Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99


Any time

2019 ( 217 )

2018 ( 458 )

2017 ( 468 )

2016 ( 500 )

Custom range...

Search Results: 1 - 10 of 217345 matches for " Wan L. Lam "
All listed articles are free for downloading (OA Articles)
Page 1 /217345
Display every page Item
Comprehensive copy number profiles of breast cancer cell model genomes
Ashleen Shadeo, Wan L Lam
Breast Cancer Research , 2005, DOI: 10.1186/bcr1370
Abstract: Breast cancer model cell lines MCF-7, BT-474, MDA-MB-231, T47D, SK-BR-3, UACC-893 and ZR-75-30 were investigated for genomic alterations with the submegabase-resolution tiling array (SMRT) array comparative genomic hybridization (CGH) platform. SMRT array CGH provides tiling coverage of the human genome permitting break-point detection at about 80 kilobases resolution. Two novel discrete alterations identified by array CGH were verified by fluorescence in situ hybridization.Whole-genome tiling path array CGH analysis identified novel high-level alterations and fine-mapped previously reported regions yielding candidate genes. In brief, 75 high-level gains and 48 losses were observed and their respective boundaries were documented. Complex alterations involving multiple levels of change were observed on chromosome arms 1p, 8q, 9p, 11q, 15q, 17q and 20q. Furthermore, alignment of whole-genome profiles enabled simultaneous assessment of copy number status of multiple components of the same biological pathway. Investigation of about 60 loci containing genes associated with the epidermal growth factor family (epidermal growth factor receptor, HER2, HER3 and HER4) revealed that all seven cell lines harbor copy number changes to multiple genes in these pathways.The intrinsic genetic differences between these cell lines will influence their biologic and pharmacologic response as an experimental model. Knowledge of segmental changes in these genomes deduced from our study will facilitate the interpretation of biological data derived from such cells.Breast cancer is the most prevalent cancer worldwide and is the second leading cause of cancer-related deaths in women in North America [1,2]. It is a complex disease in which multiple genetic factors can combine to drive pathogenesis [3-5]. Changes in copy numbers of genes such as ERBB2 and c-MYC have been extensively documented in breast cancer and are present in model cell lines [6-9]. Amplified (and overexpressed) genes are pri
A stepwise framework for the normalization of array CGH data
Mehrnoush Khojasteh, Wan L Lam, Rabab K Ward, Calum MacAulay
BMC Bioinformatics , 2005, DOI: 10.1186/1471-2105-6-274
Abstract: After an investigation of the systematic variations in the data from two array CGH platforms, SMRT (Sub Mega base Resolution Tiling) BAC arrays and cDNA arrays of Pollack et al., we have developed a stepwise normalization framework integrating novel and existing normalization methods in order to reduce intensity, spatial, plate and background biases. We used stringent measures to quantify the performance of this stepwise normalization using data derived from 5 sets of experiments representing self-self hybridizations, replicated experiments, detection of single copy changes, array CGH experiments which mimic cell population heterogeneity, and array CGH experiments simulating different levels of gene amplifications and deletions. Our results demonstrate that the three-step normalization procedure provides significant improvement in the sensitivity of detection of single copy changes compared to conventional single step normalization approaches in both SMRT BAC array and cDNA array platforms.The proposed stepwise normalization framework preserves the minute copy number changes while removing the observed systematic biases.Microarray-based Comparative Genomic Hybridization (array CGH) is used to detect the aberrations in segmental copy numbers at chromosomal loci represented by DNA clones with known genomic locations [1]. CGH microarrays typically contain tens of thousands of spotted DNA sequences such as those derived from bacterial artificial chromosomes (BACs). Sample DNA from a test and a reference genome are labelled with different fluorescent dyes (usually Cyanine-3 and Cyanine-5 dyes) and then hybridized to the genomic microarray. The fluorescent signal intensity of each spot on the microarray serves as a relative measure of the amount of sample DNA bound to the DNA sequence of that spot. The ratio between the Cyanine-3 and the Cyanine-5 intensity of each spot reflects the relative quantities of the test and reference DNA samples.The ratio of the two fluorescent
The functional role of long non-coding RNA in human carcinomas
Ewan A Gibb, Carolyn J Brown, Wan L Lam
Molecular Cancer , 2011, DOI: 10.1186/1476-4598-10-38
