Biomedical subjects

Raymond Ng

Publications and source records attributed to Raymond Ng.

8 recordsLinked to original sources

PubMed2006

Multiple dysregulated pathways in nasopharyngeal carcinoma revealed by gene expression profiling.

Gene expression profiling was conducted using primary human nasopharyngeal carcinoma (NPC) biopsy samples to improve the understanding of the molecular pathways defining NPC and to identify novel potential therapeutic targets. RNA samples were extracted from 36 patients suspected to have NPC and hybridized onto the Affymetrix U133A chip. NPC was diagnosed in 19 patients, 11 had lymphoid hyperplasia (LH), and 6 were "normal" biopsies. Clinical stages for these NPC patients ranged from I-IV, including one M1. All NPC patients (except the M1) were treated with curative intent, which included radiotherapy alone (4 patients), or combined with chemotherapy (14 patients). Unsupervised clustering demonstrated a distinct NPC expression pattern, compared to normal biopsies. Subsequent Significance Analysis of Microarrays (SAM) derived from 14 NPC and 6 normal samples discovered 1,089 differentially regulated genes. Pathway analyses revealed novel insights into the mechanisms leading to NPC, whereby upregulation of NFkappaB2 and survivin play central roles in increasing resistance to apoptosis, and changes in integrin and WNT/beta-catenin signaling leading to uncontrolled proliferation. The role of survivin in resisting apoptosis in NPC was confirmed by RNA interference. Our data provide novel insights into the development and progression of NPC, and suggest survivin as a novel therapeutic target for NPC.

Apoptosis↗

PubMed2006

Integrating copy number polymorphisms into array CGH analysis using a robust HMM.

MOTIVATION: Array comparative genomic hybridization (aCGH) is a pervasive technique used to identify chromosomal aberrations in human diseases, including cancer. Aberrations are defined as regions of increased or decreased DNA copy number, relative to a normal sample. Accurately identifying the locations of these aberrations has many important medical applications. Unfortunately, the observed copy number changes are often corrupted by various sources of noise, making the boundaries hard to detect. One popular current technique uses hidden Markov models (HMMs) to divide the signal into regions of constant copy number called segments; a subsequent classification phase labels each segment as a gain, a loss or neutral. Unfortunately, standard HMMs are sensitive to outliers, causing over-segmentation, where segments erroneously span very short regions. RESULTS: We propose a simple modification that makes the HMM robust to such outliers. More importantly, this modification allows us to exploit prior knowledge about the likely location of "outliers", which are often due to copy number polymorphisms (CNPs). By "explaining away" these outliers with prior knowledge about the locations of CNPs, we can focus attention on the more clinically relevant aberrated regions. We show significant improvements over the current state of the art technique (DNAcopy with MergeLevels) on previously published data from mantle cell lymphoma cell lines, and on published benchmark synthetic data augmented with outliers. AVAILABILITY: Source code written in Matlab is available from http://www.cs.ubc.ca/~sshah/acgh.

Artificial Intelligence↗

PubMed2006

Identification of novel lung genes in bronchial epithelium by serial analysis of gene expression.

A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases, including cancer. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based on a vast dataset of nearly two million sequence tags from 21 serial analysis of gene expression (SAGE) libraries from individuals with a history of smoking. Our analysis suggests that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. Moreover, our analysis has identified novel bronchial-enriched genes such as MS4A8B, and has demonstrated the use of SAGE for the discovery of novel transcript variants. Significantly, gene expression associated with ciliogenesis is evident in bronchial epithelium, and includes the expression of transcripts specifying axonemal proteins DNAI2, SPAG6, ASP, and FOXJ1 transcription factor. Moreover, expression of potential regulators of ciliogenesis such as MDAC1, NYD-SP29, ARMC3, and ARMC4 were also identified. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, and constitutes one of the largest human SAGE studies reported to date.

Aged↗

PubMed2006

Anticancer agents and cardiotoxicity.

Although rare, cardiotoxicity is a significant complication of cancer treatment. The incidence and severity of cardiotoxicity are dependent on the type of drugs used, dose and schedule employed, and age of patients, as well as the presence of coexisting cardiac diseases and previous mediastinal irradiation. Anthracyclines are among one of the most active agents in oncology, but their use is often hampered by their cumulative dose-limiting cardiotoxicity. Combination therapy with new drugs in the last decade, such as taxanes and trastuzumab, in the treatment of metastatic breast cancer has yielded impressive results but also unexpected cardiotoxicity. Existing methods of minimizing cardiotoxicity include the use of protective agents such as dexrazoxane, different preparations of anthracyclines such as liposomal formulations, and alternative scheduling techniques. Assessment of left ventricular ejection fraction (LVEF) with two-dimensional (2D)-echocardiography or radionuclide ventriculography (RNVG) remains the most pragmatic means of monitoring for cardiotoxicity. The increasing number of long-term survivors of pediatric cancers, as well as the use of trastuzumab, taxanes, and anthracyclines in adjuvant treatment of breast cancer, means that more than ever, cardiotoxicity will remain an important issue for clinicians.

Adult↗

PubMed2005

Affymetrix oligonucleotide analysis of gene expression in the injured heart.

Microarrays have helped researchers gain much insight into gene expression profiles in the context of many diseases including those in the injured heart. Our genomic investigations have been focused on elucidation of host gene responses to enterovirus infection. We have gained valuable technical expertise in using Affymetrix oligonucleotide arrays, also known as GeneChips, and cDNA spotted arrays to probe differential gene expression in both cultured cells and in heart tissue. Here, we provide a technique-focused supplement to the Affymetrix GeneChip Expression Analysis Manual for sample preparation, processing, and array hybridization. We provide expanded explanations to highlight important points within the existing protocol and offer variations to standard procedures when appropriate. For investigators using myocardial tissues for microarray experiments, we further address the necessity of and methods for in situ flushing of the vasculature, tissue homogenization, and considerations for limits of expression detection in rare cells. It is our intention to provide useful technical information, based on our experience, to assist those researchers using Affymetrix GeneChips in their own genomic research.

Animals↗

PubMed2005

Pegfilgrastim: evidence in support of its use with cytotoxic chemotherapy.

The advent of granulocyte colony-stimulating factor, in particular filgrastim, in clinical use more than 10 years ago made a significant impact on the management of neutropenia and its complications. More recently, the application of pegylation technology has created a second-generation molecule, pegfilgrastim, with significantly altered pharmacokinetic properties. This has allowed for a once per chemotherapy cycle dosing in contrast to the requirement of daily subcutaneous administration for filgrastim. Several randomized trials in nonmyeloid malignancies have proven that a fixed dose of pegfilgrastim 6 mg is at least equivalent to daily filgrastim therapy. Emerging evidence also suggests that pegfilgrastim may be equally employed in the setting of chemotherapy for acute myeloid leukemia, dose-dense chemotherapy and peripheral stem cell mobilization. If confirmed in subsequent Phase III trials, it is likely that pegfilgrastim will eventually succeed filgrastim as the colony-stimulating factor of choice in clinical practice.

Acute Disease↗

PubMed2005

Undertreatment of elderly patients with non-small-cell lung cancer.

The absolute number of patients with lung cancer is rising as a result of our aging population. Until recently, clinicians have been reluctant to aggressively treat elderly patients with non-small-cell lung cancer (NSCLC) because of a lack of supportive data and concern for potential toxicity. Recently, evidence has emerged that suggests that, similar to younger patients, healthy elderly patients can benefit from therapy in all stages of NSCLC. This review will discuss the findings that indicate that chronologic age alone should not be a barrier to appropriate treatment for NSCLC, but consideration should be given to more important prognostic factors such as comorbidities and performance status.

Age Factors↗

PubMed2003

Inference of transcriptional regulation relationships from gene expression data.

MOTIVATION: In order to find gene regulatory networks from microarray data, it is important to first find direct regulatory relationships between pairs of genes. RESULTS: We propose a new method for finding potential regulatory relationships between pairs of genes from microarray time series data and apply it to expression data for cell-cycle related genes in yeast. We compare our algorithm, dubbed the event method, with the earlier correlation method and the edge detection method by Filkov et al. When tested on known transcriptional regulation genes, all three methods are able to find similar numbers of true positives. The results indicate that our algorithm is able to identify true positive pairs that are different from those found by the two other methods. We also compare the correlation and the event methods using synthetic data and find that typically, the event method obtains better results. AVALIABILITY: software is available upon request.

Algorithms↗