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Biomedical subjects

L Edler

Publications and source records attributed to L Edler.

At least 91 records · Page 5Linked to original sources
PubMed1987

DNA repair synthesis in fibroblast strains from patients with actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or malignant melanoma after treatment with ultraviolet light, N-acetoxy-2-acetyl-aminofluorene, methyl methanesulfonate, and N-methyl-N-nitrosourea.

Fibroblast strains derived from skin biopsies of patients with actinic keratosis (6), malignant melanoma (18), squamous cell carcinoma (11), and basal cell carcinoma (12) were investigated for DNA repair synthesis, with 16 fibroblast strains for normal donors as controls. Cells were exposed to UV light, the "UV-like" carcinogen (Ac)2ONFln, and the methylating carcinogens MeSO2OMe and MeNOUr. Dose-response experiments, which included 10 dose levels, were performed, the data analyzed by linear regression, and the slope of the regression line (term: G0) used as a measure of DNA repair synthesis. The mean experimental variability of G0 of individual fibroblast strains was 9.5%-15.4%, depending upon exposure. For comparison of all cell strains belonging to the same skin malignancy group with those of the control group, G0 values of the individual strains were combined to yield group-specific weighted mean G0 values. In addition, the capacity to incise UV-damaged DNA was measured in 24 cell strains from patients with skin tumors using the alkaline elution technique. For quantitating DNA-incising capacity, the initial velocities of the elution curves were plotted versus the UV dose, and the slope of the resulting regression line was used to obtain the characteristic value E0. The mean experimental variability of E0 of individual strains was +/- 22%. These E0 values were combined to yield weighted mean values of groups. The fibroblast strains in the groups of patients with actinic keratosis and malignant melanoma were found to have normal mean G0 values when DNA repair synthesis was challenged with UV light or one of the three carcinogens. However, the squamous cell carcinoma group exhibited significantly lower mean G0 values after treatment with UV light (82% that of normal donors), (Ac)2ONFln (70%), MeSO2OMe (70%), and MeNOUr (69%). The basal cell carcinoma group showed significantly diminished repair synthesis upon treatment with UV light (81% that of normal donors) and MeSO2OMe (67%). In contrast to these findings, in no skin malignancy group was post UV DNA-incising capacity (E0) significantly diminished, although it should be noted that group sizes were only half as large as for G0 determinations. These data may be interpreted as indicating that DNA excision repair is impaired in fibroblast strains from patients with squamous cell carcinoma and-to a lesser extent-basal cell carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetoxyacetylaminofluorene↗
PubMed1987

A sample size program for "proving the null hypothesis".

A flexible APL computer program is presented for assistance in planning clinical trials designed to test the equivalence of two therapies. It is a substitute for the sample size graphs of Blackwelder and Chang and provides the option to calculate any of the six characteristics--sample size, significance level, power, success probability of standard therapy, success probability of experimental therapy, and minimum difference of interest--if five of them are prespecified.

Clinical Trials as Topic↗
PubMed1987

Simple elementary method for the quantification of focal liver lesions induced by carcinogens.

Quantification of focally arranged preneoplastic cell populations in the liver is relevant for numerous experiments. An easy-to-process elementary method is presented for the estimation of the number of foci per cm3 and the size distribution of the foci on the basis of classifying areas of the profiles on the histological section. Using geometrically decreasing size classes, we have obtained the formula: (Formula: see text) where Nn is the number of foci per unit of volume of the size class Kn, Fn is the number of profiles of the class Kn per surface unit and An and Bn are constants dependent on the selection of the boundaries of the size classes. The method presented provides results that are at least as accurate as the values for the numbers of foci per cm3 arrived at by other methods used so far, whereas the distribution of the focus volumes describes the real situation better. It is relatively easy to process the data collected from the section and this can also be done without specific programs developed for this purpose. The method is especially recommended for investigators who only occasionally deal with morphometric questions and are therefore not interested in more complicated methods.

Animals↗
PubMed1987

Benzoyl peroxide promotes the formation of melanotic tumors in the skin of 7,12-dimethylbenz[a]anthracene-initiated Syrian golden hamsters.

A two-stage carcinogenesis experiment was performed in Syrian golden hamsters using a single intragastric initiation with 10 mg/kg body weight of 7,12-dimethylbenz[a]anthracene (DMBA) and repetitive topical promotion on the back skin with two different doses (80 and 160 mg, respectively) of benzoyl peroxide in 1 ml acetone. Benzoyl peroxide was administered three times per week over a period of 16 months. The treatment with benzoyl peroxide alone leads to both a generalized hyperpigmentation and skin scaling without formation of any tumors. DMBA initiation alone induces a moderate number of melanotic foci and a small number of palpable melanotic tumors. Both lesions are located in the dermis. Papillomas develop in the epithelia of the tongue, esophagus and especially of the forestomach but not, however, on the back skin. The combined treatment with DMBA and both doses of benzoyl peroxide drastically increases the incidence of dermal melanotic foci and at late stages also that of melanotic tumors. Therefore, in addition to its known ability to promote papilloma and carcinoma formation in the back skin of mice, benzoyl peroxide is also able to promote the formation of melanotic tumors in the dermis of hamsters.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

[Remission in phase II and phase III studies: criteria and prerequisites].

We identify factors of influence for the observed variability of published rates of remission and we derive from these findings prerequisites and criteria for the assessment of remission in cancer therapy. As a consequence we postulate a separate assessment of patients with measurable and with non-measurable disease and a complete documentation of those patient characteristics in order to compare rates of remission of different studies. Several methods for the determination of sample sizes in phase II and phase III clinical trials are presented and discussed.

Antineoplastic Agents↗
PubMed1986

Xeroderma pigmentosum patients from Germany: repair capacity of 45 XP fibroblast strains of the Mannheim XP Collection as measured by colony-forming ability and unscheduled DNA synthesis following treatment with methyl methanesulfonate and N-methyl-N-nitrosourea.

A total of 45 XP fibroblast strains from the Mannheim XP Collection (representatives of XP complementation groups A, C, D, E, F or G, I, and XP variants) were investigated for colony-forming ability (term: D0) after treatment with up to ten doses of the methylating carcinogen MeSO2OMe. As controls 16 fibroblast strains from normal donors were used. Except for 4 XP strains (1 from group C and 3 from group D) which, however, were borderline cases, none of the remaining 41 XP strains was found to be more sensitive than normal controls. This held true within the limits of an experimental accuracy (experimental variability of D0 values) of +/- 7%. When weighted means were calculated for XP complementation groups and compared with that of normal donors at a significance level of 5%, no significant difference was detected. In contrast, after exposure of 6 XP group D strains to MeNOUr, a weighted mean D0 value was obtained which was significantly decreased by 27%. Unscheduled DNA synthesis (term: G0 which serves as a measure of excision repair) after exposure to MeNOUr was quantitatively the same (experimental variability: +/- 8%) both in the group of normal strains and in most of the XP complementation groups. Exceptions were group E and group F (or G) which had higher, and group I which had lower repair. Analogous G0 values measured after exposure to MeSO2OMe (experimental variability: +/- 13%), however, differed from that of the control strains: they were lower in XP complementation groups A, D, E, F (or G), and I. However, groups A, E, F (or G), and I including only 3 individual strains or less may be considered to be possibly ill-represented. Yet, group D including 11 XP strains did show reduction of the mean G0 value by 35%. From this it is concluded that there are repair defects in XP group D strains with regard to MeSO2OMe-induced adducts. These defects seem to be small.

Alkylation↗
PubMed1986

Prognostic factors of advanced colorectal cancer patients.

