PubMed · 11022545
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M Childs. 2000. My privilege.. https://pubmed.ncbi.nlm.nih.gov/11022545/
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A method is described for the preparation of ganciclovir triphosphate (GCV-TP) using murine colon cancer cells (MC38) transduced with the herpes simplex virus-thymidine kinase (MC38/HSV-tk). Murine cells transduced with viral-tk contain required viral and host enzymes needed for complete cellular synthesis of this potent antiviral metabolite. Dose response studies showed optimal intracellular levels of GCV-TP occurred after exposure of MC38/HSV-tk cells to 300 microM ganciclovir for 24 h producing 7.5 nmol GCV-TP/10(6) cells. This reflects cellular accumulation of GCV-TP to levels 25-fold greater than the medium concentration of parent drug. A simple isolation scheme included methanolic extraction and anion-exchange chromatography to recover the target triphosphate. Mass spectral analysis and selective enzyme degradation provided structural confirmation of the purified product. Biological activity of the purified GCV-TP was demonstrated by competitive inhibition experiments using human DNA polymerase alpha and HSV DNA polymerase that showed substantially greater sensitivity for the viral polymerase in agreement with previous reports. The GCV-TP obtained was further used to enzymatically prepare GCV mono- and diphosphate in high yield. This method provides an easily scalable means of preparing milligram amounts of the triphosphates of pharmacologically active acyclic nucleosides like ganciclovir.
There is an evidence to suggest that cdc25B phosphatase is an oncogenic. We hypothesized that cdc25B gene may be expressed in tumors of patients with non-small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of cdc25B messenger RNA was evaluated by reverse transcription polymerase chain reaction in 55 non-small cell lung carcinomas and adjacent histological normal lung samples using LightCycler. The data was analyzed in reference to clinicopathological data and survival data. There was no difference of cdc25B expression level between the NSCLC tissue and normal lung tissue. There was no relationship between cdc25B gene expression and age, gender, N or T-status and clinical stage. However, the NSCLC patients with high cdc25B expression had significantly poor survival than the patients with low cdc25B expression (P=0.0173). Thus we suggest that cdc25B may predict poor survival.
Hormone-related cancers in the prostate, breast, endometrium, ovary and testicle account for 30% of malignancies in humans. We have developed a unique model of spontaneous prostate cancer (PC) in Lobund-Wistar [L-W] rats that shares many of its characteristics with the natural history of PC in man, including (a) inherent predisposition, high production of testosterone and aging risk factors, (b) endogenous tumorigenic mechanisms, and (c) early stage testosterone-dependent and late stage testosterone-independent tumors. About 30% of L-W rats on diet L-485 develop spontaneous palpable cancer in the anterior prostate-seminal vesicle (P-SV) complex in average of 20.5 months. At age 12 months early stage spontaneous PC was prevented or reversed by testosterone-deprivation through change of diet from L-485 to soy protein isolate/isoflavone (SPII) diet, thereby preventing the late lethal clinical disease: about 75% of rats at risk of developing testosterone-independent P-SV tumors were free of detectable cancer and about 25% had developed testosterone-independent cancer at age 12 months. The duration of the dependent stage exceeded age 12 months in 75% of the rats at risk. Dietary soymeal, found in most natural ingredient diets, may promote PC tumorigenesis, but only in L-W rats.