Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor effects of the camptothecin (CPT) derivative CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin , were tested on human tumor xenografts in nude mice. CPT-11 showed antitumor activity higher than that of Adriamycin, 5-fluorouracil, or futraful, with little or no reduction of body weight being observed in the mice. The growth of colon adenocarcinoma Co-4 was significantly inhibited after a single i.v. injection of CPT-11 at 25, 50, or 100 mg/kg. The single i.v. injection was also significantly effective against mammary carcinoma MX-1 and gastric adenocarcinoma St-15. All of the mice bearing MX-1 tumors were cured by the administration of CPT-11 every 4 days for a total of three treatments at a total dose of 200 mg/kg given i.v. or of 400 mg/kg given p.o. Three i.v. or oral treatments were also effective against Co-4, St-15, gastric adenocarcinoma SC-6, and squamous-cell lung carcinoma QG-56. To achieve the same efficacy attained by i.v. injection, however, oral doses 2-4 times higher than the i.v. doses were required. When the total dose was fixed at 100 mg/kg, a triple i.v. injection was most effective, followed by a single i.v. injection and, finally daily p.o. administration for 10 days. Although SN-38 (7-ethyl-10-hydroxycamptothecin), a metabolite of CPT-11, showed much stronger cytotoxic activity in vitro than did CPT-11, its antitumor effects were similar, if not inferior, to those of CPT-11 in vivo at the same dose level. CPT-11 was converted into SN-38 by human tumors, but the sensitivity of these tumors to CPT-11 in vivo was independent of their ability to produce SN-38. These results suggest that CPT-11 may be clinically effective, depending on the schedule of administration, but that its effectiveness is not related to the ability of the tumor to produce SN-38.
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PMID:Antitumor activity of a camptothecin derivative, CPT-11, against human tumor xenografts in nude mice. 185 76

The antimetastatic effect of a new water-soluble derivative of camptothecin, 7-ethyl-10-(4-(1-piperidino)-1-piperidino) carbonyloxy-camptothecin (CPT-11), were examined in several metastatic murine tumor systems. Intravenous (i.v.) injection of CPT-11 into BALB/c mice inhibited lung metastasis by i.v. inoculated, metastatic colonic adenocarcinoma 26 (C26) cells, C26NL-17, in BALB/c mice. This treatment was also effective in C57BL/6 mice against lung metastasis by i.v. inoculated B16-F10 and B16-BL6 cells, highly metastatic variants of the B16 melanoma. Furthermore, intraperitoneal (i.p.) injection of CPT-11 significantly inhibited the growth of C26NL-22 cells, a highly metastatic variant of C26, inoculated subcutaneously (s.c.) into the left front footpads of BALB/c mice. Also, i.p. or i.v. injection of CPT-11 effectively inhibited the growth of 3LL tumors inoculated s.c. into the hind footpads of C57BL/6 mice. Moreover, following s.c. inoculation of either C26NL-22 or 3LL cells, combined surgical excision of the primary tumor and either i.p. or i.v. CPT-11 injections given before or after surgery markedly inhibited the formation of pulmonary metastases. These results show that a new derivative of camptothecin, CPT-11, has a potent inhibitory effect against both spontaneous and experimental lung metastasis.
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PMID:Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, CPT-11, in mice. 337 Jul 38

CPT-11, a semisynthetic derivative of camptothecin, exhibited strong antitumor activity against lymphoma, lung cancer, colorectal cancer, gastric cancer, ovarian cancer, and cervical cancer. CPT-11 is a pro-drug that is converted to an active metabolite, SN-38, in vivo by enzymes such as carboxylesterase. We synthesized a water-soluble and non-pro-drug analog of camptothecin, DX-8951f. It showed both high in vitro potency against a series of 32 malignant cell lines and significant topoisomerase I inhibition. The anti-proliferative activity of DX-8951f, as indicated by the mean GI50 value, was about 6 and 28 times greater than that of SN-38 or SK&F 10486-A (Topotecan), respectively. These three derivatives of camptothecin showed similar patterns of differential response among 32 cell lines, that is, their spectra of in vitro cytotoxicity were almost the same. The antitumor activity of three doses of DX-8951f administered i.v. at 4-day intervals against human gastric adenocarcinoma SC-6 xenografts was greater than that of CPT-11 or SK&F 10486-A. Moreover, it overcame P-glycoprotein-mediated multi-drug resistance. These data suggest that DX-8951f has a high antitumor activity and is a potential therapeutic agent.
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PMID:A new water-soluble camptothecin derivative, DX-8951f, exhibits potent antitumor activity against human tumors in vitro and in vivo. 755 2

