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Sample records for squamous cell cervical

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. RNA interference targeting CD147 inhibits the invasion of human cervical squamous carcinoma cells by downregulating MMP-9.

    PubMed

    Fan, Xiaobin; Wu, Weiguang; Shi, Haixia; Han, Jianqiu

    2013-07-01

    Cervical squamous carcinoma is a highly invasive tumour that has a great capacity to metastasise. Extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin superfamily, is a widely distributed cell surface glycoprotein. It is highly expressed on malignant tumour cell surfaces, including human cervical squamous carcinoma. It also plays a critical role in the invasive and metastatic activity of malignant cells by stimulating the expression of matrix metalloproteinases (MMPs). The anti-invasive effect of small interfering RNA (siRNA) against CD147 on human cervical squamous carcinoma cells and its possible pathways has been investigated. The downregulation of CD147 by transfection with siRNA resulted in MMP-9 expression and decreased activity in the cervical squamous carcinoma cell line SiHa. In vitro analysis showed that the invasive capacity of SiHa cells decreased. Thus CD147 inhibition and subsequent MMP-9 deletion may have anti-tumour effects by inhibiting the invasiveness of human cervical squamous carcinoma cells.

  7. 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. .

  8. SU-E-P-18: Intensity-Modulated Radiation Therapy for Cervical Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Bai, W; Qiao, X; Zhou, Z; Song, Y; Zhang, R; Zhen, C

    2015-06-15

    Purpose: To retrospectively analyze the outcomes and prognostic factors of cervical esophageal squamous cell carcinoma (SCC) treated with intensity modulated radiation therapy (IMRT). Methods: Thirty-seven patients with cervical esophageal SCC treated with IMRT were analyzed retrospectively. They received 54–66 Gy in 27–32 fractions. Nineteen patients received concurrent (n=12) or sequential (n=7) platinum-based two drugs chemoradiotherapy. Overall survival (OS), local control rates (LCR) and prognostic factors were evaluated. Acute toxicities and patterns of first failures were observed. Results: The median follow-up was 46 months for alive patients. The l-, 3-, 4- and 5-year OS of the all patients were 83.8%, 59.1%, 47.5% and 32.6% respectively. The median survival time was 46 months. The l-, 3-,4- and 5-year LCR were 82.9%, 63.0%, 54.5% and 54.5%, respectively. Univariate and Multivariate analysis all showed that size of GTV was an independent prognostic factor (p=0.033, p=0.039). There were no patients with Grade 3 acute radiation esophagitis and Grade 2–4 acute pneumonitis. The local failure accounted for 70.0% of all treatment-related failures. Conclusion: IMRT is safe and effective in the treatment of cervical esophageal squamous cell carcinoma. Size of GTV is an independent prognostic factor. Local failure still remains the main reason of treatment failures. The authors declare no conflicts of interest in preparing this article.

  9. Evaluating Nuclear Membrane Irregularity for the Classification of Cervical Squamous Epithelial Cells

    PubMed Central

    Tang, Jing Rui; Mat Isa, Nor Ashidi; Ch’ng, Ewe Seng

    2016-01-01

    Pap test involves searching of morphological changes in cervical squamous epithelial cells by pathologists or cytotechnologists to identify potential cancerous cells in the cervix. Nuclear membrane irregularity is one of the morphological changes of malignancy. This paper proposes two novel techniques for the evaluation of nuclear membrane irregularity. The first technique, namely, penalty-driven smoothing analysis, introduces different penalty values for nuclear membrane contour with different degrees of irregularity. The second technique, which can be subdivided into mean- or median-type residual-based analysis, computes the number of points of nuclear membrane contour that deviates from the mean or median of the nuclear membrane contour. Performance of the proposed techniques was compared to three state-of-the-art techniques, namely, radial asymmetric, shape factor, and rim difference. Friedman and post hoc tests using Holm, Shaffer, and Bergmann procedures returned significant differences for all the three classes, i.e., negative for intraepithelial lesion or malignancy (NILM) versus low grade squamous intraepithelial lesion (LSIL), NILM versus high grade squamous intraepithelial lesion (HSIL), and LSIL versus HSIL when the span value equaled 3 was employed with linear penalty function. When span values equaled 5, 7, and 9, NILM versus LSIL and HSIL showed significant differences regardless of the penalty functions. In addition, the results of penalty-driven smoothing analysis were comparable with those of other state-of-the-art techniques. Residual-based analysis returned significant differences for the comparison among the three diagnostic classes. Findings of this study proved the significance of nuclear membrane irregularity as one of the features to differentiate the different diagnostic classes of cervical squamous epithelial cells. PMID:27741266

  10. Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma

    PubMed Central

    Caffarel, Maria M; Coleman, Nicholas

    2014-01-01

    Cervical carcinoma is the second most common cause of cancer deaths in women worldwide. Treatments have not changed for decades and survival rates for advanced disease remain low. An exciting new molecular target for the treatment of cervical squamous cell carcinoma (SCC), and possibly for SCCs at other anatomical sites, is the oncostatin M receptor (OSMR). This cell surface cytokine receptor is commonly copy number gained and overexpressed in advanced cervical SCC, changes that are associated with significantly worse clinical outcomes. OSMR overexpression in cervical SCC cells results in enhanced responsiveness to the major ligand oncostatin M (OSM), which induces several pro-malignant effects, including a pro-angiogenic phenotype and increased cell migration and invasiveness. OSMR is a strong candidate for antibody-mediated inhibition, a strategy that has had a major impact on haematological malignancies and various solid tumours such as HER2-positive breast cancers. © 2013 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:24659184

  11. Prostitution, condom use, and invasive squamous cell cervical cancer in Thailand.

    PubMed

    Thomas, D B; Ray, R M; Pardthaisong, T; Chutivongse, S; Koetsawang, S; Silpisornkosol, S; Virutamasen, P; Christopherson, W M; Melnick, J L; Meirik, O; Farley, T M; Riotton, G

    1996-04-15

    Cervical cancer is probably caused by a sexually transmitted agent. A case-control study was conducted in three hospitals in Thailand to investigate further the role of male sexual behavior, particularly regarding sexual contacts with prostitutes, in the development of this disease. Data were obtained from interviews with 225 married women with invasive squamous cell cervical carcinoma and 791 hospitalized controls, all of whom reported having only one sexual partner, and from interviews with their husbands. Risk of cervical cancer was strongly related to the women's husbands having visited prostitutes without using a condom when the husbands were less than 30 years old. A strong increasing trend in risk in relation to decreasing frequency of the husbands' condom use with prostitutes was observed, and a weaker increasing trend in risk with husbands' estimated lifetime total number of visits to prostitutes was found. The average latent period between the women's likely initial exposure to a sexually transmitted oncogenic agent and her diagnosis of invasive cervical cancer was about a quarter of a century. Regular use of condoms by customers of prostitutes could reduce the number of invasive cervical cancer cases in the general population of Thailand by at least one fourth.

  12. ZEB1 promotes the progression and metastasis of cervical squamous cell carcinoma via the promotion of epithelial-mesenchymal transition

    PubMed Central

    Ma, Yihui; Zheng, Xiangyu; Zhou, Jun; Zhang, Ying; Chen, Kuisheng

    2015-01-01

    Objective: The process of epithelial-mesenchymal transition (EMT) clearly contributes to cancer metastasis. The aim of this study was to investigate the expression of the EMT-related transcription repressor ZEB1 and the expression of EMT-associated markers (E-cadherin, β-catenin and N-cadherin) in cervical squamous cell carcinoma. In addition, the role of ZEB1 and these EMT-associated markers in the progression and metastasis of cervical squamous cell carcinoma was explored. Methods: The expression of ZEB1, E-cadherin, β-catenin and N-cadherin was evaluated in 81 specimens of cervical squamous cell carcinoma by immunohistochemistry; the clinicopathological significance of these markers was then analyzed. Results: 1) Of the 81 samples, 37 cases (45.7%) were positive for ZEB1, and nuclear expression of ZEB1 in tumor cells was positively associated with the differentiation status of the tumor tissue (P < 0.05), vascular invasion (P < 0.05) and lymph node metastasis (P < 0.05). 2) The loss of E-cadherin and β-catenin expression in tumor cells and the acquisition of N-cadherin expression were positively associated with the differentiation status of the tumor tissue (P < 0.05) and with the occurrence of vascular invasion (P < 0.05). 3) A significant negative correlation was observed between ZEB1 and E-cadherin expression (Spearman = -0.636, P < 0.05) and between ZEB1 and β-catenin expression (Spearman = -0.417, P < 0.05). Moreover, a significant positive correlation was observed between ZEB1 and N-cadherin expression (Spearman = 0.557, P < 0.05). Conclusions: These results emphasize the role of EMT in cervical squamous cell carcinoma. The upregulation of ZEB1 is associated with the abnormal expression of E-cadherin, β-catenin and N-cadherin, which might promote the progression and metastasis of cervical squamous cell carcinoma. PMID:26617850

  13. 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

  14. Sexual and reproductive risk factors for invasive squamous cell cervical cancer.

    PubMed

    Brinton, L A; Hamman, R F; Huggins, G R; Lehman, H F; Levine, R S; Mallin, K; Fraumeni, J F

    1987-07-01

    A case-control study of 418 women with invasive squamous cell cervical cancer and 704 population controls enabled evaluation of risk factors for this relatively rare cancer. Consistent with an infectious etiology was a pronounced effect of multiple sexual partners, with those reporting 10 or more partners being at a significant threefold excess risk. Early first intercourse also was associated with some residual effect on risk, although the relationship was not linear, nor the explanation readily apparent. Those with multiple births were at significantly elevated risks, even after adjustment for sexual parameters. Menstrual and hygiene factors, including use of tampons, vaginal deodorants, and douching products, were not consistently related to risk. Histories of specific infections involving the genital tract were poor predictors of risk, since few women provided positive responses, but those with nonspecific diseases were at a significant twofold excess risk.

  15. Tissue transglutaminase mediates the pro-malignant effects of oncostatin M receptor over-expression in cervical squamous cell carcinoma

    PubMed Central

    Caffarel, Maria M; Chattopadhyay, Anasuya; Araujo, Angela M; Bauer, Julien; Scarpini, Cinzia G; Coleman, Nicholas

    2013-01-01

    Oncostatin M receptor (OSMR) is commonly over-expressed in advanced cervical squamous cell carcinoma (SCC), producing a significantly worse clinical outcome. Cervical SCC cells that over-express OSMR show enhanced responsiveness to the major ligand OSM, which induces multiple pro-malignant effects, including increased cell migration and invasiveness. Here, we show that tissue transglutaminase (TGM2) is an important mediator of the ligand-dependent phenotypic effects of OSMR over-expression in SCC cells. TGM2 expression correlated with disease progression and with OSMR levels in clinical samples of cervical and oral SCC. TGM2 depletion in cervical SCC cells abrogated OSM-induced migration on fibronectin-coated surfaces and invasiveness through extracellular matrix, while ectopic expression of TGM2 increased cell motility and invasiveness. Confocal microscopy and co-immunoprecipitation assays showed that TGM2 interacted with integrin–α5β1 in the presence of fibronectin in cervical SCC cells, with OSM treatment strengthening the interaction. Importantly, integrin–α5β1 and fibronectin were also over-expressed in cervical and oral SCC, where levels correlated with those of OSMR and TGM2. This combined tissue and in vitro study demonstrates for the first time that stimulation of over-expressed OSMR in cervical SCC cells activates TGM2/integrin-α5β1 interactions and induces pro-malignant changes. We conclude that an OSMR/TGM2/integrin-α5β1/fibronectin pathway is of biological significance in cervical SCC and a candidate for therapeutic targeting. Copyright © 2013 Pathological Society of Great Britain and Ireland. © 2013 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:23765377

  16. Potential impact of mTOR inhibitors on cervical squamous cell carcinoma: A systematic review

    PubMed Central

    Assad, Daniele Xavier; Elias, Silvia Taveira; Melo, Andréia Cristina; Ferreira, Carlos Gil; De Luca Canto, Graziela; Guerra, Eliete Neves Silva

    2016-01-01

    The aim of the present systematic review was to analyze the potential impact of mammalian target of rapamycin (mTOR) inhibitors on the treatment of cervical squamous cell carcinoma (CSCC). A systematic literature search was conducted in PubMed, PMC, Scopus, Cochrane Library, LILACS, Web of Science, Google Scholar and ScienceDirect on January 19, 2015, without time and language restrictions. Studies that evaluated women of any age with CSCC and who received mTOR inhibitors alone or in association with other treatments were considered. Randomized and non-randomized clinical trials were included, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed. Selected studies were methodologically appraised according to the Grades of Recommendation, Assessment, Development and Evaluation method to assess the quality of evidence. Of 642 identified citations, 43 studies were fully reviewed; however, only 3 studies met the inclusion criteria and were used for qualitative analysis. Of these, two studies were phase 1 and one was a phase 2 clinical trial. The studies included were not conclusive with regard to the association between mTOR inhibitor treatment and cervical cancer. The main analysis of secondary endpoints revealed that individuals treated with other drugs in association with mTOR inhibitors achieved partial responses (15.4–33.3%) or stable disease (17.6–28%). Treatment with mTOR inhibitors in general was well tolerated in patients with metastatic disease. The predominant toxicities were grade 1 and 2. The phase 1 trials included in this review demonstrated that mTOR inhibitor treatments are feasible and safe. However, the currently available evidence is insufficient to determine the effect of mTOR inhibitors on CSCC, and further investigation in high-quality, randomized clinical trials is required. PMID:27895779

  17. Cervical metastasis in squamous cell carcinoma of the hard palate and maxillary alveolus.

    PubMed

    Koshkareva, Yekaterina; Liu, Jeffrey C; Lango, Miriam; Galloway, Thomas; Gaughan, John P; Ridge, John A

    2016-01-01

    We conducted a retrospective study to determine the incidence and treatment outcomes of neck metastases in patients with squamous cell carcinoma (SCC) of the hard palate and/or maxillary alveolus after surgical excision of the primary tumor. We also sought to identify any risk factors for recurrence. Our study population was made up of 20 patients-9 men and 11 women, aged 46 to 88 years (mean: 72.6)-who had undergone excision of an SCC of the hard palate and/or maxillary alveolus at a tertiary care cancer center over a 7-year period. Half of all patients were former tobacco users. Of the 20 tumors, 10 involved the maxillary alveolus, 4 involved the hard palate, and 6 involved both sites. Three patients were clinically categorized as T1, 9 as T2, 6 as T3, and 2 as T4; pathologically, 8 tumors were categorized as T4a. In addition to maxillectomy, a neck dissection was performed in 7 patients-4 therapeutically and 3 electively. Eight of 20 patients experienced a recurrence: 4 local, 6 regional, and 2 distant (several patients had a recurrence at more than one site). Univariate analysis identified perineural invasion (p = 0.04) as a statistically significant risk factor for recurrence. Of 14 patients with a clinicopathologically negative neck, 5 (36%) developed a cervical recurrence, and 4 of them died of their disease. An advanced stage (T4 vs.

  18. Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer

    ClinicalTrials.gov

    2016-12-07

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  19. 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.

  20. 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.

  1. Detection, genotyping and quantitation of multiple hpv infections in south African women with cervical squamous cell carcinoma.

    PubMed

    Lebelo, Ramokone L; Bogers, Johannes J; Thys, Sofie; Depuydt, Christophe; Benoy, Ina; Selabe, S Gloria; Bida, Meshack N; Mphahlele, M Jeffrey

    2015-09-01

    In Africa, data is limited on quantitation of human papillomavirus (HPV) types in women with multiple infections. This study applied a real time PCR (qPCR) assay for detection, genotyping and quantitation of multiple HPV infections in 90 tissue blocks of South African women with cervical squamous cell carcinoma. One sample with multiple HPV types was subjected to laser micro-dissection and qPCR. Four samples were negative for β-globin and these were excluded from the analysis. The HPV DNA positivity rate was 93.0% (80/86). All 80 positives showed the presence of HR HPV types; HPV 68 was the only type negative in all the samples. Overall, HPV 16 was positive in most of the samples (88.8%), followed by HPV 56 (28.7%), HPV 18 (20.0%) and HPV 39 (18.7%). More than half of the samples (65.0%) had multiple infections. HPV 16 was present in majority of single (85.7%) and multiple infections (90.4%). HPV 16 showed higher viral loads in 70.3% of the HPV 16 co-infected samples. In one multiple infected sample laser micro-dissection and qPCR identified HPV 18 with higher viral load as the most likely cause of the invasive lesion. There is large number of multiple HPV infections in South African women with cervical squamous cell carcinoma. HPV 16 is the most frequently detected type and often presents with higher viral load, suggesting it could be responsible for pathogenesis of the lesions in the majority of cases.

  2. Phototoxicity of Liposomal Zn- and Al-phthalocyanine Against Cervical and Oral Squamous Cell Carcinoma Cells In Vitro

    PubMed Central

    Young, Jason; Yee, Michael; Kim, Hayoung; Cheung, Jennifer; Chino, Takahiro; Düzgüneş, Nejat; Konopka, Krystyna

    2016-01-01

    Background Photodynamic therapy (PDT) utilizes light to activate a photosensitizer in the presence of oxygen, and leads to local photodamage by the generation of highly reactive oxygen species (ROS). Liposomal delivery of photosensitizers is adaptable to the treatment of cancers. We examined the phototoxicity of free or liposome-embedded phthalocyanine photosensitizers using HeLa cervical carcinoma and HSC-3 oral squamous cell carcinoma cells. Material/Methods Liposomes were composed of palmitoyloleoyphosphatidylcholine (POPC): phosphatidylglycerol (PG), and contained either zinc phthalocyanine (ZnPc) or aluminum phthalocyanine chloride (AlPc). Free or liposomal ZnPc and AlPc were incubated with cells for 24 h at 37°C. Cells incubated with ZnPc were exposed to broadband visible light (350–800 nm; light dose 43.2 J/cm2), whereas cells treated with AlPc were exposed to light at 690 nm (light dose 3.6 J/cm2). The effect of folate receptor-targeted liposomal ZnPc was evaluated with HeLa cells. Cytotoxicity was analyzed by the Alamar Blue assay. Results Cell viability, expressed as a percentage of control cells, was calculated according to the formula [(A570–A600) of test cells]×100/[(A570–A600) of control cells]. The relative percentage changes then defined the phototoxic efficacy of the experimental conditions. In HeLa cells, 1 μM free ZnPc and AlPc, reduced cell viability to 52.7±2.1 and 15.4±8.0%, respectively. Liposomal phthalocyanines, at 0.1, 0.5, and 1.0 μM, reduced the viability to 68.0±8.6, 15.1±9.9 and 0% (ZnPc), and to 25.8±8.2, 0 and 0% (AlPc), respectively. In HSC-3 cells, 1 μM free ZnPc and AlPc, reduced cell viability to 22.1±2.8 and 56.6±8.6%, respectively. With 1 μM liposomal ZnPc and AlPc, the viability was reduced to 0 and 21.3±0.3%, respectively. Conclusions The embedding of phthalocyanines in liposomes enhanced their phototoxicity and this effect was dependent on cell type. PMID:27932777

  3. An animal model of buccal mucosa cancer and cervical lymph node metastasis induced by U14 squamous cell carcinoma cells.

    PubMed

    Zhao, Xin; Pang, Liang; Qian, Yu; Wang, Qiang; Li, Yong; Wu, Mingyi; Ouyang, Zilan; Gao, Zhi; Qiu, Lihua

    2013-04-01

    The buccal mucosa is the site with the highest risk of contracting a malignancy in habitual betel quid chewers who expose the buccal mucosa to high doses of carcinogens. Of all oral cancers, those of the buccal mucosa are associated with the poorest prognoses. Therefore, it would be helpful to have an animal model to evaluate new treatment modalities for buccal mucosa cancer. In the present study, we evaluated whether the imprinting control region (ICR) mouse animal model could be employed as a cancer model for buccal mucosa cancer. Sixty male ICR mice were randomly divided into two groups, a normal group (n=10) and a cancer-induced group (n=50). Each mouse in the cancer group was inoculated with 0.05 ml U14 cancer cell suspension (1×10(7)/ml) on the buccal mucosa. Histological staining and gene expression assays revealed that neck lymph node metastasis animal models were established. After 20 days, the cheek tumor formation rate of the ICR mice reached 100%. Furthermore, the neck lymph node metastasis rate was 53%. We identified that U14 cells produce strong metastasis in ICR mice. Metastasis of the tumor to the lymph node began with carcinoma metastasis encroaching on the marginal sinus. Then it infiltrated to the cortex and medulla and the infiltration continued until the normal lymph node structure was completely damaged. This animal model may be employed in medical research on buccal mucosa cancer and cervical lymph node metastasis. In conclusion, our findings indicate that U14 cell-induced mouse buccal mucosa cancer may be a potential cancer model for human buccal mucosa squamous cell carcinoma.

  4. Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2014-09-22

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer

  5. Sex-determining region Y-related high mobility group box (SOX)-2 is overexpressed in cervical squamous cell carcinoma and contributes cervical cancer cell migration and invasion in vitro.

    PubMed

    Chang, Xiaohan; Zhang, Jing; Huang, Chenglin; Pang, Xiaoao; Luo, Qingshuang; Zhang, Huijie; Zhang, Shulan

    2015-09-01

    Sex-determining region Y-related high mobility group box 2 (SOX-2) is a key pluripotency-associated transcription factor and may be implicated in the pathogenesis of cervical squamous cell carcinoma (SCC). The aim of this study was to explore SOX-2 expression in cervical SCC tissues and to examine whether and how SOX-2 regulates the malignant behaviors of cervical SCC cells in vitro. We here found that SOX-2 expression in the examined cervical SCC tissues was higher than that in the normal cervical and cervical intraepithelial neoplasia (CIN) tissues. Higher protein level of SOX-2 (nuclear positive staining cells ≥50 %) was detected in 34.9 % (29 out of 83 cases) of cervical SCC patients. We also noted that 100 % of well-differentiated and 66.7 % of moderately differentiated cervical SCCs showed lower SOX-2 expression (nuclear positive staining cells <50 %), while 58.8 % of poorly differentiated tumors had higher SOX-2 expression (P < 0.05). Furthermore, the migratory and invasive capabilities of SiHa cervical cancer cells were enhanced when SOX-2 was upregulated whereas suppressed when SOX-2 was downregulated. Also, the phosphorylation levels of protein kinase B (Akt) and extracellular regulated protein kinases (ERK) 1/2 were increased in SOX-2-overexpressed cancer cells but decreased in SOX-2-depleted cells. Additionally, LY294002 (Akt pathway inhibitor) or U0126 (ERK pathway inhibitor) significantly suppressed SOX-2-overexpression-induced migration and invasion in SiHa cells. Our results indicate that differentially expressed SOX-2 is associated with tumor differentiation (P < 0.05) and that SOX-2 contributes to the migratory and invasive behaviors of cervical SCC in vitro.

