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Preclinical-to-clinical Anti-cancer Drug Response Prediction and Biomarker Identification Using TINDL

Genomics, Proteomics & Bioinformatics 2023年第3期21卷 535-550页

作者： David Earl Hostallero Lixuan Wei Liewei Wang Junmei Cairns amin emad Department of Electrical and Computer Engineering McGill UniversityMontrealQC H3A 0E9Canada Mila–Quebec Artificial Intelligence Institute MontrealQC H2S 3H1Canada Department of Molecular Pharmacology and Experimental Therapeutics Mayo ClinicRochesterMN 55905USA The Rosalind and Morris Goodman Cancer Institute McGill UniversityMontrealQC H3A 1A3Canada

Prediction of the response of cancer patients to different treatments and identification of biomarkers of drug response are two major goals of individualized ***,we developed a deep learning framework called TINDL,completely trained on preclinical cancer cell lines(CCLs),to predict the response of cancer patients to different *** utilizes a tissue-informed normalization to account for the tissue type and cancer type of the tumors and to reduce the statistical discrepancies between CCLs and patient ***,by making the deep learning black box interpretable,this model identifies a small set of genes whose expression levels are predictive of drug response in the trained model,enabling identification of biomarkers of drug *** data from two large databases of CCLs and cancer tumors,we showed that this model can distinguish between sensitive and resistant tumors for 10(out of 14)drugs,outperforming various other machine learning *** addition,our small interfering RNA(siRNA)knockdown experiments on 10 genes identified by this model for one of the drugs(tamoxifen)confirmed that tamoxifen sensitivity is substantially influenced by all of these genes in MCF7 cells,and seven of these genes in T47D ***,genes implicated for multiple drugs pointed to shared mechanism of action among drugs and suggested several important signaling *** summary,this study provides a powerful deep learning framework for prediction of drug response and identification of biomarkers of drug response in *** code can be accessed at https://***/ddhostallero/tindl.

关键词： Drug response Deep learning Explainable AI Cancer Gene knockdown experiment

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Brand versus Generic Rosuvastatin in Egyptian Patients with Hyperlipidemia;Cost-Minimization Analysis

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International Journal of Clinical Medicine 2019年第12期10卷 631-638页

作者： Sameh Shaheen Ahmed S. H. Elserafy Mohamed amin Ramy Hassan emad R. Issak Cardiology Department Ain Shams University Cairo Egypt AstraZeneca Cairo Egypt ClinAmygate Cairo Egypt

Background: Serum level of cholesterol is one of the most vital risk factors for cardiovascular diseases (CVD). Statins are highly effective drugs for reducing serum cholesterol;hence, preventing coronary heart disease (CHD). Rosuvastatin (Crestor) is one of the most potent and widely prescribed statins. Even though generic statins have been approved based on their bioequivalence with brand-name drugs, there remains considerable concern as regards their effectiveness and safety. Most clinicians and patients welcome the generic drug decreased costs;however, it is indispensable for them that effectiveness and safety are not compromised. Thus, the rationale intended for this study is to compare brand rosuvastatin and generic rosuvastatin as regard their economic impact using a cost-minimization analysis. Methods: This cost-minimization model estimates potential impact of rosuvastatin brand versus generic on the healthcare resource utilization for one-year frame from the payer perspective. The model conforms to real practice of management of hyperlipidemia in Egypt and was validated by experts. Results: The drug costs in the rosuvastatin brand group were 3,155,250 EGP while in the generic group were 2,299,030 EGP. The costs of CVD events in the rosuvastatin brand group were 5,863,558 EGP, while in the generic group were 6,810,180 EGP. The total costs in the rosuvastatin brand group were 9,018,808 EGP, while in the generic group were 9,109,210 EGP with a difference of −100,047 EGP. Conclusions: In conclusion, the real cost of generic treatment is more than that of the brand statin when taking into consideration the cardiovascular events.

关键词： Rosuvastatin Generics Cardiovascular Events Cost-Minimization

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Impacts of mesenchymal stem cells and hyaluronic acid on inflammatory indicators and antioxidant defense in experimental ankle osteoarthritis

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World Journal of Orthopedics 2024年第11期15卷 1056-1074页

作者： Usama Ismaeil Hagag Fatma Mohamed Halfaya Hessah Mohammed Al-Muzafar Suhailah Saud Al-Jameel Kamal Adel amin Wael Abou El-Kheir emad A Mahdi Gamal Abdel-Nasser Ragab Hassan Osama Mohamed Ahmed Department of Surgery Beni-Suef UniversityBeni Suef 62111Egypt Department of Surgery Anesthesiology and RadiologyBeni-Suef UniversityBeni Suef 62111Egypt Department of Chemistry College of ScienceBasic and Applied Scientific Research CenterImam Abdulrahman Bin Faisal UniversityDammam 31441Saudi Arabia Department of Chemistry BiochemistryCollege of ScienceBasic and Applied Scientific Research Center(BASRC)Imam Abdulrahman Bin Faisal UniversityDammam 31441Saudi Arabia Department of Immunology Military Medical AcademyCairo 11511Al QāhirahEgypt Department of Pathology Beni-Suef UniversityBeni Suef 62111Egypt Department of Surgery Anesthesiology and RadiologyFaculty of Veterinary MedicineBeni-Suef UniversityBeni Suef 62521Egypt

