Scholars@Duke
Patrick Tan

Patrick Tan

Adjunct Professor in the Department of Medicine
Medicine, Medical Oncology

Selected Publications

Comprehensive genomic meta-analysis identifies intra-tumoural stroma as a predictor of survival in patients with gastric cancer.

Journal Article Gut · August 2013 OBJECTIVE: Gastric adenocarcinoma (gastric cancer, GC) is a major cause of global cancer mortality. Identifying molecular programmes contributing to GC patient survival may improve our understanding of GC pathogenesis, highlight new prognostic factors and ... Full text Link to item Cite

Current and emerging surveillance strategies to expand the window of opportunity for curative treatment after surgery in colorectal cancer.

Journal Article Expert Rev Anticancer Ther · April 2013 Colorectal cancer is the third most common cancer globally. At diagnosis, more than 70% of patients have nonmetastatic disease. Cure rates for early-stage colorectal cancer have improved with primary screening, improvements in surgical techniques and advan ... Full text Link to item Cite

Growth inhibition of pathogenic bacteria by sulfonylurea herbicides.

Journal Article Antimicrob Agents Chemother · March 2013 Emerging resistance to current antibiotics raises the need for new microbial drug targets. We show that targeting branched-chain amino acid (BCAA) biosynthesis using sulfonylurea herbicides, which inhibit the BCAA biosynthetic enzyme acetohydroxyacid synth ... Full text Link to item Cite

mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice.

Journal Article J Clin Invest · February 2013 Gastrointestinal cancers are frequently associated with chronic inflammation and excessive secretion of IL-6 family cytokines, which promote tumorigenesis through persistent activation of the GP130/JAK/STAT3 pathway. Although tumor progression can be preve ... Full text Link to item Cite

Integrated epigenomics identifies BMP4 as a modulator of cisplatin sensitivity in gastric cancer.

Journal Article Gut · January 2013 OBJECTIVE: Cisplatin is a widely used gastric cancer (GC) chemotherapy; however, genetic factors regulating GC responses to cisplatin remain obscure. Identifying genes regulating cisplatin resistance could aid clinicians in tailoring treatments, by disting ... Full text Link to item Cite

Host cell transcriptome profile during wild-type and attenuated dengue virus infection.

Journal Article PLoS Negl Trop Dis · 2013 Dengue viruses 1-4 (DENV1-4) rely heavily on the host cell machinery to complete their life cycle, while at the same time evade the host response that could restrict their replication efficiency. These requirements may account for much of the broad gene-le ... Full text Link to item Cite

Gastric cancer pathology and underlying molecular mechanisms

Journal Article Digestive Surgery · 2013 The development of gastric adenocarcinoma is a complex multistep process involving multiple genetic alterations. Based on pathology, four different macroscopic types and at least two major histological types, intestinal and diffuse, have been described. Mo ... Full text Cite

Protection against experimental melioidosis following immunization with live Burkholderia thailandensis expressing a manno-heptose capsule

Journal Article Clinical and Vaccine Immunology · 2013 Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei. It is highly resistant to antibiotic treatment, and there is currently no licensed vaccine. Burkholderia thailandensis is a close relative of Burkholderia pseudomallei but is e ... Full text Cite

Whole-genome reconstruction and mutational signatures in gastric cancer.

Journal Article Genome Biol · December 13, 2012 BACKGROUND: Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first ... Full text Link to item Cite

Workshop on treatment of and postexposure prophylaxis for Burkholderia pseudomallei and B. mallei Infection, 2010.

Journal Article Emerg Infect Dis · December 2012 The US Public Health Emergency Medical Countermeasures Enterprise convened subject matter experts at the 2010 HHS Burkholderia Workshop to develop consensus recommendations for postexposure prophylaxis against and treatment for Burkholderia pseudomallei an ... Full text Link to item Cite

Isorhamnetin inhibits proliferation and invasion and induces apoptosis through the modulation of peroxisome proliferator-activated receptor γ activation pathway in gastric cancer.

Journal Article J Biol Chem · November 2, 2012 Gastric cancer (GC) is a lethal malignancy and the second most common cause of cancer-related deaths. Although treatment options such as chemotherapy, radiotherapy, and surgery have led to a decline in the mortality rate due to GC, chemoresistance remains ... Full text Link to item Cite

Methylation subtypes and large-scale epigenetic alterations in gastric cancer.

Journal Article Sci Transl Med · October 17, 2012 Epigenetic alterations are fundamental hallmarks of cancer genomes. We surveyed the landscape of DNA methylation alterations in gastric cancer by analyzing genome-wide CG dinucleotide (CpG) methylation profiles of 240 gastric cancers (203 tumors and 37 cel ... Full text Link to item Cite

STAT3-driven upregulation of TLR2 promotes gastric tumorigenesis independent of tumor inflammation.

Journal Article Cancer cell · October 2012 Gastric cancer (GC) is associated with chronic inflammation; however, the molecular mechanisms promoting tumorigenesis remain ill defined. Using a GC mouse model driven by hyperactivation of the signal transducer and activator of transcription (STAT)3 onco ... Full text Cite

Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library.