  6. High Expression of KIF20A Is Associated with Poor Overall Survival and Tumor Progression in Early-Stage Cervical Squamous Cell Carcinoma

    PubMed Central

    Gu, Haifeng; Li, Min; Liu, Zhimin; Feng, Yanling; Zheng, Nianzhen; Xie, Chuanmiao; Zhang, Yanna

    2016-01-01

    Background The kinesin family member 20a (KIF20A) protein has been implicated in the development and progression of many human cancers; however, its precise function and role in cervical cancer remain largely unclear. This study aimed to investigate the expression profile and prognostic value of KIF20A in patients with early-stage cervical squamous cell carcinoma. Methods We examined the mRNA and protein levels of KIF20A in eight cervical cancer cell lines and eight paired cervical cancer samples, compared with normal cervical epithelial cells and adjacent normal cervical tissues, respectively. Immunohistochemistry was performed to detect the expression of KIF20A in paraffin-embedded specimens from 169 early-stage cervical squamous cell carcinoma patients. Statistical analyses were applied to analyze the association between KIF20A expression and clinical variables, as well with patient survival. Results The mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues (P < 0.05). Immunohistochemistry analysis in 169 cervical cancer cases revealed that increased KIF20A expression was strongly associated with human papillomavirus (HPV) infection (P = 0.008), clinical stage (P = 0.001), tumor recurrence (P = 0.016), vital status (P < 0.001), the property of the surgical margin (P = 0.032), the lymphovascular space involvement (P = 0.014), and pelvic lymph node metastasis (P = 0.001). The overall survival and disease-free survival of patients with high levels of KIF20A expression were significantly poorer than those with low KIF20A expression. KIF20A was an independent survival prognostic factor, as evidenced by univariate and multivariate analysis. Conclusions Our results illustrate that elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome

  7. Increased expression of long non-coding RNA XIST predicts favorable prognosis of cervical squamous cell carcinoma subsequent to definitive chemoradiation therapy

    PubMed Central

    Kobayashi, Reiko; Miyagawa, Ryu; Yamashita, Hideomi; Morikawa, Teppei; Okuma, Kae; Fukayama, Masashi; Ohtomo, Kuni; Nakagawa, Keiichi

    2016-01-01

    The present retrospective study aimed to examine the association between the expression of long non-protein-coding RNAs (lncRNAs) and clinical prognosis in the pretreatment formalin-fixed, paraffin-embedded (FFPE) tissue samples of cervical squamous cell carcinoma patients that underwent platinum-based chemoradiation therapy. Between 2001 and 2013, 49 consecutive patients with squamous cell cervical carcinoma were selected for the present study (median follow-up period, 44.1 months). The patients possessed an International Federation of Gynecology and Obstetrics stage of IB1/IIA1 (with pelvic lymph node metastasis), IB2 or IIA2-IVA, and had been treated with definitive chemoradiation therapy. The pretreatment FFPE tumor biopsies of the patients obtained diagnosis were used for analysis. Total RNAs were extracted from the FFPE tumor tissues and reverse transcription-quantitative polymerase chain reaction was performed to examine the expression level of lncRNAs. The expression level of X inactive-specific transcript (XIST) demonstrated a significant association with the overall survival rate (P=0.014). The 4-year overall survival rates were 87.1 and 54.4% in the high and low XIST expression groups, respectively. Since the expression of XIST is associated with the overall survival rate, this lncRNA has the potential to become a predictor for the prognosis of cervical squamous cell carcinoma patients that are treated with chemoradiation therapy. Additional studies are required to investigate the underlying mechanisms of XIST that are associated with prognosis. PMID:27899965

  8. 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.

  9. Overexpression of the oncostatin M receptor in cervical squamous cell carcinoma cells is associated with a pro-angiogenic phenotype and increased cell motility and invasiveness.

    PubMed

    Winder, David M; Chattopadhyay, Anasuya; Muralidhar, Balaji; Bauer, Julien; English, William R; Zhang, Xiao; Karagavriilidou, Konstantina; Roberts, Ian; Pett, Mark R; Murphy, Gillian; Coleman, Nicholas

    2011-11-01

    Oncostatin M receptor (OSMR) shows frequent copy number gain and overexpression in advanced cervical squamous cell carcinoma (SCC). We used cell-based in vitro assays, RNA interference, and integrative gene expression profiling to investigate the functional significance of this observation. CaSki and SW756 were selected as representative cervical SCC cells that overexpressed OSMR, and ME180 and MS751 as cells that did not. The STAT-dependent pro-angiogenic factors VEGF-A and ID1 were rapidly induced by OSM in CaSki/SW756 but not in ME180/MS751. However, rapid induction did occur in MS751 following forced OSMR overexpression, while depleting OSMR in CaSki abrogated VEGF-A expression. Conditioned medium from both CaSki and SW756 stimulated endothelial tube formation in vitro, effects that were inhibited by depleting OSMR in the SCC cells. For both CaSki and SW756, migration in a wound healing assay and invasion through Matrigel were stimulated by OSM and consistently inhibited by OSMR depletion. The phenotype was rescued by transfection with OSMR containing a silent mutation that provided specific siRNA resistance. Overall, there was a positive correlation between OSMR levels and invasiveness. We used gene expression profiling to identify genes induced by OSM in CaSki/SW756 but not in ME180/MS751. The most prominent gene ontology category groups for the differentially expressed genes were cell motility/invasion, angiogenesis, signal transduction, and apoptosis. We also profiled 23 cervical SCC samples, identifying genes that were differentially expressed in cases with OSMR overexpression versus those without. Integration of the datasets identified 15 genes that showed consistent differential expression in association with OSMR levels in vitro and in vivo. We conclude that OSMR overexpression in cervical SCC cells provides increased sensitivity to OSM, which induces pro-malignant changes. OSMR is a potential prognostic and therapeutic target in cervical SCC. The genes

  10. Gene Expression Changes in Cervical Squamous Cell Carcinoma After Initiation of Chemoradiation and Correlation With Clinical Outcome

    SciTech Connect

    Klopp, Ann H.; Jhingran, Anuja Ramdas, Latha; Story, Michael D.; Broadus, Russell R.; Lu, Karen H.; Eifel, Patricia J.; Buchholz, Thomas A.

    2008-05-01

    Purpose: The purpose of this study was to investigate early gene expression changes after chemoradiation in a human solid tumor, allowing identification of chemoradiation-induced gene expression changes in the tumor as well as the tumor microenvironment. In addition we aimed to identify a gene expression profile that was associated with clinical outcome. Methods and Materials: Microarray experiments were performed on cervical cancer specimens obtained before and 48 h after chemoradiation from 12 patients with Stage IB2 to IIIB squamous cell carcinoma of the cervix treated between April 2001 and August 2002. Results: A total of 262 genes were identified that were significantly changed after chemoradiation. Genes involved in DNA repair were identified including DDB2, ERCC4, GADD45A, and XPC. In addition, significantly regulated cell-to-cell signaling pathways included insulin-like growth factor-1 (IGF-1), interferon, and vascular endothelial growth factor signaling. At a median follow-up of 41 months, 5 of 12 patients had experienced either local or distant failure. Supervised clustering analysis identified a 58-gene set from the pretreatment samples that were differentially expressed between patients with and without recurrence. Genes involved in integrin signaling and apoptosis pathways were identified in this gene set. Immortalization-upregulated protein (IMUP), IGF-2, and ARHD had particularly marked differences in expression between patients with and without recurrence. Conclusions: Genetic profiling identified genes regulated by chemoradiation including DNA damage and cell-to-cell signaling pathways. Genes associated with recurrence were identified that will require validation in an independent patient data set to determine whether the 58-gene set associated with clinical outcome could be useful as a prognostic assay.

  11. Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells.

    PubMed

    Smith, Stephen P; Scarpini, Cinzia G; Groves, Ian J; Odle, Richard I; Coleman, Nicholas

    2016-07-26

    Development of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of 'master regulators' for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n = 7) or HPV16 E7 (n = 5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes in vitro. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins.

  12. Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells

    PubMed Central

    Smith, Stephen P.; Scarpini, Cinzia G.; Groves, Ian J.; Odle, Richard I.; Coleman, Nicholas

    2016-01-01

    Development of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of ‘master regulators’ for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n = 7) or HPV16 E7 (n = 5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes in vitro. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins. PMID:27457222

  13. Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16INK4a Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma

    PubMed Central

    Yoo, Su Hyun; Son, Eun-Mi; Sung, Chang Okh

    2013-01-01

    Background Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. Methods We compared histologic findings, p16INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. Results All five SCCs of cervical origin showed strong expression of p16INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. Conclusions Although a thorough histological examination is important, immunonegativity for p16INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract. PMID:24421848

  14. Transient increase in squamous cell carcinoma antigen expression in cultured cervical carcinoma CaSki cells in response to exposure to cis-diamminedichloroplatinum.

    PubMed

    Tateiwa, Y; Yoshida, S; Miyahara, Y; Hamana, S; Motoyama, S; Maruo, T

    2003-01-01

    The present study was conducted to elucidate the molecular mechanism underlying the transient increase in circulating squamous cell carcinoma antigen (SCC Ag) levels in response to CIS-diamminedichloroplatinum (CDDP) infusion using an in vitro model. The uterine cervical squamous carcinoma CaSki cells were cultured for 72 h after 3 h exposure to 5.0 microg/ml CDDP. The effects of CDDP exposure on the proliferative activity and apoptosis in cultured CaSki cells were determined by bromodeoxyuridine (BrdU) uptake and cell counting and by the TUNEL assay, respectively. SCC Ag levels in cultured CaSki cells and culture media were determined with the use of SCC-RIA kit. The expression of SCC Ag-1 mRNA and SCC Ag-2 mRNA in cultured CaSki cells was assessed using semiquantitative RT-PCR with Southern blot analysis. The number of BrdU-positive CaSki cells significantly decreased 6 h after exposure to CDDP, whereas the apoptosis-positive rate of cultured CaSki cells significantly increased 12 h after the CDDP exposure. The number of cultured CaSki cells significantly decreased 72 h after the CDDP exposure. The total SCC Ag protein levels in both cultured CaSki cells and the culture media after the 3-hour CDDP exposure increased in a time-dependent manner during the subsequent incubation for 48 h. Semiquantitative RT-PCR revealed that the expression levels of both SCC Ag-1 and SCC Ag-2 mRNA increased (1.7- and 2.7-fold, respectively) 12 h after the exposure to CDDP relative to those before the subsequent cultures. Exposure of uterine cervical squamous carcinoma CaSki cells to CDDP resulted in a transient increase in SCC Ag protein and mRNA expression in those cells during the initial 12 h after the exposure, being associated with decreased proliferative activity and increased apoptosis of those cells.

  15. Effects of docetaxel in combination with radiation on human head and neck cancer cells (ZMK-1) and cervical squamous cell carcinoma cells (CaSki ).

    PubMed

    Pradier, O; Rave-Fränk, M; Lehmann, J; Lücke, E; Boghun, O; Hess, C F; Schmidberger, H

    2001-03-15

    The purpose of this study was to determine, as we did for paclitaxel, the cytotoxic and radiosensitizing potential of docetaxel in human head and neck cancer cells (ZMK-1), and in cervical squamous cell carcinoma cells (CaSki). ZMK-1 cells were incubated with docetaxel for 3, 9 or 24 hr before irradiation and 24 hr after irradiation. CaSki cells were incubated with docetaxel 24 hr before and after irradiation. For ZMK-1 cells, the docetaxel concentrations (0.7, 0.7 and 0.35 nM) were determined to obtain approximately equivalent cell survival at the different incubation times (3, 9 and 24 hr, respectively). For CaSki cells, the necessary concentration of docetaxel was 0.07 nM. Radiation doses were given from 0 to 7 Gy. Cell survival was measured by a standard clonogenic assay after a 9-day incubation. Flow cytometry was used to measure the capacity of docetaxel to accumulate cells in the G2/M phase of the cell cycle. We observed a weak accumulation of cells in the G2/M phase for the ZMK-1 cells and a pronounced accumulation for CaSki cells. For docetaxel incubation before irradiation, the isoeffect enhancement ratios for ZMK-1 cells determined at the 37% survival level were 1.18, 2.01, and 2.40 for pre-incubation at 3, 9 and 24 hr, respectively; for CaSki cells the ratio was 1.44. For a docetaxel incubation of 24 hr after irradiation, the isoeffect enhancement ratios determined at the 37% survival level were 1.54 and 1.17 for the ZMK-1, and CaSki cells, respectively. A radiosensitizing effect of docetaxel could be demonstrated unambiguously in the two cell lines used. In contrast to our previously published results with paclitaxel, docetaxel seems to be a better radiosensitizer than paclitaxel.

  16. Expression of HIF-2α and VEGF in Cervical Squamous Cell Carcinoma and Its Clinical Significance

    PubMed Central

    Zhang, Lixia; Chen, Qiang; Hu, Jing; Chen, Yue; Liu, Chenglong; Xu, Changshui

    2016-01-01

    CSCC is a systemic disease involving polygenic alteration and multiple steps, and HIF and VEGF are closely associated with tumorigenesis. Specimens surgically resected from 64 cases of CSCC and 22 cases of normal cervical tissue were selected randomly to detect the expression of HIF-2α and VEGF in CSCC for exploring their clinical significance; information regarding the age, lymph node metastasis, and FIGO staging were collected as well; expression of HIF-2α and VEGF was detected by qPCR and immunohistochemistry. We found that the expression of HIF-2α and VEGF mRNA in CSCC was significantly higher than that of normal cervical tissues and showed a positive correlation between them. The positive rates of HIF-2α and VEGF protein expression in CSCC and normal cervical tissues were 93.8% and 18.2%, respectively, with correlation between them. The expression of both HIF-2α and VEGF mRNA did not relate closely to age but the FIGO staging and lymph node metastasis. Compared with the counterpart control group, CSCC tissues with high FIGO staging and lymph node metastasis had a higher level of HIF-2α and VEGF mRNA expression. So, HIF-2α and VEGF were overexpressed in CSCC, which has a great clinical significance for its diagnosis. PMID:27413748

  17. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

    PubMed

    Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

    2014-01-01

    The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

  18. Preoperative evaluation of cervical lymph nodes for metastasis in patients with oral squamous cell carcinoma: A comparative study of efficacy of palpation, ultrasonography and computed tomography

    PubMed Central

    Mishra, Niranjan; Rath, Krushna Chandra; Upadhyay, Upendra Nath; Raut, Subhrajit; Baig, Shadab Ali; Birmiwal, Krishna Gopal

    2016-01-01

    Introduction: Oral cancer is a major health threat in a country like India, where patients frequently present with advanced disease with regional dissemination to cervical lymph nodes. The management and prognosis depend on the status of cervical lymph nodes. Thus, it becomes imperative to diagnose and evaluate them preoperatively. Aim: This study aims to compare the efficacy of palpation, ultrasonography (USG) and computed tomography (CT) in the preoperative evaluation of cervical lymph node for metastasis in patients with oral squamous cell carcinoma. Settings: Department of Oral and Maxillofacial Surgery, SCB Dental College and Hospital, Cuttack, Odisha, India. Methodology: A total of thirty patients of either sex of age group 20–70 years, diagnosed with oral cancer were randomly selected for the study and subjected to palpation, USG and computer tomography followed by histopathology for confirmation. The results were evaluate statistically by sensitivity, specificity, positive predictive value, and negative predictive value and accuracy. Results: For level IA palpation, USG and CT were equally sensitive (100%) and specific (100%). Although palpation, USG and CT were equally sensitive (80%) for level IB, the specificity of palpation (70%) cervical lymph nodes in patients with oral squamous cell carcinoma. CT along with USG should be used for accurate preoperative evaluation of cervical lymph node. PMID:28356691

  19. Atezolizumab and Bevacizumab in Treating Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

    ClinicalTrials.gov

    2017-03-08

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  20. 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

  1. High expression of TGF-β1 in the vaginal incisional margin predicts poor prognosis in patients with stage Ib-IIa cervical squamous cell carcinoma.

    PubMed

    Fan, Dong-Mei; Wang, Xin-Jun; He, Tao; Wang, Yan; Zhou, Dan; Kong, Guo-Qiang; Jiang, Tao; Zhang, Mei-Mei

    2012-04-01

    This study evaluated the relationship between altered cytoplasmic expression of TGF-β1 in tissues of the vaginal incisional margin and vaginal cancer recurrence in patients with stage Ib-IIa cervical squamous cell carcinoma (CSCC). This paper also discusses the prognostic value of TGF-β1 expression at these locations. We found that TGF-β1 expression in the vaginal margin had a close association with vaginal recurrence of stage Ib-IIa CSCC and was an independent prognostic marker of this disease.

  2. The Characteristic of S100A7 Induction by the Hippo-YAP Pathway in Cervical and Glossopharyngeal Squamous Cell Carcinoma

    PubMed Central

    Hu, Enze; Wang, Rui; Wang, Junhao; Liu, Jin; Zhang, Jinsan; He, Dacheng; Xiao, Xueyuan

    2016-01-01

    S100A7 is expressed in many squamous cell carcinomas (SCCs). Our previous study revealed that S100A7 was dramatically induced in several SCC cells and activation of the Hippo pathway significantly promoted S100A7 in epidermoid carcinoma cells. However, whether the Hippo pathway regulates S100A7 expression in SCCs remains largely unknown. Here, we uncover that S100A7 induction by the Hippo-YAP pathway displays different characteristic in cervical and glossopharyngeal SCC. In well differentiated HCC94 cervical cells and FaDu pharyngeal cells, S100A7 is easily induced by both suspension and dense culture, which is accompanied by an increase in YAP phosphorylation and a decrease in nuclear YAP. Strikingly, these correlations of S100A7 and YAP reverse after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is significantly repressed by nuclear YAP, which is validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Subsequently, we prove that TEAD1 is required for YAP transcriptional repression of S100A7. However, S100A7 is hardly induced in poorly differentiated SiHa cervical cells and NCI-H226 pulmonary cells even in suspension or activation of the Hippo pathway. More importantly, cervical and lingual SCC tissues array analyses show that S100A7 expression displays the positive correlation with pYAP-S127 and the negative correlation with nuclear YAP in the majority of well differentiated but not in poorly differentiated tissues. Collectively, our findings demonstrate that the different induction of S100A7 toward activation of the Hippo pathway mainly depends on the degree of cell differentiation in cervical and glossopharyngeal SCC. PMID:27907036

  3. ADXS11-001 High Dose HPV+ Cervical Cancer

    ClinicalTrials.gov

    2016-06-17

    Effects of Immunotherapy; Metastatic/Recurrent Cervical Cancer; Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Small Cell Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  4. Radiation Therapy and Cisplatin With or Without Epoetin Alfa in Treating Patients With Cervical Cancer and Anemia

    ClinicalTrials.gov

    2014-12-29

    Anemia; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Drug Toxicity; Radiation Toxicity; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  5. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with locally advanced cervical cancer treated with radiation or chemoradiation

    PubMed Central

    Oh, Jinju; Lee, Hyun Joo; Lee, Tae Sung; Kim, Ju Hyun; Koh, Suk Bong

    2016-01-01

    Objective The objective of this study was to evaluate the clinical benefits of routine squamous cell carcinoma antigen (SCC-Ag) monitoring of patients with locally advanced cervical squamous cell carcinoma treated with radiation or chemoradiation. Methods A total of 53 patients with recurrent cervical squamous cell carcinoma treated with radiotherapy or chemoradiation were enrolled in this study. A retrospective review of medical records was conducted. The role of routine monitoring of serum SCC-Ag was evaluated in terms of cost effectiveness and effect on survival after diagnosis of recurrence. Results Serum SCC-Ag abnormality (≥2.5 ng/mL) was observed in 62.3% of patients when recurrent disease was diagnosed. The first indicator of relapse was abnormal serum SCC-Ag level in 21 patients (39.6%), 10 of whom had asymptomatic recurrent disease amenable to salvage therapy. Adding SCC-Ag measurement to the basic follow up protocol improved the sensitivity for detecting recurrence (The sensitivity of the basic protocol vs. addition of SCC-Ag: 49.1% vs. 88.7%, P<0.001). Twenty-three patients who were candidates for salvage therapy with curative intent showed better survival compared with those who were not candidates for therapy (5-year survival: 36.6% vs. 0%, P=0.012). Conclusion Surveillance with routine serum SCC-Ag monitoring can better detect asymptomatic recurrent disease that is potentially amenable to salvage therapy with curative intent. Early diagnosis of recurrent disease that can be treated with salvage therapy may lead to better survival. PMID:27462593

  6. Targeting the eIF4E/β-catenin axis sensitizes cervical carcinoma squamous cells to chemotherapy

    PubMed Central

    Xu, Hai; Wang, Zhiyin; Xu, Lang; Mo, Guoyan; Duan, Gangfeng; Wang, Yali; Sun, Zhengang; Chen, Hao

    2017-01-01

    Chemotherapy has improved the clinical outcomes of cervical cancer patients. However, patients develop chemoresistance, whose underlying mechanisms are not well understood. In this study, we investigated the phosphorylation levels of eukaryotic translation initiation factor 4E (eIF4E) in cervical cancer cells subjected to chemotherapy. Results showed that chemotherapeutic drugs significantly increased eIF4E phosphorylation at S209 in HeLa and SiHa cells. Upregulation of phosphorylated eIF4E (p-eIF4E) levels has also been shown in cisplatin-resistant HeLa cells and has been observed to be a common response of cervical cancer patients undergoing chemotherapy. We further showed that chemotherapeutic drugs increase β-catenin activity and mRNA levels of Wnt/β-catenin target genes in cervical cancer cells but not in eIF4E-depleted cells, suggesting that chemotherapeutic drugs activate Wnt/β-catenin signaling in an eIF4E-dependent manner. Inhibiting eIF4E via siRNA knockdown or Wnt/β-catenin using the Wnt inhibitor pyrvinium effectively enhanced the anti-proliferative and pro-apoptotic effects of cisplatin in cervical cancer cells both in vitro and in vivo. Our findings demonstrate that eIF4E/β-catenin signaling plays a positive regulatory role in the resistance of cervical cancer cell to chemotherapy and thus highlight the therapeutic value of eIF4E or β-catenin inhibition in overcoming chemoresistance. PMID:28386346

  7. Effect of different segmentation algorithms on metabolic tumor volume measured on 18F-FDG PET/CT of cervical primary squamous cell carcinoma

    PubMed Central

    Xu, Weina; Yu, Shupeng; Ma, Ying; Liu, Changping

    2017-01-01

    Background and purpose It is known that fluorine-18 fluorodeoxyglucose PET/computed tomography (CT) segmentation algorithms have an impact on the metabolic tumor volume (MTV). This leads to some uncertainties in PET/CT guidance of tumor radiotherapy. The aim of this study was to investigate the effect of segmentation algorithms on the PET/CT-based MTV and their correlations with the gross tumor volumes (GTVs) of cervical primary squamous cell carcinoma. Materials and methods Fifty-five patients with International Federation of Gynecology and Obstetrics stage Ia∼IIb and histologically proven cervical squamous cell carcinoma were enrolled. A fluorine-18 fluorodeoxyglucose PET/CT scan was performed before definitive surgery. GTV was measured on surgical specimens. MTVs were estimated on PET/CT scans using different segmentation algorithms, including a fixed percentage of the maximum standardized uptake value (20∼60% SUVmax) threshold and iterative adaptive algorithm. We divided all patients into four different groups according to the SUVmax within target volume. The comparisons of absolute values and percentage differences between MTVs by segmentation and GTV were performed in different SUVmax subgroups. The optimal threshold percentage was determined from MTV20%∼MTV60%, and was correlated with SUVmax. The correlation of MTViterative adaptive with GTV was also investigated. Results MTV50% and MTV60% were similar to GTV in the SUVmax up to 5 (P>0.05). MTV30%∼MTV60% were similar to GTV (P>0.05) in the 50.05) in the 100.05) in the SUVmax of at least 15 group. MTViterative adaptive was similar to GTV in both total and different SUVmax groups (P>0.05). Significant differences were observed among the fixed percentage method and the optimal threshold percentage was inversely correlated with SUVmax. The iterative adaptive segmentation algorithm led

  8. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    ClinicalTrials.gov

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  9. Detection of cervical lymph node micrometastasis and isolated tumor cells in oral squamous cell carcinoma using immunohistochemistry and serial sectioning

    PubMed Central

    Dhawan, Isha; Sandhu, Simarpreet V; Bhandari, Rajat; Sood, Neena; Bhullar, Ramanpreet Kaur; Sethi, Neerja

    2016-01-01

    Introduction: Oral squamous cell carcinoma (OSCC) comprises one of the largest subsets of cancers with a tendency for regional metastasis. Nodal status is a key prognostic indicator in patients with OSCC, particularly with N0 neck. Occult metastasis in the form of micrometastasis (MM) and isolated tumor cells (ITCs), often goes undetected by routine hematoxylin and eosin (H&E) examination using 1–2 sections for analysis. This limitation could be overcome by combining serial sectioning (SS) with immunohistochemistry (IHC) for the detection of MM and ITC. Pan-cytokeratin (pan-CK) (AE1/AE3) is particularly a useful marker to detect these deposits as their presence has resulted in varied interpretations and different applications of the tumor-node-metastasis system. Objectives: The objective of the study was to identify a suitable method for detecting MM and ITC in lymph nodes (LNs) of OSCC by combining SS and IHC and to compare it with conventional H&E staining. Materials and Methods: This laboratory-based, prospective study was conducted on 133 LNs harnessed from ten patients treated with radical neck dissection for primary OSCC. The LNs were subjected to SS at 100 μm intervals. The sections were stained with routine H&E staining, pan-CK and analyzed for MM and ITC according to criteria laid by Hermanek et al. Statistical Analysis: The obtained data were subjected to statistical analysis using Chi-square test. Results: The application of combination of SS and IHC using pan-CK (AE1/AE3) in our study revealed the presence of MM and ITC in 2.25% of the LNs diagnosed as negative on routine H&E examination. The detection of these occult metastatic deposits resulted in upstaging of 33.33% of the patients. Conclusion: In the view of crucial role of occult LN metastasis in prognosis and survival of OSCC patients with N0 neck, diagnostic tools such as IHC staining, particularly with pan-CK (AE1/AE3), combined with SS should be preferred over conventional methods as they

  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. Glycoprotein and Glycan in Tissue and Blood Samples of Patients With Stage IB-IVA Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  12. Comparison of Linear Array and Line Blot Assay for Detection of Human Papillomavirus and Diagnosis of Cervical Precancer and Cancer in the Atypical Squamous Cell of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study▿

    PubMed Central

    Castle, Philip E.; Gravitt, Patti E.; Solomon, Diane; Wheeler, Cosette M.; Schiffman, Mark

    2008-01-01

    We evaluated Linear Array (LA), a newly commercialized PGMY09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA testing was conducted on enrollment specimens from women referred because of an ASCUS Pap test. To gauge the performance of the new test, the results were compared to those of its prototype predecessor assay, Line Blot Assay (LBA), restricted to paired results (n = 3,335). LA testing was done masked to LBA results and clinical outcomes. The results of LA and LBA testing were compared for detection of carcinogenic HPV and clinical outcomes of cervical precancer and cancer. Overall, 50% and 55% of the women tested positive for carcinogenic HPV by LBA and LA, respectively (P < 0.0001). The percent agreement for carcinogenic HPV detection was 88%, percent positive agreement was 80%, and kappa was 0.76 for detection of carcinogenic HPV by the two assays. There was a significant increase in detection by LA for most of the 37 HPV genotypes targeted by both assays, including for 13 of 14 carcinogenic HPV genotypes. LA detected more multiple-genotype infections for all HPV genotypes among HPV-positive women (P < 0.0001) and for carcinogenic HPV genotypes among carcinogenic-HPV-positive women (P < 0.0001). LA was more sensitive (92.3% versus 87.1%; P = 0.003) and less specific (48.2% versus 54.0%; P < 0.0001) than LBA for 2-year cumulative cervical precancer and cancer as diagnosed by the Pathology Quality Control Group. In conclusion, we found LA to be a promising assay for the detection of HPV genotypes and carcinogenic HPV, and it may be clinically useful for the detection of

  13. Comparison of linear array and line blot assay for detection of human papillomavirus and diagnosis of cervical precancer and cancer in the atypical squamous cell of undetermined significance and low-grade squamous intraepithelial lesion triage study.

    PubMed

    Castle, Philip E; Gravitt, Patti E; Solomon, Diane; Wheeler, Cosette M; Schiffman, Mark

    2008-01-01

    We evaluated Linear Array (LA), a newly commercialized PGMY09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA testing was conducted on enrollment specimens from women referred because of an ASCUS Pap test. To gauge the performance of the new test, the results were compared to those of its prototype predecessor assay, Line Blot Assay (LBA), restricted to paired results (n = 3,335). LA testing was done masked to LBA results and clinical outcomes. The results of LA and LBA testing were compared for detection of carcinogenic HPV and clinical outcomes of cervical precancer and cancer. Overall, 50% and 55% of the women tested positive for carcinogenic HPV by LBA and LA, respectively (P < 0.0001). The percent agreement for carcinogenic HPV detection was 88%, percent positive agreement was 80%, and kappa was 0.76 for detection of carcinogenic HPV by the two assays. There was a significant increase in detection by LA for most of the 37 HPV genotypes targeted by both assays, including for 13 of 14 carcinogenic HPV genotypes. LA detected more multiple-genotype infections for all HPV genotypes among HPV-positive women (P < 0.0001) and for carcinogenic HPV genotypes among carcinogenic-HPV-positive women (P < 0.0001). LA was more sensitive (92.3% versus 87.1%; P = 0.003) and less specific (48.2% versus 54.0%; P < 0.0001) than LBA for 2-year cumulative cervical precancer and cancer as diagnosed by the Pathology Quality Control Group. In conclusion, we found LA to be a promising assay for the detection of HPV genotypes and carcinogenic HPV, and it may be clinically useful for the detection of

  14. Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer

    ClinicalTrials.gov

    2014-06-18

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  15. Histopathologic extent of cervical intraepithelial neoplasia 3 lesions in the atypical squamous cells of undetermined significance low-grade squamous intraepithelial lesion triage study: implications for subject safety and lead-time bias.

    PubMed

    Sherman, Mark E; Wang, Sophia S; Tarone, Robert; Rich, Laurie; Schiffman, Mark

    2003-04-01

    Cervical intraepithelial neoplasia 3 (CIN3) is the precursor of mostsquamous carcinomas and serves as a surrogate end point. However, small CIN3 lesions are rarely associated with concurrent invasion. We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer. We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study, focusing on ASCUS referrals. ASCUS referrals underwent randomized management [colposcopy for repeat cytology of high-grade squamous intraepithelial lesion (HSIL), colposcopy for oncogenic human papillomavirus (HPV) detection or repeat HSIL, or immediate colposcopy]; then all were followed with repeat cytology for 2 years, followed by colposcopy and aggressive treatment. We assessed all CIN3 lesions qualitatively and measured 39 of them. CIN3 lesions were overwhelmingly small. Compared with enrollment, lesions found at follow-up or exit involved fewer tissue fragments (P < 0.01) and showed less diffuse gland involvement (P = 0.03). CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [versus immediate colposcopy (P = 0.04) or repeat cytology of HSIL (P = 0.02)], and none showed diffuse gland involvement. The median distal-proximal length was 6.5 mm (median replacement of total epithelium = 5%) in the 39 measured cases. We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion, particularly if managed using HPV testing, suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened populations.

  16. Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2016-03-16

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  17. [Metastatic oropharyngeal squamous cell carcinoma in cervical lymph nodes associated to HPV infection type 16 and 45; clinical, morphological and molecular study of two cases].

    PubMed

    Soria-Céspedes, Danny; Canchola Aguilar, Guadalupe; Lara-Torres, César Octavio; Sánchez-Marle, Juan Felipe; Hernández-Peña, Roberto Enrique; Ortiz-Hidalgo, Carlos

    2013-01-01

    Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has been identified as a distinct entity within squamous cell carcinoma of the head and neck. In contrast to carcinomas associated with alcohol and/or tobacco, this subtype occurs at younger age, with frequent absence of classic risk factors, correlation with oral sexual habits, strong predilection for the palatial tonsils and the base of the tongue (lingual tonsils), basaloid or lymphoepithelial differentiation, higher degree of radiosensitivity, and overall better survival. We report two cases of lymph node, metastatic, poorly differentiated squamous cell carcinoma that were positive by immunohistochemistry for p16 with detection of HPV-16 and HPV-45 by PCR.

  18. Prognostic Value of Neutrophil-Related Factors in Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin-Based Concurrent Chemoradiotherapy.

    PubMed

    Wang, Yan-Yang; Bai, Zhou-Lan; He, Jian-Li; Yang, Yan; Zhao, Ren; Hai, Ping; Zhe, Hong

    2016-01-01

    The aim of this study was to explore the relationship between neutrophil-related factors, including neutrophil-lymphocyte ratio (NLR) and the responses of neutrophil to granulocyte colony-stimulating factors (RNG), and the prognosis of patients with locally advanced cervical squamous cell carcinoma (LACSCC) undergoing cisplatin-based concurrent chemoradiotherapy (CCCRT). A total of sixty LACSCC patients were enrolled in this study. We analyzed the association of NLR or RNG with clinicopathologic characteristics of these patients. The prognostic factors were evaluated by univariate and multivariate survival analysis. The optimal cut-off value of the NLR was determined to be 2.0 for the overall survival (OS). A higher level of the NLR was associated with younger age (P = 0.017) and higher baseline platelet count (P = 0.040). NLR was identified to be the only independent prognostic factor for OS by multivariate analysis (P = 0.037). The median RNG was 3.01, with a range of 1.19-16.84. RNG level was significantly associated with lymph node metastasis of these patients (P = 0.023). And higher RNG was identified as being a closely independent poor prognostic factor for OS (P = 0.055). This study showed that NLR and RNG may be used as potential biomarkers for survival prediction in patients with LACSCC receiving CCCRT.

  19. Coexistence of placental site nodule and cervical squamous carcinoma in a 72-year-old woman.

    PubMed

    Luna, Darling Valverde; Dulcey, Isabel; Nogales, Francisco F

    2013-05-01

    We report a unique case of the coexistence of cervical cancer and placental site nodule (PSN) in a 72-year-old multiparous woman presenting with vaginal bleeding. She had undergone tubal sterilization 30 years before. On admission, she had profuse vaginal bleeding, and a bulky cervical mass was seen on vaginal examination. Histology revealed the coexistence of a moderately differentiated invasive squamous cell carcinoma with a PSN in its stroma. Its immunohistochemistry revealed characteristic phenotypes for both lesions--the squamous carcinoma was strongly positive for p16. The intermediate trophoblasts of the PSN showed a diffuse positivity for CAM 5.2, human placental lactogen, CD10, and α-inhibin and, focally, for human chorionic gonadotropin. This is the first report on the coexistence of these 2 lesions in an elderly postmenopausal patient and demonstrates that PSN can be found after the menopause as an unexpected lesion in this age group, mimicking various cervical malignancies.

  20. 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.

  1. A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

    PubMed Central

    Takatori, Eriko; Shoji, Tadahiro; Takada, Anna; Nagasawa, Takayuki; Omi, Hideo; Kagabu, Masahiro; Honda, Tatsuya; Miura, Fumiharu; Takeuchi, Satoshi; Sugiyama, Toru

    2016-01-01

    Objective In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC) for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group) with patients who underwent RH without NAC (Ope group). Patients and methods The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS) and overall survival (OS) between the groups. Results There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days) in the NAC group and 25 days (21–34 days) in the Ope group; the patients in the NAC group were discharged earlier (P=0.032). The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91), and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028). Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24), and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101). Conclusion NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous cell carcinoma presenting as a bulky mass. PMID:27695343

  2. The clinical impact of p16 status in fine-needle aspirates of cervical lymph node metastasis of head and neck squamous cell carcinomas.

    PubMed

    Jakscha, Jens; Zlobec, Inti; Storck, Claudio; Obermann, Ellen C; Tornillo, Luigi; Terracciano, Luigi M; Fischer, Claude A

    2013-02-01

    Lymph node involvement is prognostically the most determinant clinical factor for patients with head and neck squamous cell carcinomas (HNSCCs). Ultrasound of the neck and fine-needle aspiration (FNA) cytology is one of the first diagnostic procedures and the most accurate diagnostic staging tool for the neck. Patients with HPV-positive oropharyngeal carcinomas (OPSCC) show a significantly better prognosis when compared with HPV-negative OPSCC. P16 overexpression is accepted as surrogate marker for HPV-positive in OPSCC. These HPV/p16-positive OPSCC are localized either in the palatal tonsils or the base of tongue and frequently present with lymph node metastases. We analyzed the correlation and reliability of p16 expression of the FNA of the lymph node metastasis with the immunohistochemical expression of p16 of the same lymph node metastasis and its corresponding primary tumor, as it could be of importance for determining the localization and different prognosis of the primary tumor. 54 HNSCC patients were evaluated, p16 expression of the primary tumors and their lymph node metastases correlated precisely. In 25 of the 54 HNSCC patients, a FNA of the lymph node metastases was taken before the treatment. The positive cytological and immunohistochemical p16 staining correlated exactly. Of the 17 histologically p16-negative lymph node metastases 15 FNA were p16-negative, whereas two samples were p16-positive. In our view, a cytological p16 analysis of cervical lymph node metastasis can facilitate the correct localization of the primary tumor and discriminate reliably HPV-positive OPSCC from HPV-negative HNSCC with their significantly diverse prognosis.

  3. Correlation Among Six Biologic Factors (p53, p21{sup WAF1}, MIB-1, EGFR, HER2, and Bcl-2) and Clinical Outcomes After Curative Chemoradiation Therapy in Squamous Cell Cervical Cancer

    SciTech Connect

    Yamashita, Hideomi; Murakami, Naoya; Asari, Takao; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

    2009-07-15

    Purpose: The expressions of six cell-cycle-associated proteins were analyzed in cervical squamous cell carcinomas in correlation in a search for prognostic correlations in tumors treated with concurrent chemoradiation therapy (cCRT). Methods and Materials: The expressions of p53, p21/waf1/cip1, molecular immunology borstel-1 (MIB-1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2), and Bcl-2 were studied using an immunohistochemical method in 57 cases of cervical squamous cell carcinoma treated with cCRT. Patients received cCRT between 1998 and 2005. The mean patient age was 61 years (range, 27-82 years). The number of patients with Stage II, III, and IVA disease was 18, 29, and 10, respectively. Results: The number of patients with tumors positive for p53, p21/waf1/cip1, MIB-1, EGFR, HER2, and Bcl-2 was 26, 24, 49, 26, 13, and 11, respectively; no significant correlation was noted. The 5-year overall survival rates of HER2-positive and -negative patients was 76% vs. 44%, which was of borderline significance (p = 0.0675). No significant correlation was noted between overall survival and expressions of p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2. No correlation was observed between local control and expression of any of the proteins. Conclusion: Expression of HER2 protein had a weak impact of borderline significance on overall survival in squamous cell carcinoma of the uterine cervix treated with cCRT. However, no clinical associations could be established for p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2 protein expressions.

  4. MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2017-02-08

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cervical Undifferentiated Carcinoma; Recurrent Cervical Carcinoma; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  5. Clinical Utility of Molecular Biomarkers in Cervical Squamous Intraepithelial Lesions in a Young Adult Population

    PubMed Central

    Spiryda, Lisa Beth; Whitaker, Kara M.; Messersmith, Amy; Banister, Carolyn E.; Creek, Kim E.; Pirisi-Creek, Lucia A.

    2015-01-01

    Objective Although human papillomavirus (HPV) infection is necessary for cervical squamous intraepithelial lesion (SIL/CIN) and cancer to develop, exposure to HPV is not predictive of which women will develop cervical squamous intraepithelial lesion and cancer. This study examines mRNA expression of several potential biomarkers in exfoliated cervical cells collected from college age women. Methods Freshman female students were recruited into the Carolina Women’s Care Study (CWCS) which was designed to prospectively evaluate factors that contribute to persistent HPV infections. One component of this study was to extract mRNA from exfoliated cervical cells. In this study, mRNA expression of FZD, GDF15, IL1β and N-cadherin was assessed through real-time PCR. Statistical analysis was performed with a Student’s t-test; all results were standardized with GAPDH. Results Fifty samples were selected that reflected the demographics of the CWCS participants. IL1β mRNA expression was 9.4-fold higher in cervical cells from women with abnormal Pap tests (p=0.0018); LSIL had 12.7-fold higher expression than negatives (p=0.0011). FZD mRNA expression was 5.7-fold higher in CIN2 as compared to CIN1 (p=0.0041) and 8.5-fold higher compared to cytology/pathology-negative (p=0.0014). Other differences in mRNA expression showed trends but not reaching statistical significance for each condition. Conclusions It appears that several biomarkers involved in the cytokine/inflammatory pathway (IL1 β), cell adhesion pathway (N-cadherin), growth factors (GDF-15), WNT signaling pathway (FZD) may be potential biomarkers in conjunction with the Pap test and HPV that help predict which women are at highest risk for developing CIN3 and cervical cancer. PMID:26579841

  6. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions

    PubMed Central

    2010-01-01

    Background Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Methods Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. Results The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. Conclusions These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation. PMID:21092209

  7. 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

  8. [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.

  9. The Association of High Risk Human Papillomaviruses in Patients With Cervical Cancer: An Evidence Based Study on Patients With Squamous Cell Dysplasia or Carcinoma for Evaluation of 23 Human Papilloma Virus Genotypes

    PubMed Central

    Piroozmand, Ahmad; Mostafavi Zadeh, Seyed Mostafa; Madani, Azita; Soleimani, Reza; Nedaeinia, Reza; Niakan, Mohammad; Avan, Amir; Manian, Mostafa; Moradi, Mohammad; Eftekhar, Zahra

    2016-01-01

    Background Cervical cancer is one of the leading causes of cancer-related death in females. Human papilloma virus (HPV) is the major risk factor of cervical cancer. Objectives The aim of the current study was to explore the frequency and role of 23 different HPVs in patients with cervical cancer. Materials and Methods Overall, 117 formalin-fix and paraffin-embedded (FFPE) tissues from cervical cancer patients with squamous cell carcinoma (SCC) or dysplasia were collected from Mirza-Kochakkhan-Jangali hospital, Tehran, Iran during year 2013, to investigate the presence of HPV- HPV- 67, 68, 6, 11, 13, 16, 17, 30, 69, 39, 40, 42, 64, 66 and 51 to 59 genotypes. Results The Pap smear report illustrated the presence of malignancy in 71 cases, while 11 cases had no evidence of malignancy. Among the patients, 26 cases had sexually transmitted disease with relative frequency of 0.58. Infection with papilloma virus was observed in 83.6% of SCC patients and 45% of the dysplasia group. The most prevalent HPV genotypes were 18 with 31.62% and 16 with 27.35% of cases. Moreover the relative frequencies of HPV-33, -6, -58, -52, -35 and -51, genotypes were 15.38, 7.69, 5.98, 5.12 and 3.41%, respectively. Among the different genotypes of HPV, 31 had the lowest and 16 had the highest relative frequency. Conclusions Our findings demonstrate that HPV-16 and -18 have a higher prevalence in our population than 31 and 51. Further investigations are required to evaluate the role of these genotypes in a larger multicenter setting for establishing their values for early detection of patients, which is useful for screening and vaccination programs of cancerous and precancerous lesions of cervical cancer. PMID:27279992

  10. Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Lymphedema; Sexual Dysfunction and Infertility; Stage IA1 Cervical Cancer; Stage IA2 Cervical Cancer; Stage IB1 Cervical Cancer

  11. Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice.

    PubMed

    Arbeit, J M; Howley, P M; Hanahan, D

    1996-04-02

    High-risk human papillomaviruses (HPVs), including type 16, have been identified as factors in cervical carcinogenesis. However, the presence and expression of the virus per se appear to be insufficient for carcinogenesis. Rather, cofactors most likely are necessary in addition to viral gene expression to initiate neoplasia. One candidate cofactor is prolonged exposure to sex hormones. To examine the possible effects of estrogen on HPV-associated neoplasia, we treated transgenic mice expressing the oncogenes of HPV16 under control of the human keratin-14 promoter (K14-HPV16 transgenic mice) and nontransgenic control mice with slow release pellets of 17beta-estradiol. Squamous carcinomas developed in a multistage pathway exclusively in the vagina and cervix of K14-HPV16 transgenic mice. Estrogen-induced carcinogenesis was accompanied by an incremental increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-HPV16 mice. Expression of the HPV transgenes in untreated transgenic mice was detectable only during estrus; estrogen treatment resulted in transgene expression that was persistent but not further upregulated, remaining at low levels at all stages of carcinogenesis. The data demonstrate a novel mechanism of synergistic cooperation between chronic estrogen exposure and the oncogenes of HPV16 that coordinates squamous carcinogenesis in the female reproductive tract of K14-HPV16 transgenic mice.

  12. Intensity-Modulated Radiotherapy for Cervical Node Squamous Cell Carcinoma Metastases From Unknown Head-and-Neck Primary Site: M. D. Anderson Cancer Center Outcomes and Patterns of Failure

    SciTech Connect

    Frank, Steven J.; Rosenthal, David I.; Petsuksiri, Janjira; Ang, K. Kian; Morrison, William H.; Weber, Randal S.; Glisson, Bonnie S.; El-Naggar, Adel K.; Garden, Adam S.

    2010-11-15

    Purpose: Conventional therapy for cervical node squamous cell carcinoma metastases from an unknown primary can cause considerable toxicity owing to the volume of tissues to be irradiated. In the present study, hypothesizing that using intensity-modulated radiotherapy (IMRT) would provide effective treatment with minimal toxicity, we reviewed the outcomes and patterns of failure for head-and-neck unknown primary cancer at a single tertiary cancer center. Methods and Materials: We retrospectively reviewed the records of 52 patients who had undergone IMRT for an unknown primary at M.D. Anderson Cancer Center between 1998 and 2005. The patient and treatment characteristics were extracted and the survival rates calculated using the Kaplan-Meier method. Results: Of the 52 patients, 5 presented with Stage N1, 11 with Stage N2a, 23 with Stage N2b, 6 with Stage N2c, 4 with Stage N3, and 3 with Stage Nx disease. A total of 26 patients had undergone neck dissection, 13 before and 13 after IMRT; 14 patients had undergone excisional biopsy and presented for IMRT without evidence of disease. Finally, 14 patients had received systemic chemotherapy. All patients underwent IMRT to targets on both sides of the neck and pharyngeal axis. The median follow-up time for the surviving patients was 3.7 years. The 5-year actuarial rate of primary mucosal tumor control and regional control was 98% and 94%, respectively. Only 3 patients developed distant metastasis with locoregional control. The 5-year actuarial disease-free and overall survival rate was 88% and 89%, respectively. The most severe toxicity was Grade 3 dysphagia/esophageal stricture, experienced by 2 patients. Conclusion: The results of our study have shown that IMRT can produce excellent outcomes for patients who present with cervical node squamous cell carcinoma metastases from an unknown head-and-neck primary tumor. Severe late complications were uncommon.

  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. 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 ...

  15. 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 ...

  16. Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

    ClinicalTrials.gov

    2017-01-31

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer; Stage IB2 Cervical Cancer; Stage II Vulvar Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Cervical Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Cervical Cancer; Stage IVA Vulvar Cancer; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

  17. [Importance of immunohistochemical studies in the diagnosis and the prognostic evaluation of cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Review].

    PubMed

    García-Tamayo, Jorge; Molina, Julia; Blasco-Olaetxea, Eduardo

    2009-06-01

    Immunohistochemical studies in cervical intraepithelial neoplasia and cervical carcinoma are evaluated in this review. A variety of proteins like p53, bcl2, C-Myc, Ki 67, Cyclines, P16 INK4a, p21, p27, beta-catenin, Wnt and MCM, have been related to the development of cervical neoplasia and human papilloma virus infection. It is described how transcriptional factors of genes induce loss of heterozygosity, numerical chromosome abnormality and inactivation of gene products or the partial loss of some membrane glycoproteins induced by oncogenic human papillomaviruses (HPV).

  18. Correlation of p16INK4a immunoexpression and human papillomavirus (HPV) detected by in-situ hybridization in cervical squamous neoplasia.

    PubMed

    Cheah, P L; Koh, C C; Nazarina, A R; Teoh, K H; Looi, L M

    2016-04-01

    Persistence and eventual integration of high-risk HPV (hrHPV) into the cervical cell is crucial to the progression of cervical neoplasia and it would be beneficial to morphologically identify this transformation in routine surgical pathology practice. Increased p16(INK4a) (p16) expression is a downstream event following HPV E7 binding to pRB. A study was conducted to assess the correlation between hrHPV detection using a commercial in-situ hybridization assay (Ventana INFORM HPV ISH) and p16 immunoexpression (CINtec Histology Kit) in cervical squamous intraepithelial lesions and squamous carcinoma. 27 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 51 squamous carcinoma (SCC) were interrogated. hrHPV was significantly more frequent in HSIL (76.2%) and SCC (88.2%) compared to LSIL(37.0%). p16 expression was similarly more frequent in HSIL (95.2%) and SCC (90.2%) compared to LSIL(3.7%). That the rates of hrHPV when compared with p16 expression were almost equivalent in HSIL and SCC while p16 was expressed in only 1 of the 10 LSIL with hrHPV, are expected considering the likelihood that transformation has occurred in HSIL and SCC but does not occur in majority of LSIL.

