Reduction of vincristine toxicity by Cronassial

Hellmann, K.; Hutchinson, Gillian; Henry, Kristin

doi:10.1007/bf00252954

Cited by 15 publications

(9 citation statements)

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“…In other experiments [3], it had been observed that doses of Cronassial less than 150 mg/kg were insufficient to give protection against the doses of mitozantrone which were employed in the present experiments. In other experiments [3], it had been observed that doses of Cronassial less than 150 mg/kg were insufficient to give protection against the doses of mitozantrone which were employed in the present experiments.…”

Section: Lewis Lung Carcinomamentioning

confidence: 47%

“…Such studies are however difficult to reproduce in animals because vincristine induces no evident signs of neurotoxicity in most laboratory species even at lethal doses, but in experiments to see if Cronassial could affect the acute or chronic lethal toxicity of vincristine in mice, it was found that Cronassial appeared to afford some degree of protection against the chronic lethal effects of vincristine [3]. Since the mechanism of this protection was difficult to define and appeared to us more related to the haemopoietic or gastro-intestinal rather than the nervous system, it seemed worthwhile to examine the effects of Cronassial on the toxicity and activity of other antitumour drugs, particularly those that are not known to have any major neurotoxic side effects.…”

Section: Introductionmentioning

confidence: 99%

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Effect of high dose mitozantrone with Cronassial on the Lewis lung carcinoma and L1210 leukaemia

1987

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Mice given mitozantrone (MTZ) in doses close to the LD100 (high dose, HD) all survive if they also receive at the same time a mixture of four defined gangliosides--Cronassial (CRN). The protective action of CRN against the toxic effects of MTZ is not accompanied by a reduction of the antitumour activity of MTZ; on the contrary the reduced toxicity permits higher doses of MTZ to be given with the result that better antitumour activity can be achieved. This is illustrated by the highly effective action of MTZ and CRN in preventing the appearance of Lewis lung carcinoma (3LL) metastases, a tumour against which MTZ when used alone is inactive even at maximum tolerated doses (MTD). However, the effect of the combination on the primary 3LL is less pronounced. HD-MTZ and CRN are also more effective than MTD-MTZ alone in preventing dissemination and proliferation of L1210 leukaemia. Although the mechanism of the CRN protective effect is as yet unclear it appears that CRN prevents the lethal effects of necrotizing enteritis produced by HD-MTZ. It is concluded that CRN by reducing MTZ toxicity without interfering with its activity increases the therapeutic index of MTZ and permits an expanded exploration of its dose response curve against a variety of malignancies.

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Section: Lewis Lung Carcinomamentioning

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Effect of high dose mitozantrone with Cronassial on the Lewis lung carcinoma and L1210 leukaemia

1987

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“…Such data could be of clinical relevance, based on prior observations indicating potential therapeutic effects of the same gangliosides in tumor-bearing patients affected by drug-induced peripheral neuropathy [7,18]. Such data could be of clinical relevance, based on prior observations indicating potential therapeutic effects of the same gangliosides in tumor-bearing patients affected by drug-induced peripheral neuropathy [7,18].…”

Section: Discussionmentioning

confidence: 99%

“…The systemic administration of purified bovine brain gangliosides has been shown (i) to enhance peripheral nerve regeneration following traumatic injury [11,12]; (ii) to reduce peripheral nerve abnormalities accompanying diabetes [30,32] and, most relevant; (iii) to limit VCR-induced loss of functional peripheral nerve fibers [7]. In addition, these gangliosides have been shown not to affect VCR antimitotic activity in vitro and in vivo [7,18].…”