Journal Article BMC Med Genomics · August 9, 2012 BACKGROUND: While there is strong evidence for phosphatidylinositol 3-kinase (PI3K) involvement in cancer development, there is limited information about the role of PI3K regulatory subunits. PIK3R3, the gene that encodes the PI3K regulatory subunit p55γ, ... Full text Link to item Cite

TP53 genomic status regulates sensitivity of gastric cancer cells to the histone methylation inhibitor 3-deazaneplanocin A (DZNep).

Journal Article Clin Cancer Res · August 1, 2012 PURPOSE: DZNep (3-deazaneplanocin A) depletes EZH2, a critical component of polycomb repressive complex 2 (PRC2), which is frequently deregulated in cancer. Despite exhibiting promising anticancer activity, the specific genetic determinants underlying DZNe ... Full text Link to item Cite

Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma.

Journal Article Cancer Discov · July 2012 UNLABELLED: The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. ... Full text Link to item Cite

Exome sequencing of liver fluke-associated cholangiocarcinoma.

Journal Article Nat Genet · May 6, 2012 Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We ... Full text Link to item Cite

A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets.

Journal Article Gut · May 2012 OBJECTIVE: Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of ex ... Full text Link to item Cite

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes.

Journal Article Nat Genet · May 2012 Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcino ... Full text Link to item Cite

First evidence that γ-tocotrienol inhibits the growth of human gastric cancer and chemosensitizes it to capecitabine in a xenograft mouse model through the modulation of NF-κB pathway.

Journal Article Clin Cancer Res · April 15, 2012 PURPOSE: Because of poor prognosis and development of resistance against chemotherapeutic drugs, the existing treatment modalities for gastric cancer are ineffective. Hence, novel agents that are safe and effective are urgently needed. Whether γ-tocotrieno ... Full text Link to item Cite

Clinical and therapeutic relevance of PIM1 kinase in gastric cancer.

Journal Article Gastric Cancer · April 2012 BACKGROUND: Gastric cancer is a leading cause of cancer-related mortality, and chemotherapeutic options are currently limited. PIM1 kinase, an oncogene that promotes tumorigenesis in several cancer types, might represent a novel therapeutic target in gastr ... Full text Link to item Cite

A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer.

Journal Article Nat Med · March 18, 2012 Tyrosine kinase inhibitors (TKIs) elicit high response rates among individuals with kinase-driven malignancies, including chronic myeloid leukemia (CML) and epidermal growth factor receptor-mutated non-small-cell lung cancer (EGFR NSCLC). However, the exte ... Full text Link to item Cite

PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.

Journal Article PLoS One · 2012 Porcupine (PORCN) is a membrane-bound O-acyl transferase that is required for the palmitoylation of Wnt proteins, and that is essential in diverse Wnt pathways for Wnt-Wntless (WLS) binding, Wnt secretion, and Wnt signaling activity. We tested if PORCN was ... Full text Link to item Cite

Modulation of caenorhabditis elegans infection sensitivity by the LIN-7 cell junction protein

Journal Article Cellular Microbiology · 2012 In Caenorhabditis elegans, the LIN-2/7/10 protein complex regulates the activity of signalling proteins. We found that inhibiting lin-7 function, and also lin-2 and lin-10, resulted in enhanced C.elegans survival after infection by Burkholderia spp., impli ... Full text Cite

Understanding the genetic basis of gastric cancer: Recent advances

Journal Article Expert Review of Gastroenterology and Hepatology · 2012 Two major gastric cancer histological subtypes are recognized with distinct morphology, epidemiology, pathogenesis and clinical behavior. Genetically, the intestinal and diffuse subtypes are also characterized by distinct germline susceptibility patterns a ... Full text Cite

Development and validation of burkholderia pseudomallei-specific real-time pcr assays for clinical, environmental or forensic detection applications

Journal Article PLoS ONE · 2012 The bacterium Burkholderia pseudomallei causes melioidosis, a rare but serious illness that can be fatal if untreated or misdiagnosed. Species-specific PCR assays provide a technically simple method for differentiating B. pseudomallei from near-neighbor sp ... Full text Cite

Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: Novel markers in biological classification

Journal Article Breast Cancer Research and Treatment · 2012 Breast phyllodes tumors are rare neoplasms which present challenges for histological classification. Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluate ... Full text Cite

A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures.

Journal Article PLoS Genet · December 2011 MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or pathway targets. Currently, only a limited number of miRNAs have been functionally linked to specific signaling pathways. Here, we explored i ... Full text Link to item Cite

Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei.

Journal Article Proc Natl Acad Sci U S A · October 11, 2011 Known mechanisms of resistance to β-lactam antibiotics include β-lactamase expression, altered drug target, decreased bacterial permeability, and increased drug efflux. Here, we describe a unique mechanism of β-lactam resistance in the biothreat organism B ... Full text Link to item Cite

The molecular pathogenesis of STAT3-driven gastric tumourigenesis in mice is independent of IL-17.

