcinomas. Seven patients had clinical evidence of tumor spreading out of the bladder (T4) and did not undergo radical cystectomy. The other 9 patients underwent cystectomy with pelvic lymph node dissection. The cystectomy specimens revealed tumors invading muscularis propria (T2) (n = 4) or perivesical soft tissue (T3) (n = 5). Two patients also had metastasis to lymph nodes. Immunohistochemical studies demonstrated that squamous cell carcinoma cells were positive for epidermal growth factor receptor (n = 16) and for p53 (n = 11). For the 9 patients who received cystectomy, 5 patients were alive at a mean of 92.8 months (range, 59-128 months) and 4 patients died of disease at a mean of 24.0 months (range, 6-58 months). For the 7 patients who did not receive cystectomy, 6 died at a mean of 5.7 months (range, 3-9 months), and no follow-up was available for the remaining patient. In conclusion, squamous cell carcinoma of the bladder frequently presents at an advanced stage and is associated with enhanced expression of EGFR and p53.

  2. Treatment of advanced squamous cell carcinoma of the lung: a review

    PubMed Central

    Mileham, Kathryn F.; Bonomi, Philip D.; Batus, Marta; Fidler, Mary J.

    2015-01-01

    Lung cancer remains the single deadliest cancer both in the US and worldwide. The great majority of squamous cell carcinoma (SCC) is attributed to cigarette smoking, which fortunately is declining alongside cancer incidence. While we have been at a therapeutic plateau for advanced squamous cell lung cancer patients for several decades, recent observations suggest that we are on the verge of seeing incremental survival improvements for this relatively large group of patients. Current studies have confirmed an expanding role for immunotherapy [including programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition], a potential opportunity for VEGFR inhibition, and even future targets in fibroblast growth factor receptor (FGFR) and PI3K-AKT that collectively should improve survival as well as quality of life for those affected by squamous cell lung cancer over the next decade. PMID:26629421

  3. Regulation of cell migration via the EGFR signaling pathway in oral squamous cell carcinoma cells

    PubMed Central

    Ohnishi, Yuichi; Yasui, Hiroki; Kakudo, Kenji; Nozaki, Masami

    2017-01-01

    Cell migration potency is essential in cancer metastasis and is often regulated by extracellular stimuli. Oral squamous cell carcinoma cell lines include those that are sensitive, as well as resistant, to the effects of the epidermal growth factor receptor (EGFR) inhibitor cetuximab on cell migration. In the present study, the molecular differences in the EGFR response to cell migration between the SAS cetuximab-sensitive and HSC4 cetuximab-resistant cell lines was examined. Treatment with the EGFR inhibitors AG1478 and cetuximab reduced the migration potency of SAS cells, but not HSC4 cells. The migration of the two cell lines was inhibited under serum-free culture conditions, and the addition of EGF to the serum-free medium promoted the migration of SAS cells, but not HSC4 cells. In addition, SAS cell migration was reduced by the mitogen-activated protein kinase kinase and protein kinase B (Akt) inhibitors PD98059 and MK2206, whereas HSC4 cell migration was only inhibited by MK2206. EGF induced an increase in extracellular signal-regulated kinase phosphorylation levels in HSC4 cells, and stimulated Akt phosphorylation levels in SAS cells. Furthermore, the staining of actin filaments with phalloidin was significantly increased by the inhibition of EGFR in SAS cells, but was not observed as altered in HSC4 cells. Conversely, the addition of EGF to the culture medium decreased the accumulation of actin filaments in SAS cells. The results suggest that the EGF-EGFR signaling pathway has an important role in SAS cell migration via the modulation of actin dynamics, and that HSC4 cell migration is regulated by a serum component other than EGFR.

  4. A novel long noncoding RNA LINC01133 is upregulated in lung squamous cell cancer and predicts survival.

    PubMed

    Zhang, Jing; Zhu, Ning; Chen, Xiaodong

    2015-09-01

    Lung adenocarcinoma (LAD) and lung squamous cell cancer (LSCC) are two major histological types of non-small cell lung cancer. LSCC differs greatly from LAD in many aspects. Accumulating evidence has shown that long noncoding RNA (lncRNA) plays an important role in the process of carcinogenesis and tumor progression. Expression of lncRNA is highly tissue-specific and could be biomarkers for cancer diagnosis and prognosis. Here, we identified differentially expressed lncRNA between LSCC and LAD by data mining of Affymetrix HG-U133 Plus 2.0 microarray. A set of 1646 differentially expressed lncRNA transcripts were identified. Among these lncRNAs, a novel lncRNA, LINC01133, showed the largest fold change among large intergenic noncoding RNAs. Quantitative real-time polymerase chain reaction (PCR) assay confirmed that LINC01133 was upregulated in LSCC (increasing fold 6.4, P < 0.01) but not in the LAD samples. LSCC patients with higher expression level of LINC01133 had shorter survival time (hazard ratio = 2.383; 95 % confidence interval 1.023-5.547, P = 0.044). Wound-healing and transwell assays demonstrated that silence of LINC01133 by small interfering RNA (siRNA) inhibited invasion ability of LSCC cell line. Thus, a set of lncRNA was differentially expressed between LAD and LSCC and could serve as potential biomarkers.

  5. Lgr5-positive cells are cancer stem cells in skin squamous cell carcinoma.

    PubMed

    Liu, Shunli; Gong, Zhenyu; Chen, Mingrui; Liu, Benli; Bian, Donghui; Wu, Kai

    2014-11-01

    Cancer stem cells (CSCs) in most human tumors are commonly identified and enriched using similar strategies for identifying normal stem cells, including flow cytometry assays for side population, high aldehyde dehydrogenase (ALDH) activity, and CD133 positivity. Thus, development of a method for isolating a specific cancer using cancer-specific characteristic appears to be potentially important. Here, we reported extremely high Lgr5 levels in the specimen from skin squamous cell carcinoma (SCC) in patients. Using SCC cell line A431, we detected high Lgr5 and CD133 levels in ALDH-high or side population from these cancer cells. To figure out whether Lgr5 is a marker of CSCs in SCC, we transfected A431 cells with a Lgr5-creERT-2A-DTR/Cag-Loxp-GFP-STOP-Loxp-RFP plasmid and purified transfected cells (tA431) based on GFP by flow cytometry. 4-Hydroxytamoxifen (4-OHT) was given to label Lgr5-positive cells with RFP, for comparison to GFP-positive Lgr5-negative cells. Lgr5-positive cells grew significantly faster than Lgr5-negative cells, and the fold increase in growth of Lgr5-positive vs Lgr5-negative cells is significantly higher than SP vs non-SP, or ALDH-high vs ALDH-low, or CD133-positive vs CD133-negative cells. Moreover, in Lgr5-negative population, Lgr5-positive re-appeared in culture with time, suggesting that Lgr5-positive cells can be regenerated from Lgr5-negative cells. Furthermore, the growth of tA431 cells significantly decreased upon a single dose of diphtheria toxin (DT)/4-OHT to eliminate Lgr5-positive cell lineage, while multiple doses of DT/4-OHT nearly completely inhibited tA431 cell growth. Taken together, our data provide compelling data to demonstrate that Lgr5-positive cells are CSCs in skin SCC.

  6. Immunohistochemical characterization of endometrial carcinomas: endometrioid, serous and clear cell adenocarcinomas in association with genetic analysis.

    PubMed

    Yasuda, Masanori

    2014-12-01

    Developments in immunohistochemistry, which are closely linked with the advances in the analyses of genetic abnormalities and their associated molecular disorders as early and late histogenetic events, have contributed greatly to the improvement of pathological diagnostic confirmation and validation. Immunohistochemistry has also generated great benefit to the innovation of therapeutic strategies for various kinds of cancers. In this article, the three representative histological types of corpus cancer, namely, endometrioid adenocarcinoma, serous adenocarcinoma and clear cell adenocarcinoma, will be histologically approached in association with their immunohistochemical profiles as well as genetic disorders. First, the focus will be on 'Conventional/prototypic features,' followed by 'Controversy over conventional histological subclassification,' and subsequently 'Tumorigenesis and re-subclassification'.

  7. Human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma.

    PubMed

    Dalianis, Tina

    2014-12-01

    Numerous reports in recent decades have shown that, in addition to smoking and alcohol, human papillomavirus (HPV) is also associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), predominantly in the tonsils and base of the tongue. In 2007, the International Agency on Research against Cancer (IARC) therefore declared HPV to be a risk factor for OPSCC and noted that 80% of those affected are men. In addition, patients with HPV-positive OPSCC, in particular never-smokers, have a much better clinical response to therapy than patients with HPV-negative OPSCC and other head and neck cancers. Most patients with HPV-positive OPSCC may thus not need the increasingly intensive chemo-radiotherapy currently administered today to most patients with head neck cancers and associated with many adverse effects. Furthermore, an increase in the incidence of OPSCC has been observed in many western countries, accompanied by a rise in the proportion of HPV-positive tumors. Patients with HPV-positive OPSCC, like those with cervical cancer, more often have an earlier sexual debut and have more sexual partners. It has therefore been proposed that the increased incidence of OPSCC observed might be due to an epidemic of sexually transmitted HPV. The important issues today regarding this growing cohort of patients with HPV-positive OPSCC are therefore individualized treatment and prevention. More specifically, selected HPV-positive OPSCC patients with biomarkers of good prognosis might be included in randomized trials with less intensive treatment. HPV vaccination should also be considered for boys, in addition to the current recommendations for immunization of girls.

  8. Pseudoangiomatous squamous cell carcinoma in the oral cavity of a dog.

    PubMed

    Cushing, Tim; Barnard, Sandra; Fleis, Rebekah; Peters, Rachel

    2010-03-01

    An 8-year-old, spayed, female Labrador Retriever mixed-breed dog was presented to the Cornell University Hospital for Animals with an invasive oral mass involving the upper left fourth premolar and first molar teeth. Initial biopsy results suggested a poorly differentiated squamous cell carcinoma, whereas further histologic examination of the surgically removed mass revealed a hemangiosarcoma-like mass composed of numerous vascular clefts and variable numbers of keratinizing epithelial cells. Histologic and immunohistochemical characteristics were compatible with pseudoangiomatous squamous cell carcinoma, a well-recognized human variant of acanthomatous squamous cell carcinoma. Because of histomorphologic similarities with canine gingival hemangiosarcoma, diagnosticians should be aware of the present tumor variant as a differential diagnosis for vascular-like growths in the oral cavity of dogs.

  9. Squamous cell carcinoma with sarcomatous stroma in the nasal cavity of a dog.

    PubMed

    Bosward, K L; Kessell, A E; Lucy, R J

    2004-09-01

    This is a report of an unusual squamous cell carcinoma in the nasal cavity of a dog. A 13-year-old Golden Retriever was presented with a unilateral nasal and ocular discharge. Although a nasal tumour was suspected, initial diagnostic investigations were unrewarding, and, with worsening clinical signs, the dog was euthanatized. Necropsy examination confirmed the presence of a nasal tumour that was composed histologically of both a well-differentiated squamous cell carcinoma component blending with a predominant spindle cell component. Immunohistochemical staining with anti-human keratin/cytokeratin (AE1/AE3, CAM 5.2 and broad spectrum cytokeratin), Vimentin, Desmin, smooth muscle actin and S-100 protein supported a diagnosis of a squamous cell carcinoma with (pseudo) sarcomatous stroma.

  10. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence.

    PubMed

    Chen, San-Yuan; Liu, Geng-Hung; Chao, Wen-Ying; Shi, Chung-Sheng; Lin, Ching-Yen; Lim, Yun-Ping; Lu, Chieh-Hsiang; Lai, Peng-Yeh; Chen, Hau-Ren; Lee, Ying-Ray

    2016-04-23

    Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC) treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.

  11. Treatment Algorithms for Patients with Metastatic Non-Small Cell, Non-Squamous Lung Cancer

    PubMed Central

    Melosky, Barbara

    2014-01-01

    A number of developments have altered the treatment paradigm for metastatic non-small cell, non-squamous lung cancer. These include increasing knowledge of molecular signal pathways, as well as the outcomes of several large-scale trials. As a result, treatments are becoming more efficacious and more personalized, and are changing the management and prognosis of non-small cell lung cancer patients. This is resulting in increased survival in select patient groups. In this paper, a simplified algorithm for treating patients with metastatic non-small cell, non-squamous lung cancer is presented. PMID:25325013

  12. Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects.

    PubMed

    Vieira, Renata Aparecida Martinez Antunes Ribeiro; Minicucci, Eliana Maria; Marques, Mariangela Esther Alencar; Marques, Silvio Alencar

    2012-01-01

    Actinic cheilitis is the main precancerous lesion of the lip. Squamous cell carcinoma of the lip is reported together with oral carcinomas in the Brazilian official statistics. Overall, they account for 40% of the head and neck carcinomas. In general, physicians and dentists know little about what causes oral tumor development and progression. Tumor suppressor genes and cell proliferation regulatory proteins play a role in the progression of actinic cheilitis to squamous cell carcinoma and in its biological behavior. Knowledge on prognostic and diagnostic markers has a positive impact on the follow-up of these patients.

  13. MicroRNA-29a suppresses the growth, migration, and invasion of lung adenocarcinoma cells by targeting carcinoembryonic antigen-related cell adhesion molecule 6.

    PubMed

    Han, Hye Sook; Son, Seung-Myoung; Yun, Jieun; Jo, Yeong Nang; Lee, Ok-Jun

    2014-10-16

    Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an important regulator of cell adhesion, invasion, and metastasis. The aim of this study was to evaluate the functional roles of CEACAM6 in lung adenocarcinoma and to identify miRNAs that inhibit the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. CEACAM6 expression is associated with poor prognosis of patients with lung adenocarcinoma, and CEACAM6 has important functional roles in controlling the growth, migration, and invasion of lung adenocarcinoma cells in vitro and in vivo. Furthermore, miR-29a can suppress the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. Therefore, miR-29a/CEACAM6 axis represents a potential therapeutic target for treatment of lung adenocarcinoma.

  14. Andrographolide inhibits oral squamous cell carcinogenesis through NF-κB inactivation.

    PubMed

    Wang, L-J; Zhou, X; Wang, W; Tang, F; Qi, C-L; Yang, X; Wu, S; Lin, Y-Q; Wang, J-T; Geng, J-G

    2011-10-01

    The NF-κB family of transcription factors is essential for promoting cell proliferation and preventing cell apoptosis. We have previously shown that Andrographolide (Andro) isolated from an herbal plant, Andrographis paniculata, covalently modifies reduced cysteine(62) in the oligonucleotide binding pocket of p50 for inhibition of NF-κB activation. Here we report that Andro, but not its inactive structural analog 4H-Andro, potently suppressed squamous cell carcinogenesis induced by 7,12-dimethyl-1,2-benzanthracene (DMBA) in the hamster model of cheek buccal pouch. Compared with 4H-Andro, Andro reduced phosphorylation of p65 (Ser536) and IκBα (Ser32/36) for inhibiting aberrant NF-κB activation, suppressed c-Myc and cyclin D1 expression and attenuated neoplastic cell proliferation, promoted cancerous cell apoptosis, and mitigated tumor-induced angiogenesis. Consistently, Andro retarded growth, decreased proliferation, and promoted apoptosis of Tb cells, a human tongue squamous cell carcinoma cell line, in time- and dose-dependent manners, with concomitant reduction of the expression of NF-κB targeting molecules in vitro. Our results thus demonstrate that NF-κB activation plays important roles in the pathogenesis of chemically induced squamous cell carcinoma. By inhibition of aberrant NF-κB activation, Andro treats chemically induced oral squamous cell carcinogenesis.

  15. Distribution and ultrastructural characteristics of dark cells in squamous metaplasias of the respiratory tract epithelium. [Rats

    SciTech Connect

    Klein-Szanto, A.J.P.; Nettesheim, P.; Pine, A.; Martin, D.

    1981-05-01

    Dark epithelial basal cells were found in both carcinogen-induced and non-carcinogen-induced squamous metaplasias of the tracheal epithelium. Formaldehyde-induced squamous metaplasias exhibited 4% dark cells in the basal layer. Metaplasias induced by vitamin A deficiency and those induced by dimethylbenz(a)anthracene (DMBA) without atypia showed 18-20% basal dark cells. DMBA-induced metaplasias with moderate to severe atypia exhibited 50% basal dark cells. The labeling index of basal cells in metaplastic epithelia, regardless of the inducing agent, was 16-18%, ie, the same as that of the normal esophageal stratified squamous epithelium. The percentage of labeled dark basal cells per total dark cell population was approximately 19% in the non-carcinogen-induced metaplasias and in the DMBA-induced metaplasias without atypia. In the atypical metaplasias induced by DMA this percentage increased to 26. On the basis of ultrastructural observations, five types of dark epithelial cells could be distinguished in the metaplastic epithelia. Each type of squamous metaplasia could thus be recognized by a determined numerical distribution of dark cells in the basal layer and a specific pattern of distribution of the ultrastructurally defined dark cell categories.

  16. [A case of squamous cell carcinoma of the hard palate in a patient with basal cell nevus syndrome].

    PubMed

    Matsuo, Mioko; Rikimaru, Fumihide; Higaki, Yuichiro; Masuda, Muneyuki

    2014-06-01

    Basal cell nevus syndrome is an autosomal dominant disorder characterized by the developmental malformations and its carcinogenic nature. This syndrome shows various symptoms of multiple cutaneous basal cell carcinoma, ketatocystic odontogenic tumors, and inborn abnormalities in the bone and skin. Although basal cell nevus syndrome itself is a rare disorder, we experienced a very rare case in which squamous cell carcinoma of the oral cavity developed, and not cutaneous basal cell carcinoma. Only 4 similar cases have been reported in the English literature. The patient was a 33-year-old woman. She was diagnosed as having squamous cell carcinoma of the hard palate, and basal cell nevus syndrome in our hospital. The patient underwent surgery for squamous cell carcinoma of the hard palate, with postoperative chemoradiothetrapy. Since patients with this syndrome tend to form basal cell carcinoma when exposed to X-ray radiation, we perform radiotherapy with care.

  17. A Case of Squamous Cell Carcinoma in the External Auditory Canal Previously Treated for Verrucous Carcinoma

    PubMed Central

    Nam, Soo Jung; Yang, Chan Joo

    2016-01-01

    Carcinoma in the external auditory canal (EAC) is a rare malignancy with an annual incidence of one per one million people, accounting for less than 0.2% of all head and neck cancers. The most common histopathological type of EAC cancer is squamous cell carcinoma. Verrucous carcinoma is a well-differentiated, low-grade variant of squamous cell carcinoma. It is a locally destructive, invasive, and slow growing tumor that rarely metastasizes. Verrucous carcinoma occurs predominantly in the oral cavity and larynx, and its occurrence in the EAC is extremely rare. In this report, we present a histologically confirmed case of verrucous carcinoma in the EAC and temporal bone, which for several years had been classified as epithelial hyperplasia. Two-and-a-half years after diagnosis of verrucous carcinoma, a recurrent mass was found and the lesion was then confirmed to be squamous cell carcinoma. PMID:27942606

  18. Oral focal fibrous hyperplasia and squamous cell papilloma treated with an erbium laser. Case presentation.

    PubMed

    Boj, J; Hernandez, M; Espasa, E; Espanya, A

    2014-01-01

    Mouth and oropharynx cancer constitute 5% of all malignancies; 95% of them are head and neck squamous cell carcinomas. Carcinogenesis is a multifactor process. Mutagenesis is also determined by the human papilloma virus which has recently been found to be etiologically associated with 20 to 25% of head and neck squamous cell carcinomas, mostly in the oropharinx. Focal fibrous hyperplasia of the connective tissue comes up as an answer to a chronic irritation in which a big amount of collagen can be found. As there exist certain clinical resemblance between squamous cell papilloma, fibrous focal hyperplasia and other mesenchimal tumors it is recommended to proceed, always, with removal and study. Two cases, one of an oral papilloma and another of a focal fibrous hyperplasia in pediatric patients, treated with an Er,Cr:YSGG laser wave length (mu) of 2780 nm are presented.

  19. Primary pure squamous cell carcinoma of the duodenum: a case report.

    PubMed

    Graur, Florin; Mois, Emil; Al Hajjar, Nadim

    2014-09-01

    Primary pure squamous cell carcinoma of the duodenum is a very rare type of duodenal neoplasm and is more likely to be presented as a metastatic tumor. The literature offers little information on this subject and includes very few articles and case reports. Laboratory tests, CT and ultrasound examinations, x-rays and immunohistochemical markers assisted us in making this rare diagnosis of primary squamous cell carcinoma of the duodenum in a 47 year old female patient, who presented with weight loss and melena. The 8 cm duodenal tumor with pancreas invasion was resected by a cephalic duodenopancreatectomy. The pathology examination revealed a primary duodenal squamous cell carcinoma moderately differentiated (G2), invasive in the head of the pancreas, with keratinization, stage II B (pT4N0MxL0V0R0). Positive outcome after surgery was highlighted, no recurrence being registered at the 6 month CT scan follow-up.

  20. Photodynamic therapy as a treatment for esophageal squamous cell carcinoma in a dog.

    PubMed

    Jacobs, T M; Rosen, G M

    2000-01-01

    Intrathoracic esophageal squamous cell carcinoma was diagnosed by endoscopy in an 11-year-old, castrated male Labrador retriever with signs of regurgitation and weight loss. Photodynamic therapy with photofrin was administered three times under endoscopic guidance over a two-month period. A partial response to photodynamic therapy was supported by a reduction in tumor size (noted on serial endoscopic examinations) and by a return to oral alimentation. The dog was euthanized due to recurrent regurgitation and aspiration pneumonia nine months after the onset of therapy. Necropsy revealed marked local invasiveness and regional lymph node metastasis of the esophageal squamous cell carcinoma in addition to pneumonia. The application of photodynamic therapy in the treatment of canine esophageal squamous cell carcinoma is discussed and compared with the human literature.

  1. Primary candidiasis and squamous cell carcinoma of the larynx: report of a case.

    PubMed

    Lee, Dong Hoon; Cho, Hyong Ho

    2013-02-01

    Primary candidiasis is rare and often confused with a pre-cancerous lesion, squamous cell carcinoma, or verrucous carcinoma. We report an extremely rare case of squamous cell carcinoma of the vocal cord following primary candidiasis. A 62-year-old man presented to our department reporting a 1-month history of hoarseness. He underwent laryngeal microscopic surgery for a presumptive diagnosis of glottic carcinoma. Histopathologic examination revealed candidiasis and scattered moderate dysplasia. He was treated with itraconazole for 4 weeks, and followed up without any recurrence of candidiasis. However, the 42-month follow-up examination revealed a focal whitish lesion on the right true vocal cord, and a repeat biopsy of this area revealed squamous cell carcinoma without evidence of candidiasis. The patient was treated with radiotherapy and remains well with no signs of tumor recurrence or candidiasis.

  2. NON-METASTATIC SQUAMOUS CELL CARCINOMA WITHIN A RATHKE’S CLEFT CYST

    PubMed Central

    O’Neill, Brian T.; Segkos, Konstantinos; Kasper, Ekkehard M.; Pallotta, Johanna A.

    2015-01-01

    Primary intracranial and sellar squamous cell carcinoma is an extremely rare entity, usually caused by malignant transformation of epidermoid cysts, or very rarely other non-malignant epithelial cysts. Malignant transformation of a Rathke’s cleft cyst has never been described. We present a 49-year-old male patient who presented with a 3-month history of progressive frontotemporal headaches. Imaging revealed a 1.2 cm cystic pituitary mass consistent with a hemorrhagic Rathke’s cleft cyst. The patient underwent trans-sphenoidal resection of the pituitary cyst, and pathologic analysis revealed a squamous cell carcinoma lining a Rathke’s cleft cyst. Extensive imaging and otorhinolaryngologic evaluation revealed no primary source for metastasis. We feel this represents the first case of a patient with a pituitary lesion in which presentation and MRI imaging were consistent with Rathke’s cleft cyst, yet histology revealed squamous cell carcinoma in situ. PMID:25715776

  3. Subcellular localization of the human papillomavirus 16 E7 oncoprotein in CaSki cells and its detection in cervical adenocarcinoma and adenocarcinoma in situ.

