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Vallespi M.G.,Center for Genetic Engineering and Biotechnology | Fernandez J.R.,Center for Genetic Engineering and Biotechnology | Torrens I.,Center for Genetic Engineering and Biotechnology | Garcia I.,Institute of Oncology and Radiobiology | And 8 more authors.
Journal of Peptide Science | Year: 2010

Novel therapeutic peptides are increasinglymaking their way into clinical application. The cationic and amphipathic properties of certain peptides allow them to cross biological membranes in a non-disruptive way without apparent toxicity increasing drug bioavailability. By modifying the primary structure of the Limulus-derived LALF32-51 peptidewe designed a novel peptide, L-2, with antineoplastic effect and cell-penetrating capacity. Interestingly, L-2 induced cellular cytotoxicity in a variety of tumor cell lines and systemic injection into immunocompetent and nude mice bearing established solid tumor, resulted in substantial regression of the tumor mass and apoptosis. To isolate the gene transcripts specifically regulated by L-2 in tumor cells, we conducted suppressive subtractive hybridization (SSH) analysis and identified a set of genes involved in biological processes relevant to cancer biology. Our findings describe a novel peptide that modifies the gene expression of the tumor cells and exhibits antitumor effect in vivo, indicating that peptide L-2 is a potential candidate for anticancer therapy. Copyright ©2009 European Peptide Society and John Wiley & Sons, Ltd. Source

Izquierdo-Kulich E.,University of Habana | De Quesada M.A.,Institute of Oncology and Radiobiology | Perez-Amor C.M.,University of Habana | Nieto-Villar J.M.,University of Habana
Mathematical Biosciences and Engineering | Year: 2011

A mathematical model was obtained to describe the relation between the tissue morphology of cervix carcinoma and both dynamic processes of mitosis and apoptosis, and an expression to quantify the tumor aggressiveness, which in this context is associated with the tumor growth rate. The proposed model was applied to Stage III cervix carcinoma in vivo studies. In this study we found that the apoptosis rate was signicantly smaller in the tumor tissues and both the mitosis rate and aggressiveness index decrease with Stage III patients' age. These quantitative results correspond to observed behavior in clinical and genetics studies. Source

Chen D.,International Agency for Research on Cancer | McKay J.D.,International Agency for Research on Cancer | Clifford G.,International Agency for Research on Cancer | Gaborieau V.,International Agency for Research on Cancer | And 24 more authors.
Human Molecular Genetics | Year: 2011

High-risk α mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers,whereas b cutaneous HPV types (e.g. HPV8) have been implicated in non-melanoma skin cancer. Although antibodies against the capsid protein L1 of HPV are considered asmarkers of cumulative exposure, not all infected persons seroconvert. To identify common genetic variants that influence HPV seroconversion,we performed a two-stage genome-wide association study. Genome-wide genotyping of 316 015 single nucleotide polymorphisms was carried out using the Illumina HumanHap300 BeadChip in 4811 subjects froma central European case-control study of lung, head and neck and kidney cancer that had serology data available on 13 HPV types. Only one association met genome-wide significance criteria, namely that between HPV8 seropositivity and rs9357152 [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.24-1.50 for theminor allele G; P = 1.2 × 10 -10], a common genetic variant (minor allele frequency = 0.33) located within the major histocompatibility complex (MHC) II region at 6p21.32. This association was subsequently replicated in an independent set of 2344 subjects from a Latin American case-control study of head and neck cancer (OR = 1.35, 95% CI = 1.18-1.56, P = 2.2 × 10 -5), yielding P = 1.3 × 10 -14 in the combined analysis (P-heterogeneity 5 0.87). No heterogeneity was noted by cancer status(controls/lung cancer cases/head and neck cancer cases/kidney cancer cases). This study provides a proof of principle that genetic variation plays a role in antibody reactivity to HPV infection. © The Author 2011. Published by Oxford University Press. All rights reserved. Source

Delahaye-Sourdeix M.,International Agency for Research on Cancer IARC WHO | Anantharaman D.,Genetic Epidemiology Group | Timofeeva M.N.,Genetic Epidemiology Group | Timofeeva M.N.,International Agency for Research on Cancer | And 48 more authors.
Journal of the National Cancer Institute | Year: 2015

Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10-10) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het =. 026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors. © 2015 © The Author 2015. Published by Oxford University Press. Source

Marks M.A.,U.S. National Cancer Institute | Chaturvedi A.K.,U.S. National Cancer Institute | Kelsey K.,Brown University | Straif K.,International Agency of Research on Cancer | And 27 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2014

Background: The incidence of oropharyngeal and oral tongue cancers has increased over the last 20 years which parallels increased use of marijuana among individuals born after 1950. Methods: A pooled analysis was conducted comprising individual-level data from nine case-control studies from the United States and Latin America in the INHANCE consortium. Self-reported information on marijuana smoking, demographic, and behavioral factors was obtained from 1,921 oropharyngeal cases, 356 oral tongue cases, and 7,639 controls. Results: Compared with never marijuana smokers, ever marijuana smokers had an elevated risk of oropharyngeal [adjusted OR (aOR), 1.24; 95% confidence interval (CI): 1.06-1.47] and a reduced risk of oral tongue cancer (aOR, 0.47; 95% CI, 0.29, 0.75). The risk of oropharyngeal cancer remained elevated among never tobacco and alcohol users. The risk of oral tongue cancer was reduced among never users of tobacco and alcohol. Sensitivity analysis adjusting for potential confounding by HPV exposure attenuated the association of marijuana use with oropharyngeal cancer (aOR, 0.99; 95% CI, 0.71-1.25), but had no effect on the oral tongue cancer association. Conclusions: These results suggest that the association of marijuana use with head and neck carcinoma may differ by tumor site. Impact: The associations of marijuana use with oropharyngeal and oral tongue cancer are consistent with both possible pro- and anticarcinogenic effects of cannabinoids. Additional work is needed to rule out various sources of bias, including residual confounding by HPV infection and misclassification of marijuana exposure. Cancer Epidemiol Biomarkers Prev; 23(1); 160-71. © 2013 AACR. Source

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