Abstract: One of modern biology's great surprises was the discovery that the human genome encodes only ~20,000 protein-coding genes, representing <2% of the total genome sequence [1,2]. However, with the advent of tiling resolution genomic microarrays and whole genome and transcriptome sequencing technologies it was determined that at least 90% of the genome is actively transcribed [3,4]. The human transcriptome was found to be more complex than a collection of protein-coding genes and their splice variants; showing extensive antisense, overlapping and non-coding RNA (ncRNA) expression [5-10]. Although initially argued to be spurious transcriptional noise, recent evidence suggests that the proverbial "dark matter" of the genome may play a major biological role in cellular development and metabolism [11-17]. One such player, the newly discovered long non-coding RNA (lncRNA) genes, demonstrate developmental and tissue specific expression patterns, and aberrant regulation in a variety of diseases, including cancer [18-27].NcRNAs are loosely grouped into two major classes based on transcript size; small ncRNAs and lncRNAs (Table 1) [28-30]. Small ncRNAs are represented by a broad range of known and newly discovered RNA species, with many being associated with 5' or 3' regions of genes [4,31,32]. This class includes the well-documented miRNAs, RNAs ~22 nucleotides (nt) long involved in the specific regulation of both protein-coding, and putatively non-coding genes, by post-transcriptional silencing or infrequently by activation [33-35]. miRNAs serve as major regulators of gene expression and as intricate components of the cellular gene expression network [33-38]. Another newly described subclass are the transcription initiation RNAs (tiRNAs), which are the smallest functional RNAs at only 18 nt in length [39,40]. While a number of small ncRNAs classes, including miRNAs, have established roles in tumorigenesis, an intriguing association between the aberrant expression of ncRNA sate
Genetic alteration and gene expression modulation during cancer progression
Cathie Garnis, Timon PH Buys, Wan L Lam
Molecular Cancer , 2004, DOI: 10.1186/1476-4598-3-9
Abstract: The accumulation of genetic alterations is thought to drive the progression of normal cells through hyperplastic and dysplastic stages to invasive cancer and, finally, metastatic disease. Since the initial efforts to link histopathological changes to the mutation of specific genes in colorectal cancer [1], progression models have been developed for many tumor types, including lung, breast, head and neck, and prostate [2-5]. Mutational and gene expression analysis of known tumor suppressors and oncogenes in the context of early tumorigenesis has provided insight into the role of these genes in cancer progression [6,7]. Gene discovery has been greatly facilitated by molecular cytogenetic technologies identifying chromosomal regions associated with various stages and outcomes. Furthermore, high throughput, genome-wide approaches and the complete sequencing of the human genome have accelerated the large-scale discovery of cancer-related genes and pathways [8].While genetic alterations in tumors are common, changes found in premalignant stages are more likely to represent causal events initiating and promoting cancer development. These events may be masked by the complex pattern of genetic alterations often associated with genetic instability in later stages of disease. For this reason all stages of progression have to be considered in order to fully understand how malignant tissues develop. To date, genomic and proteomic efforts have been primarily directed at the study of tumors. The relatively limited literature on genetic studies of earlier stage cancers is attributable to challenges associated with accessing premalignant specimens and the fact that genome-wide analysis would require quantities of material far exceeding the size of the minute specimens obtained. Recent advances in cell isolation techniques and miniaturization of genomic technologies have enabled comprehensive molecular profiling of selected cell types and high resolution mapping of gene disruption as
Computational Methods for the Analysis of Array Comparative Genomic Hybridization
Raj Chari,William W. Lockwood,Wan L. Lam
Cancer Informatics , 2006,
Abstract: Array comparative genomic hybridization (array CGH) is a technique for assaying the copy number status of cancer genomes. The widespread use of this technology has lead to a rapid accumulation of high throughput data, which in turn has prompted the development of computational strategies for the analysis of array CGH data. Here we explain the principles behind array image processing, data visualization and genomic profile analysis, review currently available software packages, and raise considerations for future software development.
Induction of Human Squamous Cell-Type Carcinomas by Arsenic
Victor D. Martinez,Daiana D. Becker-Santos,Emily A. Vucic,Stephen Lam,Wan L. Lam
