Anti-MCL1 polyclonal antibody

Introduction Targeting anti-apoptotic pathways involving the BCL2 family proteins represents a novel treatment strategy in hematologic malignancies. Venetoclax, a selective BCL2 inhibitor, represents the first approved agent of this class, and is currently used in CLL and AML. However, monotherapy is rarely sufficient for sustained responses due to the development of drug resistance and loss of dependence upon the targeted protein. Numerous pre-clinical studies have shown that combining venetoclax with other agents may represent a more effective therapeutic strategy by circumventing resistance mechanisms. In this review, we summarize pre-clinical data providing a foundation for rational combination strategies involving venetoclax. Areas covered Novel combination strategies in hematologic malignancies involving venetoclax, primarily at the pre-clinical level, will be reviewed. We emphasize novel agents that interrupt complementary or compensatory pro-survival pathways, and particularly mechanistic insights underlying synergism. PubMed, Cochrane, EMBASE, and Google scholar were searched from 2000. Expert opinion Although venetoclax has proven to be an effective therapeutic in hematologic malignancies, monotherapy may be insufficient for maximal effectiveness due to the development of resistance and/or loss of BCL2 addiction. Further pre-clinical and clinical development of combination therapies may be necessary for optimal outcomes in patients with diverse blood cancers.

Dendrobium officinale polysaccharides (DOPs) are carbohydrates predominantly composed of mannose (M1) and glucose, and are known to exhibit antitumour activities. Here, the antitumour properties of carbohydrates including monosaccharide M1, oligosaccharide mannohexaose (M6), and DOPs were investigated. Polysaccharides DOP122, DOP20, DOP8, and DOP2 with molecular weights of 1224.54, 200.99, 80.32, and 24.89 kDa, respectively, were obtained from Dendrobium officinale. Among M1, M6, and DOP122-DOP2, DOP20 exerted the strongest inhibitory effect on the proliferation of osteosarcoma (OS) U2OS and Saos-2 cells. When combined with cisplatin (DDP), DOP20 showed a synergistic inhibition of proliferation. Moreover, DOP20 enhanced DDP-induced cell apoptosis mediated by the mitochondrial pathway by up-regulating P53, Bax, and Bak expression; down-regulating Bcl-2 and Mcl-1 expression; and increasing Cleaved caspase9/Caspase9, Cleaved caspase3/Caspase3, and Cleaved PARP/PARP ratios. These findings confirmed that carbohydrate drugs, especially polysaccharides, used in the treatment of tumours need to be validated in terms of a suitable molecular weight.