Scholars@Duke
Kouros Owzar

Kouros Owzar

Professor of Biostatistics & Bioinformatics
Biostatistics & Bioinformatics, Division of Integrative Genomics
kouros.owzar@duke.edu
Duke Box 2717, Durham, NC 27710
2424 Erwin Road, 7078 Hock Plaza, Durham, NC 27705

Selected Publications

TEMPTED: time-informed dimensionality reduction for longitudinal microbiome studies.

Journal Article Genome Biol · December 19, 2024 Longitudinal studies are crucial for understanding complex microbiome dynamics and their link to health. We introduce TEMPoral TEnsor Decomposition (TEMPTED), a time-informed dimensionality reduction method for high-dimensional longitudinal data that treat ... Full text Link to item Cite

Androgen receptor monomers and dimers regulate opposing biological processes in prostate cancer cells.

Journal Article Nat Commun · September 3, 2024 Most prostate cancers express the androgen receptor (AR), and tumor growth and progression are facilitated by exceptionally low levels of systemic or intratumorally produced androgens. Thus, absolute inhibition of the androgen signaling axis remains the go ... Full text Link to item Cite

Analysis of ductal carcinoma in situ by self-reported race reveals molecular differences related to outcome.

Journal Article Breast Cancer Res · September 2, 2024 BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated. METHODS: We examin ... Full text Link to item Cite

SifiNet: a robust and accurate method to identify feature gene sets and annotate cells.

Journal Article Nucleic Acids Res · May 22, 2024 SifiNet is a robust and accurate computational pipeline for identifying distinct gene sets, extracting and annotating cellular subpopulations, and elucidating intrinsic relationships among these subpopulations. Uniquely, SifiNet bypasses the cell clusterin ... Full text Link to item Cite

Common variation in a long non-coding RNA gene modulates variation of circulating TGF-β2 levels in metastatic colorectal cancer patients (Alliance).

Journal Article BMC Genomics · May 14, 2024 BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was cond ... Full text Link to item Cite

Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance).

Journal Article Pharmacogenomics J · March 4, 2024 The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer ... Full text Link to item Cite

DYNATE: Localizing rare-variant association regions via multiple testing embedded in an aggregation tree.

Journal Article Genet Epidemiol · February 2024 Rare-variants (RVs) genetic association studies enable researchers to uncover the variation in phenotypic traits left unexplained by common variation. Traditional single-variant analysis lacks power; thus, researchers have developed various methods to aggr ... Full text Link to item Cite

The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates.

Journal Article Proc Natl Acad Sci U S A · December 12, 2023 Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to ... Full text Link to item Cite

High-fat diet and obesity are associated with differential angiogenic gene expression in epithelial ovarian cancer.

Journal Article Gynecol Oncol · December 2023 OBJECTIVE: We sought to evaluate the association between diet and angiogenic biomarkers in KpB mice, and the association between these markers, body mass index (BMI), and overall survival (OS) in high-grade serous cancers (HGSC). METHODS: Tumors previously ... Full text Link to item Cite

Single-cell landscape analysis unravels molecular programming of the human B cell compartment in chronic GVHD.

Journal Article JCI Insight · June 8, 2023 Alloreactivity can drive autoimmune syndromes. After allogeneic hematopoietic stem cell transplantation (allo-HCT), chronic graft-versus-host disease (cGVHD), a B cell-associated autoimmune-like syndrome, commonly occurs. Because donor-derived B cells cont ... Full text Open Access Link to item Cite

Clustering Deviation Index (CDI): a robust and accurate internal measure for evaluating scRNA-seq data clustering.

Journal Article Genome Biol · December 27, 2022 Most single-cell RNA sequencing (scRNA-seq) analyses begin with cell clustering; thus, the clustering accuracy considerably impacts the validity of downstream analyses. In contrast with the abundance of clustering methods, the tools to assess the clusterin ... Full text Link to item Cite

Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts.

Journal Article Cancer Cell · December 12, 2022 Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from ... Full text Link to item Cite

Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies.

Journal Article NPJ Precis Oncol · October 23, 2022 Intrahepatic cholangiocarcinoma (ICC) remains a deadly malignancy lacking systemic therapies for advanced disease. Recent advancements include selective FGFR1-3 inhibitors for the 15% of ICC patients harboring fusions, although survival is limited by poor ... Full text Link to item Cite

Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.

Conference Prostate Cancer Prostatic Dis · September 2022 BACKGROUND: Prostate cancer is a clinically and molecularly heterogeneous disease, with highest incidence and mortality among men of African ancestry. To date, prostate cancer patient-derived xenograft (PCPDX) models to study this disease have been difficu ... Full text Open Access Link to item Cite

Plasma Protein Biomarkers in Advanced or Metastatic Colorectal Cancer Patients Receiving Chemotherapy With Bevacizumab or Cetuximab: Results from CALGB 80405 (Alliance).

Journal Article Clin Cancer Res · July 1, 2022 PURPOSE: CALGB 80405 compared the combination of first-line chemotherapy with cetuximab or bevacizumab in the treatment of advanced or metastatic colorectal cancer (mCRC). Although similar clinical outcomes were observed in the cetuximab-chemotherapy group ... Full text Link to item Cite

P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia.

Journal Article Nat Cancer · July 2022 Selinexor is a first-in-class inhibitor of the nuclear exportin XPO1 that was recently approved by the US Food and Drug Administration for the treatment of multiple myeloma and diffuse large B-cell lymphoma. In relapsed/refractory acute myeloid leukemia (A ... Full text Link to item Cite

Bevacizumab-induced hypertension and proteinuria: a genome-wide study of more than 1000 patients.

Journal Article Br J Cancer · February 2022 BACKGROUND: Hypertension and proteinuria are common bevacizumab-induced toxicities. No validated biomarkers are available for identifying patients at risk of these toxicities. METHODS: A genome-wide association study (GWAS) meta-analysis was performed in 1 ... Full text Link to item Cite

Re-Examination of the Exacerbating Effect of Inflammasome Components during Radiation Injury.

Journal Article Radiat Res · February 1, 2022 Radiation can be applied for therapeutic benefit against cancer or may result in devastating harm due to accidental or intentional release of nuclear energy. In all cases, radiation exposure causes molecular and cellular damage, resulting in the production ... Full text Link to item Cite

Genome-wide association studies of survival in 1520 cancer patients treated with bevacizumab-containing regimens.