Journal of Skin Cancer , 2011, DOI: 10.1155/2011/454157
Abstract: Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epigenomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans. 1. Background Arsenic is a well-known human carcinogen (Class I, according to the International Agency for Research on Cancer—IARC [1]). Recommended thresholds for arsenic concentration in drinking water is ≤10?μg/L [2, 3] however, chronic exposure exceeding this limit has been reported worldwide affecting nearly one hundred million people worldwide daily, especially in Bangladesh, Taiwan, Mongolia, India, China, Argentina, Mexico, Canada, USA, and Chile, among others countries [4–9]. Long-term effects are a major health concern in affected areas. In the environment, arsenic can be found with an oxidation state +3 (known as arsenite or As [III]), or +5 (arsenate or As [V]), exhibiting different grades of toxicity [10]. Increased levels of inorganic arsenic (combined with oxygen, chlorine, and sulfur, among other elements) in drinking water is the major cause of arsenic toxicity [11, 12]. Both neoplastic and nonneoplastic effects have been described as consequence of arsenic exposure. Nonneoplastic effects primarily include peripheral vascular disorders (e.g., “black foot disease” almost exclusively observed in zones of Taiwan affected by arsenic contamination [13]), hypertension, diabetes, severe atherosclerosis, neuropathies, and, importantly, skin alterations, such as hyperkeratosis and hyperpigmentation [13–16]. Hyperkeratosis is particularly relevant, because it has been described as a precursor lesion of skin cancer tumors associated with arsenic exposure [17–19]. Several types of cancer have been attributed to arsenic exposure [20–25]. Skin,
Effect of active smoking on the human bronchial epithelium transcriptome
Raj Chari, Kim M Lonergan, Raymond T Ng, Calum MacAulay, Wan L Lam, Stephen Lam
BMC Genomics , 2007, DOI: 10.1186/1471-2164-8-297
Abstract: Twenty-four SAGE profiles of the bronchial epithelium of eight current, twelve former and four never smokers were generated and analyzed. In total, 3,111,471 SAGE tags representing over 110 thousand potentially unique transcripts were generated, comprising the largest human SAGE study to date. We identified 1,733 constitutively expressed genes in current, former and never smoker transcriptomes. We have also identified both reversible and irreversible gene expression changes upon cessation of smoking; reversible changes were frequently associated with either xenobiotic metabolism, nucleotide metabolism or mucus secretion. Increased expression of TFF3, CABYR, and ENTPD8 were found to be reversible upon smoking cessation. Expression of GSK3B, which regulates COX2 expression, was irreversibly decreased. MUC5AC expression was only partially reversed. Validation of select genes was performed using quantitative RT-PCR on a secondary cohort of nine current smokers, seven former smokers and six never smokers.Expression levels of some of the genes related to tobacco smoking return to levels similar to never smokers upon cessation of smoking, while expression of others appears to be permanently altered despite prolonged smoking cessation. These irreversible changes may account for the persistent lung cancer risk despite smoking cessation.Lung cancer has the highest mortality rate among all types of malignancies, accounting for approximately 29% of all cancer-related deaths in the United States [1]. It has been estimated that in 2006 alone, the number of new lung cancer cases will exceed 174,000 and approximately 163,000 people will die of this disease [1]. Tobacco smoking accounts for 85% of the lung cancers. Former heavy smokers remain at an elevated risk for developing lung cancer even years after they stop smoking [2,3]. Fifty percent of newly diagnosed lung cancer patients are former smokers [4]. It is therefore important to understand the effects of tobacco smoking on the
MicroRNA Gene Dosage Alterations and Drug Response in Lung Cancer
Katey S. S. Enfield,Greg L. Stewart,Larissa A. Pikor,Carlos E. Alvarez,Stephen Lam,Wan L. Lam,Raj Chari
Journal of Biomedicine and Biotechnology , 2011, DOI: 10.1155/2011/474632
Abstract: Chemotherapy resistance is a key contributor to the dismal prognoses for lung cancer patients. While the majority of studies have focused on sequence mutations and expression changes in protein-coding genes, recent reports have suggested that microRNA (miRNA) expression changes also play an influential role in chemotherapy response. However, the role of genetic alterations at miRNA loci in the context of chemotherapy response has yet to be investigated. In this study, we demonstrate the application of an integrative, multidimensional approach in order to identify miRNAs that are associated with chemotherapeutic resistance and sensitivity utilizing publicly available drug response, miRNA loci copy number, miRNA expression, and mRNA expression data from independent resources. By instigating a logical stepwise strategy, we have identified specific miRNAs that are associated with resistance to several chemotherapeutic agents and provide a proof of principle demonstration of how these various databases may be exploited to derive relevant pharmacogenomic results.
