ORCID Profile
0000-0002-8425-4010
Current Organisations
University of Jordan
,
Qatar Genome
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Publisher: American Society for Cell Biology (ASCB)
Date: 02-2005
Abstract: Senescence, the molecular program that limits the finite proliferative potential of a cell, acts as an important barrier to protect the body from cancer. Techniques for measuring transcriptome changes and for modulating their expression suggest that it may be possible to dissect the transcriptional networks underlying complex cellular processes. HMF3A cells are conditionally immortalized human mammary fibroblasts that can be induced to undergo coordinated senescence. Here, we used these cells in conjunction with microarrays, RNA interference, and in silico promoter analysis to promote the dissection of the transcriptional networks responsible for regulating cellular senescence. We first identified changes in the transcriptome when HMF3A cells undergo senescence and then compared them with those observed upon replicative senescence in primary human mammary fibroblasts. In addition to DUSP1 and known p53 and E2F targets, a number of genes such as PHLDA1, NR4A3, and a novel splice variant of STAC were implicated in senescence. Their role in senescence was then analyzed by RNA silencing followed by microarray analysis. In silico promoter analysis of all differential genes predicted that nuclear factor-κB and C/EBP transcription factors are activated upon senescence, and we confirmed this by electrophoretic mobility shift assay. The results suggest a putative signaling network for cellular senescence.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0RA07325C
Abstract: A new combination strategy of an active loading and active targeting approach was applied in this work.
Publisher: Springer Science and Business Media LLC
Date: 29-07-2008
Publisher: Informa UK Limited
Date: 08-10-2012
DOI: 10.3109/10717544.2012.727500
Abstract: Thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone) is a herbal-derived drug with potential chemopreventive and chemotherapeutic activity. However, thymoquinone suffers from high hydrophobicity causing poor solubility which limits its bioavailability and high lipophilicity causing poor formulation characteristics. Liposomes are versatile drug carriers that can be used to solve problems of drug solubility, instability, and bio-distribution. In this study, we were able to prepare thymoquinone-loaded liposomes (TQ-LP) and thymoquinone loaded in liposomes modified with Triton X-100 (XLP) with diameters of about 100 nm, and entrapment efficiency of more than 90% for TQ-LP and of 49.6% for XLP. The TQ-LP liposomes were effective in suppressing the proliferation of breast cancer cell lines MCF-7 and T47D, and at the same time exerting very low toxicity on normal periodontal ligament fibroblast. Altogether, this report describes the first successful encapsulation of thymoquinone into liposome which maintains stability, improves bioavailability and maintains its anticancer activity.
Publisher: Elsevier BV
Date: 08-2020
Publisher: SAGE Publications
Date: 21-10-2012
Abstract: Epstein–Barr virus (EBV) is a human virus with oncogenic potentials that is implicated in various human diseases and malignancies. In this study, the modulator activity of the potent herbal extract drug thymoquinone on EBV was assessed in vitro. Thymoquinone was tested for cytotoxicity on human cells of lymphoblastoid cells, Raji Burkitt’s lymphoma, DG-75 Burkitt’s lymphoma, peripheral blood mononuclear cells, and periodontal ligament fibroblast. Apoptosis induction was analyzed via TUNEL assay and activity studies of caspase-3. The effect of thymoquinone on EBV gene expression was determined using real-time polymerase chain reaction. We report here, for the first time, a promising selective inhibitory affect of thymoquinone on EBV-infected B cell lines in vitro, compared with lower activity on EBV negative B cell line and very low toxicity on human peripheral blood mononuclear cells and periodontal ligament fibroblasts. Moreover, the drug was found to efficiently suppress the RNA expression of EBNA2, LMP1, and EBNA1 genes. Specifically, EBNA2 expression levels were the most affected indicating that this gene might have a major contribution to thymoquinone potency against EBV infected cells. Overall, our results suggest that thymoquinone has the potential to suppress the growth of EBV-infected B cells efficiently.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.LEUKRES.2009.11.018
Abstract: The phosphatidylinositol-3-kinases PI3K/AKT pathway regulates many growth and survival mechanisms in the cell, and it has been implicated in development and progression of many human cancers, including multiple myeloma. Recently, many reports have revealed that the PIK3CA gene which encodes the p110 catalytic subunit of PI3K kinase is mutated in many human malignancies. To investigate the oncogenic role of PI3K/AKT pathway in multiple myeloma we sequenced three hot exons: exons 9 and 20 of PIK3CA gene and exon 3 of AKT1 gene in 27 multiple myeloma patients. Our results indicate the absence of the four hot spot mutations E542K, E545K, H1047R and E17K in all studied cases. These findings suggest that PI3K/AKT mutations may not play a major role in multiple myeloma.
