Enhanced antitumor potential induced by chloroacetate-loaded benzophenones acting as fused tubulin-pyruvate dehydrogenase kinase 1 (PDHK1) ligands.

Enhanced antitumor potential induced by chloroacetate-loaded benzophenones acting as fused tubulin-pyruvate dehydrogenase kinase 1 (PDHK1) ligands. Bioorg Chem. 2020 Jan 30;96:103643 Authors: Ghinet A, Thuru X, Floquet E, Dubois J, Farce A, Rigo B Abstract The majority of cancers detected every year are treated with anti-cancer compounds. Unfortunately, many tumors become resistant to antineoplastic drugs. One option is to use cocktails of compounds acting on different targets to try to overcome the resistant cells. This type of approach can produce good results, but is often accompanied by a sharp increase of associated side effects. The strategy presented herein focuses on the use of a single compound acting on two different biological targets enhancing potency and lowering the toxicity of the chemotherapy. In this light, the approach presented in the current study involves the dual inhibition of human pyruvate dehydrogenase kinase-1 (PDHK1) and tubulin polymerization using mono-, di- and tri-chloroacetate-loaded benzophenones and benzothiophenones. Synthesized molecules were evaluated in vitro on tubulin polymerization and on pyruvate dehydrogenase kinase 1. The cell cycle distribution after treatment of DA1-3b leukemic cells with active compounds was tested. Twenty-two benzo(thio)phenones have been selected by the National Cancer Institute (USA) for evaluation of their anti-proliferative potential against NCI-60 cancer cell lines including multidrug-...
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research

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Publication date: Available online 4 April 2020Source: Radiation Physics and ChemistryAuthor(s): B. Juste, R. Miró, S. Morató, G. Verdú, S. Peris
Source: Radiation Physics and Chemistry - Category: Physics Source Type: research
Publication date: Available online 5 April 2020Source: Journal of Molecular StructureAuthor(s): T. Valarmathi, R. Premkumar, A. Milton Franklin Benial
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Publication date: Available online 4 April 2020Source: Redox BiologyAuthor(s): Raúl González, María A. Rodríguez-Hernández, María Negrete, Kalina Ranguelova, Aurelie Rossin, Carmen Choya-Foces, Patricia de la Cruz-Ojeda, Antonio Miranda-Vizuete, Antonio Martínez-Ruiz, Sergio Rius-Pérez, Juan Sastre, José A. Bárcena, Anne-Odile Hueber, C. Alicia Padilla, Jordi Muntané
Source: Redox Biology - Category: Biology Source Type: research
CONCLUSIONS: This study suggests that MTC is a more immunologically active tumor that has been previously reported. Patients with advanced MTC should be screened for targetable antigens and immune checkpoints to determine their eligibility for current clinical trials. Additional studies are necessary to fully characterize the antigenic potential of MTC and may encourage the development of adoptive T cells therapies for this rare tumor. PMID: 32242507 [PubMed - as supplied by publisher]
Source: Thyroid : official journal of the American Thyroid Association - Category: Endocrinology Tags: Thyroid Source Type: research
Publication date: Available online 4 April 2020Source: Journal of Environmental PsychologyAuthor(s): Kati Peditto, Mardelle Shepley, Naomi Sachs, Jane Mendle, Anthony Burrow
Source: Journal of Environmental Psychology - Category: Psychiatry & Psychology Source Type: research
Dr. Matija Snuderl, neuropathologist and molecular pathologist at  New York University Langone Health, was featured ina recent article appearing inNature (March 26, 2020, Vol 579, p S14-S16). The article, which addresses the use of artificial intelligence (AI) in cancer diagnostics, opens with Dr. Snuderl experiencing a moment that many of us neuropathologists have had wherein we hesitate before signing out a case because of a feeling that something might be just a bit different about a particular specimen. That feeling prompts us to do something else (run more ancillary testing, get a consult, sleep on it and ta...
Source: neuropathology blog - Category: Radiology Tags: neuropathologists Source Type: blogs
In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment. Introduction Metastasis is the leading cause of breast cancer mortality, which has been one major challenge in clinical treatment (1). In particular, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR) and HER2 receptors, which is one of the most aggressive types of breast cancers, marked by high rates of relapse, visceral metastases and early death (2, 3). The...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Several TISC-based immunotherapeutic approaches are under development in various stages of preclinical studies. As outlined in this review article, a careful and more exhaustive genetic and metabolic understanding of TISC-associated phenotypes is critical to develop novel TISC based immunotherapies. Various components within the tumor microenvironment such as tumor cells, infiltrating immune cells, and supporting stromal cells impact the TISC metabolism. This unique metabolic profile leads to upregulation of certain enzymes and proteins such as ALDH1, CEP55, IDO COA1 etc., which can be utilized for development ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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