Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D01061 (CPT-11)
 1,899 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of ICRF-154 in combination with 11 anticancer agents on four human leukaemia cell lines. Cells were incubated for 3 days in the presence of two drugs (ICRF-154 and one other), and cell growth inhibition was determined by MTT assay. Effects of drug combinations at the ID50 level were analysed using the isobologram method (Steel). In the lymphoblastic leukaemia cell lines, MOLT-3, HSB, and B-ALL, supra-additive effects were observed for ICRF-154 in combination with amsacrine, bleomycin, doxorubicin, and etoposide. Additive effects were observed for its combinations with cisplatin, CPT-11, cytosine arabinoside, 5-fluorouracil, mitomycin C, and vincristine. Sub-additive to protective effects were observed in combination with methotrexate. In an erythroleukaemia cell line, K-562, no drug showed supra-additive effects with ICRF-154, while sub-additive to protective effects were observed for ICRF-154 in combination with cisplatin and methotrexate. The other drugs showed additive effects with ICRF-154. These results indicate that the combined effects of ICRF-154 with other agents vary, depending on the cell line. Against lymphoid malignancies, ICRF-154 would be advantageous when administered simultaneously with many anticancer agents. Of such agents, amsacrine, bleomycin, doxorubicin, and etoposide are the most suitable, while methotrexate is least suitable for such combined treatment.
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PMID:The effects of ICRF-154 in combination with other anticancer agents in vitro. 150 99

CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy camptothecin, is a newly developed water-soluble camptothecin derivative now undergoing phase-II evaluation. In an attempt to establish whether the combination of CPT-11 with other standard anti-cancer agents would be of any benefit, we studied the effects of CPT-11 in combination with 11 other anti-cancer agents on a human T-cell leukemia cell line, MOLT-3, in culture. We used both CPT-11 and SN-38 (active substance of CPT-11 in vivo), for our study. Cells were incubated for 3 days in the presence of 2 drugs (CPT-11 or SN-38 and another drug) and cytotoxic effects were determined by MTT assay. The effects of drug combinations on ID50 were analyzed by an improved isobologram method. Supra-additive and marginal supra-additive effects (synergism) were observed for CPT-11 in combination with cisplatin, cytosine arabinoside and mitomycin C. Additive effects were observed for its combination with amsacrine, bleomycin, doxorubicin, etoposide, 5-fluorouracil, mitoxantrone and vincristine. Alternate sub-additive and protective effects (antagonism) were observed for CPT-11 in combination with methotrexate. Similar tendencies were observed for SN-38 in combination with other agents. These results suggest that CPT-11 in simultaneous administration with a majority of anti-cancer agents has an advantage for cytokilling. Of these agents, cisplatin, cytosine arabinoside and mitomycin C are most suitable for simultaneous administration with CPT-11.
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PMID:Effects of CPT-11 in combination with other anti-cancer agents in culture. 153 25

The in vitro sensitivity testing for four human colorectal cancer cell lines to seven chemotherapeutic drugs including CPT-11, derivative of camptothecin, and its active form SN-38 were determined. MTT assay revealed that SN-38 was the most active for all four cell lines tested and its IC50's were very close to its clinically achievable plasma concentration. Relationship between exposure time and cytocidal effect of SN-38 was also investigated using MTT assay, topoisomerase-I (Topo-I) immunoblot analysis and DNA relaxation-assay, showing that IC50 value, Topo-I protein and Topo-I activity were decreased soon after the administration of SN-38 and reached to the plateau level at 24 hours. We conclude that SN-38 is very potent for colorectal cancer and the optimal schedule of CPT-11 can be the more continuous form of administration capable of as long as 24 hours exposure of its active metabolite, SN-38.
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PMID:[Antitumor effect of SN-38, active form of CPT-11, on human colorectal cancer cell line]. 806 Jan 34

To investigate the effects of CPT-11 in combination with other anticancer agents, a human Burkitt's lymphoma cell line, Dauji, was incubated for 3 days in the presence of SN-38 (active substance of CPT-11) and the combined drug and cell growth inhibition was determined by MTT assay. The effects of the drug combinations at ID50 were then analyzed by isobologram (Steel and Peckham). A supra-additive (synergistic) effect was observed for SN-38 in combination with carboplatin, cisplatin, cytosine arabinoside, and mitomycin C. An additive effect was observed for its combination with bleomycin, etoposide, 5-fluorouracil, and mitoxantrone. Additive and sub-additive (antagonistic) effects were observed in combination with doxorubicin. A Sub-additive effect was observed in combination with methotrexate and vincristine.
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PMID:[Effects of SN-38 in combination with other anticancer agents against Dauji cells]. 806 Jan 35

