Biomedical subjects

A Fadiel

Publications and source records attributed to A Fadiel.

9 recordsLinked to original sources

PubMed2006

Functional duality of merlin: a conundrum of proteome complexity.

Merlin and ezrin proteins belong to the same gene family, i.e., MERM containing merlin, ezrin radixin and moesin. Members of this family possess an extensive homology in their amino acid sequences. It has been shown that merlin is a tumor suppressor, while ezrin is a promoter in tumor progression. The expression of these two proteins is commonly found inversely proportional to each other in cancer cells, i.e. down-regulation of merlin concomitant with over-expression of ezrin and vice versa. However, when determining merlin and ezrin in ovarian carcinoma cells, we have observed that both merlin and ezrin could be over-expressed simultaneously in some ovarian cancer (OVCA) cell lines and OVCA ascites cells, suggesting that merlin could be an oncoprotein rather than a tumor suppressor protein in certain OVCA cells. The functional duality of merlin might represent a paradigm in proteome complexity and is especially important in investigating multifactorial diseases such as cancer.

Cell Line, Tumor↗

PubMed2006

'Genomemark': detecting word periodicity in biological sequences.

Identifying and predicting the structural characteristics of novel repeats throughout the genome can lend insight into biological function. Specific repeats are believed to have biological significance as a function of their distribution patterns. We have developed 'GenomeMark,' a computer program that detects and statistically analyzes candidate repeats. Specifically, 'GenomeMark' identifies the periodic distribution of unique words, calculating their chi2 and Z-score values. Using 'GenomeMark,' we identified novel sequence words present in tandem throughout genomes. We found that these sequences have remarkable spacer sequence distributions and many were genome specific, validating the genome signature theory. Further analysis confirmed that many of these sequences have a specific biological function. The program is available from the authors upon request and is freely available for non-commercial and academic entities.

Algorithms↗

PubMed2005

Circulation DNA: biological implications for cancer metastasis and immunology.

Circulation cell free DNA (cf-DNA) is of considerable interest to oncology researchers seeking to isolate specific cancer markers. Here, we focus on the origin and biological implications of cf-DNA, exploring its potential roles in cancer biology and medicine. We hypothesize that cf-DNA is primarily released by living cancer cells in addition to apoptotic or necrotic cancer cells for three reasons: (1) following radiotherapy, cf-DNA quantities are significantly reduced in a high percentage of patients although radiation-induced massive apoptosis is expected; (2) cancer cell DNA concentration in cultured supernatants increases with cell proliferation when few apoptotic or necrotic cells are present; and (3) DNA concentration increases in normal lymphocyte cultures following stimulation with phytohemagglutinin, lipopolysaccharide or antigen. Our hypotheses have major biological implications in cancer biology. First, cancer cf-DNA may transform normal cells and form adjacent or remote metastases or second primary cancer. In this context, we also have raised an alarming advice that the cancer may be potentially infectious. Secondly, if a normal cf-DNA contains cytokine sequence, it may behave like an intrinsic DNA vaccine, producing therapeutic cytokine. If normal cf-DNA contains a sequence of a non-mutated oncogene or tumor suppressor gene, homologous recombination with the cancer genome may occur leading to knock out mutated oncogene or tumor suppressor gene that could thus elicit a spontaneous remission of cancer.

Animals↗

PubMed2005

The influence of environmental adaptation on bacterial genome structure.

AIMS: Researchers have long been puzzled by the diversity of life. Now that the complete genomic sequence of many organisms has been determined, it is possible to evaluate the impact of organismal variation on sequence structure or vice versa. The aim of this investigation was to explore genomic changes mandated by organismal adaptation to its ecological niches. METHODS AND RESULTS: Coding sequences from three phylogenetically related bacterial species namely Mycoplasma genitalium, M. pneumoniae and Ureaplasma urealyticum were subject to in depth sequence analyses. M. genitalium and M. pneumoniae both belong to the genus Mycoplasma while U. urealyticum is a member of the genus Ureaplasma. However, M. genitalium and U. urealyticum are urogenital pathogens while M. pneumoniae is a respiratory pathogen. Complete transcriptomes were downloaded from NCBI for each species, and were subject to in silico investigation using in-house software, and public sequence analysis tools. Clear similarities in transcriptome structure were identified among the functionally similar species M. genitalium and U. urealyticum while no such relationship was identified among the phylogenetically related species M. genitalium and M. pneumoniae. CONCLUSIONS: It is plausible to conclude that, in these bacterial species, environmental stimuli might be more influential in shaping sequence signatures than phylogenetic relationships. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that molecular signatures within the transcriptomes of the species examined are likely to be a product of evolutionary adaptation to diverse environmental ecological stimuli, and not a result of common phylogeny.

Adaptation, Biological↗

PubMed2005

Protein misfolding and misprocessing in complex disease.

Scientists from over 20 major research centers recently convened to discuss advances and new discoveries in "Protein MisFolding and MisProcessing in Disease." Understanding protein mechanisms the underlying etiology of complex diseases lies in analyzing the associated biochemical mechanisms, which include folding patterns, processing patterns, chaperone regulators, stress pathways, and signal transduction.

Animals↗

PubMed2004

Diagnostic microarray: an array of possibilities for parasitology.

Parasites affect a majority of the world's population. Despite this fact, dreams of developing vaccines remain far off. Scientists have long studied gene expression as a hallmark of gene activities reflecting current cell conditions. Analyzing differentially expressed genes is a major initiative, and most labs recoil at the amount of time and high costs required obtaining results. By employing microarrays, researchers can decrease their reliance upon time consuming techniques; consequently, microarray is beginning to dominate other molecular diagnostic technologies. Moreover, the ability of microarrays to monitor simultaneous gene expression of thousands of genes and to produce broad arrays of data has the potential to shift the resources of the scientists from data gathering to analyzing data that are already available. As microarray technology improves and its cost decreases, the role of ability to "see" the molecular biology pathways involved in parasite host relationships will place this technology at the forefront of parasite research.

