摘要:

A brief review is presented of some recently described 5-HT3receptor antagonists. These antagonists are primarily targeted for use as anti-emetics. However, evidence is emerging that there are differences in their basic pharmacology. This evidence is reviewed in terms of the selectivity of the antagonists in binding studies and also of their efficacy in emesis and gastric emptying. The possibility that these differences may translate into meaningful clinical differences between the available 5-HT3receptor antagonists in their use as anti-emetics is also discussed.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Taxol is a new anti-cancer drug that is a natural product derived from the bark of the Pacific Yew tree. The drug promotes polymerization and stabilization of tubulin to microtubules and interferes with the mitotic spindle. Clinical trials indicate that taxol is effective in the treatment of patients with refractory ovarian cancer, breast cancer, malignant melanoma and probably other solid tumors. Toxicities include anaphylactoid reactions, leukopenia, peripheral neuropathy and oropharyngeal mucositis. Increased supplies of the drug are required to support further phase II and III testing.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

DNA has been one of the major targets of cancer chemotherapy. A variety of anti-neoplastic agents can cause different types of DNA lesions, including base alterations, single- or double-strand DNA breaks, DNA-DNA cross-links and DNA-protein cross-links. The exact processes by which these DNA lesions lead to cell death remain uncertain. However, pivotal roles of intracellular Ca2+ion mobilization, activation of Ca2+- Mg2+-dependent endonuclease and induction of several oncogenes have been proposed. Understanding the mechanism of DNA damage and subsequent cell death will be important to improve the efficacy of cancer chemotherapy.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The cellular process regulating the post-translational poly (ADP-ribosylation) of various nuclear acceptor proteins is discussed in relation to its significance as a target for cancer chemotherapy; and with particular reference to the mechanism underlying the anti-tumor effects of the cell differentiating agent, hexamethylenebisacetamide. Of especial note are the influences which may be exerted on tumor cells expressing certain major types of oncogenically-activated cellular proto-oncogenes (oncogenes). A basis for a pharmacological approach to tumor therapy is further proposed from considerations of the action of a class of anti-tumor agents, the N6-substituted adenosines, by reason of their possible effects on poly (ADP-ribosylation) processing, as well as on other cellular processes of relevance for tumor therapy.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The anti-cancer drug aclarubicin (2.0 mg/kg body weight) was injected into the left popliteal lymph node (the primary draining node of the foot-pad region) or into the tail vein, 8 days after a subcutaneous inoculation of 5 ± 105P388 leukemia cells/mouse in the left hind paw foot-pad of mouse (donor). During this time, metastases were established in the lower para-aortic nodes (the secondary draining nodes of this region). On day 10, the lower para-aortic nodes taken from each donor were transferred intraperitoneally to a normal mouse (recipient). From the recipients' survival time, the viable P388 leukemia cell number in the para-aortic nodes per donor mouse was estimated with a calibration line. The recipients' survival curve in the intralymphatic chemotherapy group was statistically significantly better than that in the intravenous chemotherapy group.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The distribution and excretion of [57Co]Bleomycin, dissolved in saline or encapsulated in liposomes, was studied in normal or tumor-bearing [P388 leukemia, reticulum cell sarcoma (RS)] mice. The free substance is cleared relatively quickly from the organism both after intravenous and intraperitoneal administration (t1/20.17 and 2.41 h, respectively), and is excreted predominantly via the urinary tract. In contrast, following entrapment in small unilamellar vesicles (SUV) or multilamellar vesicles (MLV), the57Co radioactivity remains 7− to 30-fold longer in the blood stream and is detectable in considerable amounts in liver, spleen, lung and tumor of the RS model even after 48 h. Concomitantly, the renal excretion is diminished to about 50% of the free drug and the feces excretion is slightly increased, possibly due to the higher concentrations in the liver. Whereas the renal levels of radioactivity were similar with alt application forms of [57Co]Bleomycin, there were marked differences in all the other tissues