    PubMed

    Dreier, Kerstin; Scheiden, René; Lener, Barbara; Ehehalt, Daniela; Pircher, Haymo; Müller-Holzner, Elisabeth; Rostek, Ursula; Kaiser, Andreas; Fiedler, Marc; Ressler, Sigrun; Lechner, Stefan; Widschwendter, Andreas; Even, Jos; Capesius, Catherine; Jansen-Dürr, Pidder; Zwerschke, Werner

    2011-01-05

    E7 is the major oncoprotein of high-risk human papillomaviruses (HPV) which causes cervical cancer. To date E7 oncoproteins have not been investigated in cervical adenocarcinoma. In this study we generated a rabbit monoclonal anti-HPV-16 E7 antibody, RabMab42-3, which recognizes a conformational epitope in the E7 carboxy-terminal zinc-finger resulting in a strong increase in the sensitivity for the detection of cell-associated HPV-16 E7 protein relative to conventional polyclonal anti-HPV-16 E7 antibodies. Using RabMab42-3, we show that the subcellular localization of endogenous HPV-16 E7 oncoprotein varies during the cell cycle in cervical cancer cells. Moreover, we demonstrate for the first time that the HPV-16 E7 oncoprotein is abundantly expressed in cervical adenocarcinoma in situ and adenocarcinoma, suggesting an important role of HPV-16 E7 for the development of these tumors. Our findings suggest that the HPV-16 E7 oncoprotein could be a useful marker for the detection of cervical adenocarcinoma and their precursors.

  4. Basaloid squamous cell carcinoma with 'monster' cells: a mimic of pleomorphic basal cell carcinoma.

    PubMed

    Defty, Clare L; Segen, Joseph; Carter, Jonathan J; Ahmed, Imtiaz; Carr, Richard A

    2011-04-01

    Pleomorphic giant or 'monster' cells represent a well-recognized yet uncommon finding associated with basal cell carcinoma (BCC), usually of nodular type. We present a case of basaloid squamous cell carcinoma (basaloid SCC) with 'monster' cells that closely mimicked those described in pleomorphic nodular BCC. Clinically, the lesion presented as a fleshy, hyperkeratotic nodule in an 82-year-old woman. Histopathology revealed a basaloid lesion with lobulated borders and focal retraction artifact but a lack of prominent palisading or stromal mucin. There were areas of necrosis and small foci of keratinization. Striking bizarre monstrous pleomorphic nuclei were widely scattered throughout the lesion. Ber-EP4 immunohistochemistry proved to be negative and epithelial membrane antigen (EMA) expression was moderate to strong in 70% of the basaloid epithelium. Monster cells have not previously been highlighted in cutaneous SCC or in its uncommon cutaneous basaloid variant. The prognostic significance of monster cells is unknown but, given the relative paucity of keratinization in basaloid SCC, these lesions should probably be regarded as poorly differentiated. We have not previously encountered an SCC that so closely resembles nodular BCC with pleomorphic monster cells and believe that this is the first such report in the literature.

  5. Activation of Toll-like receptor 3 induces apoptosis of oral squamous carcinoma cells in vitro and in vivo.

    PubMed

    Luo, Qingqiong; Hu, Shuiqing; Yan, Ming; Sun, Zujun; Chen, Wantao; Chen, Fuxiang

    2012-08-01

    Toll-like receptors are well known as molecular sensors of pathogen-associated molecular patterns. They control activation of the innate immune response and subsequently shape the adaptive immune response. Recent publications have demonstrated that Toll-like receptors also play important roles in multiple human cancers, yet their function in oral squamous cell carcinoma remains unclear. In this study, we showed that both oral squamous cell carcinoma cell lines and tissues from oral squamous carcinoma patients express relatively high levels of Toll-like receptor 3. We also found that synthetic dsRNA-polyinosinic-polycytidilic acid, a Toll-like receptor 3 ligand, induced apoptosis of oral squamous carcinoma cells mainly via Toll-like receptor 3, through interferon-β production and activation of caspases 3 and 9. Moreover, in an oral squamous cell carcinoma xenograft mouse model, we demonstrated for the first time that activation of Toll-like receptor 3 inhibited oral squamous cell carcinoma tumor growth in vivo. Therefore, the direct proapoptotic activity of Toll-like receptor 3 in human oral squamous carcinoma cells may make this protein a viable therapeutic target in the treatment of oral squamous cell carcinoma.

  6. Stage IB adenocarcinoma of the cervix: metastatic potential and patterns of dissemination

    SciTech Connect

    Kjorstad, K.E.; Bond, B.

    1984-10-01

    The metastatic potential patterns of dissemination have been investigated in 150 patients with Stage 1B adenocarcinoma of the cervix treated during a 20-year period from 1956 to 1977. All cases with the exception of one were treated with a combination of intracavitary radium implants followed by a radical surgical procedure with pelvic lymph node dissection. It was found that the incidence of pelvic metastases and distant recurrences and the survival rates were the same as in previously published reports for squamous cell carcinomas treated in the same manner. In one respect adenocarcinomas showed a significant difference when compared with squamous cell cancers: The incidence of residual tumor in the hysterectomy specimens after intracavitary treatment was much higher (30% versus 11%). This is considered a strong argument for surgical treatment of patients with early stages of adenocarcinoma of the cervix.

  7. Cytotoxic effects of mistletoe (Viscum album L.) in head and neck squamous cell carcinoma cell lines.

    PubMed

    Klingbeil, Ma Fátima G; Xavier, Flávia C A; Sardinha, Luiz R; Severino, Patricia; Mathor, Monica B; Rodrigues, Rodrigo V; Pinto, Décio S

    2013-11-01

    Head and neck squamous cell carcinoma is a complex disease with several etiologic factors and different molecular changes that may trigger certain events; it is also globally one of the most common malignancies in this topography. Extracts from Viscum album L. (VA) (mistletoe) have been used as adjuvant therapies with promising results in several types of cancer, mainly in European countries. In vitro studies have demonstrated that various types of VA may have cytotoxicity in carcinoma cells, activating the apoptotic cascade or leading cells to necrosis. This study aimed to verify the effects of three types of VA extracts (Iscador Qu Spezial, Iscador P and Iscador M) in squamous cell carcinoma of the tongue cell lines SCC9 and SCC25, not previously studied. A concentration of 0.3 mg/ml (IC50) of the drugs induced apoptosis, affecting gene expression and protein levels of AKT, PTEN and CYCLIN D1. It was concluded that VA extracts have a cytotoxic effect on SCC9 and SCC25 cell lines, but while SCC9 cell line was more resistant to the action of the drugs, Iscador Qu Spezial and Iscador M have higher cytotoxic potential in both cell lines compared to Iscador P.

  8. EGFR Promoter Methylation, EGFR Mutation, and HPV Infection in Chinese Cervical Squamous Cell Carcinoma.

    PubMed

    Zhang, Wei; Jiang, Yinghao; Yu, Qingmiao; Qiang, Shaoying; Liang, Ping; Gao, Yane; Zhao, Xingye; Liu, Wenchao; Zhang, Ju

    2015-10-01

    Therapy strategy toward epidermal growth factor receptor (EGFR) inhibition in cervical cancer has been ongoing. EGFR promoter methylation status and EGFR tyrosine kinase inhibitor-sensitive mutations in cervical cancer may be significant for clinical outcome prediction using anti-EGFR treatment. In this study, EGFR tyrosine kinase inhibitor-sensitive mutations, EGFR exons 18, 19, and 21 mutations, were detected by sequencing in a total of 293 Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation status was detected by an EGFR asymmetric PCR and hybridization-fluorescence polarization assay and sequencing in 293 Chinese cervical squamous cell carcinoma tissue samples. High-risk human papillomavirus (HPV) genotypes in 293 Chinese cervical squamous cell carcinoma tissue samples were detected by an asymmetric GP5+/6+ PCR and hybridization-fluorescence polarization assay. No EGFR exons 18, 19, and 21 mutations were detected, EGFR promoter methylation status was identified in 98 samples, and HPV 16 infection was the first frequent HPV genotype. The methylated EGFR promoter was identified most frequently in cervical squamous cell carcinoma samples with HPV 16 infection (53.4%). Statistical significant difference of EGFR promoter methylation prevalence was found between HPV 16 and other HPV genotypes (P<0.01). This study suggested that there was no EGFR tyrosine kinase inhibitor-sensitive mutation in EGFR exons 18, 19, and 21 in Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation was common and it might be associated with HPV 16 infection in Chinese cervical squamous cell carcinoma. The results provided a novel understanding and an applicable pharmacogenomic tool for individualized management of cervical cancer patients.

  9. The role of constitutive and inducible processes in the response of human squamous cell carcinoma cell lines to ionizing radiation

    SciTech Connect

    Schwartz, J.L.

    1993-01-01

    The inherent radiation sensitivity of the cells within a tumor is thought to contribute to the success or failure of radiation therapy. In vitro studies have shown that radiation sensitivity differences in squamous cell carcinoma cell lines reflect alterations in DNA repair. These alterations result from constitutive changes in chromosome organization, not radiation-inducible processes. While inducible responses may play some role in the radiation response of tumor cells, there is no evidence for their involvement in inherent tumor cell radiosensitivity differences or in the success or failure of radiotherapy for squamous cell carcinomas.

  10. The role of constitutive and inducible processes in the response of human squamous cell carcinoma cell lines to ionizing radiation

    SciTech Connect

    Schwartz, J.L.

    1993-06-01

    The inherent radiation sensitivity of the cells within a tumor is thought to contribute to the success or failure of radiation therapy. In vitro studies have shown that radiation sensitivity differences in squamous cell carcinoma cell lines reflect alterations in DNA repair. These alterations result from constitutive changes in chromosome organization, not radiation-inducible processes. While inducible responses may play some role in the radiation response of tumor cells, there is no evidence for their involvement in inherent tumor cell radiosensitivity differences or in the success or failure of radiotherapy for squamous cell carcinomas.

  11. Isolation and characterization of cancer stem cells from primary head and neck squamous cell carcinoma tumors

    PubMed Central

    Kim, Hong S.; Pearson, Alexander T.; Nör, Jacques E.

    2017-01-01

    Summary Drug resistance remains a significant problem in the treatment of patients with head and neck squamous cell carcinoma (HNSCC). Recent reports showed that a sub-population of highly tumorigenic cells (cancer stem cells) is uniquely resistant to chemotherapy, and suggesting that these cells play an important role in the relapse of HNSCC. The development of methods for the isolation and culture of cancer stem cells is a key step to enable studies exploring the mechanisms underlying the role of these cells in chemoresistance. Here, we describe a method to isolate cancer stem cells from primary head and neck tumors and for the generation of orospheres, i.e. the culture of these cells in suspension in ultra-low attachment plates. PMID:26910078

  12. Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2/ad.

    PubMed

    Matsubara, Daisuke; Kanai, Yoshihiko; Ishikawa, Shumpei; Ohara, Shiori; Yoshimoto, Taichiro; Sakatani, Takashi; Oguni, Sachiko; Tamura, Tomoko; Kataoka, Hiroaki; Endo, Shunsuke; Murakami, Yoshinori; Aburatani, Hiroyuki; Fukayama, Masashi; Niki, Toshiro

    2012-12-01

    Rearranged during transfection (RET) fusions have been newly identified in approximately 1% of patients with primary lung tumors. However, patient-derived lung cancer cell lines harboring RET fusions have not yet been established or identified, and therefore, the effectiveness of an RET inhibitor on lung tumors with endogenous RET fusion has not yet been studied. In this study, we report identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC-2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib, among 39 non-small lung cancer cell lines. The xenograft tumor of LC-2/ad showed cribriform acinar structures, a morphologic feature of primary RET fusion-positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to analyze molecular functions of RET-fusion protein and its response to RET inhibitors.

  13. Current Treatment Algorithms for Patients with Metastatic Non-Small Cell, Non-Squamous Lung Cancer

    PubMed Central

    Melosky, Barbara

    2017-01-01

    The treatment paradigm for metastatic non-small cell, non-squamous lung cancer is continuously evolving due to new treatment options and our increasing knowledge of molecular signal pathways. As a result of treatments becoming more efficacious and more personalized, survival for selected groups of non-small cell lung cancer (NSCLC) patients is increasing. In this paper, three algorithms will be presented for treating patients with metastatic non-squamous, NSCLC. These include treatment algorithms for NSCLC patients whose tumors have EGFR mutations, ALK rearrangements, or wild-type/wild-type tumors. As the world of immunotherapy continues to evolve quickly, a future algorithm will also be presented. PMID:28373963

  14. The etiologic spectrum of head and neck squamous cell carcinoma in young patients

    PubMed Central

    Liu, Xin; Gao, Xiao-lei; Liang, Xin-hua; Tang, Ya-ling

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC), accounting for more than 80% in head and neck malignancies, kills thousands of people a year in the world. Despite most of the patients are more than 45, and the occurrences of head and neck cancer shows a decreasing trend; however, horribly, the incidences of the patients under 45 years old is steadily increasing. Hence, it's of vital importance to get more pathogen information about risk factors of HNSCC in children and young adults. This review outlines the etiologic spectrum of HNSCC, especially oral/oropharyngeal squamous cell carcinoma, in patients under 45 years of age. PMID:27528225

  15. Basaloid squamous cell carcinoma of oral cavity: Report of two cases

    PubMed Central

    Heera, R; Ayswarya, T; Padmakumar, SK; Ismayil, P

    2016-01-01

    Basaloid squamous cell carcinoma (BSCC) is an aggressive, high-grade, variant of squamous cell carcinoma (SCC), which is uncommon in the oral cavity but slightly more common in the oropharynx. We present two cases of BSCC, one arising in the floor of the mouth and the other arising on the lateral border of the tongue. The diagnosis of this subtype of SCC is important owing to its particular behavior, with an aggressive course, a high incidence of local recurrence, regional lymph node metastases and mortality rate. PMID:27721627

  16. Pregnancy following vulvar squamous cell carcinoma: a report of two cases.

    PubMed

    Palmer, Julia E; Tidy, John A

    2009-12-01

    Pregnancy following squamous cell carcinoma of the vulvar is rare. Its rarity is reflected by a paucity of cases reported in the literature. We report two cases of pregnancy following diagnosis and treatment for vulvar squamous cell carcinoma, and review eleven prior reported cases. In successfully treated vulvar cancer subsequent pregnancy is not shown to increase the risk of disease recurrence, and there appears to be no deleterious effects during the antenatal period. It is possible, when considering prior reports, that prior vulvectomy may increase the likelihood of delivery by caesarean section, though modifications in the surgical management of vulvar carcinoma may have decreased this risk.

  17. Nanomechanical clues from morphologically normal cervical squamous cells could improve cervical cancer screening

    NASA Astrophysics Data System (ADS)

    Geng, Li; Feng, Jiantao; Sun, Quanmei; Liu, Jing; Hua, Wenda; Li, Jing; Ao, Zhuo; You, Ke; Guo, Yanli; Liao, Fulong; Zhang, Youyi; Guo, Hongyan; Han, Jinsong; Xiong, Guangwu; Zhang, Lufang; Han, Dong

    2015-09-01

    Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis.Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03662c

  18. A Case of Squamous Cell Carcinoma of the Renal Pelvis in association with Schistosoma hematobium.

    PubMed

    Khan, Muhammad A A; Kar, Ashok; Walker, Marjorie M; Lloyd, Jo; Vale, Justin A; Mayer, Erik K

    2012-01-01

    A 72-year-old man presented with painless frank haematuria. Investigations included intravenous urogram and abdominal/pelvic CT which revealed a marked focal thickening of the wall of the inferior aspect of the left renal pelvis extending into the lower pole calyx and into the pelviureteric junction resulting in left hydronephrosis. Urine cytology demonstrated clusters of malignant keratinised squamous cells and schistosome ova. He underwent left laparoscopic radical nephroureterectomy and histology revealed moderately differentiated keratinising squamous cell carcinoma in the renal pelvis.

  19. Management of a cutaneous squamous cell carcinoma in an American flamingo (Phoenicopterus ruber).

    PubMed

    Abu, Jalila; Wünschmann, Arno; Redig, Patrick T; Feeney, Daniel

    2009-03-01

    A 32-year-old female American flamingo (Phoenicopterus ruber) was presented with a squamous cell carcinoma of the middle digit of the right foot. No clinical, hematologic, or radiologic evidence of metastasis was present. Salvage amputation of the digit resulted in complete cure, whereas previous electrosurgery and radiation therapy were unsuccessful. Three years later, another squamous cell carcinoma was diagnosed in the middle digit of the left foot. The digit was also amputated. Seven months after the second amputation, the bird did not have any recurrence or signs of metastasis.

  20. Squamous Cell Carcinoma of the Oropharynx and Esophagus with Pulmonary Metastasis in a Backyard Laying Hen.

    PubMed

    Laura, Nordio; Marta, Vascellari; Giacomo, Berto; Luca, Bano

    2016-09-01

    A backyard laying hen exhibiting muscular atrophy, dyspnea, and absence of egg production was analyzed for diagnostic insights. Gross findings revealed the presence of a large ulcerated mass with irregular edges involving the caudal part of the oropharynx and the cranial part of the esophagus, occluding the lumen of the esophagus and compressing the trachea. Small nodular lesions were detected also in the lungs. Histologically, both esophageal and pulmonary masses were characterized by nests of pleomorphic epithelial cells with squamous differentiation. The diagnosis was of squamous cell carcinoma of the esophagus with the uncommon feature of pulmonary metastasis.

  1. Penile squamous cell carcinoma: a review of the literature and case report treated with Mohs micrographic surgery*

    PubMed Central

    Marchionne, Elizabeth; Perez, Caroline; Hui, Andrea; Khachemoune, Amor

    2017-01-01

    The majority of penile carcinoma is squamous cell carcinoma. Although uncommon in the United States, it represents a larger proportion of cancers in the underdeveloped world. Invasive squamous cell carcinoma may arise from precursor lesions or de novo , and has been associated with lack of circumcision and HPV infection. Early diagnosis is imperative as lymphatic spread is associated with a poor prognosis. Radical surgical treatment is no longer the mainstay, and penile sparing treatments now are often used, including Mohs micrographic surgery. Therapeutic decisions should be made with regard to the size and location of the tumor, as well as the functional desires of the patient. It is critical for the dermatologist to be familiar with the evaluation, grading/staging, and treatment advances of penile squamous cell carcinoma. Herein, we present a review of the literature regarding penile squamous cell carcinoma, as well as a case report of invasive squamous cell carcinoma treated with Mohs micrographic surgery. PMID:28225964

  2. Single-cell analyses of transcriptional heterogeneity in squamous cell carcinoma of urinary bladder

    PubMed Central

    Hou, Yong; Xu, Liqin; Li, Weidong; Zou, Zhihui; Liu, Chunxiao; Xu, Abai; Wu, Song

    2016-01-01

    Cell-to-cell expression heterogeneity within a single tumor is a common phenotype among various cancer types including squamous cell carcinoma. To further study the fundamentals and importance of heterogeneity of cell functions and its potential mechanisms, we performed single-cell RNA-seq (scRNA-seq) on human squamous cell carcinoma of the bladder (SCCB) and its corresponding physiologically normal epithelia. Extensive differentially expressed genes were uncovered by comparing cancer and normal single cells, which were preferentially enriched in cancer-correlated pathways, such as p53 signaling and bladder cancer pathway. Furthermore, the most diversely expressed genes were particularly enriched in MAPK signaling pathway, such as CACNG4, CACNA1E and CACNA1H, which involve in cancer evolution and heterogeneity formation. Co-expression network and hub-gene analyses revealed several remarkable “hub genes” of each regulatory module. Some of them are cancer related, such as POU2F3, NKD1 and CYP2C8, while LINC00189, GCC2 and OR9Q1 genes are rarely reported in human diseases. The genes within an interesting module are highly correlated with others, which could be treated as potential targets for SCCB patients. Our findings have fundamental implications for SCCB biology and therapeutic strategies. PMID:27602771

  3. CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma

    SciTech Connect

    Zhang, Heyu; Nan, Xu; Li, Xuefen; Chen, Yan; Zhang, Jianyun; Sun, Lisha; Han, Wenlin; Li, Tiejun

    2014-05-02

    Highlights: • Down-regulation of CMTM5 expression in OSCC tissues was found. • The promoter methylation status of CMTM5 was measured. • CMTM5-v1 inhibited cell proliferation and migration and induced apoptosis. • CMTM5 might act as a putative tumor suppressor gene in OSCC. - Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma.

  4. Changes in gene expression of neo-squamous mucosa after endoscopic treatment for dysplastic Barrett’s esophagus and intramucosal adenocarcinoma

    PubMed Central

    Levert-Mignon, Angelique; Bourke, Michael J; Lord, Sarah J; Taylor, Andrew C; Wettstein, Antony R; Edwards, Melanie; Botelho, Natalia K; Sonson, Rebecca; Jayasekera, Chatura; Fisher, Oliver M; Thomas, Melissa L; Macrae, Finlay; Hussey, Damian J; Watson, David I

    2016-01-01

    Background Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). Objective The purpose of this study was to investigate the molecular effects of endotherapy. Methods mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. Results Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. Conclusion Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more “normal” profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.

  5. Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

    PubMed

    Ahmed, Firoj; Toume, Kazufumi; Ohtsuki, Takashi; Rahman, Mahmudur; Sadhu, Samir Kumar; Ishibashi, Masami

    2011-01-01

    Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations.

  6. The Spatial Predilection for Early Esophageal Squamous Cell Neoplasia

    PubMed Central

    Wang, Wen-Lun; Chang, I.-Wei; Chen, Chien-Chuan; Chang, Chi-Yang; Lin, Jaw-Town; Mo, Lein-Ray; Wang, Hsiu-Po; Lee, Ching-Tai

    2016-01-01

    Abstract Early esophageal squamous cell neoplasias (ESCNs) are easily missed with conventional white-light endoscopy. This study aimed to assess whether early ESCNs have a spatial predilection and the patterns of recurrence after endoscopic treatment. We analyzed the circumferential and longitudinal location of early ESCNs, as well as their correlations with exposure to carcinogens in a cohort of 162 subjects with 248 early ESCNs; 219 of which were identified by screening and 29 by surveillance endoscopy. The circumferential location was identified using a clock-face orientation, and the longitudinal location was identified according to the distance from the incisor. The most common circumferential and longitudinal distributions of the early ESCNs were found in the 6 to 9 o’clock quadrant (38.5%) and at 26 to 30 cm from the incisor (41.3%), respectively. A total of 163 lesions (75%) were located in the lower hemisphere arc, and 149 (68.4%) were located at 26 to 35 cm from the incisor. One hundred eleven (51%) early ESCNs were centered within the “hot zone” (i.e., lower hemisphere arc of the esophagus at 26 to 35 cm from the incisor), which comprised 20% of the esophageal area. Exposure to alcohol, betel nut, or cigarette was risk factors for the development of early ESCNs in the lower hemisphere. After complete endoscopic treatment, the mean annual incidence of metachronous tumors was 10%. In addition, 43% of the metachronous recurrent neoplasias developed within the “hot zone.” Cox regression analysis revealed that the index tumor within the hot zone (hazard ratio [HR]: 3.19; 95% confidence interval [CI]: 1.17–8.68; P = 0.02) and the presence of numerous Lugol-voiding lesions in the esophageal background mucosa were independent predictors for metachronous recurrence (HR: 4.61; 95% CI: 1.36–15.56; P = 0.01). We identified a hot zone that may be used to enhance the detection of early ESCNs during endoscopic screening and surveillance

  7. FGFR as potential target in the treatment of squamous non small cell lung cancer.

    PubMed

    Tiseo, Marcello; Gelsomino, Francesco; Alfieri, Roberta; Cavazzoni, Andrea; Bozzetti, Cecilia; De Giorgi, Anna Maria; Petronini, Pier Giorgio; Ardizzoni, Andrea

    2015-06-01

    To date therapeutic options for squamous cell lung cancer patients remain scarce because no druggable targets have been identified so far. Aberrant signaling by FGFs (fibroblast growth factors) and FGFRs (fibroblast growth factors receptors) has been implicated in several human cancers and, particularly, in squamous non-small cell lung cancer (NSCLC). FGFR gene amplifications, somatic missense mutations, chromosomal translocations are the most frequent mechanisms able to induce aberrant activation of this pathway. Data from literature have established that the presence of an aberrant FGFR signaling has to be considered a possible negative prognostic factor but predictive of potential sensitivity to FGFR inhibitors. In the last years, clinical research efforts allowed to identify and evaluate promising FGFR inhibitors, such as monoclonal antibodies, ligand traps, non-selective or selective tyrosine kinase inhibitors. This review summarizes the current knowledge about FGFR alterations in NSCLC and the relative inhibitors in development, in particular in squamous NSCLC.

