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Biomedical subjects

L Edler

Publications and source records attributed to L Edler.

69 records · Page 4Linked to original sources
PubMed1984

Combination chemotherapy (VAC/FMC) with immunostimulation in metastatic breast cancer: a randomized study comparing different times and routes of administration of Corynebacterium parvum.

From January 1978 to December 1980, 222 patients with metastatic breast cancer were included into a prospective multicenter trial. All patients were treated once a month with six cycles of VAC- (vincristine, adriamycin, cyclophosphamide) chemotherapy, followed by FMC (5-fluorouracil, methotrexate, cyclophosphamide) until progression was documented. By random assignment, the patients received immunostimulation with Corynebacterium parvum (CP) by one of four methods: subcutaneous (SC) on either day 1 or day 14, intravenous (IV) on either day 1 or day 14. The 214 evaluable patients were equally distributed to the four arms. The rates of complete or partial response to VAC/FMC plus CP did not differ significantly between the treatment groups. Of our patients, 22-33% were definite treatment failures. The Kaplan-Meier curves of duration of remission (medians 14 vs. 9 vs. 13 vs. 11 months) did not differ significantly. Only small differences in survival were noted among the four study groups (medians 15.4 vs. 17.5 vs. 17.2 vs. 13.0 months). However, complete and partial responders lived significantly longer (Log rank test P = 0.008), when CP was given on day 14 by the SC rather than IV route (29+ vs. 14.3 months). Patients in the four study groups were treated with virtually identical doses of VAC/FMC chemotherapy. Patients receiving CP intravenously on day 14 experienced significantly lower mean leukocyte counts than patients in the other groups. Many patients suffered from high temperature (requiring treatment with antipyretics) and severe gastrointestinal toxicity, particularly when CP was given IV on day 1 together with the chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Treatment of autochthonous rat colonic adenocarcinomas with a thioether-lysophospholipid derivative in mono- and combination chemotherapy.

In 361 Sprague-Dawley rats autochthonous colorectal carcinomas were induced by intrarectal application of the carcinogen AMMN. Tumor-bearing animals were treated with a synthetic thioether-lysophospholipid (TLP) derivative and in combination chemotherapy with 5-fluorouracil (5-FU) and carmustine (BCNU). There was no difference in the survival time of treated and untreated animals. The median large-bowel tumor weight was significantly lower in the TLP/5-FU and TLP/5-FU/BCNU combination therapy groups than in the control groups. Transient hepatotoxicity was observed in the high-dosage (50 mg/kg body weight twice weekly) TLP group. This study confirmed the relative resistance of AMMN-induced colorectal carcinomas to antineoplastic treatment.

Adenocarcinoma↗
PubMed1984

A two-sample censored-data rank test for acceleration.

A score test for the null hypothesis of proportional hazards against rank-regression alternatives is proposed as a complement to the logrank test for comparing censored survival curves. The test statistic has an asymptotic normal distribution that is independent of the logrank distribution under the null hypothesis, and its power is good against acceleration alternatives (i.e. with crossing hazards) where the logrank test fails. Monte Carlo studies indicate that its small-sample properties are comparable to those of the logrank and ranksum procedures.

Biometry↗
PubMed1983

Spontaneous in vitro malignant transformation in a xeroderma pigmentosum fibroblast line.

This paper deals with a spontaneous malignant transformation in one of our XP fibroblast lines. This cell line, designated XP29MA, was derived from a 14-year-old boy who did not show skin tumors or precancerous alterations either at the time of clinical examination or when the biopsy was taken. We have compared the following features in both the malignant and the benign cell line from which the malignant line developed: tumor formation in nude mice, repair capacity, cytogenetic status, light and electron microscopic characteristics. The benign cell line XP29MA had a doubling time of 4.3 d, did not form tumors in nude mice, showed a very low repair capacity (as determined by colony-forming ability, unscheduled DNA synthesis and alkaline elution) but exhibited a normal cytogenetic and ultrastructural status. In contrast, the transformed cell line XP29MAmal grew three times faster, formed colonies in methyl cellulose, gave rise to fibrosarcomas in nude mice, showed a drastically higher repair capacity, and was characterized by an extreme genetic imbalance, resulting from numerical and structural chromosome alterations of Nos. 1, 3, 4, 8, 12, 16, 17, 18, 20 and 21. Ultrastructural examination revealed fusiform and polygonal cells, the latter exhibiting large indented nuclei, vesicular dilatations of the endoplasmatic reticulum and numerous lysosomes. The higher repair capacity in XP29MAmal cells is tentatively explained in terms of reversion, enhancement of post-replication repair and/or expression of SOS-type functions.

