1.Biological evaluation of MR36, a novel non-polyglutamatable thymidylate synthase inhibitor that blocks cell cycle progression in melanoma cell lines.
Giudice S1, Benassi L, Bertazzoni G, Veratti E, Morini D, Azzoni P, Costi MP, Venturelli A, Pirondi S, Seidenari S, Magnoni C. Invest New Drugs. 2012 Aug;30(4):1484-92. doi: 10.1007/s10637-011-9733-2. Epub 2011 Sep 1.
Melanoma is one of the most common cancers, and its incidence has continued to increase over the past few decades. Chemotherapy resistance and related defects in apoptotic signaling are critical for the high mortality of melanoma. Effective drugs are lacking because apoptosis regulation in this tumor type is not well understood. The folate pathway has been considered an interesting target for anticancer therapies, and approaches targeting this pathway have recently been extended to melanoma treatment. In this study, the intracellular apoptosis signaling pathways of two melanoma cells lines (SK-MEL-2 and SK-MEL-28) were investigated after treatment with a new experimental antifolate substance (MR36) that targets thymidylate synthase. In both melanoma cell lines, apoptosis induction was triggered by a p53-independent mechanism. MR36-induced apoptosis was associated with a loss of both mitochondrial membrane potential and caspase-3 activation.
2.[Measurement of plasma concentration and bioavailability of nolatrexed dihydrochloride in mice].
Wang GF1, Zhang JY, Wu SY, Xu W, Wan SH, Shao CF, Zhang JJ. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Nov;28(11):1993-5.
OBJECTIVE: To establish a methods based on high-performance liquid chromatogram-mass spectrum for measuring the plasma concentration of nolatrexed dihydrochloride and investigate the pharmacokinetic profile and absolute bioavailability of the drug in mice.
3.Metastatic nasopharyngeal carcinoma outcomes in patients on cisplatin with nolatrexed or 5-fluorouracil.
Zheng J1, Lin J, Wang L, Zhou J, Xie B, Xu T, Zhang W. Oncol Res Treat. 2014;37(10):540-4. doi: 10.1159/000368107. Epub 2014 Sep 16.
BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in southern China. In this study, we compared the clinical efficacy and toxicity of cisplatin with nolatrexed (LP) or 5-fluorouracil (FP) for NPC.
4.[Effects of RNA interference and nolatrexed on thymidylate synthase expression and cell proliferation of human colorectal carcinoma LOVO cells].
Tian SB1, Jing CQ, Li LP. Zhonghua Wei Chang Wai Ke Za Zhi. 2012 Nov;15(11):1187-91.
OBJECTIVE: To investigate the effect of the RNAi and the chemotherapy drugs nolatrxed on the expression of thymidylate synthase(TS) and the growth of the colorectal carcinoma LOVO cells.