  8. Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

    SciTech Connect

    Dudás, József; Fullár, Alexandra; Romani, Angela; Pritz, Christian; Kovalszky, Ilona; Hans Schartinger, Volker; Mathias Sprinzl, Georg; Riechelmann, Herbert

    2013-04-01

    Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells.

  9. Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma.

    PubMed

    Liu, Yao; Chen, Hao; Sun, Zheng; Chen, Xiaoxin

    2015-06-01

    Alcohol drinking is a major etiological factor of oro-esophageal squamous cell carcinoma (OESCC). Both local and systemic effects of ethanol may promote carcinogenesis, especially among chronic alcoholics. However, molecular mechanisms of ethanol-associated OESCC are still not well understood. In this review, we summarize current understandings and propose three mechanisms of ethanol-associated OESCC: (1) Disturbance of systemic metabolism of nutrients: during ethanol metabolism in the liver, systemic metabolism of retinoids, zinc, iron and methyl groups is altered. These nutrients are known to be associated with the development of OESCC. (2) Disturbance of redox metabolism in squamous epithelial cells: when ethanol is metabolized in oro-esophageal squamous epithelial cells, reactive oxygen species are generated and produce oxidative damage. Meanwhile, ethanol may also disturb fatty-acid metabolism in these cells. (3) Disturbance of signaling pathways in squamous epithelial cells: due to its physico-chemical properties, ethanol changes cell membrane fluidity and shape, and may thus impact multiple signaling pathways. Advanced molecular techniques in genomics, epigenomics, metabolomics and microbiomics will help us elucidate how ethanol promotes OESCC.

  10. Establishment of an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtaining laryngocarcinoma cells with high metastatic potential.

    PubMed

    Chen, L W; Wang, J L; Zhang, L Y; Yang, S M; Li, C S; Yu, N; Zhao W, J D; Zhao, L D; Li, K; Liu, M B; Zhai, S Q

    2013-01-01

    To establish an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtain laryngocarcinoma cells with high metastatic potential, laryngeal squamous cell carcinoma cell line HEP-2 in logarithmic phase were inoculated under the lingual margin mucosa of nude mice. HEP-2 cells metastasized to the cervical lymph nodes were isolated, cultured, and re-inoculated under the lingual margin mucosa of nude mice twice. The tumor formation in the tongue and in the cervical lymph nodes was confirmed by pathological examination. Carcinoma cells' ability of invasion and migration was detected by transwell assay. Human specific Alu sequences were detected by PCR, which indicated that the tumor cells originated from human laryngeal squamous cell carcinoma cell line HEP-2. Finally, an animal model of spontaneous lymph node metastasis of laryngeal squamous cell carcinoma was successfully established. Laryngeal squamous cell carcinoma cells with high metastatic potential to lymph nodes were obtained through repeated inoculations. .

  11. Cell death in cancer therapy of lung adenocarcinoma.

    PubMed

    Zagryazhskaya, Anna; Gyuraszova, Katarina; Zhivotovsky, Boris

    2015-01-01

    Lung cancer is the main cause of all cancer-related deaths in the world, with lung adenocarcinoma (ADC) being the most common subtype of this fatal disease. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors. This is particularly important for the successful development of new cancer therapy approaches. The high resistance of lung ADC to conventional radio- and chemotherapies represents a major challenge to treatment effectiveness. Here we discuss recent progress in understanding the mechanisms of ADC's broad resistance to treatment and its possible therapeutic implications. A number of driving oncogenic alterations were identified in a subset of lung ADCs, making them suitable for targeted therapies directed towards specific cancer-associated molecular changes. In addition, we discuss the molecular aberrations common in lung ADC that are currently being exploited or are potentially important for targeted cancer therapy, as well as limitations of this type of therapy. Furthermore, we highlight possible treatment modalities that hold promise for overcoming resistance to targeted therapies as well as alternative treatment options such as immunotherapies that are potentially promising for improving the clinical outcome of lung ADC patients.

  12. Genetic variants at 8q24 are associated with risk of esophageal squamous cell carcinoma in a Chinese population

    PubMed Central

    Dai, Ningbin; Zheng, Mingfeng; Wang, Cheng; Ji, Yong; Du, Jiangbo; Zhu, Chen; He, Yisha; Zhu, Meng; Zhu, Xun; Sun, Min; Dai, Juncheng; Ma, Hongxia; Chen, Jingyu; Hu, Zhibin; Gu, Haiyong; Jin, Guangfu; Shen, Hongbing

    2014-01-01

    Esophageal cancer and gastric cancer have shared risk factors and inherited susceptibility. Recent genome-wide association studies have identified multiple genetic loci associated with gastric cancer risk, which may also involve in the development of esophageal cancer. Herein, we evaluated the relationship of gastric cancer risk-related variants at 1q22, 3q13.3, 5p13.1, and 8q24 with the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population with a case–control study (2139 cases and 2273 controls). We found that the T allele of rs2294008, an intronic variant of the PSCA gene at 8q24 that was previously associated with an increased risk of gastric cancer, was inversely associated with a decreased risk of ESCC (odds ratio = 0.90; 95% confidence interval, 0.81–0.99; P = 0.034). Of interest, the association of rs2294008 with ESCC was consistent with that observed in esophageal adenocarcinoma and ESCC in Caucasian populations. However, no significant associations were observed for the other three variants at 1q22 (rs4072037), 3q13.31 (rs9841504), and 5p13.1 (rs13361707). Our findings suggest that the susceptibility locus of PSCA at 8q24 may be a double-edged sword, as modulator between the carcinogenesis processes of stomach and esophagus. PMID:24654646

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

    PubMed Central

    Esteban, Francisco; Ruiz-Cabello, Francisco; Gonzalez-Moles, Miguel Angel; Lopez-Gonzalez, Miguel Angel; Funez, Rafael; Redondo, Maximino

    2012-01-01

    Langerhans cells (LCs) may be involved in the immunosurveillance against tumors as antigen-presenting cells. Our objective has been to determine the relevance of LC in progression of larynx squamous cell carcinomas and their relationship with different subpopulations of tumor-infiltrating cells. LCs were investigated by immunohistochemical methods using anti-CD1 antibody. LCs were detected in most of the primary tumors studied (44 out of 50) and also in metastases (6 out of 10) and recurrences (2 out of 3), but we did not find any statistical association between number of LCs and clinical-pathological parameters or survival. However, the number of LCs was increased in patients with evident infiltration of lymphocytes, mainly cytotoxic T cells. We can conclude that although LCs did not show clinical utility as prognostic marker, they may play a role in releasing an active immune response in larynx carcinomas, according to their ability to present antigens to sensitized T cells. PMID:22481933

  14. Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma cell line.

    PubMed

    Wang, Yi; Jiang, Yang; Ikeda, Jun-Ichiro; Tian, Tian; Sato, Atsushi; Ohtsu, Hiroshi; Morii, Eiichi

    2014-10-01

    Cancer-initiating cells (CICs) are a limited number of cells that are essential for maintenance, recurrence, and metastasis of tumors. Aldehyde dehydrogenase 1 (ALDH1) has been recognized as a marker of CICs. We previously reported that ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis, and that ALDH1 high population was more tumorigenic, invasive, and resistant to apoptosis than ALDH1 low population. Histamine plays a critical role in cancer cell proliferation, migration, and invasion. Here, we examined the effect of histamine on ALDH1 expression in endometrioid adenocarcinoma cell line. The addition of histamine increased ALDH1 high population, which was consistent with the result that histamine enhanced the invasive ability and the resistance to anticancer drug. Among 4 types of histamine receptors, histamine H1 and H2 receptor (H1R and H2R) were expressed in endometrioid adenocarcinoma cell line. The addition of H1R agonist but not H2R agonist increased ALDH1. The antagonist H1R but not H2R inhibited the effect of histamine on ALDH1 expression. These results indicated that histamine increased the expression of ALDH1 via H1R but not H2R. These findings may provide the evidence for exploring a new strategy to suppress CICs by inhibiting ALDH1 expression with histamine.

  15. Assessment of cytotoxicity of Portulaca oleracea Linn. against human colon adenocarcinoma and vero cell line

    PubMed Central

    Mali, Prashant Y.

    2015-01-01

    Background: Portulaca oleracea Linn. (Portulacaceae) is commonly known as purslane in English. In traditional system it is used to cure diarrhea, dysentery, leprosy, ulcers, asthma, and piles, reduce small tumors and inflammations. Aim: To assess cytotoxic potential of chloroform extract of P. oleracea whole plant against human colon adenocarcinoma (HCT-15) and normal (Vero) cell line. Materials and Methods: Characterization of chloroform extract of P. oleracea by Fourier transform infrared (FTIR) spectroscopy was performed. Cytotoxicity (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay was used for assessment of cytotoxic potential of chloroform extract of P. oleracea. The concentrations of 1000–0.05 μg/ml were used in the experiment. Doxorubicin was considered as standard reference drug. Results: FTIR spectrum showed the peak at 1019.52 and 1396.21 center. The 50% cell growth inhibition (IC50) of chloroform extract of P. oleracea and doxorubicin was 1132.02 μg/ml and 460.13 μg/ml against human colon adenocarcinoma and 767.60 μg/ml and 2392.71 μg/ml against Vero cell line, respectively. Conclusion: Chloroform extract of P. oleracea whole plant was less efficient or does not have cytotoxic activity against human colon adenocarcinoma cell line. It was not safe to normal Vero cell line. But, there is a need to isolate, identify, and confirm the phytoconstituents present in extract by sophisticated analytical techniques. PMID:27833374

  16. Mammalian mediator 19 mediates H1299 lung adenocarcinoma cell clone conformation, growth, and metastasis.

    PubMed

    Xu, Lu-Lu; Guo, Shu-Liang; Ma, Su-Ren; Luo, Yong-Ai

    2012-01-01

    Mammalian mediator (MED) is a multi-protein coactivator that has been identified by several research groups. The involvement of the MED complex subunit 19 (MED 19) in the metastasis of lung adenocarcinoma cell line (H1299), which expresses the MED 19 subunit, was here investigated. When MED 19 expression was decreased by RNA interference H1299 cells demonstrated reduced clone formation, arrest in the S phase of the cell cycle, and lowered metastatic capacity. Thus, MED 19 appears to play important roles in the biological behavior of non-small cell lung carcinoma cells. These findings may be important for the development of novel lung carcinoma treatments.

  17. Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma

    PubMed Central

    Chahal, Harvind S.; Lin, Yuan; Ransohoff, Katherine J.; Hinds, David A.; Wu, Wenting; Dai, Hong-Ji; Qureshi, Abrar A.; Li, Wen-Qing; Kraft, Peter; Tang, Jean Y.; Han, Jiali; Sarin, Kavita Y.

    2016-01-01

    Cutaneous squamous cell carcinoma represents the second most common cutaneous malignancy, affecting 7–11% of Caucasians in the United States. The genetic determinants of susceptibility to cutaneous squamous cell carcinoma remain largely unknown. Here we report the results of a two-stage genome-wide association study of cutaneous squamous cell carcinoma, totalling 7,404 cases and 292,076 controls. Eleven loci reached genome-wide significance (P<5 × 10−8) including seven previously confirmed pigmentation-related loci: MC1R, ASIP, TYR, SLC45A2, OCA2, IRF4 and BNC2. We identify an additional four susceptibility loci: 11q23.3 CADM1, a metastasis suppressor gene involved in modifying tumour interaction with cell-mediated immunity; 2p22.3; 7p21.1 AHR, the dioxin receptor involved in anti-apoptotic pathways and melanoma progression; and 9q34.3 SEC16A, a putative oncogene with roles in secretion and cellular proliferation. These susceptibility loci provide deeper insight into the pathogenesis of squamous cell carcinoma. PMID:27424798

  18. PVM/MA-shelled selol nanocapsules promote cell cycle arrest in A549 lung adenocarcinoma cells

    PubMed Central

    2014-01-01

    Background Selol is an oily mixture of selenitetriacylglycerides that was obtained as a semi-synthetic compound containing selenite. Selol is effective against cancerous cells and less toxic to normal cells compared with inorganic forms of selenite. However, Selol’s hydrophobicity hinders its administration in vivo. Therefore, the present study aimed to produce a formulation of Selol nanocapsules (SPN) and to test its effectiveness against pulmonary adenocarcinoma cells (A549). Results Nanocapsules were produced through an interfacial nanoprecipitation method. The polymer shell was composed of poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) copolymer. The obtained nanocapsules were monodisperse and stable. Both free Selol (S) and SPN reduced the viability of A549 cells, whereas S induced a greater reduction in non-tumor cell viability than SPN. The suppressor effect of SPN was primarily associated to the G2/M arrest of the cell cycle, as was corroborated by the down-regulations of the CCNB1 and CDC25C genes. Apoptosis and necrosis were induced by Selol in a discrete percentage of A549 cells. SPN also increased the production of reactive oxygen species, leading to oxidative cellular damage and to the overexpression of the GPX1, CYP1A1, BAX and BCL2 genes. Conclusions This study presents a stable formulation of PVM/MA-shelled Selol nanocapsules and provides the first demonstration that Selol promotes G2/M arrest in cancerous cells. PMID:25149827

  19. A Rare Case of an Adult with Untreated Bladder Exstrophy Presenting with Signet-Ring Cell Adenocarcinoma of Urinary Bladder

    PubMed Central

    Kumar, Vikash; Kasat, Gaurav; Sawant, Ajit

    2016-01-01

    Untreated bladder exstrophy in an adult is rare, as the defect is obvious and primary reconstruction is usually done in infancy. There are less than 90 reported cases of primary adenocarcinoma in an untreated bladder exstrophy in literature and only two such case reports from India. Of these, only one case was of signet-ring cell type of mucinous adenocarcinoma. Here we report the second case of signet-ring cell adenocarcinoma in a 63 year old male with untreated bladder exstrophy (oldest patient in literature), to highlight the extreme rarity, yet distinct possibility and challenges faced in surgical management of such cases. PMID:28050437

  20. COX-2 mRNA expression in esophageal squamous cell carcinoma (ESCC) and effect by NSAID.

    PubMed

    Liu, X; Li, P; Zhang, S-T; You, H; Jia, J-D; Yu, Z-L

    2008-01-01

    To investigate cyclooxygenase-2 (COX-2) mRNA expression in human esophageal squamous cell carcinoma and the effect of a non-steroidal anti-inflammatory drug (NSAID) on it, in order to explore the mechanism of COX-2 in esophageal squamous cell carcinoma (ESCC) carcinogenesis and the ability of NSAID to prevent or treat ESCC. Frozen specimens of human ESCC and adjacent normal esophageal squamous epithelium pairs (n = 22) were examined for COX-2 mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR). After incubation with aspirin (a non-selective COX inhibitor) or Nimesulide (a selective COX-2 inhibitor), the proliferation status of two human esophageal squamous cancer cell lines, EC-9706 and EC-109, was quantified by 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide assay. The expression of COX-2 mRNA in these cells was detected by RT-PCR. COX-2 mRNA was expressed in 12 of 22 (54.5%) ESCC tissue samples, but it was undetectable in all the specimens of adjacent normal esophageal squamous epithelium COX-2 mRNA expression. Both aspirin (5-20 mmol/L) and Nimesulide (0.1-0.8 mmol/L) inhibited EC-9706 cell line proliferation and suppressed its COX-2 mRNA expression dose-dependently. However, only aspirin (5-20 mmol/L) could inhibit proliferation in the EC-109 cell line and suppress COX-2 mRNA expression. Nimesulide (0.1-0.8 mmol/L) could neither inhibit EC-109 cell growth nor suppress COX-2 mRNA expression. COX-2 mRNA expression is a frequent phenomenon in human ESCC tissue samples and plays an important role in the carcinogenesis of ESCC. NSAID may be useful in the chemoprevention and therapy of human ESCC and its effects are likely to be mediated by modulating COX-2 activity.

  1. Oral squamous cell carcinoma in a 7-year-old Brazilian boy.

    PubMed

    Ribeiro, C M B; Gueiros, L A M; Leon, J E; do Carmo Abreu e Lima, M; de Almeida, O P; Leão, J C

    2011-09-01

    Squamous cell carcinomas (SCCs) are amongst the commonest malignancies in adults but in paediatric patients are exceptionally rare, particularly those involving the oral mucosa. The aim of the present report is to describe the features of a gingival well-differentiated SCC in a 7-year-old Brazilian boy. Immunostaining for p53, Ki-67 and Mcm2 showed increased cellular proliferation compared with normal epithelium. In situ hybridization failed to identify human papilloma virus infection. Correct diagnosis of well-differentiated squamous carcinoma can be difficult in children and differentiation from pseudoepitheliomatous hyperplasia is essential to establish proper treatment.

  2. Nivolumab: a review in advanced squamous non-small cell lung cancer.

    PubMed

    Keating, Gillian M

    2015-11-01

    Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy. In the pivotal CheckMate 017 trial, intravenous nivolumab 3 mg/kg every 2 weeks was associated with significantly better overall survival and progression-free survival and a significantly higher overall response rate than intravenous docetaxel in the second-line treatment of advanced, squamous NSCLC. Nivolumab was also better tolerated than docetaxel in CheckMate 017, and its adverse event profile (which included immune-mediated adverse events) was manageable. In conclusion, nivolumab represents an important advance in previously-treated, advanced, squamous NSCLC.

  3. Resistance of human squamous carcinoma cells to transforming growth factor beta 1 is a recessive trait.

    PubMed Central

    Reiss, M; Muñoz-Antonia, T; Cowan, J M; Wilkins, P C; Zhou, Z L; Vellucci, V F

    1993-01-01

    Because most human squamous carcinoma cell lines of the aerodigestive and genital tracts are refractory to the antiproliferative action of transforming growth factor beta 1 (TGF beta 1) in vitro, we have begun to identify the causes for resistance of squamous carcinoma cell lines to TGF beta 1 by using somatic cell genetics. Two stable hybrid cell lines (FaDu-HKc.1 and FaDu-HKc.2) were obtained by fusing a TGF beta 1-resistant human squamous carcinoma cell line, FaDu-HygR, with a human papilloma virus 16-immortalized, TGF beta 1-sensitive, human foreskin keratinocyte cell line, HKc-neoR. Whereas TGF beta 1 did not inhibit DNA synthesis in parental FaDu-HygR cells, it reduced DNA synthetic activity of HKc-neoR, FaDu-HKc.1, and FaDu-HKc.2 cells by 75-85% (IC50, 2-5 pM). Although squamous carcinoma cells express lower than normal levels of TGF beta 1 type II receptors on their cell surface, TGF beta 1 type II receptor mRNA was detected in all four cell lines. Recessive genes involved in TGF beta 1 signaling may be localized to the distal portion of chromosome 18q, as this was the sole chromosomal region of homozygous deletion in parental FaDu-HygR cells. Furthermore, our previous observation that mutant p53 decreases sensitivity of keratinocytes to TGF beta 1 was supported by the finding that the level of the mutant p53 protein expressed by the hybrid cell lines was greatly reduced. In summary, TGF beta 1 resistance of FaDu cells appears to be recessive and is presumably due to the loss of one or more post-receptor elements of the signaling pathway. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8327510

  4. Apoptotic Index and Proliferative Index in Premalignant and Malignant Squamous Cell Lesions of the Oral Cavity

    PubMed Central

    Viswanathan, Vidya; Juluri, Ravichandra; Goel, Seema; Madan, Jyotsna; Mitra, Subir K; Gopalakrishnan, Dharmarajan

    2015-01-01

    Background: Oral squamous cell lesions are most commonly diagnosed lesions in India. Both premalignant and malignant lesions are frequently encountered. In this study, we evaluated the role and significance of apoptotic indices (AI) and proliferative indices (PI) in premalignant and malignant squamous cell lesions of the oral cavity. Materials and Methods: A total of 62 histologically proven cases of premalignant and malignant oral squamous cell lesions were analyzed. The biopsies were stained with hematoxylin and eosin and also with monoclonal antibody Ki-67. AI and PI were assessed using a light microscope. Results: AI was found to increase gradually from normal to dysplasia to carcinoma. The highest AI was seen in well-differentiated squamous cell carcinomas (SCCs). PI also was found to increase significantly from normal to dysplasia to carcinoma. The highest PI was seen in poorly differentiated SCC. Conclusion: AI in conjunction with the PI offers an accurate idea as to the nature and course of the lesion and may help to plan timely surgical intervention that results in better clinical prognosis and outcome. PMID:25709366

  5. Efficacy of oral zinc therapy in epidermodysplasia verruciformis with squamous cell carcinoma.

    PubMed

    Sharma, Sudhanshu; Barman, Krishna Deb; Sarkar, Rashmi; Manjhi, Mukesh; Garg, Vijay Kumar

    2014-01-01

    Epidermodysplasia verruciformis (EV) is a rare, inherited disorder that predisposes patients to widespread human papillomavirus (HPV) infection and cutaneous squamous cell carcinomas. There is still no definitive therapeutic modality for EV. A 24 year old male patient with EV was treated with oral zinc sulphate, one of the cheapest and safe immuno-modulator available as therapeutic agent with satisfactory result.

  6. Evaluation of glutathione S-transferase activity in human buccal epithelial dysplasias and squamous cell carcinomas.

    PubMed

    Chen, Y K; Lin, L M

    1997-06-01

    Glutathione S-transferase (GST) activity and amount of GST alpha, mu and pi isoforms were measured in 40 patients with histopathologically confirmed oral epithelial dysplasia (OED) and squamous cell carcinoma of buccal mucosa. The results were compared with those of normal mucosa in an equal number of age- and sex-matched healthy controls. Mean total GST activities were significantly elevated from normal buccal mucosa for mild OED, moderate OED, severe OED and squamous cell carcinoma. GST activity of value approximating 100 nmol/min/mg distinguished between normal and dysplasia, and of value about 400 nmol/min/mg delineated between dysplasia and squamous cell carcinoma were observed. GST pi was the predominant class in both the diseased and normal buccal mucosa examined. This class pi GST was present at an intracellular concentration, which was significantly higher in diseased buccal mucosa than in normal buccal mucosa. These results indicated that pi class GST was the major form of this enzyme in the cytosolic fraction of oral mucosa. The severity of OED related to squamous cell carcinoma development seemed to increase concomitantly with an increase in the level of this enzyme. Further studies will validate the role of GST pi estimation in predicting the potential malignancy of OED.

  7. Successful treatment of oral squamous cell carcinoma with intralesional fluorouracil in a Malayan tapir (Tapirus indicus).

    PubMed

    Miller, C L; Templeton, R S; Karpinski, L

    2000-06-01

    An oral mass was observed in a Malayan tapir (Tapirus indicus). Squamous cell carcinoma was diagnosed by histologic examination of a biopsy specimen. A series of intralesional injections using fluorouracil resulted in complete regression of the neoplasm with no recognized adverse effects.

  8. Squamous cell carcinoma of the nasal planum in cats and dogs.

    PubMed

    Thomson, Maurine

    2007-05-01

    The purpose of this article is to review the therapeutic options available for the treatment of squamous cell carcinoma of the nasal planum in cats and dogs. The techniques of complete and partial nasal planum resection in the cat are described in detail. Surgical treatment offers the greatest chance of cure, although several options are available for early, less invasive lesions.

  9. Squamous cell carcinoma of the eyelid masquerading as 'malignant' ophthalmopathy of Graves's disease.

    PubMed Central

    Ford, H C; Delahunt, J W; Teague, C A

    1983-01-01

    A patient with Graves's disease is described in whom the periorbital changes of severe ophthalmopathy and iatrogenic Cushing's syndrome delayed the diagnosis of a squamous cell carcinoma of the eyelid. It is suggested that the immunosuppressive therapy which the patient received may have enhanced the growth of a pre-existing malignancy. Images PMID:6688354

  10. Squamous cell carcinoma causing dorsal atlantoaxial spinal cord compression in a dog.

    PubMed

    Miyazaki, Yuta; Aikawa, Takeshi; Nishimura, Masaaki; Iwata, Munetaka; Kagawa, Yumiko

    2016-10-01

    A 12-year-old Chihuahua dog was presented for cervical pain and progressive tetraparesis. Magnetic resonance imaging revealed spinal cord compression due to a mass in the dorsal atlantoaxial region. Surgical treatment was performed. The mass was histopathologically diagnosed as a squamous cell carcinoma. The dog recovered to normal neurologic status after surgery.

