Publications by authors named "H Ragab"

59 Publications

An international survey of imaging practices in radiotherapy.

Phys Med 2021 Sep 22;90:53-65. Epub 2021 Sep 22.

The National Center for Applied Physics, King Abdulaziz City for Science and Technology (KACST), P.O. Box: 6086, Riyadh, Saudi Arabia; Mentorship programme, International Commission on Radiological Protection, 280 Slater Street, Ottawa, Ontario K1P 5S9, Canada.

Improvements in delivery of radiation dose to target tissues in radiotherapy have increased the need for better image quality and led to a higher frequency of imaging patients. Imaging for treatment planning extends to function and motion assessment and devices are incorporated into medical linear accelerators (linacs) so that regions of tissue can be imaged at time of treatment delivery to ensure dose distributions are delivered as accurately as possible. A survey of imaging in 97 radiotherapy centres in nine countries on six continents has been undertaken with an on-line questionnaire administered through the International Commission on Radiological Protection mentorship programme to provide a snapshot of imaging practices. Responses show that all centres use CT for planning treatments and many utilise additional information from magnetic resonance imaging and positron emission tomography scans. Most centres have kV cone beam CT attached to at least some linacs and use this for the majority of treatment fractions. The imaging options available declined with the human development index (HDI) of the country, and the frequency of imaging during treatment depended more on country than treatment site with countries having lower HDIs imaging less frequently. The country with the lowest HDI had few kV imaging facilities and relied on MV planar imaging intermittently during treatment. Imaging protocols supplied by vendors are used in most centres and under half adapt exposure conditions to individual patients. Recording of patient doses, a knowledge of which is important in optimisation of imaging protocols, was limited primarily to European countries.
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http://dx.doi.org/10.1016/j.ejmp.2021.09.004DOI Listing
September 2021

Halting colorectal cancer metastasis via novel dual nanomolar MMP-9/MAO-A quinoxaline-based inhibitors; design, synthesis, and evaluation.

Eur J Med Chem 2021 Oct 29;222:113558. Epub 2021 May 29.

Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426, Alexandria, 21321, Egypt; Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia. Electronic address:

Matrix metalloproteinase-9 (MMP-9) and monoamine oxidase-A (MAO-A) are central signaling nodes in CRC and promotors of distant metastasis associated with high mortality rates. Novel series of quinoxaline-based dual MMP-9/MAO-A inhibitors were synthesized to suppress CRC progression. The design rationale combines the thematic pharmacophoric features of MMP-9 and MAO-A inhibitors in hybrid scaffolds. All derivatives were initially screened via MTT assay for cytotoxic effects on normal colonocytes to assess their safety profiles, then evaluated for their anticancer potential on HCT116 cells overexpressing MMP-9 and MAO-A. The most promising derivatives 8, 16, 17, 19, and 28 exhibited single digit nanomolar IC against HCT116 cells within their safe doses (EC) on normal colonocytes. They suppressed HCT116 cell migration by 73.32, 61.29, 21.27, 28.82, and 27.48%, respectively as detected by wound healing assay. Enzymatic assays revealed that the selected derivatives were superior to the reference MMP-9 and MAO-A inhibitors (quercetin and clorgyline, respectively). The nanomolar dual MMP-9/MAO-A inhibitor 19 was identified as the most potent and balanced dual inhibitor among the evaluated series with considerable selectivity against MAO-A over MAO-B. Besides, qRT-PCR analysis was conducted to explore the hit compounds' potential to downregulate hypoxia-inducing factor (HIF-1α) in HCT116 cells being correlated with MAO-A mediated CRC migration and invasion. The five above-mentioned compounds significantly downregulated HIF-1α by more than 5 folds. Docking simulations predicted their possible binding modes with MMP-9 and MAO-A and highlighted their essential structural features. Finally, they recorded drug-like in silico physicochemical parameters and ADMET profiles.
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http://dx.doi.org/10.1016/j.ejmech.2021.113558DOI Listing
October 2021

Transforming iodoquinol into broad spectrum anti-tumor leads: Repurposing to modulate redox homeostasis.