Genomics and premalignant breast lesions: clues to the development and progression of lobular breast cancer
Teresa L Mastracci, Fouad I Boulos, Irene L Andrulis, Wan L Lam
Breast Cancer Research , 2007, DOI: 10.1186/bcr1785
Abstract: Breast cancer has been hypothesized to develop through a linear histological progression from hyperplasia and in situ carcinoma to invasive cancer, a progression model that is possibly similar to that described for colon cancer [1,2]. It has been suggested that this process is accompanied by increasing genomic instability, among other hallmarks of cancer [3]. Recent advances in genomic technology have improved our understanding of the accumulation of genetic events that parallel breast cancer development; they have also revealed the complexity of premalignant lesions. Two major breast cancer subtypes are ductal and lobular, and the genetics of premalignant lobular breast lesions has only recently been explored. Findings suggest that the genomic events identified in hyperplasias and in situ carcinomas may be causative for the development of premalignant lesions, thus triggering or disrupting the downstream events that lead to disease progression [4]. In this review we focus on the development, pathology, and progression of lobular breast lesions, and describe our current understanding of premalignant lesions from a genomic point of view.The mammary gland is composed of an organized ductal network. Embedded within the stroma, the branching duct system leads from the collecting ducts via the segmental and subsegmental ducts to the terminal duct lobular units (TDLUs) [5]. Two cell types compose the epithelium of the duct and lobule system, namely luminal (secretory) cells and myoepithelial cells. The myoepithelial cell layer is found between the luminal epithelial cell layer and the basement membrane [5,6].Almost all mammary carcinomas develop within the TDLU or the terminal ducts that enter the lobular units. An understanding of the development of the TDLU is fundamental to discerning the events that are involved in neoplastic growth. From studies of mouse mammary development and human mammary epithelial cells grown in three-dimensional culture, acini structures have b
Arsenic, asbestos and radon: emerging players in lung tumorigenesis
Roland Hubaux, Daiana D Becker-Santos, Katey SS Enfield, Stephen Lam, Wan L Lam, Victor D Martinez
Environmental Health , 2012, DOI: 10.1186/1476-069x-11-89
Abstract: Lung cancer is commonly associated with tobacco smoke exposure. However, lung cancer in never smokers accounts for 10 to 25% of all cases, ranking as the 7th most common cause of cancer-related death [1,2]. As lung cancer in never smokers is thought to develop through molecular pathways different from those induced by tobacco, the study of non-tobacco related carcinogens is fundamental to better understand the biology of lung tumors arising in never smokers [1-5].Arsenic, asbestos and radon are well known human carcinogens, based on evidence derived from human and animal studies [6,7]. These three agents have been strongly linked to lung cancer development, both in smoker and never smokers [5,8-19]. Due to its wide distribution on a global scale (Figure 1), chronic exposure to these agents poses a significant public health problem. Millions of people, including those who never smoke, are at risk of developing lung cancer induced by arsenic, asbestos and radon.The carcinogenic effects due to exposure to these elements are well documented [5,8,9]. Table 1 summarizes different sources that provide scientific information linking exposure to these agents with lung cancer and other diseases. These lung carcinogens can induce a wide range of molecular alterations, including genetic (from specific point mutations to genome-wide aberrations) and epigenetic (including alterations in DNA methylation, and microRNA expression) [25]. Considering the relevance of this issue to public health, this article highlights the specific molecular events associated with exposure to arsenic, asbestos and radon as environmental carcinogens driving lung cancer.Arsenic, a naturally occurring metalloid in earth’s crust, is a well-established human carcinogen [7]. Exposure occurs mainly through drinking water, but also via air and food [22,26]. Arsenic contamination has been considered the largest mass poisoning in mankind’s history, since ~160 million people live in regions with naturally elevat
Page 1 /217345
Display every page Item

Copyright © 2008-2017 Open Access Library. All rights reserved.