Biomedical subjects

J Atzpodien

Publications and source records attributed to J Atzpodien.

131 records · Page 8Linked to original sources

PubMedDate not supplied

Platelet endothelial cell adhesion molecule-1 (PECAM-1): a potential prognostic marker involved in leukocyte infiltration of renal cell carcinoma.

We investigated immunohistochemically the leukocyte infiltrate [CD3, CD4, CD8, CD11a, CD11b, CD14, CD56, VLA-4 and platelet endothelial cell adhesion molecule-1 (PECAM-1)] and the endothelial expression of cell adhesion molecules (PECAM-1, VCAM-1, ICAM-1 and ICAM-2) in 23 renal cell carcinoma tumor tissues. Tumors with a moderate or high density of PECAM-1 positive endothelia showed a stronger infiltration with PECAM-1-positive leukocytes as compared to tumors with a low density of positive endothelia (p<0.0085). Additionally, overall survival of patients who presented with tumors exhibiting a moderate or high density of PECAM-1 endothelia alone or in combination with a PECAM-1-positive infiltrate was extended (median survival: 23.5 months) as compared to patients without these tumor characteristics (median survival: 6.5 months). These results suggest an involvement of PECAM-1 in the process of leukocyte migration and a potential role as a prognostic marker in renal cell carcinoma.

Adult↗

PubMedDate not supplied

Fosfomycin does not reduce cytostatic activity of cis-platinum against human osteosarcoma cell lines in vitro.

Fosfomycin has been shown to ameliorate the dose-limiting ototoxicity and nephrotoxicity associated with the antineoplastic agent cis-platinum. Clinical use of fosfomycin in cis-platinum-treated tumor patients critically depends on retaining therapeutic efficacy of cis-platinum while designing modalities to reduce side effects. This study uses two independent assay systems for cell viability and proliferation; we demonstrate that cytocidal activity of cis-platinum against human osteosarcoma cell lines is not affected by various concentrations of fosfomycin up to 0.1 mg/ml in vitro. This suggests that in these cells there is no direct pharmacodynamic interaction of cis-platinum and fosfomycin with respect to mechanisms crucial for tumor kill.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Altered expression of beta 1 integrins in renal carcinoma cell lines exposed to vinblastine.

BACKGROUND: Cellular expression of P-glycoprotein (P-gp) which mediates a well characterized mechanism of multidrug resistance (MDR) has been reported previously to be associated with an enhanced tumor dissemination. Since adhesion receptors of the beta 1 integrin family play a substantial role in tumor spread, we studied expression of VLA-1 to -6 in a total of four renal carcinoma cell (RCC) lines prior to and after induction of MDR via exposure to vinblastine. MATERIAL AND METHODS: Surface expression of P-gp and VLA-1 to -6 was determined immunocytochemically in untreated pre-established renal carcinoma cell lines (Caki-1, Caki-2, A498) and a cell line derived from a RCC patient who had received a vinblastine-containing therapy regimen prior to the resection of a local relapse of the tumor (EH). Resistant sublines were cultivated in the presence of 1 ng/ml and 10 ng/ml of vinblastine sulfate, respectively. RESULTS: In all cell lines examined, an increased number of P-gp expressing cells was observed upon exposure to vinblastine. Significant changes of beta 1 integrin expression were observed in three of four RCC cell lines. A de novo expression of VLA-1, VLA-2, and VLA-4 as detected by immunocytochemistry occurred in resistant Caki-1 cells. A498 cells showed an increasing number of VLA-2 positive cells in drug resistant sublines. In contrast, a decrease of VLA-2 and VLA-5 expression was found in EH cells, the only cell line exhibiting P-gp expression prior to vinblastine exposure. Caki-2 cells showed no significant changes of surface integrin expression upon treatment with vinblastine. CONCLUSIONS: Our results demonstrate that induction of drug resistance can be associated with substantial changes of the integrin phenotype in renal carcinoma cell lines. In our experiments, among all VLAs studied, VLA-2 was most frequently altered in expression by RCC cell lines. The significance of these observations for aberrant metastatic properties of multidrug resistant tumor cells will be the subject of further studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

In vivo and ex vivo antitumor activity in patients receiving low-dose subcutaneous recombinant interleukin-2.

Alterations in cell-mediated cytotoxicity levels were studied in patients receiving recombinant interleukin-2 (rIL-2) via subcutaneous injection. Fourteen outpatients, aged 36-68 years, with progressive metastatic malignancies, were treated with weekly escalated doses of rIL-2, starting at 1.8 IU/m2/day for 6 days a week, up to 14.4 IU/m2/day during the 4th week of therapy. Patients presenting with stable disease thereafter were started on maintenance therapy and received 10.8 IU/m2 once weekly for up to 12 weeks. Patient mononuclear cells were isolated from fresh peripheral blood at various times throughout the treatment. Cells were assayed prior to and after further in vitro stimulation by rIL-2 (600 IU/ml for 7 days). Natural killing (NK) activity was measured by cytolysis of K 562 target cells, and lymphokine-activated killing (LAK) was determined by cytotoxicity against Daudi targets, respectively, in four effector:target ratios (E:T), using a standard 2-hour europium3+ release assay. Spontaneous NK cell function (E:T = 25:1) of freshly isolated peripheral blood mononuclear cells (PBMC) was enhanced significantly after 28 days of therapy (27.8 vs. 9.1% on day 0). LAK activity also markedly increased during therapy (26.2 vs. 5.4% on day 0). Further in vitro culture of these PBMC in the presence of rIL-2 resulted in day 28 non-MHC-restricted cytolytic activity of 63.2% (40.3% on day 0) against K 562 targets, and 64.9% (39.6% on day 0) against Daudi targets. Activation of cytolytic function by rIL-2 appeared to be dose-dependent, as measurable lytic capability decreased throughout maintenance therapy, while neither sex nor tumor entity prior to therapy or clinical response were correlated with cytotoxicity levels. Taken together, our observations demonstrate that stimulation of the non-MHC-restricted pathway of cytolytic activation, as measured by lysis of target cells, arises in patients treated with rIL-2 doses 5- to 30-fold lower than used previously in intravenous protocols, connecting effective clinical response rates with acceptable tolerability.

Adult↗

PubMedDate not supplied

Increased serum levels of basic fibroblast growth factor (bFGF) are associated with progressive lung metastases in advanced renal cell carcinoma patients.

Basic fibroblast growth factor (bFGF) has been detected in body fluids of patients with various malignancies including renal cancer. Cytoplasmatic expression of bFGF in primary renal cell carcinoma cells has been reported recently to correlate with an impaired patient survival. In the present study, we analysed the statistical association of spontaneous serum bFGF levels in 23 patients with advanced renal cell carcinoma and progressive metastasis in different organ sites. Increased bFGF serum levels (>90% percentile for healthy donors i.e., > 14 pg/ml) were found in eight patients (35%) with a mean of 24.1 pg/ml. All patients in this subgroup presented with progressive pulmonary metastases at the time of sample collection (p < or = 0.007). In a total of fifteen patients exhibiting progressive pulmonary metastasis, bFGF serum levels were found to be significantly higher when compared to patients lacking progressive lung lesions (p < or = 0.0006). Of fifteen patients with bFGF levels lower than 14 pg/ml, six showed bone metastases at the time of sample collection (p < or = 0.04). Our results suggest that increased serum bFGF levels may be associated with a higher frequency of progressive pulmonary metastases. Interactions between soluble angiogenic factors and components of the extracellular matrix or basement membranes in remote sites of metastasis will be subject to further experiments.

Adult↗