Journal Article J Pathol · October 2011 Chronic activation of the gastric mucosal adaptive immune response is a characteristic trait of gastric cancer. It has recently emerged that a new class of T helper (Th) cells, defined by their ability to produce interleukin (IL)-17A (Th17), is associated ... Full text Link to item Cite

First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum.

Journal Article Genome Biol · September 28, 2011 BACKGROUND: Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exom ... Full text Link to item Cite

Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy.

Journal Article Gastroenterology · August 2011 BACKGROUND & AIMS: Gastric cancer (GC) is a heterogeneous disease comprising multiple subtypes that have distinct biological properties and effects in patients. We sought to identify new, intrinsic subtypes of GC by gene expression analysis of a large pane ... Full text Link to item Cite

IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1δ/ɛ and Wnt/β-catenin independent inhibition of mitotic spindle formation.

Journal Article Oncogene · June 2, 2011 Casein kinase 1 delta and epsilon (CK1δ/ɛ) are key regulators of diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. Recent studies suggest that they have an important role in oncogenesis. RNA interfere ... Full text Link to item Cite

Genomic profiles specific to patient ethnicity in lung adenocarcinoma.

Journal Article Clin Cancer Res · June 1, 2011 PURPOSE: East-Asian (EA) patients with non-small-cell lung cancer (NSCLC) are associated with a high proportion of nonsmoking women, epidermal growth factor receptor (EGFR)-activating somatic mutations, and clinical responses to tyrosine kinase inhibitors. ... Full text Link to item Cite

Paradoxical relationship between chromosomal instability and survival outcome in cancer.

Journal Article Cancer Res · May 15, 2011 Chromosomal instability (CIN) is associated with poor prognosis in human cancer. However, in certain animal tumor models elevated CIN negatively impacts upon organism fitness, and is poorly tolerated by cancer cells. To better understand this seemingly con ... Full text Link to item Cite

Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer.

Journal Article Clin Cancer Res · May 1, 2011 PURPOSE: MicroRNAs (miRNA) play pivotal oncogenic and tumor-suppressor roles in several human cancers. We sought to discover novel tumor-suppressor miRNAs in gastric cancer (GC). EXPERIMENTAL DESIGN: Using Agilent miRNA microarrays, we compared miRNA expre ... Full text Link to item Cite

Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes.

Journal Article Genome Res · May 2011 Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long-span paired-end-tag (PET) sequencing approach using 10-Kb genomic DNA inserts to study human genome structural variations (SVs). The use of a 10-Kb ... Full text Link to item Cite

CD44-SLC1A2 gene fusions in gastric cancer.

Journal Article Sci Transl Med · April 6, 2011 Fusion genes are chimeric genes formed in cancers through genomic aberrations such as translocations, amplifications, and rearrangements. To identify fusion genes in gastric cancer, we analyzed regions of chromosomal imbalance in a cohort of 106 primary ga ... Full text Link to item Cite

Assessing matched normal and tumor pairs in next-generation sequencing studies.

Journal Article PLoS One · March 18, 2011 Next generation sequencing technology has revolutionized the study of cancers. Through matched normal-tumor pairs, it is now possible to identify genome-wide germline and somatic mutations. The generation and analysis of the data requires rigorous quality ... Full text Link to item Cite

Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing.

Journal Article Cancer Res · January 1, 2011 Genetic alterations in kinases have been linked to multiple human pathologies. To explore the landscape of kinase genetic variation in gastric cancer (GC), we used targeted, paired-end deep sequencing to analyze 532 protein and phosphoinositide kinases in ... Full text Link to item Cite

A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A

Journal Article Science · 2011 The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal whe ... Full text Cite

Molecular classification of breast phyllodes tumors: Validation of the histologic grading scheme and insights into malignant progression

Journal Article Breast Cancer Research and Treatment · 2011 Phyllodes tumors of the breast are rare fibroepithelial neoplasms with a potential for recurrence. Current histological classification is not always predictive of clinical behavior. The aim of this study was to identify genetic changes associated with the ... Full text Cite

Genetics: An 18-gene signature (ColoPrint®) for colon cancer prognosis

Journal Article Nature Reviews Clinical Oncology · 2011 coloprint® is an 18-gene expression signature designed to predict disease relapse in patients with early-stage colorectal cancer (cRc). we discuss the potential impact of coloprint® on clinical practice, and its contribution to our knowledge of cRc molecul ... Full text Cite

Molecular-assisted immunohistochemical optimization.

Journal Article Acta Histochem · November 2010 Immunohistochemistry (IHC) is an essential tool in diagnostic surgical pathology, allowing analysis of protein subcellular localization. The use of IHC by different laboratories has lead to inconsistencies in published literature for several antibodies, du ... Full text Link to item Cite

Lethal-7 is down-regulated by the hepatitis B virus x protein and targets signal transducer and activator of transcription 3.

Journal Article J Hepatol · July 2010 BACKGROUND & AIMS: The pleiotropic hepatitis B virus (HBV) x protein (HBx), associated with hepatocellular carcinoma (HCC), has been implicated in the deregulation of cellular gene expression at the transcriptional level. To date, it remains unknown if HBx ... Full text Link to item Cite

Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma.