  19. Cervical lymph node metastases of squamous cell carcinoma of unknown origin: the diagnostic value of FDG PET/CT and clinical outcome.

    PubMed

    Dale, Einar; Moan, Jon M; Osnes, Terje A; Bogsrud, Trond V

    2017-02-01

    FDG PET/CT is perceived as a valuable diagnostic tool in addition to the standard diagnostic workup for patients with isolated neck lymph nodes of squamous cell carcinoma of unknown primary (SCCUP). For patients with SCCUP intended for primary radiotherapy, we hypothesize that the previously reported FDG PET/CT detection rates are too high. From 2008 to 2015, 30 SCCUP patients were examined with FDG PET/CT. The objective of the FDG PET/CT examination was twofold: (1) improve the radiotherapy target definition, and (2) identify the primary cancer. Before the FDG PET/CT, the patients had been through a standard workup consisting of CT of the neck and chest, examination with flexible endoscopy with patient awake, panendoscopy and examination under general anesthesia, tonsillectomy and sometimes blind sampling biopsies, and MRI (floor of the mouth). All FDG PET/CTs were performed applying a flat table, head support and fixation mask as part of the radiotherapy treatment planning. Diagnostic CT with contrast was an integrated part of the PET/CT examination. Only 1/30 patients (cancer of the vallecula) had their primary cancer detected by FDG PET/CT. In addition, a non-biopsied patient with high uptake in the ipsilateral palatine tonsil was included, giving a detection rate of ≤7 % (95 % CI 2-21 %). In this retrospective study, we found that the FDG PET/CT detection rate of the primary for SCCUP patients is lower than previously reported. It is questionable whether FDG PET/CT is necessary for these patients when improved, advanced workup is available.

  20. Comparison of Xpert(®) HPV and Hybrid Capture(®) 2 DNA Test™ for detection of high-risk HPV infection in cervical atypical squamous cells of undetermined significance.

    PubMed

    Rabaan, Ali A; Taylor, Donald R; Dawamneh, Mohammed F; Al-Tawfiq, Jaffar A

    This study compares Xpert(®) HPV and Hybrid Capture(®) 2 High-Risk HPV DNA Test™ (hc2) for the detection of high-risk HPV infection in cervical smears. Papanicolaou smears with atypical squamous cells of undetermined significance (ASC-US) constituted the study specimens. Of the 168 ASC-US samples, 134 (79.8%) were from Saudi patients. The hc2 test was positive in 33 (19.6%) of the total patients, 20% among Saudi patients, and 17.6% among non-Saudi patients. Xpert(®) HPV produced positive results in 30 (17.8%) of the samples. The overall concordance rate between the two tests was 98.2%, and the positive concordance rate was 91%. There were three samples tested positive by hc2 that tested negative by Xpert(®) HPV. HPV 16, HPV 18/45 and HPV other types were the most common types. Both tests have a reasonable positive concordance rate, although hc2 detected more cases than Xpert(®) HPV. Xpert(®) HPV provides a viable alternative to the hc2 test with similar detection results for samples with ASC-US.

  1. 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

  2. Fludeoxyglucose F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

    ClinicalTrials.gov

    2016-11-14

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage IVA Cervical Cancer

  3. Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

    ClinicalTrials.gov

    2017-03-08

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Positive Para-Aortic Lymph Node; Positive Pelvic Lymph Node; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

    PubMed Central

    Kefala, Maria; Kottaridi, Christine; Spathis, Aris; Gouloumi, Alina-Roxani; Pouliakis, Abraham; Pappas, Asimakis; Sioulas, Vasileios; Chrelias, Charalambos; Karakitsos, Petros; Panayiotides, Ioannis

    2017-01-01

    Background γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Methods Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Results Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. Conclusions γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state. PMID:28118377

  10. Wnt-11 overexpression promoting the invasion of cervical cancer cells.

    PubMed

    Wei, Heng; Wang, Ning; Zhang, Yao; Wang, Shizhuo; Pang, Xiaoao; Zhang, Shulan

    2016-09-01

    Wnt-11 is a positive regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, Wnt-11 expression in cervical cancer has not been well investigated. The aim of this study was to investigate the role of Wnt-11 in cervical tumor proliferation and invasion. This study examined 24 normal cervical squamous epithelia, 29 cervical intraepithelial neoplasia (CIN), and 78 cervical cancer samples. The expression of Wnt-11 was investigated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction analysis. The expression of the high-risk human papilloma virus (HR-HPV) E6 oncoprotein was also investigated by immunohistochemistry. In addition, the expression of Wnt-11, HR-HPV E6, JNK-1, phosphorylated JNK-1(P-JNK1), and β-catenin was examined by western blot analysis following Wnt-11 knockdown or overexpression in HeLa or SiHa cells, respectively. The promotion of cervical cancer cell proliferation and invasion was investigated using the cell counting kit-8 and Matrigel invasion assay, respectively. Wnt-11 and HR-HPV E6 expression increased in a manner that corresponded with the progression of cervical cancer and was significantly correlated with the International Federation of Gynecology and Obstetrics cancer stage, lymph node metastasis, tumor size, and HPV infection. Wnt-11 protein expression was positively associated with HR-HPV E6 protein expression in all 78 cervical cancer samples (P < 0.001). Furthermore, Wnt-11 was positively associated with P-JNK1 expression and promoted cervical cancer cell proliferation and invasion. These observations suggest that the increased Wnt-11 expression observed in cervical cancer cells may lead to the phosphorylation and activation of JNK-1 and significantly promote tumor cell proliferation and cell migration/invasion through activation of the Wnt/JNK pathway. Consequently, Wnt-11 may serve as a novel target for cervical cancer therapy.

  11. 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

  12. 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.

  13. [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.

  14. 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.

  15. Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Chemotherapeutic Agent Toxicity; Cognitive Side Effects of Cancer Therapy; Psychological Impact of Cancer; Radiation Toxicity; Sexual Dysfunction and Infertility; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  16. Development and evaluation of topotecan loaded solid lipid nanoparticles: A study in cervical cancer cell lines.

    PubMed

    Chen, Zhao-Jie; Zhang, Zhen; Xie, Bei-Bei; Zhang, Hai-Yan

    2016-12-01

    The study aims at statistical development of solid lipid nanoparticles (SLNs) loaded with topotecan hydrochloride for avoiding the drawbacks of conventional drug therapies used in cervical cancer. Twenty SLN batches were prepared using organic solvent evaporation method to provide response surface curves. Thereafter, optimized SLNs were obtained using numeric method based on desirability functions providing maximum drug loading and appropriate particle size. Physical characterization of optimized TPH loaded SLNs was performed in terms of particle size, zeta potential, transmission and scanning electron microscopic evaluation. Cytotoxicity studies were performed against cervical cancer cell lines, including cervical squamous cell carcinoma cell line (HeLa) and human squamous cell carcinoma cell line (SiHa). Also, Swiss mouse embryo fibroblast cells (3T3-L1) and African green monkey kidney epithelial (Vero) cells were used to evaluate biocompatibility in normal cells. As pronounced from the results, optimized SLNs may provide an attractive alternative to conventional cervical cancer drug products.

  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. Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

    PubMed Central

    2012-01-01

    Background Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Methods Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766). Results Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Conclusion Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression. PMID:22443139

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Revised terminology for cervical histopathology and its implications for management of high-grade squamous intraepithelial lesions of the cervix.

    PubMed

    Waxman, Alan G; Chelmow, David; Darragh, Teresa M; Lawson, Herschel; Moscicki, Anna-Barbara

    2012-12-01

    In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is "low-grade" or "high-grade squamous intraepithelial lesion (SIL)." This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using "intraepithelial neoplasia" (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology.

  4. 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

  5. Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    ClinicalTrials.gov

    2017-03-23

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB2 Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Vaginal Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Vaginal Cancer

  6. 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.

  7. 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

  8. 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.

  9. Characterization of Single-Nucleotide Polymorphisms in the Tumor Necrosis Factor α Promoter Region and in Lymphotoxin α in Squamous Intraepithelial Lesions, Precursors of Cervical Cancer1

    PubMed Central

    Nieves-Ramirez, Miriam Enriqueta; Partida-Rodriguez, Oswaldo; Alegre-Crespo, Pedro Eduardo; Tapia-Lugo, Maria del Carmen; Perez-Rodriguez, Martha Esthela

    2011-01-01

    Development of cervical cancer is a long process of abnormal cancerous cell growth in the cervix and is primarily the result of infection with specific high-risk types of human papillomavirus (HPV). The cytokines tumor necrosis factor α (TNFα) and lymphotoxin α (LTA) have an important role in all stages of cervical cancer and have the ability to induce the regression or promote the development of human tumors. Biologically important single-nucleotide polymorphisms (SNPs) occur within the TNFα and LTA genes. Therefore, the purpose of this study was to investigate the SNPs in the TNFα promoter region (-163, -238, -244, -308, -376, -857, -863, and -1031) and in the first intron of LTA (+252) in women with precursor lesions of cervical cancer. Overall, we studied 396 women from Mexico City. A total of 191 patients with HPV infection and precursor cervical lesions were subdivided in two groups: those with low-grade squamous intraepithelial lesions (n = 132) and those with high-grade squamous intraepithelial lesions (n = 59). Women (n = 205) negative for HPV and without cervical lesions were also included in the study. DNA was extracted from peripheral white blood cells and from cervical samples, and detection of biallelic polymorphisms of TNFα and LTA was performed using the polymerase chain reaction-sequence-specific oligonucleotide probe and restriction fragment length polymorphism techniques, respectively. We demonstrated that risk is associated with the genotype G/A (odds ratio = 2.48) and that protection is associated with the genotype G/G of SNP TNFα -376 (odds ratio = 0.37). PMID:22190997

  10. 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

  11. Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study

    PubMed Central

    Andrae, Bengt; Sundström, Karin; Ström, Peter; Ploner, Alexander; Elfström, K Miriam; Arnheim-Dahlström, Lisen; Dillner, Joakim; Sparén, Pär

    2016-01-01

    Objectives To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. Design Nationwide population based cohort study. Setting Cancer and population registries in Sweden. Participants 3 054 328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2 899 968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. Main outcome measures Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. Results The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment

  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. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Elective neck management for squamous cell carcinoma metastatic to the parotid area lymph nodes.

    PubMed

    Herman, Michael P; Amdur, Robert J; Werning, John W; Dziegielewski, Peter; Morris, Christopher G; Mendenhall, William M

    2016-11-01

    The objective of this study is to determine if radiotherapy (RT) alone to the cervical lymphatics is a suitable alternative to elective neck dissection (END) in patients who undergo parotidectomy and postoperative RT for squamous cell carcinoma metastatic to the parotid area lymph nodes (PALN). We retrospectively reviewed the medical records of 107 patients consecutively treated from November 1969 to March 2012 for cutaneous squamous cell carcinoma metastatic to the PALN with a clinically node-negative neck. Primary therapy consisted of parotidectomy in all cases. We compared regional (cervical) control in two subgroups: 42 patients treated with END and RT and 65 patients treated with elective neck irradiation (ENI) alone. The median time of follow-up was 5.5 years (range 0.3-30 years) for all patients and 11 years for living patients (range 1.8-26 years). There was 1 neck recurrence in each subgroup: END and RT, 1/42 (2 %); and ENI alone, 1/65 (1.5 %). No patient experienced a complication related to neck RT. ENI to a dose of approximately 50-60 Gy is a suitable alternative to END and postoperative RT in patients with squamous cell carcinoma metastatic to the PALN.

  1. [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.

  2. Inhibiting CD146 by its Monoclonal Antibody AA98 Improves Radiosensitivity of Cervical Cancer Cells

    PubMed Central

    Cheng, Huawen

    2016-01-01

    Background Cervical cancer is one of the major causes of cancer death of females worldwide. Radiotherapy is considered effective for cervical cancer treatment, but the low radiosensitivity found in some cases severely affects therapeutic outcomes. This study aimed to reveal the role of CD146, an important adhesion molecule facilitating tumor angiogenesis, in regulating radiosensitivity of cervical cancer cells. Material/Methods CD146 protein expression was compared in normal cells, cervical cancer cells with lower radiosensitivity, and cervical cancer cells with higher sensitivity from cervical squamous cell carcinoma patients. Anti-CD146 monoclonal antibody AA98 was used to inhibit CD146 in human cervical cancer SiHa cells with relatively low radiosensitivity, and then the cell survival and apoptosis changes after radiation were detected by colony formation assay and flow cytometry. Results CD146 protein was significantly up-regulated in cervical cancer cells (P<0.001), especially in cancer cells with lower radiosensitivity. The SiHa cells treated with AA98 showed more obvious inhibition in cell survival (P<0.05) and promotion in cell apoptosis (P<0.01) after radiation, compared to the untreated cells. More dramatic changes in apoptotic factors Caspase 3 and Bcl-XL were also detected in AA98-treated cells. Conclusions These results indicate that inhibiting CD146 improves the effect of radiation in suppressing SiHa cells. This study shows the potential of CD146 as a target for increasing radiosensitivity of cervical cancer cells, which might allow improvement in treatment outcome in cervical cancer. Further studies are necessary for understanding the detailed mechanism of CD146 in regulating radiosensitivity. PMID:27647179

  3. 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

  4. Human papilloma virus genotypes in women from Nayarit, Mexico, with squamous intraepithelial lesions and cervical cancer

    PubMed Central

    Ortega-Cervantes, Laura; Aguilar-Lemarroy, Adriana; Rojas-García, Aurora Elizabeth; Barrón-Vivanco, Briscia Socorro; Vallejo-Ruiz, Verónica; León, David Cantú-De; Hernández, Yael Yvette Bernal; Jáuregui-Martínez, Armando; Medina-Díaz, Irma Martha

    2016-01-01

    Objective In Mexico cervical cancer (CC) is the most common cause of death from neoplasia in women. Study aimed to analyze the current distribution of Human papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous intraepithelial lesions (SIL) and Cervical cancer (CC). Methodology Between January 2011 and July 2013, cervical samples were collected from female residents of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY® HPV genotyping test. Data analyses were performed using Stata ver. 8.0 statistical software. Results Of the samples analyzed, 91.2%, HPV DNA was detected. Of these positive samples, 82% were High-risk (HR) viral types. The most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two percent of participants had a single infection, while 23 and 26% of participants were infected with two or more HPV genotypes, respectively. HPV 16 was the most prevalent genotype identified and was frequently present as a co-infection with HPV types 18, 51, 52, 59, 66, or 70. Conclusion Women <20 years of age were most often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and 11), currently available in Mexico, no confers protection against a subset of the HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is important evaluate the geographical distribution of specific HPV genotypes in all health of center across Mexico in order to implement a successful vaccination program and to diagnose CC in its early stages. PMID:27610056

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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 ...

  11. 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.

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

    PubMed Central

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

    2014-01-01

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

  13. CLDN1 expression in cervical cancer cells is related to tumor invasion and metastasis

    PubMed Central

    Wang, Xiao-li; Hu, Zheng; Zhu, Da; Ding, Wen-cheng; Liu, Dan; Li, Ke-zhen; Ma, Ding; Wang, Hui

    2016-01-01

    Even though infection with human papillomaviruses (HPV) is very important, it is not the sole cause of cervical cancer. Because it is known that genetic variations that result from HPV infection are probably the most important causes of cervical cancer, we used human whole genome array comparative genomic hybridization to detect the copy number variations of genes in cervical squamous cell carcinoma. The results of the array were validated by PCR, FISH and immunohistochemistry. We find that the copy number and protein expression of claudin-1 (CLDN1) increase with the progression of cervical cancer. The strong positive staining of CLDN1 in the cervical lymph node metastasis group received a significantly higher score than the staining in the group with no lymph node metastasis of cervical cancer tissues. The overexpression of CLDN1 in SiHa cells can increase anti-apoptosis ability and promote invasive ability of these cells accompanied by a decrease in expression of the epithelial marker E-cadherin as well as an increase in the expression of the mesenchymal marker vimentin. CLDN1 induces the epithelial-mesenchymal transition (EMT) through its interaction with SNAI1. Furthermore, we demonstrate that CLDN1 overexpression has significant effects on the growth and metastasis of xenografted tumors in athymic mice. These data suggest that CLDN1 promotes invasion and metastasis in cervical cancer cells via the expression of EMT/invasion-related genes. Therefore, CLDN1 could be a potential therapeutic target for the treatment of cervical cancer. PMID:27974683

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Apoptosis in cervical squamous carcinoma: predictive value for survival following radiotherapy

    PubMed Central

    Paxton, J; Bolger, B; Armour, A; Symonds, R; Mao, J; Burnett, R

    2000-01-01

    Background—Apoptosis, or programmed cell death, can be induced by radiotherapy. The extent of apoptosis in a tumour before treatment may have important implications for response to radiotherapy and long term survival. Aim—To examine the extent of apoptosis in tumour tissue from patients with squamous carcinoma of the cervix before radiotherapy, and to correlate this with response to treatment and prognosis. Methods—The percentage of apoptotic cells was assessed in 146 carcinomas of the cervix from patients scheduled to receive radiotherapy. The CAS 200 static image analysis system was used to count the number of tumour nuclei per high power field, while the numbers of apoptotic cells in the same field were visualised simultaneously on the image analyser and recorded manually. Results—The median apoptotic level was 0.73%. Patients were divided into two groups around the median. There was no statistically significant difference in outcome between the two groups as determined by long term survival following radiotherapy. Conclusions—The CAS 200 static image analyser system can be used to assist in the rapid semiautomated assessment of apoptosis in conventionally prepared tissue. The results suggest that the apoptotic state of a tumour before treatment is of no value in predicting response to radiotherapy and subsequent prognosis. Tumour stage, size, and BrdU labelling index, as a measure of proliferation rate, remain the most important prognostic factors in terms of predicting local tumour control. Key Words: apoptosis • uterine cervix • squamous cell carcinoma PMID:10823138

  20. [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.

  1. 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

  2. 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 ...

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy

    NASA Astrophysics Data System (ADS)

    Zhao, Xueqin; Zhong, Yunxin; Ye, Ting; Wang, Dajing; Mao, Bingwei

    2015-12-01

    The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Transcriptome Sequencing Demonstrates that Human Papillomavirus is not Active in Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Arron, Sarah Tuttleton; Ruby, J. Graham; Dybbro, Eric; Ganem, Don; DeRisi, Joseph L.

    2011-01-01

    Beta-papillomavirus (β-HPV) DNA is present in some cutaneous squamous cell carcinomas (cuSCC), but no mechanism of carcinogenesis has been determined. We used ultra-high throughput sequencing of the cancer transcriptome to assess whether papillomavirus transcripts are present in these cancers. Sixty-seven cuSCC samples were assayed for β-HPV DNA by PCR, and viral loads were measured with type-specific qPCR. Thirty-one SCCs were selected for whole transcriptome sequencing. Transcriptome libraries were prepared in parallel from the HPV18 positive HeLa cervical cancer cell line and HPV16 positive primary cervical and periungual SCC. Thirty percent (20/67) of the tumors were positive for β-HPV DNA, but there was no difference in β-HPV viral load between tumor and normal tissue (p=0.310). Immunosuppression and age were significantly associated with higher viral load (p=0.016 for immunosuppression; p=0.0004 for age). Transcriptome sequencing failed to identify papillomavirus expression in any of the skin tumors. In contrast, HPV 16 and 18 mRNA transcripts were readily identified in primary cervical and periungual cancers and HeLa cells. These data demonstrate that papillomavirus mRNA expression is not a factor in the maintenance of cuSCC. PMID:21490616

  3. 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

  4. 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

  5. Immunohistochemical detection of the X-linked inhibitor of apoptosis protein (XIAP) in cervical squamous intraepithelial neoplasia and squamous carcinoma.

    PubMed

    Burstein, David E; Idrees, Muhammad T; Li, Gon; Wu, Maoxin; Kalir, Tamara

    2008-04-01

    Premalignant and invasive squamous lesions of the uterine cervix were surveyed for the immunohistochemical detectability of the X-linked inhibitor of apoptosis protein (XIAP), believed to be the most potent of a novel group of proteins designated inhibitor of apoptosis proteins (IAPs). IAPs bind and prevent the activation of apoptosis-mediating caspases. Recent cancer biologic studies have implicated IAPs in therapeutic resistance and tumor aggressiveness. XIAP in particular is considered a highly promising target for drug discovery. Forty-four formalin-fixed and paraffin-embedded archival tissue sections were deparaffinized; subjected to citrate-based antigen retrieval; and immunostained with anti-XIAP monoclonal antibody (clone 48, BD Biosciences, San Jose, Calif) diluted 1:250, 4 degrees C x 72 hours; and developed using EnVision-Plus (Dako, Carpinteria, Calif) and diaminobenzidine as chromagen. Particulate or heterogeneous cytoplasmic staining was considered positive. Normal squamous epithelium was XIAP-positive in 7 of 34 cases (20.6%). Preinvasive intraepithelial lesions were positively stained in 54.5% of cases. Nineteen of 22 invasive squamous carcinomas were positive (86.4%). The intensity and extensiveness of XIAP immunostaining varied among individual cases, but trended upward with loss of tumor differentiation: 8 of 9 cases with strong staining were poorly differentiated carcinomas. The present study suggests the characteristic link between poor tumor differentiation and more aggressive clinical behavior could in some malignancies be based upon the concomitant induction of XIAP. Induction of XIAP appears to occur in a subset of intraepithelial lesions; in others, XIAP is detected only upon progression to invasive carcinoma. Detection of enhanced XIAP expression may also pinpoint those lesions that might benefit from pharmacologic disruption of XIAP's actions.

  6. Saracatinib Impairs Head and Neck Squamous Cell Carcinoma Invasion by Disrupting Invadopodia Function

    PubMed Central

    Ammer, Amanda Gatesman; Kelley, Laura C.; Hayes, Karen E.; Evans, Jason V.; Lopez-Skinner, Lesly Ann; Martin, Karen H.; Frederick, Barbara; Rothschild, Brian L.; Raben, David; Elvin, Paul; Green, Tim P.; Weed, Scott A.

    2010-01-01

    Elevated Src kinase activity is linked to the progression of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Src regulates HNSCC proliferation and tumor invasion, with the Src-targeted small molecule inhibitor saracatinib displaying potent anti-invasive effects in preclinical studies. However, the pro-invasive cellular mechanism(s) perturbed by saracatinib are unclear. The anti-proliferative and anti-invasive effects of saracatinib on HNSCC cell lines were therefore investigated in pre-clinical cell and mouse model systems. Saracatinib treatment inhibited growth, cell cycle progression and transwell Matrigel invasion in HNSCC cell lines. Dose-dependent decreases in Src activation and phosphorylation of the invasion-associated substrates focal adhesion kinase, p130 CAS and cortactin were also observed. While saracatinib did not significantly impact HNSCC tumor growth in a mouse orthotopic model of tongue squamous cell carcinoma, impaired perineural invasion and cervical lymph node metastasis was observed. Accordingly, saracatinib treatment displayed a dose-dependent inhibitory effect on invadopodia formation, extracellular matrix degradation and matrix metalloprotease 9 activation. These results suggest that inhibition of Src kinase by saracatinib impairs the pro-invasive activity of HNSCC by inhibiting Src substrate phosphorylation important for invadopodia formation and associated matrix metalloprotease activity. PMID:20505783

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. The Combined Influence of Oral Contraceptives and Human Papillomavirus Virus on Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Efird, Jimmy T.; Toland, Amanda E.; Lea, C. Suzanne; Phillips, Christopher J.

