Potential medical applications of ruthenium isotopes

Waters, S.L.

doi:10.1016/0010-8545(83)85020-6

Cited by 6 publications

(2 citation statements)

References 33 publications

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“…Thus it appears that the interaction of Na[trans-RuC14(DMSO)Im] with tumor cells in the lungs cannot be simply attributed to a greater localization of the compound at this site, but is probably ascribable to a selective interaction with one or more properties of metastatic cells not shared with the tumor cells of the primary tumor, or with cells of healthy tissues. This consideration is in agreement with the reported findings of a preferential deposition of ruthenium ions and of ruthenium complexes in tumor cells [10][11][12], and with the proposed role of ruthenium isotopes as markers of residual and disseminated tumors [13], a role that seems to be superior to that of other compounds including gallium citrate [11]. On the one hand toxicity for the metastatic cells seems to fulfill the proposed criterion for a selective activation of ruthenium(III) complexes to cytotoxic products in tu/nor cells, compared with cells of healthy tissues [14].…”

Section: Discussionsupporting

confidence: 92%

Antimetastatic action and toxicity on healthy tissues of Na[trans-RuCl4(DMSO)Im] in the mouse

Gagliardi¹,

Sava²,

Pacor³

et al. 1994

Clin Exp Metast

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The ruthenium-dimethylsulfoxide complex Na(trans-RuCl4(DMSO)Im] was given i.v. to mice bearing MCa mammary carcinoma and its effects on tumor growth and on healthy host tissues were studied by macroscopic examination of primary tumor growth, by survival time, and by histological analysis using light microscopy and SEM. Either by means of vivo-vivo bioassays or by microscopic examination it appeared that the growth of lung tumors was markedly reduced, whereas the growth of the i.m. primary tumor was much less affected. These effects account for the prolongation of survival time and for the cure rate observed. The favourable effect on survival time was also influenced by the lack of significant cytotoxicity for normal tissues such as lung and kidney epithelia, muscle and liver cells, splenocytes and bone marrow. It thus appears that the selective interaction with tumor cells in the lungs cannot simply be attributed to a selectively higher localization of the compound at this site, nor to a modification of the histological structure of primary tumor. These results highlight the pharmacologic properties of this compound for the control of solid tumor metastases, an effect that was shown to be similarly exerted on advanced tumor metastases.

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Section: Discussionsupporting

confidence: 92%

Antimetastatic action and toxicity on healthy tissues of Na[trans-RuCl4(DMSO)Im] in the mouse

Gagliardi¹,

Sava²,

Pacor³

et al. 1994

Clin Exp Metast

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“…Ruthenium was indicated as a metal of potential medical application [4,5] and of value in cancer chemotherapy [6]. The possibility was postulated taking advantage of its chemical behavior by developing complexes which are activated to cytotoxic products by a reduction mechanism in the tumor tissue [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Na[trans-RuCl4(DMSO)Im], a metal complex of ruthenium with antimetastatic properties

et al. 1992

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The antitumor and antimetastatic effects of a ruthenium(III) complex, Na[trans-RuCl4(DMSO)Im], have been examined in mice bearing MCa mammary carcinoma. Na[trans-RuCl4(DMSO)Im] is capable of reducing primary tumor growth and of prolonging the survival time with different schedules of administration. However, better effects were obtained (a) with treatments started soon after tumor implantation, (b) with daily administration rather than with treatments at 4-day intervals and (c) using relatively low daily doses. The prolongation of survival time in tumor-bearing hosts, greater than that obtained with cisplatin, cannot be simply related to the effect on primary tumor growth, always less than that of cisplatin. Rather, emphasis is placed on the reduction of lung metastasis formation, obtained either by i.v. injection of tumor cells (lung colonization or spontaneously from i.m. tumor implants, which is significantly greater than the reduction of primary tumor growth. The antimetastatic effect depends on the treatment schedule and is greater with low doses given daily than with high doses administrated with drug-free intervals. Metastasis reduction involved mainly large metastatic nodules, reducing the average weight of each metastasis by 8-fold for spontaneous metastases and by 5-fold for lung colonies. The antimetastatic action of Na[trans-RuCl4(DMSO)Im] thus indicates the possibility that related analogs can represent a new generation of antitumor compounds capable of selectively interacting with metastasis formation of solid tumors.

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