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The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways are two pathways crucial to many aspects of cell growth and survival, in physiological as well as in pathological conditions (e.g., cancer). Indeed, they are so interconnected that, in a certain sense, they could be regarded as a single, unique(More)
OBJECTIVE •To conduct a retrospective, multicentre, cohort analysis to assess the sequential use of the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib. PATIENTS AND METHODS •Records of 189 patients with renal-cell carcinoma (RCC) who were treated with sorafenib and sunitinib sequentially between March 2004 and April 2009 at 12 Italian study(More)
As newer, molecularly targeted, anticancer drugs are entering clinical practice, a wide array of previously unrecognised and ill defined side effects of these drugs are increasingly observed. Sorafenib and sunitinib are two of these novel agents, acting on tumour angiogenesis as well as on other key proliferative pathways; recently approved for the(More)
Although over 70% of patients with metastatic renal cell carcinoma (RCC) respond to initial therapy with tyrosine kinase inhibitors (disease control rate 70-80%), approximately 20-30% of patients do not respond to first-line therapy and progress within ≤3 months. Understanding the mechanisms of resistance to targeted therapies is vital in the development of(More)
BACKGROUND Renal cell carcinoma (RCC)-induced immune dysfunction in patients at first diagnosis was investigated. PATIENTS AND METHODS The main circulating lymphocyte subsets, the total number of circulating and intratumor dendritic cells and the titers of circulating VEGF were quantified in 47 RCC patients, using flow cytometric, immunohistochemical and(More)
BACKGROUND Sorafenib has proven efficacy in metastatic renal cell carcinoma (mRCC). Interferon (IFN) has antiangiogenic activity that is thought to be both dose- and administration-schedule dependent. OBJECTIVE To compare two different schedules of IFN combined with sorafenib. DESIGN, SETTING, AND PARTICIPANTS Single-stage, prospective, noncomparative,(More)
What has happened in the past 8 yr with regard to advanced renal cell carcinoma is something new and unprecedented in the field of urologic oncology and in medical oncology as a whole. In such a limited timespan, seven novel molecularly targeted agents—sorafenib, sunitinib, temsirolimus, bevacizumab plus interferon, pazopanib, everolimus, and axitinib—have(More)
BACKGROUND A large amount of evidence suggests a possible role of interleukin-6 (IL-6) in the pathogenesis of hepatocellular carcinoma (HCC). PATIENTS AND METHODS We studied both IL-6 and A(1)FP in patients with HCC, non-neoplastic liver disease or in healthy controls. RESULTS IL-6 titers were four-fold higher in cancer than in cirrhotic patients and(More)
OBJECTIVES This study included a cohort of advanced renal cell carcinoma patients treated with sunitinib. Since resistance to sunitinib may be mediated through angiogenic cytokines other than VEGF, we measured the circulating levels of three pro-angiogenic cytokines: basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin(More)
Even though Sorafenib has radically changed the natural history of those hepatocellular carcinoma patients who are not amenable for curative treatments, further therapeutic improvements are badly needed. As it was for Sorafenib, our increasingly refined understanding of the complex mechanisms underlying HCC carcinogenesis are the starting point for the(More)