PubMed Health⌕ Search

Biomedical subjects

T Brodowicz

Publications and source records attributed to T Brodowicz.

40 records · Page 3Linked to original sources

[The significance of adhesion molecules in oncology].

Adhesion molecules are membrane proteins responsible for the complex functions of cell adhesion and cellular recognition and are thus of importance in inflammatory as well as neoplastic diseases. Adhesion molecules seem to play a significant role at each level of the metastatic cascade, including the destruction of normal cell-cell as well as cell-substrate cohesion, the penetration of tumor cells into the vascular system and the further spread into distant organs. In this summary an overview of subtypes, structure and function of the major groups of adhesion molecules is given and their possible role in the development, propagation and metastatic spread of malignancies discussed. Cell adhesion and its defects may be of importance in the behaviour of tumor cells and their spread. A better understanding of their function and possible manipulation of their expression, e.g., by cytokines could provide new therapeutic approaches in clinical oncology.

Cell Adhesion↗

Tissue expression and serum levels of HER-2/neu in patients with breast cancer.

We have analyzed serum levels of soluble HER-2/neu in 42 primary breast cancer patients prior to any therapy and studied the relationship between the overexpression and amplification of HER-2/neu in the primary tumor after surgical excision and data obtained by pathohistological staging. In addition, we have investigated the sera of 62 patients with stage IV breast cancer. Using an enzyme-linked immunosorbent assay, we observed elevated serum HER-2/neu levels in 6/42 (14.2%) preoperative patients. In 42.8% of the patients with HER-2/neu tumor expression/amplification serum levels were increased. In contrast, only 8.5% of the patients without HER-2/neu expression/amplification in the primary tumor presented with elevated serum levels. There was a significant correlation between serum concentrations of soluble HER-2/neu and tumor size (p < 0.0001) or axillary lymph node involvement (p < 0.0001). In patients with stage IV disease, 27 of 62 (43.5%) had elevated soluble HER-2/neu serum levels. A highly significant correlation between soluble HER-2/ neu and CA 15-3 (p < 0.002) was observed. The correlation of serum concentrations of HER-2/neu with estrogen and progesterone receptor status of the primary tumor was not significant in both groups. In conclusion, the measurement of serum HER-2/neu levels at diagnosis defines a small subgroup of breast cancer patients with a relatively advanced stage of disease. Its strong correlation with tumor load in patients with stage II disease and the high prevalence in patients with stage IV disease could make it a promising tool for the assessment of disease activity and biologic behavior in breast cancer.

Biomarkers, Tumor↗

Sequential administration of interferon-gamma, GM-CSF, and interleukin-2 in patients with metastatic renal cell carcinoma: results of a phase II trial.

Various cytokine combinations have been tested for efficacy in the treatment of metastatic renal cell carcinoma (MRCC). Because several immunologic synergisms between granulocyte-macrophage colony-stimulating-factor (GM-CSF) and interleukin-2 (IL-2) have been demonstrated, this phase II trial was conducted on the efficacy and toxicity of subcutaneous, sequentially administered, interferon-gamma (IFNgamma), GM-CSF, and IL-2. Fifty-five consecutive patients with MRCC were treated with 100 microg recombinant IFNgamma1b administered thrice weekly during weeks 1 and 4, followed by 400 microg GM-CSF on 5 consecutive days during weeks 2 and 5. In weeks 3 and 6, patients received 4.5 MU recombinant IL-2 from days 1 to 4. The treatment was repeated every 8 weeks. Five (10%) of patients experienced an objective response (complete response [CR]: 2%, partial response [PR]: 8%). Fourteen (26%) patients had stable disease with a median duration of 19 months (6-47+). The median overall survival was 12 months (range: 0.3-44 months). No toxicity greater than World Health Organization grade II was observed, with fever (43%) and erythema (43%) being the most frequent side effects. Compared with other phase II trials with IFN-gamma and IL-2 alone, the addition of GM-CSF failed to improve response or survival in patients with MRCC.

Adult↗

Serum levels of vasoactive intestinal peptide (VIP) in patients with adenocarcinomas of the gastrointestinal tract.

BACKGROUND: VIP acts as a neuroendocrine mediator under physiological conditions, with an important role in water and electrolyte secretion in the gut. Recent findings suggest that VIP also promotes growth and proliferation of normal as well as malignant cells. We have investigated the VIP-serum levels in patients with pancreatic cancer and colonic adenocarcinoma as compared to healthy controls. This was accompanied by immunohistochemical investigations and in vitro experiments to further define the role of the peptide in pancreatic and colorectal cancer. MATERIALS AND METHODS: Serum levels of VIP were evaluated under standardized conditions in a total of 135 patients; 45 patients had metastatic colorectal cancer, 45 suffered from metastatic pancreatic cancer, and 45 healthy volunteers served as controls. Human pancreatic and colorectal carcinoma cell lines were incubated over 5 days with VIP in increasing concentrations. RESULTS: In healthy controls, a median VIP-serum level of 42.44 +/- 2.540 pg/ml (range, 12.9-98.5 pg/ml) was found, while patients with pancreatic cancer had a median level of 40.58 +/- 3.013 pg/ml (range, 6.9-102.4 pg/ml). In patients with cancer originating in the colon, however, a median serum level of 116 +/- 10.14 pg/ml (range, 51.6-487 pg/ml) was found. While no difference between healthy controls and patients with pancreatic cancer could be detected (p = 0.6381), a significant difference between patients with colorectal cancer and healthy controls (p < 0.0001) and patients with pancreatic cancer (p < 0.0001) was demonstrated. The median VIP-concentrations found in the patients sera for pancreatic and colonic tumor patient groups, 40 pg/ml and 115 pg/ml respectively, had no significant effect on the proliferation of PANC-1 and HT29, inhibited ASPC-1, BxPC3, COLO201 and HCT-15 cells, and stimulated the growth of one pancreatic (CAPAN-1) and one colonic (COLO320DM) cell line under these conditions. CONCLUSIONS: As opposed to pancreatic cancer and healthy controls, patients in our series had elevated serum VIP-levels. Further studies are warranted to evaluate whether VIP can be used as a tumor marker in this disease.

Adenocarcinoma↗