Journal Article Int J Cancer · January 15, 2022 Germline variants might predict cancer progression. Bevacizumab improves overall survival (OS) in patients with advanced cancers. No biomarkers are available to identify patients that benefit from bevacizumab. A meta-analysis of genome-wide association stu ... Full text Link to item Cite

Clinical Trials with Biologic Primary Endpoints in Immuno-oncology: Concepts and Usage.

Journal Article Clin Cancer Res · January 1, 2022 Clinical trials that have a pharmacokinetic or a pharmacodynamic immunologic mechanism of action-based primary outcome could substantially improve the validity and efficiency of early development of immuno-oncology agents. Here, we outline different trial ... Full text Link to item Cite

APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell-Mediated Antitumor Immune Responses.

Journal Article Cancer Immunol Res · January 2022 The APOBEC family of cytidine deaminases is one of the most common endogenous sources of mutations in human cancer. Genomic studies of tumors have found that APOBEC mutational signatures are enriched in the HER2 subtype of breast cancer and are associated ... Full text Link to item Cite

Pharmacogenetic study in gastric cancer patients treated with adjuvant fluorouracil/leucovorin or epirubicin/cisplatin/fluorouracil before and after chemoradiation on CALGB 80101 (Alliance).

Journal Article Pharmacogenet Genomics · December 1, 2021 There is a lack of pharmacogenetic predictors of outcome in gastric cancer patients. The aim of this study was to assess previously identified candidate genes associated with 5-fluorouracil (5-FU), cisplatin, or epirubicin toxicity or response in a cohort ... Full text Link to item Cite

Obesity and altered angiogenic-related gene expression in endometrial cancer.

Journal Article Gynecol Oncol · November 2021 OBJECTIVES: Evaluate association between obesity and angiogenic-related gene expression in endometrial cancer (EC). Evaluate interaction between diet and metformin on angiogenic-related gene expression. METHODS: We evaluated the association between 168 hum ... Full text Link to item Cite

Comparative analysis of RNA enrichment methods for preparation of Cryptococcus neoformans RNA sequencing libraries.

Journal Article G3 (Bethesda) · October 19, 2021 RNA sequencing (RNA-Seq) experiments focused on gene expression involve removal of ribosomal RNA (rRNA) because it is the major RNA constituent of cells. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper se ... Full text Link to item Cite

A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.

Journal Article Cancer · August 15, 2021 BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednison ... Full text Link to item Cite

Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma.

Journal Article Cancer Res · July 15, 2021 Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-cell lymphoblastic leukemia/lymphoma. Here we aimed to identify key oncogenic dri ... Full text Link to item Cite

Clinical Results and Biomarker Analyses of Axitinib and TRC105 versus Axitinib Alone in Patients with Advanced or Metastatic Renal Cell Carcinoma (TRAXAR).

Journal Article Oncologist · July 2021 LESSONS LEARNED: The combination of carotuximab with axitinib did not provide a benefit over axitinib monotherapy in patients with metastatic clear cell renal cell carcinoma who had previously progressed on one or more vascular endothelial growth factor (V ... Full text Link to item Cite

Differential alternative RNA splicing and transcription events between tumors from African American and White patients in The Cancer Genome Atlas.

Journal Article Genomics · May 2021 Individuals of African ancestry suffer disproportionally from higher incidence, aggressiveness, and mortality for particular cancers. This disparity likely results from an interplay among differences in multiple determinants of health, including difference ... Full text Link to item Cite

RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry.

Journal Article Lung Cancer · March 2021 OBJECTIVES: Despite disparities in lung cancer incidence and mortality, the molecular landscape of lung cancer in patients of African ancestry remains underexplored, and race-related differences in RNA splicing remain unexplored. MATERIALS AND METHODS: We ... Full text Link to item Cite

DNA-Damage-Induced Alternative Splicing of p53.

Journal Article Cancers (Basel) · January 12, 2021 Cellular responses to DNA damage and other stresses are important determinants of mutagenesis and impact the development of a wide range of human diseases. TP53 is highly mutated in human cancers and plays an essential role in stress responses and cell fat ... Full text Link to item Cite

Genomic Analysis of Germline Variation Associated with Survival of Patients with Colorectal Cancer Treated with Chemotherapy Plus Biologics in CALGB/SWOG 80405 (Alliance).

Journal Article Clin Cancer Res · January 1, 2021 PURPOSE: Irinotecan/5-fluorouracil (5-FU; FOLFIRI) or oxaliplatin/5-FU (FOLFOX), combined with bevacizumab or cetuximab, are approved, first-line treatments for metastatic colorectal cancer (mCRC). We aimed at identifying germline variants associated with ... Full text Link to item Cite

Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy.

Journal Article Nat Commun · December 17, 2020 Immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Most preclinical immunotherapy studies utilize transplant tumor models, which ov ... Full text Link to item Cite

Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence.

Journal Article Nat Commun · October 6, 2020 The survival and recurrence of residual tumor cells following therapy constitutes one of the biggest obstacles to obtaining cures in breast cancer, but it remains unclear how the clonal composition of tumors changes during relapse. We use cellular barcodin ... Full text Link to item Cite

The Long Noncoding RNA NEAT1 Promotes Sarcoma Metastasis by Regulating RNA Splicing Pathways.

Journal Article Mol Cancer Res · October 2020 Soft-tissue sarcomas (STS) are rare malignancies showing lineage differentiation toward diverse mesenchymal tissues. Half of all high-grade STSs develop lung metastasis with a median survival of 15 months. Here, we used a genetically engineered mouse model ... Full text Link to item Cite

Prognostic and Predictive Biomarkers in Patients with Metastatic Colorectal Cancer Receiving Regorafenib.

Journal Article Mol Cancer Ther · October 2020 Regorafenib is a tyrosine kinase inhibitor approved by the FDA for the treatment of patients with chemotherapy refractory metastatic colorectal cancer (mCRC). Regorafenib inhibits signaling through multiple receptors associated with angiogenesis, metastasi ... Full text Link to item Cite

Genomewide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy.

Journal Article Clin Pharmacol Ther · September 2020 Microtubule targeting agents (MTAs) are anticancer therapies commonly prescribed for breast cancer and other solid tumors. Sensory peripheral neuropathy (PN) is the major dose-limiting toxicity for MTAs and can limit clinical efficacy. The current pharmaco ... Full text Link to item Cite

Predictive accuracy of markers or risk scores for interval censored survival data.

Journal Article Stat Med · August 15, 2020 Methods for the evaluation of the predictive accuracy of biomarkers with respect to survival outcomes subject to right censoring have been discussed extensively in the literature. In cancer and other diseases, survival outcomes are commonly subject to inte ... Full text Link to item Cite

Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma.

