摘要:

5-HT3receptor antagonists, ondansetron, granlsetron and tropisetron are highly specific for the 5-HT3receptor and have a selectivity ratio of approximately 1000:1 compared with affinities for other receptors. Other 5-HT3receptor antagonists, largely those having a benzamlde structure, are non-selective. These Include metoclopramide, renzapride and zacoprlde which stimulate gastric motility via activation of 5-HT4receptors; metoclopramide is also a potent dopamine receptor antagonist. Selective 5-HT3receptor antagonists are a major advance in the treatment of chemotherapy- and radiotherapy-induced emesls In cancer patients. These agents Inhibit emesls by blocking 5-HT3receptors on vagal afferent nerve terminals in the gastrointestinal mucosa and on terminals on the same vagal nerves In the vomiting system. Inhibition of acute emesls appears to be produced by blocking the Initiation of the emetic reflex Induced via 5-HT3receptors and by 5-HT released from enterochromaffin cells in the small intestine, as well as by blocking 5-HT3receptors In the hlndbraln vomiting system.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Twenty postmenopausal women (aged between 46 and 67 years old) with skeletal metastases from breast carcinoma were treated with clodronate 450 mg i.v. daily for 5 days and thereafter with 100 mg i.m. daily for 10 days. All patients received standard hormonal therapy (tamoxifen). Symptomatic pain (evaluated according to a linear analog scale), performance status (according to Karnofsky), serum alkaline phosphatase, serum creatinine and osteocalcin were measured before and after treatment on days 5, 15, 30 and 45. Scaning by radiology were performed pre- and post-therapy. Bone pain was significantly reduced in 15 out of 20 patients. After clodronate treatment the base line value of circulating osteocalcin (3.2 ± 1.6 ng/ml) showed a significant increase on days 30 and 45 (p< 0.001). Radiological assessment of bone lesions showed stable disease in 18 patients and progression in two patients. No adverse side effects were observed. These data show that clodronate provided pain relief in 75% of treated patients and the increase in circulating osteocalcin levels can be considered a marker of the stabilization of skeletal metastatic lesions.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Suramin exhibited morphine-like analgesic activity in mice. It antagonized both thermal (hot-plate) and acetic acid-evoked writhing responses with ED50values 1/100 and 1/68, respectively, that of morphine. The suramin-and morphine-induced hot-plate analgesia was suppressed by administration of 0.5 mg/kg naloxone. However, lower doses (5–30 μ/kg) of naloxone produced dose-related potentiation or suppression of suramin and morphine analgesia. This potentiation effect may be due to the inhibition of writhing by naloxone itself rather than be a direct antagonism of the morphine effect.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A number of highly lipophilic dineodecanoato(trans-R,R-andtrans-S,S-1,2-diaminocyclohexane) platinum (II) complexes were entrapped in multilamellar vesicles composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidyl-glycerol at a molar ratio of 7:3. The entrapment efficiency and stability of liposomal platinum (L-Pt) preparations was >90%. The subacute mouse LD50of L-Pt preparations tested ranged from 60 to 104 mg/kg. All L-Pt preparations tested had no significant nephrotoxicity at the LD50dose except for L-Pt 5, which caused renal dysfunctions (as evidenced by elevated blood urea nitrogen levels) at the LD50dose. L-Pt preparations had shown goodIn vivoantltumor activity against i.p. L1210 leukemia when an optimal dose was administered i.p. to mice on days 1, 5 and 9 (% T/C 230–300; cisplatin 220). L-Pt preparations were also markedly active, by the i.p. route, against L1210 leukemia resistant to cisplatin (% T/C 237–355; cisplatin 112). All L-R preparations exhibited significant antitumor activity against B16 melanoma when administered i.p. on day 1 (% T/C 144–155; cisplatin 161). L-Pt 1, 3 and 5 were all tested by the l.v. route on days 4, 8 and 12 against M5076 reticulosarcoma, but none of these preparations showed any significant antltumor activity against this tumor system (% T/C 120–127; cisplatin 173). Current studies aimed at optimizing the liposomal formulation of these compounds should result in the selection of a single isomeric L-Pt formulation for clinical development.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Liposome-entrapped doxorubicin (Lip-Dox) was evaluated in two phase I clinical trials in patients with hepatic malignancy. Patients with metastases from primary gastric or colonic tumours and patients with hepatoma were eligible. Lip-Dox was extremely well tolerated and acute toxicities such as nausea and vomiting were totally eliminated; no antiemetics were used even at doses of 80 mg/m2. Toxicities such as alopecia and myelosuppression were also ameliorated. There were tumor regressions and reductions in hepatomegaly in patients treated on both the weekly and 21-day studies. The maximum tolerated dose (MTD) in the weekly study was 22.5 mg/m2/week and in the 21-day trial the MTD was 70 mg/m2.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Cytotoxic luteinizing hormone-releasing hormone (LH-RH) analogs, AJ-004 (agonist [D-Lys6]LH-RH linked to methotrexate (MTX)), T-98 ([D-Lys6]LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone) (G-HMAQ) and T-121/B (antagonist containing two residues of G-HMAQ) were tested in female BDF, mice bearing MXT ((3.2)/Ovex) estrogen-independent mammary tumors. All three cytotoxic LH-RH analogs, administered from Alzet Osmotic Minipumps for 3 weeks, produced a significant inhibition of tumor growth. The effects of T-98 and T-121/B were superior to those obtained by treatment with equimolar doses of cytotoxic moiety anthraquinone or the LH-RH carrier alone. We assume that cytotoxic LH-RH analogs have a combined hormonal and cytotoxic activity with a reduced toxicity after administrationIn vivo.This is the first demonstration ofIn vivotumor inhibition by targeted LH-RH analogs bearing cytotoxic radicals.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Changes in the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in the plasma, lung, liver, stomach, small intestine, spleen and kidney in two-thirds partially hepatectomized rats. Concentrations of tegafur and 5-FU in plasma and tissues were determined 30 min after injecting 100 mg/kg of tegafur via the tail vein. The 5-FU concentration in the plasma remained unchanged for the first 7 days after hepatectomy. The tissue level of 5-FU was higher in the liver and kidney than in other organs examined, but there were no changes in levels of 5-FU in each organ examined. Our observations support the peroposal that the conversion of tegafur to 5-FU is maintained in partially hepatectomized rats.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Taxotere (RP 56976, NSC 628503) is a new semisynthetic analog of taxol (NSC 125973) with promising antitumor activity in a variety of preclinical screening systems. Clinical responses after treatment with taxol have been observed in ovarian cancer, breast, lung cancer and melanoma. Both agents act through induction of microtubule polymerization. We have studied and compared the antiproliferative action of Taxotere and taxol against a variety of freshly explanted human tumor specimens using anIn vitrosoft agar cloning system. Final concentrations of 0.025–10 μg/ml were used for both agents in short-term (1 h) or continuous (14 days) incubations. Taxotere was studied using a 1 h incubation in a total of 167 tumor specimens of which 85 (51%) were evaluable. At 10μg/ml, Taxotere inhibited 32 out of 78 (41%) specimens (colony formation ≤0.5 ± control). Cytotoxicity of Taxotere was observed against breast, lung, ovarian, colorectal cancer and melanoma tumor colony forming units. For comparison, 227 specimens were exposed to taxol for 1 h. At 10μg/ml, 32 out of 97 evaluable specimens (33%) were significantly inhibited. Cytotoxicity was observed against breast, lung, ovarian, colorectal cancer and melanoma tumor colony forming units. In head-to-head comparisons, 29 specimens were found more sensitive to Taxotere than taxol, while only 13 were more sensitive to taxol than to Taxotere. These data indicate that cross-resistance between the two agents is incomplete and that on a concentration basis Taxotere is more cytotoxic than taxol in the majority of human primary tumor specimens evaluated.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The effect of galactose-6-mustard (G-6-M) on cell growth and cell cycle kinetics was studied in murine P388 leukemia and Chinese hamster ovary (CHO) cellsIn vitroand compared with the effect of L-phenylalanine mustard (L-PAM). The IC50values of G-6-M for the P388 and CHO cells were 10 and 100 μM, respectively. No difference of the IC50value of L-PAM (2 μM) between the two cell lines was found. The effect of G-6-M and L-PAM on cell kinetics was similar for the two cell lines at IC50doses. The relative cell outflow from the G2stage was inhibited to a higher extent than the relative cell outflow from the S phase. The relative cell outflow from the G1stage was only partly inhibited. These results are discussed in relation to growth conditions, differences in DNA repair capacity, and cellular uptake of G-6-M between P388 and CHO cells.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Organotypic cultures of human A549 cells were used as a tumor model to investigate sequence effects for combination treatments with adriamycin (ADR) and X-irradiation. Initial drug exposure led to the greatest cytotoxic effect especially when X-rays were delivered 24 h later and this subsequent irradiation did not significantly modify the intracellular ADR concentration. In contrast, post-irradiation drug exposure gave rise to a lower cytotoxic effect, and induced a marked reduction of intracellular and more specifically intranuclear ADR uptake and retention, especially when the drug was given 24 h later.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID