Polymorphisms of XRCC1 and ADPRT genes and risk of noncardia gastric cancer in a Chinese population: a case-control study.

Objective: Gastric cancer (GC) is one of the most common malignancies and its mortality ranks third among all cancers in China. We previously noted that XRCC1 Arg194Trp was associated with GC risk in Western China in a study on XRCC1 Arg194Trp and ADPRT Val762Ala. We aimed to further explore the association of these polymorphisms with risk of the noncardia subtype.

Liquid formulations for long-term storage of monoclonal IgGs.

Proteins like immunoglobulin (IgGs) are prone to degradation by a variety of pathways. In this study, a stabilizing formulation for long-term storage of a panel of seven monoclonal IgGs was found using differential scanning calorimetry (DSC). In the chosen formulations, the IgGs were subjected to stress, accelerated and real-time storage, and analyzed by size exclusion chromatography to determine fragment and aggregate content, and fluorescence-activated cell sorting to measure immunoreactivity.

Molecular characteristics of a pancreatic adenocarcinoma associated with Shwachman-Diamond syndrome.

Background: Shwachman-Diamond syndrome (SDS) is characterized by hypoplasia of the bone marrow and exocrine pancreas and a high risk of leukemia. It is unknown whether solid tumors are part of the disease phenotype.

Procedure: We performed copy number alterations using Affymetrix human SNP 6.

Lymphocytic follicles and aggregates are a determinant of mucosal damage and duration of diarrhea.

Context: Nonspecific changes (nonspecific chronic inflammation) in patients with chronic diarrhea represent the commonest diagnosis in colorectal biopsy interpretation, but these changes are of little clinical significance.

Objective: To find, within this group, histologic and immunohistologic diagnostic criteria to predict the duration and resolution of diarrhea.

Design: Detailed clinical features and histologic findings were analyzed in a cohort of 47 patients with chronic diarrhea, with near-normal histology and no clear-cut known etiologic agent.

Children's Oncology Group's 2013 blueprint for research: acute lymphoblastic leukemia.

Approximately 90% of the 2,000 children, adolescents, and young adults enrolled each year in Children's Oncology Group acute lymphoblastic leukemia (ALL) trials will be cured. However, high-risk subsets with significantly inferior survival remain, including infants, newly diagnosed patients with age ≥10 years, white blood count ≥50,000/µl, poor early response or T-cell ALL, and relapsed ALL patients. Effective strategies to improve survival include better risk stratification, optimizing standard chemotherapy and combining targeted therapies with cytotoxic chemotherapy, the latter of which is dependent upon identification of key driver mutations present in ALL.

Genome-wide study of methotrexate clearance replicates SLCO1B1.

Methotrexate clearance can influence the cure of and toxicity in children with acute lymphoblastic leukemia (ALL). We estimated methotrexate plasma clearance for 1279 patients with ALL treated with methotrexate (24-hour infusion of a 1 g/m2 dose or 4-hour infusion of a 2 g/m2 dose) on the Children’s Oncology Group P9904 and P9905 protocols. Methotrexate clearance was lower in older children (P = 7 x 10(-7)), girls (P = 2.

Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project.

One recently identified subtype of pediatric B-precursor acute lymphoblastic leukemia (ALL) has been termed BCR-ABL1-like or Ph-like because of similarity of the gene expression profile to BCR-ABL1 positive ALL suggesting the presence of lesions activating tyrosine kinases, frequent alteration of IKZF1, and poor outcome. Prior studies demonstrated that approximately half of these patients had genomic lesions leading to CRLF2 overexpression, with half of such cases harboring somatic mutations in the Janus kinases JAK1 and JAK2. To determine whether mutations in other tyrosine kinases might also occur in ALL, we sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pediatric ALL cases with either a Ph-like gene expression profile or other alterations suggestive of activated kinase signaling.

Liquid formulations for stabilizing IgMs during physical stress and long-term storage.

Purpose: To develop a liquid formulation for IgMs to survive physical stress and storage.

Methods: Stabilizing formulations for 8 monoclonal immunoglobulin (IgMs) were found using differential scanning calorimetry (DSC). In these formulations, the IgMs were subjected to stress and storage and analyzed by size exclusion chromatography and fluorescence activated cell sorting.

