Identification of the possible therapeutic targets in the insulin-like growth factor 1 receptor pathway in a cohort of Egyptian hepatocellular carcinoma complicating chronic hepatitis C type 4.

BACKGROUND: Molecular targeted drugs are the first line of treatment of advanced hepatocellular carcinoma (HCC) due to its chemo- and radioresistant nature. HCC has several well-documented etiologic factors that drive hepatocarcinogenesis through different molecular pathways. Currently, hepatitis C virus (HCV) is a leading cause of HCC. Therefore, we included a unified cohort of HCV genotype 4-related HCCs to study the expression levels of genes involved in the insulin-like growth factor 1 receptor (IGF1R) pathway, which is known to be involved in all aspects of cancer growth and progression. AIM: Determine the gene expression patterns of IGF1R pathway genes in a cohort of Egyptian HCV-related HCCs. Correlate them with different patient/tumor characteristics. Determine the activity status of involved pathways. METHODS: Total ribonucleic acid (RNA) was extracted from 32 formalin-fixed paraffin-embedded tissues of human HCV-related HCCs and 6 healthy liver donors as controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RT2 Profiler PCR Array for Human Insulin Signaling Pathway was done to determine significantly up- and downregulated genes with identification of most frequently coregulated genes, followed by correlation of gene expression with different patient/tumor characteristics. Finally, canonical pathway analysis was performed using the Ingenuity Pathway Analysis software. RESULTS: Six genes - AEBP1, AKT2, C-FOS, PIK3R1, PRKCI, SHC1 - were significantly overexpressed. Thirteen genes - ADRB3, CEBPA, DUSP14, ERCC1, FRS3, IGF2, INS, IRS1, JUN, MTOR, PIK3R2, PPP1CA, RPS6KA1 - were significantly underexpressed. Several differentially expressed genes were related to different tumor/patient characteristics. Nitric oxide and reactive oxygen species production pathway was significantly activated in the present cohort, while the growth hormone signaling pathway was inactive. CONCLUSIONS: The gene expression patterns identified in this study may serve as possible therapeutic targets in HCV-related HCCs. The most frequently coregulated genes may serve to guide combined molecular targeted therapies. The IGF1R pathway showed evidence of inactivity in the present cohort of HCV-related HCCs, so targeting this pathway in therapy may not be effective.

MicroRNA155 Expression in Different Phenotypes and Genotypes of Behçet's Disease in a Sample of Egyptian Patients.

AIM: To display microRNA155 (miRNA155) expression in different entities of Behçet's disease (BD), and to find out if expression is affected in more than one of disease status than another, either phenotypically, according to HLA B51 expression, presence of family history, or patients' age. METHODS: Thirty BD patients (13 of which were HLAB51 positive) and 15 healthy subjects' samples were obtained. White blood cell miRNA155 expression in both types of samples was estimated. RESULTS: Results showed that there is a degree of relation between decrease of miRNA155 expression and different disease aspects, and also, that miRNA155 has an inverse relation with the patients' ages. CONCLUSION: MiRNA155 might be used as a measure of disease of different phenotypes, and that any manifestation of the disease can happen when the expression level decreases.

MicroRNA155 Expression in Relation to BDCAF Scored Behçet's Disease in an Egyptian Patients' Sample.

OBJECTIVE: To discover the possibility of using microRNA155 (miRNA155) expression level as a biomarker of Behçet's Disease (BD) activity or remission. METHODS: Thirty BD patients' white blood cells (WBCs) miRNA155 expression was measured and compared to WBCs miRNA155 expression in 15 healthy subjects. Assessment of disease activity was done using Behçet's Disease Current Activity Form (BDCAF). RESULTS: miRNA155 expression significantly decreases with the increase of BD activity scored by BDCAF. CONCLUSION: Increased miRNA155 may be used as a biomarker of BD remission and thus in the disease follow up. There could be a prospect of treating the disease via microRNA 155 effect enhancement.

Associating functional groups to multiple clinical types using combined t-test scores and contingency-based measures: a study on breast cancer genes.

Stemming from the need to score relations between functional groups of genes and multiple clinical types associated with a tumour, this study proposes to use contingency-based measures to quantify such relations. It aims at reflecting a relative measure of association within a specific set of functional groups, and a specific set of clinical statuses. The proposed methodology is based on extracting features (scores) from expression sets that relate genes to multiple cancer subtypes (clinical statuses), and use those features (scores) to associate cancer subtypes with functional groups. It proposes combining t-test scores at several levels of cancer statuses' differentiation to calculate such gene features. It also proposes using contingency based measures as Jaccard and F-measure to associate gene functional groups to multiple cancer subtypes/statuses. Variations from the original Jaccard measure are proposed to reflect scores of genes' relations to classes/groups rather than using binary relations. The core objective of the experimental study is to identify the functional categories of genes that mark the change in lymph node status under each of oestrogen receptor positive and negative statuses in breast cancer expression sets.

Telomerase activity in Philadelphia positive chronic myeloid leukaemia.

Telomerase is a specialized type of reverse transcriptase that catalyzes the synthesis and extension of telomeric DNA. Activation of telomerase and stabilization of telomeres are considered necessary for immortalization of tumor cells. Chronic Myeloid Leukaemia (CML) is a good example to investigate the reactivation of telomerase as; after a variable period in chronic phase, CML undergoes further evolution. The aim of this work is to study telomerase activity in patients with philadelphia- positive CML and to compare the relative amount of telomerase activity between chronic phase, accelerated phase and blastic crisis. The study is conducted on 3 groups. Group I comprised ten newly diagnosed CML patients in chronic phase; five males and five females their ages ranged from 24-63 years (X = 44.1 +/- 11.2 years). Group II comprised ten patients in acute transformation (accelerated or blastic crisis phase); seven were males and three were females their ages ranged from 14 to 63 years ( X = 35.7 +/- 16.2 years). Ten healthy subjects comprised the control group III; five males and five females their ages ranged from 14-50 years ( X = 31.8 +/- 12.4 years). All patients were subjected to thorough history taking and clinical examination, complete blood picture with differential cell counts, bone marrow aspiration and/or biopsy, neutrophil alkaline phosphatase scoring by cytochemistry, immunophenotyping to identify the type of blast crisis, chromosomal analysis to detect Ph-positive cases, and measurement of telomerase activity by PCR-ELISA technique. Telomerase activity was highest in acute transformation with a range of (0.252-1.896) and mean of 1.521 0.496, while in chronic phase ranged between 0.67 and 0.743 with a mean of 0.305 +/- 0.109 and in normal controls the range was 0.45 to 0.195 with a mean of 0.102 +/- 0.048. The difference between groups was statistically significant. No correlation was found between the activity of the telomerase and hemoglobin, platelet, leucocyte counts, percentage of peripheral blood, bone marrow blasts, basophils, bone marrow cellularity, the type of crisis as well as leucocyte alkaline phosphatase scoring. In conclusion; The increased level of telomerase activity as noticed in the different stages of CML indicates its association with disease progression and can be used as a useful marker for evaluating development of the course.