Diabetes mellitus (DM) poses a major public health problem worldwide, with ever-increasing incidence and prevalence in recent years. The Institute for Alternative Futures (IAF) expects that the total number of people with type 1 and type 2 DM in the United States will increase by 54%, from 19,629,000 to 54,913,000 people, between 2015 and 2030. Diabetic Nephropathy (DN) affects about one-third of patients with DM and currently ranks as the first cause of end-stage kidney disease in the Western world. The complexity of interactions of Vitamin D is directly related with progressive long-term changes implicated in the worsening of renal function. These changes result in a dysregulation of the vitamin D-dependent pathways. Various studies demonstrated a pivotal role of Vitamin D supplementation in regression of albuminuria and glomerulosclerosis, contrasting the increase of glomerular basement membrane thickening and podocyte effacement, with better renal and cardiovascular outcomes. The homeostasis and regulation of the nephron’s function are absolutely dependent from the cross-talk between endothelium and podocytes. Even if growing evidence proves that vitamin D may have antiproteinuric, anti-inflammatory and renoprotective effects in patients with DN, it is still worth investigating these aspects with both more in vitro studies and randomized controlled trials in larger patient series and with adequate follow-up to confirm the effects of long-term vitamin D analogue supplementation in DN and to evaluate the effectiveness of this therapy and the appropriate dosage.

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Renal carcinoma represents about 3% of all adult tumors, with an estimate of 31,900 new cases diagnosed in 2003 in the United States. In the early phase of its natural history, renal cancer is potentially curable by surgery, but if the disease presents any signs of metastasis, the chances of survival are remote, even though anecdotal cases characterized by long survival have been reported. In fact, the treatment of metastatic renal cancer remains unsatisfactory. Systemic treatment with single agents and with polychemotherapy, with or without cytokine-based immunotherapy, has not been successful, obtaining very low response rates without a significant benefit in overall survival. This review highlights the most interesting issues regarding conventional therapeutic strategies, in localized and in advanced disease. New approaches such as monoclonal antibodies, vaccines, gene therapy, angiogenesis inhibitors and allogeneic cell transplantation and their possible clinical applications are also discussed.

BackgroundSecond-line treatment for advanced non-small-cell lung cancer (NSCLC) patients includes monotherapy with a third-generation cytotoxic drug (CT) or a tyrosine kinase inhibitor (TKI). These options are the actual standard for EGFR wild-type (WT) status, as patients with EGFR mutations achieve greater benefit by the use of TKI in first-line treatment. Some clinical trials and meta-analyses investigated the comparison between CT and TKI in second-line, but data are conflicting.MethodsWe designed a retrospective trial to gather information about TKI sensitivity in comparison with CT. We selected from clinical records patients treated with at least 1 line of CT and at least 1 line of TKI. We collected data about age, sex, performance status, comorbidity, smoking status, histotype, metastatic sites, EGFR status, treatment schedule, better response and time-to-progression (TTP) for each line of treatment and overall survival (OS).Results93 patients met selection criteria. Mean age 66,7 (range: 46–84). M/F ratio is 3:1. 39 EGFR-WT and 54 EGFR-UK. All patients received erlotinib or gefitinib as second-line treatment or erlotinib as third-line treatment. No TTP differences were observed for both second-line (HR:0,91; p = 0,6333) and third-line (HR:1.1; p = 0,6951) treatment (TKI vs CT). A trend of a benefit in OS in favor of 3rd-line TKI (HR:0,68; p = 0,11).ConclusionsThis study explores the role of TKIs in EGFR non-mutated NSCLC patients. OS analysis highlights a trend to a benefit in patients who received TKI in third-line, even if this result is statistically non-significant. Further analysis are needed to find an explanation for this observation.

Abstract. Pegylated liposomal doxorubicin (PLD) has the advantage of delivering active anthracycline directly to the tumor site, while exposing the patient to a lesser degree of doxorubicin-associated toxicities. Recently, a regimen in which paclitaxel is infused weekly over 1 h produced substantial antitumor activity with little myelosuppression. We designed a phase II trial to study the efficacy and toxicity of 10 mg/m 2 PLD on Days 1, 8 and 15, plus 70 mg/m 2 paclitaxel weekly in patients with untreated metastatic breast cancer and a high risk of cardiotoxicity. The study included 35 patients, with 31 (88.5%) evaluable for efficacy and 35 (100%) for toxicity. A total of 28 patients (80%) had two or more sites of disease. Overall, 4 complete and 16 partial responses were noted with an overall response rate of 64.5%, with 6 cases of stable and 5 cases of progressive disease. Toxicity was found to be manageable in that the only grade 3-4 side effects recorded were palmar-plantar erythrodysesthesia, 8.5%; mucositis, 2.8%; leucopenia, 12.5%; anemia, 2.8% and AST/ALT, 2.8%. No cardiotoxicity was observed. In conclusion, weekly PLD plus paclitaxel appears to be a well-tolerated and effective approach for metastatic breast cancer patients with a high risk of cardiotoxicity.