Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several newly synthesized boron betaine analogs had antitumor activity in Ehrlich ascites, Walker 256 ascites carcinosarcoma, and Lewis lung screens and marginal activity in the B-16 melanotic melanoma screen. In vivo testing demonstrated that trimethylamine-cyanoborane inhibied Ehrlich ascites cell DNA and protein syntheses as well as gene modulation by chromatin protein phosphorylation and methylation. Trimethylamine-cyanoborane increased cyclic-AMP levels. In vitro testing showed that nuclear DNA polymerase, thymidylate synthetase, S-adenosylmethyltransferase, nonhistone chromatin methylation, deoxyribonuclease, ribonuclease, and cathepsin were inhibited by the boron analogs. These compounds did not demonstrate high antitumor activity at the doses employed, but blockage of methyl transfer from S-adenosylmethionine was established as a feasible method for controlling cell proliferation.
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PMID:Boron betaine analogs: antitumor activity and effects on Ehrlich ascites tumor cell metabolism. 22 87

Evidence is presented that a number of sesquiterpene lactones isolated from plants and synthesized pyrimidines containing the alpha-methylene-gamma-lactone moiety are potent inhibitors of Walker 256 carcinosarcoma and Ehrlich ascites tumor growth and marginal inhibitors of P-388 lymphocytic leukemia and Lewis lung tumor growth. In vitro aerobic basal respiration and oxidative phosphorylation processes of Ehrlich ascites cells were inhibited by these agents as well as deoxyribonucleic acid polymerase and thymidylate synthetase enzymatic activities. These studies indicate that the alpha-methylene-gamma-lactone moiety, the beta-unsubstituted cyclopentenone ring, and the alpha-epoxycyclopentanone system are the essential moieties for inhibition of these biochemical parameters.
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PMID:Antitumor agents XXX: Evaluation of alpha-methylene-gamma-lactone-containing agents for inhibition of tumor growth, respiration, and nucleic acid synthesis. 69 Aug 26

Cervical carcinosarcoma is an extremely rare type of neoplasm that lacks standard of care. Preclinical and clinical evidence has suggested that cryoablation in combination with immunotherapy may result in a synergistic effect, generating a more robust immune response to distant lesions. A few clinical trials have evaluated the efficacy of such combination treatment in a variety of solid tumors, but with conflicting results. This report describes the first clinical efficacy of cryoablation followed by pembrolizumab observed in a patient with tumor mutational burden (TMB)-high metastatic cervical carcinosarcoma that was negative for programmed cell death protein 1 expression, microsatellite instability stable, and had mutations in DNA polymerase epsilon (POLE). She had achieved complete response (CR) after 3 months of pembrolizumab treatment and had maintained CR as of the time of submission of this manuscript, with a progression-free survival of 11 months and counting. The case exhibited an exceptional response to cryoablation followed by pembrolizumab, potentially attributed to mutations in POLE, which lead to an extremely high TMB. This report paves the avenue for establishing treatment regimens for patients with TMB-high cervical carcinosarcoma. KEY POINTS: Owing to its rarity, cervical carcinosarcoma has not been well characterized, and currently, there is no standard of care for this disease. This report describes the first case of clinical efficacy of cryoablation followed by pembrolizumab observed in a patient with tumor mutational burden-high metastatic cervical carcinosarcoma. The case exhibited an exceptional response (maintained CR as of the time of submission of this article: 11 months) to cryoablation followed by pembrolizumab. This is the first POLE-mutated cervical carcinosarcoma case.
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PMID:Exceptional Response of Cryoablation Followed by Pembrolizumab in a Patient with Metastatic Cervical Carcinosarcoma with High Tumor Mutational Burden: A Case Report. 3184 13