Section: Introductionmentioning

confidence: 99%

Exogenously administered gangliosides fail to increase in vivo metastatic frequency or in vitro growth of murine neoplastic cells

et al. 1990

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The influence of gangliosides on tumor growth and frequency of metastasis in vivo, as well as growth of neoplastic cells in vitro, was tested utilizing the mouse fibrosarcoma cell line MN4. In mice receiving intramuscular tumor transplants, injections of a ganglioside mixture twice daily did not influence the tumor volume or the number of spontaneous metastases per animal. Furthermore, in mice receiving the cells by tail vein injection, injections of a ganglioside mixture once or twice daily did not affect the number of metastatic foci in the lungs. Preincubation of neoplastic cells with the ganglioside mixture decreased the number of metastatic foci in the lungs of mice receiving the cells by tail i.v. injection. The addition of ganglioside mixture to the culture medium for up to a 48-h incubation period had no effect, independently of the cell density utilized, on either the rate of DNA synthesis or the relative numbers of neoplastic cells as compared to controls; at higher ganglioside concentrations, growth was actually reduced. These results are interpreted to indicate that gangliosides, under the present conditions, do not influence tumor growth and metastatic neoplastic capacity in vivo, and growth in vitro.

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“…Intravenous injection of gangliosides has been employed in many countries to treat neuropathies due to their neuroprotective effect and potential to promote nerve repair by enhancing nerve sprouting [11]. As early as in the 1980s, ganglioside treatment was found to be useful in the mitigation of vincristine-associated neuropathy, both in rabbit models and cancer patients [12,13]. Preclinical animal models suggested that porcine GM1 could be effective in the prevention and treatment of paclitaxel-induced neuropathy [14].…”

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confidence: 99%

Ganglioside-monosialic acid (GM1) for prevention of chemotherapy-induced peripheral neuropathy: a meta-analysis with trial sequential analysis

Bai

Guo³

et al. 2021

Preprint

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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect that largely remains an unresolved clinical issue, leading to long-term morbidity. This meta-analysis aimed to evaluate the efficacy and safety of Ganglioside-monosialic acid (GM1) in preventing CIPN.Methods: Systematic literature searches of Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were performed to identify randomized controlled trials and cohort studies that evaluated the efficacy of GM1 for preventing CIPN. Ameta-analysis was conducted to calculate odds ratios (ORs) and 95% confidential intervals (CIs) using a random-effects model. Trial sequential analyses (TSA) also were conducted to control for random errors. Results: A total of five studies involving 868 participants were included. The results showed that GM1 did not reduce the overall incidence of grade ≥2 CIPN when the common terminology criteria for adverse events (CTCAE) was used (OR 0.34, 95% CI 0.34-1.11). Subgroup analyses showed that GM1 could not reduce the risk of CTCAE grade ≥2 CIPN (OR 0.63, 95% CI 0.35-1.13) and neurotoxicity criteria of Debiopharm (DEB-NTC) grade ≥2 CIPN (OR 0.25, 95% CI 0.01-7.10) in oxaliplatin-treated patients, although GM1 might reduce the risk of CTCAE grade≥2 CIPN in the taxane subgroup in one study (OR 0.003, 95% CI 0.00-0.05). Besides, TSA suggested that the results in the taxane subgroup were robust, while that of the oxaliplatin subgroup were inconclusive. Furthermore, GM1 did not influence the rate of response to chemotherapy and CTCAE grade ≥2 adverse events such as fatigue, nausea, diarrhea, and rash.Conclusions: GM1 was not associated with a lower risk of oxaliplatin-induced peripheral neuropathy nor could improve the response or safety to chemotherapy; however, it might be able to prevent taxane-induced peripheral neuropathy. Higher-quality trials are required to clarify the preventive effect of GM1 in oxaliplatin-treated patients.

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Reduction of vincristine toxicity by Cronassial

Cited by 15 publications

References 2 publications

Effect of high dose mitozantrone with Cronassial on the Lewis lung carcinoma and L1210 leukaemia

Effect of high dose mitozantrone with Cronassial on the Lewis lung carcinoma and L1210 leukaemia

Exogenously administered gangliosides fail to increase in vivo metastatic frequency or in vitro growth of murine neoplastic cells

Ganglioside-monosialic acid (GM1) for prevention of chemotherapy-induced peripheral neuropathy: a meta-analysis with trial sequential analysis

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