  11. Squamous Cell Carcinoma Arising from the Pleural Cavity After Pneumonectomy for Chronic Empyema

    PubMed Central

    Jeon, Yeong Jeong; Shin, Sumin; Shim, Young Mog

    2017-01-01

    Malignant tumors associated with chronic empyema have been reported in the literature, and a majority of these tumors are lymphomas. Epithelial tumors originating from the post-pneumonectomy space in patients with chronic empyema are extremely rare. Here, we present the cases of 2 patients with squamous cell carcinoma arising from the pleural cavity after pneumonectomy for chronic empyema. PMID:28382273

  12. [Rectal squamous cell carcinoma treatment: Retrospective experience in two French university hospitals, review and proposals].

    PubMed

    Schernberg, A; Servagi-Vernat, S; Loganadane, G; Touboul, E; Bosset, J-F; Huguet, F

    2016-12-01

    After publishing a retrospective series of 23 patients treated for a rectal squamous cell carcinoma with exclusive curative and conservative intent chemoradiation, we aim to propose a review of the literature about this rare tumour. We identified 11 retrospective studies, on 106 patients, treated between 2007 and 2016. Treatment of rectal squamous cell carcinoma should be similar to anal carcinoma, based on exclusive chemoradiation, displaying a 5-year overall survival rate over 80%, while it was 32% in surgical series. Baseline explorations should be similar as for anal carcinoma, with an interest in PET-CT at diagnosis and monitoring, after a delay over 6 weeks after chemoradiation. Intensity-modulated radiotherapy is legitimate, to a prophylactic dose between 36 and 45Gy, and over 54Gy to the tumour. Concomitant chemotherapy should combine an antimetabolite (5-fluorouracil or capecitabine) and mitomycin C, or cisplatin. This treatment seems well tolerated, associated with grade 2 or above toxicity below 30%. Follow-up should be established on anal squamous cell carcinoma schedule, with endoscopic ultrasonography and PET-CT. Rectal squamous cell carcinoma is a rare tumour; it management should be based on anal curative and conservative intent chemoradiation.

  13. Squamous cell carcinoma invading the right temporomandibular joint in a Belgian mare

    PubMed Central

    Perrier, Melanie; Schwarz, Tobias; Gonzalez, Olga; Brounts, Sabrina

    2010-01-01

    This report describes a rare case of squamous cell carcinoma invading the right temporomandibular joint, right guttural pouch, and calvarium. Radiography, computed tomography, and histopathology were performed in the diagnostic workup. Computed tomography depicted more accurately than radiography the invasive nature, exact location, and extent of the lesion. PMID:21037891

  14. The role of miR-21 in proliferation and invasion capacity of human tongue squamous cell carcinoma in vitro

    PubMed Central

    Wang, Yin; Zhu, Yu; Lv, Pin; Li, Longjiang

    2015-01-01

    Tongue squamous cell carcinoma is one of the most common cancers, which has the highest incidence in oral maxillofacial malignant tumors. MiR-21 may promote tumorigeness by down-regulating tumor suppressing genes and/or controlling the genes for cell differentiation and apoptosis, and it has been identified as the most expressive and unusual in a number of profiling experiments. The study shows there are high expressions of miR-21 in tongue squamous cell carcinoma cell lines (Tca8113 and its high metastatic lines), especially in high metastatic lines. miR-21 silencing could suppress the capacity of proliferation, migration and invasion, arrest the cell cycle and induce apoptosis of tongue squamous cell carcinoma cell lines (Tca8113 and its high metastatic lines). All the results indicate that miR-21 will probably open a new path to the gene therapy for oral squamous cell carcinoma. PMID:26191145

  15. Berberine-induced anticancer activities in FaDu head and neck squamous cell carcinoma cells.

    PubMed

    Seo, Yo-Seob; Yim, Min-Ji; Kim, Bok-Hee; Kang, Kyung-Rok; Lee, Sook-Young; Oh, Ji-Su; You, Jae-Seek; Kim, Su-Gwan; Yu, Sang-Joun; Lee, Gyeong-Je; Kim, Do Kyung; Kim, Chun Sung; Kim, Jin-Soo; Kim, Jae-Sung

    2015-12-01

    In the present study, we investigated berberine‑induced apoptosis and the signaling pathways underlying its activity in FaDu head and neck squamous cell carcinoma cells. Berberine did not affect the viability of primary human normal oral keratinocytes. In contrast, the cytotoxicity of berberine was significantly increased in FaDu cells stimulated with berberine for 24 h. Furthermore, berberine increased nuclear condensation and apoptosis rates in FaDu cells than those in untreated control cells. Berberine also induced the upregulation of apoptotic ligands, such as FasL and TNF-related apoptosis-inducing ligand, and triggered the activation of caspase-8, -7 and -3, and poly(ADP ribose) polymerase, characteristic of death receptor-dependent extrinsic apoptosis. Moreover, berberine activated the mitochondria‑dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bax, Bad, Apaf-1, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. In addition, berberine increased the expression of the tumor suppressor p53 in FaDu cells. The pan-caspase inhibitor Z-VAD-fmk suppressed the activation of caspase-3 and prevented cytotoxicity in FaDu cells treated with berberine. Interestingly, berberine suppressed cell migration through downregulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38, components of the mitogen-activated protein kinase pathway that are associated with the expression of MMP and VEGF, was suppressed in FaDu cells treated with berberine for 24 h. Therefore, these data suggested that berberine exerted anticancer effects in FaDu cells through induction of apoptosis and suppression of migration. Berberine may have potential applications as a chemotherapeutic agent for the management of head and neck squamous carcinoma.

  16. Ghrelin and obestatin expression in oral squamous cell carcinoma: an immunohistochemical and biochemical study.

    PubMed

    Alnema, Manar M; Aydin, Suleyman; Ozkan, Yusuf; Dagli, Adile F; Ozercan, Hanifi I; Yildirim, Nezahat; Sahin, Ibrahim; Karaoglu, Aziz; Kilic, Nermin; Yilmaz, Mustafa; Ozercan, Mehmet R; Donder, Emir

    2010-06-01

    The underlying molecular mechanism of carcinogenesis in oral squamous cell carcinoma (OSCC) is poorly understood and appears to be controlled on many genetic, environmental, and hormonal factors. Obestatin and ghrelin, two recently discovered hormones, are co-expressed in endocrine cells. The purpose of this investigation was to examine the immunohistochemical features of OSCCs in relation to the tissue concentration of ghrelin and obestatin. The association between OSCC and Epstein Barr Virus (EBV) status was also explored. The expression of ghrelin and obestatin was examined by immunohistochemistry and immunoassay in oral biopsy specimens: 10 benign squamous epithelial cell samples, 10 microinvasive squamous cell carcinomas, and seven well-differentiated and seven poorly differentiated OSCCs. The presence of EBV was evaluated in these samples using immunohistochemistry. The concentrations of ghrelin and obestatin in tissue homogenates were measured by RIA and ELISA, respectively. Squamous cell carcinomas and benign tissue samples were positive for anti-EBV antibody, and obestatin and ghrelin were shown to be co-expressed in all stratified squamous epithelium samples. Expression of ghrelin and obestatin was decreased or absent in OSCCs in relation to the invasiveness of the carcinoma; ghrelin and obestatin levels in cancerous tissue homogenates were lower than in benign tissue homogenates. These results indicate that the concentrations and distribution of immunoreactive obestatin and ghrelin might be helpful in distinguishing OSCC from benign tumors. Maintaining normal levels of these hormones might be required for regulation of normal cell division. However, detailed studies will be required for better understanding of the complex mechanism of carcinogenesis relating to OSCCs.

  17. Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion

    DTIC Science & Technology

    2015-08-01

    AWARD NUMBER: W81XWH-14-1-0223 TITLE: Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion...COVERED 1Aug2014 - 31Jul2015 4. TITLE AND SUBTITLE Genetic and Epigenetic Determinants of Lung Cancer Subtype: 5a. CONTRACT NUMBER W81XWH-14-1-0223...histologies of lung cancer is made difficult in part because of the extensive genetic and epigenetic changes that occur in lung carcinogenesis, the

  18. Induction of apoptosis by grape seed extract (Vitis vinifera) in oral squamous cell carcinoma.

    PubMed

    Aghbali, Amirala; Hosseini, Sepideh Vosough; Delazar, Abbas; Gharavi, Nader Kalbasi; Shahneh, Fatemeh Zare; Orangi, Mona; Bandehagh, Ali; Baradaran, Behzad

    2013-08-01

    Development of novel therapeutic modalities is crucial for the treatment of oral squamous cell carcinoma (OSCC). Recent scientific studies have been focused on herbal medicines as potent anti-cancer drug candidates. This study is the first to investigate the cytotoxic effects and the mechanism of cell death induced by grape seed extract (GSE) in oral squamous cell carcinoma (KB cells). MTT (3-(4,5-dimetylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) and trypan blue assays were performed in KB cells as well as human umbilical vein endothelial cells (HUVEC) were used to analyze the cytotoxic activity of GSE. Furthermore, the apoptosis-inducing action of the extract was determined by TUNEL, DNA fragmentation and cell death analysis. Statistical significance was determined by analysis of variance (ANOVA), followed by Duncan's test at a significance level of P≤0.05. The results showed apoptotic potential of GSE, confirmed by significant inhibition of cell growth and viability in a dose- and time- dependent manner without inducing damage to non-cancerous cell line HUVEC. The results of this study suggest that this plant contains potential bioactive compound(s) for the treatment of oral squamous cell carcinoma.

  19. Isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma

    PubMed Central

    Huang, Peng; Wang, Chun-You; Gou, Shan-Miao; Wu, He-Shui; Liu, Tao; Xiong, Jiang-Xin

    2008-01-01

    AIM: To explore the method of isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma cell line PANC-1. METHODS: The PANC-1 cells were cultured in Dulbecco modified eagle medium F12 (1:1 volume) (DMEM-F12) supplemented with 20% fetal bovine serum (FBS). Subpopulation cells with properties of tumor stem cells were isolated from pancreatic adenocarcinoma cell line PANC-1 according to the cell surface markers CD44 and CD24 by flow cytometry. The proliferative capability of these cells in vitro were estimated by 3-[4,5-dimehyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method. And the tumor growth of different subpopulation cells which were injected into the hypodermisof right and left armpit of nude mice was studied, and expression of CD44 and CD24 of the CD44+CD24+ cell-formed nodules and PANC-1 cells were detected by avidin-biotin-peroxidase complex (ABC) immunohistochemical staining. RESULTS: The 5.1%-17.5% of sorted PANC-1 cells expressed the cell surface marker CD44, 57.8% -70.1% expressed CD24, only 2.1%-3.5% of cells were CD44+ CD24+. Compared with CD44-CD24- cells, CD44+CD24+ cells had a lower growth rate in vitro. Implantation of 104 CD44-CD24- cells in nude mice showed no evident tumor growth at wk 12. In contrast, large tumors were found in nude mice implanted with 103 CD44+CD24+ cells at wk 4 (2/8), a 20-fold increase in tumorigenic potential (P < 0.05 or P < 0.01). There was no obvious histological difference between the cells of the CD44+CD24+ cell-formed nodules and PANC-1 cells. CONCLUSION: CD44 and CD24 may be used as the cell surface markers for isolation of pancreatic cancer stem cells from pancreatic adenocarcinoma cell line PANC-1. Subpopulation cells CD44+CD24+ have properties of tumor stem cells. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, it may be a very promising target for new drug development. PMID

  20. Computer aided morphometric analysis of oral leukoplakia and oral squamous cell carcinoma.

    PubMed

    Gupta, K; Gupta, J; Miglani, R

    2016-01-01

    We compared the changes in the cells in the basal layer of normal mucosa, oral leukoplakia with dysplasia and different grades of oral squamous cell carcinoma (OSCC) using computer aided image analysis of tissue sections. We investigated three morphometric parameters: nuclear area (NA), cell area (CA) and their ratio (NA:CA). NA and NA:CA ratio showed a statistically significant increase from dysplasia to increasing grades of OSCC. Nuclear size was useful for differentiating normal tissue, potentially malignant leukoplakia and OSCC.

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

    SciTech Connect

    Lin, Charles; Tripcony, Lee; Keller, Jacqui; Poulsen, Michael; Martin, Jarad; Jackson, James; Dickie, Graeme

    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.

  2. A clear cell adenocarcinoma of the gallbladder with hepatoid differentiation: case report and review of literature

    PubMed Central

    Zhang, Chengsheng; Zhang, Wei; Mu, Dianbin; Shi, Xuetao; Zhao, Lei

    2016-01-01

    An 80-year-old male was referred to our department for a gallbladder mass. He denied any history of alcohol consumption or cholecystitis and smoking. Hepatitis B surface antigen test and antihepatitis C antibody test were found to be negative. Serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen were elevated (CA19-9 was 59.92 U/mL and carcinoembryonic antigen was 12.64 ng/mL), whereas alpha-fetoprotein was below the normal limit (2.46 ng/mL). Computed tomography scan revealed a solid mass with measurements of 4.6×5.6×7.1 cm, which nearly filled the whole gallbladder space. Radical cholecystectomy, including segments IV B and V of the liver and lymphadenectomy, was performed. The neoplasm in gallbladder was completely resected, and the patient obtained a negative margin. Histological and immunohistochemical profile suggested a clear cell adenocarcinoma of the gallbladder with hepatoid differentiation. After reviewing the literature, we reported that this case is the first identified case of cell adenocarcinoma of the gallbladder with extensive hepatoid differentiation. However, clinical features of clear cell adenocarcinoma with hepatoid differentiation remain unclear due to the extremely rare incidence. There was no indication of adjuvant chemotherapy and no literature has been reported on the application of chemotherapy. This case showed a promising clinical outcome after curative resection, which indicated that surgical treatment could be potentially considered for suitable patients. PMID:27703378

  3. miR-448 is a novel prognostic factor of lung squamous cell carcinoma and regulates cells growth and metastasis by targeting DCLK1.

    PubMed

    Shan, Changting; Fei, Fan; Li, Fengzhu; Zhuang, Bo; Zheng, Yulong; Wan, Yufeng; Chen, Jianhui

    2017-03-15

    MicroRNA-448 (miR-448) has been showed to be low-expressed and function as tumor suppressor in most human cancers. However, there are limited reports on the clinical significance and biological function of miR-448 in lung squamous cell carcinoma. In this study, we observed that miR-448 expression was decreased in lung squamous cell carcinoma tissues and cell lines. Meanwhile, miR-448 expression associated with differentiated degree, T classification (tumor size), N classification (lymph node metastasis), M classification (distant metastasis), clinical stage and prognosis of lung squamous cell carcinoma patients. In survival analysis, low expression of miR-448 was a poor independent prognostic factor for lung squamous cell carcinoma patients. Moreover, gain-of-function and loss-of-function studies showed miR-448 acted as a tumor suppressor regulating lung squamous cell carcinoma cells growth and metastasis. Furthermore, DCLK1 has been identified as a potential target for miR-448 to regulate lung squamous cell carcinoma cells growth and metastasis. In conclusion, miR-448 low-expression was a poor prognostic factor for lung squamous cell carcinoma patients, and miR-448 served as a tumor suppressor in lung squamous cell carcinoma cells via targeting DCLK1.

  4. Cell surface glycopeptides from human intestinal epithelial cell lines derived from normal colon and colon adenocarcinomas

    SciTech Connect

    Youakim, A.; Herscovics, A.

    1985-11-01

    The cell surface glycopeptides from an epithelial cell line (CCL 239) derived from normal human colon were compared with those from three cell lines (HCT-8R, HCT-15, and CaCo-2) derived independently from human colonic adenocarcinomas. Cells were incubated with D-(2-TH)mannose or L-(5,6-TH)fucose for 24 h and treated with trypsin to release cell surface components which were then digested exhaustively with Pronase and fractionated on Bio-Gel P-6 before and after treatment with endo-beta-N-acetylglucosaminidase H. The most noticeable difference between the labeled glycopeptides from the tumor and CCL 239 cells was the presence in the former of an endo-beta-N-acetylglucosaminidase H-resistant high molecular weight glycopeptide fraction which was eluted in the void volume of Bio-Gel P-6. This fraction was obtained with both labeled mannose and fucose as precursors. However, acid hydrolysis of this fraction obtained after incubation with (2-TH)mannose revealed that as much as 60-90% of the radioactivity was recovered as fucose. Analysis of the total glycopeptides (cell surface and cell pellet) obtained after incubation with (2-TH)mannose showed that from 40-45% of the radioactivity in the tumor cells and less than 10% of the radioactivity in the CCL 239 cells was recovered as fucose. After incubation of the HCT-8R cells with D-(1,6-TH)glucosamine and L-(1- UC)fucose, strong acid hydrolysis of the labeled glycopeptide fraction excluded from Bio-Gel P-6 produced TH-labeled N-acetylglucosamine and N-acetylgalactosamine.

  5. Fucan-coated silver nanoparticles synthesized by a green method induce human renal adenocarcinoma cell death.

    PubMed

    Rocha Amorim, Monica Oliveira; Lopes Gomes, Dayanne; Dantas, Larisse Araujo; Silva Viana, Rony Lucas; Chiquetti, Samanta Cristina; Almeida-Lima, Jailma; Silva Costa, Leandro; Oliveira Rocha, Hugo Alexandre

    2016-12-01

    Polysaccharides containing sulfated L-fucose are often called fucans. The seaweed Spatoglossum schröederi synthesizes three fucans, among which fucan A is the most abundant. This polymer is not cytotoxic against various normal cell lines and is non-toxic to rats when administered at high doses. In addition, it exhibits low toxicity against tumor cells. With the aim of increasing the toxicity of fucan A, silver nanoparticles containing this polysaccharide were synthesized using a green chemistry method. The mean size of these nanoparticles was 210nm. They exhibited a spherical shape and negative surface charge and were stable for 14 months. When incubated with cells, these nanoparticles did not show any toxic effects against various normal cell lines; however, they decreased the viability of various tumor cells, especially renal adenocarcinoma cells 786-0. Flow cytometry analyses showed that the nanoparticles induced cell death responses of 786-0 cells through necrosis. Assays performed with several renal cell lines (HEK, VERO, MDCK) showed that these nanoparticles only induce death of 786-0 cells. The data obtained herein leads to the conclusion that fucan A nanoparticles are promising agents against renal adenocarcinoma.

  6. Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines.

    PubMed

    Michishita, Masaki; Akiyoshi, Rui; Yoshimura, Hisashi; Katsumoto, Takuo; Ichikawa, Hitoshi; Ohkusu-Tsukada, Kozo; Nakagawa, Takayuki; Sasaki, Nobuo; Takahashi, Kimimasa

    2011-10-01

    There is increasing evidence for the presence of cancer stem cells in several solid tumors, and these cancer stem cells have a potential role in tumor initiation, aggression, and recurrence. The stem cell-like properties of spheres derived from canine mammary tumors remain largely elusive. We attempted to induce sphere formation using four cell lines of canine mammary adenocarcinoma, and characterized the spheres derived from a CHMp line in vitro and in vivo. The CHMp-derived spheres showed predominantly CD44+CD24- population, higher expression of stem cell-related genes, such as CD133, Notch3 and MDR, and higher resistance to doxorubicin compared with the CHMp-derived adherent cells. Xenograft transplantations in nude mice demonstrated that only 1 × 10(4)sphere cells were sufficient for tumor formation. Use of the sphere assay on these sphere-derived tumors showed that sphere-forming cells were present in the tumors, and were maintained in serial transplantation. We propose that spheres derived from canine mammary adenocarcinoma cell lines possess a potential characteristic of cancer stem cells. Spheres derived from canine mammary tumors could be a powerful tool with which to investigate novel therapeutic drugs and to elucidate the molecular and cellular mechanisms that underlie tumorigenesis.

  7. Pembrolizumab and Vorinostat in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer or Salivary Gland Cancer That Is Metastatic and/or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-03-07

    Head and Neck Squamous Cell Carcinoma; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharynx Carcinoma; Recurrent Salivary Gland Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage III Major Salivary Gland Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage IV Nasopharyngeal Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma

  8. Sodium azide induces necrotic cell death in rat squamous cell carcinoma SCC131.

    PubMed

    Sato, Eiju; Suzuki, Toshimitsu; Hoshi, Nobuo; Sugino, Takashi; Hasegawa, Hiroshi

    2008-12-01

    Sodium azide (NaN(3)) is widely used in industry and agriculture, and also in laboratories as a potent preservative. NaN(3) induces cell death when applied to cultured cells. However, whether the mode of cell death is apoptosis or necrosis remains a subject of debate. There have been no previous reports on NaN(3)-induced cell death in squamous cell carcinoma (SCC), and so we studied the mode of cell death induced by NaN(3) using the rat SCC cell line, SCC131. In this experiment, SCC131 cells died 48-72 h after NaN(3) treatment with concentrations greater than 5 mM. The NaN(3) treatment reduced the mitochondrial membrane potential and ATP content. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and DNA ladder detection assay indicated that no DNA fragmentation occurred. In addition, phosphatidyl serine did not appear on the cell surface, according to the findings of dye-uptake bioassay and flow cytometric analysis of Annexin V labeling. Electron microscopic analysis revealed that the NaN(3)-treated cells showed mitochondrial swelling and rupture of the cell membrane. In conclusion, NaN(3) induces necrotic cell death in SCC131. This experimental model may be used in the study of necrotic cell death.

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

    PubMed

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

    2015-07-01

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

  10. Effect of silencing SATB1 on proliferation, invasion and apoptosis of A549 human lung adenocarcinoma cells

    PubMed Central

    Huang, Bo; Zhou, Hongli; Wang, Siwang; Lang, Xian Ping; Wang, Xiaodong

    2016-01-01

    The present study aimed to explore the clinical characteristics of special adenine-thymine-rich sequence-binding protein 1 (SATB1) in lung adenocarcinoma and its role in the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cell line A549. The expression of SATB1 was first studied in tumor tissues of lung adenocarcinoma and adjacent non-tumor tissues. The siRNA green fluorescent protein expression vector of SATB1 was constructed and transfected into the lung adenocarcinoma cell line A549, then a fluorescence microscope was used to study the transfection efficiency. Western blot analysis was adopted to measure the silencing efficiency. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and scratch assays were used to study cell proliferation, invasion and migration activity, and the apoptosis rate was tested by flow cytometry. SATB1 expression was low in the adjacent non-tumor tissues but high in lung adenocarcinoma tissues, and it was reversely proportional to the differentiation degree. Following transfection with SATB1-siRNA, the expression of SATB1 in A549 cells was blocked (P<0.01). In addition, the proliferation, invasion and migration abilities of cells decreased significantly while the apoptosis rate increased significantly (P<0.01). In conclusion SATB1 is closely associated with the pathogenesis and development of lung adenocarcinoma. PMID:27895736

  11. Quantitative Analysis of High-Resolution Microendoscopic Images for Diagnosis of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Shin, Dongsuk; Protano, Marion-Anna; Polydorides, Alexandros D.; Dawsey, Sanford M.; Pierce, Mark C.; Kim, Michelle Kang; Schwarz, Richard A.; Quang, Timothy; Parikh, Neil; Bhutani, Manoop S.; Zhang, Fan; Wang, Guiqi; Xue, Liyan; Wang, Xueshan; Xu, Hong; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.

    2014-01-01

    Background & Aims High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can readily be interpreted by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. Methods We performed image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and 1 in the United States from May 2010 to October 2012. Biopsies were collected from imaged sites (n=375); a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. Results Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. Conclusions High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies. PMID:25066838

  12. Goblet cells carcinoid with mucinous adenocarcinoma of the vermiform appendix: a step towards the unitary intestinal stem cell theory?

    PubMed

    Gravante, G; Yahia, S; Gopalakrishnan, K; Mathew, G

    2014-06-01

    Associations of various histotypes in appendiceal neoplasms may help elucidate the histogenesis of such uncommon tumors. We present the fourth published case of Goblet Cell Carcinoid (GCC) associated with mucinous adenocarcinoma of the appendix. This association has been described only for GCC and not for classic appendix carcinoids which are thought to originate from neuroendocrine-committed cells. The GCC-mucinous association adds more towards the theory of a pluripotent intestinal stem cell with amphicrine possibilities of differentiation.

  13. Efficacy of cobalt-60 radiation therapy for the treatment of nasal cavity nonkeratinizing squamous cell carcinoma in the dog.