Journal Article Nat Med · July 2010 Although recurrent gene fusions involving erythroblastosis virus E26 transformation-specific (ETS) family transcription factors are common in prostate cancer, their products are considered 'undruggable' by conventional approaches. Recently, rare targetable ... Full text Link to item Cite

Triple negative breast cancer: outcome correlation with immunohistochemical detection of basal markers.

Journal Article Am J Surg Pathol · July 2010 We earlier evaluated the relationship of 653 triple negative breast cancers (TNBC) with basal immunophenotypic expression by using antibodies to basal cytokeratins (CK5/6, CK14, CK17, 34betaE12), p63, smooth muscle actin (SMA), epidermal growth factor rece ... Full text Link to item Cite

Identification of a regulatory cascade controlling Type III Secretion System 3 gene expression in Burkholderia pseudomallei.

Journal Article Mol Microbiol · May 2010 A major and critical virulence determinant of many Gram-negative bacterial pathogens is the Type III Secretion Systems (T3SS). T3SS3 in Burkholderia pseudomallei is critical for bacterial virulence in mammalian infection models but its regulation is unknow ... Full text Link to item Cite

A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence.

Journal Article PLoS Pathog · April 1, 2010 Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence"). To understand this process, we compared eleven isolate gen ... Full text Link to item Cite

Continuing evolution of Burkholderia mallei through genome reduction and large-scale rearrangements.

Journal Article Genome Biol Evol · January 22, 2010 Burkholderia mallei (Bm), the causative agent of the predominately equine disease glanders, is a genetically uniform species that is very closely related to the much more diverse species Burkholderia pseudomallei (Bp), an opportunistic human pathogen and t ... Full text Link to item Cite

Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells

Journal Article International Journal of Oncology · 2010 Palladin is a scaffold protein involved in the formation of actin-associated protein complexes. Gene expression array analysis on the poorly metastatic HCT116 colon cancer cell line and a metastatic derivative cell line (E1) with EMT (epithelial-mesenchyma ... Full text Cite

Genomic acquisition of a capsular polysaccharide virulence cluster by non-pathogenic Burkholderia isolates.

Journal Article Genome Biol · 2010 BACKGROUND: Burkholderia thailandensis is a non-pathogenic environmental saprophyte closely related to Burkholderia pseudomallei, the causative agent of the often fatal animal and human disease melioidosis. To study B. thailandensis genomic variation, we p ... Full text Link to item Cite

A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence.

Journal Article PLoS pathogens · 2010 Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence"). To understand this process, we compared eleven isolate gen ... Cite

Triple-negative breast cancer: clinicopathological characteristics and relationship with basal-like breast cancer.

Journal Article Mod Pathol · January 2010 Triple-negative breast cancer, defined as that with negative expression of estrogen and progesterone receptors and cerbB2, accounted for 11% of invasive breast cancers in our study, drawn from an original cohort of 7048 women diagnosed with breast cancer f ... Full text Link to item Cite

Oncogenic pathway combinations predict clinical prognosis in gastric cancer.

Journal Article PLoS Genet · October 2009 Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using ge ... Full text Link to item Cite

G-CSF induces a potentially tolerant gene and immunophenotype profile in T cells in vivo.

Journal Article Clin Immunol · July 2009 G-CSF can induce functional immune tolerance in man. In this study, purified T cells from G-CSF-mobilized peripheral blood stem cell (PBSC) donors were analysed by gene expression profiling and immunophenotyping. Results suggested a predominantly immune to ... Full text Link to item Cite

Prediction of clinical outcome in multiple lung cancer cohorts by integrative genomics: implications for chemotherapy selection.

Journal Article Cancer Res · February 1, 2009 The role of adjuvant chemotherapy in patients with stage IB non-small-cell lung cancer (NSCLC) is controversial. Identifying patient subgroups with the greatest risk of relapse and, consequently, most likely to benefit from adjuvant treatment thus remains ... Full text Link to item Cite

CDKN1C (p57) is a direct target of EZH2 and suppressed by multiple epigenetic mechanisms in breast cancer cells.

Journal Article PLoS One · 2009 CDKN1C (encoding tumor suppressor p57(KIP2)) is a cyclin-dependent kinase (CDK) inhibitor whose family members are often transcriptionally downregulated in human cancer via promoter DNA methylation. In this study, we show that CDKN1C is repressed in breast ... Full text Link to item Cite

Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer

Journal Article BMC Biology · 2009 Background: Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial spe ... Full text Cite

Post-treatment tumor gene expression signatures are more predictive of treatment outcomes than baseline signatures in breast cancer

Journal Article Pharmacogenetics and Genomics · 2009 Objective: Tumor gene expression signatures have been used to classify, prognosticate and predict chemotherapy sensitivity in breast cancer, although almost all efforts have been focused on the unchallenged baseline tumor. Most cancer patients receive syst ... Full text Cite

Divide and conquer: Progress in the molecular stratification of cancer

Journal Article Yonsei Medical Journal · 2009 Cancer remains an outstanding cause of global morbidity and mortality, despite intensive research and unprecedented insights into the basic mechanisms of cancer development. A plethora of clinical and experimental evidence suggests that cancers from indivi ... Full text Cite

