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BackgroundSunitinib is a protein tyrosine kinase-inhibitor targeting VEGFR, c-kit and PDGFR. It has been approved for the treatment of metastatic renal-cell carcinoma and gastrointestinal stromal tumors. Although it has been shown to prolong disease-free and overall survival in renal-cell carcinoma patients, only 70% of the treated population receive a clinical benefit (CB) from the treatment. Markers that could predict clinical benefit to sunitinib would be an important aid in monitoring and following their treatment. We assessed the outcome and plasma proangiogenic factors in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib in our institution.MethodsWe have treated 42 patients with metastatic clear-cell renal carcinoma with sunitinib. Plasma concentrations of VEGF-A, sVEGFR2 and PDGF were determined by ELISA.ResultsAt the time of analysis 39 patients were evaluable for response and 30 patients had obtained a clinical benefit (CB). Median progression-free survival was 268 days (8.93 months) and median overall survival was 487 days (16.23 months). Interestingly, disease stabilization or objective response resulted in comparable overall survival. Most treatment-related adverse events were of mild-to-moderate intensity with one treatment-related death. Plasma sVEGFR2 and PDGF levels had no predictive value. Fold-increase in plasma VEGF was significantly lower in patients that obtained a CB as compared to patients that progressed after two cycles of treatment. Plasma VEGF did not increase in patients with initial CB at the time of progression.ConclusionSunitinib showed substantial activity in mRCC. Disease stabilization or objective response resulted in comparable overall survival and both outcomes should be considered positive. Fold-increase in plasma VEGF predicts for CB and could be a candidate marker. Progression after initial CB is not associated with elevated plasma VEGF, implying a different mechanism of resistance.

Prophylaxis with mesna prevents oxidative stress induced by I/R in the intestine via inhibition of NF-kappaB activation.

Presented study was conducted to investigate the prognostic significance of the coexpression of serum interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in breast cancer, by correlating their presence with clinicopathological characteristics indicative of tumor progression and the overall survival of breast cancer patients. One hundred twelve consecutive patients with primary breast cancer were prospectively included and evaluated. Serum concentrations of IL-6 and TNF-a were measured by quantitative sandwich enzyme immunoassay (ELISA). Median split was used to subdivide patients with low or high IL-6 and TNF-a levels. A positive association between the expression of the two cytokines was found. The coexpression of high IL-6 and TNF-α was independently associated with extended lymph node (>3) involvement (aOR, 7.8) and lymphovascular invasion (aOR, 14.1), increasing the prognostic significance of each cytokine separately; it also provided additional prognostic information regarding survival, defining a high-risk subgroup of patients with significantly shorter survival and higher risk of death compared to patients with both cytokines low (aHR, 4.45) and patients with only one cytokine high (aHR, 3.63). Our findings suggest that the coexpression of these two cytokines could be used clinically as a useful tumor marker for the extension and the outcome of the disease.

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