Adolescent↗
PubMed1983

Computational methods for the screening of pharmacokinetic parameters in metabolism experiments.

A computational strategy is presented which is useful for the qualitative and quantitative assessment of reaction-kinetic parameters in a one-compartment open model for the metabolism of substances in a biological system, especially the metabolism of dialkylnitrosamines to the ultimate carcinogen. The mathematical model used is that of first order kinetics and results in Bateman-functions. The strategy allows to decide about stability or instability of a substance occurring in a chain of transformations. In the case of stability quantitative estimates of the half life are provided. The procedure compares parameter estimates from models of different qualitative nature. These estimates are derived by linear or non-linear regression methods.

Biotransformation↗
PubMed1982

A randomized study of combination chemotherapy (VAC-FMC) with or without immunostimulation by Corynebacterium parvum in metastatic breast cancer.

A total of 156 patients with metastatic breast cancer were entered into a prospective multi-center trial in September 1975. All patients were treated monthly with vincristine, adriamycin and cyclophosphamide (VAC) six times, followed by 5-fluorouracil, methotrexate and cyclophosphamide (FMC) until progression was documented. By random assignment, the patients received 5 mg/m2 Corynebacterium parvum (CP) subcutaneously on day 1, in addition to VAC/FMC. Of the 150 evaluable patients, 33 of 76 (45%) and 36 of 74 (49%) had complete or partial response to VAC/FMC plus CP, respectively. The Kaplan-Maier curves of duration of remission and survival were almost identical (medians 14.5 vs 12.1 months and 22.2 vs 21.1 months, respectively). The hematologic and gastrointestinal toxicity were also similar in the two study groups. However, 19 of 74 (26%) patients developed skin ulcers after repeated injections of CP. These patients showed prolonged survival (P = 0.002, log rank test). These results suggest that adding nonspecific immunostimulation with CP to currently available chemotherapy on day 1 is of no benefit to most patients with metastatic breast cancer, but may select an "immunoreactive subgroup with increased local toxicity and survival.

Adjuvants, Immunologic↗
PubMed1982

Xeroderma pigmentosum patients from Germany: clinical symptoms and DNA repair characteristics.

Dermatologic, ophthalmologic, and neurologic examinations were carried out on 33 patients with clinical symptoms of xeroderma pigmentosum (XP). Complementation groups were determined for 23 patients. Types of tumors and complementation group were found to be related in the following way: In the XP variant groups basaliomas were the most frequently occurring malignant tumors, whereas in the D group pigmentary tumors, such as melanotic precanceroses and melanomas prevailed; in the A and the C group, spinaliomas seem to be the most frequent malignomas. The DNA repair activity was measured using colony-forming ability and unscheduled DNA synthesis. Colony-forming ability was quantitated as a function of 12 different UV doses and expressed in terms of D0. Unscheduled DNA synthesis was determined autoradiographically by establishing dose-response curves, which were analyzed by the characteristic value of linear regression. G0, defined as the linear increase in the mean number of silver grains per nucleus when the UV dose is multiplied by the factor of e (i.e., 2.72), was derived from the slopes of the regression lines. The repair capability of XP fibroblast lines was classified on the basis of D0 and G0.

Adolescent↗
PubMed1982

XP patients from Germany: correlation of colony-forming ability, unscheduled DNA synthesis and single-strand breaks after UV damage in xeroderma pigmentosum fibroblasts.

DNA repair capacity was investigated in 25 normal and XP fibroblast lines after UV damage was induced, using the following methods: colony-forming ability, unscheduled DNA synthesis, and alkaline elution (which can serve as a measure of repair-specific DNA incision). The majority of the XP fibroblast lines was derived from biopsies of patients who are at present under clinical observation by Dr. E.G. Jung (Dept. of Dermatology, Mannheim Medical School). Colony-forming ability was determined at 12 different UV dose levels and expressed in terms of D0. Unscheduled DNA synthesis was measured autoradiographically. Dose-response curves (grains per nucleus versus UV dose) were established and analyzed by linear regression. The characteristic value of G0, defined as the linear increase in the mean number of grains per nucleus when the UV dose is multiplied by the factor e (i.e., 2.72), was derived from the slope of the regression lines. For quantitating DNA-incising activity of a cell line, DNA elution curves were determined at several UV dose levels. Plotting of the initial velocities of the elution curves versus the UV doses yielded a regression line, the slope of which was used to obtain the characteristic elution value, E0. A descriptive correlation of all three characteristic values, D0, G0 and E0, showed that in all cell lines in which colony-forming ability and unscheduled DNA synthesis were diminished, a reduction of DNA-incising activity occurred. We conclude that this reduction accounts for both the decreased colony-forming ability and unscheduled DNA synthesis.

