A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study.

BACKGROUND:The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls. METHODS:The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n = 4533) and controls (n = 4171) were also asked about seizures less than 2 years from diagnosis and previous seizure history more than 2 years prior to tumor diagnosis, including childhood seizures. RESULTS:Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p < 0.009). No significant difference was found between glioma cases and controls in terms of seizure occurring more than 2 years before diagnosis or during childhood. CONCLUSIONS:Our study showed that glioma-related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma

Can immunotherapy be useful as a “functional cure” for infection with Human Immunodeficiency Virus-1?

<p>Abstract</p> <p>Immunotherapy aims to assist the natural immune system in achieving control over viral infection. Various immunotherapy formats have been evaluated in either therapy-naive or therapy-experienced HIV-infected patients over the last 20 years. These formats included non-antigen specific strategies such as cytokines that stimulate immunity or suppress the viral replication, as well as antibodies that block negative regulatory pathways. A number of HIV-specific therapeutic vaccinations have also been proposed, using <it>in vivo</it> injection of inactivated virus, plasmid DNA encoding HIV antigens, or recombinant viral vectors containing HIV genes. A specific format of therapeutic vaccines consists of <it>ex vivo</it> loading of autologous dendritic cells with one of the above mentioned antigenic formats or mRNA encoding HIV antigens.</p> <p>This review provides an extensive overview of the background and rationale of these different therapeutic attempts and discusses the results of trials in the SIV macaque model and in patients. To date success has been limited, which could be explained by insufficient quality or strength of the induced immune responses, incomplete coverage of HIV variability and/or inappropriate immune activation, with ensuing increased susceptibility of target cells.</p> <p>Future attempts at therapeutic vaccination should ideally be performed under the protection of highly active antiretroviral drugs in patients with a recovered immune system. Risks for immune escape should be limited by a better coverage of the HIV variability, using either conserved or mosaic sequences. Appropriate molecular adjuvants should be included to enhance the quality and strength of the responses, without inducing inappropriate immune activation. Finally, to achieve a long-lasting effect on viral control (i.e. a “functional cure”) it is likely that these immune interventions should be combined with anti-latency drugs and/or gene therapy.</p