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Biomedical subjects

G R Gale

Publications and source records attributed to G R Gale.

At least 73 records · Page 4Linked to original sources
PubMed1978

Synergistic action of high-dose hydroxyurea when used with cyclophosphamide and certain new organoplatinum complexes in treatment of advanced L1210 leukemia.

Seven new organoplatinum (Pt) compounds, cyclophosphamide (CY), and hydroxyurea (HU) were used singly and in combination in treatment of advanced L1210 leukemia in C57BL/6 X DBA/2 mice. In each experiment the Pt + CY combination was supra-additive, as has been shown with other Pt compounds when used with CY. HU at the dose used (1000 mg/kg) was only minimally effective when used alone. However, six of the seven Pt + CY + HU combination regiments enhanced markedly the increased life span of treated mice when compared with the corresponding dual Pt + CY combination. The triple drug regimen yielded cure rates (760-day survival) up to 70% in individual experiments. Collectively, the cure rate was 11% with the various Pt + CY combinations, and was increased to 53% upon inclusion of HU in the regimen. It is suggested that HU may inhibit a process whereby potentially lethal DNA damage produced by Pt + CY would otherwise be repaired. A reduced efficacy of HU when used at a single, high-dose level was also noted, and a possible mechanism and potential significance of this observation are discussed.

Animals↗
PubMed1978

Effects of certain antitumor platinum compounds on kidney esterases.

In a study of the biochemical mechanism of renal toxicity of certain antitumor platinum compounds, particularly cis-dichlorodiammineplatinum(II) (NSC-119875), qualitative and quantitative studies of the soluble nonspecific kidney esterases were carried out using (C57BL/L X DBA/2) mice. There was a major suppression of the testosterone-dependent esterases of treated male mice; these levels dropped to levels below those found in untreated females within 72 h after certain of the drugs were administered. This effect appeared to be in inverse relationship to the numerical value of the LD50 values of the compounds investigated.

Animals↗
PubMed1978

Potentiating action of 5-fluorouracil when used in combination with platinium compounds and cyclophosphamide in treatment of advanced L1210 leukemia.

Nine new organoplatinum (Pt) compounds, cyclophosphamide (CY), and 5-fluorouracil (FU) were used singly and in combination in treatment of advanced L1210 leukemia in C57BL/6 X DBA/2 hybrid mice. In each experiment the Pt + CY dual combination was minimally supra-additive at the doses chosen. However, eight of the nine Pt + CY + FU combination regimens enhanced markedly the increased life span of treated mice as compared with the corresponding dual Pt + CY combination. Collectively, the cure rate (greater than 60-day survival) was less than 6% with the various Pt + CY combinations, and was increased to over 63% upon inclusion of FU in the regimens.

Animals↗
PubMed1977

Some effects of dieldrin and mirex on Ehrlich ascites tumor cells in vivo and in vitro.

The effects of dieldrin and mirex on Ehrlich ascites tumor cells were assessed, using certain in vivo (in mice) and in vitro measurements. Mirex retarded the development of Ehrlich ascites tumor in vivo, but dieldrin did not. Effects of dieldrin on de nova RNA purine synthesis from formate in vivo were slight, while mirex inhibited the synthesis of both RNA purines. Dieldrin inhibited the in vitro incorporation if thymidine, uridine, and L-leucine into DNA, RNA, and protein, respectively, but mirex was virtually without effect.

Animals↗
PubMed1977

Accelerated tumor growth following experimental burns.

When mice are given a 30% scald burn, the growth of subsequently inoculated Ehrlich ascites tumor is markedly accelerated. This effect, which parallels the well documented suppression of cell-mediated immunity occurring postburn, disappears 10 days postinjury. Possible clinical implications are discussed and an illustrative case report is presented.

Animals↗
PubMed1977

Preparation and antitumor evaluation of water-soluble derivatives of dichloro(1,2-diaminocyclohexane)platinum(II).

The structure of the antitumor agent, dichloro(1,2-diaminocyclohexane)platinum(II) (NSC-194814), was modified by replacing the chlorides with organic or inorganic anions. Eighteen new platinum complexes were so isolated and their antitumor properties against the L1210 leukemia in C57BL/6 X DBA/2 mice were evaluated. Most of the complexes were readily soluble in water and some had enhanced antitumor activity compared to the parent dichloro complex. In addition, increased solubility with retention of significant antitumor activity was obtained by oxidizing the parent dichloroplatinum(II) complex with halogen or peroxide to give two platinum(IV) complexes. Some previously reported platinum complexes with phosphorus, selenium, or tellurium electron donor ligands were also synthesized and assessed for antitumor action, but these did not show appreciable activity.

