University of Naples Federico II

About: University of Naples Federico II is a education organization based out in Naples, Campania, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 29291 authors who have published 68803 publications receiving 1920149 citations. The organization is also known as: Università degli Studi di Napoli Federico II & Naples University.

Circulating sex hormones and breast cancer risk factors in postmenopausal women: Reanalysis of 13 studies

Abstract: BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. British Journal of Cancer (2011) 105, 709-722. doi:10.1038/bjc.2011.254 www.bjcancer.com Published online 19 July 2011 (C) 2011 Cancer Research UK

EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers

Abstract: The involvement of the MET oncogene in de novo and acquired resistance of non-small cell lung cancers (NSCLCs) to tyrosine kinase inhibitors (TKIs) has previously been reported, but the precise mechanism by which MET overexpression contributes to TKI-resistant NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand their role in TKI-resistant NSCLCs, we examined changes in miRNA that are mediated by tyrosine kinase receptors. Here we report that miR-30b, miR-30c, miR-221 and miR-222 are modulated by both epidermal growth factor (EGF) and MET receptors, whereas miR-103 and miR-203 are controlled only by MET. We showed that these miRNAs have important roles in gefitinib-induced apoptosis and epithelial-mesenchymal transition of NSCLC cells in vitro and in vivo by inhibiting the expression of the genes encoding BCL2-like 11 (BIM), apoptotic peptidase activating factor 1 (APAF-1), protein kinase C ɛ (PKC-ɛ) and sarcoma viral oncogene homolog (SRC). These findings suggest that modulation of specific miRNAs may provide a therapeutic approach for the treatment of NSCLCs.

Study of the B- → J/ΨK -π+π- decay and measurement of the B - → X(3872)K- branching fraction

Abstract: The authors study the decay B{sup -} {yields} J/{psi}K{sup -}{pi}{sup +}{pi}{sup -} using 117 million B{bar B} events collected at the {Upsilon}(4S) resonance with the BaBar detector at the PEP-II e{sup +}e{sup -} asymmetric-energy storage ring. They measure the branching fractions {Beta}(B{sup -} {yields} J/{psi}K{sup -} {pi}{sup +}{pi}{sup -}) = (116 {+-} 7(stat.) {+-} 9(syst.)) x 10{sup -5} and {Beta}(B{sup -} {yields} X(3872)K{sup -}) x {Beta}(X(3872) {yields} J/{psi}{pi}{sup +}{pi}{sup -}) = (1.28 {+-} 0.41) x 10{sup -5} and find the mass of the X(3872) to be 3873.4 {+-} 1.4MeV/c{sup 2}. They search for the h{sub c} narrow state in the decay B{sup -} {yields} h{sub c} K{sup -}, h{sub c} {yields} J/{psi}{pi}{sup +}{pi}{sup -} and for the decay B{sup -} {yields} J/{psi}D{sup 0}{pi}{sup -}, with D{sup 0} {yields} K{sup -}{pi}{sup +}. They set the 90% C.L. limits {Beta}(B{sup -} {yields} h{sub c}K{sup -}) x {Beta}(h{sub c} {yields} J/{psi}{pi}{sup +}{pi}{sup -}) < 3.4 x 10{sup -6} and {Beta}(B{sup -} {yields} J/{psi}D{sup 0}{pi}{sup -}) < 5.2 x 10{sup -5}.

SLC2A9 Is a High-Capacity Urate Transporter in Humans

Abstract: BackgroundSerum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man.Methods and FindingsWe expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200-500 mu M). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (K-i = 27 mu M). Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio 0.98, 95% confidence interval [CI] 0.9 to 1.05, p > 0.33) by meta-analysis of an SLC2A9 variant in six case-control studies including 11,897 participants. In a separate meta-analysis of four population studies including 11,629 participants we found no association of SLC2A9 with systolic (effect size -0.12 mm Hg, 95% CI -0.68 to 0.43, p = 0.664) or diastolic blood pressure (effect size -0.03 mm Hg, 95% CI -0.39 to 0.31, p = 0.82).ConclusionsThis study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. We did not find an association of the SLC2A9 gene with blood pressure in this study. Our findings suggest potential pathogenic mechanisms that could offer a new drug target for gout.

Early and Late Complications After Radiofrequency Ablation of Malignant Liver Tumors in 608 Patients

Abstract: A burgeoning number of direct intratumoral therapies are being used to treat human solid tumors. One of the most common sites of application of these tumor-directed treatments has been the liver. The liver is second only to lymph nodes as a common site of metastasis from nonhepatic malignancies.1 Primary liver cancer, specifically hepatocellular carcinoma (HCC), is 1 of the most common human solid malignancies worldwide, with an annual incidence of over 1 million new diagnoses.2 A proportion of patients with primary or secondary hepatic malignancies with disease confined to the liver will derive long-term survival benefit from surgical resection of their disease. Unfortunately, less than 10%–30% of patients with primary or secondary hepatic malignancies are candidates for surgical resection because of the number of tumors, location of tumors that preclude a margin-negative resection, or because of coexistent chronic liver dysfunction producing an unacceptable risk of liver failure after partial hepatectomy.3–7 Patients with liver-only malignant disease who are not candidates for resection may be offered a rapidly evolving menu of direct tumor cytodestructive treatments. The in situ destruction of unresectable primary and secondary hepatic malignancies can potentially improve the median survival of patients and provide palliative relief of symptoms. The latter is particularly true in patients with pain related to tumor displacement of the hepatic capsule or in patients with symptoms related to excess hormone production from metastatic neuroendocrine tumors. Destruction of unresectable hepatic tumors has been performed by direct intratumoral injection of cytotoxic substances, including absolute ethanol, acetic acid, heated hypertonic saline, or chemotherapy agents; by intratumoral placement of cryoprobes to freeze tumors; or more recently by intratumoral placement of needles or fibers that generate heat with radiofrequency electrical current, microwaves, or laser to produce thermal tissue necrosis. An ideal direct in situ antitumor therapy would produce complete destruction of all malignant cells with no significant side effects or complications. Clearly, no such treatment exists and all in situ cytodestructive treatments must be evaluated based on improvements in patient survival rates, local tumor control rates, and complications associated with treatment. Thermal ablation techniques, particularly radiofrequency ablation (RFA), to treat primary and secondary hepatic malignancies have gained widespread availability and use over the past 5 years.8–11 The local control and complication rates associated with microwave and laser ablation have been reported rarely; thus, it is difficult to assess the treated tumor control efficacy and risk to patients using these treatment modalities.8 Treatment-related complications are not always reported in hepatic tumor RFA studies and the complication types and incidence rates in a large, prospective series of patients have not been previously reported.10–12