BACKGROUND No effective treatment guarantees full recovery from osteoarthritis(OA),and few therapies have *** To determine if bone marrow mesenchymal stem cells(BMMSCs)and hyaluronic acid(HA)treat ankle OA in Wistar *** BMMSCs were characterized using flow cytometry with detection of surface markers[cluster of differentiation 90(CD90),CD105,CD34,and CD45].Fifty male Wistar rats were divided into five groups of 10 rats each:Group I,saline into the right tibiotarsal joint for 2 days;Group II,monosodium iodate(MIA)into the same joint;Groups III,MIA+BMMSCs;Group IV,MIA+HA;and Group V,MIA+BMMSCs+***(1×106 cells/rat),HA(75μg/rat),and BMMSCs(1×106 cells/rat)alongside HA(75μg/rat)were injected intra-articularly into the tibiotarsal joint of the right hind leg at the end of weeks 2,3,and 4 after the MIA *** The elevated right hind leg circumference values in the paw and arthritis clinical score of osteoarthritic rats were significantly ameliorated at weeks 4,5,and *** peroxide significantly increased in the serum of osteoarthritic rats,whereas reduced serum glutathione and glutathione transferase levels were *** and HA significantly improved *** significantly elevated ankle matrix metalloproteinase 13(MMP-13)mRNA and transforming growth factor beta 1(TGF-β1)protein expression,and tumor necrosis factor alpha(TNF-α)and interleukin-17(IL-17)serum levels in osteoarthritic rats were significantly downregulated by BMMSCs and *** effects of BMMSCs and HA on serum TNF-αand IL-17 were more potent than their *** lowered serum IL-4 levels in osteoarthritic rats were significantly upregulated by BMMSCs and ***,BMMSCs and HA caused a steady decrease in joint injury and cartilage *** BMMSCs and/or HA have anti-arthritic effects mediated by antioxidant and anti-inflammatory effects on MIAinduced ***-13 and TGF-β1 expression improves BMMSCs and/or HA effects on OA in Wistar rats.

关键词： Osteoarthritis Anti-inflammatory Antioxidant Bone marrow mesenchymal stem cells Hyaluronic acid

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Optimization of Liver Iron Load Assessment by Pixel-Based T2* MRI in Thalassemic Patients

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Open Journal of Radiology 2012年第2期2卷 46-51页

作者： Neda Gholizadeh Shahram Akhlaghpoor Hamid Soltanian-Zadeh emad Fatemizadeh Mohammad Reza Alinaghizadeh amin Shams Akhtari Mohammad Nourizadeh Cardivascular Disease Research Center Ahvaz Joundishapour University Ahvaz Iran Control and Intelligent Processing Center of Excellence (CIPCE) School of Electrical Engineering College of Engineering University of Tehran Tehran Iran Department of CT & MRI Imaging Tehran Medical Imaging Center Tehran Iran Department of Magnetic Resonance Imaging Noor Medical Imaging Center Tehran Iran Department of Nuclear Engineering Science and Research Branch of Azad University Tehran Iran School of Electrical Engineering Sharif University of Technology Tehran Iran

Purpose: To improve liver iron load assessment by investigating the precision of different approaches of T2* Measurement. Background: Iron overload is a major problem in the treatment of thalassemic patients. Liver iron concentration (LIC) is an important index toward the management of body iron load. The accuracy of iron load estimation may suffer from the methodology of T2* measurement and there is no complete agreement upon the best approach of T2* calculation. Methods: 32 β-thallasemic patients (18 male) with the mean age of 20.0 ± 6.5 years were involved in this study. A multi-echo fast gradient-echo technique on a 1.5 T MRI system was used to measure liver iron overload and the T2* map of liver was reconstructed on a pixel-by-pixel basis. The T2* map and MRI images were utilized to deter- mine accurate location of ROI (region of interest). The mean of T2* were computed from the ROIs. The reproducibility of calculated T2* values in two methods were obtained. Moreover, the mean of the pixel’s T2* was calculated in the entire liver parenchyma of one slice. The T2* value of the entire slice was compared with the ROI approach. Results: In the ROI based method, the CoV for the intra-observer reproducibility was 8.5% and for the inter-observer was 9.78%. In the pixel based method, the CoVs for intra-observer and inter-observer reproducibility were 2.79% and 3.91%. There was an acceptable correlation (r = 0.96) between the T2* values calculated by the ROI and the entire slice. Conclusions: The pixel-based approach is more precise to determine the appropriate placement of the ROI. The assessment of T2* in the entire slice reduces the user-based errors significantly.

关键词： Thalassemia Liver Iron Overload MRI T2*

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