    2011-01-01

    The vast majority of cutaneous squamous cell carcinoma (CSCC) will occur in those with fair complexion, tendency to burn, and high ultraviolet radiation (UVR) exposure. Organ transplant recipients also are an important population at great risk for CSCC. An association has been reported between oral contraceptive (OC) use, human papillomavirus virus (HPV) and cervical cancer, and there could be a similar association for CSCC. The cutaneous HPV β-E6 protein, a close cousin of the transformative E6 protein underlying anogenital cancers, has been shown to inhibit apoptosis in response to UVR damage and stimulate morphologic transformation in rodent fibroblast cell lines. Furthermore, OC use has been shown to enhance HPV transcription and may contribute to CSCC risk through this pathway. PMID:21499554

  17. Meta-analysis of type-specific human papillomavirus prevalence in Iranian women with normal cytology, precancerous cervical lesions and invasive cervical cancer: Implications for screening and vaccination.

    PubMed

    Jalilvand, Somayeh; Shoja, Zabihollah; Nourijelyani, Keramat; Tohidi, Hamid Reza; Hamkar, Rasool

    2015-02-01

    To predict the impact of current vaccines on cervical cancer and for the improvement of screening programs, regional data on distribution of human papillomavirus (HPV) types in women with or without cervical cancer is crucial. The present meta-analysis intend to comprehensively evaluate the HPV burden in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology, as these data will help decision making in regards with screening programs and HPV vaccination in Iran. To determine the HPV prevalence and type distribution in Iranian women with or without cervical cancer, 20 published studies were included in this meta-analysis. In total, 713, 124, 104, 60, and 2577 women invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal were reviewed, respectively. Overall HPV prevalence in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology were 77.4%, 71.8%, 65.3%, 61.7%, and 8.4%, respectively. The six most common types were HPV 16, 18, 6/11, 31, and 33; among them HPV 16 was the most frequent type in all five different groups. According to this study, it was estimated that HPV vaccines could have a great impact on prevention of cervical cancer in Iran. In conclusion, this meta-analysis highlights the necessity of introducing vaccination program in Iran.

  18. 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

  19. 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

  20. HPV Integration in Head and Neck Squamous Cell Carcinomas: Cause and Consequence.

    PubMed

    Speel, Ernst Jan M

    Human papillomaviruses (HPVs) are a necessary cause of anogenital squamous cell carcinomas (SCC) and a subgroup of head and neck SCC, i.e., those originating in the oropharynx. The key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells, local immune suppression and the accumulation of chromosomal alterations. Evidence for these events particularly comes from studies of uterine cervical carcinogenesis; primary premalignant HRHPV-positive lesions of the head and neck mucosa are seldomly detected. Integration of virus DNA into host chromosomes is considered an important driver of carcinogenesis and observed in 40 up to 90 % of uterine cervical SCC (UCSCC) and oropharyngeal SCC (OPSCC), dependent on the integration detection method used and HRHPV type. In OPSCC, > 90 % HPV-positive tumors are infected with HPV16. Ten up to 60 % of HPV-positive tumors thus contain extrachromosomal (episomal) virus. In this chapter, causes and consequences of HPV integration are summarized from the literature, with special focus on the site of HPV integration in the cellular genome, and its effect on expression of viral oncogenes (particularly E6 and E7), on human (tumor) gene expression and on deregulation of cell proliferation, apoptosis and cell signaling pathways. Also data on DNA methylation, viral load and clinical outcome in relation to HPV integration are provided.

  1. 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.

  2. 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.

  3. Spectral Cytopathology of Cervical Samples: Detecting Cellular Abnormalities in Cytologically Normal Cells

    PubMed Central

    Schubert, Jennifer M.; Bird, Benjamin; Papamarkakis, Kostas; Miljković, Miloš; Bedrossian, Kristi; Laver, Nora; Diem, Max

    2010-01-01

    Aim Spectral Cytopathology (SCP) is a novel spectroscopic method for objective and unsupervised classification of individual exfoliated cells. The limitations of conventional cytopathology are well-recognized within the pathology community. In SCP, cellular differentiation is made by observing molecular changes in the nucleus and the cytoplasm, which may or may not produce morphological changes detectable by conventional cytopathology. This proof of concept study demonstrates SCP’s potential as an enhancing tool for cytopathologists by aiding in the accurate and reproducible diagnosis of cells in all states of disease. Method Infrared spectra are collected from cervical cells deposited onto reflectively coated glass slides. Each cell has a corresponding infrared spectrum that describes its unique biochemical composition. Spectral data are processed and analyzed by an unsupervised chemometric algorithm, Principal Component Analysis (PCA). Results In this blind study, cervical samples are classified by analyzing the spectra of morphologically normal looking squamous cells from normal samples and samples diagnosed by conventional cytopathology with low grade squamous intraepithelial lesions (LSIL). SCP discriminated cytopathological diagnoses amongst twelve different cervical samples with a high degree of specificity and sensitivity. SCP also correlated two samples with abnormal spectral changes: these samples had a normal cytopathological diagnosis but had a history of abnormal cervical cytology. The spectral changes observed in the morphologically normal looking cells are most likely due to an infection with human papillomavirus, HPV. HPV DNA testing was conducted on five additional samples, and SCP accurately differentiated these samples by their HPV status. Conclusions SCP tracks biochemical variations in cells that are consistent with the onset of disease. HPV has been implicated as the cause of these changes detected spectroscopically. SCP does not depend on

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. Girdin expression in cervical carcinoma and its role in the malignant properties of HeLa cells.

    PubMed

    Jiang, Ping; Ren, Ya-Li; Li, Jia-Liang; Luo, Jun

    2016-04-01

    Cervical cancer is a major cause of mortality in females worldwide, with the majority of cases reported in developing countries. The molecular mechanisms of this disease are unclear. However, increasing evidence indicates that the expression or overexpression of Girdin is associated with a poor prognosis in a variety of cancer types. Therefore, the aim of the current study was to evaluate the potential association between Girdin expression, and malignant properties of cervical cancer lesions and HeLa cells. Girdin protein expression was examined in 87 samples of cervical squamous cell lesions, including intraepithelial neoplasia (grades I and III) and invasive carcinoma, using immunohistochemical (IHC) staining. A short-hairpin RNA (shRNA) approach was employed to specifically suppress the expression of Girdin mRNA in HeLa cells in vitro, allowing the role of Girdin in a number of malignant properties to be evaluated. Girdin protein was observed in the cytoplasm of 79/87 (90.8%) cervical cancer lesion specimens. However, no positive Girdin signals were identified in healthy cervical squamous epithelium samples. Furthermore, a significant correlation between Girdin expression and lesion grade was identified (Spearman's correlation coefficient, 0.566; P<0.001). When Girdin was suppressed by Girdin shRNA, the rate of HeLa cell growth was significantly reduced in vitro (P<0.05). Additional analysis determined that Girdin was associated with serum-deprived induced HeLa apoptosis. Thus, patients with high-grade cervical cancer tumors exhibited a strong expression for Girdin, and Girdin appears to key in HeLa cell proliferation and serum-deprived induced apoptosis, supporting the hypothesis that Girdin may be important in the process of cervical carcinogenesis.

  2. FOXL2 suppresses proliferation, invasion and promotes apoptosis of cervical cancer cells

    PubMed Central

    Liu, Xing-Long; Meng, Yu-Han; Wang, Jian-Li; Yang, Biao-Bing; Zhang, Fan; Tang, Sheng-Jian

    2014-01-01

    FOXL2 is a transcription factor that is essential for ovarian function and maintenance, the germline mutations of which give rise to the blepharophimosis ptosis epicanthus inversus syndrome (BPES), often associated with premature ovarian failure. Recently, its mutations have been found in ovarian granulosa cell tumors (OGCTs). In this study, we measured the expression of FOXL2 in cervical cancer by immunohistochemistry and its mRNA level in cervical cancer cell lines Hela and Siha by RT-PCR. Then we overexpressed FOXL2 in Hela cells and silenced it in Siha cells by plasmid transfection and verified using western blotting. When FOXL2 was overexpressed or silenced, cells proliferation and apoptosis were determined by Brdu assay and Annexin V/PI detection kit, respectively. In addition, we investigated the effects of FOXL2 on the adhesion and invasion of Hela and Siha cells. Finally, we analyzed the influences of FOXL2 on Ki67, PCNA and FasL by flow cytometry. The results showed that FOXL2 was highly expressed in cervical squamous cancer. Overexpressing FOXL2 suppressed Hela proliferation and facilitated its apoptosis. Silencing FOXL2 enhanced Siha proliferation and inhibited its apoptosis. Meanwhile, silencing FOXL2 promoted Siha invasion, but it had no effect on cells adhesion. In addition, overexpressing FOXL2 decreased the expression of Ki67 in Hela and Siha cells. Therefore, our results suggested that FOXL2 restrained cells proliferation and enhanced cells apoptosis mainly through decreasing Ki67 expression. PMID:24817949

  3. 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.

  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. Serum squamous cell carcinoma antigen in the monitoring of radiotherapy treatment response in carcinoma of the cervix

    SciTech Connect

    Ngan, H.Y.; Chan, S.Y.; Wong, L.C.; Choy, D.T.; Ma, H.K. )

    1990-05-01

    In this study, squamous cell carcinoma antigen (SCC) was detected in 96 of 157 patients with squamous cell carcinoma of the cervix and the percentage of patients with raised SCC levels increased with the stage of disease (P less than 0.01). The use of serial SCC assays and cervical biopsy histology during the course of radiotherapy to predict tumor response to irradiation was assessed. In patients who were given external irradiation before intracavitary radium, a high SCC level or the presence of viable tumor cells in the biopsy was found to be of no predictive value. However, at completion of radiotherapy, i.e., after intracavitary radium application, patients with persistently high SCC levels had a significantly higher incidence of residual tumor than patients whose SCC levels returned to normal (P less than 0.01). In 60% of patients with a persistently high SCC level, viable tumor was found in the cervical biopsy at the end of radiotherapy. On the other hand, only 5.4% of patients whose SCC level returned to normal had residual tumor.

  6. 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.

  7. 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.

  8. Expression of ezrin and moesin related to invasion, metastasis and prognosis of laryngeal squamous cell carcinoma.

    PubMed

    Wang, X; Liu, M; Zhao, C Y

    2014-09-29

    We examined the expression of ezrin and moesin in laryngeal squamous cell carcinoma (LSCC) and their correlation with patient clinicopathological characteristics and overall survival. Immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) for ezrin and moesin were applied to 60 carcinoma tissues, adjacent normal tissues, and 33 metastatic lymph nodes. Survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test. RT-PCR demonstrated that the intensity ratios of ezrin and moesin to β-actin were higher in LSCC than in adjacent normal mucous membrane (P < 0.05). Furthermore, intensity ratios were higher in cervical metastatic lymph nodes than in LSCC (P < 0.05). Immunohistochemical staining showed that ezrin and moesin were well distributed in the cell membrane and cytoplasm. Expression was significantly different between LSCC and adjacent normal tissues (P < 0.05); moreover, expression in the cervical metastatic lymph nodes was higher than in LSCC (P < 0.05). Expression of ezrin and moesin was significantly related to clinical stage, T stage, and cervical lymph node metastasis (P < 0.05), except that moesin showed no significant relationship with clinical stage (P > 0.05). Patients with negative ezrin and moesin expression had a significantly longer overall survival time compared to patients with moderate and intense ezrin and moesin expression (P < 0.001, P < 0.05). Ezrin and moesin expression is related to LSCC invasion and metastasis, and may be important molecular markers for predicting prognosis and therapeutic targets in LSCC patients.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Diagnostic Approach to Patients with Atypical Squamous Cells of Undetermined Significance Cytologic Findings on Cervix

    PubMed Central

    Jahic, Mahira; Jahic, Elmir

    2016-01-01

    Background: Atypical squamous cells of undetermined significance (ASCUS) is a term that refers to inflammatory, reactive and reparative processes which are atypical and of higher level and insufficient to be classified as cervical intraepithelial lesions (CIN). Aims: Examine of frequency of HPV infection in ASCUS lesions and regression, stagnation and progression during six-month period. Subjects and Methods: Prospective study was conducted over a period of 3 years. In private gynecological ambulance „Dr Mahira Jahic”. Analysis of PAP smears and HPV typization have been done in 50 patients and PAP test has been repeated after six months. X² test was used for statistical analysis. Results: Analysis of 1784 PAP smears showed normal results in 86,6% (N-1530), and abnormal in 13% (N-254). ASCUS in 7,4% (N-133) and ASC-H in 0,5% (N-9), LSIL in 4,4% (N-80), HSIL in 1,3% (N-24), CIN II in 1,2% (N-20), CIN III in 0,2% (N-4). Progression occurred in 18% (9), persistence in 74% (37) and regression in 8%. Patients with ASC-H lesion 0,5% (N-9), PH results showed 22% (N-2) Carcinoma in situ, 33% (N-3) CIN II, 22% (N-2) CIN I and 22% (N-2) chronic cervicitis. Patients with CIN I in 88% (N-7) were positive on HPV of high risk. Patients with persistent ASCUS result were positive in 51% (N-19). The number of CIN I lesions found in women with ASCUS is bigger and statistically significant (p<0,05) in relation to number of CIN I findings found in regular examinations. Conclusion: Monitoring women with ASCUS lesion, especially HPV positive to high risk group is the best way of selection of women who should be treated and monitored in order to prevent cervical cancer. PMID:27703293

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. AEG-1 activates Wnt/PCP signaling to promote metastasis in tongue squamous cell carcinoma.

    PubMed

    Pan, Yunping; Guo, Xu; Yang, Zheng; Chen, Shan; Lei, Yiyan; Lin, Millicent; Wang, Liantang; Feng, Chongjin; Ke, Zunfu

    2016-01-12

    Despite advances in therapy, survival among patients with locally advanced squamous cell carcinoma of tongue (TSCC) and cervical lymph node metastasis remains dismal. Here, we estimated the functional effect of AEG-1 on TSCC metastasis and explored the molecular mechanism by which AEG-1 stimulates epithelial-mesenchymal transition (EMT). We initially found that AEG-1 mRNA levels were much higher in metastatic TSCC than in non-metastatic TSCC and that AEG-1 expression strongly correlates with EMT status. Receiver operating characteristic analysis showed that the combined AEG-1 and EMT statuses are predictive of the survival rate among TSCC patients. In addition, AEG-1 knockdown inhibited EMT in cultured TSCC cell lines and in a xenograft-mouse model. Recombinant AEG-1 activated Wnt/PCP-Rho signaling, and its stimulatory effects on TSCC cell invasiveness and EMT were reversed by an anti-Wnt5a neutralizing antibody or by inhibition of Rac1 or ROCK. These results highlight the critical stimulatory effect of AEG-1 on cancer cell invasiveness and EMT and indicate that AEG-1 may be a useful prognostic biomarker for TSCC patients.

  12. Twist1 Enhances Hypoxia Induced Radioresistance in Cervical Cancer Cells by Promoting Nuclear EGFR Localization

    PubMed Central

    Xiong, Hua; Nie, Xin; Zou, Yanmei; Gong, Chen; Li, Yang; Wu, Hua; Qiu, Hong; Yang, Lin; Zhuang, Liang; Zhang, Peng; Zhang, Jing; Wang, Yihua; Xiong, Huihua

    2017-01-01

    Twist1 is a crucial transcription factor that regulates epithelial mesenchymal transition and involves in metastasis. Recent evidence suggests that Twist1 plays important role in hypoxia-induced radioresistance, but the underlying mechanism remains elusive. Here we investigated the change of Twist1 expression in human cervical squamous cancer cell line SiHa after hypoxia treatment. We also explored the role of Twist1 in radioresistance by manipulating the expression level of Twist1. We observed that hypoxia treatment elevated the expression of Twist1 in SiHa cells. Knockdown of Twist1 with siRNA increased the radiosensitivity of SiHa cells under hypoxia condition, accompanied by reduced levels of nuclear Epidermal Growth Factor Receptor (EGFR) and DNA-dependent protein kinase (DNA-PK). Conversely, overexpression of Twist1 led to increased radioresistance of SiHa cells, which in turn increased nuclear EGFR localization and expression levels of nuclear DNA-PK. Moreover, concomitant high expression of hypoxia-inducible factor-1α (HIF-1α) and Twist1 in primary tumors of cervical cancer patients correlated with the worse prognosis after irradiation treatment. Taken together, these data provide new insights into molecular mechanism underlying hypoxia-induced radioresistance in cervical cancer cells, and suggest that Twist1 is a promising molecular target to improve the efficacy of cancer radiotherapy. PMID:28261334

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Effect of Thin Prep® imaging system on laboratory rate and relative sensitivity of atypical squamous cells, high-grade squamous intraepithelial lesion not excluded and high-grade squamous intraepithelial lesion interpretations

    PubMed Central

    Koltz, Brooke R.; Russell, Donna K.; Lu, Naiji; Bonfiglio, Thomas A.; Varghese, Sharlin

    2013-01-01

    Introduction: Automated screening of Thin Prep® Papanicolaou Tests has become increasingly common in clinical practice. Increased productivity has initiated laboratory use of the Thin Prep® Imaging System (TIS). Increased sensitivity is a potential additional benefit of TIS. Published studies have shown an increase in discovery of dysplastic cells. This study evaluates the effect of TIS on the incidence of atypical squamous cells high-grade squamous intraepithelial lesion not excluded (ASC-H) and high-grade squamous intraepithelial lesion (HGSIL) results on Thin Prep® Pap Tests by comparing TIS-assisted and manual screening findings and the diagnoses on subsequent follow-up in a screening population over a 1-year time period. Materials and Methods: A compilation of all ASC-H and HGSIL cases was prepared by conducting a computerized search over a 1-year period (7/06-6/07). The accumulated cases include Thin Prep Pap tests that were both TIS and manually screened. Follow-up results of cytologic and histologic cervical specimens were obtained for a time period extending to 2010. Interpretation utilizing TIS was in place 10 months prior to the study's initiation. Results: During the study period 70,522 Pap tests were performed in our laboratory. One third (33%) of Pap tests were screened with assistance of TIS. Manual screening was performed on 47,380 Pap tests of which 153 (0.32%) were interpreted as ASC-H and 164 (0.35%) were interpreted as HGSIL. During the same time period automated screening (TIS) was performed on 23,111 Pap tests. Interpretation of 62 (0.27%) cases provided an ASC-H result, while 71 (0.31%) were HGSIL. Follow-up cervical dysplasia by colposcopic biopsy and cone biopsy was distributed proportionally between TIS and manual screening for both ASC-H and HGSIL categories. Cervical intraepithelial neoplasia (CIN II/III) was identified on follow-up biopsy of 41% TIS cases and 45% manually screened cases for ASC-H. In the HGSIL subset 71% of TIS cases

  20. 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

  1. 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

  2. Evaluation of prognostic markers for patients with curatively resected thoracic esophageal squamous cell carcinomas

    PubMed Central

    Ikeguchi, Masahide; Kouno, Yusuke; Kihara, Kyoichi; Suzuki, Kazunori; Endo, Kanenori; Nakamura, Seiichi; Sawada, Takashi; Shimizu, Tetsu; Matsunaga, Tomoyuki; Fukumoto, Yoji; Saito, Hiroaki

    2016-01-01

    The Glasgow Prognostic Score (GPS), neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are prognostic parameters for malignancies. Additionally, serum squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA 21-1) are tumor markers for squamous cell carcinoma. In the present study, the prognostic importance of these markers in patients with resectable thoracic esophageal cancer was investigated. In this retrospective study, 84 enrolled patients diagnosed with resectable clinical stage I–III thoracic esophageal squamous cell carcinomas (ESCCs) underwent thoracic esophageal resection and three-field lymph node dissection at Tottori University Hospital between January 2007 and December 2013. The correlations among preoperative patient markers (GPS, NLR, PNI, SCC-Ag and CYFRA 21-1) and the occurrence of postoperative complications and patient survival were analyzed. The operative mortality was 2.4%, and morbidity was 42.9%. Strong correlations between occurrence of postoperative complications and open thoracotomy (P=0.083) and high-serum CYFRA 21-1 (P=0.007) were observed. In 15 patients with high-serum CYFRA 21-1, postoperative complications were detected in 11 of them (73.3%); on the other hand, complications occurred in 25 of 69 (36.2%) with low-serum CYFRA 21-1. The 5-year disease-free survival rate and 5-year overall survival rate of all the patients were 52.2 and 50.8%, respectively. Among the prognostic parameters, preoperative high NLR was determined to be a poor prognostic factor, independent of the tumor stage in the multivariate analysis. These results may indicate that, in patients with preoperative high-serum CYFRA 21-1, more attention should be paid to the occurrence of postoperative complications. Therefore, in such cases, anastomosis between blood vessels of the substitute esophagus and cervical vessels would be recommended. Furthermore, in patients with high preoperative NLR, effective adjuvant

  3. 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

  4. 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

  5. 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.

  6. Expression/localization patterns of sirtuins (SIRT1, SIRT2, and SIRT7) during progression of cervical cancer and effects of sirtuin inhibitors on growth of cervical cancer cells.

    PubMed

    Singh, Sapna; Kumar, P Uday; Thakur, Suresh; Kiran, Shashi; Sen, Bijoya; Sharma, Shreya; Rao, Vishnu Vardhan; Poongothai, A R; Ramakrishna, Gayatri

    2015-08-01

    Sirtuins belong to the family of class III histone deacetylases; its role in neoplasia is controversial as both tumor-suppressive and promoting functions have been reported. There are very few reports available, where expressions of sirtuin isoforms are comprehensively analyzed during neoplasia. Therefore, in the present study, the expression of SIRT1, SIRT2, and SIRT7 during different stages of cervical cancer progression was analyzed. The normal cervical epithelium showed feeble expression of sirtuin isoforms, SIRT1, SIRT2, and SIRT7. A significant increase in SIRT1 expression was noted in the cytoplasm as well as in the nucleus of proliferative layers of cervical epithelium in squamous intraepithelial lesions (SIL); however, in the squamous cell carcinomas (SCC), a heterogeneous pattern of SIRT1 expression varying from low to high was noted. A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal < preneoplasia < cancer. Cervical cancer cell lines, HeLa and SiHa, showed higher levels of SIRT1 and SIRT2 in comparison to the immortalized cell counterpart, HaCaT. Specific inhibitors of SIRT1 (Ex527) and SIRT2 (AGK2) impaired the growth of the cervical cancer cells, SiHa, but not of the HaCaT cells. SIRT1 inhibition caused cell death, while SIRT2 inhibition resulted in cell cycle arrest. In conclusion, we report the overexpression of SIRT2 and SIRT7 proteins in cervical cancer and suggest probable application of sirtuin inhibitors as therapeutic targets. Further, a specific increase in the levels of SIRT1 in intraepithelial lesion makes it a promising candidate for identification of preneoplastic changes.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Cervical Shedding of Human T Cell Lymphotropic Virus Type I Is Associated with Cervicitis

    PubMed Central

    Zunt, Joseph R.; Dezzutti, Charlene S.; Montano, Silvia M.; Thomas, Katherine K.; Alarcón, Jorge O. V.; Quijano, Eberth; Courtois, Barry N.; Sánchez, Jorge L.; Campos, Pablo; Gotuzzo, Eduardo; Guenthner, Patricia C.; Lal, Renu B.; Holmes, King K.

