Cancer Research Institute

About: Cancer Research Institute is a nonprofit organization based out in New York, New York, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 1061 authors who have published 754 publications receiving 26712 citations.

Raman Spectroscopy: An Exploratory Study to Identify Post-Radiation Cell Survival

Abstract: Resistance to radiotherapy has been an impediment in the treatment of cancer, and the inability to detect it at an early stage further exacerbates the prognosis. We have assessed the feasibility of...

Discerning the mechanism of action of HtrA4: a serine protease implicated in the cell death pathway

Abstract: High-temperature requirement protease A4 (HtrA4) is a secretary serine protease whose expression is up-regulated in pre-eclampsia (PE) and hence is a possible biomarker of PE. It has also been altered in cancers such as glioblastoma, breast carcinoma, and prostate cancer making it an emerging therapeutic target. Among the human HtrAs, HtrA4 is the least characterized protease pertaining to both structure and its functions. Although the members of human HtrA family share a significant structural and functional conservation, subtle structural changes have been associated with certain distinct functional requirements. Therefore, intricate dissection of HtrA4 structural and functional properties becomes imperative to understand its role in various biological and pathophysiological processes. Here, using inter-disciplinary approaches including in silico, biochemical and biophysical studies, we have done a domain-wise dissection of HtrA4 to delineate the roles of the domains in regulating oligomerization, stability, protease activity, and specificity. Our findings distinctly demonstrate the importance of the N-terminal region in oligomerization, stability and hence the formation of a functional enzyme. In silico structural comparison of HtrA4 with other human HtrAs, enzymology studies and cleavage assays with X-linked inhibitor of apoptosis protein (XIAP) show overall structural conservation and allosteric mode of protease activation, which suggest functional redundancy within this protease family. However, significantly lower protease activity as compared with HtrA2 indicates an additional mode of regulation of the protease activity in the cellular milieu. Overall, these studies provide first-hand information on HtrA4 and its interaction with antiapoptotic XIAP thus implicating its involvement in the apoptotic pathway.

Histone H2A isoforms: Potential implications in epigenome plasticity and diseases in eukaryotes

Abstract: Epigenetic mechanisms including the post-translational modifications of histones, incorporation of histone variants and DNA methylation have been suggested to play an important role in genome plasticity by allowing the cellular environment to define gene expression and the phenotype of an organism. Studies over the past decade have elucidated how these epigenetic mechanisms are significant in orchestrating various biological processes and contribute to different pathophysiological states. However, the role of histone isoforms and their impact on different phenotypes and physiological processes associated with diseases are not fully clear. This review is focussed on the recent advances in our understanding of the complexity of eukaryotic H2A isoforms and their roles in defining nucleosome organization. We elaborate on their potential roles in genomic complexity and regulation of gene expression, and thereby on their overall contribution towards cellular phenotype and development of diseases.

Dose-Related Modulatory Effects of Polymeric Black Tea Polyphenols (PBPs) on Initiation and Promotion Events in B(a)P and NNK-Induced Lung Carcinogenesis.

Abstract: Our understanding of dose-related effects of polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, is limited. In the present study, the effect of various doses of black tea (0.75, 1.5, and 3%)-derived PBP-rich extract on biochemical parameters and lung carcinogenicity in A/J mice was investigated. Pretreatment with PBPs showed the dose-related decrease in B(a)P-induced expression and activity of CYP1A1 in the liver while CYP1A2 expression and activity in the lung. Dose-dependent significant increase in PBP-mediated over-expression and activity of GSTs (alpha in the liver while pi in the lung) were observed in polyphenol-treated groups. Significant dose-related decrease in number and intensity of BPDE-DNA adducts were observed in liver and lung. Black tea (1.5%, 3%)-derived PBPs showed dose-mediated decrease in lung tumor incidence and multiplicity which was further correlated with different molecular markers like cell proliferation and apoptosis in B(a)P and NNK model. In conclusion, dose-dependent chemopreventive effects of PBPs, both anti-initiating (induction of phase II and inhibition of carcinogen-induced phase-I enzymes leading to decrease in BPDE-DNA adducts) and anti-promoting (decreased cell proliferation and increased apoptosis lowering incidence and/or multiplicity of lung lesions), were observed in A/J mice without significant toxicity.

Infiltration of mammary carcinoma as an indicator of axillary node metastasis. A preliminary report.

Abstract: The mammographic and pathologic material of 58 women who underwent radical mastectomy for infiltrating duct carcinoma was reviewed. A statistically significant increase in the frequency of axillary lymph node metastasis accompanied carcinomas which in mammograms appeared highly rather than slightly infiltrative. Among the 52 cases in which approximate tumor volume could be determined, a significantly greater proportion of highly infiltrative tumors was found among small tumors than among large tumors. Highly infiltrative tumors of large size metastasized to axillary lymph nodes more often than did those of small size. These results imply that the extent of macroscopic local tumor infiltration as recorded by mammography can serve as a guide to the frequency of concomitant metastasis to the axillary lymph nodes.