    PubMed

    Correa, Stephanie Shank; Mauldin, G Neal; Mauldin, Glenna E; Patnaik, Amiya K

    2003-01-01

    The purposes of this study were to evaluate the efficacy of cobalt-60 radiotherapy in the treatment of nonkeratinizing squamous cell carcinoma of the nasal cavity in dogs and to compare this treatment group to historical controls. Six dogs with histopathologically confirmed nasal cavity nonkeratinizing squamous cell carcinoma were treated with cobalt-60 radiotherapy to a total dose of either 63 Gy or 54 Gy. Overall survival times ranged from 30 days to 330 days, with a median survival time of 165 days. Nasal cavity nonkeratinizing squamous cell carcinoma in the dog is an aggressive tumor that responds poorly to radiotherapy.

  14. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma

    PubMed Central

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R.; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A.; Bielenberg, Diane R.

    2017-01-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. PMID:26877262

  15. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    PubMed

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.

  16. CXCR2 expression in tumor cells is a poor prognostic factor and promotes invasion and metastasis in lung adenocarcinoma

    PubMed Central

    Saintigny, Pierre; Massarelli, Erminia; Lin, Steven; Chen, Yulong; Goswami, Sangeeta; Erez, Baruch; O’Reilly, Michael S.; Liu, Diane; Lee, J. Jack; Zhang, Li; Ping, Yuan; Behrens, Carmen; Soto, Luisa M. Solis; Heymach, John V.; Kim, Edward S.; Herbst, Roy S.; Lippman, Scott M.; Wistuba, Ignacio I.; Hong, Waun Ki; Kurie, Jonathan M.; Koo, Ja Seok

    2012-01-01

    CXCR2 in non-small cell lung cancer (NSCLC) has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. Here, we examined the prognostic importance of CXCR2 in NSCLC and the role of CXCR2 and its ligands in lung cancer cells. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from a murine KRAS/p53-mutant lung adenocarcinoma cell line with high metastatic potential and an orthotopic syngeneic mouse model and in vitro using a CXCR2 small molecule antagonist (SB225002). CXCR2 protein expression was analyzed in tumor cells from 262 NSCLC. Gene expression profiles for CXCR2 and its ligands (CXCR2 axis) were analyzed in 52 human NSCLC cell lines and 442 human lung adenocarcinomas. Methylation of CXCR2 axis promoters was determined in 70 human NSCLC cell lines. Invasion and metastasis were decreased in CXCR2 knockdown clones in vitro and in vivo. SB225002 decreased invasion in vitro. In lung adenocarcinomas, CXCR2 expression in tumor cells was associated with smoking and poor prognosis. CXCR2 axis gene expression profiles in human NSCLC cell lines and lung adenocarcinomas defined a cluster driven by CXCL5 and associated with smoking, poor prognosis and RAS pathway activation. Expression of CXCL5 was regulated by promoter methylation. The CXCR2 axis may be an important target in smoking-related lung adenocarcinoma. PMID:23204236

  17. Per2 participates in AKT-mediated drug resistance in A549/DDP lung adenocarcinoma cells.

    PubMed

    Chen, Bo; Tan, Yaoxi; Liang, Yan; Li, Yan; Chen, Lei; Wu, Shuangshuang; Xu, Wei; Wang, Yan; Zhao, Weihong; Wu, Jianqing

    2017-01-01

    Period2 (Per2) is a key mammalian circadian clock protein, and additionally has a tumor suppressive function. The present study aimed to investigate its role in drug resistance in A549/cisplatin (DDP) lung adenocarcinoma cells. Per2 knockdown and overexpression in A549/DDP cells were used to compare cell proliferation (by MTT assay), apoptosis (active-caspase 3 western blot) and clone forming assay. The activation of AKT/mechanistic target of rapamycin (mTOR) was investigated by a western blot assay. The Per2 expression level was decreased in A549/DDP cells compared with A549 cells. Per2 knockdown by short hairpin RNA protects A549/DDP cells from apoptosis, and promotes proliferation and migration. Per2 knockdown results in increased activation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway. Overexpression of Per2 in A549/DDP cells may reduce the activity of the PI3K/AKT/mTOR signaling pathway, and promote apoptosis of A549 cells. The results of the present study suggest that Per2 participates in AKT-mediated drug resistance in A549/DDP lung adenocarcinoma cells.

  18. Per2 participates in AKT-mediated drug resistance in A549/DDP lung adenocarcinoma cells

    PubMed Central

    Chen, Bo; Tan, Yaoxi; Liang, Yan; Li, Yan; Chen, Lei; Wu, Shuangshuang; Xu, Wei; Wang, Yan; Zhao, Weihong; Wu, Jianqing

    2017-01-01

    Period2 (Per2) is a key mammalian circadian clock protein, and additionally has a tumor suppressive function. The present study aimed to investigate its role in drug resistance in A549/cisplatin (DDP) lung adenocarcinoma cells. Per2 knockdown and overexpression in A549/DDP cells were used to compare cell proliferation (by MTT assay), apoptosis (active-caspase 3 western blot) and clone forming assay. The activation of AKT/mechanistic target of rapamycin (mTOR) was investigated by a western blot assay. The Per2 expression level was decreased in A549/DDP cells compared with A549 cells. Per2 knockdown by short hairpin RNA protects A549/DDP cells from apoptosis, and promotes proliferation and migration. Per2 knockdown results in increased activation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway. Overexpression of Per2 in A549/DDP cells may reduce the activity of the PI3K/AKT/mTOR signaling pathway, and promote apoptosis of A549 cells. The results of the present study suggest that Per2 participates in AKT-mediated drug resistance in A549/DDP lung adenocarcinoma cells. PMID:28123577

  19. Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia

    PubMed Central

    Schwab, K.S.; Heine, A.; Weimann, T.; Kristiansen, G.; Brossart, P.

    2016-01-01

    Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications. PMID:27462240

  20. Primary cell culture of human adenocarcinomas--practical considerations.

    PubMed

    Lerescu, Lucian; Tucureanu, Cătălin; Caraş, Iuliana; Neagu, Stefan; Melinceanu, Laura; Sălăgeanu, Aurora

    2008-01-01

    Cell culture is one of the major tools for oncology research, being an excellent system in which to study the biochemistry and molecular biology associated with individual cancer types and to understand cancer cell physiology. Progress in understanding the biology of any type of carcinoma has been impeded by the inability to culture adequately malignant cells from most epithelial tissues. The ultimate in vitro tumor model would completely reflect the in vivo tumor microenvironment in function and mechanism. Unfortunately, such a model does not currently exist. Homogeneous cell lines that can be continuously propagated on plastic surfaces have been extensively used as a surrogate for tumor environment; however they are very different from the in vivo tumor cells. Model systems involving primary culture represent the situation most closely related to the original tissue although they have a number of disadvantages over cell lines, such as the limited ability to repeat studies with a well characterized culture system that can be used in multiple laboratories. The primary culture may contain many types of stromal and infiltrating cell types potentially complicating the interpretation of data. Yet, their properties better reflect the cellular interactions present in intact tissue. The present article reviews the critical steps in obtaining, routine maintenance and cryopreservation of primary tumor cell cultures, based on information from literature and personal experience on the subject. The article also includes an updated protocol for primary tumor cell isolation and culture.

  1. CD44 expression in intraoral salivary ductal papillomas and oral papillary squamous cell carcinoma.

    PubMed

    Fitzpatrick, Sarah G; Montague, Lindsay J; Cohen, Donald M; Bhattacharyya, Indraneel

    2013-06-01

    CD44 is a transmembrane adhesion molecule which has been previously shown to be useful in the differentiation of benign papillary lesions from invasive carcinoma in several different areas including sinonasal mucosa and breast tissue. CD44 expression has previously been shown to be lost in invasive carcinoma and retained in benign papillary lesions in both of the above locations. In addition, studies have evaluated oral mucosal lesions for CD44 expression and found a loss with invasive squamous cell carcinoma when compared to normal epithelium, hyperplasia, and squamous papillomas, which stained particularly strongly. To the best of our knowledge, no study has evaluated CD44 expression when comparing salivary ductal papillomas in comparison to oral papillary SCCA. In this study 18 cases of intraductal papilloma were compared to 19 cases of oral papillary SCCA. Within the ductal papilloma group, all cases stained either absent (6%), weakly (33%), or moderately (61%) with 76% expressing the stain diffusely and 24% focally. In comparison, the papillary squamous cell carcinoma cases expressed the CD44 moderately (26%) or strongly (74%) with 100 % showing diffuse staining. Thus, the CD44 expression was contrary to expectation based on previous studies, which we hypothesize is due to the extremely well differentiated nature of papillary SCCA which expressed CD44 staining compatible with levels previously reported with oral squamous papillomas than invasive carcinoma.

  2. Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells.

    PubMed

    Yajima, Ichiro; Uemura, Noriyuki; Nizam, Saika; Khalequzzaman, Md; Thang, Nguyen D; Kumasaka, Mayuko Y; Akhand, Anwarul A; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

    2012-06-01

    Our fieldwork showed more than 1 μM (145.1 μg/L) barium in about 3 μM (210.7 μg/L) arsenic-polluted drinking well water (n = 72) in cancer-prone areas in Bangladesh, while the mean concentrations of nine other elements in the water were less than 3 μg/L. The types of cancer include squamous cell carcinomas (SCC). We hypothesized that barium modulates arsenic-mediated biological effects, and we examined the effect of barium (1 μM) on arsenic (3 μM)-mediated apoptotic cell death of human HSC-5 and A431 SCC cells in vitro. Arsenic promoted SCC apoptosis with increased reactive oxygen species (ROS) production and JNK1/2 and caspase-3 activation (apoptotic pathway). In contrast, arsenic also inhibited SCC apoptosis with increased NF-κB activity and X-linked inhibitor of apoptosis protein (XIAP) expression level and decreased JNK activity (antiapoptotic pathway). These results suggest that arsenic bidirectionally promotes apoptotic and antiapoptotic pathways in SCC cells. Interestingly, barium in the presence of arsenic increased NF-κB activity and XIAP expression and decreased JNK activity without affecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer effect of arsenic is mainly dependent on cancer apoptosis, barium-mediated inhibition of arsenic-induced apoptosis may promote progression of SCC in patients in Bangladesh who keep drinking barium and arsenic-polluted water after the development of cancer. Thus, we newly showed that barium in the presence of arsenic might inhibit arsenic-mediated cancer apoptosis with the modulation of the balance between arsenic-mediated promotive and suppressive apoptotic pathways.

  3. Collision Tumour of Squamous Cell Carcinoma and Malignant Melanoma in the Oral Cavity of a Dog.

    PubMed

    Rodríguez, F; Castro, P; Ramírez, G A

    2016-05-01

    A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies. Protein markers involved in tumorigenesis or cell proliferation (i.e. COX-2, p53, c-kit and Ki67), were overexpressed by the neoplastic cells. To the authors' knowledge, this is the first description of an oral collision tumour involving malignant melanoma and squamous cell carcinoma in the dog.

  4. Molecular Mechanism of Cinnamomum verum Component Cuminaldehyde Inhibits Cell Growth and Induces Cell Death in Human Lung Squamous Cell Carcinoma NCI-H520 Cells In Vitro and In Vivo.

    PubMed

    Yang, Shu-Mei; Tsai, Kuen-Daw; Wong, Ho-Yiu; Liu, Yi-Heng; Chen, Ta-Wei; Cherng, Jonathan; Hsu, Kwang-Ching; Ang, Yao-Uh; Cherng, Jaw-Ming

    2016-01-01

    Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the effects and the molecular mechanisms of cuminaldehyde (CuA), a constituent of the bark of Cinnamomum verum, on human lung squamous cell carcinoma NCI-H520 cells. Specifically, cell viability was evaluated by colorimetric assay; cytotoxicity by LDH release; apoptosis was determined by Western blotting, and morphological analysis with, acridine orange and neutral red stainings and comet assay; topoisomerase I activity was assessed using assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VAC) were evaluated with neutral red staining. The results show that CuA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and a down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, and morphological characteristics of apoptosis, including blebbing of the plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. In addition, CuA also induced lysosomal vacuolation with increased VAC, cytotoxicity, as well as suppressions of both topoisomerase I and II activities in a dose-dependent manner. Further study revealed the growth-inhibitory effect of CuA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of CuA against NCI-H520 cells is accompanied by downregulations of proliferative control involving apoptosis and both topoisomerase I and II activities, and upregulation of lysosomal with increased VAC and cytotoxicity. Similar effects were found in other cell lines, including human lung adenocarcinoma A549 cells and colorectal adenocarcinoma COLO 205 (results not

  5. Agrin and perlecan mediate tumorigenic processes in oral squamous cell carcinoma.

    PubMed

    Kawahara, Rebeca; Granato, Daniela C; Carnielli, Carolina M; Cervigne, Nilva K; Oliveria, Carine E; Rivera, César; Martinez, César A R; Yokoo, Sami; Fonseca, Felipe P; Lopes, Marcio; Santos-Silva, Alan R; Graner, Edgard; Coletta, Ricardo D; Paes Leme, Adriana Franco

    2014-01-01

    Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels.

  6. Telomerase activity in the occurrence and progression of oral squamous cell carcinoma.

    PubMed

    Miyazaki, Yuji; Yoshida, Noriaki; Nozaki, Tadashige; Inoue, Harumi; Kikuchi, Kentaro; Kusama, Kaoru

    2015-01-01

    Chronic inflammation is considered to be one of the risk factors for carcinogenesis. It was recently reported that telomerase plays an important role in inducing such chronic inflammation. Although high telomerase activity is detected in cancer tissues, the activator of telomerase is still unknown. In this study, we used an immunohistochemical method to examine the expression of human telomerase reverse transcriptase (hTERT) in the dysplasia-carcinoma sequence in the oral cavity. Furthermore, the effects of inflammatory cytokines on the telomerase activity and migration of oral cancer cell lines (Ca9-22, HSC-3, and HSC-4) were examined. Immunoreactivity for hTERT was observed in squamous intraepithelial neoplasia 3 and squamous cell carcinoma. Telomerase activity in Ca9-22 cells was increased by treatment with TNF-α and INF-γ, while its activity in HSC-4 cells was decreased by IL-1β. Although inflammatory cytokines did not affect the proliferative activity of any of the oral cancer cell lines, cytokines and hTERT siRNA promoted the migration of HSC-3 cells. These results suggest that the presence of long-term chronic inflammation may increase telomerase activity and therefore contribute to malignant transformation of the oral mucosal epithelium. Furthermore, inhibition of telomerase activity by inflammatory stimuli increases the invasion of certain types of oral squamous cell carcinomas.

  7. Agrin and Perlecan Mediate Tumorigenic Processes in Oral Squamous Cell Carcinoma

    PubMed Central

    Kawahara, Rebeca; Granato, Daniela C.; Carnielli, Carolina M.; Cervigne, Nilva K.; Oliveria, Carine E.; Martinez, César A. R.; Yokoo, Sami; Fonseca, Felipe P.; Lopes, Marcio; Santos-Silva, Alan R.; Graner, Edgard; Coletta, Ricardo D.; Leme, Adriana Franco Paes

    2014-01-01

    Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels. PMID:25506919

  8. Ultrastructural Assessment of 2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide activity on human breast adenocarcinoma cells.

    PubMed

    de Almeida, Sinara Mônica Vitalino; da Silva, Lúcia Patrícia Bezerra Gomes; de Lima, Luiza Rayanna Amorim; Longato, Giovanna Barbarini; Padilha, Rafael José Ribeiro; Alves, Luiz Carlos; Brayner, Fábio André; Ruiz, Ana Lucia Tasca Gois; de Carvalho, João Ernesto; Beltrão, Eduardo Isidoro Carneiro; de Lima, Maria do Carmo Alves; de Carvalho Júnior, Luiz Bezerra

    2016-11-01

    The aim of the present study was to investigate ultrastructural changes induced by (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide (APHCA) treatment on human breast adenocarcinoma cancer cells MCF-7, besides the evaluation of phosphatidylserine externalization and DNA fragmentation in treated cells. Cell viability analysis demonstrated concentration and time-manner cytotoxicity. Treated MCF-7 cells did not expose phosphatidylserine residues to the external plasma membrane surface and DNA fragmentation was not visualized by electrophoresis. Light microscopy showed compromised cell density and presence of vacuolization after APHCA treatment with 60μM. Scanning and transmission electron microscopies revealed hallmarks of autophagy, namely the presence of membrane bebbling and autophagosomes, besides shrunken cells and cell debris in treated MCF-7 cells. However, more specific tests such as the quantification of mammalian autophagy proteins are necessary to determine the kind of death that is trigged by APHCA.

  9. Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

    PubMed Central

    Pfeifer, A M; Lechner, J F; Masui, T; Reddel, R R; Mark, G E; Harris, C C

    1989-01-01

    The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous [e.g., transforming growth factor beta 1 (TGF-beta 1) and serum] and exogenous [e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes] modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells. PMID:2538323

  10. Basal stem cells contribute to squamous cell carcinomas in the oral cavity.

    PubMed

    Tang, Xiao-Han; Scognamiglio, Theresa; Gudas, Lorraine J

    2013-05-01

    The cells of origin of oral cavity squamous cell carcinoma (OCSCC) are unknown. We used a cell lineage tracing approach (adult K14-CreER(TAM); ROSA26 mice transiently treated with tamoxifen) to identify and track normal epithelial stem cells (SCs) in mouse tongues by X-gal staining and to determine if these cells become neoplastically transformed by treatment with a carcinogen, 4-nitroquinoline 1-oxide (4-NQO). Here, we show that in normal tongue epithelia, X-gal(+) cells formed thin columns throughout the entire epithelium 12 weeks after tamoxifen treatment, indicating that the basal layer contains long-lived SCs that produce progeny by asymmetric division to maintain homeostasis. Carcinogen treatment results in a ~10-fold reduction in the total number of X-gal(+) clonal cell populations and horizontal expansion of X-gal(+) clonal cell columns, a pattern consistent with symmetric division of some SCs. Finally, X-gal(+) SCs are present in papillomas and invasive OCSCCs, and these long-lived X-gal(+) SCs are the cells of origin of these tumors. Moreover, the resulting 4-NQO-induced tumors are multiclonal. These findings provide insights into the identity of the initiating cells of oral cancer.

  11. The Effect of Titanium Dioxide Nanoparticles on Keratinocyte Cell (KC) and Squamous Cell Carcinoma (SCC-13)

    NASA Astrophysics Data System (ADS)

    Lin, Chienhsiu; Simon, Marcia; Jurukovski, Vladimir; Lee, Wilson; Rafailovich, Miriam

    2009-03-01

    We have studied the effects of TiO2 nanoparticles on cell keratinocyte and SCC (Squamous Cell Carcinoma) cells. We found that the concentration of particles required to adversely affect the cells was many times higher for keratinocyte than SCC cells. Confocal microscope shows that the particles in keratinocyte culture are sequestered in membranes between the cell colonies. The particles penetrated into the cells in the case of the SCC cells. TEM images revealed very few particles in the keratinocyte, many more particles were observed sequestered in vacuole of the SCC cells. These results indicate that the keratinocyte layer behaves very different from the fibroblast layers which are much more sensate to TiO2 nanoparticle damage and may suggest a protection mechanism of the dermal tissue. The effect of UV exposure in the presence of DNA was also investigated. We found that adsorbed proteins, as well as grafted polymer provided a measure of protection against free radical formation. The effects of low level UV exposure when the particles are near in-vitro cell culture will be presented.

  12. Stromal interaction molecule 1 regulates growth, cell cycle, and apoptosis of human tongue squamous carcinoma cells.

    PubMed

    Cui, Xiaobo; Song, Laixiao; Bai, Yunfei; Wang, Yaping; Wang, Boqian; Wang, Wei

    2017-04-30

    Oral tongue squamous cell carcinoma (OTSCC) is the most common type of oral carcinomas. However, the molecular mechanism by which OTSCC developed is not fully identified. Stromal interaction molecule 1 (STIM1) is a transmembrane protein, mainly located in the endoplasmic reticulum (ER). STIM1 is involved in several types of cancers. Here, we report that STIM1 contributes to the development of human OTSCC. We knocked down STIM1 in OTSCC cell line Tca-8113 with lentivirus-mediated shRNA and found that STIM1 knockdown repressed the proliferation of Tca-8113 cells. In addition, we also showed that STIM1 deficiency reduced colony number of Tca-8113 cells. Knockdown of STIM1 repressed cells to enter M phase of cell cycle and induced cellular apoptosis. Furthermore, we performed microarray and bioinformatics analysis and found that STIM1 was associated with p53 and MAPK pathways, which may contribute to the effects of STIM1 on cell growth, cell cycle, and apoptosis. Finally, we confirmed that STIM1 controlled the expression of MDM2, cyclin-dependent kinase 4 (CDK4), and growth arrest and DNA damage inducible α (GADD45A) in OTSCC cells. In conclusion, we provide evidence that STIM1 contributes to the development of OTSCC partially through regulating p53 and MAPK pathways to promote cell cycle and survival.

  13. Adenocarcinoma of the urinary bladder.

    PubMed

    Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

    2015-01-01

    Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma.

  14. Adenocarcinoma of the urinary bladder

    PubMed Central

    Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

    2015-01-01

    Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma. PMID:26309895

  15. Boletus edulis biologically active biopolymers induce cell cycle arrest in human colon adenocarcinoma cells.

    PubMed

    Lemieszek, Marta Kinga; Cardoso, Claudia; Ferreira Milheiro Nunes, Fernando Hermínio; Ramos Novo Amorim de Barros, Ana Isabel; Marques, Guilhermina; Pożarowski, Piotr; Rzeski, Wojciech

    2013-04-25

    The use of biologically active compounds isolated from edible mushrooms against cancer raises global interest. Anticancer properties are mainly attributed to biopolymers including mainly polysaccharides, polysaccharopeptides, polysaccharide proteins, glycoproteins and proteins. In spite of the fact that Boletus edulis is one of the widely occurring and most consumed edible mushrooms, antitumor biopolymers isolated from it have not been exactly defined and studied so far. The present study is an attempt to extend this knowledge on molecular mechanisms of their anticancer action. The mushroom biopolymers (polysaccharides and glycoproteins) were extracted with hot water and purified by anion-exchange chromatography. The antiproliferative activity in human colon adenocarcinoma cells (LS180) was screened by means of MTT and BrdU assays. At the same time fractions' cytotoxicity was examined on the human colon epithelial cells (CCD 841 CoTr) by means of the LDH assay. Flow cytometry and Western blotting were applied to cell cycle analysis and protein expression involved in anticancer activity of the selected biopolymer fraction. In vitro studies have shown that fractions isolated from Boletus edulis were not toxic against normal colon epithelial cells and in the same concentration range elicited a very prominent antiproliferative effect in colon cancer cells. The best results were obtained in the case of the fraction designated as BE3. The tested compound inhibited cancer cell proliferation which was accompanied by cell cycle arrest in the G0/G1-phase. Growth inhibition was associated with modulation of the p16/cyclin D1/CDK4-6/pRb pathway, an aberration of which is a critical step in the development of many human cancers including colon cancer. Our results indicate that a biopolymer BE3 from Boletus edulis possesses anticancer potential and may provide a new therapeutic/preventive option in colon cancer chemoprevention.

  16. Alcohol, smoking and papillomavirus infection as risk factors for esophageal squamous-cell papilloma and esophageal squamous-cell carcinoma in Italy.

    PubMed

    Talamini, G; Capelli, P; Zamboni, G; Mastromauro, M; Pasetto, M; Castagnini, A; Angelini, G; Bassi, C; Scarpa, A

    2000-06-15

    Esophageal papilloma, an infrequent benign tumor, and esophageal squamous-cell carcinoma sometimes appear to be associated with human papillomavirus (HPV) infection, HPV being implicated in anogenital carcinogenesis. Our aim was to assess whether there is any epidemiological difference in terms of risk factors for papilloma and cancer. From 1989 to 1996, a total of 12,011 patients (53% male, median age 52.7 years) were submitted to esophagogastroduodenoscopy by our Digestive Endoscopy Service. The genome of HPV was sought by PCR using 2 different primer sets. Of the total, 42 subjects (0.35%), 50% male with a mean age of 45.1 years, were suffering from esophageal squamous-cell papilloma and 45 (0.37%), 91% male with a mean age of 63.0 years, from esophageal squamous-cell carcinoma. Of these patients, only 2 with papilloma were HPV(+). Compared with the general endoscopic population, patients with papilloma do not present significantly different characteristics (even in terms of frequency of esophagitis and hiatal hernia). Those with carcinoma differ significantly both from the general endoscopic population and from those with papilloma in that they are more often male (p < 0. 0001), older (p < 0.0001) and drinkers (p < 0.0001); they differ significantly only from the general population, but not from the papilloma patients, in smoking habits. Papilloma appears to be neither a lesion involving a risk of development into a malignancy nor a marker for any such risk. Environmental factors, such as alcohol and smoking, appear to play a decisive role in esophageal carcinogenesis in northern Italy.