In recent years, the incidence of endometrial cancer has tended to increase gradually in Japan. Most cases (early cancer of stage I and II) are treated by hysterectomy alone, and the prognosis has been relatively good. From analysis of the poor prognostic factors in endometrial cancer, we understood that additional therapy is necessary for patients who have the following factors: degree of differentiation: G3; invasion to > 1/2 myometrium; metastases to pelvic or para-aortic lymph node, isthumus-cervix extension; surgical stage III and more. However, for patients with advanced inoperable and recurrent cancer, a radiotherapy, is not so sensitive to endometrial cancer has been used. A first line establish a chemotherapy has not been established either. Various attempts have been made to establish a chemotherapy for endometrial cancer. As a result, adriamycin (ADR) and cisplatin (CDDP) have proved effective as single agents. For patients with early cancer who have the poor prognostic factors mentional above, irradiation and polychemotherapy regimens (CAP and AP) are effective. Since the progression of endometrial cancer is dependent on sex steroid hormones, antitumor effects of Medroxyprogesterone acetate (MPA) are expected to be effective for patients with estrogen receptor (ER) positive and progesterone receptor (PR) positive cancer, or with well-differentiated adenocarcinoma (G1 type) histologically. Although several forms of therapy are capable of inducing objective remission as adjuvant treatment, all treatment for advanced and recurrent disease remains palliative, and responses and survival for patients treated with irradiation and chemotherapy remain short. Furthermore, we should examine new methods such as new drug application of key drugs like ADR and Pt pharmaceutical preparation, improvement of Dose intensity of the key drugs and Biochemical modulation, CPT-11, Taxol and assembly of key drugs, along with the Circadian approach in the light of Biochronology.
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PMID:[Chemotherapy of uterine endometrial cancer]. 766 68

The projected cure rate for patients who develop lung cancer in 1993 is only 13%. The majority of these patients have metastatic disease at the time of diagnosis, and are therefore ineligible for curative surgery. Among the minority of patients who undergo surgical therapy with curative intent, the majority experience relapse in metastatic sites. Patients with metastatic disease cannot be cured with currently available therapies. Recent randomized studies suggest that cisplatin-based chemotherapy regimens can prolong survival in patients with metastatic non-small cell lung cancer and small cell lung cancer. It was thus logical to evaluate cisplatin-based chemotherapy in early disease stages. Many randomized studies have compared radiation therapy alone with radiation plus cisplatin-based chemotherapy in locally advanced, inoperable, stages IIIA and IIIB non-small cell lung cancer. Most, but not all, of these studies show a survival benefit for the combined-modality approach. Although the improvement in median length of survival in these studies is modest, long-term survival rates are often doubled or tripled. The optimal chemoradiotherapy combination is unknown. Fewer randomized trials have evaluated cisplatin-based chemotherapy as an adjuvant to surgery in operable stages I through IIIA disease. A trial of the Lung Cancer Study Group comparing postoperative cyclophosphamide/doxorubicin/cisplatin with immunotherapy in stages II and IIIA adenocarcinoma and large cell carcinoma showed a small survival advantage for the chemotherapy. A European postoperative randomized study comparing cisplatin-based chemotherapy with no therapy also showed a survival advantage for chemotherapy, as did a small ongoing study from M.D. Anderson Cancer Center (Houston, TX) with preoperative chemotherapy. However, there are many negative randomized studies evaluating postoperative chemotherapy, especially with non-cisplatin-based regimens, and further studies are obviously needed. Many new agents have produced exciting preliminary results. Response rates in excess of 20% were reported for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), irinotecan (CPT-11), topotecan, and gemcitabine. Studies in the next few years will help to define the ultimate role of these agents. Further developments in understanding the biology (and molecular biology) of lung cancer are leading to preclinical studies of antigrowth factors and genetic therapy.
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PMID:The treatment of non-small cell lung cancer: current perspectives and controversies, future directions. 805 74