Chemotherapy-induced tumor gene expression changes in human breast cancers

Journal Article Pharmacogenetics and Genomics · 2009 Objective Studying chemotherapy-induced gene expression changes in vivo, which could provide insights into mechanisms of chemotherapy resistance. Methods We analyzed and compared tumor gene expression changes of about 38500 genes before and 3 weeks after d ... Full text Cite

Integrative functional genomics in cancer research and its clinical implications

Journal Article Journal of Cancer Molecules · 2009 Many cancer predisposition and causative genes have been identified in the past few decades and have been extensively evaluated in primary tumors. The complex and highly heterogeneous nature of tumors requires more clinically useful candidate genes as prog ... Cite

Finding exclusively deleted or amplified genomic areas in lung adenocarcinomas using a novel chromosomal pattern analysis

Journal Article BMC Medical Genomics · 2009 Background. Genomic copy number alteration (CNA) that are recurrent across multiple samples often harbor critical genes that can drive either the initiation or the progression of cancer disease. Up to now, most researchers investigating recurrent CNAs cons ... Full text Cite

Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC)

Journal Article Journal of Thoracic Oncology · 2009 BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detecti ... Full text Cite

Cryopreservation of neurospheres derived from human glioblastoma multiforme.

Journal Article Stem Cells · January 2009 Cancer stem cells have been shown to initiate and sustain tumor growth. In many instances, clinical material is limited, compounded by a lack of methods to preserve such cells at convenient time points. Although brain tumor-initiating cells grown in a sphe ... Full text Link to item Cite

The core and accessory genomes of Burkholderia pseudomallei: implications for human melioidosis.

Journal Article PLoS Pathog · October 2008 Natural isolates of Burkholderia pseudomallei (Bp), the causative agent of melioidosis, can exhibit significant ecological flexibility that is likely reflective of a dynamic genome. Using whole-genome Bp microarrays, we examined patterns of gene presence a ... Full text Link to item Cite

A precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers.

Journal Article PLoS Genet · July 18, 2008 Successful tumor development and progression involves the complex interplay of both pro- and anti-oncogenic signaling pathways. Genetic components balancing these opposing activities are likely to require tight regulation, because even subtle alterations i ... Full text Link to item Cite

Bevacizumab and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma.

Journal Article J Hepatol · July 2008 BACKGROUND/AIMS: Hepatocellular carcinoma is a leading cause of global cancer mortality, with standard chemotherapy being minimally effective in prolonging survival. We investigated if combined targeting of vascular endothelial growth factor protein and ex ... Full text Link to item Cite

Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer.

Journal Article Cancer Res · June 15, 2008 Recurrent genomic amplifications and deletions are frequently observed in primary gastric cancers (GC). However, identifying specific oncogenes and tumor suppressor genes within these regions can be challenging, as they often cover tens to hundreds of gene ... Full text Link to item Cite

Inhibition of gastric cancer invasion and metastasis by PLA2G2A, a novel beta-catenin/TCF target gene.

Journal Article Cancer Res · June 1, 2008 Elevated expression of the PLA2G2A phospholipase in gastric cancer (GC) is associated with improved patient survival. To elucidate function and regulation of PLA2G2A in GC, we analyzed a panel of GC cell lines. PLA2G2A was specifically expressed in lines w ... Full text Link to item Cite

Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target.

Journal Article J Biol Chem · May 9, 2008 Like other cancers, aberrant gene regulation features significantly in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) were recently found to regulate gene expression at the post-transcriptional/translational levels. The expression profiles of 157 miRNA ... Full text Link to item Cite

Novel breast cancer biomarkers identified by integrative proteomic and gene expression mapping.

Journal Article J Proteome Res · April 2008 Proteomic and transcriptomic platforms both play important roles in cancer research, with differing strengths and limitations. Here, we describe a proteo-transcriptomic integrative strategy for discovering novel cancer biomarkers, combining the direct visu ... Full text Link to item Cite

Amplification and overexpression of PPFIA1, a putative 11q13 invasion suppressor gene, in head and neck squamous cell carcinoma.

Journal Article Genes Chromosomes Cancer · April 2008 Chromosomal amplifications of the 11q13 genomic region are frequent in head and neck squamous cell carcinoma (HNSCC). To identify novel 11q13 amplification targets, we integrated high-resolution array-based comparative genomic hybridization and Affymetrix ... Full text Link to item Cite

A comparative synteny map of Burkholderia species links large-scale genome rearrangements to fine-scale nucleotide variation in prokaryotes.

Journal Article Mol Biol Evol · March 2008 Genome rearrangement events, including inversions and translocations, are frequently observed across related microbial species, but the impact of such events on functional diversity is unclear. To clarify this relationship, we compared 4 members of the Gra ... Full text Link to item Cite

Clinical validation of a customized multiple signature microarray for breast cancer.