The cooperative oncology group for Chemotherapy of Gastrointestinal Tumors (CGT) retrospectively examined 139 patients with metastatic colorectal cancer for prognostic factors. Clinical characteristics, tumor parameters, and blood parameters were investigated for prognostic explanation of survival from the start of chemotherapy for the advanced disease. A combination of a univariate regression and a multivariate step down procedure with Cox's regression model led to the identification of performance status, sex, white blood count and, to a lesser degree, blood sedimentation rate and albumin as important prognostic factors. Based on these variables an individual risk score was calculated for each patient.

Colombia↗
PubMed1986

Establishment and growth kinetics of the mutant Ehrlich-Lettré ascites cell strain HD33 in permanent suspension culture.

Cells of a mutant in vivo subline of the Ehrlich-Lettré mouse ascites tumour (ELAT) were converted to growth in suspension culture. Kinetic analysis revealed the selective character of the conversion process; without a detectable adaptation period, a fraction of about 2 X 10(-5) of the explanted cells continued to grow in vitro. The resulting, mutant Ehrlich-Lettré ascites cell strain was designated HD33 and propagated uninterruptedly from 1974 on. The corresponding in vivo ELAT subline HD33 was derived from the HD33 ascites cell strain by intraperitoneal retransplantation. In HD33 cell suspension cultures, the population doubling time, the average intermitotic interval, as determined by videomonitoring, and the average duration of the cell cycle, as determined from percentage of labelled mitoses (PLM) data, were all measured at 15 hr. Cell loss and quiescent compartments were insignificant. The duration of the G1 phase was effectively zero. Both PLM data and [3H]/[14C] thymidine double-labelling measurements revealed an S-phase duration of between 11 and 12 hr. The G2 phase lasted 3-5 hr. The HD33 strain differs from comparable suspension strains of wild-type Ehrlich ascites cells in the insignificant role of density-dependent inhibition in growth, and the striking prolongation of the S phase which is associated with an excessive, cytoplasmic storage of glycogen by the mutant cells.

Animals↗
PubMed1986

Prospective randomized trial concerning hyper- and normoprolactinemia and the use of bromoergocryptine in patients with metastatic breast cancer.

This prospective trial was designed to help in selecting therapy for patients with elevated and normal plasma prolactin. Ninety-two patients entered this trial, of whom 86 were evaluable for final analysis. Hyperprolactinemic patients (n = 31) were randomized to receive VAC/FMC chemotherapy with or without bromoergocryptine. Normoprolactinemic patients with 'low risk' metastatic disease (disease-free interval greater than 30 months, ER/PR positive or unknown) were treated with medroxyprogesterone acetate or VAC/FMC chemotherapy. Normoprolactinemic 'high risk' patients (n = 42) (disease-free interval less than 30 months, EP/PR negative) received VAC/FMC chemotherapy with or without medroxyprogesterone acetate (MAP). The results show that bromoergocryptine does not improve response rate, duration of response and survival. Median survival of patients with elevated basal plasma prolactin (greater than 15 ng/ml) is reduced to 9 months compared to patients with normal basal plasma prolactin (17 months, log-rank p = 0.005). Unexpectedly, TRH stimulation proved inappropriate to separate normo- and hyperprolactinemic patients in terms of survival. Normoprolactinemic 'low risks' (tamoxifen failures) were observed to qualify for further hormone therapy (median survival 21+ months). Normoprolactinemic 'high risks' showed median survival of about 12 months with no apparent benefit for those receiving MAP, additionally. The results suggest that basal hyperprolactinemia, disease free interval, ER/PR receptor status, and liver metastasis are important prognostic variables. Endocrine and cytotoxic chemotherapy should be selected according to these risk factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The predictive role of delayed cutaneous hypersensitivity testing in postoperative complications.

