1,720,988 research outputs found
Long-term use of sorafenib (SOR) in metastatic renal cell carcinoma (mRCC) previously treated with systemic therapy
No full textBackground: The recent development of new targeted agents for the treatment of advanced RCC has definitely changed the approach and the outcome of this disease. Among them, SOR, has proved to be highly active in the treatment of mRCC. The aim of this study was to assess the activity and the safety of SOR in pts with mRCC relapsed after prior systemic therapy. Methods: Between 2/2007 and 10/2008, 22 pts with mRCC relapsed after 1–2 prior lines of chemotherapy (gemcitabine, vinorelbine, 5-FU) have been treated with SOR orally administered at the dose of 400mg b.i.d. continuous dosing. They were18 males and 4 females, with a median age 67 years, an ECOG PS 0–2, and the majority (96%) had undergone prior nephrectomy. Patients were assessed for activity every three months (mos.) by CT. The primary endpoints were response rate (RR) evaluated by RECIST criteria and time to progression (TTP). Results: To date, 20 pts are evaluable for response: of them, 13 (59%) achieved a partial response (PR) after 3 mos. of therapy whose median duration was 13 mos. (range, 7–18), while 7 (31%) remained with stable disease (SD) with a median length of 14 mos. (range, 5–17). No complete responses have been observed. Among those who progressed (2 pts), the median time to disease progression was 7 mos. At a median length of time of 15 mos., 18 pts. are continuing the therapy with SOR and in all of them the benefit achieved remained unchanged. Two pts discontinued the treatment because of the onset of side effects, while in 4 pts dose reductions were required. Grade 3/4 toxicities were: hypertension in 3 pts (13%), hand-foot skin reactions in 5 (22%), rash/desquamation in 4 (18%), diarrhoea in 2 (9%), fatigue in 6 (27%), bleeding in 2 (9%). Conclusions: These data confirm other experiences showing the efficacy of SOR in previously treated patients with mRCC. However, notwithstanding the rather small sample size of pts., the overall clinical benefit rate (PR+SD) turned out particularly high (> 90%): chiefly, the evidence of a long lasting disease control both for patients achieving partial response and for those with stable disease makes SOR a very useful treatment for patients with mRCC
IMMUNOLOGICAL EFFECTS OF LONG-TERM THYMOPENTIN TREATMENT IN PATIENTS WITH HIV-INDUCED LYMPHADENOPATHY SYNDROME
No full text
Impiego preferenziale del promotore P1 dell’oncogene c-myc in corso di Mieloma Multiplo (MM)
No full text
HBeAg/anti-HBe circulating immune complexes in patients chronically infected with hepatitis B virus
No full textAn enzyme-linked immunosorbent assay based on the ability of polyethylene-glycol (PEG) fixed on a solid support to adsorb circulating macromolecules (PEG-solid phase test) was developed in order to provide evidence for the existence of immune complexes of HBeAg/anti-HBe (HBeAg/anti-HBe complex) in sera of HBsAg chronic carriers. The method can detect HBeAg in immune complexes whether antigen or antibody is in excess. In the chronic phase of HBV infection, HBeAg/anti-HBe complexes are formed transiently in the course of the disease, unrelated to the phases of virus replication or peaks of hepatocytolysis, or to the histologic picture of liver disease. Our study indicates that this method offers a new approach to the understanding of biological and clinical problems of the HBeAg/anti-HBe antigenic system in chronic HBV infection
Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells
No full textAlthough statins are lipid-lowering drugs that block cholesterol biosynthesis, they exert immunomodulatory, anti-inflammatory, anti-angiogenic and anti-proliferative functions by reducing the isoprenylation of proteins involved in cell signal transduction such as Ras and RhoA. In this study, we provide evidence that several natural (lovastatin, simvastatin and pravastatin) and synthetic (cerivastatin and atorvastatin) statins exert a cytotoxic effect on human T, B and myeloma tumor cells by promoting their apoptosis. Dissimilar susceptibility to apoptosis has been detected in these lines, presumably in relation to the altered expression of proteins involved in the regulation of cellular signals. Cerivastatin promptly activated the cell death even in doxorubicin resistant cell lines such as MCC-2, whereas pravastatin, a hydrophilic compound, failed to induce any effect on either proliferation or apoptosis. The statin-induced apoptotic pathway in these cell lines was presumably regulated by altered prenylation of either Ras or RhoA, as measured by the defective membrane localization of these small GTPases. In addition the cell proliferation was rescued by both farnesylpyrophosphate (FPP) and geranyl-geranylpyrophosphate (GGPP), whereas no effect was obtained with squalene, a direct precursor of cholesterol. Statins primed apoptosis through its intrinsic pathway involving the mitochondria. In fact, we observed the reduction of mitochondrial membrane potential and the cytosolic release of the second mitochondria-derived activator of caspases (Smac/DIABLO). The apoptotic pathway was caspase-dependent since caspases 9, 3 and 8 were efficiently activated. These results support the potential use of statins in association with conventional treatment as apoptosis-triggering agents in these tumors
- …