Bioorg Chem 2021 08 31;113:105035. Epub 2021 May 31.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt. Electronic address:

We managed to repurpose the old drug iodoquinol to a series of novel anticancer 7-iodo-quinoline-5,8-diones. Twelve compounds were identified as inhibitors of moderate to high potency on an inhouse MCF-7 cell line, of which 2 compounds (5 and 6) were capable of reducing NAD level in MCF-7 cells in concentrations equivalent to half of their ICs, potentially due to NAD(P)H quinone oxidoreductase (NQO1) inhibition. The same 2 compounds (5 and 6) were capable of reducing p53 expression and increasing reactive oxygen species levels, which further supports the NQO-1 inhibitory activity. Furthermore, 4 compounds (compounds 5-7 and 10) were qualified by the Development Therapeutic Program (DTP) division of the National Cancer Institute (NCI) for full panel five-dose in vitro assay to determine their GI on the 60 cell lines. All five compounds showed broad spectrum sub-micromolar to single digit micromolar GI against a wide range of cell lines. Cell cycle analysis and dual staining assays with annexin V-FITC/propidium iodide on MCF-7 cells confirmed the capability of the most active compound (compound 5) to induce cell cycle arrest at Pre-G1 and G2/M phases as well as apoptosis. Both cell cycle arrest and apoptosis were affirmed at the molecular level by the ability of compound 5 to enhance the expression levels of caspase-3 and Bax together with suppressing that of CDK1 and Bcl-2. Additionally, an anti-angiogenic effect was evident with compound 5 as supported by the decreased expression of VEGF. Interesting binding modes within NQO-1 active site had been identified and confirmed by both molecular docking and dymanic experiments.
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http://dx.doi.org/10.1016/j.bioorg.2021.105035DOI Listing
August 2021

Design, Synthesis, and Anticancer Screening for Repurposed Pyrazolo[3,4-d]pyrimidine Derivatives on Four Mammalian Cancer Cell Lines.

Molecules 2021 May 16;26(10). Epub 2021 May 16.

Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21500, Egypt.

The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two ( and ) of the three synthesized compounds (, , and ) showed high cytotoxic activity against all tested cell lines with IC values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug . The overall results indicate that these pyrazolopyrimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.
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http://dx.doi.org/10.3390/molecules26102961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156061PMC
May 2021

Making every death count: institutional mortality accuracy at Ola During Children's Hospital, Sierra Leone.

Pan Afr Med J 2020 18;37:356. Epub 2020 Dec 18.

Medical Superintendence, Ola During Children's Hospital, Freetown, Sierra Leone.

Introduction: health care data accuracy feeds the development of sound healthcare policy and the prioritisation of interventions in scarce resource environments. We designed a retrospective study at the sole paediatric government hospital in Sierra Leone to examine mortality statistics, specifically: the accuracy of mortality data collected in 2017; and the quality of cause of death (CoD) reporting for 2017.

Methods: the retrospective audit included all available mortality statistics collected at the hospital during the 2017 calendar year. For the purpose of calculating a mortality rate, admission data was additionally gathered. Four different hospital entities were identified that collected mortality data (the Monitoring and Evaluation (M&E) office; the nurse ledgers; the office of births and deaths; and the mortuary). Data from each hospital entity were used for the comparative analysis.

Results: striking differences were found in the rate of hospital mortality reported by different entities. The M&E office (responsible for providing data to the ministry of health and sanitation) reported a hospital mortality rate of 2.94% in 2017. Mortuary and nursing admissions records showed a hospital mortality rate of 18.7%. Discrepancies and issues of quality in CoD reporting between hospital entities were identified.

Conclusion: significant variations were found in the generation of official hospital mortality data. Mortality data informs health service prioritisation, resource distribution, outcome measures and epidemiological surveillance. Resources to support quality improvement initiatives are needed in the creation of an in-hospital system that reports accurate data with a process for real-time institutional data feedback.
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http://dx.doi.org/10.11604/pamj.2020.37.356.23607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992407PMC
April 2021
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