Genomic analysis of atypical fibroxanthoma

Atypical fibroxanthoma (AFX), is a rare type of skin cancer affecting older individuals with sun damaged skin. Since there is limited genomic information about AFX, our study seeks to improve the understanding of AFX through whole-exome and RNA sequencing of 8 matched tumor-normal samples. AFX is a highly mutated malignancy with recurrent mutations in a number of genes, including COL11A1, ERBB4, CSMD3, and FAT1. The majority of mutations identified were UV signature (C>T in dipyrimidines). We observed deletion of chromosomal segments on chr9p and chr13q, including tumor suppressor genes such as KANK1 and CDKN2A, but no gene fusions were found. Gene expression profiling revealed several biological pathways that are upregulated in AFX, including tumor associated macrophage response, GPCR signaling, and epithelial to mesenchymal transition (EMT). To further investigate the presence of EMT in AFX, we conducted a gene expression meta-analysis that incorporated RNA-seq data from dermal fibroblasts and keratinocytes. Ours is the first study to employ high throughput sequencing for molecular profiling of AFX. These data provide valuable insights to inform models of carcinogenesis and additional research towards tumor-directed therapy

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival

The histology of ovarian cancer: worldwide distribution and implications for international survival comparisons (CONCORD-2)

Objective Ovarian cancers comprise several histologically distinct tumour groups with widely different prognosis. We aimed to describe the worldwide distribution of ovarian cancer histology and to understand what role this may play in international variation in survival. Methods The CONCORD programme is the largest population-based study of global trends in cancer survival. Data on 681,759 women diagnosed during 1995â\u80\u932009 with cancer of the ovary, fallopian tube, peritoneum and retroperitonum in 51 countries were included. We categorised ovarian tumours into six histological groups, and explored the worldwide distribution of histology. Results During 2005â\u80\u932009, type II epithelial tumours were the most common. The proportion was much higher in Oceania (73.1%), North America (73.0%) and Europe (72.6%) than in Central and South America (65.7%) and Asia (56.1%). By contrast, type I epithelial tumours were more common in Asia (32.5%), compared with only 19.4% in North America. From 1995 to 2009, the proportion of type II epithelial tumours increased from 68.6% to 71.1%, while the proportion of type I epithelial tumours fell from 23.8% to 21.2%. The proportions of germ cell tumours, sex cord-stromal tumours, other specific non-epithelial tumours and tumours of non-specific morphology all remained stable over time. Conclusions The distribution of ovarian cancer histology varies widely worldwide. Type I epithelial, germ cell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions

Role of natural phenolics in hepatoprotection: A mechanistic review and analysis of regulatory network of associated genes

The liver is not only involved in metabolism and detoxification, but also participate in innate immune function and thus exposed to frequent target Thus, they are the frequent target of physical injury. Interestingly, liver has the unique ability to regenerate and completely recoup from most acute, non-iterative situation. However, multiple conditions, including viral hepatitis, non-alcoholic fatty liver disease, long term alcohol abuse and chronic use of medications can cause persistent injury in which regenerative capacity eventually becomes dysfunctional resulting in hepatic scaring and cirrhosis. Despite the recent therapeutic advances and significant development of modern medicine, hepatic diseases remain a health problem worldwide. Thus, the search for the new therapeutic agents to treat liver disease is still in demand. Many synthetic drugs have been demonstrated to be strong radical scavengers, but they are also carcinogenic and cause liver damage. Present day various hepatic problems are encountered with number of synthetic and plant based drugs. Nexavar (sorafenib) is a chemotherapeutic medication used to treat advanced renal cell carcinoma associated with several side effects. There are a few effective varieties of herbal preparation like Liv-52, silymarin and Stronger neomin phages (SNMC) against hepatic complications. Plants are the huge repository of bioactive secondary metabolites viz; phenol, flavonoid, alkaloid etc. In this review we will try to present exclusive study on phenolics with its mode of action mitigating liver associated complications. And also its future prospects as new drug lead

