Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors

Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Preclinical safety evaluation of hepatic arterial infusion of oncolytic poxvirus

Euna Cho,1,2,* Eun Jin Ryu,2,3,* Fen Jiang,2,4 Ung Bae Jeon,3 Mong Cho,1,2 Cy Hyun Kim,1 Miyoung Kim,1 Nam Deuk Kim,5 Tae-Ho Hwang1,2 1Department of Pharmacology and Medical Research Center (MRC), Pusan National University School of Medicine, Yangsan, Korea; 2Department of Research and Development, Bionoxx Inc, Seongnam-si, Korea; 3Department of Radiology, Pusan National University Yangsan Hospital, Yangsan, Korea; 4School of Pharmaceutical Science (Shenzhen), Sun Yat-sen University, Guangzhou, China; 5Department of Pharmacy and Pusan Cancer Research Center, Pusan National University, Busan, Korea *These authors contributed equally to this work Purpose: Oncolytic poxvirus has shown promise in treating various solid tumors, such as liver cancer, and administration of oncolytic poxvirus via the hepatic artery may provide more survival benefits than other routes of administration. However, there is a lack of safety information to guide the application of hepatic arterial infusion (HAI) of oncolytic poxvirus in human studies. To investigate the acute and chronic toxicity of HAI administration of oncolytic poxvirus in animals and provide safety information for future human studies. Methods: VVtk-, a vaccinia poxvirus with inactivated thymidine kinase gene, was administered via HAI to rabbits with normal liver function under angiography (1×108 or 1×109 pfu), and rats with N-nitrosomorpholine-induced precancerous liver cirrhosis under open surgery (1×108 pfu). Body weights and survival were monitored and blood samples were collected for hematological and biochemical tests. Distribution of A56 (a specific marker for poxvirus infection) in rabbit organs was evaluated using immunofluorescence assays. Results: HAI of high doses of VVtk- did not cause any acute or chronic changes in body weight, survival or in biochemical, hematological tests in the 2 animal models, and none of the changes showed dose dependency (in rabbit study), or were influenced by liver cirrhosis (in rat study). A56 was not detected in any of the major rabbit organs. Conclusion: HAI may provide a safe alternative route of oncolytic poxvirus administration for human studies. Keywords: oncolytic virus, transhepatic angiography, hepatocellular carcinoma, liver cirrhosi