  17. Squamous cell carcinomas of the lung and of the head and neck: new insights on molecular characterization

    PubMed Central

    Polo, Valentina; Pasello, Giulia; Frega, Stefano; Favaretto, Adolfo; Koussis, Haralabos; Conte, Pierfranco; Bonanno, Laura

    2016-01-01

    Squamous cell carcinomas of the lung and of the head and neck district share strong association with smoking habits and are characterized by smoke-related genetic alterations. Driver mutations have been identified in small percentage of lung squamous cell carcinoma. In parallel, squamous head and neck tumors are classified according to the HPV positivity, thus identifying two different clinical and molecular subgroups of disease. This review depicts different molecular portraits and potential clinical application in the field of targeted therapy, immunotherapy and chemotherapy personalization. PMID:26933818

  18. HDAC2 regulates cell proliferation, cell cycle progression and cell apoptosis in esophageal squamous cell carcinoma EC9706 cells

    PubMed Central

    Li, Shenglei; Wang, Feng; Qu, Yunhui; Chen, Xiaoqi; Gao, Ming; Yang, Jianping; Zhang, Dandan; Zhang, Na; Li, Wencai; Liu, Hongtao

    2017-01-01

    Increasing evidence has demonstrated that histone deacetylase 2 (HDAC2) participates in the regulation of a variety of biological processes in numerous tumors. However, the potential role of HDAC2 in the development and progression of esophageal squamous cell carcinoma (ESCC) remains elusive. Immunohistochemistry was utilized to detect the expression of HDAC2, Cell Counting Kit-8 was used to determine the cell proliferation, and flow cytometry was employed to investigate cell cycle and cell apoptosis. Finally, western blotting was employed to detect the protein expression of cyclin D1, p21, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). The present study found that expression of HDAC2 protein in ESCC tissues was significantly increased compared with atypical hyperplasia tissues and normal esophageal mucosa (P<0.001). The expression of HDAC2 was not associated with the age or gender of patients (P>0.05), but was closely associated with the histological grade, invasion depth, tumor-node-metastasis stage and lymph node metastasis, respectively (all P<0.001). HDAC2 small interfering RNA effectively downregulated the expression of HDAC2 protein in ESCC EC9706 cells. Downregulation of HDAC2 expression evidently inhibited cell proliferation, arrested cell cycle at the G0/G1 phase and induced cell apoptosis in ESCC EC9706 cells, coupled with increased expression of p21 and Bax proteins and decreased expression of cyclin D1 and Bcl-2 proteins. Overall, the present findings suggest that HDAC2 may play an important role in the development and progression of ESCC and be considered as a novel molecular target for the treatment of ESCC. PMID:28123574

  19. Paraneoplastic Limbic Encephalitis in a Male with Squamous Cell Carcinoma of the Lung

    PubMed Central

    Sauri, Tamara; Izquierdo, Àngel; Ramió-Torrentà, LLuis; Sanchez-Montañez, Àngel; Bosch-Barrera, Joaquim

    2015-01-01

    Background Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, symptoms of hypothalamic dysfunction, and seizures. It commonly precedes the diagnosis of cancer. Small-cell lung cancer is the neoplasm that is most frequently reported as the etiology underlying PLE. Case Report This report describes a male patient who presented with neurologic symptoms consistent with anterograde amnesia, apathy, and disorientation. MRI revealed diffuse hyperintensities located predominantly in the medial bitemporal lobes, basal ganglia, frontal lobes, and leptomeninges on fluid attenuated inversion recovery images, suggesting PLE. Study of the primary tumor revealed squamous cell carcinoma of the lung. The patient was treated with neoadjuvant chemotherapy followed by surgery and adjuvant chemoradiotherapy, which resulted in his neurologic symptoms gradually improving. Conclusions PLE might be a rare debut of squamous cell carcinoma of the lung. Treatment of the primary tumor may improve the neurologic symptoms. PMID:25628742

  20. Inhibitory effect of berberine on human skin squamous cell carcinoma A431 cells.

    PubMed

    Li, D X; Zhang, J; Zhang, Y; Zhao, P W; Yang, L M

    2015-09-08

    Berberine (BBR) is a natural alkaloid with significant anti-tumor activity against many types of cancer cells. In this study, we investigated the molecular mechanisms employed by BBR to repress the proliferation and growth of skin squamous cell carcinoma A431 cells. Berberine was reported to inhibit the proliferation of A431 cells in a dose- and time-dependent manner and was observed to induce a series of biochemical events, including the loss of mitochondrial membrane potential, release of cytochrome-c to cytosol, induction of proteins of the Bcl-2 family and caspases, and the cleavage of poly(ADP)-ribose polymerase. This suggested its ability to induce apoptosis. The results of a wound healing test revealed that berberine inhibited the migration of A431 cells. Ezrin was transfected into A431 cells by RNA interference. The level of expression of Ezrin in the transfected A431 cells was observed to decrease with berberine treatment, which suggested that berberine might inhibit the invasion of A431 cells through Ezrin. The results of this study demonstrated that berberine could potentially inhibit proliferation, induce apoptosis, and inhibit the invasion of A431 cells.

  1. Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.

    PubMed

    Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria

    2016-10-01

    Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.

  2. [Current recommendations in the treatment of basal cell carcinoma and squamous cell carcinoma of the skin].

    PubMed

    Kunte, C; Konz, B

    2007-05-01

    The incidence of the most common tumors of the skin, basal cell carcinoma and squamous cell carcinoma, has risen rapidly in recent years. Dermatologists see in their daily practice many different clinical and histological variants of these tumors. They must be able to develop therapeutic strategies adapted to the tumor and the patient. Surgical excision remains the standard treatment. Micrographic histological evaluation should be employed in difficult locations, for large tumors and when there is increased risk of recurrence or metastasis. For initial or superficial lesions, other approaches such as radiation therapy, as well as curettage, cryosurgery, laser therapy and photodynamic therapy can be employed. An additional option is topical treatment with imiquimod or 5-flourouracil.

  3. Targeting BMI1(+) Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma.

    PubMed

    Chen, Demeng; Wu, Mansi; Li, Yang; Chang, Insoon; Yuan, Quan; Ekimyan-Salvo, Mari; Deng, Peng; Yu, Bo; Yu, Yongxin; Dong, Jiaqiang; Szymanski, John M; Ramadoss, Sivakumar; Li, Jiong; Wang, Cun-Yu

    2017-03-08

    Squamous cell carcinoma in the head and neck (HNSCC) is a common yet poorly understood cancer, with adverse clinical outcomes due to treatment resistance, recurrence, and metastasis. Putative cancer stem cells (CSCs) have been identified in HNSCC, and BMI1 expression has been linked to these phenotypes, but optimal treatment strategies to overcome chemotherapeutic resistance and eliminate metastases have not yet been identified. Here we show through lineage tracing and genetic ablation that BMI1(+) CSCs mediate invasive growth and cervical lymph node metastasis in a mouse model of HNSCC. This model and primary human HNSCC samples contain highly tumorigenic, invasive, and cisplatin-resistant BMI1(+) CSCs, which exhibit increased AP-1 activity that drives invasive growth and metastasis of HNSCC. Inhibiting AP-1 or BMI1 sensitized tumors to cisplatin-based chemotherapy, and it eliminated lymph node metastases by targeting CSCs and the tumor bulk, suggesting potential regimens to overcome resistance to treatments and eradicate HNSCC metastasis.

  4. Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells.

    PubMed

    Mishra, Nawneet; Timilsina, Uddhav; Ghimire, Dibya; Dubey, Ravi C; Gaur, Ritu

    2017-01-22

    Mitochondrial Dysfunction has been implicated in multiple human diseases, including cancer. Among all cancer, lung cancer is the most common type of cancer worldwide with low survival rates. Mammals possess multiple subunits of the mitochondrial enzyme Cytochrome C oxidase (COX). The COX subunits are expressed in a tissue specific manner and have been implicated in cancer cell metabolism although their molecular and regulatory mechanisms are not clearly understood. In this study, we aimed at identifying novel gene signatures in lung cancer. We performed extensive analysis of seven different Gene Expression Omnibus (GEO) datasets pertaining to different stages of lung adenocarcinoma and identified that multiple subunits of COX genes are differentially expressed in these patients. Amongst all COX genes, the expression of COX7A1 gene was observed to be highly down regulated in these patients. In order to validate the GEO datasets, we looked at the expression of multiple COX genes using quantitative real time PCR (qPCR) using human lung adenocarcinoma cell line A549. Our results confirmed that COX 7A1 gene expression was indeed highly reduced in these cells. Overexpression of COX7A1 in human lung cancer cells led to inhibition of cell proliferation and increase in cell death via apoptosis. These results indicated that low level of COX7A1 gene expression is essential to regulate cell viability and inhibit cell death in lung adenocarcinoma. Our study has identified COX7A1 as a novel gene that might play a crucial role in the etiology of lung adenocarcinoma and can serve as a biomarker for lung cancer disease progression.

  5. Different muscarinc receptors are involved in the proliferation of murine mammary adenocarcinoma cell lines.

    PubMed

    Español, Alejandro J; Sales, María E

    2004-02-01

    We described that two different murine mammary adenocarcinoma cell lines, LM3 and LM2 constitutively expressed muscarinic acetylcholine receptors (mAchR). We here demonstrate, by competitive binding experiments with the tritiated muscarinic antagonist quinuclidinyl benzilate that M2 subtype predominates in both tumor cell lines. Concordantly immunoblotting assays indicate that mAchR exhibit the following order of expression: M2 > M4 > M3 > M1 > M5 in both tumor cell lines. Activation of mAchR with carbachol (CARB) increased proliferation in both tumor cell lines in a concentration dependent manner. In LM3 cells CARB promoted proliferation via M3 receptor activation via inositol 1,4,5-triphosphate and nitric oxide production. CARB-induced LM2 cells proliferation needed both M2 and M1 receptor activation, promoting prostaglandin E2 liberation and arginase catabolism respectively, both of them involved in tumor cell growth.

  6. Combined neuroendocrine cell carcinoma and adenocarcinoma of the gallbladder: report of a case.

    PubMed

    Shimizu, Tetsuya; Tajiri, Takashi; Akimaru, Koho; Arima, Yasuo; Yoshida, Hiroshi; Yokomuro, Shigeki; Mamada, Yasuhiro; Taniai, Nobuhiko; Mizuguchi, Yoshiaki; Kawahigashi, Yutaka; Naito, Zenya

    2006-04-01

    A 58-year-old man with a chief complaint of epigastralgia was admitted to our hospital. Physical examination disclosed a large, firm mass in the right hypochondrium. Abdominal computed tomography confirmed thickening of the gallbladder wall and a 15 x 8 cm mass occupying almost all of the right lobe and medial segment of the liver. With a preoperative diagnosis of malignant gallbladder tumor infiltrating the liver, right hepatic trisegmentectomy was performed. Histopathologic examination showed atypical cells with small round to oval nuclei and sparse eosinophilic cytoplasm, proliferating in a solid and focal nesting pattern. Near this small cell proliferation was a focus of tubular adenocarcinoma that showed a zone of transition from the small cell neuroendocrine pattern. The small cells demonstrated immunohistochemical reactivity for chromogranin A. Electron microscopy disclosed neurosecretory granules 150 nm in diameter, representing dense round core vesicles, confirming a neuroendocrine cell lineage. The patient was diagnosed with neuroendocrine cell carcinoma combined with adenocarcinoma of the gallbladder. Tumor recurrence became evident 3 months after surgery, and he died 4 months after surgery.

  7. Aptamers Selected to Postoperative Lung Adenocarcinoma Detect Circulating Tumor Cells in Human Blood

    PubMed Central

    Zamay, Galina S; Kolovskaya, Olga S; Zamay, Tatiana N; Glazyrin, Yury E; Krat, Alexey V; Zubkova, Olga; Spivak, Ekaterina; Wehbe, Mohammed; Gargaun, Ana; Muharemagic, Darija; Komarova, Mariia; Grigorieva, Valentina; Savchenko, Andrey; Modestov, Andrey A; Berezovski, Maxim V; Zamay, Anna S

    2015-01-01

    Circulating tumor cells (CTCs) are rare cells and valuable clinical markers of prognosis of metastasis formation and prediction of patient survival. Most CTC analyses are based on the antibody-based detection of a few epithelial markers; therefore miss an important portion of mesenchymal cancer cells circulating in blood. In this work, we selected and identified DNA aptamers as specific affinity probes that bind to lung adenocarcinoma cells derived from postoperative tissues. The unique feature of our selection strategy is that aptamers are produced for lung cancer cell biomarkers in their native state and conformation without previous knowledge of the biomarkers. The aptamers did not bind to normal lung cells and lymphocytes, and had very low affinity to A549 lung adenocarcinoma culture. We applied these aptamers to detect CTCs, apoptotic bodies, and microemboli in clinical samples of peripheral blood of lung cancer and metastatic lung cancer patients. We identified aptamer-associated protein biomarkers for lung cancer such as vimentin, annexin A2, annexin A5, histone 2B, neutrophil defensin, and clusterin. Tumor-specific aptamers can be produced for individual patients and synthesized many times during anticancer therapy, thereby opening up the possibility of personalized diagnostics. PMID:26061649

  8. Prognostic significance of NDRG1 expression in oral and oropharyngeal squamous cell carcinoma.

    PubMed

    Dos Santos, Marcelo; da Cunha Mercante, Ana Maria; Nunes, Fábio Daumas; Leopoldino, Andréia Machado; de Carvalho, Marcos Brasilino; Gazito, Diana; López, Rossana Verónica Mendoza; Chiappini, Paula Blandina Olga; de Carvalho Neto, Paulo Bentes; Fukuyama, Erica Erina; Tajara, Eloiza Helena; Louro, Iúri Drumond; da Silva, Adriana Madeira Álvares

    2012-12-01

    Human N-myc downstream-regulated gene 1 (NDRG1) is a metastasis suppressor gene with several potential functions, including cell differentiation, cell cycle regulation and response to hormones, nickel and stress. The purpose of this study was to investigate the immunoexpression of NDRG1 in oral and oropharyngeal squamous cell carcinomas searching for its role in the clinical course of these tumors. We investigated immunohistochemical expression of NDRG1 protein in 412 tissue microarray cores of tumor samples from 103 patients with oral and oropharyngeal squamous cell carcinomas and in 110 paraffin-embedded surgical margin sections. The results showed NDRG1 up-regulation in 101/103 (98.1 %) tumor samples, but no expression in any normal tissue sample. Western blot assays confirmed the immunohistochemical findings, suggesting that lower levels of NDRG1 are associated with a high mortality rate. NDRG1 overexpression was related to long-term specific survival (HR = 0.38; p = 0.009), whereas the presence of lymph-node metastasis showed the opposite association with survival (HR = 2.45; p = 0.013). Our findings reinforce the idea that NDRG1 plays a metastasis suppressor role in oral and oropharyngeal squamous cell carcinomas and may be a useful marker for these tumors.

  9. Mechanisms of asbestos-induced squamous metaplasia in tracheobronchial epithelial cells

    SciTech Connect

    Cameron, G.; Woodworth, C.D.; Edmondson, S.; Mossman, B.T. )

    1989-03-01

    Within 1 to 4 weeks after exposure to asbestos, differentiated rodent and human tracheobronchial epithelial cells in organ culture undergo squamous metaplasia, a putative preneoplastic lesion characterized by conversion of mucociliary cell types to keratinizing cells. The exogenous addition of retinal acetate (RA) to culture medium of hamster tracheal organ cultures reverses preestablished, asbestos-induced squamous metaplasia, although data suggest that the effectiveness of RA decreases as the length of time between exposure to asbestos and initial application of RA increases. Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), inhibits squamous metaplasia caused by asbestos or vitamin A deficiency, whereas addition of methylglyoxal bis(guanyl-hydrazone) (MGBG), a structural analog of spermidine and inhibitor of S-adenosylmethionine decarboxylase, causes an enhancement of metaplasia under both circumstances. Basal cell hyperplasia and increased incorporation of {sup 3}H-thymidine by tracheal epithelial cells also are seen after addition of the polyamines, putrescine or spermidine, to tracheal organ cultures, an observation supporting the importance of polyamines in the development of this lesion. The use of retinoids and inhibitors of ODC could be promising as preventive and/or therapeutic approaches for individuals at high risk for development of asbestos-associated diseases.

  10. Impact of genetic targets on therapy in head and neck squamous cell carcinoma.

    PubMed

    Chaikhoutdinov, Irina; Goldenberg, David

    2013-01-01

    Despite advances in surgical technique, radiation therapy and chemotherapy, the mortality from head and neck squamous cell carcinoma (HNSCC) has not improved significantly. Squamous cell carcinoma is caused by tobacco use, alcohol consumption and infection with high-risk types of human papillomavirus. It is the 6th most common cancer in the world, with upwards of 45,000 new cases reported yearly in the United States alone.In recent years, there has been a significant increase in the understanding of the molecular and genetic pathogenesis of head and neck cancer, shedding light on the unexpected heterogeneity of the disease. Genetic analysis has led to new classification schemes for HNSCC, with different subgroups exhibiting different prognoses. In addition, multiple targets in aberrant signaling pathways have been identified using increasingly sophisticated bio-informatics tools. Advances in technology have allowed for novel delivery mechanisms to introduce genetic material into cells to produce a therapeutic effect by targeting cancer cells via a number of different approaches.A pressing need to develop novel therapies to augment current treatment modalities has led to a number of translational studies involving gene therapy in the treatment of HNSCC. This article will focus on a review of the most recent developments in molecular biology of head and neck squamous cell carcinoma in regards to possible targets for gene therapy, as well as the array of novel therapeutic strategies directed at these targets.

  11. IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study

    PubMed Central

    Soddu, S.; Di Felice, E.; Cabras, S.; Castellanos, M.E.; Atzori, L.; Faa, G.; Pilloni, L.

    2013-01-01

    The protein insulin-like growth factor II mRNA binding protein 3 (IMP-3) is an important factor for cell migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP-3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. The purpose of this study is to compare IMP-3 immunostaining in cutaneous squamous cell tumors and determine whether IMP-3 can aid in the differential diagnosis of these lesions. To our knowledge, IMP-3 expression has not been investigated in skin squamous cell proliferations thus far. Immunohi-stochemical staining for IMP-3 was performed on slides organized by samples from 67 patients, 34 with keratoacanthoma (KA) and 33 with primary cutaneous squamous cell carcinoma (SCC) (16 invasive and 17 in situ). Seventyfour percent of KAs (25/34) were negative for IMP-3 staining, while 57% of SCCs (19/33) were positive for IMP-3 staining. The percentage of IMP-3 positive cells increased significantly in the invasive SCC group (P=0.0111), and particularly in the SCC in situ group (P=0.0021) with respect to the KA group. IMP-3 intensity staining was significantly higher in invasive SCCs (P=0.0213), and particularly in SCCs in situ (P=0.008) with respect to KA. Our data show that IMP-3 expression is different in keratoacanthoma with respect to squamous cell carcinoma. IMP-3 assessment and staining pattern, together with a careful histological study, can be useful in the differential diagnosis between KA e SCC. PMID:23549465

  12. Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

    ClinicalTrials.gov

    2016-03-17

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer

  13. Autophagy as a Survival Mechanism for Squamous Cell Carcinoma Cells in Endonuclease G-Mediated Apoptosis

    PubMed Central

    Masui, Atsushi; Hamada, Masakazu; Kameyama, Hiroyasu; Wakabayashi, Ken; Takasu, Ayako; Imai, Tomoaki; Iwai, Soichi; Yura, Yoshiaki

    2016-01-01

    Safingol, L- threo-dihydrosphingosine, induces cell death in human oral squamous cell carcinoma (SCC) cells through an endonuclease G (endoG) -mediated pathway. We herein determined whether safingol induced apoptosis and autophagy in oral SCC cells. Safingol induced apoptotic cell death in oral SCC cells in a dose-dependent manner. In safingol-treated cells, microtubule-associated protein 1 light chain 3 (LC3)-I was changed to LC3-II and the cytoplasmic expression of LC3, amount of acidic vesicular organelles (AVOs) stained by acridine orange and autophagic vacuoles were increased, indicating the occurrence of autophagy. An inhibitor of autophagy, 3-methyladenine (3-MA), enhanced the suppressive effects of safingol on cell viability, and this was accompanied by an increase in the number of apoptotic cells and extent of nuclear fragmentation. The nuclear translocation of endoG was minimal at a low concentration of safingol, but markedly increased when combined with 3-MA. The suppressive effects of safingol and 3-MA on cell viability were reduced in endoG siRNA- transfected cells. The scavenging of reactive oxygen species (ROS) prevented cell death induced by the combinational treatment, whereas a pretreatment with a pan-caspase inhibitor z-VAD-fmk did not. These results indicated that safingol induced apoptosis and autophagy in SCC cells and that the suppression of autophagy by 3-MA enhanced apoptosis. Autophagy supports cell survival, but not cell death in the SCC cell system in which apoptosis occurs in an endoG-mediated manner. PMID:27658240

  14. CD30+ cells in regressing keratoacanthoma and in non-keratoacanthomatous squamous cell carcinoma.

    PubMed

    Fernandez-Flores, A

    2008-01-01

    In a previous report, we demonstrated how a percentage of CD30+ cells was nearly constant in the inflammatory infiltrate that accompanies keratoacanthoma (KA), but we saw a lack of CD30 cells when KA was regressing. In the current study we investigated the presence of CD30+ cells in the inflammatory infiltrate of regressing KA as well as in well-differentiated squamous cell carcinomas of non-keratoacanthomatous type. We examined 80 keratoacanthomas from our archives, and selected those with the pattern of advanced regression. We also examined 14 well-differentiated non-KA type SCCs from our archives. In all the cases, we performed a immunohistochemical study for CD30. Of the 80 KAs, 6 cases (7.5%) showed the pattern of regression. While the mean of the percentages of CD30+ cells in the infiltrate was 0.58 for the regressing KAs, it was 1.77 for SCCs. While cells with the paranuclear-dot pattern of immunostaining plus membranous pattern of immunostaining could be easily found in SCC cases, cells only with membranous expression of the marker were the rule in KA. We conclude that CD30 positive cells might play a role in KA regression (Tab. 2, Fig. 4, Ref. 24).

  15. 9-{beta}-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

    SciTech Connect

    Heaton, D.; Mustafi, R.; Schwartz, J.L. |

    1992-06-01

    The effect of 9-{beta}-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D{sub 0} values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D{sub 0} values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 {mu}M) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 {mu}M were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo.

  16. Para-toluenesulfonamide induces tongue squamous cell carcinoma cell death through disturbing lysosomal stability.

    PubMed

    Liu, Zhe; Liang, Chenyuan; Zhang, Zhuoyuan; Pan, Jian; Xia, Hui; Zhong, Nanshan; Li, Longjiang

    2015-11-01

    Para-toluenesulfonamide (PTS) has been implicated with anticancer effects against a variety of tumors. In the present study, we investigated the inhibitory effects of PTS on tongue squamous cell carcinoma (Tca-8113) and explored the lysosomal and mitochondrial changes after PTS treatment in vitro. High-performance liquid chromatography showed that PTS selectively accumulated in Tca-8113 cells with a relatively low concentration in normal fibroblasts. Next, the effects of PTS on cell viability, invasion, and cell death were determined. PTS significantly inhibited Tca-8113 cells' viability and invasive ability with increased cancer cell death. Flow cytometric analysis and the lactate dehydrogenase release assay showed that PTS induced cancer cell death by activating apoptosis and necrosis simultaneously. Morphological changes, such as cellular shrinkage, nuclear condensation as well as formation of apoptotic body and secondary lysosomes, were observed, indicating that PTS might induce cell death through disturbing lysosomal stability. Lysosomal integrity assay and western blot showed that PTS increased lysosomal membrane permeabilization associated with activation of lysosomal cathepsin B. Finally, PTS was shown to inhibit ATP biosynthesis and induce the release of mitochondrial cytochrome c. Therefore, our findings provide a novel insight into the use of PTS in cancer therapy.