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Synthesis, characterization and reactivity of single-sitealuminium amides bearing benzotriazole phenoxideligands: catalysis for ring-opening polymerization oflactide and carbon dioxide/propylene oxide coupling

New aluminium complexes containing bis-BTP ligands (BTP = N,O-bidentate benzotriazole phenoxide) were synthesized and structurally characterized. Amine elimination of Al(NMe2)3 with RBTP-H ligands (CMe2PhBTP-H = 2-(2H-benzotriazol-2-yl)-4,6-bis(1-methyl-1-phenylethyl)phenol, t-BuBTP-H = 2-(2H-benzotriazol-2-yl)-4,6-di-tert-butylphenol and TMClBTP-H = 2-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)-4-methylphenol) (2.0 mol equiv.) in toluene or hexane afforded the penta-coordinated single-site amidoaluminium complexes [(RBTP)2Al(NMe2)] (R = CMe2Ph for 1; R = t-Bu for 2; R = TMCl for 3) in satisfactory yields. With the addition of H2O (0.5 molar equiv.), the hydrolysis of Al amides 2 and 3 in a mixed solvent of THF/toluene at 25 °C produced oxo-bridged bimetallic aluminium complexes [{(RBTP)2Al}2(μ-O)] (R = t-Bu for 4 and R = TMCl for 5) in ≥70% yield. According to single crystal X-ray diffraction studies, complex 2 shows a monomeric Al(III) amide with bis(t-BuBTP) ligands and one –NMe2 group, whereas alumoxane 4 is a dinuclear species, in which the bonding mode of the Al–O–Al moiety from μ2-oxo assumes a linear type. Catalysis for ring-opening polymerization of lactide (LA) and CO2/propylene oxide (PO) coupling was systematically studied. Single-site Al amide 3 is an efficient initiator for LA polymerizations with a living character; the polymerization displays a first-order dependence on the concentration of L-LA. Bimetallic BTP-ligated alumoxane 5 is an active catalyst (TOF: 120 h−1) for the coupling of CO2 with PO in the presence of n-Bu4NBr to give propylene carbonate under mild conditions

Reliability and Validity of a Chinese Version of Urinary Tract Infection Symptom Assessment Questionnaire

ABSTRACTObjectives:Our study evaluates the reliability and validity of a Chinese version of the Urinary Tract Infection Symptom Assessment questionnaire (UTISA).Material and Methods:Our study enrolled women who were diagnosed with uncomplicated urinary tract infection (uUTI) at clinics. The Chinese version of UTISA was completed upon first visit to the clinic for uUTI and at 1-week follow-up. We enrolled 124 age-matched women without uUTI from the community as the control group. The UTISA consists of 14 items (seven symptom items and seven related to quality of life), with each item scoring 0 to 3. The internal consistency was assessed with Chronbach's alpha test. Factor analysis was used to classify symptoms into latent factors. The predictive validity was analyzed by using logistic regression and Receiver Operating Characteristic (ROC) curve analysis.Results:Mean total symptom scores of the UTISA in the 169 cases and 124 controls were 8.9±4.6 and 1.4±2.4, respectively (p<0.01). The alpha coefficient was 0.77, showing a homogeneous composition of symptoms. At a cut-off value of greater than 3, the UTISA symptom score had good predictive value for uUTI (sensitivity of 87.0%, and specificity of 93.1%). Factor analysis revealed two latent variables: 1) lower urinary tract symptoms and 2) physical symptoms. Among the seven items, we found that urinary frequency (OR=2.6), dysuria (OR=5.0), sense of incomplete emptying (OR=2.0), and hematuria (OR=7.6) were significant predictors for uUTI.Conclusions:The Chinese version of UTISA is reliable to predict uncomplicated UTI in women with an optimal cut-off point at >3