कैंसर विज्ञान एवं चिकित्सा

The estrogen receptor (ER) is a ligand-activated transcription factor that mediates the actions of the estrogen in target tissues. Several ERα gene polymorphisms are associated with changes in the receptor expression and function. The aim of this study is to verify the hypothesis that the ERα gene polymorphisms could be associated with high mammographic density(HMD), a well known independent risk factor for breast cancer ( BC ) in a casecontrol study carried out in the city of São Paulo (SP, Brazil) from 2010 to 2013 . Two ERα gene polymorphisms named PvuII and XbaI was examined in 308 cases and 155 controls. The PvuII polymorphism was associated with an increased risk of having high mammographic density (HMD) post menopause, after adjustment for other risk factors, the odds ratio for pp genotypes was 1.75 (confidence interval of 95% CI 95%=1.10-2.79 ) compared with the genotypes PP and Pp. The XbaI polymorphism was also associated with a high risk of HMD, but not statistically significant, odds ratio for xx genotype was 1.31 (95% CI=0.7 to 1.9). No apparent synergistic effects of these two polymorphisms were identified. It was concluded that the Pvull polymorphism in the gene ERα was associated with an increasing chance of have HMD, a strong risk factor for BC. Thus recognizing these risk factors will be of great importance in the analyses of individual susceptibility to BC, in both the study of the response to various drugs and the prognosis.

Despite the obvious promise of the strategy, pharmaceutical angioinhibition has had variable success in clinical cancer management. Thyroid hormone is a potent pro-angiogenic factor. Endogenous circulating levels of proangiogenic thyroid hormone in cancer patients treated with anti-angiogenic drugs may contribute to host resistance to angioinhibition and explain, at least in part, the variable cancer chemotherapeutic responses obtained with anti-angiogenic agents. The chick chorioallantoic membrane (CAM) angiogenesis assay accepts human tumor xenografts and is a system in which individual patient blood samples can be tested in xenograft vasculature for anti-angiogenic content—including thyroid hormone—in the presence of angioinhibitory drug dose escalation. The assay may also be used to screen individual patient tumor biopsy xenografts for susceptibility to angioinhibition.

Angiogenesis is the process of neovascularization from parent blood vessels, which is a prerequisite for many physiological and pathological conditions and is regulated by a balance between endogenous angioinhibitors and angioactivators or angiogenic factors. Imbalance between angioinhibitors and angioactivators is associated with neovascularization capacity during progression of tumor development and Choroidal Neovascularization (CNV). Normalization of pathological angiogenesis is considered as an alternative strategy to prevent the tumor growth in cancer progression or retinal damage in CNV. Various angioinhibitors are being identified and evaluated for their pathological angiogenesis regulation, of which endogenous angioinhibitors are one class derived either from extra cellular matrix or from non-extra cellular matrix of human origin. Endogenous angioinhibitors are gaining much significance as they interact with proliferating endothelial cells by binding to distinct integrins and non-integrin receptors, regulating different intracellular signaling mechanisms leading to inhibition of choroidal neovascularization and tumor growth. This review will focus on endogenous angioinhibitors and their receptor(s) mediated angioinhibitory signaling, which are of major concern in angiogenesis and their clinical and pharmaceutical implications.