Journal Article Biol Blood Marrow Transplant · August 2020 CALGB (Alliance) 100001 was a phase II study evaluating autologous stem cell transplant (ASCT) followed by nonmyeloablative allogeneic stem cell transplant (alloSCT) in patients with multiple myeloma who had received no more than 18 months of prior therapy ... Full text Link to item Cite

Plasmonic nanobiosensors for detection of microRNA cancer biomarkers in clinical samples.

Journal Article Analyst · July 7, 2020 MicroRNAs (miRNAs) play an important role in the regulation of biological processes and have demonstrated great potential as biomarkers for the early detection of various diseases, including esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE), the ... Full text Link to item Cite

Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218.

Journal Article Clin Cancer Res · March 15, 2020 PURPOSE: GOG-0218, a double-blind placebo-controlled phase III trial, compared carboplatin and paclitaxel with placebo, bevacizumab followed by placebo, or bevacizumab followed by bevacizumab in advanced epithelial ovarian cancer (EOC). Results demonstrate ... Full text Link to item Cite

Differential expression of immune related genes in high-grade ovarian serous carcinoma.

Journal Article Gynecol Oncol · March 2020 OBJECTIVE: To identify novel immunologic targets and biomarkers associated with overall survival (OS) in high-grade serous ovarian cancer (HGSC). METHODS: In this retrospective study, microarray data from 51 HGSC specimens were analyzed (Affymetrix HG-U133 ... Full text Link to item Cite

A Phase II Multicenter Study of the Addition of Azacitidine to Reduced-Intensity Conditioning Allogeneic Transplant for High-Risk Myelodysplasia (and Older Patients with Acute Myeloid Leukemia): Results of CALGB 100801 (Alliance).

Journal Article Biol Blood Marrow Transplant · October 2019 Relapse remains the major cause of death in older patients transplanted for acute myeloid leukemia (AML) in first complete remission or for patients with advanced myelodysplastic syndrome (MDS) at any age. Conventional myeloablative conditioning followed b ... Full text Link to item Cite

An initial genetic analysis of gemcitabine-induced high-grade neutropenia in pancreatic cancer patients in CALGB 80303 (Alliance).

Journal Article Pharmacogenet Genomics · August 2019 OBJECTIVES: One of the standard of care regimens for advanced pancreatic cancer is gemcitabine-based chemotherapy. The efficacy of gemcitabine is limited by dose-limiting hematologic toxicities especially neutropenia. Uncovering the variability of these to ... Full text Link to item Cite

Mutational landscape in genetically engineered, carcinogen-induced, and radiation-induced mouse sarcoma.

Journal Article JCI Insight · July 11, 2019 Cancer development is influenced by hereditary mutations, somatic mutations due to random errors in DNA replication, or external factors. It remains unclear how distinct cell-intrinsic and -extrinsic factors impact oncogenesis within the same tissue type. ... Full text Link to item Cite

fastJT: An R package for robust and efficient feature selection for machine learning and genome-wide association studies.

Journal Article BMC Bioinformatics · June 13, 2019 BACKGROUND: Parametric feature selection methods for machine learning and association studies based on genetic data are not robust with respect to outliers or influential observations. While rank-based, distribution-free statistics offer a robust alternati ... Full text Link to item Cite

Efficient estimation of grouped survival models.

Journal Article BMC Bioinformatics · May 28, 2019 BACKGROUND: Time- and dose-to-event phenotypes used in basic science and translational studies are commonly measured imprecisely or incompletely due to limitations of the experimental design or data collection schema. For example, drug-induced toxicities a ... Full text Link to item Cite

A Pharmacogenetic Prediction Model of Progression-Free Survival in Breast Cancer using Genome-Wide Genotyping Data from CALGB 40502 (Alliance).

Journal Article Clin Pharmacol Ther · March 2019 Genome-wide genotyping data are increasingly available for pharmacogenetic association studies, but application of these data for development of prediction models is limited. Prediction methods, such as elastic net regularization, have recently been applie ... Full text Link to item Cite

SET alpha and SET beta mRNA isoforms in chronic lymphocytic leukaemia.

Journal Article Br J Haematol · February 2019 Alteration in RNA splicing is implicated in carcinogenesis and progression. Mutations in spliceosome genes and alternative splicing of other genes have been noted in chronic lymphocytic leukaemia (CLL), a common B cell malignancy with heterogeneous outcome ... Full text Link to item Cite

Late effects of total body irradiation on hematopoietic recovery and immune function in rhesus macaques.

Journal Article PLoS One · 2019 While exposure to radiation can be lifesaving in certain settings, it can also potentially result in long-lasting adverse effects, particularly to hematopoietic and immune cells. This study investigated hematopoietic recovery and immune function in rhesus ... Full text Link to item Cite

Sample size calculation for studies with grouped survival data.

Journal Article Stat Med · November 30, 2018 Grouped survival data arise often in studies where the disease status is assessed at regular visits to clinic. The time to the event of interest can only be determined to be between two adjacent visits or is right censored at one visit. In data analysis, r ... Full text Open Access Link to item Cite

Genetic variation determines VEGF-A plasma levels in cancer patients.

Journal Article Sci Rep · November 5, 2018 Angiogenesis is essential in tumor biology and is regulated by vascular endothelial growth factor (VEGF) ligands and receptors. Here we aimed to discover genetic variants associated with levels of circulating angiogenic proteins in cancer patients. Plasma ... Full text Link to item Cite

bcSeq: an R package for fast sequence mapping in high-throughput shRNA and CRISPR screens.

Journal Article Bioinformatics · October 15, 2018 SUMMARY: CRISPR-Cas9 and shRNA high-throughput sequencing screens have abundant applications for basic and translational research. Methods and tools for the analysis of these screens must properly account for sequencing error, resolve ambiguous mappings am ... Full text Link to item Cite

Identification of a Genomic Region between SLC29A1 and HSP90AB1 Associated with Risk of Bevacizumab-Induced Hypertension: CALGB 80405 (Alliance).

Journal Article Clin Cancer Res · October 1, 2018 Purpose: Bevacizumab is a VEGF-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of multiple cancers. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy or lead ... Full text Link to item Cite

The Vitamin D receptor gene as a determinant of survival in pancreatic cancer patients: Genomic analysis and experimental validation

Journal Article PLoS ONE · August 1, 2018 Purpose Advanced pancreatic cancer is a highly refractory disease almost always associated with survival of little more than a year. New interventions based on novel targets are needed. We aim to identify new genetic determinants of overall survival (OS) i ... Full text Cite

Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk.

Journal Article Int J Cancer · April 1, 2018 The platelet-derived growth factor (PDGF) signaling pathway plays important roles in development and progression of human cancers. In our study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer (PC) risk in ... Full text Open Access Link to item Cite

Post-Irradiation Treatment with a Superoxide Dismutase Mimic, MnTnHex-2-PyP5+, Mitigates Radiation Injury in the Lungs of Non-Human Primates after Whole-Thorax Exposure to Ionizing Radiation.

Journal Article Antioxidants (Basel) · March 7, 2018 Radiation injury to the lung is the result of acute and chronic free radical formation, and there are currently few effective means of mitigating such injury. Studies in rodents indicate that superoxide dismutase mimetics may be effective in this regard; h ... Full text Link to item Cite

Novel genetic variants in the P38MAPK pathway gene ZAK and susceptibility to lung cancer.

Journal Article Mol Carcinog · February 2018 The P38MAPK pathway participates in regulating cell cycle, inflammation, development, cell death, cell differentiation, and tumorigenesis. Genetic variants of some genes in the P38MAPK pathway are reportedly associated with lung cancer risk. To substantiat ... Full text Open Access Link to item Cite

Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci.

Journal Article Pharmacogenet Genomics · February 2018 OBJECTIVE: Taxane containing chemotherapy extends survival for breast cancer patients. However, taxane-induced peripheral neuropathy (TIPN) cannot be predicted, prevented or effectively treated. Using genome-wide analyses, we sought to identify common risk ... Full text Link to item Cite

Facilitating the Calculation of the Efficient Score Using Symbolic Computing.

Journal Article Am Stat · 2018 The score statistic continues to be a fundamental tool for statistical inference. In the analysis of data from high-throughput genomic assays, inference on the basis of the score usually enjoys greater stability, considerably higher computational efficienc ... Full text Link to item Cite

An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD.

Journal Article Blood · November 9, 2017 B-cell receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B-cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded function ... Full text Link to item Cite

Mapping eQTL by leveraging multiple tissues and DNA methylation.

Journal Article BMC Bioinformatics · October 18, 2017 BACKGROUND: DNA methylation is an important tissue-specific epigenetic event that influences transcriptional regulation of gene expression. Differentially methylated CpG sites may act as mediators between genetic variation and gene expression, and this rel ... Full text Link to item Cite

Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial.

Journal Article Lancet Haematol · September 2017 BACKGROUND: In the CALGB (Alliance) 100104 study, lenalidomide versus placebo after autologous stem-cell transplantation (ASCT) was investigated for patients with newly diagnosed myeloma. That study showed improved time to progression and overall survival ... Full text Link to item Cite

Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033.

Journal Article JAMA Oncol · July 1, 2017 IMPORTANCE: After identification of activating mutations of the KIT gene in gastrointestinal stromal tumor (GIST)-the most common sarcomaof the gastrointestinal tract-a phase 2 study demonstrated efficacy of imatinib mesylate in patients with metastatic GI ... Full text Link to item Cite

Identification of a DNA Damage-Induced Alternative Splicing Pathway That Regulates p53 and Cellular Senescence Markers.

Journal Article Cancer Discov · July 2017 Cellular responses to DNA damage are critical determinants of cancer development and aging-associated pathogenesis. Here, we identify and characterize a DNA-damage response (DDR) pathway that regulates alternative splicing of numerous gene products, includ ... Full text Link to item Cite

Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus.

Journal Article Mol Carcinog · June 2017 The fatty acids (FAs) metabolism is suggested to play a pivotal role in the development of lung cancer, and we explored that by conducting a pathway-based analysis. We performed a meta-analysis of published datasets of six genome wide association studies ( ... Full text Link to item Cite

Reduced mRNA expression of nucleotide excision repair genes in lymphocytes and risk of squamous cell carcinoma of the head and neck.

Journal Article Carcinogenesis · May 1, 2017 Nucleotide excision repair (NER) plays a critical role in the development of smoking-related cancers. We hypothesize that mRNA expression levels of NER genes are associated with risk of the squamous cell carcinoma of head and neck (SCCHN). To test this hyp ... Full text Link to item Cite

Functional variants in DCAF4 associated with lung cancer risk in European populations.

Journal Article Carcinogenesis · May 1, 2017 Cullin-RING ubiquitin ligases (CRLs) responsible for substrate specificity of ubiquitination play a key role in cell-cycle control and DNA damage response. In this study, we assessed associations between 16 599 SNPs in 115 CRL genes and lung cancer risk by ... Full text Link to item Cite

Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: a pathway-based analysis from published GWASs.

Journal Article Sci Rep · March 17, 2017 mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of this process may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes wit ... Full text Open Access Link to item Cite

Apoptotic capacity and risk of squamous cell carcinoma of the head and neck.

Journal Article Eur J Cancer · February 2017 BACKGROUND: Tobacco smoke and alcohol drinking are the major risk factors for squamous cell carcinoma of the head and neck (SCCHN). Smoking and drinking cause DNA damage leading to apoptosis, and insufficient apoptotic capacity may favour development of ca ... Full text Link to item Cite

Targeted Exome Sequencing of the Cancer Genome in Patients with Very High-risk Bladder Cancer.

Journal Article Eur Urol · November 2016 UNLABELLED: We completed targeted exome sequencing of the tumors of 50 patients with pTis-pT4b bladder cancer. Mutations were categorized by type, stratified against previously identified cancer loci in the Catalogue of Somatic Mutations in Cancer and The ... Full text Link to item Cite

A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with Risk of Lung Cancer.

Journal Article Sci Rep · October 7, 2016 Lung cancer etiology is multifactorial, and growing evidence has indicated that long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. We performed a large-scale meta-analysis of 690,564 SNPs in 15,531 autosomal lncRNAs by using datas ... Full text Open Access Link to item Cite

Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy.

Journal Article Clin Cancer Res · October 1, 2016 PURPOSE: Discovery of SNPs that predict a patient's risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with doc ... Full text Link to item Cite

Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance).

Journal Article Cancer Med · September 2016 Circulating protein markers were assessed in patients with colorectal cancer (CRC) treated with cetuximab in CALGB 80203 to identify prognostic and predictive biomarkers. Patients with locally advanced or metastatic CRC received FOLFOX or FOLFIRI chemother ... Full text Link to item Cite

SparkScore: Leveraging apache spark for distributed genomic inference

Conference Proceedings - 2016 IEEE 30th International Parallel and Distributed Processing Symposium, IPDPS 2016 · July 18, 2016 The method of the efficient score statistic is used extensively to conduct inference for high throughput genomic data due to its computational efficiency and abilityto accommodate simple and complex phenotypes. Inference based on these statistics can readi ... Full text Cite

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi-institutional study.

