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Dive into the research topics where Pascale F. Macgregor is active.

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Featured researches published by Pascale F. Macgregor.


Journal of Virology | 2001

Herpes Simplex Virus Triggers and Then Disarms a Host Antiviral Response

Karen L. Mossman; Pascale F. Macgregor; Jacob Rozmus; Andrew B. Goryachev; A. Edwards; James R. Smiley

ABSTRACT Virus infection induces an antiviral response that is predominantly associated with the synthesis and secretion of soluble interferon. Here, we report that herpes simplex virus type 1 virions induce an interferon-independent antiviral state in human embryonic lung cells that prevents plaquing of a variety of viruses. Microarray analysis of 19,000 human expressed sequence tags revealed induction of a limited set of host genes, the majority of which are also induced by interferon. Genes implicated in controlling the intracellular spread of virus and eliminating virally infected cells were among those induced. Induction of the cellular response occurred in the absence of de novo cellular protein synthesis and required viral penetration. In addition, this response was only seen when viral gene expression was inhibited, suggesting that a newly synthesized viral protein(s) may function as an inhibitor of this response.


Journal of Computational Biology | 2001

Unfolding of microarray data.

Andrew B. Goryachev; Pascale F. Macgregor; A. Edwards

The use of DNA microarrays for the analysis of complex biological samples is becoming a mainstream part of biomedical research. One of the most commonly used methods compares the relative abundance of mRNA in two different samples by probing a single DNA microarray simultaneously. The simplicity of this concept sometimes masks the complexity of capturing and processing microarray data. On the basis of the analysis of many of our microarray experiments, we identified the major causes of distortion of the microarray data and the sources of noise. In this study, we provide a systematic statistical approach for extraction of true expression ratios from raw microarray data, which we describe as an unfolding process. The results of this analysis are presented in the form of a model describing the relationship between the measured fluorescent intensities and the concentrations of mRNA transcripts. We developed and tested several algorithms for inference of the model parameters for the microarray data. Special emphasis is given to the statistical robustness of these algorithms, in particular resistance to outliers. We also provide methods for measurement of noise and reproducibility of the microarray experiments.


Expert Review of Molecular Diagnostics | 2003

Gene expression in cancer: the application of microarrays

Pascale F. Macgregor

Genome-wide monitoring of gene expression using DNA microarrays represents one of the latest breakthroughs in experimental molecular biology and provides unprecedented opportunity to explore the biological processes underlying human diseases by providing a comprehensive survey of a cell’s transcriptional landscape. In the cancer field, this revolutionary technology allows the simultaneous assessment of the transcription of tens of thousands of genes, and of their relative expression between normal cells and malignant cells. As microarray analysis emerges from its infancy, there is widespread hope that microarrays will significantly impact on our ability to explore the genetic changes associated with cancer etiology and development, and ultimately lead to the discovery of new biomarkers for disease diagnosis and prognosis prediction, and of new therapeutic tools. This review provides an overview of microarray technology, specifically in the context of cancer research and describes some of its recent applications to the study of cancer. In addition, the challenges of translating microarray findings into molecular cancer diagnosis and prognosis tools, with the potential of altering clinical practice through individualized cancer care and ultimately of contributing to the battle against cancer, are discussed.


Laboratory Investigation | 2005

Karyotypic imbalances and differential gene expressions in the acquired doxorubicin resistance of hepatocellular carcinoma cells

Elizabeth W. Pang; Ying Hu; Kathy Yuen Yee Chan; Paul B.S. Lai; Jeremy A. Squire; Pascale F. Macgregor; Ben Beheshti; Monique Albert; Thomas W.T. Leung; Nathalie Wong

Administration of doxorubicin has been shown to prolong survival of patients with hepatocellular carcinoma (HCC). However, treatment regimen is often complicated by the emergence of drug resistance. The goal of our study is to enhance our understanding on the genetic changes that confer cellular chemoresistance to doxorubicin. To model this insensitive response, we established five doxorubicin-resistant (DOR) sublines through repeated exposure of escalating doses of doxorubicin to HCC cell lines (HKCI-2, -3, -4, -C1 and -C2). The DOR sublines developed displayed an average ∼17-fold higher IC50 value than their sensitive parental cell lines. The resistant phenotype displayed was investigated by the genome-wide analyses of comparative genomic hybridization (CGH) and complementary DNA microarray for the affected genomic anomalies and deregulated genes expressed, respectively. Over-representations of regional chr. 7q11–q21, 8q22–q23 and 10p13–pter were indicated in the DOR sublines from CGH analysis. Of particular interest was the finding of amplicon augmentations from regional or whole chromosome gains during the clonal expansion of resistant sublines. Most notably, recurring amplicon 7q11.2–q21 identified coincided with the location of the multi-drug-resistant gene, MDR1. The potential involvement of MDR1 was examined by quantitative reverse transcription-polymerase chain reaction RT-PCR (qRT-PCR), which indicated an upregulation in all DOR sublines (P=0.015). Consistent overexpression of the translated MDR1 gene, P-glycoprotein, in all five DOR sublines was further confirmed in Western blot analysis. Two distinct cluster dendrograms were achieved between the DOR sublines and their sensitive parental counterparts in expression profiling. Within the doxorubicin-resistant group, distinct features of candidate genes overexpressions including ABC transporting proteins, solute carriers and TOP2A were suggested. Further assessment of TOP2A messenger RNA levels by qRT-PCR confirmed array findings and pinpointed to a common up-regulation of TOP2A in DOR sublines. Our present study highlighted areas of genomic imbalances and candidate genes in the acquired doxorubicin-resistance behavior of HCC cells.


International Journal of Cancer | 2005

Transcriptional profiling on chromosome 19p indicated frequent downregulation of ACP5 expression in hepatocellular carcinoma

Kathy Yuen Yee Chan; Nathalie Wong; Paul B.S. Lai; Jeremy A. Squire; Pascale F. Macgregor; Ben Beheshti; Monique Albert; Ka Fai To; Philip J. Johnson

Chromosomal rearrangements unraveled by spectral karyotyping (SKY) indicated frequent chromosome 19 translocations in hepatocellular carcinoma (HCC). In an effort to characterize the aberrant 19 rearrangements in HCC, we performed positional mapping by fluorescence in‐situ hybridization (FISH) in 10 HCC cell lines. SKY analysis indicated structural rearrangements of chromosome 19 in 6 cell lines, 4 of which demonstrated recurring 19p translocations with different partner chromosomes. Using fluorescence‐labeled BAC probes, physical mapping indicated a breakpoint cluster between 19p13.12 and 19p12. A corresponding transcriptional mapping by cDNA array on 19p suggested the differential expression of a single downregulated gene ACP5 (tartrate‐resistant acid phosphatase type 5). Quantitative RT‐PCR confirmed the reduced expression of ACP5 and indicated a strong correlation of its repressed expression only in cell lines that contain a 19p rearrangement (p = 0.004). We further examined the expression of ACP5 in a cohort of 82 primary tumors and 74 matching nonmalignant liver tissues. In the primary HCC examined, a reduction of ACP5 transcripts by 2 to as much as 1,000‐fold was suggested in 67% of tumors (55/82 cases). When compared to adjacent nonmalignant tissues, 46% of tumors (34/74 cases) demonstrated a lower expression level (p = 0.015). On closer examination, a high significance of ACP5 repression was suggested in the cirrhotic HCC subgroup that was derived from chronic hepatitis B infected patients (55%; 30/54 cases; p = 0.001). Functional examination of ACP5 ectopic expression in HCC cells further demonstrated a significant growth inhibitory effect of ACP5 on tumor cell survival (p < 0.001). In our study, the novel finding of common ACP5 downregulation in HCC may provide basis for further investigations on the role of acid phosphatase in hepatocarcinogenesis.


Cancer Research | 2002

Parallel Analysis of Sporadic Primary Ovarian Carcinomas by Spectral Karyotyping, Comparative Genomic Hybridization, and Expression Microarrays

Jane Bayani; James D. Brenton; Pascale F. Macgregor; Ben Beheshti; Monique Albert; Dhani Nallainathan; Jana Karaskova; Barry Rosen; Joan Murphy; Stephanie Laframboise; Brent W. Zanke; Jeremy A. Squire


Neoplasia | 2005

High-Resolution Mapping of Genomic Imbalance and Identification of Gene Expression Profiles Associated with Differential Chemotherapy Response in Serous Epithelial Ovarian Cancer

Marcus Q. Bernardini; Chung-Hae Lee; Ben Beheshti; Mona Prasad; Monique Albert; Paula Marrano; Heather Begley; Patricia Shaw; Al Covens; Joan Murphy; Barry Rosen; Salomon Minkin; Jeremy A. Squire; Pascale F. Macgregor


Hepatology | 2003

Altered expression of genes involved in hepatic morphogenesis and fibrogenesis are identified by cDNA microarray analysis in biliary atresia

Limin Chen; Andrew B. Goryachev; Jin Sun; Peter K. Kim; Hui Zhang; M. James Phillips; Pascale F. Macgregor; Sylvie Lebel; A. Edwards; Qiongfang Cao; Katryn N. Furuya


Clinical Cancer Research | 2005

Transcriptional Profiling Identifies Gene Expression Changes Associated with IFN-α Tolerance in Hepatitis C–Related Hepatocellular Carcinoma Cells

Nathalie Wong; Kathy Yuen Yee Chan; Pascale F. Macgregor; Paul Bs Lai; Jeremy A. Squire; Ben Beheshti; Monique Albert; Thomas W.T. Leung


Oncology Reports | 2007

Microarray expression identification of differentially expressed genes in serous epithelial ovarian cancer compared with bulk normal ovarian tissue and ovarian surface scrapings

Dan Grisaru; Jan Hauspy; Mona Prasad; Monique Albert; K. Joan Murphy; Allan Covens; Pascale F. Macgregor; Barry Rosen

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Monique Albert

University Health Network

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Nathalie Wong

The Chinese University of Hong Kong

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Kathy Yuen Yee Chan

The Chinese University of Hong Kong

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Paul B.S. Lai

The Chinese University of Hong Kong

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Thomas W.T. Leung

The Chinese University of Hong Kong

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