Journal Article Clin Cancer Res · January 15, 2008 PURPOSE: Current histopathologic systems for classifying breast tumors require evaluation of multiple variables and are often associated with significant interobserver variability. Recent studies suggest that gene expression profiles may represent a promis ... Full text Link to item Cite

Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer

Journal Article Science · 2008 Enhancer of zeste homolog 2 (EZH2) is a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes and regulates the survival and metastasis of cancer cells. EZH2 is overexpressed in aggressive solid tumors by mechanis ... Full text Cite

Germline polymorphisms as modulators of cancer phenotypes

Journal Article BMC Medicine · 2008 Identifying the complete repertoire of genes and genetic variants that regulate the pathogenesis and progression of human disease is a central goal of post-genomic biomedical research. In cancer, recent studies have shown that genome-wide association studi ... Full text Cite

The airbone metagenome in an indoor urban environment

Journal Article PLoS ONE · 2008 The indoor atmosphere is an ecological unit that inmpacts on public health. To investigate the composition of organisms in this space we applied culture-independent approaches to microbes harvested from the air of two densely populated urban buildings, fro ... Full text Cite

Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells.

Journal Article Genes Dev · May 1, 2007 Polycomb-repressive complex 2 (PRC2)-mediated histone methylation plays an important role in aberrant cancer gene silencing and is a potential target for cancer therapy. Here we show that S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A (DZNe ... Full text Link to item Cite

An alternative approach to determining therapeutic choices in advanced non-small cell lung carcinoma (NSCLC): Maximizing the diagnostic procedure and the use of low-volume lung biopsies

Journal Article Journal of Thoracic Oncology · 2007 BACKGROUND: Accurate mutational analysis, especially epidermal growth factor receptor (EGFR) mutations, of diagnostic biopsies from all Asian NSCLC patients is crucial to their clinical management, but faces problems. Here, we explore, within usual hospita ... Full text Cite

Targets of genome copy number reduction in primary breast cancers identified by integrative genomics

Journal Article Genes Chromosomes and Cancer · 2007 The identification of specific oncogenes and tumor suppressor genes in regions of recurrent aneuploidy is a major challenge of molecular cancer research. Using both oligonucleotide single-nucleotide polymorphism and mRNA expression arrays, we integrated ge ... Full text Cite

Global map of growth-regulated gene expression in Burkholderia pseudomallei, the causative agent of melioidosis

Journal Article Journal of Bacteriology · 2006 Many microbial pathogens express specific virulence traits at distinct growth phases. To understand the molecular pathways linking bacterial growth to pathogenicity, we have characterized the growth transcriptome of Burkholderia pseudomallei, the causative ... Full text Cite

Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression

Journal Article Annals of Oncology · 2006 Background: Celecoxib is a selective cyclooxygenase-2 inhibitor with antitumor and antiangiogenic activity. We sought to determine pharmacodynamic change in tumors of patients with nasopharyngeal carcinoma (NPC) treated with celecoxib. Methods: Tumor biops ... Full text Cite

Quantitative profiling of drug-associated proteomic alterations by combined 2-nitrobenzenesulfenyl chloride (NBS) isotope labeling and 2DE/MS identification

Journal Article Journal of Proteome Research · 2006 The identification of drug-responsive biomarkers in complex protein mixtures is an important goal of quantitative proteomics. Here, we describe a novel approach for identifying such drug-induced protein alterations, which combines 2-nitrobenzenesulfenyl ch ... Full text Cite

A modular analysis of breast cancer reveals a novel low-grade molecular signature in estrogen receptor-positive tumors

Journal Article Clinical Cancer Research · 2006 Purpose: Previous reports using genome-wide gene expression data to classify breast tumors have typically used standard unsupervised or supervised techniques, both of which have known limitations. We hypothesized that novel clinically relevant information ... Full text Cite

Genomic patterns of pathogen evolution revealed by comparison of Burkholderia pseudomallei, the causative agent of melioidosis, to avirulent Burkholderia thailandensis

Journal Article BMC Microbiology · 2006 Background: The Gram-negative bacterium Burkholderia pseudomallei (Bp) is the causative agent of the human disease melioidosis. To understand the evolutionary mechanisms contributing to Bp virulence, we performed a comparative genomic analysis of Bp K96243 ... Full text Cite

Atransforming growth factor-β-induced protein stimulates endocytosis and is up-regulated in immature dendritic cells

Journal Article Blood · 2006 Dendritic cells (DCs) exhibit distinct functional properties at immature and mature states. To identify genes preferentially regulated in monocyte-derived immature DCs (imDCs), 13 000-element microarrays were hybridized with RNA isolated from imDCs, mature ... Full text Cite

Topological and functional discovery in a gene coexpression meta-network of gastric cancer

Journal Article Cancer Research · 2006 Gastric cancer is a leading cause of global cancer mortality, but comparatively little is known about the cellular pathways regulating different aspects of the gastric cancer phenotype. To achieve a better understanding of gastric cancer at the levels of s ... Full text Cite

Evidence for selective expression of the p53 codon 72 polymorphs: Implications in cancer development