Journal Article Am J Hematol · July 2016 Monocyte-derived cells, constituents of the cancer microenvironment, support chronic lymphocytic leukemia (CLL) cell survival in vitro via direct cell-cell interaction and secreted factors. We hypothesized that circulating absolute monocyte count (AMC) ref ... Full text Link to item Cite

Exploiting expression patterns across multiple tissues to map expression quantitative trait loci.

Journal Article BMC Bioinformatics · June 24, 2016 BACKGROUND: In order to better understand complex diseases, it is important to understand how genetic variation in the regulatory regions affects gene expression. Genetic variants found in these regulatory regions have been shown to activate transcription ... Full text Link to item Cite

Fitting Cox Models with Doubly Censored Data Using Spline-Based Sieve Marginal Likelihood.

Journal Article Scand Stat Theory Appl · June 2016 In some applications, the failure time of interest is the time from an originating event to a failure event, while both event times are interval censored. We propose fitting Cox proportional hazards models to this type of data using a spline-based sieve ma ... Full text Link to item Cite

Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta-analysis of 14,463 cases and 44,188 controls.

Journal Article Carcinogenesis · March 2016 Centrosome abnormalities are often observed in premalignant lesions and in situ tumors and have been associated with aneuploidy and tumor development. We investigated the associations of 9354 single-nucleotide polymorphisms (SNPs) in 106 centrosomal genes ... Full text Link to item Cite

Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502.

Journal Article J Clin Oncol · December 10, 2015 PURPOSE: Long-term survival rates for older patients with newly diagnosed acute myeloid leukemia (AML) are extremely low. Previous observational studies suggest that allogeneic hematopoietic stem-cell transplantation (HSCT) may improve overall survival (OS ... Full text Link to item Cite

Prognostic significance of differential expression of angiogenic genes in women with high-grade serous ovarian carcinoma.

Journal Article Gynecol Oncol · October 2015 OBJECTIVES: To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC). METHODS: 51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts ... Full text Link to item Cite

Participation in Cancer Pharmacogenomic Studies: A Study of 8456 Patients Registered to Clinical Trials in the Cancer and Leukemia Group B (Alliance).

Journal Article J Natl Cancer Inst · October 2015 BACKGROUND: Clinically annotated specimens from cancer clinical trial participants offer an opportunity for discovery and validation of pharmacogenomic findings. The purpose of this observational study is to better understand patient/institution factors th ... Full text Link to item Cite

Incorporating Functional Information in Tests of Excess De Novo Mutational Load.

Journal Article Am J Hum Genet · August 6, 2015 A number of recent studies have investigated the role of de novo mutations in various neurodevelopmental and neuropsychiatric disorders. These studies attempt to implicate causal genes by looking for an excess load of de novo mutations within those genes. ... Full text Link to item Cite

Functional FLT1 Genetic Variation is a Prognostic Factor for Recurrence in Stage I-III Non-Small-Cell Lung Cancer.

Journal Article J Thorac Oncol · July 2015 BACKGROUND: We propose that single-nucleotide polymorphisms (SNPs) in genes of the vascular endothelial growth factor pathway of angiogenesis will associate with survival in non-small-cell lung cancer (NSCLC) patients. METHODS: Fifty-three SNPs in vascular ... Full text Link to item Cite

Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques.

Journal Article Int J Radiat Biol · June 2015 PURPOSE: The threat of radiation exposure requires a mechanistic understanding of radiation-induced immune injury and recovery. The study objective was to evaluate responses to ionizing radiation in ovariectomized (surgically post-menopausal) female cynomo ... Full text Link to item Cite

Genomic profiling in locally advanced and inflammatory breast cancer and its link to DCE-MRI and overall survival.

Journal Article Int J Hyperthermia · June 2015 PURPOSE: We have previously reported that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns obtained from locally advanced breast cancer (LABC) patients prior to neoadjuvant therapy predicted pathologic clinical response. Ge ... Full text Link to item Cite

Bevacizumab and the risk of arterial and venous thromboembolism in patients with metastatic, castration-resistant prostate cancer treated on Cancer and Leukemia Group B (CALGB) 90401 (Alliance).

Journal Article Cancer · April 1, 2015 BACKGROUND: Bevacizumab is associated with an increased risk of arterial thromboembolism (ATE); however, its effect on venous thromboembolism (VTE) remains controversial. Scant data exist on the factors that increase the risk of ATE/VTE in patients with pr ... Full text Link to item Cite

Gene expression markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance).

Journal Article Clin Cancer Res · March 1, 2015 PURPOSE: Formalin-fixed, paraffin-embedded tumor samples from CALGB 80203 were analyzed for expression of EGFR axis-related genes to identify prognostic or predictive biomarkers for cetuximab treatment. PATIENTS AND METHODS: Patients (238 total) with first ... Full text Link to item Cite

Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103).

Journal Article Cancer Chemother Pharmacol · November 2014 PURPOSE: Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome have often been excluded from myeloablative-conditioning regimens containing busulfan because of non-disease-related morbidity and mortality. We hypothesized that busulf ... Full text Link to item Cite

Vatalanib population pharmacokinetics in patients with myelodysplastic syndrome: CALGB 10105 (Alliance).

Conference Br J Clin Pharmacol · November 2014 AIMS: Vatalanib is an oral anti-angiogenesis agent that inhibits vascular endothelial growth factor receptor tyrosine kinases, which in patients showed auto induction of metabolism and variability in pharmacokinetic (PK) disposition. The objective was to c ... Full text Link to item Cite

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.

Journal Article Nat Genet · September 2014 We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = ... Full text Link to item Cite

Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance).

Journal Article Pharmacogenomics J · August 2014 Peripheral neuropathy is a common dose-limiting toxicity for patients treated with paclitaxel. For most individuals, there are no known risk factors that predispose patients to the adverse event, and pathogenesis for paclitaxel-induced peripheral neuropath ... Full text Link to item Cite

25-Hydroxyvitamin D levels and survival in advanced pancreatic cancer: findings from CALGB 80303 (Alliance).

Journal Article J Natl Cancer Inst · August 2014 BACKGROUND: Data from animal and cell-line models suggest that vitamin D metabolism plays an important role in pancreatic tumor behavior. Although vitamin D deficiency has been implicated in numerous cancers, the vitamin D status of patients with advanced ... Full text Link to item Cite

Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial.

Journal Article J Clin Oncol · May 20, 2014 PURPOSE: The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that 1 year of adjuvant imatinib prolonged recurrence-free survival (RFS) after resection of primary GI stromal t ... Full text Link to item Cite

Loss of β-catenin triggers oxidative stress and impairs hematopoietic regeneration.

