Eppley Institute for Research in Cancer and Allied Diseases

About: Eppley Institute for Research in Cancer and Allied Diseases is a based out in . It is known for research contribution in the topics: Pancreatic cancer & Cancer. The organization has 965 authors who have published 1396 publications receiving 58994 citations.

Cancer-associated mucins: role in immune modulation and metastasis.

Abstract: Mucins (MUC) protect epithelial barriers from environmental insult to maintain homeostasis. However, their aberrant overexpression and glycosylation in various malignancies facilitate oncogenic events from inception to metastasis. Mucin-associated sialyl-Tn (sTn) antigens bind to various receptors present on the dendritic cells (DCs), macrophages, and natural killer (NK) cells, resulting in overall immunosuppression by either receptor masking or inhibition of cytolytic activity. MUC1-mediated interaction of tumor cells with innate immune cells hampers cross-presentation of processed antigens on MHC class I molecules. MUC1 and MUC16 bind siglecs and mask Toll-like receptors (TLRs), respectively, on DCs promoting an immature DC phenotype that in turn reduces T cell effector functions. Mucins, such as MUC1, MUC2, MUC4, and MUC16, interact with or form aggregates with neutrophils, macrophages, and platelets, conferring protection to cancer cells during hematological dissemination and facilitate their spread and colonization to the metastatic sites. On the contrary, poor glycosylation of MUC1 and MUC4 at the tandem repeat region (TR) generates cancer-specific immunodominant epitopes. The presence of MUC16 neo-antigen-specific T cell clones and anti-MUC1 antibodies in cancer patients suggests that mucins can serve as potential targets for developing cancer therapeutics. The present review summarizes the molecular events involved in mucin-mediated immunomodulation, and metastasis, as well as the utility of mucins as targets for cancer immunotherapy and radioimmunotherapy.

Synthesis and characterization of estrogen 2,3- and 3,4-quinones. Comparison of DNA adducts formed by the quinones versus horseradish peroxidase-activated catechol estrogens.

Abstract: Catechol estrogens (CE) are among the major metabolites of estrone (E1) and 17 beta-estradiol (E2). Oxidation of these metabolites to semiquinones and quinones could generate ultimate carcinogenic forms of E1 and E2. The 2,3- and 3,4-quinones of E1 and E2 were synthesized by MnO2 oxidation of the corresponding CE, following the method for synthesizing E1-3,4-quinone [Abul-Hajj (1984) J. Steroid Biochem. 21, 621-622]. Characterization of these compounds was accomplished by UV, nuclear magnetic resonance, and mass spectrometry. The relative stability of these compounds was determined in DMSO/H2O (2:1) at room temperature, and the 3,4-quinones were more stable than the 2,3-quinones. The four quinones directly reacted with calf thymus DNA to form DNA adducts analyzed by the 32P-postlabeling method. The adducts were compared to those formed when the corresponding CE were activated by horseradish peroxidase (HRP) to bind to DNA. The E1- and E2-2,3-quinones formed much higher levels of DNA adducts than the corresponding 3,4-quinones. In addition, many of the adducts (70-90%) formed by the E1- and E2-2,3-quinones appeared to be the same as those formed by activation of 2-OHE1 or 2-OHE2 by HRP to bind to DNA. Little overlap was observed between the adducts formed by E1- and E2-3,4-quinones and HRP-activated 4-OHE1 and 4-OHE2. These results suggest that semiquinones and/or quinones are ultimate reactive intermediates in the peroxidatic activation of catechol estrogens.

A three-helix homo-oligomerization domain containing BH3 and BH1 is responsible for the apoptotic activity of Bax

Abstract: Homo-oligomerization of Bax (or Bak) has been hypothesized to be responsible for cell death through the mitochondria-dependent apoptosis pathway. However, partly due to a lack of structural information on the Bax homo-oligomerization and apoptosis inducing domain(s), this hypothesis has remained difficult to test. In this study, we identified a three-helix unit, comprised of the BH3 (helix 2) and BH1 domains (helix 4 and helix 5), as the homo-oligomerization domain of Bax. When targeted to mitochondria, this minimum oligomerization unit induced apoptosis in Bax �/� Bak �/� mouse embryonic fibroblasts (DKO). Strikingly, the central helix of Bax (helix 5), when replacing the corresponding helix (helix 5) of Bcl-xL, an anti-apoptotic Bcl-2 family protein structurally homologous to Bax, converted Bcl-xL into a Bax-like molecule capable of forming oligomers and causing apoptosis in the DKO cells. Finally, a series of systematic mutagenesis analyses revealed that homo-oligomerization is both necessary and sufficient for the apoptotic activity of Bax. These results suggest that active Bax causes mitochondrial damage through homo-oligomers of a three-helix functional unit.