Mammary Tumour Inhibition and Subacute Toxicity in Rats of Prednimustine and of Its Molecular Components Chlorambucil and Prednisolone

Fredholm, Bertil B.; Gunnarsson, Kjell; Jensen, Gunborg; Müntzing, Jonas

doi:10.1111/j.1600-0773.1978.tb02185.x

Cited by 13 publications

(3 citation statements)

References 8 publications

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“…The observation that prednimustine showed a higher cytotoxic activity than equimolar concentrations of its alkylating or steroid components when used single or in combination, is in agreement with animal and patient studies (Harrap eta/. 1977;Fredholm et a/. 1978;Rorth et a/.…”

Section: Discussionsupporting

confidence: 82%

Comparison of the Cytotoxic Effect of Prednimustine in Cultured Cells with High or Low Levels of Metallothionein

Endresen¹

1984

Acta Pharmacologica et Toxicologica

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The purpose of this investigation was to evaluate the ability of the cysteinyl‐rich protein metallothionein (MT) to protect cells against the cytotoxic effects of prednimustine, an ester of chlorambucil and prednisolone. The cells studied were MT‐rich substrains of murine fibroblasts (CI 1D100) and human epithelial cells (HE100), both demonstrated in an earlier report to exhibit an approximate 3‐fold increase in resistance to chlorambucil compared to their parent lines (C) 1D and HE) (Endresen et al. 1983). Both in cloning and in growth rate studies the MT‐rich strains proved to be significantly more resistant also to predinimustine. E.g. in cloning studies D0 for C11D cells (D0 = the dose of drug reducing survival to 1/e) was 8.7 μg/ml prednimustine, whereas D0 for C11D 100 was 12.4 μg/ml, representing an approximate 1.5‐fold increase in resistance, P<0.001, t‐test. Other cloning studies revealed that prednimustine had a significantly higher cell killing activity in the resistant cells than equimolar concentrations of its components, single or in combination. Following treatment with 3H, l4C‐prednimustine (3H in the prednisolone moiety, 14C in the chlorambucil moiety) and subsequent gel filtration, about 40% of the cytosolic chlorambucil eluted with MT. However, no intact prednimustine was recovered in the MT fractions. The data indicate that the MT‐rich cells possess increased resistance to prednimustine due to a sequestration by MT of the alkylating moiety. Since the interaction probably does not take place until after hydrolysis, it is possible that the intact conjugate may bypass this cellular defence mechanism.

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Section: Discussionsupporting

confidence: 82%

Comparison of the Cytotoxic Effect of Prednimustine in Cultured Cells with High or Low Levels of Metallothionein

Endresen¹

1984

Acta Pharmacologica et Toxicologica

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“…where a 2 [0, 1] means that data come from Nðm 2 ; s 2 2 Þ with probability of a, and from Nðm 1 ; s 2 1 Þ with probability of 1 − a. For convenience, we fix μ 1 = 0, s 2 1 ¼ 1 and choose the nominal significance level α = 0.05.…”

Section: Bimodal Normal Distributionmentioning

confidence: 99%

“…Normal distribution is often used to describe the pattern of data in biomedical research [1][2][3]. Usually before conducting statistical analyses such as t-test, Hotelling T 2 test and ANOVA, the normality test is performed.…”

Section: Introductionmentioning

confidence: 99%

Cauchy combination omnibus test for normality

Meng

Jiang

2023

PLoS ONE

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Testing whether data are from a normal distribution is a traditional problem and is of great concern for data analyses. The normality is the premise of many statistical methods, such as t-test, Hotelling T2 test and ANOVA. There are numerous tests in the literature and the commonly used ones are Anderson-Darling test, Shapiro-Wilk test and Jarque-Bera test. Each test has its own advantageous points since they are developed for specific patterns and there is no method that consistently performs optimally in all situations. Since the data distribution of practical problems can be complex and diverse, we propose a Cauchy Combination Omnibus Test (CCOT) that is robust and valid in most data cases. We also give some theoretical results to analyze the good properties of CCOT. Two obvious advantages of CCOT are that not only does CCOT have a display expression for calculating statistical significance, but extensive simulation results show its robustness regardless of the shape of distribution the data comes from. Applications to South African Heart Disease and Neonatal Hearing Impairment data further illustrate its practicability.

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Phase II trial of prednimustine, L-1031, (NSC-134087) in advanced breast cancer

Mouridsen¹,

Kristensen²,

Nielsen³

et al. 1980

Cancer

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The therapeutic effect of prednimustine was studied in 35 patients with advanced breast cancer resistant to previous cytotoxic and/or endocrine therapy. Response (PR + CR) was obtained in 14 patients (40%) of a median duration of five months. Among the 14 responding patients, 10 were resistant to previous endocrine therapy and chemotherapy, in all cases including alkylating agents, and 4 were resistant to previous endocrine therapy. Hematologic toxicity was rather pronounced, but other toxicities were only moderate.

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Mammary Tumour Inhibition and Subacute Toxicity in Rats of Prednimustine and of Its Molecular Components Chlorambucil and Prednisolone

Cited by 13 publications

References 8 publications

Comparison of the Cytotoxic Effect of Prednimustine in Cultured Cells with High or Low Levels of Metallothionein

Comparison of the Cytotoxic Effect of Prednimustine in Cultured Cells with High or Low Levels of Metallothionein

Cauchy combination omnibus test for normality

Phase II trial of prednimustine, L-1031, (NSC-134087) in advanced breast cancer

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