Purpose:To study the relationship of chemosen sitivity in vitro and clinical experience.Methods:To analyze the results of chemosensitivity test in v itro using the MTT assay for 210 cases of five kinds of tumor specimens(85 ova rian cancer, 30 cervical cancer, 26 gastric cancer,41 colorectal cancer and 28 breast cancer), calculate the inhibitory average of each paclitaxel drug to diff erent tumor specimens,then compare the drugs haveing higher inhibitory average w ith the drugs frequently applied clinicaly to that tumor.Results:there is obvious individual variation in in vitro c hemosensitivity test, the variation can be from 0 to more than 60%;however the d rugs having higher inhibitory average correlated to clinical experience.The main theraputic drugs used clinically and also sensitive in in vitro assay were as follows:Taxol,DDP for ovarian cancer; DDP,e-ADM,MMC for cervical cancer ; DDP,5-FU,BLM,MMC for gastric cancer; DDP,MMC,BLM,5-FU for colorectal cancer; e-ADM,ADM,NVB for breast cancer.Conclusions:the chemosensitivity test using the MTT assay may b e useful for individual chemotherapy.

Purpose:To study the pharmacokinetic characteristics and systemic exposure of intraperitoneal chemotherapy drugs for ovarian cancer. Methods:Ten ovarian cancer patients received intraperitoneal chemotherapy with 5 FU 750mg/m 2 and DDP 60mgm 2 a week later after operating at Shanghai Cancer Hospital. The blood samples were extracted at 0.5, 1, 2, 6, 24 hour after infusion and then the concentration of drugs in the samples were analyzed by HPLC and the atomic absorption spectrum methods. Results:The curve of concentration via time of two drugs could be described well by a one compartment model with first order absorption. The pharmacokinetic parameters were: 5 FU: Ke = 0.45?0.18 /h, Ka = 7.59?4.63 /h, T(peak) = 0.87?0.30 h, C(max) = 2.46 ? 1.12 ?g/ml, AUC = 8.38?4.71 ?g?h/ml, Vd = 316?69.4 ml/kg; DDP: Ke = 0.014?0.01 /h, Ka = 1.31?1.03 /h, T(peak) = 4.72?2.81 h, C(max) = 0.85?0.28 ?g/ml, AUC = 85.6?55.7 ?g?h/ml, Vd = 60.3?32.6 ml/kg. The AUC 0～24h of 5 FU was 8.4 ?g?h/ml. The AUC 0～24h of DDP was 14.4 ?g?h/ml. Conclusions:The systemic exposure of 5 FU in intraperitoneal chemotherapy was not lower than in intravenous injection on the pharmcokinetics, and that of the DDP was lower.

OBJECTIVETo study the concentration change of chemotherapeutic agents in plasma and tissue after intraarterial and intravenous injection.

METHODSTen mature female New Zealand rabbits were divided randomly into two groups. Fluorouracil, etopiside, and cisplatin were injected into the rabbits through the ear vein in one group and through the internal iliac artery in the other group. Blood samples and the uterus tissue specimens were collected at various time points after injection. Drug concentration in plasma and tissue was determined by high performance liquid chromatography (HPLC) method. The data were analyzed by the pharmacokinetic program 3P97.

RESULTSRegular concentration change of the three drugs in plasma and tissue was observed after the intravenous and intraarterial injection, which met the two - compartment model. The pharmacokinetic parameters of the three drugs after intravenous and intraarterial injection were different. The peak concentration in plasma after intraarterial injection was lower than that after intravenous injection and the peak concentration and area under curve (AUC) value in tissue after intraarterial injections were higher than those after intravenous injection.

CONCLUSIONIntraarterial chemotherapy has advantages to intravenous chemotherapy in fluorouracil, etopiside and cisplatin. These advantages depend on the drug pharmacological properties.

Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Cisplatin ; administration & dosage ; blood ; pharmacokinetics ; Etoposide ; administration & dosage ; blood ; pharmacokinetics ; Female ; Fluorouracil ; administration & dosage ; blood ; pharmacokinetics ; Injections, Intra-Arterial ; Injections, Intravenous ; Rabbits

Background and purpose:Huachansu has been widely used to treat cancer in China.But maximum tolerated dose(MTD) of huachansu is still not well defined.The purpose of this study was to conduct a Phase Ⅰ study to determine the MTD of huachansu in the treatment of patients with hepatocellular carcinoma,non-small cell lung or pancreatic cancer.Toxic profile and efficacy of huachansu were also assessed qualitatively.Methods:Huachansu was intravenously administered to patients with stage Ⅲ/Ⅳ hepatocellular carcinoma,non-small cell lung cancer,or pancreatic cancer.Each cycle consisted of daily huachansu for 14 days with an interval of 7 days between two cycles.2 or more cycles were delivered to the patients if no severe adverse event occurred.The planned dose escalation schedule for huachansu was as follows,10,20,40,60,90 and 120 ml/(m2?d).Results:Fifteen patients(3 at each level) have been recruited to the study(11 with hepatocellular carcinoma,2 with pancreatic cancer,and 2 with lung cancer).There were no dose limiting toxicities found after dose level 5.Among all these patients,the efficacy in 14 patients could be valued,in which,6 were SD(42.9%),8 were PD(57.1%).At dose level 1,there was one patient with hepatocellular carcinoma achieving a 20% reduction in tumor mass that lasted 11 months,6 of 15(42.9%) patients with stable disease and 8 of 15(57.1%) with progress disease after the treatment.Conclusions:To date,dose limiting toxicity has not been seen with doses up to eight times higher than that typically used before.Of interest, several patients had prolonged stable disease or minor tumor shrinkage.

BACKGROUNDStudies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs (miRNAs). We investigated the role of miR-503 in the development of cisplatin resistance in human gastric cancer cell lines.

METHODSMiR-503 expression was measured by quantitative real-time PCR. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) and clonogenic assays were used to examine changes in cell viability and the drug resistance phenotype of cancer cells associated with upregulation or downregulation of the miRNA. A dual-luciferase activity assay was used to verify target genes of miR-503. Immunohistochemistry, Western blotting analysis, and a flow cytometric apoptosis assay were used to elucidate the mechanism by which miR-503 modulates drug resistance in cancer cells.

RESULTSMiR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell lines. Additionally, downregulation of miR-503 in the cisplatin (DDP)-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor (IGF1R) and B-cell lymphoma 2 (BCL2) expression compared with the parental SGC7901 cell line. An in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin. The luciferase activity of reporters driven by IGF1R and BCL2 3'-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of miR-503. Enforced miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins, inhibited proliferation, and sensitized the cells to DDP-induced apoptosis.

CONCLUSIONOur findings suggest that hsa-miR-503 modulates cisplatin resistance of human gastric cancer cells at least in part by targeting IGF1R and BCL2.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Humans ; Immunohistochemistry ; MicroRNAs ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Real-Time Polymerase Chain Reaction ; Stomach Neoplasms ; genetics