Journal Article Cancer Epidemiology Biomarkers and Prevention · 2005 Polymorphism at codon 72 of p53 results in either the arginine or proline form of p53, whose functional significance in carcinogenesis is controversial. We have investigated if the expression of these p53 polymorphs is selectively regulated, using mRNA fro ... Full text Cite

Drug discovery in the lion city

Journal Article Drug Discovery Today · 2005 Full text Cite

Integrative genomic, transcriptional, and proteomic diversity in natural isolates of the human pathogen Burkholderia pseudomallei

Journal Article Journal of Bacteriology · 2005 Natural isolates of pathogenic bacteria can exhibit a broad range of phenotypic traits. To investigate the molecular mechanisms contributing to such phenotypic variability, we compared the genomes, transcriptomes, and proteomes of two natural isolates of t ... Full text Cite

Immunohistochemical detection of Ki67 in breast cancer correlates with transcriptional regulation of genes related to apoptosis and cell death

Journal Article Modern Pathology · 2005 Ki67 is a nuclear protein that is tightly linked to the cell cycle. It is a marker of cell proliferation and has been used to stratify good and poor prognostic categories in invasive breast cancer. Its correlation with gene expression patterns has not been ... Full text Cite

Wavelet transformations of tumor expression profiles reveals a pervasive genome-wide imprinting of aneuploidy on the cancer transcriptome

Journal Article Cancer Research · 2005 Aneuploidy is frequently observed in many human cancers, but its global effects on the cancer transcriptome are controversial. We did a systematic and unbiased genome-wide survey to determine the extent a tumor's abnormal karyotype (chromosomal amplificati ... Cite

Patterns of large-scale genomic variation in virulent and avirulent Burkholderia species

Journal Article Genome Research · 2004 The human diseases melioidosis and glanders are caused by the bacteria Burkholderia pseudomallei and B. mallei respectively, and both species are regarded as potential biowarfare agents. We used B. pseudomallei DNA microarrays to compare the genomes of sev ... Full text Cite

In vitro biological characteristics of human cord blood-derived megakaryocytes

Journal Article Annals of the Academy of Medicine Singapore · 2004 Introduction: Umbilical cord blood (CB) has been used as an alternative source for haematopoietic stem cell transplantation (HSCT) in recent years. However, delayed platelet recovery is frequently associated with CB HSCT. Megakaryocytes (Mk) are the specia ... Cite

Identifying patterns of DNA for tumor diagnosis using capillary electrophoresis-amplified fragment length polymorphism (CE-AFLP) screening

Journal Article Journal of Bioinformatics and Computational Biology · 2004 Amplified Fragment Length Polymorphism (AFLP) screening is a genome-wide genotyping strategy that has been widely used in plants and bacteria, but little has been reported concerning its use in humans. We investigated if the AFLP procedure could be coupled ... Full text Cite

Conservation of breast cancer molecular subtypes and transcriptional patterns of tumor progression across distinct ethnic populations

Journal Article Clinical Cancer Research · 2004 Purpose: Breast cancers can display distinct clinical characteristics in different ethnic populations. Previous studies involving European and United States patients have shown that breast tumors can be divided by their gene expression profiles into distin ... Full text Cite

Successful treatment of idiopathic hypereosinophilic syndrome with imatinib mesylate: A case report

Journal Article International Journal of Hematology · 2004 Patients with idiopathic hypereosinophilic syndrome (HES) show persistent hypereosinophilia of unknown etiology that is associated with end-organ damage. Different treatments, including the use of corticosteroids and cytotoxics, have been investigated for ... Full text Cite

A Molecular Signature of the Nottingham Prognostic Index in Breast Cancer

Journal Article Cancer Research · 2004 The Nottingham prognostic index (NPI) is a widely used clinicopathological staging system for breast cancer prognostication. Using a step-wise classification approach where breast tumor expression profiles were first divided into general "molecular subtype ... Full text Cite

Role of phenytoin in wound healing: Microarray analysis of early transcriptional responses in human dermal fibroblasts

Journal Article Biochemical and Biophysical Research Communications · 2004 Wound healing is a complex process involving a number of related genes and receptors. Using cDNA microarrays, we explored the global gene expression profile of phenytoin (20μg/ml) induced changes to human dermal fibroblasts. Microarray data analysis reveal ... Full text Cite

Classifying the estrogen receptor status of breast cancers by expression profiles reveals a poor prognosis subpopulation exhibiting high expression of the ERBB2 receptor

Journal Article Human Molecular Genetics · 2003 Recent work using expression profiling to computationally predict the estrogen receptor (ER) status of breast tumors has revealed that certain tumors are characterized by a high prediction uncertainty ('low-confidence'). We analyzed these 'low-confidence' ... Full text Cite

Feasibility of Using Low-Volume Tissue Samples for Gene Expression Profiling of Advanced Non-Small Cell Lung Cancers

Journal Article Clinical Cancer Research · 2003 Purpose: The majority of patients with non-small cell lung cancer (NSCLC) present at an advanced clinical stage, when surgery is not a recommended therapeutic option. In such cases, tissues for molecular research are usually limited to the low-volume sampl ... Cite

