Polymorphism of Xeroderma Pigmentosum group G and the risk of lung cancer and squamous cell carcinomas of the oropharynx, larynx and esophagus

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.

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Expression of endogenous xenotropic retrovirus by methylcholanthrene-induced squamous cell carcinoma of the mouse respiratory tract.

Journal of Experimental Medicine ◽

10.1084/jem.150.6.1567 ◽

1979 ◽

Vol 150 (6) ◽

pp. 1567-1570 ◽

Cited By ~ 2

Author(s):

P Ebenstein ◽

B Kinder ◽

D O Bankole ◽

F F Richards ◽

M Y Armstrong

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Squamous Cell ◽

Murine Leukemia Virus ◽

Human Lung ◽

Leukemia Virus ◽

Squamous Cell Carcinomas ◽

Human Lung Cancer ◽

Induction System ◽

Murine Leukemia

As a model for human lung cancer, squamous cell carcinomas were induced by 3-methylcholanthrene in mouse tracheas which had been explanted to a subcutaneous site. The tumors that developed were examined for both ecotropic and xenotropic infectious murine leukemia virus (MuLV). From all squamous carcinomas--six out of six--a xenotropic MuLV was isolated. From some of the fibrosarcomas that occurred incidentally in our induction system, ecotropic MuLV was isolated. However, in the fibrosarcomas, no xenotropic MuLV at all was found.

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Topical 5-fluorouracil to treat multiple or unresectable facial squamous cell carcinomas in xeroderma pigmentosum

Journal of the American Academy of Dermatology ◽

10.1067/mjd.2001.113476 ◽

2001 ◽

Vol 44 (6) ◽

pp. 1054 ◽

Cited By ~ 18

Author(s):

Boussen Hamouda ◽

Zwik Jamila ◽

Rammeh Najet ◽

Touati Slim ◽

Nouira Rafiaa ◽

...

Keyword(s):

Squamous Cell ◽

Xeroderma Pigmentosum ◽

Squamous Cell Carcinomas

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p63 immunoreactivity in lung cancer: yet another player in the development of squamous cell carcinomas?

The Journal of Pathology ◽

10.1002/path.1166 ◽

2002 ◽

Vol 198 (1) ◽

pp. 100-109 ◽

Cited By ~ 106

Author(s):

Giuseppe Pelosi ◽

Felice Pasini ◽

Catharina Olsen Stenholm ◽

Ugo Pastorino ◽

Patrick Maisonneuve ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell ◽

Squamous Cell Carcinomas

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Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.8.1893 ◽

1995 ◽

Vol 13 (8) ◽

pp. 1893-1903 ◽

Cited By ~ 100

Author(s):

J S Lee ◽

A Yoon ◽

S K Kalapurakal ◽

J Y Ro ◽

J J Lee ◽

...

Keyword(s):

Lung Cancer ◽

Lymph Node ◽

Prognostic Factor ◽

Small Cell Lung Cancer ◽

Squamous Cell ◽

Small Cell ◽

Squamous Cell Carcinomas ◽

Small Cell Lung ◽

Survival Difference ◽

Favorable Prognostic Factor

PURPOSE Mutation of the p53 gene is one of the most common genetic abnormalities found in lung cancer. The purpose of this study was to evaluate the prognostic value of p53 oncoprotein expression in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS We studied 156 resected primary NSCLCs by the immunohistochemical staining technique, using the p53 antibody DO7. There were 81 adenocarcinomas, 16 large-cell carcinomas, and 59 squamous cell carcinomas; stages were I in 67, II in 30, and III in 59 cases. For each tumor, the percentage of p53 positivity was calculated by scoring a minimum of 1,000 cells on an arbitrary intensity scale of 0 to 3+. RESULTS Overall, 103 (66%) tumors expressed p53 in more than 0.1% of cells, and squamous cell carcinomas tended to express more p53 than adenocarcinomas. Since 50% positivity marked the most distinct change in overall survival duration (P = .0008), we divided the cases into three groups, as follows: p53-negative (< or = 0.1%, n = 53), low p53 (0.1% to 50%, n = 54), and high p53 (> 50%, n = 49). Overall, patients in the high-p53 group survived longer than those in the low or negative groups, with respective median survival durations of more than 65, 26, and 33 months (P = .002). The survival difference among the three groups was statistically significant for non-squamous cell (P = .008), but not for squamous cell (P = .17) carcinomas. Among lymph node-negative patients, the survival difference between groups was not statistically significant. However, among lymph node-positive patients (n = 78), more than 65% of the high-p53 group survived for more than 70 months, while the median survival durations for the low and negative groups were 21 and 18 months, respectively (P = .001). A Cox regression analysis with multiple covariates showed that p53 positivity in more than 50% of tumor cells was an independent prognostic factor for better outcome. CONCLUSION These results suggest that high expression of the p53 oncoprotein is a favorable prognostic factor in a subset of patients with NSCLC.