In vitro studies with drug combinations of carboplatin and other anticancer agents were carried out in MOLT-3 human lymphoblastic leukemia and HL-60 human promyelocytic leukemia cell lines. Cells were incubated for 3 days in the presence of various concentrations of carboplatin and other drugs and cell growth inhibition was determined by MTT assay. The antitumor effects of the drug combinations at ID50 were analyzed using an improved isobologram. In MOLT-3 cells, supra-additive (synergistic) effects were observed for carboplatin in combination with cytosine arabinoside, mitoxantrone and CPT-11. Additive effects were observed for combinations of carboplatin with bleomycin, daunorubicin, doxorubicin, etoposide, 6-mercaptopurine, and vincristine. Sub-additive and protective (antagonistic) effects were observed with methotrexate. Synergistic or antagonistic effects for combinations of carboplatin and CPT-11, cytosine arabinoside, mitoxantrone and methotrexate were also observed in HL-60 cells. These findings suggest that carboplatin has additive or synergistic cytotoxic effects with most of the agents tested. Determination of the usefulness of these drug combinations awaits appropriate in vivo experiments that should assess both tumorcidal effects and possible increased toxicity. The simultaneous administration of carboplatin and methotrexate would be of little effect. To find optimal schedules for this combination, further pre-clinical studies of various combinations schedule would appear to be warranted.
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PMID:Effects of carboplatin in combination with other anticancer agents on human leukemia cell lines. 842 87

To determine the optimal combination of commonly used anticancer agents with 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of 7-ethyl-10-[4(1-piperidino)-1-piperidino] carbonyloxy camptothecin (CPT-11), for chemotherapy of lung cancer, we studied the effects of SN-38 in combination with six representative anticancer agents on the human small cell lung cancer (SCLC) cell line, NCl N417, and the non-small cell lung cancer (NSCLC) cell line, PC-9. The anticancer activity was evaluated by MTT assay and the effects of drug combinations on ID50 were analyzed by an improved isobologram method. In the SCLC cell line, supra-additive effect was observed for SN-38 in combination with cisplatin, etoposide (VP-16) and paclitaxel (Taxol). An additive effect was observed for its combination with bleomycin. Sub-additive and protective effects were found in combination with adriamycin (ADR) and 5-fluorouracil (5-FU). In the NSCLC cell line, supra-additive and marginal supra-additive effects were found for SN-38 in combination with VP-16, ADR, 5-FU and bleomycin. The others showed additive effects with SN-38. No drug showed sub-additive and protective effects with SN-38. These results suggest that all the drugs we selected can be used with SN-38 simultaneously for NSCLC, while for SCLC, cisplatin, VP-16 and Taxol are the most suitable for combination with SN-38.
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PMID:Effect of CPT-11 in combination with other anticancer agents in lung cancer cells. 909 27

In an effort to evaluate the efficacy of CPT-11 on prostate cancer we utilized the PC-3 human prostate cancer cell line (in vitro), and the Dunning R3327 AT-3 rat prostate cancer tumor line (in vivo). PC-3 cells were initially seeded and cultured prior to the addition of CPT-11 at different concentrations 48 and 120 h later. After an additional 48 h the number of cells was determined using MTT dye uptake. CPT-11 at concentrations between 10 ng/ml and 50 micrograms/ml inhibited the growth of the PC-3 prostate human cancer cell line up < 0.001). AT-3 prostate rat cancer cells were injected into the right flank of 30 Copenhagen X Fischer rats, divided into treated and control groups. A total dose of CPT-11 (200 mg/kg) was given intraperitoneally, administered 1, 3 and 5 days postimplantation. We evaluated tumor growth by size and weight (5 and 10 days postimplantation). A total dose of 200 mg/kg inhibited the rapid growth of the prostate AT-3 tumor in vivo (p < 0.001).
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PMID:Antitumor effect of CPT-11, a new derivative of camptothecin, against human prostate cancer (PC-3) in vitro and prostate rat tumor (AT-3) in vivo. 912 Dec 21

