Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.
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PMID:[LY188011 phase I study. Research Group of Gemcitabine (LY188011)]. 868 15

Gemzar is a nucleoside analog that has been shown to be superior to 5-fluorouracil for the treatment of advanced pancreatic cancer in terms of both clinical benefit and survival. This open label program enrolled 214 patients. Patients eligible for this program had advanced or metastatic pancreatic cancer, received up to one previous chemotherapy, a baseline Karnofsky performance status (KPS) of at least 50, measurable or evaluable disease, adequate organ function defined as: absolute leucocyte count > 3 x 10(9)/L, platelet count > 100 x 10(9)/L, hemoglobin > 9 gr/dL, total bilirubin < 2 x upper limit of normal (ULN), creatinine < 2 x ULN, ALT and AST levels < 5 x ULN and were at least 18 years. A 1000 mg/m2 of Gemzar was administered weekly up to 7 weeks followed by a week of rest, then once weekly for 3 weeks out of every 4 weeks. The median age at inclusion was 64 years, 52% of the patients were male, 27% were 70 year or older, 66% had stage IV disease, 66% had a KPS of 80 or higher and 34% had received no prior chemotherapy. The overall response rate is 7%. A time-to-first-serious-event analysis was performed since only a limited number of dates of death were available. The first serious event (FSE) was considered as the earliest of the following: increase by at least 2 of the pain score, deterioration of KPS of at least 20, documentation of progressive disease or death. The median time to FSE was 4 months, the free FSE rate at 1 year was 14%. We conclude that the results observed in this program confirm the established efficacy of Gemzar in pancreatic cancer.
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PMID:Compassionate use of Gemzar in advanced pancreatic cancer: a Belgian experience. 1188 32

Previously, we identified rare missense mutations of complement component 2 (C2) to be associated with chronic hepatitis B (CHB) by exome sequencing. However, up to now, little is known about the role of C2 in CHB. In the present study, we aimed to perform preliminary exploration about the underlying role of C2 in CHB. Serum samples from 113 CHB patients and 30 healthy controls, and liver biopsy samples from 5 CHB patients and 3 healthy controls were obtained from the Third Affiliated Hospital of Sun Yat-sen University between January 2018 and January 2020. HepG2.2.15 and HepG2-NTCP cells infected with HBV were used to examine the influence of HBV infection on C2 expression. IFN-treated HepG2.2.15 cells were used to assess the effect of IFN on C2 expression. C2-overexpressing or C2-silencing HepG2.2.15 cells were constructed to evaluate the effect of C2 on HBV infection. Western blot and RT-qPCR were used to measure C2 expression in biopsy samples. HBeAg and HBsAg in culture medium and C2 of serum samples were measured by ELISA. HBV-DNA was measured by RT-qPCR. GSE84044, GSE54747 and GSE27555 were downloaded from GEO. C2 expression in liver tissue and serum was significantly lower in CHB patients compared to healthy controls, and significantly higher C2 expression was found in CHB patients with lower ALT, AST, Scheuer grade and stages compared to CHB patients with higher ALT, AST, Scheuer grades and Scheuer stage. Besides, HBV infection could decrease C2 expression by increasing expression of Sp1 and reducing expression of HDAC4. Moreover, C2 could enhance the anti-virus effect of IFN on HepG2.2.15 cells and also inhibit HBV replication in HepG2.2.15 cells by inhibition of p38-MAPK signalling pathway. In conclusion, HBV may promote viral persistence in CHB patients by inhibiting C2 expression.
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PMID:Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients. 3238 93