studied. After administration of SUV there was a higher activity in liver, brain and tumor, whereas MLV were more concentrated in spleen and lung. Therapeutic experiments confirmed the favorable results obtained with liposomes. While the free Bleomycin in the P388 leukemia had only a moderate influence on the lifetime of the animals with a treated/control value of 111%, encapsulation of the drug in SUV or MLV improved the results to 194 and 167%, respectively. In the intramuscular transplanted RS model, the SUV in a day 1 schedule had the same effect on tumor growth as the free drug in a day 1–4 schedule. These favorable results obtained with Bleomycin-containing liposomes make this drug formulation attractive for clinical use.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The effects of a combination of melphalan and dexamethasone on cell growth, cell cycle flow, cell loss and DNA cross-links were studied on a myeloma cell line (RPMI 8226). At low concentrations melphalan reduced the cell growth by prolonging the S and G2stages. Steroid sensitivity of the cell line was characterized by dose-dependentinhibition of cell growthafter exposure of up to 1 μm dexamethasone with no cell loss found even at 10-fold saturation concentration. Dexamethasone induced prolongation of all cell cycle phases without any preferences. In combined treatment with melphalan and dexamethasone, inhibition of cell growth was found after 24 h followed bycell lossafter 48 h. This cell loss was obtained with concentrations of the drugs which by themselves are only growth inhibitory. Calculation of cell flow showed that cell loss is a delayed process occurring after the cells have left the G1phase. By alkaline elution it was found that dexamethasone treatment caused an increase in melphalan-induced DNA interstrand crosslinks.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Sixty-one patients with breast cancer who received chemotherapy participated in a double-blind randomized cross-over study with methylprednisolone (MP) 250 mg as a single i.v. injection before chemotherapy and placebo as antiemetic treatment. The determining efficacy parameter was preference. Other parameters used were a visual analogue scale for nausea, a categorical four-point nausea intensity scale recorded by a nurse observer, emetic amounts, emetic episodes, acceptance of nausea and vomiting, and global assessments for nausea and vomiting. MP showed a significant antiemetic effect compared with placebo which was most pronounced for moderately emetogenic chemotherapy. The visual analogue scale, emetic amounts, acceptance and global assessments were easy to handle and showed coherence with preference, whereas nausea intensity and emetic episodes were resource demanding to record and showed no coherence with preference. It is concluded that for a precise evaluation of nausea and vomiting the visual analogue scale and emetic amounts are most reliable; for ambulatory patients global assessments seem to be sufficient.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Human keratinocytes, obtained from bioptic specimens of healthy and preneoplastic oral mucosa, and from human cell lines from oral cavity tumors (KB and SCC-25) were treated with β-carotene (10 μM). The colony forming efficiency (CFE), the proliferation rate and the frequency of micronucleated cells were measured in these cultures. CFE was significantly reduced (p < 0.05) by β-carotene treatment in cells from healthy mucosa and in KB cells. Decreases (p < 0.05; NS) were also observed in cells from pathological mucosa and in SCC-25 cells. Cell proliferation rate was not substantially affected by β-carotene in all cultures. Finally, a decreased frequency of micronucleated cells was found in treated cultures, but significant reductions (p < 0.05) were only observed in cultures from oral mucosa (healthy and pathological) as well as in KB cell cultures. Our results indicate that β-carotene is able to reduce the clonogenic activity (CFE), even if it does not seem to influence cell proliferation, and that it has a protective effect against genotoxic damage.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Nitroxyl radicals of a series of piperidineoxyles and pirrolinoxyles increase the tolerance of experimental animals to the injection of otherwise lethal doses of anti-tumor cytostatic agents. Simultaneous injection of nitroxyl radicals in different doses with 6-mercaptopurine, thiophosphamide, cyclophosphamide and the other cytostatic agents results in decreased toxicity and survival of animals. Nitroxyl radicals normalize the level of the oxidized form of P450 cytochrome that is decreased by the injection of lethal doses of cytostatic agents.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID