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J Grosse

Publications and source records attributed to J Grosse.

57 records · Page 4Linked to original sources

Tumour microdissemination and survival in metastatic melanoma.

The value of tyrosinase messenger RNA (mRNA) detection by reverse-transcriptase polymerase chain reaction (RT-PCR) as a marker for circulating melanoma cells remains controversial. However, it has been suggested that detection of melanoma cell mRNA may be used to evaluate prognosis and disease progression in patients with advanced malignant melanoma. We used a highly sensitive tyrosinase RT-PCR detection assay to test peripheral blood specimens of 80 patients with metastatic malignant melanoma. Moreover, we developed a multiple marker RT-PCR assay detecting a variety of additional melanocyte/tumour specific markers addressing the potential heterogeneity of gene expression of circulating melanoma cells. Thus subgroups of 32 and 12 out of all the 80 patients were also analysed for multimarker gene expression in their peripheral blood and bone marrow specimens, respectively. Altogether, 15 out of 80 patients tested positive for one or more molecular markers with heterogeneous melanocyte/tumour gene expression patterns. All RT-PCR positive patients presented with progressive and widely disseminated disease. We concluded that the detection of melanoma cell mRNA occurs in a stage of massive tumour progression and may predict poor clinical outcome in advanced malignant melanoma patients (p < 0.001). In addition, the multiple marker RT-PCR analysis was more reliable and sensitive than a single molecular marker assay for the detection of melanoma cells.

Adult↗

In vivo tumor necrosis factor-alpha as indicator of biologic and clinical response to low-dose SC recombinant interleukin 2.

The effect of low-dose human recombinant interleukin-2 (rIL-2) on the induction of secondary tumor necrosis factor-alpha (TNF-alpha) in vivo was studied in 16 patients with metastatic renal cell carcinoma. In all patients s.c. rIL-2 resulted in a significant increase in TNF-alpha serum levels within 4 to 8 hours, as determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha serum concentrations remained elevated up to 24 hours following single s.c. administration of rIL-2. Total secondary TNF-alpha release, as assessed by the area under the curve (AUC), appeared to be independent of dose distribution of rIL-2 (10 million IU rIL-2 q12 hours versus 20 million IU rIL-2 q24 hours). rIL-2 induced TNF-alpha release was significantly higher in patients who had received prior rIL-2 immunotherapy, while steroids resulted in a significant suppression of TNF-alpha release. Secondary TNF-alpha release was statistically associated with progression-free survival of renal cell carcinoma patients and may be a prognostic factor in patients receiving rIL-2.

Adult↗

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↗