The new bis-naphthalimide antitumor agent (R,R)2,2'-[1,2-ethanediylbis[imino(1-methyl-2.1-ethanediyl)]-bis(5 -nitro 1H-benz[de]-isoquinoline-1,3-2H) dione] dimethanesulfonate (DMP 840) was evaluated against parental and multidrug-resistant human KB cell lines in vitro and against these lines growing as xenografts in immune-deprived mice. In vitro, KB8-5 cells were 50-fold resistant to vincristine but only 16-fold resistant to DMP 840 as measured by clonogenic survival. For in vivo evaluation, DMP 840 was given by i.v. injection daily for 9 days or for 5 days/week for 2 consecutive weeks [(dx5)2]. In contrast to the cross-resistance of KB cell lines in vitro, both KB3-1 and KB8-5 tumors were highly and equally sensitive to DMP 840; only KB3-1 xenografts demonstrated sensitivity to vincristine, which was consistent with the in vitro results. DMP 840 was also evaluated against a panel of human tumors comprising colon adenocarcinoma and rhabdomyosarcoma xenografts. Against eight lines of colon adenocarcinoma, DMP 840 caused a high frequency of partial and complete regressions in two lines and significant inhibition of growth in two lines. DMP 840 caused complete regressions in five of six lines of advanced rhabdomyosarcomas, demonstrating a broad range of effective dose levels. The pattern of activity against this tumor panel was similar but not identical to that of two inhibitors of topoisomerase I. There was no cross-resistance to DMP 840 in xenografts selected for resistance to vincristine or in a rhabdomyosarcoma selected for resistance to the topoisomerase I inhibitor topotecan. In contrast, a colon tumor selected for topotecan resistance was completely resistant to DMP 840. Slight cross-resistance to DMP 840 was demonstrated in a rhabdomyosarcoma xenograft that was selected for primary resistance to melphalan and was cross-resistant to topoisomerase I inhibitors. The pattern of activity and cross-resistance in these tumors was compared with that shown by two agents that inhibit topoisomerase I: topotecan and CPT-11.
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PMID:Evaluation of a novel bis-naphthalimide anticancer agent, DMP 840, against human xenografts derived from adult, juvenile, and pediatric cancers. 828 18

Irinotecan (CPT-11) is a semi-synthetic derivative of camptothecin currently in clinical trials. In vitro, CPT-11 presented preferential cytotoxicity toward some solid tumor cells (mouse colon 38 and pancreas 03; human pancreas MIA PaCa-2) as compared to leukemia cells (L1210), whereas SN-38, a metabolite of CPT-11, was not solid tumor selective. In vivo, schedule of administration studies in P388 leukemia and mammary adenocarcinoma 16/C (MA16/C) showed that CPT-11 was not markedly schedule dependent. In order to determine its spectrum of anticancer activity, CPT-11 was evaluated against a variety of mouse and human tumors. The end points used were total log cell kill (Lck) for solid tumors and increase in life span (% ILS) for leukemia. Intravenous CPT-11 was found highly active against both early and advanced stage pancreatic ductal adenocarcinoma 03 (P03), with 60% long-term survivors and 100% complete regressions, respectively. Other responsive tumors included: colon adenocarcinomas 38 and 51 (both 1.0 Lck); MA16/C (3.4 Lck); MA13/C (1.0 Lck); human Calc18 breast adenocarcinoma (2.8 Lck); Glasgow osteogenic sarcoma (1.8 Lck); Lewis lung carcinoma (1.4 Lck); B16 melanoma (1.4 Lck); P388 leukemia (170% ILS) and L1210 leukemia (64% ILS). Of interest, CPT-11 was active against tumors with acquired resistance to vincristine (P388/Vcr), to doxorubicin (P388/Dox) and to docetaxel (Calc18/TXT). CPT-11 was also found highly active after oral administration in mice bearing P03 and MA16/C tumors. Pharmacokinetic evaluations performed i.v. at the highest non-toxic dosage in mice bearing P03 tumors revealed CPT-11 peak plasma concentrations (Cmax) of 8.9 micrograms/ml and a terminal half-life of 0.6 h. The metabolite SN-38 plasma concentrations presented a Cmax of 1.6 micrograms/ml and a terminal half-life of 7.4 h. Although the CPT-11 tumor levels were similar to the plasma concentrations for early time points, drug levels decreased more slowly in the tumor compared to plasma (half-life, 5.0 h). SN-38 tumor levels reached concentrations in the range of 0.32-0.34 micrograms/g and decayed with a half-life of 6.9 h. No significant difference in plasma or tumor pharmacokinetics of either CPT-11 or SN-38 were noted after one or five daily i.v. injections. Overall, these data show that CPT-11 has good activity in experimental models, when administered both by the i.v. and the oral routes. Compared to humans, a similar schedule of administration independence was observed and similar CPT-11 levels could be reached at efficacious dosages although metabolite SN-38 levels were found higher in mice.
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PMID:Experimental antitumor activity and pharmacokinetics of the camptothecin analog irinotecan (CPT-11) in mice. 882 13