A cell line derived from human endometrial clear cell adenocarcinoma was newly established and named TEN. The tumor cells were obtained from uterine body of a 74-year-old who had been undergone an abdominal simple hysterectomy. The histologic features of the tumor cells showed abundant clear cytoplasm with diastase digested glycogen granule growing in solid nest and tubular pattern. The TEN cells were continuously propagated in vitro during the past 45 months and they were at 75th passage. They grew in a monolayered sheet with a doubling time of about 53 hours. The TEN cells resembled the structure of the original tumor and had abundant glycogen granules, lipid droplets in the cytoplasm. The histopathology of the transplanted tumor in SCID mice resembled that of the original tumors. The TEN cells secreted a high content of CA125. Immunohistochemically, the TEN cells had c-erbB-2 and Cathepsin D immunoreactivity in some parts of the cell population. But they did not have estrogen, progesterone and EGF receptor. Sensitivities of the TEN cells to a variety of anti-cancer drugs were examined. In in-vitro tests, MTT assays employed. The results suggested that the TEN cells were not sensitive to any of 13 agents. On the other hand, in-vivo sensitivity test of transplanted tumor in SCID mice, the tumors were sensitive to CPT-11 and paclitaxel. We conclude that the TEN cell line will be effective material for chemosensitivities against the endometrial clear cell adenocarcinoma.
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PMID:Characterization of a newly established human tumor cell line (TEN) from a patient with clear cell carcinoma of the uterine body and its sensitivity to anti-cancer agents. 943 40

Irinotecan (CPT-11) is a semisynthetic camptothecin derivative with a broad spectrum of anti-tumour activity. Carboxylesterase (CE) catalyses the conversion of CPT-11 to SN-38 (7-ethyl-10-hydroxycamptothecin), the active form of CPT-11. The antiproliferative effects of CPT-11 and SN-38, CE-activity and topoisomerase I protein expression were investigated in five human small-cell lung cancer (SCLC) cell lines and four human non-small-cell lung cancer (NSCLC) cell lines. Antiproliferative activity, expressed as IC50 values, was determined using the MTT assay. CPT-11 was significantly more active in SCLC than in NSCLC cell lines (P = 0.0036), whereas no significant difference between histological types was observed with SN-38. A significant correlation (r2 = 0.52, P = 0.028) was observed between CE activity and chemosensitivity to CPT-11 but not to SN-38, and significantly higher CE activity was observed in SCLC compared with NSCLC cell lines (P = 0.025). Western blotting experiments showed topoisomerase I protein expressions within a factor of 2, and a granular nuclear staining was detectable in all cell lines by immunocytochemistry of cytospins. No correlation was observed between protein expression and sensitivity to CPT-11 or SN-38. Cellular and medium concentrations of CPT-11 and SN-38 were measured by high-performance liquid chromatography (HPLC) in one SCLC cell line with high CE activity and high sensitivity to CPT-11, and one NSCLC cell line with low sensitivity to CPT-11 and CE activity. Intracellular concentrations of CPT-11 and SN-38 were higher in the SCLC cell line, and this was associated with an increase in cellular uptake of CPT-11 compared with the medium, and an increased intracellular formation of SN-38. In conclusion, CE activity appears to be associated with higher sensitivity to CPT-11 in human lung cancer cell lines and may partly explain the difference in the in vitro sensitivity to CPT-11 between SCLC and NSCLC cells. The assessment of CE activity in clinical material of lung cancer patients undergoing treatment with CPT-11 may be warranted. However, other mechanisms may influence sensitivity to CPT-11, possibly including drug transport.
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PMID:Determinants of CPT-11 and SN-38 activities in human lung cancer cells. 964 29

To investigate the possible involvement of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and/or other glutathione S-conjugate export pump (GS-X pump) family members on the active efflux of irinotecan [(7-ethyl-10-[4-(1-piperidino)-1-pipertidino)-1-piperidino]carb onylox y camptothecin (CPT-11)] and its metabolites, as well as their contribution to the acquisition of resistance, we studied the uptake of CPT-11, its active metabolite SN-38, and glucuronide conjugate (SN38-Glu) using membrane vesicles from human epidermoid KB-3-1-derived cell lines. These lines included KB-C2, C-A500, and KCP-4, which overexpress P-gp, MRP, and the unidentified GS-X pump, respectively. The carboxylate form of SN-38 exhibited significant ATP-dependent transport, with a Michaelis constant of 17 microM, into membrane vesicles from C-A500 but not from other cell lines. Among these KB-derived cells, significant ATP-dependent uptake of the carboxylate form of CPT-11 was only observed in KB-C2 vesicles. In addition, the uptake of the lactone and carboxylate forms of SN38-Glu into membrane vesicles from C-A500 and KB-C2, but not KCP-4, was ATP dependent, although the transport activity in C-A500 was much higher than that in KB-C2. The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay revealed that the resistance of KB-C2 to CPT-11 and SN-38, compared with that of KB-3-1, was 6.3- and 6.8-fold, respectively; the corresponding figures for C-A500 were 12- and 27-fold, respectively, whereas those for KCP-4 were 2.3- and 20-fold, respectively. These results suggest that MRP and P-gp are involved in the active efflux of SN-38 and CPT-11, respectively, from human KB-derived cells. In addition, a difference in substrate specificity among GS-X pump members was demonstrated.
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PMID:Active efflux of CPT-11 and its metabolites in human KB-derived cell lines. 991 83


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