    2009-01-01

    Human T cell lymphotropic virus type I (HTLV-I) is sexually transmitted. The purpose of this study was to determine the prevalence and risk factors for cervical shedding of HTLV-I DNA among Peruvian sex workers. HTLV tax DNA was detected in cervical specimens from 43 (68%) of 63 HTLV-I–infected sex workers and in samples obtained during 113 (52%) of 216 clinic visits between 1993 and 1997. Detection of HTLV DNA was associated with the presence of ≥30 polymorphonuclear cells (PMNs) within cervical mucus per 100×microscopic field (odds ratio [OR], 4.3, 95% confidence interval [CI], 1.8–10.1) and with the presence of cervical secretions (OR, 2.0; 95% CI 1.2–3.4). Hormonal contraceptive use (OR 1.7; 95% CI, 0.8–3.6) and concomitant cervical infection by Chlamydia trachomatis (OR, 1.5; 95% CI, 0.3–4.3) or Neisseria gonorrhoeae (OR, 1.1; 95% CI, 0.6–3.7) were not significantly associated with HTLV-I shedding. Our results suggest that cervicitis may increase cervical HTLV-I shedding and the sexual transmission of this virus. PMID:12447745

  12. Cervical shedding of human T cell lymphotropic virus type I is associated with cervicitis.

    PubMed

    Zunt, Joseph R; Dezzutti, Charlene S; Montano, Silvia M; Thomas, Katherine K; Alarcón, Jorge O V; Quijano, Eberth; Courtois, Barry N; Sánchez, Jorge L; Campos, Pablo; Gotuzzo, Eduardo; Guenthner, Patricia C; Lal, Renu B; Holmes, King K

    2002-12-01

    Human T cell lymphotropic virus type I (HTLV-I) is sexually transmitted. The purpose of this study was to determine the prevalence and risk factors for cervical shedding of HTLV-I DNA among Peruvian sex workers. HTLV tax DNA was detected in cervical specimens from 43 (68%) of 63 HTLV-I-infected sex workers and in samples obtained during 113 (52%) of 216 clinic visits between 1993 and 1997. Detection of HTLV DNA was associated with the presence of > or =30 polymorphonuclear cells (PMNs) within cervical mucus per 100x microscopic field (odds ratio [OR], 4.3, 95% confidence interval [CI], 1.8-10.1) and with the presence of cervical secretions (OR, 2.0; 95% CI 1.2-3.4). Hormonal contraceptive use (OR 1.7; 95% CI, 0.8-3.6) and concomitant cervical infection by Chlamydia trachomatis (OR, 1.5; 95% CI, 0.3-4.3) or Neisseria gonorrhoeae (OR, 1.1; 95% CI, 0.6-3.7) were not significantly associated with HTLV-I shedding. Our results suggest that cervicitis may increase cervical HTLV-I shedding and the sexual transmission of this virus.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. Cigarette smoking and invasive cervical cancer

    SciTech Connect

    Brinton, L.A.; Schairer, C.; Haenszel, W.; Stolley, P.; Lehman, H.F.; Levine, R.; Savitz, D.A.

    1986-06-20

    A case-control study of 480 patients with invasive cervical cancer and 797 population controls, conducted in five geographic areas in the United States, included an evaluation of the relationship of several cigarette smoking variables to cervical cancer risk. Although smoking was correlated with both age at first intercourse and number of sexual partners, a significant smoking-related risk persisted for squamous cell carcinoma after adjustment for these factors (relative risk, 1.5). Twofold excess risks were seen for those smoking 40 or more cigarettes per day and those smoking for 40 or more years. Increased risks, however, were observed only among recent and continuous smokers. In contrast to squamous cell cancer, no relationship was observed between smoking and risk of adenocarcinoma or adenosquamous carcinoma. These results suggest a causal relationship between cigarette smoking and invasive squamous cell cervical cancer, perhaps through a late-stage or promotional event, although the mechanisms of action require further elucidation.

  5. 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.

  6. 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

  7. Prevalence of human papillomaviruses in patients with head and neck squamous cell carcinoma in Lithuania and Belarus.

    PubMed

    Gudleviciene, Zivile; Didziapetriene, Janina; Mackeviciene, Irina; Cicenas, Saulius; Smolyakova, Raisa; Zhukavetc, Aliaksandr; Zivile, Gudleviciene; Janina, Didziapetriene; Irina, Mackeviciene; Saulius, Cicenas; Raisa, Smolyakova; Aliaksandr, Zhukavetc

    2014-03-01

    Overall, head and neck sqamous cell carcinoma accounts for more than 550,000 cases annually worldwide. It is well known that human papillomavirus (HPV) is the main risk factor for cervical cancer development. As the incidence and the mortality of cervical cancer are closely related to the HPV prevalence, we hypothesized that there is the same association between HPV prevalence and head and neck squamous cell carcinoma. Therefore we performed the study aiming to compare the level of HPV infection and HPV type distribution between two groups of Lithuanian and Belarusian patients with head and neck sqamous cell carcinoma. One hundred ninety head and neck sqamous cell carcinoma patients were included in the study, 75 from Lithuania and 115 from Belarus. PCR was used for HPV detection and typing. The distribution of HPV infection among head and neck sqamous cell carcinoma patients was similar in the Lithuanian (20.0%) and Belarusian (18.3%) patient groups, however differences were found in the distribution of HPV types.

  8. Elastic scattering spectroscopy findings in formalin-fixed oral squamous cell carcinoma specimens

    NASA Astrophysics Data System (ADS)

    Swinson, B.; Elmaaytah, M.; Jerjes, W.; Hopper, C.

    2005-11-01

    Oral squamous cell carcinoma (OSCC) has been shown to spread locally and infiltrate adjacent bone or via the lymphatic system to the cervical lymph nodes. This usually necessitates a surgical neck dissection and either a local or segmental resection for bone clearance. While histopathology remains the gold standard for tissue diagnosis, several new diagnostic techniques are being developed that rely on physical and biochemical changes that mirror or precede malignant changes within tissue. The aim of this study was to compare findings of Elastic Scattering Spectroscopy (ESS) with histopathology on formalin-fixed specimens of both neck lymph node dissections and de-calcified archival bone from patients with OSCC. We wished to see if this technique could be used as an adjunct or alternative to histopathology in defining cervical nodal involvement and if it could be used to identify bone resection margins positive for tumour. 130 lymph nodes were examined from 13 patients. The nodes were formalin-fixed, bivalved and examined by ESS. The intensity of the spectrum at 4 points was considered for comparison; at 360nm, 450nm, 630nm and 690nm. 341 spectra were taken from the mandibular specimens of 21 patients, of which 231 spectra were taken from histologically positive sites and the rest were normal. The nodes and bone specimens were then routinely processed with haematoxylin and eosin-stained sections, examined histopathologically, and the results compared. Using Linear Discriminant Analysis (LDA) as a statistical method, a sensitivity of 98% and a specificity of 68% was obtained for the neck nodes and a sensitivity of 87% and a specificity of 80% for the bone margins.

  9. Testosterone-induced "Virilization" of Mesonephric Duct Remnants and Cervical Squamous Epithelium in Female-to-Male Transgenders: A Report of 3 Cases.

    PubMed

    Singh, Kamaljeet; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

    2016-08-26

    Mesonephric ducts regress in genotypic females, leaving behind few remnants. These vestigial structures are often recognized in the mesosalpinx and paracervical regions. We report here 3 cases of female-to-male transgenders who underwent hysterectomy following testosterone treatment. Both female and male genital structures were identified on histologic examination. Although the morphologic appearances of the specimens were unremarkable, histologically 1 case revealed a well-formed fallopian tube as well as an epididymis and 2 cases showed prostate glands to be present in the cervical squamous epithelium.

  10. 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.

  11. Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions

    PubMed Central

    Sellors, John W.; Lorincz, Attila T.; Mahony, James B.; Mielzynska, Iwona; Lytwyn, Alice; Roth, Paula; Howard, Michelle; Chong, Sylvia; Daya, Dean; Chapman, William; Chernesky, Max

    2000-01-01

    Background Certain types of human papillomavirus (HPV) in cervical samples are strongly associated with squamous intraepithelial lesions (SIL) and invasive cervical carcinoma. We determined and compared the test characteristics of testing for HPV with samples obtained by patients and with samples obtained by their physicians. Methods In a consecutive series of women referred to a colposcopy clinic at a teaching hospital because of abnormalities on cervical cytologic screening, 200 agreed to collect vulvar, vaginal and urine samples for HPV testing. The physician then collected cervical samples for HPV testing, and colposcopy, with biopsy as indicated, was performed. Presence of HPV was evaluated using the hybrid capture II assay (Digene Corp., Silver Spring, Md.) with a probe cocktail for 13 carcinogenic types. Cervical specimens were also tested for HPV by polymerase chain reaction and hybridization with type-specific probes. Cervical smears for cytologic examination were obtained from all women. Results High-grade lesions (high-grade squamous intraepithelial lesions [HSIL], equivalent to cervical intraepithelial neoplasia [CIN] grade 2 or 3, and adenocarcinoma) were found in 58 (29.0%) of the 200 women. Carcinogenic types of HPV were detected in the self-collected vaginal samples of 50 (86.2%) of these 58 women, in the self-collected vulvar samples of 36 (62.1%) and in the self-collected urine samples of 26 (44.8%). Carcinogenic types of HPV were detected in the cervical samples collected by physicians for 57 (98.3%) of these 58 women. The remaining 142 women (71.0%) had normal findings or low-grade squamous intraepithelial lesions (LSIL, CIN grade 1). Test results were negative or noncarcinogenic types of HPV were detected in the self-collected vaginal samples of 76 (53.5%) of these 142 women, in the self-collected vulvar samples of 89 (62.7%) and in the self-collected urine samples of 99 (69.7%). The sensitivity for self-collected samples ranged from 44.8% to

  12. Immunohistochemical Expression of VEGF and Podoplanin in Uterine Cervical Squamous Intraepithelial Lesions

    PubMed Central

    Belfort-Mattos, Patrícia Napoli; Focchi, Gustavo Rubino de Azevedo; Ribalta, Julisa Chamorro Lascasas; Megale De Lima, Tatiana; Nogueira Carvalho, Carmen Regina; Kesselring Tso, Fernanda; De Góis Speck, Neila Maria

    2016-01-01

    VEGF and podoplanin (PDPN) have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone) and podoplanin (D2-40 clone). Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (P < 0.001). Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (P = 0.016). We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (P = 0.018). Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression. PMID:27313335

  13. 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

  14. 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

  15. 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

  16. Surgical management of squamous cell vulvar cancer without clitoris, urethra or anus involvement.

    PubMed

    Kaban, Alpaslan; Kaban, Işık; Afşar, Selim

    2017-05-01

    Vulvar cancers, which constitute 5% of all gynecologic cancers, are the fourth most common female genital cancers, preceded by uterine, ovarian and cervical cancers. The treatment methods employed for vulvar cancers have changed over the years, with previously applied radical surgical approaches, such as en bloc resection, being gradually suspended in favor of treatment approaches that require dissection of less tissue. While the removal of less tissue, which today's approaches have focused on, prevents morbidity, this method seems to result in higher risks of recurrence. It is therefore important that the balance between preventing the recurrence of the disease and forefending against postoperative complications and vulvar deformity be properly understood. As a working assumption, if patients with vulvar cancer are diagnosed at an early stage, properly evaluated and administered appropriate treatment, the most positive results can be obtained. This paper aims to highlight this assumption and demonstrate, through the provision of actual data, how to plan the treatment approach for patients who are diagnosed early. Statements extracted from the National Comprehensive Cancer Network (NCCN) Guidelines Version 1.2016 Sub-Committees on vulvar squamous cell carcinoma and articles by the European Society of Gynaecological Oncology (ESGO) regarding Vulvar Cancer Recommendations were used to obtain updated information.

  17. 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

  18. LAMP3 and TP53 overexpression predicts poor outcome in laryngeal squamous cell carcinoma.

    PubMed

    Qiu, Xiaoxia; You, Yiwen; Huang, Jianfei; Wang, Xudong; Zhu, Huijun; Wang, Zhiwei

    2015-01-01

    Lysosomal associated membrane protein 3 (LAMP3) is a newly identified tumor-specific and hypoxia-induced protein. It is a downstream target gene of tumor suppressor TP53 and its expression has been associated with hypoxia-induced metastasis and poor overall survival in cervical, breast and gastrointestinal cancers. However, little is known of LAMP3 protein expression in laryngeal squamous cell carcinoma (LSCC) and its prognostic value. We determined protein expression of LAMP3 and TP53 in LSCC tissues (n=117) by immunohistochemistry analysis on tissue microarray (TMA), their expression was correlated with patients' clinical parameters and overall survival. LAMP3 and TP53 protein expression was significantly higher in cancerous tissues compared to adjacent normal surgical margin tissues. Both high LAMP3 and high TP53 protein expression was significantly associated with tumor stage and size. Significant correlation between LAMP3 and TP53 expression was observed. Patients with high LAMP3 or high TP53 expression had a poor overall survival. Our data suggest that both epithelial LAMP3 expression and TP53 expression are independent prognostic markers for LSCC.

  19. 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

  20. 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.

  1. 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.

  2. [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.

  3. 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.

  4. 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

  5. Univariate and multivariate methods for chemical mapping of cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei

    2012-01-01

    Visualization of cells and subcellular organelles are currently carried out using available microscopy methods such as cryoelectron microscopy, and fluorescence microscopy. These methods require external labeling using fluorescent dyes and extensive sample preparations to access the subcellular structures. However, Raman micro-spectroscopy provides a non-invasive, label-free method for imaging the cells with chemical specificity at sub-micrometer spatial resolutions. The scope of this paper is to image the biochemical/molecular distributions in cells associated with cancerous changes. Raman map data sets were acquired from the human cervical carcinoma cell lines (HeLa) after fixation under 785 nm excitation wavelength. The individual spectrum was recorded by raster-scanning the laser beam over the sample with 1μm step size and 10s exposure time. Images revealing nucleic acids, lipids and proteins (phenylalanine, amide I) were reconstructed using univariate methods. In near future, the small pixel to pixel variations will also be imaged using different multivariate methods (PCA, clustering (HCA, K-means, FCM)) to determine the main cellular constitutions. The hyper-spectral image of cell was reconstructed utilizing the spectral contrast at different pixels of the cell (due to the variation in the biochemical distribution) without using fluorescent dyes. Normal cervical squamous cells will also be imaged in order to differentiate normal and cancer cells of cervix using the biochemical changes in different grades of cancer. Based on the information obtained from the pseudo-color maps, constructed from the hyper-spectral cubes, the primary cellular constituents of normal and cervical cancer cells were identified.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. Absence of the sternocleidomastoid muscle in a patient that underwent neck dissection for squamous cell carcinoma of the tongue.

    PubMed

    Takahashi, Hidenori; Umeda, Masahiro; Sakakibara, Akiko; Shigeta, Takashi; Minamikawa, Tsutomu; Shibuya, Yasuyuki; Komori, Takahide

    2014-05-20

    The congenital absence of a skeletal muscle is a rare cause of congenital muscular torticollis, and the condition is associated with various unusual anatomical structures. We describe a rare case of congenital absence of the sternocleidomastoid muscle associated with squamous cell carcinoma of the tongue in a patient who underwent neck dissection. In this case, both the external jugular vein and the spinal accessory nerve were absent. However, we found that branches of the C3 nerve extended from the cervical plexus to the trapezius muscle and seemed to be acting as trapezius muscle motor nerves in place of the accessory nerve. After the operation, the patient was able to lift and abduct his right arm, and his shoulder did not droop.

  12. Pediatric Upper Cervical Spine Giant Cell Tumor: Case Report

    PubMed Central

    Alfawareh, Mohammad D.; Shah, Irfanullah D.; Orief, Tamer I.; Halawani, Mohammad M.; Attia, Walid I.; Almusrea, Khaled N.

    2014-01-01

    Study Design Case report. Objective The purpose of this work is to report the case of a giant cell tumor involving the second cervical vertebra in a pediatric patient. Surgical management included a combined posterior and anterior cervical approach. There has been no recurrence in 2 years of follow-up. Case Report A 13-year-old girl presented with scoliosis with incidentally lytic lesion involving the second cervical vertebra. The radiologic investigations and biopsy result indicated a giant cell tumor of the bone. A combined posterior and anterior cervical approach was performed to resect the lesion, reconstruct the spine, and restore stability. Two years of follow-up revealed no recurrence of the lesion with stable reconstruction of the spine. Results The lesion was surgically managed for excision and spinal fusion by combining a posterior occipitocervical arthrodesis with an anterior retropharyngeal cervical approach. The final histopathology result confirmed a giant cell tumor of the bone. Conclusions Giant cell tumor involving the second cervical vertebra is uncommon; this tumor can be managed surgically by using a combined posterior and anterior cervical retropharyngeal approach. The presented case was unique in terms of the tumor location, patient age, and surgical management. PMID:26225290

  13. 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.

  14. Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

    SciTech Connect

    Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank; Graeff, Pauline de; Pras, Elisabeth; Schuuring, Ed; Wisman, G. Bea A.; Bock, Geertruida H. de; Zee, Ate G.J. van der

    2011-02-01

    The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in {>=}50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1{alpha}). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.

  15. Associations of P16INK4a promoter hypermethylation with squamous intra-epithelial lesion, cervical cancer and their clinicopathological features: a meta-analysis

    PubMed Central

    Cui, Ning-hua; Zhang, Shuai; Wang, Chen; Zheng, Fang

    2017-01-01

    To assess the associations of P16INK4a methylation status with low-grade squamous intra-epithelial lesion (LSIL), high-grade squamous intra-epithelial lesion (HSIL), cervical cancer (CC) and their clinicopathological features, a meta-analysis with 29 eligible studies was conducted. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to assess the strength of the associations. Heterogeneity, sensitivity of pooled results and publication bias were also evaluated. Overall, there was an increasing trend of P16INK4a hypermethylation rates among LSIL (21.4%), HSIL (30.9%) and CC (35.0%) specimens. P16INK4a hypermethylation was significantly associated with the increased risk of LSIL, HSIL and CC, with the pooled ORs of 3.26 (95% CI: 1.86-5.71), 5.80 (95% CI: 3.80-8.84) and 12.17 (95% CI: 5.86-25.27), respectively. A significant association was also found between P16INK4a hypermethylation and smoking habit (OR = 3.88, 95% CI: 2.13-7.08). Taken together, meta-analysis results support P16INK4a hypermethylation as an epigenetic marker for the progression of cervical carcinogenesis. PMID:27669738

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. [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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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%).

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression.

    PubMed

    Canel, M; Secades, P; Garzón-Arango, M; Allonca, E; Suarez, C; Serrels, A; Frame, Mc; Brunton, V; Chiara, M-D

    2008-04-08

    Focal adhesion kinase (FAK) is considered intimately involved in cancer progression. Our previous research has demonstrated that overexpression of FAK is an early and frequent event in squamous cell carcinomas of the supraglottic larynx, and it is associated with the presence of metastases in cervical lymph nodes. The purpose of this study was to examine the functional role of FAK in the progression of head and neck squamous cell carcinomas (HNSCC). To this end, expression of FAK-related nonkinase (FRNK) or small interfering RNA (siRNA) against FAK was used to disrupt the FAK-induced signal transduction pathways in the HNSCC-derived SCC40 and SCC38 cell lines. Similar phenotypic effects were observed with the two methodological approaches in both cell lines. Decreased cell attachment, motility and invasion were induced by FRNK and FAK siRNA, whereas cell proliferation was not impaired. In addition, increased cell invasion was observed upon FAK overexpression in SCC cells. FRNK expression resulted in a downregulation of MMP-2 and MMP-9 expression. Interestingly, MMP-2 overexpression in FRNK-expressing cells rescued FRNK inhibition of cell invasion. This is the first demonstration of a direct rescue of impaired cell invasion by the re-expression of MMP-2 in a tumour cell type with decreased expression of functional FAK. Collectively, these data reported here support the conclusion that FAK enhances invasion of HNSCC by promoting both increased cell motility and MMP-2 production, thus providing new insights into possible therapeutic intervention strategies.

  2. Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression

    PubMed Central

    Canel, M; Secades, P; Garzón-Arango, M; Allonca, E; Suarez, C; Serrels, A; Frame, M C; Brunton, V; Chiara, M-D

    2008-01-01

    Focal adhesion kinase (FAK) is considered intimately involved in cancer progression. Our previous research has demonstrated that overexpression of FAK is an early and frequent event in squamous cell carcinomas of the supraglottic larynx, and it is associated with the presence of metastases in cervical lymph nodes. The purpose of this study was to examine the functional role of FAK in the progression of head and neck squamous cell carcinomas (HNSCC). To this end, expression of FAK-related nonkinase (FRNK) or small interfering RNA (siRNA) against FAK was used to disrupt the FAK-induced signal transduction pathways in the HNSCC-derived SCC40 and SCC38 cell lines. Similar phenotypic effects were observed with the two methodological approaches in both cell lines. Decreased cell attachment, motility and invasion were induced by FRNK and FAK siRNA, whereas cell proliferation was not impaired. In addition, increased cell invasion was observed upon FAK overexpression in SCC cells. FRNK expression resulted in a downregulation of MMP-2 and MMP-9 expression. Interestingly, MMP-2 overexpression in FRNK-expressing cells rescued FRNK inhibition of cell invasion. This is the first demonstration of a direct rescue of impaired cell invasion by the re-expression of MMP-2 in a tumour cell type with decreased expression of functional FAK. Collectively, these data reported here support the conclusion that FAK enhances invasion of HNSCC by promoting both increased cell motility and MMP-2 production, thus providing new insights into possible therapeutic intervention strategies. PMID:18349846

  3. 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

  4. Routine Treatment of Cervical Cytological Cell Changes

    PubMed Central

    Huber, J.; Pötsch, B.; Gantschacher, M.; Templ, M.

    2016-01-01

    Introduction: Diagnosis and treatment of vaginal and cervical cytological cell changes are described in European and national guidelines. The aim of this data collection was to evaluate the remission rates of PAP III and PAP III D cytological findings in patients over a period of 3–4 months. Method: The current state of affairs in managing suspicious and cytological findings (PAP III, and III D) in gynecological practice was assessed in the context of a data collection survey. An evaluation over a period of 24 months was conducted on preventative measures, the occurrence and changes to normal/suspect/pathological findings and therapy management (for suspicious or pathological findings). Results: 307 female patients were included in the analysis. At the time of the survey 186 patients (60.6 %) had PAP III and 119 (38.8 %) had PAP III D findings. The spontaneous remission rate of untreated PAP III patients was 6 % and that of untreated PAP III D patients was 11 %. The remission rates of patients treated with a vaginal gel were 77 % for PAP III and 71 % for PAP III D. Conclusion: A new treatment option was used in gynecological practice on patients with PAP III and PAP III D findings between confirmation and the next follow-up with excellent success. PMID:27761030

  5. Primary squamous cell carcinoma of the thyroid. Initial assessment and follow-up using (18)F-FDG PET/CT.

    PubMed

    Caballero Gullón, L; Carmona González, E; Martínez Estévez, A; Gómez Camarero, M P; Corral, J J; Borrego Dorado, I

    2017-02-16

    Squamous cell carcinoma of thyroid is an uncommon, very aggressive neoplasm, having a poor prognosis and poor response to chemotherapy and radiotherapy. Surgery is the initial treatment of choice, although it often presents as a widespread disease at the time of diagnosis, usually with cervical swelling that causes most of the symptoms due to local infiltration or metastasis. Local infiltration from adjacent tumour and metastatic disease needs to be excluded from other primary epidermoid carcinomas, in order to make a correct diagnosis. This also requires the typical cytokeratin pattern seen in histological studies. The case is presented of a 53 year-old man with a medical history of hepatocarcinoma, with a cervical hypermetabolic lesion detected in an (18)F-FDG PET/CT performed to exclude widespread disease. The follow-up of this lesion with this technique and its usefulness is also described.

  6. 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

  7. Immunoexpression of HPV 16/18 E6 and E7 oncoproteins in high-grade cervical squamous intraepithelial lesions in HIV-positive women.

    PubMed

    Rodrigues, L C; Speck, N M de Gois; Focchi, G R de Azevedo; Schimidt, M A; Marques, R M; Ribalta, J C Lascasas

    2016-02-19

    The aim of this study was to assess the immunoexpression of human papillomavirus genotypes 16 and 18 (E6 and E7) oncoproteins in cervical high-grade squamous intraepithelial lesions (HSIL) of human immunodeficiency virus (HIV)-positive women. These results were also compared to the persistence and/or recurrence of lesions after loop electrosurgical excision procedure. Cervical samples from 158 patients were divided into three groups according to the presence or absence of HSIL in women who were or were not HIV-positive. By using the tissue microarray technique, immunohistochemistry was performed to analyze the expression of HPV 16/18 E6 and E7 oncoproteins. Cervical samples from 95 HIV-positive women and 63 HIV-negative women were studied. A statistically significant difference was found in the immunoexpression of E6 and E7 oncoproteins in samples from HIV-positive women with HSIL and that of women with non-neoplastic tissue (P < 0.001). There was also a statistically significant correlation between the immunoexpression of E6 (P = 0.012) and E7 (P < 0.001) oncoproteins in lesion persistence among HIV-positive women. Within the limitations of this study, the immunoexpression of HPV 16/18 E6 and E7 oncoproteins may have prognostic value regarding lesion persistence in HIV-positive women.

  8. S100A8/A9 induces apoptosis and inhibits metastasis of CasKi human cervical cancer cells.

    PubMed

    Qin, Fengjin; Song, Yao; Li, Zijian; Zhao, Ling; Zhang, Youyi; Geng, Li

    2010-09-01

    S100 proteins, a family of Ca(2+)-binding proteins, have been linked to several human diseases in recent years. Deregulated expression of S100 proteins, including S100A9 and its partner S100A8, was reported to be associated with neoplastic disorders. In our previous study using serial analysis of gene expression, we identified decreased expressions of S100A9 and S100A8 in human cervical squamous cell carcinoma. To investigate the functions of S100A8 and S100A9 in cervical cancer, we purified recombinant S100A8 and S100A9 proteins and treated CaSki human cervical cancer cells with these proteins. We found that S100A8/A9 induced apoptosis and inhibited migration of CaSki cells; S100A8/A9 also reduced the expression of matrix metalloproteinase (MMP)-2 in CaSki cells. In summary, this study suggests that S100A8 and S100A9 have inhibitory effects on the proliferation of CaSki carcinoma cells by inducing cell apoptosis and on the invasiveness of CaSki cells.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer cells

    PubMed Central

    Kong, Lu; Hao, Qi; Wang, Ying; Zhou, Ping; Zou, Binbin; Zhang, Yu-xiang

    2015-01-01

    nc886 or VRNA2-1 has recently been identified as a noncoding RNA instead of a vault RNA or a pre-microRNA. Several studies have reported that pre-miR-886 plays a tumor-suppressive role in a wide range of cancer cells through its activity as a cellular protein kinase RNA-activated (PKR) ligand and repressor. However, by sequencing stem-PCR products, we found that a microRNA originating from this precursor, vault RNA2-1-5p (VTRNA2-1-5p), occurs in cervical cancer cells. The expression levels of the predicted targets of VTRNA2-1-5p are negatively correlated with VTRNA2-1-5p levels by quantitative reversion transcription PCR (qRT-PCR). Previous results have shown that VTRNA2-1-5p is overexpressed in human cervical squamous cell carcinomas (CSCCs) compared with adjacent healthy tissues. Inhibition of VTRNA2-1-5p increases Bax protein expression and apoptotic cell death in cervical cancer cells. Our findings suggest that VTRNA2-1-5p has oncogenic activity related to the progression of cervical cancer. Here, we report that VTRNA2-1-5p directly targeted p53 expression and functioned as an oncomir in cervical cancer. VTRNA2-1-5p inhibition decreased cervical cancer cell invasion, proliferation, and tumorigenicity while increasing apoptosis and p53 expression. Interestingly, VTRNA2-1-5p inhibition also increased cisplatin-induced apoptosis of HeLa and SiHa cells. In human clinical cervical cancer specimens, low p53 expression and high VTRNA2-1-5p expression were positively associated. In addition, VTRNA2-1-5p was found to directly target the 5′ and 3′ untranslated regions (UTRs) of p53. We propose that VTRNA2-1-5p is a direct regulator of p53 and suggest that it plays an essential role in the apoptosis and proliferation of cervical cancer cells. PMID:26318295

  15. 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.

  16. Cervicitis

    MedlinePlus

    ... results from a sexually transmitted infection, such as chlamydia or gonorrhea. Cervicitis can develop from noninfectious causes, ... from common sexually transmitted infections (STIs), including gonorrhea, chlamydia, trichomoniasis and genital herpes. Allergic reactions. An allergy, ...

  17. Cervicitis

    MedlinePlus

    ... much growth of normal bacteria in the vagina (bacterial vaginosis) can also cause cervicitis. ... under a microscope (may show candidiasis , trichomoniasis , or bacterial vaginosis) Pap test Tests for gonorrhea or chlamydia Rarely, ...

  18. Downregulation of p16(ink4a) inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells.

    PubMed

    Zhang, Chu-Yue; Bao, Wei; Wang, Li-Hua

    2014-06-01

    Studies have suggested that p16(ink4a) may be a surrogate biomarker for the diagnosis of cervical cancer; however, the function of p16(ink4a) in human cervical cancer cells remains largely unknown. Therefore, in this study, we aimed to investigate the role of p16(ink4a) in human cervical cancer cells. Immunocytochemistry was used to examine invasive squamous cell carcinoma and its precancerous lesions. p16(ink4a)-siRNA was transfected into SiHa and HeLa cells to deplete its expression. The cellular levels of p16(ink4a) mRNA and protein were detected by qRT-PCR and western blot analysis. Proliferation rates were assessed by methyl thiazolyl tetrazolium (MTT) and plate colony formation assays. Cellular migration and invasion ability were assessed by a wound healing assay and Transwell assay. Cellular apoptosis and the cell cycle were measured by flow cytometry. The protein levels of retinoblastoma (Rb), phosphorylated Rb (phospho-Rb), cyclin D1 and caspase-3 were determined by western blot analysis. The results revealed that p16(ink4a) was overexpressed in the cervical cancer and precancerous lesions (P<0.05). The downregulation of p16(ink4a) in the SiHa and HeLa cells inhibited their proliferation, migration and invasion. In the SiHa cells, p16(ink4a)-siRNA also induced G1 cell cycle arrest and apoptosis. Western blot analysis revealed that the downregulation of p16(ink4a) in the SiHa cells markedly induced caspase-3 activation and decreased cyclin D1 expression. These data suggest that the overexpression of p16(ink4a) appears to be useful in monitoring cervical precancerous lesions, which supports that the hypothesis that p16(ink4a) is a surrogate biomarker for the diagnosis of cervical cancer. The therapeutic targeting of overexpressed p16(ink4a) in the p16(ink4a)-cyclin-Rb pathway may be a useful strategy in the treatment of cervical cancer.

  19. 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.

  20. 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.

  1. Detection of Human Papillomavirus in Chronic Cervicitis, Cervical Adenocarcinoma, Intraepithelial Neoplasia and Squamus Cell Carcinoma

    PubMed Central

    Mirzaie-Kashani, Elahe; Bouzari, Majid; Talebi, Ardeshir; Arbabzadeh-Zavareh, Farahnaz

    2014-01-01

    Background: Cervical cancer is the second most common cancer in women worldwide. Recent studies show that human papillomavirus (HPV) DNA is present in all cervical carcinomas and in some cervicitis cases, with some geographical variation in viral subtypes. Therefore determination of the presence of HPV in the general population of each region can help reveal the role of these viruses in tumors. Objectives: This study aimed to estimate the frequency of infection with HPV in cervicitis, cervical adenocarcinoma, intraepithelial neoplasia and squamus cell carcinoma samples from the Isfahan Province, Iran. Patients and Methods: One hundred and twenty two formalin fixed paraffin embedded tissue samples of crevicitis cases and different cervix tumors including cervical intraepithelial neoplasia (CIN) (I, II, III), squamus cell carcinoma (SCC) and adenocarcinoma were collected from histopathological files of Al-Zahra Hospital in Isfahan. Data about histopathological changes were collected by reexamination of the hematoxylin and eosin stained sections. DNA was extracted and subjected to Nested PCR using consensus primers, MY09/MY11 and GP5+/GP6+, designed for amplification of a conserved region of the genome coding for L1 protein. Results: In total 74.5% of the tested samples were positive for HPV. Amongst the tested tumors 8 out of 20 (40%) of CIN (I, II, III), 5 out of 21 (23.8%) of adenocarcinoma cases and 78 out of 79 chronic cervicitis cases were positive for HPV. Conclusions: The rate of different carcinomas and also the rate of HPV infection in each case were lower than other reports from different countries. This could be correlated with the social behavior of women in the area, where they mostly have only one partner throughout their life, and also the rate of smoking behavior of women in the studied population. On the other hand the rate of HPV infection in chronic cervicitis cases was much higher than cases reported by previous studies. This necessitates more

  2. Rapid hyperfractionated radiotherapy. Clinical results in 178 advanced squamous cell carcinomas of the head and neck

    SciTech Connect

    Nguyen, T.D.; Demange, L.; Froissart, D.; Panis, X.; Loirette, M.

    1985-07-01

    The authors present a series of 178 patients with Stage III or IV squamous cell carcinoma of the head and neck treated by rapid irradiation using multiple and small fractions per day. An initial group of 91 patients (G1) received a total dose of 72 Gy in 80 sessions and 10 days, according to the following split course schedule: J1 to J5, 36 Gy in 40 sessions, eight daily fractions of .9 Gy separated by 2 hours; J6 to J20, rest period; J21 to J25, same as in J1 except that the spinal cord was shielded. This protocol was altered for the following 87 patients (G2) by lessening the total dose to 60 to 66 Gy and the number of fractions to 60. The rest period was lengthened to 4 weeks. All patients but five completed the whole program and the minimal follow-up period was 24 months. At the end of irradiation, 121 patients achieved a total remission, but local recurrences occurred in 56%. Moreover, acute intolerance was considered as severe in 34% of G1 patients, and included extensive mucosal necrosis and bleeding. Although this rate was significantly reduced in G2 patients, late complications were observed in 20 of the 25 survivors, and included trismus, cervical sclerosis, and recurrent laryngeal edema. The crude survival rate is 13% at 2 years. Although this study was not randomized, this particular type of accelerated and hyperfractionated combination of irradiation did not really improve the clinical results in advanced carcinoma of the head and neck. Other schedules and probably other tumors, less extended, should be tested.

  3. Anatomical coverage in elective irradiation of the neck for squamous cell carcinoma of the oral tongue

    SciTech Connect

    Meoz, R.T.; Fletcher, G.H.; Lindberg, R.D.

    1982-11-01

    From January 1954 through December 1978, 146 patients with squamous cell carcinoma of the oral tongue and clinically negative neck had their primary lesion conrolled with irradiation. Metastases to the neck developed later in: 27 of 76 patients (36%) treated by interstitial implantation; nine of 27 patients (33%) who received 2,000 rad in five fractions to the upper neck prior to the implant; eight of 19 (42%) patients who received 5,000 rad through an upper ipsilateral neck field prior to the implant; four of 24 patients (16.6%) who received 5,000 rad through bilateral portals to the upper neck with or without irradiation of the lower neck. In the 43 ipsilateral neck failures, 23 were in the upper jugular chain, (posterior subdigastric nodes), 12 in the mid-jugular, three in the lower jugular, and four in the more anterior part of the subdigastric area. There was one failure in the posterior cervical chain, and five contralateral neck failures. A review of the treatment charts showed that the patients who had an ipsilateral upper neck field only, had smaller portals because the irradiation was tailored to produce shrinkage of the primary tumor prior to needling. To include adequate coverage of the posterior subdigastric nodes (upper jugular), the bodies of the vertebrae must be seen on the simulator films. Also the junction of the subdigastric and the mid-jugular lymphatics must be covered. Although there were only three failures in the lower jugular nodes, it is technically easier to treat the upper mid-jugular nodes through an anterior appositional portal to the lower neck. A dose of 5,000 rad must be given since 2,000 rad, even if delivered in five fractions, gives a failure rate as if there had been no irradiation to the neck.

  4. Anatomical coverage in elective irradiation of the neck for squamous cell carcinoma of the oral tongue

    SciTech Connect

    Meoz, R.T.; Fletcher, G.H.; Lindberg, R.D.

    1982-11-01

    From January 1954 through December 1978, 146 patients with squamous cell carcinoma of the oral tongue and clinically negative neck had their primary lesion controlled with irradiation. Metastases to the neck developed later in: 27 of 76 patients (36%) treated by interstitial implantation: nine of 27 patients (33%) who received 2,000 rad in five fractions to the upper neck prior to the implant; eight of 19 (42%) patients who received 5,000 rad through an upper ipsilateral neck field prior to the implant; four of 24 patients (16.6%) who received 5,000 rad through bilateral portals to the upper neck with or without irradiation of the lower neck. In the 43 ipsilateral neck failures, 23 were in the upper jugular chain, (posterior subdigastric nodes), 12 in the mid-jugular, three in the lower jugular, and four in the more anterior part of the subdigastric area. There was one failure in the posterior cervical chain, and five contralateral neck failures. A review of the treatment charts showed that the patients who had ipsilateral upper neck field only, had smaller portals because the irradiation was tailored to produce shrinkage of the primary tumor prior to needling. To include adequate coverage of the posterior subdigastric nodes (upper jugular), the bodies of the vertebrae must be seen on the simulator films. Also the junction of the subdigastric and the mid-jugular lymphatics must be covered. Although there were only three failures in the lower jugular nodes, it is technically easier to treat the upper mid-jugular nodes through an anterior appositional portal to the lower neck. A dose of 5,000 rad must be given since 2,000 rad, even if delivered in five fractions, gives a failure rate as if there had been no irradition to the neck.

  5. Local control of squamous cell carcinoma of the mobile tongue: an experience of different modalities

    SciTech Connect

    Kondo, M.; Hashimoto, S.; Dokiya, T.; Inuyama, Y.; Murakami, Y.; Nagai, T.; Asanami, S.; Fukutake, K.

    1986-05-01

    From 1966 through 1983, 163 patients with squamous cell carcinoma of the mobile tongue were treated. Fifty-two patients were staged as T1N0, 77 as T2N0, 14 as T2N+, 8 as T3N0, 7 as T3N+, and 5 as T4. The follow-ups were complete. Treatment modalities varied considerably during that period, because of increasing difficulty to use radioactive sources by regulations. All T3N+ and T4 patients died shortly after treatment. Five year absolute survivals for the T1N0, T2N0, T2N+, and T3N0 patients were 87%, 60%, 27% and 63%, respectively. Local recurrence free survivals at 5 years for the T1N0, T2N0, T2N+, and T3N0 patients were 72, 48, 58, and 88%, respectively. Local recurrence free survivals seemed to be better with Ra-226 needling +/- external irradiation (EXT) than other modalities. Because many patients with local recurrence were salvaged, ultimate local-disease-free survivals should also be considered. They were 96 and 70% at 5 years for the T1N0 patients treated with Ra-226 +/- EXT, and with surgery +/- EXT, respectively; the corresponding figures for the T2N0 patients were 83 and 64%. For these reasons, Ra-226 needling may be preferable to other modalities as initial treatment. Although cervical failures did not develop after 2 years of treatment, late local recurrences were rather common, even after 5 years. Long-term follow-up is mandatory for the management of the patients, and analyzing and comparing the results.

  6. Higher blood vessel density in comparison to the lymphatic vessels in oral squamous cell carcinoma

    PubMed Central

    Maturana-Ramírez, Andrea; Espinoza, Iris; Reyes, Montserrat; Aitken, Juan Pablo; Aguayo, Francisco; Hartel, Steffen; Rojas-Alcayaga, Gonzalo

    2015-01-01

    Introduction: Oral squamous cell carcinoma (OSCC) is characterized by local invasion and the development of cervical metastasis. In the tongue, an association between the invasion of the lymphatic vessels and the development of metastasis in the regional lymph nodes has been demonstrated. Moreover, invasion of the blood vessels is associated with greater recurrence and poorer prognoses. Therefore, the presence and density of lymphatic and blood vessels in intra- and peritumoral tissues should play an important role in the progression, dissemination and metastasis of carcinomas. However, the evidence regarding OSCC is inconclusive. The aim of this study was to determine the comparison and association between the lymphatic (D2-40) and blood vessel (CD34) densities in intratumoral OSCC tissue. Materials and Methods: Thirty-seven cases diagnosed as OSCC between the years 2000 and 2008 were obtained from the Anatomic Pathology Service of the School of Dentistry, University of Chile. The immunohistochemical markers D2-40 and CD34 were used, and the densities (mm2) of lymphatic vessels (LVD) and blood vessels (BVD) in the intratumoral region were determined. The relationship between LVD and BVD values was evaluated. Results: There were significant association between the CD34 and D2-40 expression (rho=0.4, P<0.05) and between the LVD and the location in the tongue (P=0.019). The BVD was greater (128.0 vessels/mm2) than the LVD (42.9 vessels/mm2), and there was a positive correlation between the LVD and BVD. Conclusions: In OSCC, the BVD is greater than the LVD, and there is a moderate correlation between the two quantities. PMID:26722595

  7. DNA Methylation Status of PAX1 and ZNF582 in Esophageal Squamous Cell Carcinoma

    PubMed Central

    Huang, Jin; Wang, Guo; Tang, Jie; Zhuang, Wei; Wang, Li-Ping; Liou, Yu-Ligh; Liu, Ying-Zi; Zhou, Hong-Hao; Zhu, Yuan-Shan

    2017-01-01

    Hypermethylation of specific gene promoters is an important mechanism of carcinogenesis. A high frequency of promoter methylation of PAX1 and ZNF582 genes has been detected in cervical cancer. In the present study, we investigated the methylation status of PAX1 and ZNF582 genes in esophageal squamous cell carcinoma (ESCC) tissues. Tumor and paracancerous tissues were obtained from 14 ESCC patients. Genomic DNA was extracted from both tumor and paracancerous tissues, and the concentration of DNA were determined. DNA methylation analysis of PAX1 and ZNF582 genes was carried out using quantitative methylation-specific PCR. To assess the diagnostic performance of the two methylated genes for cancer detection, receiver operating characteristic (ROC) curves were generated. Sensitivities and specificities were tested at cut-offs obtained from the ROC curves. The methylation levels of both PAX1 and ZNF582 genes were significantly higher in tumor tissues compared to non-tumor paracancerous tissues. The methylation rates of PAX1 and ZNF582 in ESCC tumor and paracancerous tissues were 100% and 21.4% (p = 0.006), 85.7% and 0% (p < 0.001), respectively. The sensitivities and specificities of PAX1 and ZNF582 methylation for the detection of cancer were 100% and 85.7%, and 78.6% and 100%, respectively. The DNA methylation levels and frequencies of PAX1 and ZNF582 genes were markedly higher in ESCC tumor tissues compared to those in paracancerous tissues. Moreover, the conclusions were verified by using The Cancer Genome Atlas (TCGA) datasets. DNA methylation status of these two genes showed a relatively good sensitivity and specificity for the detection of ESCC tumors. This data suggests that DNA methylation testing holds a great promise for ESCC screening and warrants further prospective population-based studies. PMID:28241446

  8. 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.

  9. 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

  10. 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.

  11. LncRNA expression profile of ΔNp63α in cervical squamous cancers and its suppressive effects on LIF expression.

    PubMed

    Qian, Lili; Xu, Fei; Wang, Xiaolin; Jiang, Ming; Wang, Juan; Song, Weiguo; Wu, Dabao; Shen, Zhen; Feng, Dingqing; Ling, Bin; Cheng, Yong; Xiao, Weihua; Shan, Ge; Zhou, Ying

    2017-04-06

    We aim to determine the lncRNA targets of ΔNp63α in cervical cancer and molecular programs in cancerous differentiation. Different profiles of the lncRNAs were assayed and validated in overexpressing p63 SiHa cells (SiHa/ΔNp63α) and the control cell lines (SiHa/pCon). ENST00000422259, ENST00000447565 (Lnc-LIF-AS) and ENST00000469965, together with their related antisense mRNA DPYD (dihydropyrimidine dehydrogenase, a pyrimidine catabolic pathway gene), LIF (leukemia inhibitor factor) and FLNC (filamin C) were all notably differentially expressed in both ΔNp63α overexpression cells and knockdown cells. Here, we illustrated that ΔNp63α can inhibit the levels of LIF mRNA by direct transcription regulation and decrease LIF mRNA stability by suppressing the expression of Lnc-LIF-AS. An inverse interaction of LIF and ΔNp63α expression was as well validated in clinical samples of cervical cancer, and high level of LIF in cervical cancers was related with poor patient survival. The decrease of ΔNp63α also attenuated the differentiation of cervical cancerous cells. Suggesting that ΔNp63α may be form a complex network in regulation cervical cancerous differentiation.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  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. Cell membrane softening in human breast and cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

    2015-08-01

    Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection.

    PubMed

    Visalli, Giuseppa; Riso, Romana; Facciolà, Alessio; Mondello, Placido; Caruso, Carmela; Picerno, Isa; Di Pietro, Angela; Spataro, Pasquale; Bertuccio, Maria Paola

    2016-02-01

    The Human papillomavirus is responsible for the most common sexually transmitted infection and is also known to be an oncogenic virus that is associated with cervical, anogenital, and head-neck cancers. The present study aims to assess whether oxidative DNA damage is correlated with the grade of HPV-related lesions. Moreover, we evaluated clinical data and unhealthy lifestyles to verify their possible influence on the genesis of oxidative DNA damage in cervical cells. We quantified the amount of 8-Oxo-2'-deoxyguanosine in DNA as a biomarker of oxidative damage in women with and without HPV infection. We also correlated oxidative damage with different stages of cervical lesions and available clinical data (e.g., HPV genotypes). To identify HPV infections, in which proteins with a transforming potential are produced, we performed a qualitative detection of HPV E6/E7 mRNA. Our results showed greater oxidative damage in HPV-related dysplastic cervical lesions compared to samples with normal cytology, especially in women with high-grade squamous intraepithelial lesions. The latter showed a closed link with high-risk HPV genotypes. Reactive oxygen species can induce DNA double-strand breaks in both the host DNA and in the circular viral episome; this could facilitate the integration of the virus, promoting HPV carcinogenesis. Therefore, in HPV-infected women, it could be useful to reduce additional resources of reactive oxygen/nitrogen species (RONS) with a healthy lifestyle.

  5. 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.

  6. 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.

  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. 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.

  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.

    1993-06-01

    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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. Virus transcript levels and cell growth rates after naturally occurring HPV16 integration events in basal cervical keratinocytes.

    PubMed

    Scarpini, Cinzia G; Groves, Ian J; Pett, Mark R; Ward, Dawn; Coleman, Nicholas

    2014-07-01

    Cervical carcinogenesis is characterized by a clonal selection process in which the high-risk human papillomavirus (HRHPV) genome usually changes from the extra-chromosomal (episomal) state seen in productive infections to DNA that is integrated into host chromosomes. However, it is not clear whether all HRHPV integration events provide cells with a selective growth advantage compared with the episome-containing cells from which they originate. It is also unclear whether selection of cells containing a particular integrant from a mixed population simply reflects the highest levels of virus oncogene expression or has additional determinants. These early events in cervical carcinogenesis cannot readily be addressed by cross-sectional studies of clinical samples. We used the W12 model system to generate a panel of cervical squamous cell clones that were derived from an identical background under non-competitive conditions and differed only by the genomic site of HPV16 integration. Compared with the 'baseline' episome-containing cells from which they were isolated, only 9/17 clones (53%) showed significantly greater growth rates and only 7/17 (41%) showed significantly greater expression of the major virus oncogenes E7/E6. There were significant variations in levels of HPV16 transcription per DNA template, changes that were associated with histone modifications in the integrated virus chromatin. Cell growth rates showed only weak and non-significant associations with protein and mRNA levels for E7, E6, and the mean E7/E6 values. We conclude that HPV16 integration in basal cervical cells does not necessarily lead to increased levels of virus oncogenes, or to a competitive growth advantage, when compared with the initiating episome-containing cells.