Journal Article Genes Dev · May 1, 2014 Accidental or deliberate ionizing radiation exposure can be fatal due to widespread hematopoietic destruction. However, little is known about either the course of injury or the molecular pathways that regulate the subsequent regenerative response. Here we ... Full text Link to item Cite

A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469.

Journal Article Pharmacogenet Genomics · February 2014 XK469 (NSC 697887) is a selective topoisomerase II β inhibitor eliminated mainly by aldehyde oxidase I (AOX1). We performed a candidate gene study to investigate whether AOX1 genetic variation contributes to interindividual variability in XK469 clearance. ... Full text Link to item Cite

Robust rat pulmonary radioprotection by a lipophilic Mn N-alkylpyridylporphyrin, MnTnHex-2-PyP(5+).

Journal Article Redox Biol · 2014 With the goal to enhance the distribution of cationic Mn porphyrins within mitochondria, the lipophilic Mn(III)meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP(5+) has been synthesized and tested in several different model of diseases, where ... Full text Link to item Cite

Robust rat pulmonary radioprotection by a lipophilic Mn N-alkylpyridylporphyrin, MnTnHex-2-PyP5+

Journal Article Redox Biology · January 1, 2014 With the goal to enhance the distribution of cationic Mn porphyrins within mitochondria, the lipophilic Mn(III)meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP5+ has been synthesized and tested in several different model of diseases, where i ... Full text Cite

Differential Angiogenic Gene Expression in TP53 Wild-Type and Mutant Ovarian Cancer Cell Lines.

Journal Article Front Oncol · 2014 OBJECTIVES: Underlying mechanisms regulating angiogenesis in ovarian cancer have not been completely elucidated. Evidence suggests that the TP53 tumor suppressor pathway and tumor microenvironment play integral roles. We utilized microarray technology to s ... Full text Link to item Cite

Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance)

Journal Article Pharmacogenomics Journal · January 1, 2014 Peripheral neuropathy is a common dose-limiting toxicity for patients treated with paclitaxel. For most individuals, there are no known risk factors that predispose patients to the adverse event, and pathogenesis for paclitaxel-induced peripheral neuropath ... Full text Cite

Next generation distributed computing for cancer research.

Journal Article Cancer Inform · 2014 Advances in next generation sequencing (NGS) and mass spectrometry (MS) technologies have provided many new opportunities and angles for extending the scope of translational cancer research while creating tremendous challenges in data management and analys ... Full text Link to item Cite

MicroRNA expression differentiates squamous epithelium from Barrett's esophagus and esophageal cancer.

Journal Article Dig Dis Sci · November 2013 BACKGROUND: Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neopla ... Full text Link to item Cite

A phase II study of the oral VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK222584) in myelodysplastic syndrome: Cancer and Leukemia Group B study 10105 (Alliance).

Journal Article Invest New Drugs · October 2013 BACKGROUND: Angiogenesis is implicated in the pathophysiology and progression of myelodysplastic syndromes (MDS). Vatalanib (PTK787/ZK222584; Novartis and Schering AG) inhibits receptor tyrosine kinases of vascular endothelial growth factor, platelet deriv ... Full text Link to item Cite

Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial.

Journal Article Ann Surg · September 2013 OBJECTIVE: To conduct the first adjuvant trial of imatinib mesylate for treatment of gastrointestinal stromal tumor (GIST). BACKGROUND: GIST is the most common sarcoma. Although surgical resection has been the mainstay of therapy for localized, primary GIS ... Full text Link to item Cite

Gastric cancer pharmacogenetics: progress or old tripe?

Journal Article Pharmacogenomics · July 2013 Gastric cancer remains the second most frequent cause of cancer-related mortality. While surgery is traditionally the initial treatment for early-stage disease, the addition of chemotherapy has been shown to significantly increase overall survival and prog ... Full text Link to item Cite

Analysis of single nucleotide polymorphisms and radiation sensitivity of the lung assessed with an objective radiologic endpoin.

Journal Article Clin Lung Cancer · May 2013 BACKGROUND: The primary objective of this study was to evaluate the association between radiation sensitivity of the lungs and candidate single nucleotide polymorphisms (SNP) in genes implicated in radiation-induced toxicity. METHODS: Patients with lung ca ... Full text Link to item Cite

Integration of cell line and clinical trial genome-wide analyses supports a polygenic architecture of Paclitaxel-induced sensory peripheral neuropathy.

Journal Article Clin Cancer Res · January 15, 2013 PURPOSE: We sought to show the relevance of a lymphoblastoid cell line (LCL) model in the discovery of clinically relevant genetic variants affecting chemotherapeutic response by comparing LCL genome-wide association study (GWAS) results to clinical GWAS r ... Full text Link to item Cite

The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (Alliance).

Journal Article Pharmacogenet Genomics · January 2013 Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those ... Full text Link to item Cite

A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101.

Journal Article Clin Cancer Res · September 15, 2012 Featured Publication PURPOSE: Sensory peripheral neuropathy is a common and sometimes debilitating toxicity associated with paclitaxel therapy. This study aims to identify genetic risk factors for the development of this toxicity. EXPERIMENTAL DESIGN: A prospective pharmacogen ... Full text Link to item Cite

Power and sample size calculations for SNP association studies with censored time-to-event outcomes.

Journal Article Genet Epidemiol · September 2012 Featured Publication For many clinical studies in cancer, germline DNA is prospectively collected for the purpose of discovering or validating single-nucleotide polymorphisms (SNPs) associated with clinical outcomes. The primary clinical endpoint for many of these studies are ... Full text Link to item Cite

Dr. McCarthy and colleagues reply

Journal Article New England Journal of Medicine · August 9, 2012 Full text Cite

Lenalidomide after stem-cell transplantation for multiple myeloma.

Journal Article N Engl J Med · May 10, 2012 Featured Publication BACKGROUND: Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma. METHODS: Between April 2005 and July 2009, we rand ... Full text Link to item Cite

A polymorphism within the promoter of the TGFβ1 gene is associated with radiation sensitivity using an objective radiologic endpoint.

Journal Article Int J Radiat Oncol Biol Phys · February 1, 2012 Featured Publication PURPOSE: To evaluate whether single nucleotide polymorphisms (SNPs) in the transforming growth factor-β1 (TGFβ1) gene are associated with radiation sensitivity using an objective radiologic endpoint. METHODS AND MATERIALS: Preradiation therapy and serial p ... Full text Link to item Cite

Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303).

