摘要:

Benzamide riboside (3-(1-deoxy-β-D-ribofuranosyl)benzamide, BR) a new analog of nicotinamide riboside, is toxic to Chinese hamster ovary cells and inhibits guanine nucleotide synthesis in a manner comparable to that of tiazofurin (2-β-D-ribofuranosylthiazole-4-carboxamide). Adenosine kinase deficient cells demonstrate slight resistance but retain the ability to form the NAD analog, benzamide adenine dinucleotide (BAD). HPLC analysis of BAD containing cells is described. A BR resistant cell line was isolated that demonstrates cross-resistance to both tiazofurin and 6-aminonicotinamide, suggesting a common metabolic step; enzymatic analysis indicates reduced levels of NAD pyrophosphorylase in these cells. BR toxicity was only partially reversed or prevented by the presence of guanosine, suggesting either that BR inhibits guanine salvage to some extent or, more probably, that BR can, at high concentration, inhibit cell growth by another mechanism in addition to inhibition of guanine nucleotide synthesis. Cells incubated with BR for several hours retain the ability to salvage exogen-ously provided guanosine. The demonstration that BAD can be phosphorylated by NAD kinase, presumably to form BADP, suggests that this metabolite may be formed in cells and may have inhibitory activity at high concentrations of BR.

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

A three-drug combination, PMA, consisting of (phos-phonacetyl)-L-aspartic acid + 6-methylmercaptopurine riboside+5-aminonlcotinamide, preceding either 5-fluorouraell (5-FU) or adriamycin (Adr), produced tumorregressing activity in a murine advanced breast tumor model not attainable with either 5-FU or Adr as single agents, or with any lesser combination of these drugs administered at maximally tolerated doses. Marked tumor-regressing activity was further increased signifi-cantly by using 5-FU and Adr together in conjunction with the modulatory biochemical conditioning (particularly ATP depletion) provided by pretreatment with PMA.

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Previously inAnti-cancer Drugswe have reported a high correlation between clinical Plasms concentration-time products (CxT) and the concentration of cytotoxic drugs giving 50% cell survival (IC50) In primary cultures of human lymphatic cells. in the present study we investigated the relationship separately for cell cycle-specific (type 1) and cell cycle non-specific (type 2) drugs in chronic lymphatic leukemla cells. A high correlation (R=0.92) was observed betweenCxTand IC50for cell cycle non-specific drugs, while for cell cycle-specific, orCxT-dependent, drugs, the relationship was much weaker (R=0.58). Since the opposite pattern has been observed for the relationship between clinicalCxTand LD10in mice, these results further imply that drug sensitivity assays may be a useful complement to animal data in the selection of starting dose and dose escalation procedure in phase 1 clinical trials of new cytotoxic drugs.

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

There has been considerable interest and controversy over the potential clinical role of combination antiretroviral therapy, primarily in the treatment of patients with established HIV infection. in order to model the hema-tologic toxicity of high-dose combination antiretroviral therapy, the HL60 myelold leukemla cell line was exposed to zidovudine, dideoxycytidine and/or didanosine. The results suggest that the myelotoxicity of high-dose combination antiretroviral therapy may be controlled by using very brief periods of drug exposure. Brief Intense antiretroviral therapy may offer a useful approach, particularly in the treatment of patients with AIDS-related neoplasms who are also receiving myelotoxic antineoplastic drugs.

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The effects of adriamycin (Adr) and cisplatin on body weight, organ weight, and the contents of putrescine, spermidine and spermine in 15 different tissues were examined in rats that had been given these drugs for 5 days. The weight of the spleen in clsplatin-treated rats, and of the thymus, spleen, kidney and heart in Adrtreated rats showed statistically significant decreases. Neither Adr nor cisplatin should be used to treat cancers in the seminal vesicle, and Adr should not be used to treat those in the large intestine due to significant increases in spermidine and spermine, which are associated with a risk of re-growth. However, Adr is recommended in the treatment of cancers in the thymus, kidney, skeletal muscle (femoral), heart, prostate, testis, liver, small intestine and lung, based on decreases in some of the polyamines, while cisplatin is not recommended in the thymus, kidney, skeletal muscle or heart for the same reason that Adr is not recommended to treat cancers of the large intestine (rectum). The ratio of spermidine to spermine was significantly higher in the skeletal muscle of cisplatin-treated rats and in the small intestine and brain of Adr-treated rats, and was lower in the prostate, seminal vesicle and spleen of Adr-treated rats than in control rats.

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The first report on the administration of the chemoprotective agent Ethyol (amifostine) in conjunction with high dose carboplatin to a patient in the pediatric/adolescent age group is presented. A 17 year old teenager with recurrent cerebellar medulloblastoma received a total of five courses of high dose carboplatin 2 x 600 mg/ m2(1200 mg/m2total) in each cycle. A complete response has been observed following the third treatment cycle. However, cumulative grade IV hematological toxicity developed following each of the first four treatments. Therefore, the fiftth treatment was administered in conjunction with amifostine, at a dose of 2 x 740 mg/ m22.0 G/1, platelets> 100 G/I) was 52, 58, 72, 78 and 50 days, respectively, following treatments nos 1, 2, 3, 4 and 5. The duration of grade III-IV neutropenia (

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0959-4973    

出版商:OVID    

年代:1996

数据来源: OVID