OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of topotecan, camptothecin analogue topoisomerase I inhibitor, as the combination therapy with platinum in patients with recurrent epithelial ovarian carcinoma and primary peritoneal carcinomatosis. METHOD: In this study, patients who were treated with topotecan between January 2000 and June 2007 at Asan Medical Center, Seoul, Korea were reviewed. Fifty-one patients with recurrent ovarian carcinoma and peritoneal carcinomatosis were included. These patients' data were analyzed by review of medical records and pathologic and laboratory reports retrospectively. Response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for patients with measurable disease and CA-125 response criteria for patients with non-measurable disease. The toxicities were evaluated according to NCI CTC (Common Toxicity Criteria) version 3.0. RESULTS: The mean age of patients was 53.4 years (ranged between 37 and 69). Forty-four patients had been evaluated by RECIST criteria. The overall response rate was 22.8% (10/44). Platinum-sensitive patients showed more favorable response rate (26.9%) than platinum-resistant patients (16.7%), however, it was not significant statistically (p=0.425). Platinum-sensitive group had significantly longer response duration (12.14 vs. 3.33 months, p=0.022) and time-to-progression (11.34 vs. 7.33 months, p=0.042) than platinum-resistant group. Heavily pretreated group, three or more prior regimens were used, had no significant differences from another group. The most common adverse effect of topotecan in combination with platinum was hematologic toxicity; grade 3/4 neutropenia was 30.6%, anemia was 42.7%, and thrombocytopenia was 8.37% in total 265 cycles of chemotherapy, however, it was tolerable. CONCLUSION: Topotecan in combination with platinum is considered as effective regimen with acceptable toxicity in treating recurrent epithelial ovarian carcinoma and primary peritoneal carcinomatosis who have failed previous treatment with platinum-containing chemotherapy.
Anemia ; Camptothecin ; Carcinoma ; DNA Topoisomerases, Type I ; Humans ; Korea ; Medical Records ; Neoplasms, Glandular and Epithelial ; Neutropenia ; Ovarian Neoplasms ; Platinum ; Retrospective Studies ; Thrombocytopenia ; Topotecan

Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Camptothecin ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Humans ; Lung Neoplasms ; drug therapy ; Structure-Activity Relationship ; Topotecan ; chemistry ; therapeutic use ; Tumor Cells, Cultured ; drug effects

Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; DNA Damage ; Humans ; Topoisomerase I Inhibitors ; Topotecan ; chemical synthesis ; chemistry ; pharmacology ; Tumor Cells, Cultured ; drug effects

No abstract available.
Camptothecin ; Recurrence ; Small Cell Lung Carcinoma

OBJECTIVETo establish the mothod to dectect the microdialysis recovery of HCPT and to investigate the influencing factors, thus to supply experimental basis for in-vivo microdialysis of HCPT.

METHODThe in vitro recovery of HCPT was detected by concentration difference method (increment method and decrement method). The influence of flow rates, medium concentration and temperature on the HCPT recovery and the stability were studied.

RESULTThe recovery detected by increment method was the same as by decrement method. The recovery was independent of HCPT concentrations in the medium. The hydroxycamptothecine recovery had good stability and increased as the temperature rose.

CONCLUSIONMicrodialysis sampling can be used for the pharmacokinetic study of HCPT. Retrodialysis can be used for the determination of the HCPT in vivo recovery.

Camptothecin ; analogs & derivatives ; chemistry ; isolation & purification ; Drug Stability ; Microdialysis ; Temperature

Surgery is the best and the only treatment modality for cure if a patient has resectable gastric cancer. The outcome can be improved by a strategy of perioperative (neoadjuvant or adjuvant) chemotherapy or chemoradiotherapy. Whereas, advanced gastric cancer is treated primarily with chemotherapy; however, no chemotherapy regimen has been considered a standard. First-line chemotherapy generally includes fluoropyrimidine and cisplatin, sometimes with the addition of a third drug (epirubicin or docetaxel). In second-line setting, chemotherapy with single-agent irinotecan or docetaxel has emerged as a new standard of care. With improved understanding of the biology of gastric cancer and the identification of key signaling pathways, a number of promising molecularly-targeted agents have been studied that broaden the therapeutic options in the future. Regardless of the extent of disease or treatment modality, a multidisciplinary team approach is always desired since it can provide best treatment options for the patients.
Biology ; Camptothecin ; Chemoradiotherapy ; Cisplatin ; Humans ; Standard of Care ; Stomach Neoplasms ; Taxoids

AIMTo improve the profile of 20 (S)-camptothecin, a series of 20-O-linked camptothecin phenoxyacetic acid ester derivatives have been designed.

METHODSThese derivatives were synthesized by the method of acylation. Their chemical structures were confirmed with 1HNMR, IR, MS, and HRMS. The cytotoxicities of the compounds were tested by MTT assay. The in vivo antitumor activities of these esters were evaluated against mouse liver tumor H22 in mice.

RESULTSTwelve derivatives of camptothecin ester are new compounds.

CONCLUSIONIn vitro and in vivo antitumor activity has indicated that some derivatives appeared significantly more effective than topotecan in the H22 mouse liver tumoral model.

Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Esters ; chemistry ; Female ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms ; pathology ; Mice ; Mice, Inbred ICR ; Molecular Structure ; Neoplasm Transplantation ; Topotecan ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the effects of nitrogen concentration on the camptothecin (CPT) content in Camptotheca acuminata seedlings:

METHODThe seedlings of C. acuminata with 6 pair of leaves were subjected to five nitrogen concentrations treatments by sand culture in a greenhouse. The CPT content in the seedlings was determined by HPLC on the 20th, 35th, 50th, 65th and 80th day respectively.

RESULTThe CPT content in the young leaves of C. acuminata seedlings supplied with different nitrogen concentration was significantly higher than that in other organs (P < 0.01), and it showed a single peak curve with the time course, the highest CPT content was observed on the 50th day after treatment. The CPT content in the young leaves obviously declined with increasing nitrogen concentration, and it reached the highest (6.72%) when nitrogen concentration was 4 mmol x L(-1), equal to 1.1 times that of 16 mmol x L(-1) nitrogen.

CONCLUSIONThe results demonstrate that proper deficient nitrogen stress can significantly enhance CPT accumulation in young leaves of C. acuminata seedlings.

Camptotheca ; drug effects ; metabolism ; Camptothecin ; metabolism ; Chromatography, High Pressure Liquid ; Nitrogen ; pharmacology ; Seedlings ; drug effects ; metabolism

PURPOSE: CKD-602, a newly developed water-soluble campthotecin analogue, is a anticancer agent which act as a DNA topoisomerase I inhibitor. CKD-602 is known as more potent and tolerable agent. The main purposes of this study were to measure the cytotoxic effect of CKD-602 on the oral cancer cell lines and to evaluate the apoptotic aspect of dead cells. MATERIALS AND METHODS: To determine the cytotoxic effect of CKD-602 on the oral cancer cell lines in comparison with various cell lines, such as lung cancer and colon cancer cell lines, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was performed. And apoptosis was analyzed using fluorescence-activated cell sorting(FACS) system. RESULTS: CKD-602 decreased the viability of malignant cells in a dose dependent manner and in a time dependent manner. CKD-602 showed excellent cytotoxicity to the oral cancer cell lines. Also, apoptotic portion was increased in a dose dependent manner. CONCLUSION: These findings indicated that CKD-602 induced apoptotic cell death in the various cell lines including oral cancer cell lines. From the results, it was suggested that CKD-602 would be a potential therapeutic agent for the oral cancer. More successive researches on the anticancer effect of CKD-602 should be performed.
Apoptosis ; Camptothecin ; Cell Death ; Cell Line* ; Colonic Neoplasms ; DNA Topoisomerases, Type I ; Lung Neoplasms ; Mouth Neoplasms*

Camptothecin is a strong anti-tumor compound isolated from Camptotheca acuminata. One of the most important way for the production of Camptothecin is by cell cultures of Camptotheca acuminata. The effect of Cu2+ on camptothecin accumulation in Camptotheca acuminata cell line was described in this paper. The results showed that the optimum CuCl2 concentration in B5 medium was 0.008 mg/mL, which increased camptothecin production for 30 times compare to the control while has no inhibitive effects on cell growth, at the same time, the peroxidase activity was increased and the anthocyanidin accumulation was inhibited. The promotive effects of Cu2+ on camptothecin accumulation in light was higher than that in dark.
Anthocyanins ; biosynthesis ; Antineoplastic Agents, Phytogenic ; biosynthesis ; Camptotheca ; growth & development ; metabolism ; Camptothecin ; biosynthesis ; Copper ; pharmacology ; Light