Journal Article Cancer · January 15, 2012 Featured Publication BACKGROUND: Patients with advanced stage adenocarcinoma of the pancreas have a poor prognosis. The identification of prognostic and/or predictive biomarkers may help stratify patients so that therapy can be individualized. METHODS: Serum samples from patie ... Full text Link to item Cite

A genome-wide association study of overall survival in pancreatic cancer patients treated with gemcitabine in CALGB 80303.

Journal Article Clin Cancer Res · January 15, 2012 Featured Publication BACKGROUND AND AIMS: Cancer and Leukemia Group B 80303 was a randomized, phase III study in patients with advanced pancreatic cancer treated with gemcitabine plus either bevacizumab or placebo. We prospectively collected germline DNA and conducted a genome ... Full text Link to item Cite

Statistical considerations for analysis of microarray experiments.

Journal Article Clin Transl Sci · December 2011 Featured Publication Microarray technologies enable the simultaneous interrogation of expressions from thousands of genes from a biospecimen sample taken from a patient. This large set of expressions generates a genetic profile of the patient that may be used to identify poten ... Full text Link to item Cite

Whole blood gene expression analyses in patients with single versus recurrent venous thromboembolism.

Journal Article Thromb Res · December 2011 Featured Publication INTRODUCTION: Venous thromboembolism may recur in up to 30% of patients with a spontaneous venous thromboembolism after a standard course of anticoagulation. Identification of patients at risk for recurrent venous thromboembolism would facilitate decisions ... Full text Link to item Cite

"Sowing dragon's teeth?" Myeloma and AML.

Journal Article Blood · October 13, 2011 Featured Publication Full text Link to item Cite

Reduced-intensity allogeneic transplantation provides high event-free and overall survival in patients with advanced indolent B cell malignancies: CALGB 109901.

Journal Article Biol Blood Marrow Transplant · September 2011 Featured Publication Cancer and Leukemia Group B conducted a phase II study to evaluate the safety and efficacy of a reduced-intensity conditioning regimen with allogeneic transplantation to treat patients with recurrent low-grade B cell malignancies. Patients over age 18 with ... Full text Link to item Cite

Hematopoietic cell infusion for the treatment of nuclear disaster victims: new data from the Chernobyl accident.

Journal Article Int J Radiat Biol · August 2011 Featured Publication PURPOSE: To present previously unavailable data on the use of stem cell administration to aid recovery of victims of the Chernobyl disaster. On 26 April 1986, an accident at Unit 4 of the Chernobyl Nuclear Power Plant took place during the planned test of ... Full text Link to item Cite

Multiple testing for gene sets from microarray experiments.

Journal Article BMC Bioinformatics · May 26, 2011 Featured Publication BACKGROUND: A key objective in many microarray association studies is the identification of individual genes associated with clinical outcome. It is often of additional interest to identify sets of genes, known a priori to have similar biologic function, a ... Full text Open Access Link to item Cite

Discriminating between latent and active tuberculosis with multiple biomarker responses.

Journal Article Tuberculosis (Edinb) · May 2011 Featured Publication We sought to identify biomarker responses to tuberculosis specific antigens which could 1) improve the diagnosis of tuberculosis infection and 2) allow the differentiation of active and latent infections. Seventy subjects with active tuberculosis (N = 12), ... Full text Link to item Cite

Reduced-intensity conditioning allogeneic hematopoietic cell transplantation for patients with hematologic malignancies who relapse following autologous transplantation: a multi-institutional prospective study from the Cancer and Leukemia Group B (CALGB trial 100002).

Journal Article Biol Blood Marrow Transplant · April 2011 Featured Publication We prospectively treated 80 patients with relapse of malignancy or secondary myelodysplasia after autologous hematopoietic cell transplantation (AHCT) with allogeneic HCT (allo-HCT) using a reduced-intensity conditioning regimen of fludarabine 150 mg/m(2) ... Full text Link to item Cite

SNPpy--database management for SNP data from genome wide association studies.

Journal Article PLoS One · 2011 Featured Publication BACKGROUND: We describe SNPpy, a hybrid script database system using the Python SQLAlchemy library coupled with the PostgreSQL database to manage genotype data from Genome-Wide Association Studies (GWAS). This system makes it possible to merge study data w ... Full text Open Access Link to item Cite

Robust test method for time-course microarray experiments.

Journal Article BMC Bioinformatics · July 22, 2010 Featured Publication BACKGROUND: In a time-course microarray experiment, the expression level for each gene is observed across a number of time-points in order to characterize the temporal trajectories of the gene-expression profiles. For many of these experiments, the scienti ... Full text Open Access Link to item Cite

permGPU: Using graphics processing units in RNA microarray association studies.

Journal Article BMC Bioinformatics · June 16, 2010 Featured Publication BACKGROUND: Many analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, ... Full text Open Access Link to item Cite

Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates.

Journal Article PLoS One · June 16, 2010 Featured Publication Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7 ... Full text Open Access Link to item Cite

Early and late administration of MnTE-2-PyP5+ in mitigation and treatment of radiation-induced lung damage.

Journal Article Free Radic Biol Med · April 15, 2010 Featured Publication Chronic production of reactive oxygen and nitrogen species is an underlying mechanism of irradiation (IR)-induced lung injury. The purpose of this study was to determine the optimum time of delivery of an antioxidant and redox-modulating Mn porphyrin, MnTE ... Full text Link to item Cite

The importance of identifying and validating prognostic factors in oncology.

Journal Article Semin Oncol · April 2010 Featured Publication Prognosis plays a vital role in patient management and decision making. The assessment of prognostic factors, which relate baseline clinical and experimental covariables to outcomes, is one of the major objectives in clinical research. Historically, the im ... Full text Link to item Cite

Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1-T2 oral squamous cell carcinomas: results of a prospective multi-institutional trial.

Journal Article J Clin Oncol · March 10, 2010 Featured Publication PURPOSE: The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck dissection. METHODS: This prospective, cooperativ ... Full text Link to item Cite

A permutation-based multiple testing method for time-course microarray experiments.

Journal Article BMC Bioinformatics · October 15, 2009 Featured Publication BACKGROUND: Time-course microarray experiments are widely used to study the temporal profiles of gene expression. Storey et al. (2005) developed a method for analyzing time-course microarray studies that can be applied to discovering genes whose expression ... Full text Link to item Cite

Auto-SCT for AML in second remission: CALGB study 9620.

