Biomedical subjects

Lutz Edler

Publications and source records attributed to Lutz Edler.

7 recordsLinked to original sources

PubMed2003

L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas.

BACKGROUND: Ovarian and uterine carcinomas are the most common cause of cancer-related deaths in gynecological malignant diseases. We aimed to assess whether the L1 adhesion molecule, an important mediator for cell migration for neural and tumour cells, is expressed in these carcinomas. METHODS: We investigated L1 expression by immunohistochemistry, RT-PCR, and Western blot analysis of tumour samples. Soluble L1 in the serum was detected by ELISA and immunoprecipitation. FINDINGS: We detected the L1 adhesion molecule in ovarian and uterine tumours in a stage-dependent manner. In a retrospective study L1 was found in 46 of 58 ovarian carcinomas and 20 of 72 uterine adenocarcinomas. L1 expression was an excellent predictor of poor outlook (p<0.00001). Patients with L1 positive uterine tumours were at high risk for progression even in the endometrioid-type tumours, which usually have a favourable prognosis. In uterine tumours, expression of L1 in curettage samples enabled us to identify aggressive tumours before the operation. Soluble L1 was specifically detected in serum samples from patients with ovarian and uterine tumours. ADAM10, which was implicated in previous studies as L1 sheddase, was expressed in tumours in which soluble L1 was present in the serum. INTERPRETATION: L1 is overexpressed in ovarian and uterine carcinomas and is associated with short survival. L1 can serve as a new marker for prediction of clinical outcome and could be helpful to identify patients with uterine tumours who are at high risk for recurrent disease. L1 expression and cleavage could promote dissemination of tumours by facilitating cell migration.

Antigens, Neoplasm↗

PubMed2003

Improvement in muscular performance and decrease in tumor necrosis factor level in old age after antioxidant treatment.

Aging-related loss of muscle function is a predictor of mortality and a surrogate parameter of the aging process. Its consequences include a high risk for falls, hip fractures, and loss of autonomy. Aging is associated with changes in the oxidant/antioxidant balance including a decrease in plasma thiol (cysteine) concentration. To assess the importance of cysteine, we determined in a double-blind study the effects of N-acetylcysteine on the functional capacity of frail geriatric patients and their response to physical exercise. The subjects on placebo showed only a relatively weak response, and 31% showed even a decrease in more than one parameter during the observation period. Low plasma arginine levels were correlated with a weak overall performance before exercise and a poor response to exercise. N-Acetylcysteine strongly enhanced the increase in knee extensor strength and significantly increased the sum of all strength parameters if adjusted for baseline arginine level as a confounding parameter. N-acetylcysteine had no significant effect on growth hormone and IGF-1 levels but caused a significant decrease in plasma TNF-alpha. These findings may provide a basis for therapeutic intervention and suggest that the loss of function involves limitations in cysteine and one or more other amino acids which may compromise muscular protein synthesis.

Acetylcysteine↗

PubMed2003

Association between human papillomavirus 16 E6 variants and human leukocyte antigen class I polymorphism in cervical cancer of Swedish women.

Persistent infection with human papillomavirus (HPV), particularly HPV16, represents the prime risk factor in cervical carcinogenesis. HPV variants (e.g., within the E6 gene) together with immunogenetic factors of the host may be responsible either for effective viral clearance, or alternatively, for viral persistence. Peripheral blood from 27 HPV16 positive Swedish women with cervical carcinoma, who had previously been tested for HPV16 E6 variants, was used for human leukocyte antigen (HLA) class I typing. Women with HLA-B*44, HLA-B*51, or HLA-B*57 who were infected with the HPV16 E6 variant L83V had an approximately four- to fivefold increased risk for cancer compared with controls (odds ratio [OR] = 3.5, 95% CI = 1.1-11.1, OR = 4.2, 95% CI = 1.19-14.69, or OR = 4.67, 95% CI = 1.2-18.6, respectively). Epitope predictive algorithm with SYFPEITHI revealed that the variant at amino acid 83 affects the binding affinity in association with HLA-B*44. Interestingly, the HLA-B*15 allele seems protective because it was absent in HPV16 positive cancer. It is concluded that specific HLA class I alleles, combined with certain HPV16 E6 variants, may be crucial for immune surveillance in cervical carcinogenesis. The evaluation of associations of HLA alleles with HPV variants may be helpful in defining prognostic markers and in designing vaccines capable of mediating immune protection against HPV infection.

Algorithms↗

PubMed2002

Myeloperoxidase (MPO) genotype and lung cancer histologic types: the MPO -463 A allele is associated with reduced risk for small cell lung cancer in smokers.

MPO participates in the metabolic activation of tobacco carcinogens such as PAHs. A frequent MPO -463 G-->A polymorphism in the promoter region reduces MPO transcription and has been correlated with >4-fold lower benzo[a]pyrene-DNA adduct levels in the skin of coal tar-treated patients. Four of 7 case-control studies found significantly reduced lung cancer risk associated with the A allele. Due to their different etiologies, we examined whether the MPO genotype affects histologic lung cancer types differentially. A case-control study was conducted in 625 ever-smoking lung cancer patients, including 228 adenocarcinomas, 224 SCCs, 135 SCLCs and 340 ever-smoking hospital controls. MPO genotyping was performed by capillary PCR followed by fluorescence-based melting curve analysis. Combining the MPO -463 (G/A+A/A) genotypes, a protective effect approaching significance (OR = 0.75, 95% CI 0.55-1.01) was observed when comparing all lung cancer cases to controls. Among histologic types of lung cancer, a weak protective effect was found for both adenocarcinoma (OR = 0.81, CI 0.55-1.19) and SCC (OR = 0.82, CI 0.56-1.21); a stronger and significant effect was found for SCLC (OR = 0.58, CI 0.36-0.95; p = 0.029). Our results also suggest that the MPO genotype varies among inflammatory nonmalignant lung diseases. In conclusion, our results emphasize the need for a separate analysis of lung cancer histologic types and an adjustment for inflammatory nonmalignant lung diseases in future MPO-related studies. We confirm that the MPO -463 A variant affords a protective effect against lung cancer risk in smokers, which was strongest for SCLC patients.

Adenocarcinoma↗

PubMed2002

Expression of CEACAM1 in adenocarcinoma of the lung: a factor of independent prognostic significance.

PURPOSE: To evaluate the prognostic relevance of CEACAM1 and sialyl Lewis X expression in adenocarcinomas of the lung. PATIENTS AND METHODS: Paraffin wax sections of 93 patients with adenocarcinomas of the lung who underwent surgery between 1990 and 1995 were immunohistochemically investigated using monoclonal anti-CEACAM1 and sialyl Lewis X antibodies. The clinical course of all patients was followed up for a minimum of 5 years. RESULTS: Sixty-one tumors were classified as CEACAM1-positive, and 32 were classified as CEACAM1-negative. Patients with CEACAM1-positive tumors had a significantly poorer overall (P =.00025) and relapse-free (P =.00029) survival than those with CEACAM1-negative tumors. Only three patients did not express the sialyl Lewis X glycotope, whereas 90 tumors (97%) were sialyl Lewis X-positive. In multivariate Cox regression analysis, next to tumor stage and sex, only the expression of CEACAM1 was a significant independent prognostic factor for survival. CONCLUSION: Expression of CEACAM1 was an independent prognostic factor in our patient population and can be used to stratify patients with adenocarcinomas of the lung into low-risk and high-risk groups. In contrast, the expression of sialyl Lewis X was of no prognostic relevance because it was expressed in 97% of all investigated tumors, and most likely has no influence on the function of CEACAM1 in this tumor entity.

Adenocarcinoma↗

PubMed2002

New measure of DNA repair in the single-cell gel electrophoresis (comet) assay.

Since its introduction by Ostling and Johanson [1984; Biochem Biophys Res Commun 123:291-298] and independent modifications by Singh et al. [1990; Exp Cell Res 175:184-191] and Olive et al. [1988; Radiat Res 112:86-94], the comet assay has been widely used in genetic toxicology, environmental biomonitoring, molecular and human epidemiology, and clinical investigations. There are still several issues to be resolved before the comet assay is accepted as a standard assay for detecting DNA damage and repair in a single cell. One of the major issues is the proper quantification of DNA damage/repair. The aim of this article is to develop a new quantitative measure of DNA damage/repair which is represented in the dose-time-response surface. We propose to use the second derivative (2D) of the dose-time-response surface for measuring DNA repair activity. This approach enables us to represent the DNA repair activity of cells exposed to a DNA-damaging agent with a single number by combining all the information of a dose-time-response experiment. The computation procedure includes the application of linear regression. An SAS/AF-based program, "Comet Assay," was developed for this computation and is freely available on the Internet. We considered the response of each of four DNA damage parameters: tail moment, tail length, tail DNA, and tail inertia for constructing the dose-time-response surface. Using data from 25 patients, we observed that 2Ds based on tail moment and tail DNA were highly correlated and that tail inertia might provide information on a somewhat different aspect of DNA damage/repair.

Breast Neoplasms↗

PubMed2002

Lectin histochemistry of resected adenocarcinoma of the lung: helix pomatia agglutinin binding is an independent prognostic factor.

The worldwide incidence of adenocarcinoma of the lung is rising. Unfortunately, no significant prognostic marker beyond the classical TNM staging exists to stratify these patients for appropriate therapy. Because lectins, carbohydrate-binding proteins, have been shown to be useful prognostic markers in several other adenocarcinomas, a panel of lectins [Helix pomatia agglutinin (HPA), Phaseolus vulgaris leukoagglutinin, Ulex europaeus agglutinin, Maackia amurenis agglutinin, Sambucus nigra agglutinin] with different carbohydrate-binding specificities were tested for their prognostic relevance. Paraffin wax sections of 93 patients with adenocarcinomas of the lung who had undergone surgery between 1990 and 1995 were investigated by lectin histochemistry. Lectin-binding data and other known prognostic factors were correlated with survival. In univariate analysis, binding of HPA, Phaseolus vulgaris leukoagglutinin, and Ulex europaeus agglutinin to adenocarcinoma cells were prognostic indicators for overall and relapse-free survival, whereas Maackia amurenis agglutinin and Sambucus nigra agglutinin binding had no prognostic value. However, in a multivariate analysis next to stage and gender only HPA was a significant independent prognostic factor on survival. In conclusion, HPA binding was the primary marker-based predictor of prognosis in our patient population and allows to stratify patients with adenocarcinomas of the lung into a low- and a high-risk group.

Adenocarcinoma↗