  1. HPV-16 E2 gene disruption and sequence variation in CIN 3 lesions and invasive squamous cell carcinomas of the cervix: relation to numerical chromosome abnormalities

    PubMed Central

    Graham, D A; Herrington, C S

    2000-01-01

    Aim—To test the hypothesis that, because the human papillomavirus (HPV) E2 protein represses viral early gene transcription, E2 gene sequence variation or disruption could play a part in the induction of the numerical chromosome abnormalities that have been described in squamous cervical lesions. Methods—The integrity and sequence of the E2 gene from 11 cervical intraepithelial neoplasia (CIN) grade 3 lesions and 14 invasive squamous cell carcinomas, all of which contained HPV-16, were analysed by the polymerase chain reaction (PCR). The E2 gene was amplified in three overlapping fragments and PCR products sequenced directly. Chromosome abnormalities were identified by interphase cytogenetics using chromosome specific probes for chromosomes 1, 3, 11, 17, 18, and X. Results—E2 gene disruption was present in significantly more invasive carcinomas (eight of 14) than CIN 3 lesions (one of 11) (p = 0.03). No association was found between E2 disruption and the presence of a numerical chromosome abnormality. The E2 gene from the non-disrupted isolates was sequenced and wild-type (n = 5) and variant (n = 11) sequences identified. Variant sequences belonged to European and African classes and contained from one to 15 amino acid substitutions. Although numerical chromosome abnormalities were significantly more frequent in invasive squamous cell carcinoma than CIN 3 (p = 0.04), there was no significant relation between the presence of sequence variation and either histological diagnosis or chromosome abnormality. Conclusions—These data do not support the hypothesis that E2 gene disruption or variation is important in the induction of chromosome imbalance in these lesions. However, there is a relation between E2 gene disruption and the presence of invasive disease. PMID:11040943

  2. NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells

    PubMed Central

    Tao, Tao; Yang, Xiaomei; Qin, Qiong; Shi, Wen; Wang, Qiqi; Yang, Ying; He, Junqi

    2017-01-01

    Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal–regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors. PMID:28085111

  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. 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

  5. Overexpression of pyruvate kinase M2 associates with aggressive clinicopathological features and unfavorable prognosis in oral squamous cell carcinoma

    PubMed Central

    Wang, Yanling; Zhang, Xiaomin; Zhang, Yuchao; Zhu, Yuming; Yuan, Chunping; Qi, Bin; Zhang, Wei; Wang, Dongmiao; Ding, Xu; Wu, Heming; Cheng, Jie

    2015-01-01

    Abnormal glucose metabolism mediated by pyruvate kinase M2 (PKM2) fuels cancer overgrowth and propagation. However, its expression and oncogenic roles in in oral squamous cell carcinoma (OSCC) remains incompletely known. Here, we aimed to investigate the expression of PKM2, its prognostic values and oncogenic functions using 7,12-dimethyl-1,2-bezan-tracene (DMBA)-induced hamster buccal pouch SCC model, primary OSCC specimens as well as in vitro cellular assays. We found that in DMBA-induced OSCC model, negative PKM2 expression was commonly observed in normal epithelial, while more PKM2 abundance was detected in hyperplasia, dysplasia and SCC. Overexpression of PKM2 in a major fraction of OSCC significantly associated with tumor size (P = 0.027), cervical node metastasis (P = 0.004) and clinical stages (P = 0.000). Patients with increased PKM2 had remarkably reduced overall and disease-free survival. Multivariate survival analysis further revealed that PKM served as a critical independent prognostic factor for patients' overall survival. Furthermore, impaired cell proliferation and migration, and reduced apoptosis were detected upon PKM2 knockdown in HN4 and HN12 cells. Taken together, our findings reveal that PKM2 is critically involved in OSCC initiation and progression probably by promoting cell proliferation and migration as well as reducing apoptosis. Its overexpression correlates with aggressive clinicopathological features and poor patients' outcome. PMID:25970228

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  12. 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

  13. Cantharidin Induced Oral Squamous Cell Carcinoma Cell Apoptosis via the JNK-Regulated Mitochondria and Endoplasmic Reticulum Stress-Related Signaling Pathways

    PubMed Central

    Su, Chin-Chuan; Lee, Kuan-I; Chen, Mu-Kuan; Kuo, Chun-Ying; Tang, Chih-Hsin; Liu, Shing Hwa

    2016-01-01

    Oral cancer is a subtype of head and neck cancer which represents 2.65% of all human malignancies. Most of oral cancer is histopathologically diagnosed as oral squamous cell carcinoma (OSCC). OSCC is characterized by a high degree of local invasion and a high rate of metastasis to the cervical lymph nodes. How to prevention and treatment of OSCC is important and imperative. Here, we investigated the therapeutic effect and molecular mechanism of cantharidin, an active compound isolated from blister beetles, on OSCC in vitro. Results showed that cantharidin significantly decreased cell viability in human tongue squamous carcinoma-derived SAS, CAL-27, and SCC-4 cell lines. The further mechanistic studies were carried out in SAS cells. Cantharidin also significantly increased apoptosis-related signals, including caspase-9, caspase-7 and caspase-3 proteins. Besides, cantharidin decreased mitochondrial transmembrane potential (MMP) and induced cytochrome c and apoptosis inducing factor (AIF) release. Cantharidin also increased Bax, Bid, and Bak protein expressions and decreased Bcl-2 protein expression. Cantharidin could also increase the endoplasmic reticulum (ER) stress signals, including the expressions of phosphorylated eIF-2α and CHOP, but not Grp78 and Grp94. Furthermore, cantharidin reduced pro-caspase-12 protein expression. In signals of mitogen-activated protein kinases, cantharidin increased the phosphorylation of JNK, but not ERK and p38. Transfection of shRNA-JNK to OSCC cells effectively reversed the cantharidin-induced cell apoptotic signals, including the mitochondrial and ER stress-related signaling molecules. Taken together, these findings suggest that cantharidin induces apoptosis in OSCC cells via the JNK-regulated mitochondria and ER stress-related signaling pathways. PMID:27930712

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Innovations in understanding the biology of cervical cancer.

    PubMed

    Wolf, Judith K; Franco, Eduardo L; Arbeit, Jeffery M; Shroyer, Kenneth R; Wu, Tzyy-Choou; Runowicz, Carolyn D; Tortolero-Luna, Guillermo; Herrero, Rolando; Crum, Christopher P

    2003-11-01

    Revelation of the connection between the human papillomavirus (HPV) and cervical neoplasia and invasive cervical cancer is prompting new investigations to expand that understanding and promote vaccines, gene therapy, and other interventions. At the Second International Conference on Cervical Cancer (Houston, TX, April 11-14, 2002), laboratory and clinical researchers reported advances in new studies meant to increase understanding of the natural history of HPV and cervical intraepithelial neoplasia, to evaluate new cervical cancer screening techniques, and to promote new therapies. Using K14-HPV type 16 transgenic mice, researchers are investigating the effects of estrogen on cervical cancer carcinogenesis, and results are lending support to epidemiological theories showing a difference in HPV infection rates and the development of cervical lesions in women using oral contraceptives. Other work involves investigating genes that are up-regulated by HPV infection and the role of the p53 homologue, p63, in cervical neoplasia evolution. Telomerase also is under investigation as a biomarker in high-risk populations. Gene therapy that replaced p53 in cervical cancer cell lines in vitro and a nude mouse model inhibited cell and tumor growth, confirming previous findings in squamous epithelial carcinomas of the head and neck. Furthermore, research in intracellular targeting of antigens to subcellular locations shows promise for treating cervical cancer preclinically. Identification of molecular changes in cervical cancer and knowledge about the importance of HPV infection in cervical cancer can lead to new therapies to treat existing cervical cancer and, in the long term, prevent the disease.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. [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.

  8. 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

  9. 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

  10. Inhibitory effects of Arhgap6 on cervical carcinoma cells.

    PubMed

    Li, Junping; Liu, Yang; Yin, Yihua

    2016-02-01

    Ras homology GTPase activation protein 6 (Arhgap6), as a member of the rhoGAP family of proteins, performs vital functions on the regulation of actin polymerization at the plasma membrane during several cellular processes. The role of Arhgap6 in the progression and development of cancer remains nearly unknown. This study aimed at exploring the effects of Arhgap6 on cervical carcinoma. Human cervical cancer cells HeLa and SiHa were transduced with a lentivirus targeting Arhgap6 (Arhgap6+), while CaSki and C4-1 cells were transfected with miRNA. Cell proliferation was identified by Cell Counting Kit-8 (CCK-8). Cell cycle distribution and cell apoptosis were identified by flow cytometry. The capacity of cell migration, invasion, and adhesion were detected by Transwell assay. Further, quantitative real-time PCR (qRT-PCR) and western blot were used to analyze the expression levels of Arhgap6 and several tumor-related genes. Co-immunoprecipitation assay was performed to validate the interaction between Arhgap6 and Rac3 (Ras-related C3 botulinum toxin substrate 3). Results showed that Arhgap6 inhibited cell proliferation, migration, invasion, and adhesion of cervical carcinoma, induced cell apoptosis, and caused cell cycle arrest in the G0/G1 phase (n = 3, p < 0.05). Expression of the tumor suppressor genes and oncogenes were up- and down-regulated respectively by Arhgap6, and Rac3 was proved to be the target of Arhgap6. Besides, in in vivo assays, tumor size and weight were destructed in Arhgap6+ athymic nude mouse. This study indicated that Arhgap6 may play a role in the treatment of cervical cancer as a tumor supressor.

  11. 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.

  12. 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.

  13. 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.

  14. Optoelectronic method for detection of cervical intraepithelial neoplasia and cervical cancer

    NASA Astrophysics Data System (ADS)

    Pruski, D.; Przybylski, M.; Kędzia, W.; Kędzia, H.; Jagielska-Pruska, J.; Spaczyński, M.

    2011-12-01

    The optoelectronic method is one of the most promising concepts of biophysical program of the diagnostics of CIN and cervical cancer. Objectives of the work are evaluation of sensitivity and specificity of the optoelectronic method in the detection of CIN and cervical cancer. The paper shows correlation between the pNOR number and sensitivity/specificity of the optoelectronic method. The study included 293 patients with abnormal cervical cytology result and the following examinations: examination with the use of the optoelectronic method — Truscreen, colposcopic examination, and histopathologic biopsy. Specificity of the optoelectronic method for LGSIL was estimated at 65.70%, for HGSIL and squamous cell carcinoma of cervix amounted to 90.38%. Specificity of the optoelectronic method used to confirm lack of cervical pathology was estimated at 78.89%. The field under the ROC curve for the optoelectronic method was estimated at 0.88 (95% CI, 0.84-0.92) which shows high diagnostic value of the test in the detection of HGSIL and squamous cell carcinoma. The optoelectronic method is characterised by high usefulness in the detection of CIN, present in the squamous epithelium and squamous cell carcinoma of cervix.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    SciTech Connect

    Huang, Eng-Yen; Chanchien, Chan-Chao; Lin, Hao; Wang, Chung-Chi; Wang, Chong-Jong; Huang, Chao-Cheng

    2013-12-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Determining the potential of desmoglein 3 as a sensitive and specific immunohistochemical marker for the detection of micrometastasis in patients with primary oral squamous cell carcinoma

    PubMed Central

    Spadigam, Anita; Dhupar, Anita

    2016-01-01

    Aim of the study Despite advances in surgical and radiotherapy techniques, the presence of lymph node metastasis drastically decreases the survival rate of patients with primary oral squamous cell carcinoma (OSCC). Thus the accurate pathological staging of the neck is critical. Desmoglein 3 (DSG3), a desmosomal cadherin protein is said to be highly expressed in head and neck squamous cell carcinoma (HNSCC) and in metastatic cervical lymph nodes, but absent in non-invaded nodes. With an aim to improve the sensitivity of tumour cell detection, we investigated the potential of DSG3 as an immunohistochemical marker for the detection of occult lymph node metastasis in patients with primary OSCC. Material and methods Forty-seven lymph node specimens from 10 patients who underwent neck dissection for primary OSCC were immunostained with DSG3. Results The DSG3 positivity was noted in the six positive lymph nodes. However, when using DSG3 as an immunohistochemical marker, no additional micrometastatic deposits were evident in the histologically negative nodes. Interestingly, tumour marker DSG3-positive macrophages could be identified within the subcapsular sinuses, medullary sinuses, and the interfollicular areas. Conclusions Our findings suggest that although DSG3 is overexpressed in HNSCC, it is not specific and may not prove to be a potent immunohistochemical marker to detect micrometastasis. The role of tumour marker-positive macrophages within the lymph nodes needs to be investigated further.

  14. 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

  15. Carbon nanowall scaffold to control culturing of cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Watanabe, Hitoshi; Kondo, Hiroki; Okamoto, Yukihiro; Hiramatsu, Mineo; Sekine, Makoto; Baba, Yoshinobu; Hori, Masaru

    2014-12-01

    The effect of carbon nanowalls (CNWs) on the culturing rate and morphological control of cervical cancer cells (HeLa cells) was investigated. CNWs with different densities were grown using plasma-enhanced chemical vapor deposition and subjected to post-growth plasma treatment for modification of the surface terminations. Although the surface wettability of the CNWs was not significantly dependent on the CNW densities, the cell culturing rates were significantly dependent. Morphological changes of the cells were not significantly dependent on the density of CNWs. These results indicate that plasma-induced surface morphology and chemical terminations enable nanobio applications using carbon nanomaterials.

  16. 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.

  17. 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.

  18. 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.

  19. Differential targets of CpG island hypermethylation in primary and metastatic head and neck squamous cell carcinoma (HNSCC)

    PubMed Central

    Smiraglia, D; Smith, L; Lang, J; Rush, L; Dai, Z; Schuller, D; Plass, C

    2003-01-01

    Head and neck squamous cell carcinomas (HNSCC) often metastasise to the cervical lymph nodes. It is known for HNSCC as well as other cancers that progression from normal tissue to primary tumour and finally to metastatic tumour is characterised by an accumulation of genetic mutations. DNA methylation, an epigenetic modification, can result in loss of gene function in cancer, similar to genetic mutations such as deletions and point mutations. We have investigated the DNA methylation phenotypes of both primary HNSCC and metastatic tumours from 13 patients using restriction landmark genomic scanning (RLGS). With this technique, we were able to assess the methylation status of an average of nearly 1300 CpG islands for each tumour. We observed that the number of CpG islands hypermethylated in metastatic tumours is significantly greater than what is found in the primary tumours overall, but not in every patient. Interestingly, the data also clearly show that many loci methylated in a patient's primary tumour are no longer methylated in the metastatic tumour of the same patient. Thus, even though metastatic HNSCC methylate a greater proportion of CpG islands than do the primary tumours, they do so at different subsets of loci. These data show an unanticipated variability in the methylation state of loci in primary and metastatic HNSCCs within the same patient. We discuss two possible explanations for how different epigenetic events might arise between the primary tumour and the metastatic tumour of a person. PMID:12525538

  20. Diagnosing oral squamous cell carcinoma: How much imaging do we really need? A review of the current literature.

    PubMed

    Blatt, Sebastian; Ziebart, Thomas; Krüger, Maximilian; Pabst, Andreas Max

    2016-05-01

    Complementary imaging techniques that round out the clinical examination are fundamentally important in the work-up of patients with oral squamous cell carcinoma (OSCC). Above all, exact determination of primary tumour extent, metastatic spread, and treatment response highly depend on accurate imaging methods. Despite a multitude of recently published reviews, there is still an ongoing debate regarding the best imaging method. In order to update the current literature with the latest evidence, a systematic literature search via Pubmed was performed. In total, 56 studies were enrolled, 4170 patients were analysed, and twenty different imaging methods were evaluated referring to their sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). In summary, CT (computed tomography) and MRI (magnetic resonance imaging) currently remain the gold standard for evaluating extension of the primary tumour site. No additional evidence could be obtained for functional imaging methods displaying metastatic spread in the cervical lymph nodes, but was found for distant metastases. Furthermore, functional imaging seems to be beneficial in evaluating treatment response. There is further evidence in the accuracy of the different imaging methods found in this update that could possibly be implemented into the revision of the current guidelines and obtain a clear and coherent approach in the clinical set-up.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. [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.

  8. Computer-aided screening system for cervical precancerous cells based on field emission scanning electron microscopy and energy dispersive x-ray images and spectra

    NASA Astrophysics Data System (ADS)

    Jusman, Yessi; Ng, Siew-Cheok; Hasikin, Khairunnisa; Kurnia, Rahmadi; Osman, Noor Azuan Bin Abu; Teoh, Kean Hooi

    2016-10-01

    The capability of field emission scanning electron microscopy and energy dispersive x-ray spectroscopy (FE-SEM/EDX) to scan material structures at the microlevel and characterize the material with its elemental properties has inspired this research, which has developed an FE-SEM/EDX-based cervical cancer screening system. The developed computer-aided screening system consisted of two parts, which were the automatic features of extraction and classification. For the automatic features extraction algorithm, the image and spectra of cervical cells features extraction algorithm for extracting the discriminant features of FE-SEM/EDX data was introduced. The system automatically extracted two types of features based on FE-SEM/EDX images and FE-SEM/EDX spectra. Textural features were extracted from the FE-SEM/EDX image using a gray level co-occurrence matrix technique, while the FE-SEM/EDX spectra features were calculated based on peak heights and corrected area under the peaks using an algorithm. A discriminant analysis technique was employed to predict the cervical precancerous stage into three classes: normal, low-grade intraepithelial squamous lesion (LSIL), and high-grade intraepithelial squamous lesion (HSIL). The capability of the developed screening system was tested using 700 FE-SEM/EDX spectra (300 normal, 200 LSIL, and 200 HSIL cases). The accuracy, sensitivity, and specificity performances were 98.2%, 99.0%, and 98.0%, respectively.

  9. The role of MALAT1 correlates with HPV in cervical cancer

    PubMed Central

    JIANG, YAN; LI, YUEHUI; FANG, SHUJUAN; JIANG, BINYUAN; QIN, CHANGFEI; XIE, PINGLI; ZHOU, GUOHUA; LI, GUANCHENG

    2014-01-01

    Cervical cancer, the second most common type of cancer in women worldwide, is responsible for >275,100 mortalities each year and is associated with high-risk human papilloma virus (HR-HPV). HPVs have two important oncogenes, E6 and E7, which have crucial roles in malignant transformation in cervical cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA originally identified in non-small cell lung cancer. Previous studies have revealed that MALAT1 is expressed in numerous tissue types, and is significant in maintaining the normal function of the body. However, it also appeared to be notably upregulated in numerous carcinoma types compared with adjacent non-cancerous tissues. In the present study, it was identified that MALAT1 expression was upregulated in cervical cancer cell lines compared with normal cervical squamous cell samples. Further study into the effect of MALAT1 on cellular phenotype revealed that MALAT1 was able to promote cell migration and proliferation. Of note, it was revealed that the expression of MALAT1 was decreased with the knockdown of HPV16 E6/E7 in CaSki cells. Furthermore, the investigations in clinical samples also revealed that MALAT1 was expressed in HPV-positive cervical squamous cells, but not in HPV-negative normal cervical squamous cells. These results indicate that HPV correlates with MALAT1 deregulation in cervical cancer. PMID:24932303

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Multivariate Analysis of Para-Aortic Lymph Node Recurrence After Definitive Radiotherapy for Stage IB-IVA Squamous Cell Carcinoma of Uterine Cervix

    SciTech Connect

    Huang, E.-Y.; Wang, C.-J.; Chen, H.-C.; Fang, F.-M.; Huang, Y.-J.; Wang, C.-Y.; Hsu, H.-C.

    2008-11-01

    Purpose: To evaluate the pretreatment risk factors of para-aortic lymph node (PALN) recurrence after primary radiotherapy for cervical cancer. Methods and Materials: Between May 1992 and January 2006, the data from 758 patients with squamous cell carcinoma of the uterine cervix were retrospectively analyzed. No patient had undergone PALN radiotherapy as their initial treatment. PALN recurrence was diagnosed by computed tomography. PALN relapse-free status was determined clinically or radiographically. We analyzed the actuarial rates of PALN recurrence using Kaplan-Meier curves. Multivariate analyses were performed with Cox regression models. Results: Of the 758 patients, 38 (5%) and 42 (6%) had isolated and nonisolated PALN recurrences after a median follow-up of 50 months (range, 2-159 months), respectively. The 3-year and 5-year overall survival rate after PALN recurrence was 35% and 28%, respectively. A squamous cell carcinoma antigen (SCC-Ag) level >40 ng/mL (p <0.001), advanced parametrial involvement (score 4-6; p = 0.002), and the presence of pelvic lymphadenopathy (p = 0.007) were independent factors associated with PALN relapse on multivariate analysis. The 5-year PALN recurrence rate in patients with a SCC-Ag level >40 ng/mL, SCC-Ag level of 20-40 ng/mL, parametrial score of 4-6, pelvic lymphadenopathy, and no risk factors was 57%, 22%, 34%, 37%, and 9%, respectively. Conclusions: Patients with squamous cell carcinoma of the uterine cervix and a high SCC-Ag level, pelvic lymphadenopathy, or advanced PM involvement were predisposed to PALN recurrence after definitive radiotherapy. More intensive follow-up schedules are suggested for early detection and salvage in high-risk patients.

  15. 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

  16. Induced Pluripotent Stem Cell Therapies for Cervical Spinal Cord Injury

    PubMed Central

    Doulames, Vanessa M.; Plant, Giles W.

    2016-01-01

    Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs) to date. Despite the increase in survival rates due to emergency medicine improvements, overall quality of life remains poor, with patients facing variable deficits in respiratory and motor function. Therapies aiming to ameliorate symptoms and restore function, even partially, are urgently needed. Current therapeutic avenues in SCI seek to increase regenerative capacities through trophic and immunomodulatory factors, provide scaffolding to bridge the lesion site and promote regeneration of native axons, and to replace SCI-lost neurons and glia via intraspinal transplantation. Induced pluripotent stem cells (iPSCs) are a clinically viable means to accomplish this; they have no major ethical barriers, sources can be patient-matched and collected using non-invasive methods. In addition, the patient’s own cells can be used to establish a starter population capable of producing multiple cell types. To date, there is only a limited pool of research examining iPSC-derived transplants in SCI—even less research that is specific to cervical injury. The purpose of the review herein is to explore both preclinical and clinical recent advances in iPSC therapies with a detailed focus on cervical spinal cord injury. PMID:27070598

  17. 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).

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Fine-needle aspiration biopsy of HPV-related squamous cell carcinoma of the head and neck: Current ancillary testing methods for determining HPV status.

    PubMed

    Bernadt, Cory T; Collins, Brian T

    2017-03-01

    Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is a unique form of carcinoma that largely arises from the tonsillar tissue in the oropharynx. These tumors often present with cervical lymphadenopathy resulting in a fine needle aspiration (FNA) biopsy. Use of the cytology specimen to determine the HPV-status has significant prognostic and treatment implications as HPV-related tumors have a more favorable prognosis and response to nonsurgical therapies. While several different ancillary testing methods are available that have proven effective for determining HPV status in FNA specimens from HNSCCs, there is currently no consensus regarding HPV testing in this setting. Diagn. Cytopathol. 2017;45:221-229. © 2016 Wiley Periodicals, Inc.

  4. Uterine cervical cancer with brain metastasis as the initial site of presentation.

    PubMed

    Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

    2015-07-01

    Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis.

  5. Near-Infrared Micro-Raman Spectroscopy for in Vitro Detection of Cervical Cancer

    PubMed Central

    KAMEMOTO, LORI E.; MISRA, ANUPAM K.; SHARMA, SHIV K.; GOODMAN, MARC T.; LUK, HUGH; DYKES, AVA C.; ACOSTA, TAYRO

    2010-01-01

    Near-infrared Raman spectroscopy is a powerful analytical tool for detecting critical differences in biological samples with minimum interference in the Raman spectra from the native fluorescence of the samples. The technique is often suggested as a potential screening tool for cancer. In this article we report in vitro Raman spectra of squamous cells in normal and cancerous cervical human tissue from seven patients, which have good signal-to-noise ratio and which were found to be reproducible. These preliminary results show that several Raman features in these spectra could be used to distinguish cancerous cervical squamous cells from normal cervical squamous cells. In general, the Raman spectra of cervical cancer cells show intensity differences compared to those of normal squamous cell spectra. For example, several well-defined Raman peaks of collagen in the 775 to 975 cm −1 region are observed in the case of normal squamous cells, but these are below the detection limit of normal Raman spectroscopy in the spectra of invasive cervical cancer cells. In the high frequency 2800 to 3100 cm −1 region, it is found that the peak area under the CH stretching band is lower by a factor of approximately six in the spectra of cervical cancer cells as compared with that of the normal cells. The Raman chemical maps of regions of cancer and normal cells in the cervical epithelium made from the spectral features in the 775 to 975 cm −1 and 2800 to 3100 cm −1 regions are also found to show good correlation with each other. PMID:20223058

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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