Journal Article Bone Marrow Transplant · September 2009 Featured Publication We studied the feasibility and efficacy of a two-step approach to Auto-SCT for patients with AML in second remission. Step 1 consisted of consolidation chemotherapy using cytarabine 2000 mg/m(2) i.v. every 12 h for 4 days plus etoposide 40 mg/kg total dose ... Full text Link to item Cite

Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer.

Journal Article J Clin Oncol · June 10, 2009 Featured Publication PURPOSE: To explore whether progression-free survival (PFS) or biochemical PFS can be used as a predictor of overall survival (OS) and to investigate the dependence between PFS and OS in men with castrate-resistant prostate cancer. PATIENTS AND METHODS: Da ... Full text Link to item Cite

Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers.

Journal Article AIDS · May 15, 2009 Featured Publication OBJECTIVE: To determine the spectrum of antiviral antibodies in HIV-1-infected individuals in whom viral replication is spontaneously undetectable, termed HIV controllers (HICs). DESIGN: Multicenter French trial ANRS EP36 studying the viral control in HICs ... Full text Link to item Cite

Phase I and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction: CALGB 60301.

Journal Article J Clin Oncol · April 10, 2009 Featured Publication PURPOSE: We sought to characterize the pharmacokinetics (PK) and determine a tolerable dose of oral sorafenib in patients with hepatic or renal dysfunction. PATIENTS AND METHODS: Patients were assigned to one of nine cohorts: cohort 1, bilirubin < or = upp ... Full text Link to item Cite

Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial.

Journal Article Lancet · March 28, 2009 Featured Publication BACKGROUND: Gastrointestinal stromal tumour is the most common sarcoma of the intestinal tract. Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived growth factor receptor alpha proteins, and is effective in first- ... Full text Link to item Cite

Authors' response

Journal Article Clinical Trials · December 1, 2008 Full text Cite

Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery.

Journal Article Cancer Epidemiol Biomarkers Prev · December 2008 Featured Publication BACKGROUND: Prostate cancer affects one of six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies ... Full text Link to item Cite

Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group.

Journal Article J Clin Oncol · November 20, 2008 Featured Publication PURPOSE: Imatinib mesylate is standard treatment for patients who have advanced gastrointestinal stromal tumor (GIST), but not all patients benefit equally. In previous studies, GIST genotype correlated with treatment outcome and optimal imatinib dosing. P ... Full text Link to item Cite

Statistical challenges in preprocessing in microarray experiments in cancer.

Journal Article Clin Cancer Res · October 1, 2008 Featured Publication Many clinical studies incorporate genomic experiments to investigate the potential associations between high-dimensional molecular data and clinical outcome. A critical first step in the statistical analyses of these experiments is that the molecular data ... Full text Link to item Cite

Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection.

Journal Article Free Radic Biol Med · March 15, 2008 Featured Publication Development of radiation therapy (RT)-induced lung injury is associated with chronic production of reactive oxygen and nitrogen species (ROS/RNS). MnTE-2-PyP5+ is a catalytic Mn porphyrin mimic of SOD, already shown to protect lungs from RT-induced injury ... Full text Link to item Cite

Designing phase II studies in cancer with time-to-event endpoints.

Journal Article Clin Trials · 2008 Featured Publication BACKGROUND: The primary clinical endpoint in many phase II studies in cancer is a time-to-event outcome subject to potential censoring. The decision in favor of abandoning or continuing investigation of the protocol regimen is typically based on the amount ... Full text Link to item Cite

A copula approach for detecting prognostic genes associated with survival outcome in microarray studies.

Journal Article Biometrics · December 2007 Featured Publication A challenging and crucial issue in clinical studies in cancer involving gene microarray experiments is the discovery, among a large number of genes, of a relatively small panel of genes whose elements are associated with a relevant clinical outcome variabl ... Full text Link to item Cite

Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101.

Journal Article J Clin Oncol · July 20, 2007 Featured Publication PURPOSE: We investigated dose and pharmacokinetics of erlotinib in patients with hepatic dysfunction or renal dysfunction. PATIENTS AND METHODS: Patients were assigned to one of three cohorts: cohort 1, AST > or = 3x upper limit of normal; cohort 2, direct ... Full text Link to item Cite

Rejoinder

Journal Article Journal of Biopharmaceutical Statistics · December 1, 2006 Full text Cite

Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis.

Journal Article Carcinogenesis · April 2006 Featured Publication Hedgehog (Hh) pathway activation promotes tumors in several endodermally derived tissues, but its role in the pathogenesis of hepatocellular carcinoma (HCC) is unknown. Although normal hepatocytes lack Hh signaling, activation of the Hh pathway in endoderm ... Full text Link to item Cite

Unirhinal olfactory function in schizophrenia patients and first-degree relatives.

Journal Article J Neuropsychiatry Clin Neurosci · 2006 Previous studies report birhinal impairments in odor identification in patients with schizophrenia and their family members. The authors employed unirhinal odor identification and detection threshold sensitivity tests in schizophrenia patients, healthy fir ... Full text Link to item Cite

P-value calculation for multistage phase II cancer clinical trials.

Journal Article J Biopharm Stat · 2006 Featured Publication Due to ethical and practical issues, clinical trials are conducted in multiple stages, but the reported p-values often fail to reflect the design aspect of the trials. We investigate some approaches to p-value calculation in analyzing multi-stage Phase II ... Full text Link to item Cite

A multiple testing procedure to associate gene expression levels with survival.

Journal Article Stat Med · October 30, 2005 Featured Publication In many microarray studies the primary objective is to identify, from a large panel of genes, those which are prognostic markers of a censored survival endpoint such as time to disease recurrence or death. Often, these genes are considered prognostic in th ... Full text Link to item Cite

Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A.

Journal Article N Engl J Med · September 15, 2005 Featured Publication BACKGROUND: Medullary thyroid carcinoma is the most common cause of death in patients with multiple endocrine neoplasia (MEN) type 2A (MEN-2A) or type 2B or familial medullary thyroid carcinoma. We sought to determine whether total thyroidectomy in asympto ... Full text Link to item Cite

Copulas: Concepts and novel applications

Journal Article Metron · December 1, 2003 A bivariate copula can be statistically interpreted as a bivariate distribution function with uniform marginals. Sklar (1959) argues that for any bivariate distribution function, say H with marginals F and G, there exists a copula functional, say C, such t ... Cite

Physiologic impairment of olfactory stimulus processing in schizophrenia.

Journal Article Biol Psychiatry · March 1, 2003 BACKGROUND: Behavioral studies of olfaction have demonstrated impairments in the ability to detect and identify odors in patients with schizophrenia. These deficits appear to be independent of either symptom severity or other cognitive impairment. Only lim ... Full text Link to item Cite