  17. Squamous cell carcinoma developing in a long-standing case of tuberous xanthoma: An incident unreported hitherto

    PubMed Central

    Sancheti, Karan; Das, Anupam; Podder, Indrashis; Mohanty, Swosti; Gharami, Ramesh C.; Jash, Prabir K.

    2015-01-01

    Cutaneous squamous cell carcinoma, characterized by malignant transformation of normal epidermal keratinocyte is the second most common nonmelanoma skin cancer that has many predisposing factors. Tuberous xanthomas have not yet been reported as a predisposing factor. We report here the case of long-standing tuberous xanthoma in a middle-aged gentleman complicated by cutaneous squamous cell carcinoma, probably the first such report in the Indian literature. PMID:26904452

  18. Unusual presentation of squamous cell carcinoma in young female patient: A case report and review of literature

    PubMed Central

    Kaur, Jasbir; Singh, Anantpreet; Chopra, Rohit

    2016-01-01

    Oral squamous cell carcinoma is the most common “malignant neoplasm” of epithelial origin usually affecting individuals over 50 years of age. It is rare in patients aged <40 years old. This report describes a case of squamous cell carcinoma involving anterior mandibular alveolar region in a 17-year-old female patient, with no history of deleterious habits. This report focuses on etiological factors, diagnosis and prognosis related to the case. PMID:27194884

  19. Cutaneous squamous cell carcinoma presenting as a wound with discharging sinus tracts in a wild African lion (Panthera leo).

    PubMed

    Mwase, M; Mumba, C; Square, D; Kawarai, S; Madarame, H

    2013-11-01

    A female wild African lion (Panthera leo) was presented with an 8-month history of a wound with multiple discharging sinus tracts on the left paw. Microscopical examination revealed squamous cell carcinoma (SCC). To the best of our knowledge, this is the first report of cutaneous SCC in an African lion. Cutaneous SCC presenting as discharging sinus tracts lined by neoplastic squamous cells has not been reported previously in animals.

  20. In vivo gene transfer targeting in pancreatic adenocarcinoma with cell surface antigens

    PubMed Central

    2012-01-01

    Background Pancreatic ductal adenocarcinoma is a deadly malignancy resistant to current therapies. It is critical to test new strategies, including tumor-targeted delivery of therapeutic agents. This study tested the possibility to target the transfer of a suicide gene in tumor cells using an oncotropic lentiviral vector. Results Three cell surface markers were evaluated to target the transduction of cells by lentiviruses pseudotyped with a modified glycoprotein from Sindbis virus. Only Mucin-4 and the Claudin-18 proteins were found efficient for targeted lentivirus transductions in vitro. In subcutaneous xenografts of human pancreatic cancer cells models, Claudin-18 failed to achieve efficient gene transfer but Mucin-4 was found very potent. Human pancreatic tumor cells were modified to express a fluorescent protein detectable in live animals by bioimaging, to perform a direct non invasive and costless follow up of the tumor growth. Targeted gene transfer of a bicistronic transgene bearing a luciferase gene and the herpes simplex virus thymidine kinase gene into orthotopic grafts was carried out with Mucin-4 oncotropic lentiviruses. By contrast to the broad tropism VSV-G carrying lentivirus, this oncotropic lentivirus was found to transduce specifically tumor cells, sparing normal pancreatic cells in vivo. Transduced cells disappeared after ganciclovir treatment while the orthotopic tumor growth was slowed down. Conclusion This work considered for the first time three aspect of pancreatic adenocarcinoma targeted therapy. First, lentiviral transduction of human pancreatic tumor cells was possible when cells were grafted orthotopically. Second, we used a system targeting the tumor cells with cell surface antigens and sparing the normal cells. Finally, the TK/GCV anticancer system showed promising results in vivo. Importantly, the approach presented here appeared to be a safer, much more specific and an as efficient way to perform gene delivery in pancreatic tumors

  1. Multistep process of squamous differentiation in tracheobronchial epithelial cells in vitro: analogy with epidermal differentiation.

    PubMed Central

    Jetten, A M

    1989-01-01

    The lung, in particular the bronchial epithelium, is a major site for tumor formation in humans. Environmental factors, such as cigarette smoke, in conjunction with genetic factors are important determinants in this disease. Malignant cells exhibit alterations in their control of proliferation and differentiation. It is believed that the acquisition of defects in the regulation of these processes is important in the process of carcinogenesis. A clear insight into the basic mechanisms of the regulation of proliferation and differentiation is required to understand the molecular mechanisms involved in tumor development and in other pathological conditions. Studies using in vitro cell culture systems of tracheobronchial epithelial cells provide useful models in which to study the regulation of differentiation and proliferation. The clonogenic cells derived from the treacheobronchial epithelium are pluripotent: They have self-renewal capacity and can differentiate along either a normal, mucosecretory, or a squamous cell pathway. Squamous differentiation in tracheobronchial epithelial cells has many morphological, biochemical, and regulatory properties in common with epidermal differentiation. This pathway of differentiation is a multistep process consisting of at least three stages. In the initial stage, cells become committed to terminal cell division. This is followed by the expression of the squamous differentiated phenotype and finally cornification. Various factors, such as several growth factors, retinoids, calcium ions, and phorbol esters, regulate the program of differentiation at different stages. Studies have indicated that the controls of proliferation and differentiation are interrelated. Cell lines established from tracheobronchial epithelial cells expressing SV 40 large T-antigen, as well as carcinoma cell lines, exhibit altered responses to growth and differentiation regulatory factors. Alterations in the commitment to terminal cell division must be a

  2. Bax is not involved in the resveratrol-induced apoptosis in human lung adenocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Zhang, Wei-wei; Wang, Zhi-ping; Chen, Tong-sheng

    2010-02-01

    Resveratrol (RV) is a natural plant polyphenol widely present in foods such as grapes, wine, and peanuts. Previous studies indicate that RV has an ability to inhibit various stages of carcinogenesis and eliminate preneoplastic cells in vitro and in vivo. However, little is known about the molecular mechanism of RV-induced apoptosis in human lung adenocarcinoma (ASTC-a-1) cell. In this report, we analyzed whether Bax translocation from cytoplasm to mitochondria during RV-induced apoptosis in single living cell using onfocal microscopey. Cells were transfected with GFP-Bax plasmid. Cell counting kit (CCK-8) assay was used to assess the inhibition of RV on the cells viability. Apoptotic activity of RV was detected by Hoechst 33258 and propidium iodide (PI) staining. Our results showed that RV induced a dose-dependent apoptosis in which Bax did not translocate to mitochondrias.

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

    PubMed Central

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

    2015-01-01

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

  4. Retracted: Knockdown of tumor protein D52-like 2 induces cell growth inhibition and apoptosis in oral squamous cell carcinoma.

    PubMed

    2016-03-01

    The above article, published online on 13 October 2014 in Wiley Online Library (http://onlinelibrary.wiley.com/doi/10.1002/cbin.10388/abstract), has been retracted by agreement between the authors, the journal Editor, Sergio Schenkman, and John Wiley & Sons Ltd. The retraction has been agreed because the authors discovered after publication that one of the cell lines described in the article had been unintentionally misidentified. The experiments described in the article as being conducted on Human Oral Squamous Cell Carcinoma cell line KB were in fact conducted on a Human Oral Epidermal-like Cancer cell line. The authors and publisher apologise for any inconvenience. References He Y, Chen F, Cai Y and Chen S (2015) Knockdown of tumor protein D52-like 2 induces cell growth inhibition and apoptosis in oral squamous cell carcinoma. Cell Biology International 39: 264-271. doi: 10.1002/cbin.10388.

  5. Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas

    PubMed Central

    WU, JEAN; MU, QINGSHAN; THIVIYANATHAN, VARATHARASA; ANNAPRAGADA, ANANTH; VIGNESWARAN, NADARAJAH

    2014-01-01

    Fanconi anemia (FA) patients have an increased risk of head and neck squamous cell carcinoma (HNSCC) at a higher rate with no apparent risk factors. HNSCC of FA patients is an aggressive tumor characterized by multifocal origin, early metastases and frequent recurrences. Given that cancer stem cells (CSC) drive tumorigenesis, tumor recurrence and metastasis, in this study, we characterized the CSC population in FA and sporadic HNSCC. The Aldefluor assay was used to characterize and isolate CSC with high aldehyde dehydrogenase (ALDH) activity (ALDHpos) in cell lines derived from FA and sporadic HNSCC. Isolated ALDHpos and ALDHneg cells were examined for the expression of stemness genes using reverse transcription-polymerase chain reaction (RT-PCR) array. Tumor cell-derived FA and sporadic HNSCC were examined for their ability to form tumorspheres in vitro. Stem-like cell population in FA and sporadic HNSCC in human and mouse xenograft tumors were evaluated using ALDH isoform 1 (ALDH1) immunohistochemistry. FA-HNSCC cell lines harbor a greater proportion of ALDHpos cells (15–31%) compared to sporadic HNSCC (10%). Expression of Nanog, Oct-3/4 and Stella, molecular markers of undifferentiated embryonic stem (ES) cells were detected in the ALDHpos FA-HNSCC cells and not in the ALDHneg cells. FA-HNSCC cell lines revealed enhanced in vitro tumorsphere formation compared to sporadic HNSCC cells. A higher percentage of ALDH1pos tumor cells are noted in the human and mouse xenograft tumors of FA-HNSCC compared to sporadic HNSCC tumors. FA-HNSCC are highly enriched for CSC and may serve as a model to develop CSC-targeted therapies for HNSCC. PMID:25340704

  6. Therapeutic effects of sorafenib on the A549/DDP human lung adenocarcinoma cell line in vitro.

    PubMed

    Chen, Xiang-Qi; Wang, Yu-Lan; Li, Zhi-Ying; Lin, Ting-Yan

    2014-07-01

    The aim of the present study was to observe the effects of sorafenib on the proliferation, apoptosis and invasion of A549/DDP cisplatin-resistant lung adenocarcinoma cells cultured in vitro. The A549/DDP cisplatin-resistant lung adenocarcinoma cell strain was cultured in vitro, the cell culture group incubated in culture medium only was set as the control group (Group S0) and the four concentration gradients of sorafenib were added to the culture groups as the experimental groups: S1, 2 µmol/l; S2, 4 µmol/l; S3, 8 µmol/l; and S4, 16 µmol/l. The MTT assay was used to determine the growth inhibition rate of the cells, which were respectively subjected to sorafenib treatment for 24, 48 and 72 h. Flow cytometry was used to determine the rate of apoptosis of cells in each group following sorafenib treatment for 72 h. Furthermore, the Transwell invasion experiment was used to determine the effect on A549/DDP cell invasion following sorafenib treatment for 24 h. Based on the MTT assay, it was found that the inhibition rates of A549/DDP cisplatin-resistant lung adenocarcinoma cells in groups S1-4 following sorafenib treatment for 24 h were 4.58±2.82, 14.93±2.62, 37.58±7.13 and 58.39±8.15%, respectively. For 48 h, inhibition rates in S1-4 were 14.98±2.93, 26.28±7.31, 63.00±3.05 and 78.84±3.96%, respectively, and for 72 h, inhibition rates were 18.80±2.82, 32.71±2.55, 75.51±4.73 and 87.50±3.36%, respectively. The difference in the inhibition rates of cells among the experimental groups for the same incubation time showed statistical significance (P<0.05). Flow cytometric analysis indicated that the rate of apoptosis in the control group was 8.88±0.81% following sorafenib treatment for 72 h, and the rates of apoptosis in groups S1-4 were, 12.84±0.24, 17.27±0.78, 21.98±0.75 and 49.67±1.38%, respectively. The rate of apoptosis in each experimental group was higher compared with that in the control group (P<0.05). The difference in the rate of apoptosis

  7. Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma.

    PubMed

    Lee, H Z; Hsu, S L; Liu, M C; Wu, C H

    2001-11-23

    Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum. The study investigated the effects and mechanisms of aloe-emodin-induced cell death in human lung squamous cell carcinoma cell line CH27. Aloe-emodin (40 microM)-induced CH27 cell apoptosis was confirmed by DNA fragmentation (DNA ladders and sub-G(1) formation). Aloe-emodin-induced apoptosis of CH27 cells involved modulation of the expression of Bcl-2 family proteins, such as BclX(L), Bag-1, and Bak, and was associated with the translocation of Bak and Bax from cytosolic to particulate fractions. Aloe-emodin-treated CH27 cells had an increased relative abundance of cytochrome c in the cytosolic fraction. Results demonstrated that the activation of caspase-3, caspase-8, and caspase-9 is an important determinant of apoptotic death induced by aloe-emodin. These results suggest that aloe-emodin induces CH27 cell death by the Bax and Fas death pathway.

  8. Deguelin Induces Both Apoptosis and Autophagy in Cultured Head and Neck Squamous Cell Carcinoma Cells

    PubMed Central

    Bi, Zhi-gang; Lu, Chun-cheng; Wang, Rong; Gu, Bing; Cheng, Lei

    2013-01-01

    Head and neck squamous cell carcinoma (HNSCC) represents more than 5% of all cancers diagnosed annually in United States and around the world. Despite advances in the management of patients with this disease, the survival has not been significantly improved, and the search for potential alternative therapies is encouraging. Here we demonstrate that deguelin administration causes a significant HNSCC cell death. Deguelin induces both cell apoptosis and autophagy by modulating multiple signaling pathways in cultured HNSCC cells. Deguelin inhibits Akt signaling, and down-regulates survivin and cyclin-dependent kinase 4 (Cdk4) expressions, by disrupting their association with heat shock protein-90 (Hsp-90). Deguelin induces ceramide production through de novo synthase pathway to promote HNSCC cell death. Importantly, increased ceramide level activates AMP-activated protein kinase (AMPK), which then directly phosphorylates Ulk1 and eventually leads to cell autophagy. We found that a low dose of deguelin sensitized HNSCC cells to 5-FU. Finally, using a nude mice Hep-2 xenograft model, we also showed a significant anti-tumor ability of deguelin in vivo. Together, we suggest that deguelin may represent a novel and effective chemo-agent against HNSCC. PMID:23372762

  9. Effect of ionizing radiation on the physical biology of head and neck squamous cell carcinoma cells

    PubMed Central

    Baker-Groberg, Sandra M.; Bornstein, Sophia; Zilberman-Rudenko, Jevgenia; Schmidt, Mark; Tormoen, Garth W.; Kernan, Casey; Thomas, Charles R.; Wong, Melissa H.; Phillips, Kevin G.; McCarty, Owen J.T.

    2015-01-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide. Although there are numerous treatment options for HNSCC, such as surgery, cytotoxic chemotherapy, molecularly targeted systemic therapeutics, and radiotherapy, overall survival has not significantly improved in the last 50 years. This suggests a need for a better understanding of how these cancer cells respond to current treatments in order to improve treatment paradigms. Ionizing radiation (IR) promotes cancer cell death through the creation of cytotoxic DNA lesions, including single strand breaks, base damage, crosslinks, and double strand breaks (DSBs). As unrepaired DSBs are the most cytotoxic DNA lesion, defining the downstream cellular responses to DSBs are critical for understanding the mechanisms of tumor cell responses to IR. The effects of experimental IR on HNSCC cells beyond DNA damage in vitro are ill-defined. Here we combined label-free, quantitative phase and fluorescent microscopy to define the effects of IR on the dry mass and volume of the HNSCC cell line, UM-SCC-22A. We quantified nuclear and cytoplasmic subcellular density alterations resulting from 8 Gy X-ray IR and correlated these signatures with DNA and γ-H2AX expression patterns. This study utilizes a synergistic imaging approach to study both biophysical and biochemical alterations in cells following radiation damage and will aid in future understanding of cellular responses to radiation therapy. PMID:26417394

  10. Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas.

    PubMed

    Shahrabi-Farahani, Shokoufeh; Wang, Lili; Zwaans, Bernadette M M; Santana, Jeans M; Shimizu, Akio; Takashima, Seiji; Kreuter, Michael; Coultas, Leigh; D'Amore, Patricia A; Arbeit, Jeffrey M; Akslen, Lars A; Bielenberg, Diane R

    2014-07-01

    Neuropilins (NRPs) are cell surface receptors for vascular endothelial growth factor (VEGF) and SEMA3 (class 3 semaphorin) family members. The role of NRPs in neurons and endothelial cells has been investigated, but the expression and role of NRPs in epithelial cells is much less clear. Herein, the expression and localization of NRP1 was investigated in human and mouse skin and squamous cell carcinomas (SCCs). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of the skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did co-localize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or epidermal growth factor-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity.

  11. Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas

    PubMed Central

    Shahrabi-Farahani, Shokoufeh; Wang, Lili; Zwaans, Bernadette M. M.; Santana, Jeans M.; Shimizu, Akio; Takashima, Seiji; Kreuter, Michael; Coultas, Leigh; D'Amore, Patricia A.; Arbeit, Jeffrey M.; Akslen, Lars A.; Bielenberg, Diane R.

    2014-01-01

    Neuropilins (NRP) are cell surface receptors for VEGF and SEMA3 family members. The role of NRP in neurons and endothelial cells has been investigated, but the expression and role of NRP in epithelial cells is much less clear. Herein, the expression and localization of neuropilin 1 (NRP1) was investigated in human and mouse skin and squamous cell carcinomas (SCC). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did colocalize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or EGF-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity. PMID:24791743

  12. Integrin α7 is a functional cancer stem cell surface marker in oesophageal squamous cell carcinoma

    PubMed Central

    Ming, Xiao-Yan; Fu, Li; Zhang, Li-Yi; Qin, Yan-Ru; Cao, Ting-Ting; Chan, Kwok Wah; Ma, Stephanie; Xie, Dan; Guan, Xin-Yuan

    2016-01-01

    Non-CG methylation has been associated with stemness regulation in embryonic stem cells. By comparing differentially expressed genes affected by non-CG methylation between tumour and corresponding non-tumour tissues in oesophageal squamous cell carcinoma (OSCC), we find that Integrin α7 (ITGA7) is characterized as a potential cancer stem cell (CSC) marker. Clinical data show that a high frequency of ITGA7+ cells in OSCC tissues is significantly associated with poor differentiation, lymph node metastasis and worse prognosis. Functional studies demonstrate that both sorted ITGA7+ cells and ITGA7 overexpressing cells display enhanced stemness features, including elevated expression of stemness-associated genes and epithelial–mesenchymal transition features, as well as increased abilities to self-renew, differentiate and resist chemotherapy. Mechanistic studies find that ITGA7 regulates CSC properties through the activation of the FAK-mediated signalling pathways. As knockdown of ITGA7 can effectively reduce the stemness of OSCC cells, ITGA7 could be a potential therapeutic target in OSCC treatment. PMID:27924820

  13. Effect of ionizing radiation on the physical biology of head and neck squamous cell carcinoma cells.

    PubMed

    Baker-Groberg, Sandra M; Bornstein, Sophia; Zilberman-Rudenko, Jevgenia; Schmidt, Mark; Tormoen, Garth W; Kernan, Casey; Thomas, Charles R; Wong, Melissa H; Phillips, Kevin G; McCarty, Owen J T

    2015-09-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide. Although there are numerous treatment options for HNSCC, such as surgery, cytotoxic chemotherapy, molecularly targeted systemic therapeutics, and radiotherapy, overall survival has not significantly improved in the last 50 years. This suggests a need for a better understanding of how these cancer cells respond to current treatments in order to improve treatment paradigms. Ionizing radiation (IR) promotes cancer cell death through the creation of cytotoxic DNA lesions, including single strand breaks, base damage, crosslinks, and double strand breaks (DSBs). As unrepaired DSBs are the most cytotoxic DNA lesion, defining the downstream cellular responses to DSBs are critical for understanding the mechanisms of tumor cell responses to IR. The effects of experimental IR on HNSCC cells beyond DNA damage in vitro are ill-defined. Here we combined label-free, quantitative phase and fluorescent microscopy to define the effects of IR on the dry mass and volume of the HNSCC cell line, UM-SCC-22A. We quantified nuclear and cytoplasmic subcellular density alterations resulting from 8 Gy X-ray IR and correlated these signatures with DNA and γ-H2AX expression patterns. This study utilizes a synergistic imaging approach to study both biophysical and biochemical alterations in cells following radiation damage and will aid in future understanding of cellular responses to radiation therapy.

  14. Cancer stem cells and field cancerization of oral squamous cell carcinoma.

    PubMed

    Simple, M; Suresh, Amritha; Das, Debashish; Kuriakose, Moni A

    2015-07-01

    Oral squamous cell carcinoma (OSCC) has a high propensity for local failure, which is attributed to recurrence at the primary site or the development of second primary tumors (SPT). Field cancerization that refers to the existence of transformed cells in areas adjacent to the primary tumor, has been attributed to be one of the probable reasons underlying disease relapse. The carcinogenic process necessitates multiple molecular events for the transformation of a normal cell into a cancer cell. This implies that only the long-time residents of the epithelium, such as the stem cells, might be the candidates capable of accumulating these genetic hits. These transformed stem cells- the 'Cancer stem cells' (CSCs), are further known to be equipped with the properties of tumor initiation and migration, both of which are essential for orchestrating field cancerization. The concept that the CSCs might be responsible for field cancerization in OSCC has not been explored extensively. If the role of CSCs as the primary units of field cancerization process is established, their presence in the mucosa adjacent to the tumor may be an indicator for local recurrence and/or development of second primary tumors. In this review, we examine the available evidence in literature exploring the possibilities of CSCs driving the process of field cancerization and thereby being the underlying mechanism for disease recurrence and development of SPT.

  15. A case of squamous cell carcinoma of the skin due to the molecularly confirmed Lynch Syndrome.

    PubMed

    Sorscher, Steven

    2015-01-01

    Patients with Lynch Syndrome are at high risk for developing a variety of cancers including cancers of the colon or rectum, small bowel, stomach, uterus, renal pelvis, ureter, biliary tract, ovaries, brain and pancreas (N Engl J Med 348: 919-32, 2003; Gut 57:1097-101, 2008; NCCN, Inc Guideline. Ft. Washington, PA. Online Version 2.2014). Lack of MLH-1 and MSH-2 expression commonly result from germline mutations in this inherited cancer syndrome. Here, we report the case of a patient with a molecularly confirmed germline mutation in MLH-1 along with a colon cancer showing lack of expression of MLH-1 as well as a squamous cell cancer of the skin from the abdominal wall also demonstrating lack of expression of MLH-1. This case appears to represent the second case report of a squamous cell skin cancer apparently due to the Lynch Syndrome and further supports a proposed relationship between Lynch Syndrome and these tumors.

  16. Squamous cell carcinoma of the umbilicus: management of an unusual localization.

    PubMed

    Macripò, Giuseppe; Caliendo, Virginia; Grassi, Marcella; Lista, Patrizia; Ribero, Simone; Giacone, Elena; Milanese, Enrica; Ciuffreda, Libero

    2011-01-01

    We describe the case of a squamous cell carcinoma spreading to the skin and regional lymph nodes from the umbilicus. Bilateral inguinal lymphadenectomy and a session of electrochemotherapy with bleomycin 15 mg/m2 were performed. However, because of the development of new cutaneous nodules in the abdominopelvic region, we performed targeted palliative therapy with erlotinib 150 mg/day. Targeted adjuvant therapy was preferred to the use of a major cytotoxic agent because of the high risk of superinfection and heart failure. Erlotinib produced a partial clinical response with reduction of the number and size of the skin nodules. CT scan performed after 60 days of treatment did not show any new lesions. To our knowledge, this is the first report of an umbilical metastatic squamous cell carcinoma treated with modern targeted therapy. This therapeutic strategy can be considered a valid palliative option in the management of metastatic cutaneous nodules of this rare primary site.