Autoradiography↗
PubMed1982

Dose-response analysis of the enhancement of liver tumour formation in CF-1 mice by dieldrin.

The current study was undertaken to investigate the dose-response characteristics of dieldrin-mediated enhancement of liver tumour formation in CF-1 mice. The median time to tumour development was established in controls, and in dieldrin-treated animals at six levels of continuous exposure (0.1, 1, 2.5, 5, 10 and 20 p.p.m.). The results of the analysis, which was based on liver tumour data from two parallel chronic feeding studies involving 1800 mice, are at variance with those reported by Druckrey for various established chemical carcinogens. In a double-logarithmic system of coordinates there was no linear relationship between the median total dose or the median time to tumour formation and the daily dieldrin exposure level. These results suggest that the tumourigenicity of this compound in CF-1 mouse liver is determined not by the sum of all consecutive doses, but rather by the level of daily exposure, and, presumably, the duration of treatment. This concept is consistent with the observed dose-dependency and reversible nature of dieldrin-induced subcellular changes in mouse liver. These considerations, together with evidence that dieldrin and its mammalian metabolites possess neither genotoxic activity nor potential, are not inconsistent with the concept that this compound is devoid of initiating potential, and operates by enhancing the effect of a genetically linked oncogenic factor in CF-1 mouse liver.

Adenoma↗
PubMed1980

[Discriminant analysis in the quantitative evaluation of lung scintigrams (author's transl)].

Lung scintigrams made with 99mTc-MAA in a group of patients and a control group were compared and classified by a discriminant analysis based on two regional methods and several parameters for quantitative characterisation of the regions. Improved results are gained by a regional division of the lung orientated in the pulmonary lobes and segments and by combining several parameters.

Analysis of Variance↗
PubMedDate not supplied

Implications of the carcinogenic hazard of low doses of three hepatocarcinogenic N-nitrosamines.

The data of a large-scale experiment on single and combination effects of very low doses of the hepatocarcinogenic N-nitrosamines N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), and N-nitrosodiethanolamine (NDElA) were modeled by new statistical methods to derive implications of the carcinogenic hazard of dose ranges so low as to result in long-term toxic effects only slightly different from the background. According to this model a linear relationship was found to exist between daily exposure to low N-nitrosamine levels and time to death with liver tumor. Extrapolation of these data to zero exposure suggested the occurrence of one to ten percent of spontaneous liver tumors in animals surviving more than 1000 days. At this advanced age a further reduction of carcinogen-induced liver tumor incidence does not contribute to a longer overall survival due to competitive, probably independent, causes of death. A quasi-threshold in terms of a "no-observed-effect level" can thus be derived from the data. The observed combination effect indicates a mere additivity in liver tumor occurrence, even at very low doses which alone cause no significant carcinogenic effect during the animal's lifetime. Within the combination of NDEA, NPYR and NDElA, N-nitrosodiethylamine was found to be the most carcinogenic agent: it contributes by at least 17 orders of magnitude more to the relative risk of dying with liver tumor than the other two compounds, if the daily dose is increased by one unit (0.1 mg/kg). Likewise, NDEA shows the steepest slope when assessing the relationship between daily carcinogen doses and time to liver tumor occurrence; relative to NDElA--the least potent carcinogen on a weight basis--and NPYR a 40-fold and 9-fold quicker appearance of liver tumors has to be expected, if the daily doses are increased by an equivalent amount.

Animals↗
PubMedDate not supplied

Quantitative analysis of resistance and cross-resistance to cytotoxic agents by tumour cell lines.

The published literature describing the spectrum of resistance and cross-resistance to cytotoxic agents by human and murine tumour cell lines maintained in long-term culture is reviewed. The data available demonstrate that for many cytotoxic agents, especially those of higher molecular weight, cross-resistance is proportional to the degree of resistance against the selecting agent. Furthermore, the degree of cross-resistance correlates with the molecular weight of the drug in adriamycin-, vincristine- and colchicine-resistant cell lines.

Animals↗