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Mutation analysis of the human homologue ofdrosophila patched and the xeroderma pigmentosum complementation group A genes in squamous cell carcinomas of the skin

Molecular Carcinogenesis ◽

10.1002/(sici)1098-2744(199802)21:2<87::aid-mc2>3.0.co;2-l ◽

1998 ◽

Vol 21 (2) ◽

pp. 87-92 ◽

Cited By ~ 14

Author(s):

Lena K. Eklund ◽

Erika Lindström ◽

Anne Birgitte Undén ◽

Barbro Lundh-Rozell ◽

Mona Ståhle-Bäckdahl ◽

...

Keyword(s):

Mutation Analysis ◽

Squamous Cell ◽

Xeroderma Pigmentosum ◽

Complementation Group ◽

Squamous Cell Carcinomas ◽

Human Homologue ◽

Group A

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Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1510837112 ◽

2015 ◽

Vol 112 (32) ◽

pp. 9990-9995 ◽

Cited By ~ 18

Author(s):

Zhijie Wang ◽

Zhirong Shen ◽

Zhenxiang Li ◽

Jianchun Duan ◽

Shuai Fu ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell ◽

Combined Treatment ◽

Lung Squamous Cell Carcinoma ◽

Squamous Cell Carcinomas ◽

Egfr Mutations ◽

Driver Mutations ◽

Dual Inhibitor ◽

Egfr Tki ◽

Egfr Tkis

The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non–small cell lung cancer (NSCLC). However, the clinical benefit of molecularly targeted therapy on NSCLC appears to be different between lung adenocarcinomas and squamous cell carcinomas (SqCCs). We report here that the resistance of lung SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was due to the activation of BMP-BMPR-Smad1/5-p70S6K. The combined treatment of these tumor cells with EGFR-TKI, together with inhibitors specific to BMPR or downstream mTOR, effectively reversed the resistance to EGFR-TKI. Moreover, blocking the whole PI3K-AKT-mTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC. This study details the empirical basis for a feasible clinical solution for squamous cell carcinomas with EGFR mutations.

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Association of expression of bcl-2 with outcome in non-small cell lung cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22039 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22039-e22039

Author(s):

V. Anagnostou ◽

F. Lowery ◽

K. Syrigos ◽

K. Frangia ◽

V. Zolota ◽

...

Keyword(s):

Lung Cancer ◽

Protein Expression ◽

Cancer Patients ◽

Squamous Cell ◽

Squamous Cell Carcinomas ◽

University Hospital ◽

Lung Cancer Patients ◽

Protein Levels ◽

Risk Of Death ◽

The Impact

e22039 Background: BCL-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. It is preferentially expressed in squamous cell carcinomas of the lung and has been investigated as a potential prognostic parameter in lung cancer patients with conflicting results. Here, we quantitatively assessed BCL-2 protein expression in two large and independent data sets to investigate the impact of BCL-2 on patient survival. Methods: AQUA, a fluorescent-based method for analysis of in situ protein expression, was used to measure BCL-2 protein levels and classify tumor by BCL-2 expression in a cohort of 180 lung cancer patients from Yale New Haven Hospital (training set). An independent cohort of 360 lung cancer patients from Sotiria General Hospital and Patras University Hospital in Greece was used to validate BCL-2 classification and evaluate outcome (validation set). Results: Tumors expressed BCL-2 in 57% and 53% of the cases in training and validation cohorts respectively and squamous cell carcinomas expressed higher levels of BCL-2 expression compared to adenocarcinomas (mean AQUA score 42 and 26 respectively, p=0.007); BCL-2 was not associated with other standard clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median overall survival compared to the low expressers (20 vs 15 months, log rank p=0.016). Multivariate analysis revealed an independent lower risk of death for lung cancer patients with BCL-2 expressing tumors (HR=0.58, 95% CI 0.39–0.86, p=0.006). Conclusions: BCL-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of lung cancer patients as well as incorporation of BCL-2 into clinical decisions. [Table: see text]

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