FK 506 HAS HAD A major beneficial effect on the survival of transplanted organs. However. the use of FK 506 is limited by its toxicity. To circumvent this problem. we attempted to amplify the therapeutic efficacy of lowdose FK 506 bv the combined use of various antimetabolites, including' RS-61443 (RS),1 mizoribine (MIZ),2 and azathioprine (AZA). Therapeutic interaction was evaluated with rat a...

Bear HD et al. The effect on pCR of bevacizumab and/or antimetabolites added to standard neoadjuvant chemotherapy: NSABP protocol B-40. Proc ASCO 2011;Abstract LBA1005. Burris HA 3rd et al. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol 2011;...

position and two alkylthio side chains at the 5and 6-position were synthesized as possible antimetabolites of coenzyme Q. These compounds were tested for inhibition of coenzyme Q in mitochondrial succinoxidase and reduced nicotinamide adenine dinucleotide (NADH)-oxidase systems, and were found to show greater inhibition of the NADH-oxidase system than of the succinoxidase system. 5, 6Di-octylth...

anisms are altered in part by the particular disease process and also, at times, by the therapeutic measures used in these disorders. Antimetabolite therapy, for example, can inhibit both primary and secondary antibody responses, impair the development of delayed hypersensitivity, and block homograft rejection.2 Page and coworkers,3 in a study of the effects of 6-mercaptopurine ( 6-MP) on infla...

Recently, we demonstrated that sterile α motif and HD domain containing protein 1 (SAMHD1) is a major barrier in acute myelogenous leukemia (AML) cells to the cytotoxicity of cytarabine (ara-C), the most important drug in AML treatment. Ara-C is intracellularly converted by the canonical dNTP synthesis pathway to ara-CTP, which serves as a substrate but not an allosteric activator of SAMHD1. Us...

Chemotherapy (chemo) is the specific systematic treatment administered in oncological practice for malignant neoplasms in order to destroy chaotically dividing abnormal cells. Chemo is a part of anticancer treatment along with radiotherapy, immunotherapy and surgery. The drugs used in chemotherapeutic protocols cannot be purchased over the counter; they can be taken with prescription only. Canc...

Thymidylate synthase (TYMS; EC 2.1.1.15) catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) by N(5),N(10)-methyhlenetetrahydrofolate, forming dTMP for the maintenance of DNA replication and repair. Inhibitors of TYMS have been widely used in the treatment of neoplastic disease. A number of fluoropyrimidine and folate analogs have been developed that lead to inhibitio...

The prediction of the cellular direction of metabolic pathways toward either DNA synthesis or DNA methylation is crucial for determining the susceptibility of cancers to anti-metabolites such as fluorouracil (5-FU). We genotyped the methylenetetrahydrofolate reductase (MTHFR) gene in NCI-60 cancer cell lines, and identified the methylation status of 24 tumor suppressor genes using methylation-s...

A large number of antimetabolites of nucleic acid components have been tried as antitumor agents (11). While some have retarded tumor growth, they are in general toxic to the host ani mal. This is perhaps to be expected, since protein synthesis is an essential phenomenon in all tissues. In the studies to be described, we have at tempted to interfere with the energy sources of the cell. Since th...

This is a review of reserpine, haloperidol, and various phenothiazines that produce parkinsonism and other movement disorders. The by-products of illicit meperidine synthesis, MPTP and its more sinister companion, MPP, are also discussed. Movement disorders, transient or fixed, frank parkinsonism and/or dyskinesia, due to a variety of other medications and toxic agents are included. These are m...