  17. Low frequency of human papillomavirus infection in conjunctival squamous cell carcinoma of Mexican patients

    PubMed Central

    2011-01-01

    Background The relationship between Human Papillomavirus (HPV) infection and conjunctiva cancer is controversial. HPV detection will provide more information about the role of this infectious agent in the biology of conjunctiva cancer. In the present study, DNA extracted and purified from 36 Conjunctival Squamous Cell Carcinomas (CSCC) was evaluated by PCR for HPV DNA sequences. The results were correlated with the clinical and histopathological variables. Results The results showed that HPV DNA was present in 8 CSCC samples (22%); HPV16 was the sole type detected. Significant association was found between HPV detection and the limbus tumor subtype (p = 0.03). All the samples were non-metastatic squamous cell carcinoma. Conclusions The HPV presence in CSCC from Mexican patients is not a common event. PMID:22099431

  18. Management of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma.

    PubMed

    Arslanoğlu, Seçil; Eren, Erdem; Özkul, Yılmaz; Ciğer, Ejder; Kopar, Aylin; Önal, Kazım; Etit, Demet; Tütüncü, G Yazgı

    2016-02-01

    The objective of this study was to determine the incidence of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma; and the association between clinicopathological parameters and thyroid gland invasion. Medical records of 75 patients with laryngeal and hypopharyngeal squamous cell carcinoma who underwent total laryngectomy with thyroidectomy were reviewed, retrospectively. Preoperative computed tomography scans, clinical and operative findings, and histopathological data of the specimens were evaluated. There were 73 male and two female patients with an age range of 41-88 years (mean 60.4 years). Hemithyroidectomy was performed in 62 (82.7 %) and total thyroidectomy was performed in 13 patients (17.3 %). Four patients had histopathologically proven thyroid gland invasion (5.3 %). In three patients, thyroid gland involvement was by means of direct invasion. Thyroid gland invasion was significantly correlated with thyroid cartilage invasion. Therefore, prophylactic thyroidectomy should not be a part of the treatment policy for these tumors.

  19. Squamous cell carcinoma and dental implants: A systematic review of case reports

    PubMed Central

    Jeelani, S.; Rajkumar, E.; Mary, G. Geena; Khan, Parvez Ahmad; Gopal, Harish; Roy, Soumya; Maheswaran, T.; Anand, B.

    2015-01-01

    Cancer is one of the leading causes of death world-wide. Apart from the most common etiopathological factors related to cancer, at times very rare causes such as irritant or foreign body induced carcinogenesis is not to be overlooked. To systematically review case reports concerned with the association between dental implants and oral squamous cell carcinoma. A Medline (PubMed), Cochrane database, and Google Scholar search was conducted of dental article published in English related to case reports concerned with oral squamous cell carcinoma occurring around dental implants from 2000 to 2014. Twenty articles were retrieved, which included 20 rare case reports which were systematically reviewed and the results were obtained pertaining to age, clinical symptoms, habits, previous history of cancer, potentially malignant disorders, systemic illness, and local factors. It is imperative to identify promptly persisting inflammation associated with implants. Since malignancy may disguise as periimplantitis, especially in patients who are at risk with contributing prominent predisposing factors. PMID:26538881

  20. Squamous cell carcinoma of the conjunctiva with extraocular involvement: case report and literature review.

    PubMed

    Goñi Espildora, Ignacio; Jans, Jaime; Petric Guajardo, Militza; Manzor Veliz, Manuel; Flores Pérez, Juan C; Varas Marchant, Gonzalo; Muñoz-Schuffenegger, Pablo; Zoroquiain, Pablo

    2016-05-26

    Squamous cell carcinoma of the conjunctiva is the most frequent malignant tumor of the ocular surface. It is a rare disease with an incidence of 0.13 to 1.9 per 100,000 inhabitants, mainly affecting individuals between 50 and 75 years of age. It tends to have a slow, non-aggressive course. Treatment depends on the extent of the tumor. If there is intraocular involvement, enucleation is indicated, and in the presence of extraocular involvement the orbital exenteration is the standard treatment. We report and discuss the case of an 82 year old male patient having a conjunctival squamous cell carcinoma with intra and extraocular involvement, together with a review of the literature.

  1. Combined radical radiation therapy and chemotherapy for primary squamous cell carcinoma of the anal canal

    SciTech Connect

    Cummings, B.J.; Rider, W.D.; Harwood, A.R.; Keane, T.J.; Thomas, G.M.; Erlichman, C.; Fine, S.

    1982-03-01

    Radical radiation therapy (5000 rads in 20 fractions in 4 weeks) combined with iv mitomycin (10 mg/m2) and 5-FU (1000 mg/m2/24 hours for 4 days) was used to treat 13 patients with locally advanced but operable squamous cell carcinoma of the anal canal. All patients achieved local control and retained anal continence, and none developed metastases. The patients were followed from 4 to 34 months (median, 12). Severe acute gastrointestinal toxic effects were seen in three patients; the same patients had significant thrombocytopenia or leukopenia. Treatment with this combined program may allow conservative management of squamous cell carcinoma of the anal canal and should be considered as an alternative to abdominoperineal resection.

  2. Multifocal aggressive squamous cell carcinomas induced by prolonged voriconazole therapy: a case report.

    PubMed

    Morice, C; Acher, A; Soufir, N; Michel, M; Comoz, F; Leroy, D; Verneuil, L

    2010-01-01

    Voriconazole is a treatment for severe fungal infections. Prolonged voriconazole therapy may induce skin reactions, with 1% of severe photosensitivity accidents. Recently the imputability of voriconazole in skin carcinogenesis has been suggested. This report concerns a 55-year-old man suffering from pulmonary aspergillosis who presented a phototoxic reaction a few months after introduction of voriconazole, followed by multiple squamous cell carcinomas of sun-exposed skin areas. After voriconazole discontinuation, no new carcinoma was observed. The detection of EBV and HPV in skin lesions was negative. Exploration of gene mutations involved in skin carcinogenesis showed two variants of the MICR gene. The occurrence of multiple, recurrent, aggressive squamous cell carcinomas is rare with voriconazole, but its imputability is strongly suggested. A plausible hypothesis is that several factors including voriconazole uptake, immunosuppression, and genetic background could explain the phenotype of fast-developing skin carcinomas. Voriconazole therapy should be accompanied by stringent photoprotection and skin monitoring.

  3. Intermittent self-catheterization and the risk of squamous cell cancer of the bladder: An emerging clinical entity?

    PubMed Central

    Casey, Rowan G.; Cullen, Ivor M.; Crotty, Tom; Quinlan, David M.

    2009-01-01

    There are only 7 cases reported in the literature of squamous cell cancer of the bladder in patients performing intermittent self-catheterization (ISC). We report on an eighth case, and the first case described in a patient with a Mitrofanoff continent appendicovesicostomy. A description of the case and review of the literature are presented. Risk factors for squamous cell cancer include recurrent urinary tract infections, keratinising squamous metaplasia (leukoplakia) and local mucosal trauma from intermittent self-catheterization. There is no recognized or validated monitoring program for patients performing ISC who may also have these risk factors. Reasonable protocols may include regular urinary cytology and cystoscopy with random or targeted bladder biopsies. Squamous cell cancer may present late in this cohort of patients and is associated with a dismal prognosis. PMID:19829719

  4. Expression of the CXCR4 ligand SDF-1/CXCL12 is prognostically important for adenocarcinoma and large cell carcinoma of the lung.

    PubMed

    Sterlacci, William; Saker, Shereen; Huber, Bettina; Fiegl, Michael; Tzankov, Alexandar

    2016-04-01

    The SDF-1/CXCR4 axis is associated with tumor progression and has been reported as a prognostic parameter, although with conflicting data for non-small cell lung cancer (NSCLC). This study examines a large cohort of clinically and pathologically well-characterized NSCLC patients and includes the activated form of CXCR4 (pCXCR4), which has not been studied in this context so far. SDF-1, CXCR4, and pCXCR4 were assessed immunohistochemically in 371 surgically resected NSCLC using a standardized tissue microarray platform. Extensive clinical and pathological data and a postoperative follow-up period of 17 years enabled detailed correlations. CXCR4 and pCXCR4 were frequently expressed on squamous cell carcinoma. Membranous expression of SDF-1 was a marker of poor prognosis and proved to be an independent prognostic parameter for the entire cohort and for patients with adenocarcinoma (ACA) and large cell carcinoma (LCC). Targeted cancer therapies blocking SDF-1/CXCR4 interaction already exist, and our data suggest that expression of SDF-1, especially on poorer prognosis subgroups of LCC and ACA, indicates patients that might benefit more than others. This should be taken into account when assessing the effectiveness of such targeted approaches for NSCLC patients and could lead to important implications.

  5. Sulforaphane‐induced apoptosis in Xuanwei lung adenocarcinoma cell line XWLC‐05

    PubMed Central

    Zhou, Lan; Yao, Qian; Huang, Yun‐chao; Jiang, Hua; Wang, Chuan‐qiong; Fan, Lei

    2016-01-01

    Background Xuanwei district in Yunnan Province has the highest incidence of lung cancer in China, especially among non‐smoking women. Cruciferous vegetables can reduce lung cancer risk by prompting a protective mechanism against respiratory tract inflammation caused by air pollution, and are rich in sulforaphane, which can induce changes in gene expression. We investigated the effect of sulforaphane‐induced apoptosis in Xuanwei lung adenocarcinoma cell line (XWCL‐05) to explore the value of sulforaphane in lung cancer prevention and treatment. Methods Cell growth inhibition was determined by methyl thiazolyl tetrazolium assay; cell morphology and apoptosis were observed under transmission electron microscope; cell cycle and apoptosis rates were detected using flow cytometry; B‐cell lymphoma 2 (Bcl‐2) and Bcl‐2‐like protein 4 (Bax) messenger RNA expression were determined by quantitative PCR; and p53, p73, p53 upregulated modulator of apoptosis (PUMA), Bax, Bcl‐2, and caspase‐9 protein expression were detected by Western blotting. Results Sulforaphane inhibited XWLC‐05 cell growth with inhibitory concentration (IC)50 of 4.04, 3.38, and 3.02 μg/mL at 24, 48, and 72 hours, respectively. Sulforaphane affected the XWLC‐05 cell cycle as cells accumulated in the G2/M phase. The proportion of apoptotic cells observed was 27.6%. Compared with the control, the sulforaphane group showed decreased Bcl‐2 and p53 expression, and significantly increased p73, PUMA, Bax, and caspase‐9 protein expression (P < 0.05). Conclusion Sulforaphane induces Xuanwei lung adenocarcinoma cell apoptosis. Its possible mechanism may involve the upregulation of p73 expression and its effector target genes PUMA and Bax in lung cancer cells, downregulation of the anti‐apoptotic gene B cl ‐2, and activation of caspase‐9. It may also involve downregulation of the mutant p53 protein. PMID:27878984

  6. Intestinal Type Adenocarcinoma from Inverted Papilloma: A Rare Recurrence

    PubMed Central

    Singh, Garima; Singh, Meeta; Chandana, Mansi; Nargotra, Namrata

    2016-01-01

    Inverted Papilloma (IP) is an uncommon and locally aggressive benign tumour of sinonasal region, which tends to recur after surgical resection. Most tumours are confined to the lateral nasal wall and sinuses, with maxillary sinus being most commonly affected and a male preponderance. It has a known association with in situ and invasive carcinomas with a <10% rate of malignant transformation. Most common association has been seen with squamous cell carcinoma and extremely rare association with adenocarcinoma and small cell carcinoma. A 36-year-old male presented with a left sided polypoidal nasal mass and underwent a polypectomy. Pathology results showed IP with mild dysplasia. The polypoidal growth reappeared on the same side after a period of 10 months and on histopathological examination, the growth revealed features of intestinal type adenocarcinoma. IP recurring as adenocarcinoma is rare and even after exhaustive literature search only few cases could be found. Two studies have described recurrence of adenocarcinoma in existing IP previously. We report an unusual case of inverted papilloma showing malignant transformation into an intestinal type adenocarcinoma in a 36-year-old male patient within 10 months of previous surgery. PMID:28050382

  7. Adjunctive radiotherapy with strontium-90 in the treatment of conjunctival squamous cell carcinoma

    SciTech Connect

    Kearsley, J.H.; Fitchew, R.S.; Taylor, R.G.

    1988-03-01

    Squamous cell carcinoma of the ocular conjunctiva is a relatively rare malignancy which is attended by a high rate of local recurrence following simple surgical excision. To date, the management of conjunctival squamous cell cancer has been controversial. From 1950 to 1985, 146 consecutive patients with superficial conjunctival squamous cell cancer were treated at the Queensland Radium Institute. All patients were treated by simple surgical excision of the visible conjunctival lesion followed by adjunctive radiotherapy. Of 140 patients with histologically confirmed squamous cell cancer, 123 were treated with a strontium-90 source, 10 with a radon ring, and 7 with superficial X ray therapy. Standard policy since 1960 has been to deliver an incident dose of 30 Gy in a single fraction within the first 48 post-operative hours to the surgical bed using a strontium-90 source on a stand-off eye applicator. This report will largely focus on the 123 patients who were treated with a strontium-90 source, of whom 107 received 30 Gy, 14 received 40 Gy (pre 1960) and one patient each received 20 and 25 Gy incident dose. Of 131 evaluable patients, there were only 3 who developed local recurrence. All 3 local recurrences developed in elderly men who had presented with extensive superficial primary tumors. Two of the three recurrences occurred in the two patients who were treated with doses less than 30 Gy. Both early and late radiation-induced complications following ablative surgery and treatment with strontium-90 were very uncommon. Three patients developed unsightly conjunctival telangiectasia, 2 patients developed a persistent scleral ulcer and 2 patients developed clinically significant cataracts.

  8. [Ulceration of the heel in a woman from Djibouti: squamous cell carcinoma with carcinomatous lymphangitis].

    PubMed

    Bertani, A; Massoure, P L; Menguy, P; Lamblin, G; Eve, O; Morand, J J

    2011-02-01

    The purpose of this report is to describe a case in which a heel ulcer with atypical features, i.e., large size and rapid progression, led to diagnosis of squamous cell carcinoma. Patient management was based on specialist advice obtained by "tele-dermatology" based on pictures and comments transmitted over the Internet. However, due to the risk of spreading and impossibility of providing other medical treatment (radiotherapy-chemotherapy), the lower limb was amputated at the top of the thigh.

  9. Vulvar lymphangioma circumscriptum: a rare complication of therapy for squamous cell carcinoma of the cervix

    SciTech Connect

    LaPolla, J.; Foucar, E.; Leshin, B.; Whitaker, D.; Anderson, B.

    1985-11-01

    The clinical and pathological features of a case of multifocal lymphangioma circumscriptum of the vulva are reported in a patient with chronic lymphedema of a lower extremity. Ten years previously the patient had been treated for squamous cell carcinoma of the cervix. Although lymphangioma circumscriptum is an extremely rare complication of altered lymphatic drainage, the presence of multiple noninflammatory vesicular appearing lesions in this setting should suggest the correct diagnosis.

  10. Primary squamous cell carcinoma of the rectum: a case report and literature review.

    PubMed

    Vyas, Neil; Ahmad, Sumair; Bhuiyan, Khaled; Catalano, Carmine; Alkhawam, Hassan; Sogomonian, Robert; Nguyen, James; Walfish, Aaron; Aron, Joshua

    2016-01-01

    Squamous cell carcinoma (SCC) of the rectum is a rare occurrence with an incidence rate of 0.1-0.25% per 1,000 cases. Herein, we report a case of a 52-year-old female who presented with a 2-month history of diffuse lower abdominal pain and hematochezia. Abdominal CT scan revealed a 7-cm irregular rectal mass, and the biopsy showed SCC.

  11. Primary squamous cell carcinoma of the rectum: a case report and literature review

    PubMed Central

    Vyas, Neil; Ahmad, Sumair; Bhuiyan, Khaled; Catalano, Carmine; Alkhawam, Hassan; Sogomonian, Robert; Nguyen, James; Walfish, Aaron; Aron, Joshua

    2016-01-01

    Squamous cell carcinoma (SCC) of the rectum is a rare occurrence with an incidence rate of 0.1–0.25% per 1,000 cases. Herein, we report a case of a 52-year-old female who presented with a 2-month history of diffuse lower abdominal pain and hematochezia. Abdominal CT scan revealed a 7-cm irregular rectal mass, and the biopsy showed SCC. PMID:27406458

  12. Molecular Characterization of Squamous Cell Carcinomas From Recessive Dystrophic Epidermolysis Bullosa

    DTIC Science & Technology

    2006-09-01

    Biology Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and **Unitat de Biologia Cellular Molecular , Institute Municipal d’Investigacio...AD Award Number: DAMD17-02-1-0215 TITLE: Molecular Characterization of Squamous Cell Carcinomas from Recessive Dystrophic Epidermolysis Bullosa...TYPE 3. DATES COVERED (From - To) 01-09-2006 Final 29 May 2002 - 31 Aug 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Molecular Characterization of

  13. Sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma.

    PubMed

    Stoeckli, Sandro J; Alkureishi, Lee W T; Ross, Gary L

    2009-06-01

    The appearance of lymph node metastases represents the most important adverse prognostic factor in head and neck squamous cell carcinoma. Therefore, accurate staging of the cervical nodes is crucial in these patients. The management of the clinically and radiologically negative neck in patients with early oral and oropharyngeal squamous cell carcinoma is still controversial, though most centers favor elective neck dissection for staging of the neck and removal of occult disease. As only approximately 30% of patients harbor occult disease in the neck, most of the patients have to undergo elective neck dissection with no benefit. The sentinel node biopsy concept has been adopted from the treatment of melanoma and breast cancer to early oral and oropharyngeal squamous cell carcinoma during the last decade with great success. Multiple validation studies in the context of elective neck dissections revealed sentinel node detection rates above 95% and negative predictive values for negative sentinel nodes of 95%. Sentinel node biopsy has proven its ability to select patients with occult lymphatic disease for elective neck dissection, and to spare the costs and morbidity to patients with negative necks. Many centers meanwhile have abandoned routine elective neck dissection and entered in observational trials. These trials so far were able to confirm the high accuracy of the validation trials with less than 5% of the patients with negative sentinel nodes developing lymph node metastases during observation. In conclusion, sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma can be considered as safe and accurate, with success rates in controlling the neck comparable to elective neck dissection. This concept has the potential to become the new standard of care in the near future.

  14. A Case of Squamous Cell Carcinoma Developing Within a Red-Ink Tattoo.

    PubMed

    Sherif, Sara; Blakeway, Elizabeth; Fenn, Chris; German, Alyn; Laws, Philip

    Cutaneous reactions to tattoos are well reported and include allergic reactions, infections, and foreign body granuloma or may be a presenting sign of sarcoidosis. There have been very few reported cases of squamous cell carcinoma (SCC) arising in tattoo-treated skin. We report a case of SCC arising within a red-ink tattoo and discuss the potential the role of chronic low-grade inflammation in pathogenesis. This should serve to raise awareness of potential tattoo-related serious adverse effects.

  15. Small cell carcinoma of the ureter with squamous cell and transitional cell carcinomatous components associated with ureteral stone.

    PubMed

    Kim, T S; Seong, D H; Ro, J Y

    2001-12-01

    We report a case of primary small cell carcinoma of the ureter with squamous cell and transitional cell carcinomatous components associated with ureteral stone, which is unique in that the patient has remained free of tumor recurrence for 36 months after the surgery without adjuvant chemotherapy or radiotherapy. A 60-yr-old man presented himself with a right flank pain. Computed tomography revealed an ill-defined mass and a stone in the lower one third of the right ureter, and hydronephroureterosis above the stone-impacted site. The patient underwent right nephroureterectomy and stone removal. Upon gross examination, a 3.8 x 1.8 x 1.2 cm white and partly yellow mass was noted in the anterior part of the ureter, resulting in indentation of the ureteral lumen on the posterior side. Light microscopic examination revealed that the mass was mainly composed of small cell carcinoma, and partly squamous cell and transitional cell carcinomatous components. The overlying ureteral mucosa and renal pelvis also contained multifocal dysplastic transitional epithelium and transitional cell carcinoma in situ. There was no vascular invasion, and the surgical margins were free of tumor. The small cell carcinomatous component was positive for chromogranin, neuron specific enolase, synaptophysin, and pancytokeratin but negative for high molecular-weight cytokeratin (K-903) by immunohistochemistry.

  16. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2012-12-13

    Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  17. Epidermal Growth Factor Receptor Inhibition in the Management of Squamous Cell Carcinoma of the Lung

    PubMed Central

    Spaans, Johanna N.

    2016-01-01

    Molecular therapies targeting epidermal growth factor receptor (EGFR) have had a profound impact on the management of advanced non-small cell lung cancer (NSCLC). EGFR inhibition with EGFR tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR monoclonal antibodies (mAbs) in squamous NSCLC (sqNSCLC) remains controversial in patients whose tumors are not known to harbor EGFR mutations. Recent meta-analyses of EGFR-inhibition randomized trials that are adequately powered for histological subgroup analysis and anti-EGFR trials limited to patients with squamous histology afford the opportunity to revisit EGFR treatment in sqNSCLC. In unselected patients with sqNSCLC who are not eligible for chemotherapy, EGFR-TKI therapy is a valid treatment option over placebo or best supportive care, with improved progression-free survival noted in randomized controlled trials in both the first- and second-line setting and improved overall survival (OS) in the second-line setting. In patients eligible for chemotherapy, first-line combination regimens with anti-EGFR mAbs have been shown to improve OS over chemotherapy alone in patients with squamous histology in meta-analysis and more recently in the SQUIRE sqNSCLC trial (chemotherapy with and without necitumumab). In sqNSCLC patients who respond to induction chemotherapy, maintenance therapy with erlotinib delays disease progression and may improve the survival of patients with stable disease. In the second-line setting, survival outcomes are comparable between chemotherapy and EGFR-TKIs in meta-analysis, with the latter being more tolerable as a second-line therapy. Newer-generation EGFR-TKI therapies may further benefit patients with sqNSCLC who have failed first-line chemotherapy, given the positive trial results from LUX-Lung 8 (afatinib vs. erlotinib). EGFR is a valid therapeutic target in unselected/EGFR wild-type patients with squamous cell carcinoma of the lung. With the recent approval of immune checkpoint inhibitors in the

  18. High interstitial fluid pressure promotes tumor cell proliferation and invasion in oral squamous cell carcinoma.

    PubMed

    Yu, Tao; Liu, Kun; Wu, Yingying; Fan, Jinchuan; Chen, Jianchao; Li, Chao; Zhu, Guiquan; Wang, Zhaohui; Li, Longjiang

    2013-11-01

    It has been shown that interstitial fluid pressure (IFP) is elevated in many solid tumors. The elevated IFP in tumors is responsible, at least in part, for the poor blood supply, inadequate delivery of therapeutic agents to solid tumors and poor treatment response in patients. The present study was carried out to examine alterations in malignant phenotypes in oral squamous cell carcinoma cells subjected to conditions mimicking IFP and to identify the relevant molecular mechanisms. We investigated tumor cell proliferation and invasion using SCC-4 and SCC-9 cells subjected to an increased extracellular pressure of 0, 15 and 30 mmHg in vitro. The results revealed that the increased IFP resulted in a marked increase in cancer cell proliferation, survival and invasion in vitro and altered the expression of >1,800 genes involved in invasion and metastasis, the heat shock pathway, the p38 and JNK signaling pathway, apoptosis and the cell growth and differentiation signaling pathway. These results suggest the important potential clinical application of measuring IFP, which can be used as a generic marker of prognosis and response to therapy.

  19. Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma

    PubMed Central

    Cammareri, Patrizia; Rose, Aidan M.; Vincent, David F.; Wang, Jun; Nagano, Ai; Libertini, Silvana; Ridgway, Rachel A.; Athineos, Dimitris; Coates, Philip J.; McHugh, Angela; Pourreyron, Celine; Dayal, Jasbani H. S.; Larsson, Jonas; Weidlich, Simone; Spender, Lindsay C.; Sapkota, Gopal P.; Purdie, Karin J.; Proby, Charlotte M.; Harwood, Catherine A.; Leigh, Irene M.; Clevers, Hans; Barker, Nick; Karlsson, Stefan; Pritchard, Catrin; Marais, Richard; Chelala, Claude; South, Andrew P.; Sansom, Owen J.; Inman, Gareth J.

    2016-01-01

    Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFβ Smad signalling, which is localized to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through BrafV600E or KrasG12D knockin) and TGFβ signalling ablation (through Tgfbr1 deletion) in LGR5+ve stem cells enables rapid cSCC development in the mouse. Mutation of Tp53 (which is commonly mutated in sporadic cSCC) coupled with Tgfbr1 deletion in LGR5+ve cells also results in cSCC development. These findings indicate that LGR5+ve stem cells may act as cells of origin for cSCC, and that RAS/RAF/MAPK pathway hyperactivation or Tp53 mutation, coupled with loss of TGFβ signalling, are driving events of skin tumorigenesis. PMID:27558455