Animals↗

PubMed2001

Ovarian epithelial carcinoma tyrosine phosphorylation, cell proliferation, and ezrin translocation are stimulated by interleukin 1alpha and epidermal growth factor.

BACKGROUND: Ezrin is a member of the ezrin, radixin, and moesin family. These proteins are membrane-actin cross-linking proteins. Furthermore, ezrin is an important signal transduction protein that undergoes phosphorylation and translocation on stimulation by growth factors. Ezrin phosphorylation and translocation are thought to be correlated with cell motility, invasion, and carcinoma metastasis. Recently, the authors reported that an ezrin antisense phosphorothionate could significantly inhibit endometrial carcinoma cells' penetration in the Matrigel membrane cancer invasion assay. In the current study, the authors measured ezrin content in clinical ovarian epithelial carcinoma (OVCA) specimens and cell lines and investigated whether interleukin (IL)-1alpha and epidermal growth factor (EGF) induce an invasive phenotype in OVCA cells via ezrin phosphorylation and translocation. METHODS: Twenty-five normal ovary, 25 primary OVCA, 21 metastatic OVCA tissue (7 in omentum, 16 in ascites), and 3 OVCA cell lines were collected for Western blot detection of ezrin content. The OVCA cell line SKOV3 was treated with IL-1alpha or EGF. Indirect immunofluorescence staining followed by confocal laser scanning and double-staining electron microscopic immunohistochemistry were used to investigate changes in the intracellular distribution of ezrin and cell morphology after IL-1alpha or EGF treatment. The content of ezrin was measured by Western blotting and analyzed by the National Institutes of Health Image computer program. Immunoprecipitation and Western blot techniques were used for ezrin phosphorylation studies. Genistein was used to block tyrosine phosphorylation. RESULTS: (1) Ezrin was overexpressed in OVCA, with the highest values in metastases. (2) Interleukin-1alpha and EGF significantly increased OVCA tyrosine phosphorylation, ezrin translocation, and cell growth. (3) These effects were abolished by treatment with the tyrosine kinase inhibitor, genistein. (4) Treatment with IL-1alpha or EGF induced an invasive phenotype, i.e., membrane ruffling, and process formation. CONCLUSIONS: High expression and activation of ezrin appear to be related to OVCA metastatic behavior. Interleukin-1alpha and EGF may regulate OVCA invasive behavior by activating ezrin tyrosine phosphorylation, translocation, and cancer cell proliferation. The authors' results may partially explain why OVCA patients with positive macrophage colony stimulating factor (a chemoattractant of IL-1alpha secreting monocytes) or EGF receptors (c-erb B-2) have a poor prognosis.

Blotting, Western↗

PubMed2001

Influence of intercodon and base frequencies on codon usage in filarial parasites.

Base frequency, codon usage, and intercodon identity were analyzed in five filarial parasite species representing five Onchocercidae genera. Wucheria bancrofti, Brugia malayi, Onchocerca volvulus, Acanthocheilonema viteae, and Dirofilaria immitis gene sequences were downloaded from NCBI, and analysis was performed using locally designed computer programs and other freely available applications. A clear sequence bias was observed among the nematode species examined. At the nucleotide level, AT basepairs were present in gene sequences at higher frequencies than GC. In addition, codons ending in A or T were used proportionately more than those with G or C in the third-codon position. In addition, the amino acids used most often corresponded to codons ending in AT basepairs. Intercodon base proportion was biased in that A was found most often at N4, second only to T in certain specific cases. Since all of these sequence biases were observed in a relatively consistent fashion among all of the organisms studied, we conclude that sequence bias is a genetic characteristic, which is associated with multiple filarial genera.

Animals↗

PubMed1999

Induction of apoptosis and suppression of clonogenicity of ovarian carcinoma cells with estrogen mustard.

BACKGROUND: This study was conducted to evaluate whether estramustine (estrogen mustard [EM]) is a promising alternative in the treatment of patients with epithelial ovarian carcinoma (OVCA). EM is a microtubule-associated protein (MAP) specific antimicrotubule agent with low toxicity. METHODS: The authors investigated the ability of EM to induce apoptosis and suppress colony formation of OVCA cells. Paclitaxel was used as a positive control. DNA electrophoresis and terminal deoxynucleotidyl dUTP-X nick end labeling (TUNEL) assays were used to detect internucleosomal DNA fragmentation. Flow cytometry was used to identify apoptotic cells and disturbance of the cell cycle of EM-treated OVCA cells further. Quantitation of detached cultured cells also provided a relative estimate of the apoptotic response of OVCA cells to treatment with EM. The colony formation assay was used to evaluate the effects of EM on clonogenicity. RESULTS: The effects of EM on four OVCA cell lines in culture were highly similar to those of paclitaxel in causing apoptosis and inhibiting clonogenicity. DNA electrophoresis and TUNEL assays showed that EM induced internucleosomal DNA fragmentation in OVCA cells. Flow cytometry showed changes typical of apoptotic changes and cell cycle block and synchronization at the G2/M-phase. Counting of detached cells showed a log-dose response to EM treatment. The colony formation assay also showed a log-dose response suppression of OVCA cell clonogenicity after treatment with EM. CONCLUSIONS: EM may be a promising candidate in the clinical treatment of patients with OVCA. The lower toxicity and MAP specific action of EM is a novel chemotherapy for OVCA.

Antineoplastic Agents, Alkylating↗