Effect of comorbidity on relative survival following hospitalisation for fall-related hip fracture in older people.

Aim: To assess the effect of comorbidity on relative survival after hip fracture.

Methods: Relative survival analysis was undertaken in 16 838 fall-related hip fracture hospitalisations in New South Wales, Australia. Comorbidity was measured on the basis of additional diagnosis codes on the same hospital separation as the hip fracture using the Charlson Comorbidity Index (CCI).

Genome-wide association study identifies germline polymorphisms associated with relapse of childhood acute lymphoblastic leukemia.

With the use of risk-directed therapy for childhood acute lymphoblastic leukemia (ALL), outcome has improved dramatically in the past 40 years. However, a substantial portion of patients, many of whom have no known risk factors, experience relapse. Taking a genome-wide approach, in the present study, we evaluated the relationships between genotypes at 444 044 single nucleotide polymorphisms (SNPs) with the risk of relapse in 2535 children with newly diagnosed ALL after adjusting for genetic ancestry and treatment regimen.

Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia.

CRLF2 rearrangements, JAK1/2 point mutations, and JAK2 fusion genes have been identified in Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), a recently described subtype of pediatric high-risk B-precursor ALL (B-ALL) which exhibits a gene expression profile similar to Ph-positive ALL and has a poor prognosis. Hyperactive JAK/STAT and PI3K/mammalian target of rapamycin (mTOR) signaling is common in this high-risk subset. We, therefore, investigated the efficacy of the JAK inhibitor ruxolitinib and the mTOR inhibitor rapamycin in xenograft models of 8 pediatric B-ALL cases with and without CRLF2 and JAK genomic lesions.

The topography of DNA methylation in the non-neoplastic colonic mucosa surrounding colorectal cancers.

The degree of gene hypermethylation in non-neoplastic colonic mucosa (NNCM) is a potentially important event in the development of colorectal cancer (CRC), particularly for the subgroup with a CpG island methylator phenotype (CIMP). In this study, we aimed to use an unbiased and high-throughput approach to evaluate the topography of DNA methylation in the non-neoplastic colonic mucosa (NNCM) surrounding colorectal cancer (CRC). A total of 61 tissue samples comprising 53 NNCM and 8 tumor samples were obtained from hemicolectomy specimens of two CRC patients (Cases 1 and 2).

ADPRT Val762Ala and XRCC1 Arg194Trp polymorphisms and risk of gastric cancer in Sichuan of China.

Objective: Gastric cancer remains a major health problem in China. We hypothesized that XRCC1 Arg194Trp and ADPRT Val762Ala may be associated with risk.

Methods: We designed a multicenter 1:1 matched case- control study of 307 pairs of gastric cancers and controls between October 2010 and August 2011.

Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.

Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2, and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2-negative regulator LNK.

Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies?

Inter-ethnic differences in drug handling and frequencies of pharmacogenetic variants are increasingly being characterized. In this study, we systematically assessed the feasibility of inferring ethnic trends in chemotherapy outcomes from inter-ethnic differences in pharmacogenetic variant frequencies. Frequencies of 51 variants and chemotherapy outcomes of East Asian and Caucasian colorectal cancer patients on standard chemotherapy regimens were summarized by meta-analyses, and variant frequencies were validated by MassARRAY analysis.

Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia.

Adults and children with high-risk CRLF2-rearranged acute lymphoblastic leukemia (ALL) respond poorly to current cytotoxic chemotherapy and suffer unacceptably high rates of relapse, supporting the need to use alternative therapies. CRLF2 encodes the thymic stromal lymphopoietin (TSLP) receptor, which activates cell signaling in normal lymphocytes on binding its ligand, TSLP. We hypothesized that aberrant cell signaling occurs in CRLF2-rearranged ALL and can be targeted by signal transduction inhibitors of this pathway.

High-throughput sequencing detects minimal residual disease in acute T lymphoblastic leukemia.

