Biomedical subjects
W Brenner
Publications and source records attributed to W Brenner.
Beta 1 integrin expression in adenocarcinoma of Barrett's esophagus.
BACKGROUND/AIMS: In vitro and in vivo studies did not show that beta 1 integrin expression is associated with malignant transformation or that it is of prognostic value in some malignant tumors. There are no data on the expression or prognostic value of beta 1 integrins in adenocarcinoma of Barrett's esophagus. METHODOLOGY: We assessed the expression pattern and the prognostic impact of beta 1 integrins in paraffin-embedded specimens of 41 patients with adenocarcinoma of Barrett's esophagus by immunochemistry. At the time of investigation, neither histomorphological parameters nor the survival time were known. RESULTS: There was no correlation between histomorphological parameters and the expression of beta 1 integrins. The expression of beta 1 integrins had no influence on long- term survival. There was a relationship between the prognosis and the following histopathological parameters: pT, pN and pM category, the UICC stage, the presence of lymphangiosis, and the DNA content of the tumor cells. CONCLUSIONS: The preliminary results obtained in this study did not show that the expression of beta 1 integrins was of prognostic value in patients with adenocarcinoma of Barrett's esophagus. Further studies in a larger number of patients are required to confirm the results obtained in this investigation.
Comparative study on the clinical use of protein S-100B and MIA (melanoma inhibitory activity) in melanoma patients.
BACKGROUND: The guidelines for the care of melanoma patients have not recommended the routine use of tumor markers up till now. In comparison to the blood parameters, two serum proteins have demonstrated their usefulness in the follow-up of melanoma patients: protein S-100B, a member of the S100 protein family, and "Melanoma-inhibitory activity" (MIA), a recently described 11 kd soluble protein. We analysed the serum levels of S-100B and MIA in non-melanoma control patients and in melanoma patients in different stages of disease (stage I-IV) to report on the sensitivity and specificity of both tumor markers. PATIENTS AND METHODS: The serum concentration of S-100B was evaluated by a luminoimmunometric assay (LIA) in 670 blood samples of 87 melanoma patients and, as controls, in 169 blood samples of patients with different skin diseases apart from melanoma. MIA serum levels were measured by an enzyme-linked immunoassay (ELISA) in 791 serial blood samples of 87 melanoma patients and in 158 blood samples of control patients. A cut-off of 0.12 microgram/l (S-100B) and 6.5 micrograms/l (MIA) served as upper normal values in the melanoma group as recommended by the producing industrial companies. In the control patient group, we additionally used the cut-off value of 0.2 microgram/l for S-100B and 8.5 micrograms/l for MIA, respectively. RESULTS: In stage I/II 37.5%, in stage III 50% and in stage IV 80% of the blood samples were S-100B positive (> or = 0.12 microgram/l) prior to treatment. Post treatment (after complete surgery) S-100B was below the cut-off value in stage I/II 83.9%, in stage III 82% and in stage IV 85.7%, respectively. For MIA we found in stage I/II 0%, stage III 53.8% and in stage IV 68.3% of the blood samples positive (> or = 6.5 micrograms/l) prior to treatment. Post treatment: stage I/II 88.3%, stage III 90.3% and stage IV 93.1% were below the cut-off value. In the control group we found 85.8% and 89.9% of the blood samples beneath the cut-off values for S-100B and MIA, respectively. CONCLUSION: We were able to identify the majority of patients with advanced metastatic melanoma by analysing the serum levels of S-100B and MIA. The specificity of both tumor markers was within acceptable limits. However, the available data suggest that a slightly higher cut-off value might be of clinical value.
Angiogenesis and fibroblast proliferation precede formation of recurrent tumors after radiation therapy in nude mice.
Recently, the combination of ionizing radiation with inhibitors of angiogenesis has been reported to improve tumor eradication compared to treatment with irradiation alone. However, the mechanisms of this effect have not been defined. For this purpose [corrected] we established a non-small cell lung cancer model in nude mice. Tumor vascularization was visualized in vivo by MRI using gadolinium-DTPA as contrast agent. Further, cryosections were produced as close as possible to the MRI slice positions. Since we were interested in examining the formation of a recurrent tumor, irradiation was performed with a single fraction of 4 Gy. This dose caused a partial remission followed by recurrent tumor growth 25 to 35 days after therapy. The process of partial remission as well as formation of the recurrent tumor was examined in 28 nude mice analysing the following parameters: (i) contrast agent enhancement using high-resolution MRI, (ii) proliferation of tumor cells and fibroblasts using Ki-67 immunohistochemistry and (iii) formation of microvessels using CD31 immunohistochemistry. The latter analyses led to differentiation of three stages. Stage 1 (day 1 to day 15 after irradiation) was characterized by increasing areas of dead cell mass in hematoxylin-eosin-stained slides that corresponded to a decrease in tumor cell proliferation as well as contrast agent enhancement in MRI. The percentage of Ki-67-positive tumor cells decreased from initially 45.1% +/- 6.0% (mean +/- standard deviation) to 1.4% +/- 1.2% (mean +/- standard deviation) on day 15. Stage 2 (day 6 to day 20 after irradiation; overlapping with stage 1) was characterized by proliferation of fibroblasts leading to formation of fibrotic septae with abundant microvessels. Already during late stage 2, MRI identified new contrast agent enhancing areas. Stage 3 (day 20 to day 40 after irradiation) was characterized by new tumor cell proliferation. Interestingly, tumor cells almost exclusively proliferated in the direct neighbourhood of the fibrotic septae that had been formed in stage 2. Obviously, proliferation of fibroblasts and blood vessels was a condition prior to formation of recurrent tumor tissue. Thus, our results are in contrast with the view that tumors or recurrent tumors begin as avascular masses that later induce neovascularization. With respect to clinical practice, our results suggest that: (i) adjuvant anti-angiogenic therapy should not be limited to the day of irradiation but should cover a critical period until day 5 to day 20 after radiotherapy, (ii) adjuvant therapy should also include inhibition of fibroblast proliferation and (iii) MRI can identify a recurrent tumor 10 to 15 days before occurrence of new tumor growth.
N-acetylation of drugs: search for INH acetylation polymorphism in baboons.
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Heavy water slows down the photoperiodic timing of flower induction in Chenopodium rubrum.
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