Ovarian carcinoma can be classified into the following distinct two groups in terms of chemosensitivity. The chemosensitive group includes serous, endometrioid, transitional cell carcinoma (TCC), and undifferentiated carcinoma, with a response rate to CDDP-based chemotherapy (CTX) being approximately 80 to 90%. Even within this chemosensitive group, the mode of the response to chemotherapy may vary by the histologic subtype or the grade of differentiation. The chemo-resistant group consists of mucinous and clear-cell adenocarcinoma (CCA), with a response rate to CDDP-based regimen being less than 5% or none. Especially, for pure CCA of the ovary, no one case has ever been reported to have shown an appreciable response to a CDDP-based regimen. As a result, advanced patients with mucinous carcinoma or CCA of the ovary not amenable to a complete surgery have a poor prognosis. The author developed a promising new regimen consisting of CPT-11 with mitomycin-C based both on in vitro and in vivo chemosensitivity tests. Thus, an individualized regimen may be required for both CDDP-sensitive and resistant diseases.
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PMID:Individualized chemotherapeutic regimen for each histological subtype of ovarian carcinoma. 921 Aug 89

The case was a 67-year-old female. In March, 1993, bilateral oophrectomy + total hysterectomy+omentectomy were done, for stage III ovarian cancer with peritoneal dissemination, and high CA 125 level (2100 U/ml). As postoperative chemotherapy, intraperitoneal injection of CDDP 150 mg (4 courses), and intravenous injection of CAP (CPA 500 mg/ m2 + epirubicin 25 mg/m2 + CDDP 50 mg/m2) (10 courses) were undertaken. In March, 1995, in abdominal CT scan, a solitary splenic tumor was found and the tumor marker (CA 125) was again elevated, and splenic metastasis was suspected. In June, 1995, intravenous injection of CDDP 70 mg/m2 + CPT-11 60 mg/m2 (1 course) was given, and the splenic tumor enlarged gradually. In February, 1996, a splenectomy was done. In pathological findings, the tumor proved to be poorly-differentiated adenocarcinoma the same as primary ovarian cancer, and after splenectomy, CA 125 fell below the normal value. The diagnosis was solitary splenic metastasis from ovarian carcinoma.
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PMID:[A case of solitary metastatic splenic tumor of ovarian carcinoma]. 927 57

The purpose of this study was to describe a new anti-cancer drug regimen for uterine cervical cancer. The cytotoxicities of some anti-cancer drugs regimens against the human uterine cervical cancer xenografted into nude mice have been studied. The activities of CDDP, CPT-11, TXL, CDDP + BLM, CDDP + MMC, CPT-11 + BLM, CPT-11 + CDDP, CDDP + 5-FU, CPT-11 + MMC, CPT-11 + TXL and CDDP + TXL for squamous cell carcinoma (TCR, TCK, TCG), and CDDP, MMC, TXL, CDDP + TXL, CDDP + MMC and MMC + TXL for adenocarcinoma (TCO, TCM, TCY), were evaluated comparing with a control group using saline. Five mice were used for each groups. When the xenografted tumor reached 6 mm in diameter, 1/5 LD50 of these drugs were administered into the peritoneal cavity of the mice once a week for three weeks. The effective regimens were CDDP + MMC, CDDP + BLM, CDDP + CPT-11 and CPT-11 + MMC for squamous cell carcinoma of the uterine cervix. CDDP + MMC, CDDP + TXL, MMC + TXL and CDDP were effective for endocervical adenocarcinoma. It was suggested that these new drug regimens should be used in clinical studies.
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PMID:[Evaluation of a new anti-cancer drug regimen against uterine cervical cancer in nude mice]. 935 Feb 46


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