Expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Tissue and peripheral blood samples were collected from 49 advanced NSCLC patients treated with gemcitabine plus carboplatin. The expressions of RRM1 and ERCC1 mRNA in tumor tissue and peripheral lymphocytes were detected by real-time fluorescent quantitative PCR. The relationship of gene expression with clinical characteristics,chemotherapy response and prognosis was analyzed.</p><p><b>RESULTS</b>The RRM1 expression in tumor tissues was positively correlated with that in peripheral blood lymphocytes,while no significant correlation was observed between ERCC1 expression in tumor tissues and that in peripheral blood (rs=0.332 and 0.258; P=0.020 and 0.073, respectively). The expression of RRM1 and ERCC1 in tumor tissues peripheral lymphocytes was synchronous (rs=0.634 and 0.351; P<0.001 and 0.013, respectively). There was no significant correlation of gene expression with gender, age, smoking status, performance status, clinical stages and histological types of patients (P>0.05). Significant difference was found in response rate to chemotherapy (P<0.05,P<0.01,P<0.05),median survival time (P<0.05,P<0.01,P<0.05) and 1-year survival rate (P<0.01,<0.05,P<0.05) between patients with low RRM1 and ERCC1 expression levels in tumor tissues or low RRM1 expression levels in peripheral blood and those with high RRM1 and ERCC1 expression levels. The patients with low ERCC1 expression levels in tumor tissues gained higher 2-year survival rate (P<0.05). There was no correlation of the expression of ERCC1 in peripheral blood with the response to chemotherapy and prognosis (P>0.05).</p><p><b>CONCLUSION</b>The expression of RRMI and ERCC1 genes in tumor tissues and RRM1 in peripheral blood lymphocytes is closely correlated with the response to chemotherapy and prognosis of patients with advanced NSCLC treated with gemcitabine plus carboplatin.</p>

Detection of RRM1, ERCC1 and BRCA1 gene expression in non-small cell lung cancer tissues and peripheral blood by SYBR real-time fluorescent quantitative PCR / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To develop a method for the detection of RRM1, ERCC1 and BRCA1 gene expression by SYBR real-time fluorescent quantitative PCR in non-small cell lung cancer tissues and peripheral blood.</p><p><b>METHODS</b>The plasmid standard of RRM1, ERCC1, BRCA1 and β-actin genes was constructed. SYBR real-time PCR was performed, and the standard curve was established. The expressions of RRM1, ERCC1 and BRCA1 mRNA in non-small cell lung cancer tissues and peripheral blood were detected.</p><p><b>RESULT</b>The standard curve presented linearity. The liquate curves of standard gene were all single apex, indicating that a good specificity was obtained.</p><p><b>CONCLUSION</b>The developed SYBR real-time fluorescent quantitative PCR has advantage of convenient operation, low cost, good specificity and high veracity.</p>

Peak concentration of gemcitabine at fixed-dose-rate and its hematological toxicity profile / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the relationship between peak concentration (Cmax) of gemcitabine at fixed-dose-rate and its hematological toxicity profile in patients with advanced non-small-cell lung cancer (NSCLC).</p><p><b>METHODS</b>Twenty-one patients received gemcitabine at a fixed dose rate (1200 mg/m2 over 120 min) with carboplatin. Plasma concentrations of gemcitabine were measured by ion-pair reversed-phase high-performance liquid chromatography.</p><p><b>RESULTS</b>The mean value of Cmax in 21 eligible patients was(4.95+/-2.42) microg *ml(-1). The main hematological toxicity was grade III-IV thrombocytopenia and neutropenia. The mean percentages of reduction of WBC, NEC, PLTC and Hb of 21 patients were (38.3+/-38.1)%, (31.3+/-73.6)%, (31.8+/-53.5)% and (12.0+/-12.2)%, respectively. The C(max)of gemcitabine and the percentage of reduction in WBC showed a significant correlation (r2=0.4575, P<0.05). A significant correlation (r2=0.5671, P<0.05) was also observed between the percentage of reduction of PLTC and Cmaxof gemcitabine.</p><p><b>CONCLUSION</b>The results of relationship between Cmax and toxicity profile suggest that gemcitabine administration should be individualized in order to decrease the occurrence of ADR.</p>

Comparison of pharmacokinetics, efficacy and toxicity profile of gemcitabine using two different administration regimens in Chinese patients with non-small-cell lung cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To conduct a randomized comparative trial of pharmacokinetics, efficacy and toxicity profile treatment with 1200 mg/m(2) gemcitabine using standard 30-min infusion or fixed dose rate (FDR) infusion [10 mg/(m(2) x min)] on days 1 and 8 plus carboplatin AUC (area under curve) 5 on day 1 in Chinese non-small-cell cancer patients. Twelve patients were enrolled in this study.</p><p><b>METHODS</b>Plasma gemcitabine concentrations were measured by ion-pair reversed phase high performance liquid chromatography. Antitumoral activity and toxicity of gemcitabine was assessed according to World Health Organization criteria.</p><p><b>RESULTS</b>The obtained mean parameters, such as T(1/2) (elimination half time), AUC, and CL (clearance), were consistent with those reported in literature. Qualified response rate in our study was 33.3% for standard arm and 50% for FDR arm. Additional 50% and 33.3% patients contracted stable disease (SD) in standard arm and FDR arm, respectively. The predominant toxicity was hematologic, and patients in the standard infusion arm experienced consistently more hematologic toxicity.</p><p><b>CONCLUSION</b>Pharmacokinetic and clinical data in this trial support the continued evaluation of the FDR infusion strategy with gemcitabine.</p>

Pharmacokinetics of gemcitabine in Chinese patients with non-small-cell lung cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

To determine the pharmacokinetics of gemcitabine (2',2'-difluorodeoxycytidine) in Chinese non-small-cell lung cancer (NSCLC) patients. Six study subjects were administered gemcitabine at a fixed dose rate of 10 mg/m(2) per min (1200 mg/m(2), two hours infusion), and carboplatin and plasma gemcitabine concentrations were measured by ion-pair reversed-phase high-performance liquid chromatography (HPLC). 3P97 Pharmaceutical Kinetics Software was used for the calculation of pharmacokinetic parameters. The obtained mean parameters, elimination half life (t(1/2)) (10.67+/-3.38 min), area under the curve (AUC) (7.55+/-1.53 (microg x h)/ml), and clearance (CL) (3940.05+/-672.08 ml/min), were consistent with those reported in literature. The hematologic toxicology result showed that the regimen was effective on and tolerated by the patients.

HPLC determination of metformin hydrochloride-related substances / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To develop a HPLC assay for the determination of metformin hydrochloride-related substances.</p><p><b>METHODS</b>The separation was performed on SHIMADZU VP-ODS (250 4.6 mm, 5 microm) column. The mobile phase of dicyandiamide was composed of methyl alcohol-1 mmol x L(-1) sodium dodecylsulfate in 10 mmol x L(-1) phosphate salt solution (60:40) (pH=5.5). The mobile phase of other related substances was composed of methyl alcohol-1 mmol x L(-1) sodium dodecysulfate in 10 mmol x L(-1) phosphate salt solution (55:45)(pH=5.5). The detection wavelength was 232 nm, and the running speed was 0.8 ml min(-1) at room temperature.</p><p><b>RESULT</b>Good resolution of dicyandiamide and main peak was obtained. The test results were reproducible.</p><p><b>CONCLUSION</b>The method is simple, rapid and suitable for the determination of dicyandiamide and other metformin hydrochloride-related substances.</p>