Ten parameters, including delayed cutaneous hypersensitivity testing (DCH), were evaluated with regard to their predictive value in instances of postoperative septic complications. In 302 patients undergoing surgical treatment, 45 complications, including wound infection, abscess, pneumonia and sepsis, were seen postoperatively in 42 patients. When these patients were compared with 260 patients without complications, hemoglobin, leukocyte count, serum albumin, total protein, blood sedimentation rate, age and sex were found not to contribute to the prediction of postoperative complications. In DCH testing, the complication rate increased from 7.5 per cent in normergic patients to 20.6 per cent in anergic patients. With increasing length and severity of operation, the complication rate increased from 6.5 to 26.4 per cent and from 6.5 to 31.8 per cent, respectively. Only in severe, long lasting operations could DCH testing differentiate the complication risk. Normergic patients had a 8.6 per cent complication rate; hypoergic patients, 36.6 per cent, and anergic patients, 37.5 per cent. The results of DCH testing did not correlate with the complication rate in any of the other operative groups. In conclusion, the predictive value of DCH testing is clearly greater in groups of patients highly affected by the operative trauma. The results of this study show that it is important to consider both host defense mechanisms and environmental factors in the assessment of operative risks.

Adult↗
PubMed1985

Xeroderma pigmentosum patients from the Federal Republic of Germany: decrease in post-UV colony-forming ability in 30 xeroderma pigmentosum fibroblast strains is quantitatively correlated with a decrease in DNA-incising capacity.

A total of 16 normal and 46 XP fibroblast strains from the Mannheim Collection were investigated for colony-forming ability following exposure to both UV light and the "UV-like" carcinogen (Ac)2ONFln. The dose-response experiments included up to 13 dose levels. The exponential segments of the curves were analysed by linear regression and the negative reciprocal of the regression coefficient (D0) was calculated for each cell strain. For quantitating the DNA-incising capacity, DNA elution curves were determined at several UV dose levels. Plotting the initial velocities of the elution curves versus the UV dose yielded a regression line, the slope of which was used to obtain the characteristic value E0. Comparing D0 with E0 values showed that cell strains in which colony-forming ability was reduced suffered a reduction of DNA-incising capacity of the same magnitude. There were only 3 exceptional strains in which reduction of DNA-incising capacity was less pronounced than reduction of colony-forming ability. We have previously shown (Fischer et al. 1982) that D0 values from 27 XP strains of the Mannheim Collection were correlated with clinical symptoms. This correlation is now being extended by relating colony-forming ability to the magnitude of the DNA incision defect. From our data we conclude that the best quantitative biochemical denominator to explain the sun sensitivity of XP is that of a defective incision of UV-damaged DNA. A considerable similarity in sensitivity towards both UV light and (Ac)2ONFln was found in 16 normal and 46 XP strains. This seems to indicate that UV- and (Ac)2ONFln-induced DNA damage are removed to a large extent by the same pathways in human fibroblasts.

Acetoxyacetylaminofluorene↗
PubMed1985

A ninth complementation group in xeroderma pigmentosum, XP I.

A new complementation group of excision-deficient xeroderma pigmentosum (XP) is described in 2 patients living in the F.R.G. Dermatological, ophthalmological and neurological symptoms of XP are presented together with DNA repair characteristics such as unscheduled DNA synthesis, colony-forming ability and alkaline elution studied in cultured fibroblasts. The results are compared to normal controls.

Adolescent↗
PubMed1985

Computational statistics for cell survival curves. I. Evaluation of the colony-forming ability of a single cell strain by the APL function CFALINE.

An interactive program for the statistical analysis of cell survival curves by a linear regression approach is described. It allows for the computational determination of the linear part of a cell survival curve and the determination of a common slope estimate in the presence of repeated experiments for a particular cell strain with the appropriate variance estimates and confidence intervals.

Biometry↗
PubMed1985

An investigation of the adequacy of a randomization.

A randomization actually performed in an individual-based double-blind intervention trial in cancer epidemiology is investigated concerning the resulting imbalance of treatment assignment. Complete randomization, permuted block procedures, and adaptive urn models are simulated in order to assess how representative the achieved distribution is for the procedure used and how other procedures would have performed on the given study population. The achieved randomization is deemed to be satisfactory and the different procedures are discussed in light of different logistic requirements. It is argued that such investigations should be carried out when debating the implications of a given randomization.

Adult↗
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↗