High-throughput sequencing (HTS) of lymphoid receptor genes is an emerging technology that can comprehensively assess the diversity of the immune system. Here, we applied HTS to the diagnosis of T-lineage acute lymphoblastic leukemia/lymphoma. Using 43 paired patient samples, we then assessed minimal residual disease (MRD) at day 29 after treatment.

Advances in the genetics of high-risk childhood B-progenitor acute lymphoblastic leukemia and juvenile myelomonocytic leukemia: implications for therapy.

Hematologic malignancies of childhood comprise the most common childhood cancers. These neoplasms derive from the pathologic clonal expansion of an abnormal cancer-initiating cell and span a diverse spectrum of phenotypes, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and myelodysplastic syndromes (MDS). Expansion of immature lymphoid or myeloid blasts with suppression of normal hematopoiesis is the hallmark of ALL and AML, whereas MPN is associated with proliferation of 1 or more lineages that retain the ability to differentiate, and MDS is characterized by abnormal hematopoiesis and cytopenias.

Clinical potential of DNA methylation in gastric cancer: a meta-analysis.

Background: Accumulating evidence indicates aberrant DNA methylation is involved in gastric tumourigenesis, suggesting it may be a useful clinical biomarker for the disease. The aim of this study was to consolidate and summarize published data on the potential of methylation in gastric cancer (GC) risk prediction, prognostication and prediction of treatment response.

Methods: Relevant studies were identified from PubMed using a systematic search approach.

Differences in outcome and toxicity between Asian and caucasian patients with lung cancer treated with systemic therapy.

It is increasingly recognized that differences in overall survival and toxicity exist between Asian and caucasian patients with small-cell and non-small-cell lung cancer, with a longer survival, higher response rates and greater toxicity to chemotherapy and targeted therapy reported in Asian patients. Two global studies are used to illustrate how the proportions of Asian patients can influence survival outcome. Ethnicity is an important and complex characteristic that should considered in the design and conduct of a global clinical study, as the safety, tolerability and response may vary between Asian and caucasian patients.

Poly(2,5-bis(2-octyldodecyl)-3,6-di(furan-2-yl)-2,5-dihydro-pyrrolo[3,4-c]pyrrole-1,4-dione-co-thieno[3,2-b]thiophene): a high performance polymer semiconductor for both organic thin film transistors and organic photovoltaics.

A new diketopyrrolopyrrole (DPP)-containing donor-acceptor polymer, poly(2,5-bis(2-octyldodecyl)-3,6-di(furan-2-yl)-2,5-dihydro-pyrrolo[3,4-c]pyrrole-1,4-dione-co-thieno[3,2-b]thiophene) (PDBF-co-TT), is synthesized and studied as a semiconductor in organic thin film transistors (OTFTs) and organic photovoltaics (OPVs). High hole mobility of up to 0.53 cm(2) V(-1) s(-1) in bottom-gate, top-contact OTFT devices is achieved owing to the ordered polymer chain packing and favoured chain orientation, strong intermolecular interactions, as well as uniform film morphology of PDBF-co-TT.

Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children's Oncology Group study.

As controversy exists regarding the prognostic significance of genomic rearrangements of CRLF2 in pediatric B-precursor acute lymphoblastic leukemia (ALL) classified as standard/intermediate-risk (SR) or high-risk (HR), we assessed the prognostic significance of CRLF2 mRNA expression, CRLF2 genomic lesions (IGH@-CRLF2, P2RY8-CRLF2, CRLF2 F232C), deletion/mutation in genes frequently associated with high CRLF2 expression (IKZF1, JAK, IL7R), and minimal residual disease (MRD) in 1061 pediatric ALL patients (499 HR and 562 SR) on COG Trials P9905/P9906. Whereas very high CRLF2 expression was found in 17.5% of cases, only 51.

OMNI Scale of Perceived Exertion: mixed gender and race validation for Singapore children during cycle exercise.

The children's OMNI Scale of Perceived Exertion (RPE) has not been validated for children of Asian origin. The purpose was to validate the RPE for Singapore children, 12-15 years. 81 children of male and female of Chinese, Malay, and Indian ethnicities participated in the study.

ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia.

Purpose: Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome.

Patients And Methods: We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls).