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Biomedical subjects

Farid E Ahmed

Publications and source records attributed to Farid E Ahmed.

15 recordsLinked to original sources
PubMed2006

Gene-gene, gene-environment & multiple interactions in colorectal cancer.

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.

Cocarcinogenesis↗
PubMed2006

Role of genes, the environment and their interactions in the etiology of inflammatory bowel diseases.

Few of the studied genes demonstrate association with inflammatory bowel disease (IBD). Three mutations in the nucleotide-binding oligomerization domain 2 gene have consistently shown to be independent risk factors for Crohn's disease, but none of the alleles exhibited high sensitivity or specificity for IBD. Linkage analysis implicated several loci on various chromosomes, and epistasis has been demonstrated. The etiopathogenesis of IBD remains unknown, and environmental contribution to their pathogenesis is evident from genetic studies that demonstrated incomplete monozygotic twins concordandance rate for both Crohn's and ulcerative colitis. Smoking has shown an opposite effect on disease phenotype, with an adverse effect on disease course for Crohn's disease, but a slight beneficial effect in ulcerative colitis. The contribution of infectious agents to susceptibility to IBD appears to be strong. However, the role of nutrition on the etiology and therapy of IBD is not clear. Inconsistencies in environmental risk factors could be due to gene-environment interactions, making it essential to study the role of genetics and environmental contribution to the etiopathology of IBD. Transgenic or knockout mice, such as interleukin-10(-/-), T-cell receptor alpha(-/-), Galphai(2) (-/-) and N-cadherin(-/-), develop colitis-like inflammation similar to humans. Therefore, animal models must be further studied to explore mechanistic interactions.

Animals↗
PubMed2006

Microarray RNA transcriptional profiling: part I. Platforms, experimental design and standardization.

This review summarizes, in a balanced and comprehensive manner, the various components of microarrays and their types, substrate architecture, platforms for microarray probe implementation, standardizations and confounders. The review is intended to familiarize the beginner with the principles of experimental design and the selection of an appropriate microarray platform. This parallel technology has revolutionized transcriptomic approaches to data profiling and has a major role in the identification of expressed genes, classification and diagnosis studies. The technology is still evolving and guidelines for standardization and reporting have been developed and are being improved.

Equipment Design↗
PubMed2006

Microarray RNA transcriptional profiling: part II. Analytical considerations and annotation.

This review summarizes the various data filtration, transformation and normalization processes for different array platforms (cDNA, oligos, one- and two-color), data analysis methods and their validation, and databases and annotation for RNA transcriptional profiling microarrays. This review is intended to introduce the beginner to the analyses and interpretation of gene expression studies using a nonmathematical approach for easier comprehension. Microarray analysis is not a trivial undertaking as there is no single method that works well for all, and results obtained from these analyses should be considered as a complement to other approaches.

Computational Biology↗
PubMed2005

Artificial neural networks for diagnosis and survival prediction in colon cancer.

ANNs are nonlinear regression computational devices that have been used for over 45 years in classification and survival prediction in several biomedical systems, including colon cancer. Described in this article is the theory behind the three-layer free forward artificial neural networks with backpropagation error, which is widely used in biomedical fields, and a methodological approach to its application for cancer research, as exemplified by colon cancer. Review of the literature shows that applications of these networks have improved the accuracy of colon cancer classification and survival prediction when compared to other statistical or clinicopathological methods. Accuracy, however, must be exercised when designing, using and publishing biomedical results employing machine-learning devices such as ANNs in worldwide literature in order to enhance confidence in the quality and reliability of reported data.

Colonic Neoplasms↗
PubMed2005

Development of novel diagnostic and prognostic molecular markers for sporadic colon cancer.

Gene expression studies are informative about changes in colon cancer, increase understanding of the biology of tumorigenesis and aid in developing diagnostic and prognostic markers. In this review, expression techniques used to examine the multistage process of colon cancer are discussed. Many genes have been found to differ in expression between normal and tumorigenic states, as early as the seemingly normal colonic crypts. The clinical usefulness of markers varies with stage, ethnicity and anatomic location of colon cancer. Thus, combinations of markers can be used to develop an approach to molecularly screen and follow the progression of this prevalent cancer.

Biomarkers, Tumor↗
PubMed2005

Molecular markers that predict response to colon cancer therapy.