A combined comparative genomic hybridization and expression microarray analysis of gastric cancer reveals novel molecular subtypes

Journal Article Cancer Research · 2003 Comparative genomic hybridization (CGH), microsatellite instability (MSI) assays, and expression microarrays were used to molecularly sub-classify a common set of gastric tumor samples. We identified a number of novel genomic aberrations associated with ga ... Cite

Genetic algorithms applied to multi-class prediction for the analysis of gene expression data

Journal Article Bioinformatics · 2003 Motivation: An important challenge in the use of large-scale gene expression data for biological classification occurs when the expression dataset being analyzed involves multiple classes. Key issues that need to be addressed under such circumstances are t ... Full text Cite

Characterization of Burkholderia pseudomallei infection and identification of novel virulence factors using a Caenorhabditis elegans host system

Journal Article Molecular Microbiology · 2002 The environmental saphrophyte Burkholderia pseudomallei is the causative agent of melioidosis, a systemic, potentially life-threatening condition endemic to many parts of south-east Asia and northern Australia. We have used the soil nematode Caenorhabditis ... Full text Cite

Fish analysis of tel-aml 1 in childhood leukaemia in a local multiracial asian population

Journal Article Blood · 2001 Acute Lymphoblastic Leukaemia (ALL) is the most common cancer in childhood. Chromosomal rearrangements occur in approximately 75% of children with ALL, most frequently involving chromosomes 12 and 21. The helix-loop-helix domain of the TEL gene on chromoso ... Cite

Randomised trial of fluconazole versus lowdose amphotericin b in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation

Journal Article Blood · 2000 Background:Over the past decade, invasive fungal infections has become an increasingly important problem in patients undergoing hematopoietic cell transplantation(HCT). Effective prevention of invasive fungal infection has been unsatisfactory because of ei ... Cite

Signaling specificity: the RTK/RAS/MAP kinase pathway in metazoans.

Journal Article Trends Genet · April 1999 The molecular basis by which commonly used signaling pathways are able to elicit tissue-specific responses in multicellular organisms is an important yet poorly understood problem. In this review, we use the receptor tyrosine kinase (RTK)/RAS/MAP kinase si ... Full text Link to item Cite

MAP kinase signaling specificity mediated by the LIN-1 Ets/LIN-31 WH transcription factor complex during C. elegans vulval induction.

Journal Article Cell · May 15, 1998 The let-23 receptor/mpk-1 MAP kinase signaling pathway induces the vulva in C. elegans. We show that MPK-1 directly regulates both the LIN-31 winged-helix and the LIN-1 Ets transcription factors to specify the vulval cell fate. lin-31 and lin-1 act genetic ... Full text Link to item Cite

Acute promyelocytic leukemia with a dicentric chromosome involving chromosomes 11, 17, and 18

Journal Article Cancer Genetics and Cytogenetics · 1998 We report a case of acute promyelocytic leukemia with dicentric chromosome resulting from translocation of chromosomes 11, 17, and 18. ... Full text Cite

A case of t(8;14) with total and partial trisomy 3 in Waldenstrom macroglobulinemia

Journal Article Cancer Genetics and Cytogenetics · 1998 A case of Waldenstrom macroglobulinemia with Burkitt-type t(8;14)(q24.1;q32) and total and partial trisomy 3 is reported. This is an unusual combination of chromosomal abnormalities in Waldenstrom macroglobulinemia. ... Full text Cite

The Saccharomyces cerevisiae SPT7 gene encodes a very acidic protein important for transcription in vivo

Journal Article Genetics · 1995 Mutations in the SPT7 gene of Saccharomyces cerevisiae originally were identified as suppressors of Ty and δ insertion mutations in the 5' regions of the HIS4 and LYS2 genes. Other genes that have been identified in mutant hunts of this type have been show ... Cite

Inhibition by Brefeldin A of protein secretion from the apical cell surface of Madin-Darby canine kidney cells

Journal Article Journal of Biological Chemistry · 1991 The effect of brefeldin A (BFA) on total and polarized protein secretion was examined in MDCK cells. Increasing concentrations of BFA have increasingly inhibitory effects on total protein secretion. The total protein secretion was essentially unaffected by ... Cite

Bone marrow transplantation for treatment of chronic myelogenous leukaemia (CML)--preliminary experience in Singapore.

Journal Article Annals of the Academy of Medicine Singapore · 1990 Chronic Myelogenous Leukaemia (CML) is a clonogeneic disease with the Philadelphia (Ph') chromosome as a cytogenetic marker. Conventional therapy rarely leads to cure in CML. Treatment of CML by bone marrow transplantation (BMT) is thus a reasonable altern ... Cite

Allogeneic bone marrow transplantation for acute non-lymphoblastic leukaemia--the Singapore experience.

Journal Article Annals of the Academy of Medicine Singapore · 1990 Eleven patients with acute non-lymphoblastic leukaemia (ANNL) underwent allogeneic bone marrow transplant (BMT) from the period, September 1985 to June 1989 in the Singapore General Hospital. Five of the six patients (83%) transplanted in the first remissi ... Cite