Publisher: Springer Science and Business Media LLC
Date: 28-07-2009
DOI: 10.1007/S12041-009-0032-Z
Abstract: Five patients, four brothers and their paternal aunt, presented with a history of overt hyperthyroidism and goiter. Hyperthyroidism in this family was remarkable for its poor response to carbimazole (30-50 mg/d). The thyroid ultrasound showed a diffusely enlarged gland in all the affected members, and thyroid stimulating antibodies (TSAB) were negative. Screening for germline mutations in thyroid stimulating hormone (TSH) receptor (TSHR) gene was performed by direct sequencing of genomic DNA extracted from peripheral blood leukocytes of all family members. The sequence analysis of all TSHR gene exons and intron borders revealed two genomic variants. The first was a single nucleotide polymorphism (SNP) within exon seven (Asn187Asn), whereas the other was located in intron seven (IVS7+68TG). All affected members, two asymptomatic brothers with sub-clinical hyperthyroidism, and their father were heterozygous for those two genomic variants. Anti-thyroid drug treatment for several months successfully relieved symptoms in one subject, whereas the remaining patients required total thyroidectomy to control their disease. This is the first Jordanian family with familial non-autoimmune hyperthyroidism, with mutations affecting the TSHR gene.
Publisher: Elsevier BV
Date: 11-2019
Publisher: MDPI AG
Date: 18-12-2019
DOI: 10.3390/MOLECULES25010003
Abstract: Soon after they were first described in 1990, aptamers were largely recognized as a new class of biological ligands that can rival antibodies in various analytical, diagnostic, and therapeutic applications. Aptamers are short single-stranded RNA or DNA oligonucleotides capable of folding into complex 3D structures, enabling them to bind to a large variety of targets ranging from small ions to an entire organism. Their high binding specificity and affinity make them comparable to antibodies, but they are superior regarding a longer shelf life, simple production and chemical modification, in addition to low toxicity and immunogenicity. In the past three decades, aptamers have been used in a plethora of therapeutics and drug delivery systems that involve innovative delivery mechanisms and carrying various types of drug cargos. However, the successful translation of aptamer research from bench to bedside has been challenged by several limitations that slow down the realization of promising aptamer applications as therapeutics at the clinical level. The main limitations include the susceptibility to degradation by nucleases, fast renal clearance, low thermal stability, and the limited functional group ersity. The solution to overcome such limitations lies in the chemistry of aptamers. The current review will focus on the recent arts of aptamer chemistry that have been evolved to refine the pharmacological properties of aptamers. Moreover, this review will analyze the advantages and disadvantages of such chemical modifications and how they impact the pharmacological properties of aptamers. Finally, this review will summarize the conjugation strategies of aptamers to nanocarriers for developing targeted drug delivery systems.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.CANEP.2010.10.006
Abstract: The association between Human Herpes Virus-8 (HHV-8), also called Kaposi's sarcoma associated herpesvirus (KSHV), and the pathogenesis of multiple myeloma remains controversial. Many past studies conducting on different populations have come to contradicting conclusions. In this study, we attempted to investigate the presence of HHV-8 in Jordanian multiple myeloma patients. We carried out nucleic acid lification reactions targeting specific viral DNA sequences on 35 fresh bone marrow aspirate s les from 17 patients with multiple myeloma, 9 patients with various hematological malignancies and 9 normal subjects. HHV-8 specific sequences were detected in 7 out of 17 multiple myeloma patients (41%) using primers specific for the open reading frame region 26 (ORF26). All patients with other hematological malignancies as well as the normal subjects did not harbour the virus. These findings support the previous reports of frequent detection of HHV-8 in bone marrow of multiple myeloma patients.
Location: United Kingdom of Great Britain and Northern Ireland
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