Progress in the treatment of colon cancer depends on the development of target-based molecules built on an improved understanding of the molecular biology of the disease. Defining end points for chemotherapy resistance is needed as drug resistance develops quickly and patients demonstrate variation in response to chemotherapy. Many techniques that measure a marker's preponderance have been developed including biochemical, immunohistochemical, genomics, proteomics or a combination thereof. However, standardization of these techniques that measure either genes or their protein products is urgently needed. This article reviews several markers (TS,TP, DPD, FT, EGFR, VEGF, CD44v6, TRAIL, microsatellite instability, allelic deletions, oncogenes and suppressor genes [c-myc, Ki-Ras, p53, p21, Topo I, Topo IIalpha, Fos, hMLH1, Bcl-2/Bax and MDR1], MDR-related proteins [Pgp, MRP and LRP], genomic polymorphisms [XPD, ERCC1, GSTP1 and TS 3 -UTR] and COX-;2) that influence DNA metabolism, DNA damage, programmed cell death, the immune or vascular system, or lead to mutations. When combined together and tested by newly developed genomic and proteomic approaches, many of these markers provide a more sensitive indicative predictor of response than when evaluated separately or by older biochemical, immunohistologic or morphologic methods. A global approach involving the simultaneous testing of several predictive multimarkers will provide critical information for improving chemotherapy to alleviate suffering from this disease.

Animals↗
PubMed2004

Effect of diet, life style, and other environmental/chemopreventive factors on colorectal cancer development, and assessment of the risks.

This review presents a comprehensive, evenhanded evaluation of the evidence from experimental, in vitro and human studies associating environmental and therapeutic factors with risk of colorectal cancer. Life styles correlated with the greatest increase in colorectal cancer risk are the ones that typify a diet rich in fat and calories, alcohol drinking and tobacco smoking, and low intake of vegetable, fruits and fibers, referred to as a "western diet," as well as sedentary style (i.e., no- or low-exercise). This kind of life style has also been associated with other chronic diseases (other cancers, obesity, dyslipedemia, diabetes, hypertension cardiovascular, and hypertension). The evidence does not implicated red meat as a risk factor, and fiber has been shown to protect against colorectal adenomas and carcinomas. Calcium, vitamin D, folate, and some antioxidant vitamins and minerals (gamma-tocopherol and selenium) have protective effects, and daily exercise for > or =30 min results in a significant decrease in risk. Estrogen use (hormone replacement therapy) substantially reduces colorectal cancer risk in postmenopausal women. Nonsteroidal anti-inflammatory drugs (e.g., aspirin) in excessive doses is protective, especially in high risk populations, but the side effects of its use and cost incurred due to its continued intake over long periods must be carefully scrutinized before any recommendations are made for the general public.

Adult↗
PubMed2003

Genetically modified probiotics in foods.

Probiotics have many potential therapeutic uses, but have not been universally accepted because of a lack of understanding of their action. Lactic acid bacteria (LAB) have been modified by traditional and genetic engineering methods to produce new varieties. Modern techniques of molecular biology have facilitated the identification of probiotic LAB strains, but only a few LAB have been modified by recombinant-DNA technology because of consumer resistance to their introduction to markets, especially in Europe.

Animals↗
PubMed2003

Colon cancer: prevalence, screening, gene expression and mutation, and risk factors and assessment.

Colon cancer detection at an early stage and identifying susceptible individuals can result in reduced mortality from this prevalent cancer. Genetic events leading to the development of this cancer involve a multistage progression of adenoma polyps to invasive metastatic carcinomas. Currently, there is no satisfactory screening method that is highly specific, sensitive, or reliable. Dietary patterns associated with the greatest increase in colon cancer risk are the ones that typify a diet rich in fat and calories, and low in vegetable, fruits, and fibers. Genetic susceptibility to environmental carcinogenesis must be factored into the risk assessment for this cancer. Many genes have been shown to be associated with increased expression and mutations in colorectal cancer patients. These genes have been reviewed; it is hoped that by carefully selecting a number of them, a molecular approach that is suitable for arriving at a tumorigenic expression index is developed, which will reliably detect this cancer at an early stage (i.e., before it metastasizes), especially in exfoliated samples (e.g., stool and blood), so that appropriate intervention strategies can be implemented. Illustrated herein is the utility of employing real-time reverse transcriptase polymerase chain reaction (RT-PCR) to quantitatively measure gene expression, and develop an index that is specific for this cancer, which if perfected may result in a reliable and sensitive screening technique for colorectal cancer detection.

Adenomatous Polyposis Coli↗
PubMed2002

Detection of genetically modified organisms in foods.