Animals↗
PubMed1976

Antileukemic properties of organoplatinum complexes.

The antitumor activity of 46 cis-amineplatinum congeners was evaluated against L1210 leukemia in (C57BL/L X DBA/2)F1 mice. Several compounds in this series significantly prolonged the life-spans of mice with the leukemia. During the selection of the compound that yielded optimal activity [dichloro(1,2-diaminocyclohexane)platinum], the chlorides were substituted with various organic and inorganic anions. The aqueous solubility was greatly increased with retention of significant antileukemic activity. Most of the active compounds were synergistic with cyclophosphamide, and cure rates up to 80% were obtained with certain combinations.

Animals↗
PubMed1976

The effects of single administration of an antitumor platinum compound on ornithine decarboxylase activity in certain tissues of mice bearing L1210 leukemia.

A single dose of cis-dichloro(dipyridine)platinum(II) (cis-PPC), when given to BDF1 mice bearing 1-day-old L1210 leukemia, suppressed the increase of spleen and liver ornithine decarboxylase (ODC) activity which occurs concomitantly with development of the leukemia. The inhibition of ODC, the rate-limiting enzyme in polyamine synthesis, appeared to correlate with the prolonged chemotherapeutic efficacy of a single dose of the platinum complex. These observations suggest an additional mechanism by which platinum complexes express their antitumor actions and, in addition, support the view that polyamine synthesis and excretion patterns can be used as predictors of chemotherapeutic response.

Animals↗
PubMed1976

Effects of Dintrato(1,2-diaminocyclohexane)platinum (NSC 239851) On murine myeloma and hemopoietic precursor cells.

We studied the effects of dinitrato (1,2,-diaminocyclohexane)platinum (NSC 239851) on murine myeloma Adj. PC-5 and hemopoietic precursor cells. The median survival time of tumor-bearing mice was significantly affected by i.p. injections of this agent. While 14 mg/kg was a toxic dose, as little as 2 mg/kg prolonged the survival for over 100 days. When cells from normal marrow and actively regenerating marrows were exposed to the agent in culture tubes, washed, and assayed for the surviving hemopoietic precursors, similar sensitivity curves were observed. This result indicates the absence of cell cycle dependency of the agent. When marrow cells were exposed to NSC 239851 at 4 degrees in culture, almost total abrogation of the cytotoxicity was noted. This observation, unlike that from the experiment with the inorganic platinum congener, cis-diamminedichloroplatinum, suggests that the transport of this agents is an active process.

Animals↗
PubMed1975

Comparative effects of Yoshi-864 and busulfan on certain transplantable murine tumors.

Yoshi-864 extends markedly the survival times of mice bearing L1210 leukemia or Ehrlich ascites carcinoma. Busulfan, with methanesulfonate leaving groups identical with those of Yoshi-864, is without effect. Tumor cells from mice bearing the Ehrlich tumor and treated with Yoshi-864 have a persistent reduction in ability to synthesize DNA. Synthesis of DNA in cells from mice treated with busulfan is moderately suppresed at 48 hr after treatment, but returns virtually to the control value at 72 hr.

Alkylating Agents↗
PubMed1975

Effects of cis-diamminedichloroplatinum (NSC 119875) on murine and human hemopoietic precursor cells.

The effects of cis-diamminedichloroplatinum (NSC 119875) on murine and human hemopoietic precursor cells were studied in culture. When murine cells from normal and actively regenerating marrows were exposed to cis-diamminedichloroplatinum in culture, washed free of the agent, and assayed for the surviving hemopoietic precursor cells, similar sensitivity curves were obtained. This result indicates the absence of cell-cycle dependency of cis-diaminedichloroplatinum. When marrow cells were exposed to cis-diamminedichloroplatinum in culture at various temperatures, only minimal reduction of cytotoxicity was noted at 4 degrees. This observation, unlike that from the experiment with nitrogen mustard, suggests that the transport of this agent is by passive diffusion. Finally, when the sensitivity of human hemopoietic precursor cells to this agent was assessed using similar conditions and compared to that of murine hemopoietic precursor cells, a significant species difference was observed.

Animals↗