Legislation enacted worldwide to regulate the presence of genetically modified organisms (GMOs) in crops, foods and ingredients, necessitated the development of reliable and sensitive methods for GMO detection. In this article, protein- and DNA-based methods employing western blots, enzyme-linked immunosorbant assay, lateral flow strips, Southern blots, qualitative-, quantitative-, real-time- and limiting dilution-PCR methods, are discussed. Where information on modified gene sequences is not available, new approaches, such as near-infrared spectrometry, might tackle the problem of detection of non-approved genetically modified (GM) foods. The efficiency of screening, identification and confirmation strategies should be examined with respect to false-positive rates, disappearance of marker genes, increased use of specific regulator sequences and the increasing number of GM foods.

Blotting, Southern↗
PubMed2002

Molecular techniques for studying gene expression in carcinogenesis.

Many genes and signaling pathways controlling cell proliferation, death, differentiation, and genomic integrity are involved in cancer development. Various methods are available for detection and quantification of messenger RNA. Older methods such as Northern blots, nuclease protection, plaque hybridization, and slot blots suffer from being inherently serial, measure a single mRNA at a time, or being difficult to automate. New techniques for analysis of gene expression include: (a) comprehensive open systems such as serial analysis of gene expression (SAGE), differential display (DD) analysis, RNA arbitrarily primer (RAP)-PCR, restriction endonucleolytic analysis of differentially expressed sequences (READS), amplified restriction fragment-length polymorphism (AFLP), total gene expression analysis (TOGA), and use of internal standard competitive template primers (CTs) in a quantitative multiplex RT-PCR method [StaRT-(PCR)], and (b) focused closed systems such as: high density cDNA filter hybridization (HDFCA) analysis, suppression subtractive hybridization (SSH), differential screening (DS), several forms of high-density cDNA arrays, or oligonucleotide chips, and tissue microarrays. Sometimes, a combination of these systems is used to enhance the sensitivity and specificity of the assays. While closed systems are excellent for the initial screening of large number of sequences, the value of the information generated is generally limited to an often arbitrarily chosen known sequence. On the other hand, only the open system platform has the potential to evaluate the expression patterns of tens of thousands of genes that have not yet been cloned or partially sequenced in a quantitative manner. A cost analysis of the most commonly used expression technologies is provided. A method for purifying tumors from surrounding stroma and normal tissue employing laser microdissection, and subsequent RNA isolation/amplification from few cells employing sensitive kits are also discussed.

Cell Transformation, Neoplastic↗
PubMedDate not supplied

Improved methods for extracting RNA from exfoliated human colonocytes in stool and RT-PCR analysis.

In order to diagnose colon cancer at an earlier, more localized stage, there is a need to develop diagnostic markers (genes) which can detect early patterns of gene expression in exfoliated colonocytes shed in the stool during routine screening for this disease. An RNA-based detection is more pertinent than either a DNA-based or a protein-based method as a screening procedure, but it has not been widely used as a cancer screen because of the difficulty of handling and stabilizing the RNA molecule. We describe a method that permits extraction of intact nondegraded total RNA from human colonocytes in stool and from normal and malignant colon tissues (which were employed for comparison with stool). Because it utilizes commercially available kits, this method is simpler than other published methods and does not require isolation of messenger (m)RNA, thereby reducing the chances of contaminating the preparations with degrading nucleases, and even a small amount of isolated total RNA can be adequately reverse transcribed, making high-quality copy (c) DNA. This is followed by PCR (either qualitative end point or semiquantitative real-time) using colon cancer-specific gene primers. By routinely and systematically being able to perform quantitative gene expression measurements on noninvasive samples, the goal of this pilot work is to lay the groundwork for conducting a large clinical study to identify groups of selected genes whose expression is consistently altered at an early stage in the neoplastic process. Such work will permit noninvasive monitoring of at-risk patients through the analysis of their stool samples. Correct diagnosis will allow for surgical and/or other interventions before the tumor is well established and, thus, should decrease mortality from this preventable disease.

Adenocarcinoma↗
PubMedDate not supplied

Molecular markers for human colon cancer in stool and blood identified by RT-PCR.

There is a need for sensitive and specific diagnostic and prognostic molecular markers which can monitor early patterns of gene expression in non-invasive exfoliated colonocytes shed in the stool, and aggression in carcinoma cells in blood of resected colorectal cancer patients. RNA-based detection methods are more comprehensive than either DNA- or protein-based methods. By routinely and systematically being able to perform quantitative gene expression studies on non-invasive samples using carefully selected tumor-specific colon cancer genes, we can quantitatively and accurately monitor changes at various stages in the neoplastic process, allowing for surgical and/or other therapies, and thus, decrease mortality from colorectal cancer.

Adenocarcinoma↗