539 results on '"Abdul-Sater A"'
Search Results
2. Bibliometric analysis of focal therapy in prostate cancer research
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Mohammed Shahait, Sarah Ibrahim, Laith Baqain, and Zahi Abdul‐Sater
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bibliometric ,focal therapy ,prostate cancer ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Introduction The use of focal therapies for prostate cancer (PCa) has soared, as it controls disease and is associated with minimal side effects. Bibliometric analysis examines the global research landscape on any topic to identify gaps in the research and areas for improvement and prioritize future research efforts. This study aims to examine the research outputs and trends and collaboration landscape in the field of focal therapy for PCa on a global scale. Methods We searched Medline, PubMed and Scopus for peer‐reviewed publications on our research topic using controlled keywords. Search results were limited to the period between 1980 and 2022, screened for duplicates and then included in our study based on prespecified eligibility criteria. The Bibliometrix Package was used for comprehensive science mapping analysis of co‐authorship, co‐citation and co‐occurrence analysis of countries, institutions, authors, references and keywords in this field. Results This analysis included 2578 research articles. The annual scientific production increased from one article in 1982 to 143 in 2022 (13.21%). The average citation per year was incrementally increasing, and these documents were cited around 32.52 times. The documents included in this analysis were published in 633 sources. The international collaboration index was 22.7. In total, 6280 author keywords were identified. The most used keywords were ‘prostate cancer’, ‘focal therapy’, ‘prostate’ and ‘photodynamic therapy’. Conclusion This bibliometric analysis has provided a comprehensive review of focal therapy in PCa research, highlighting both the significant growth in the field and the existing gaps that require further exploration. The study points to the need for more diverse international collaboration and exploration of various treatment modalities within the context of focal therapy.
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- 2024
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3. Development of a non-invasive bioassay for adiponectin target engagement in mice
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Jialing Tang, Yubin Lei, Angelica Pignalosa, Henry H. Hsu, Ali A. Abdul-Sater, and Gary Sweeney
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Human metabolism ,Genetics ,Cell biology ,Science - Abstract
Summary: Adiponectin-based therapeutic strategies are promising for managing metabolic diseases and reducing inflammation, prompting the development of adiponectin receptor agonists. However, monitoring their pharmacodynamic actions in clinical applications is challenging. This study aimed to identify peripheral biomarkers to monitor adiponectin actions using ALY688, an adiponectin receptor agonist peptide. RNA sequencing analysis of whole blood identified a cluster of genes that were significantly increased in the ALY688-treated group compared to the control. This gene cluster was validated by qPCR and further confirmed in human peripheral blood mononuclear cells treated with ALY688 ex vivo. We also confirmed a functional outcome of ALY688 action in mice as our study also demonstrated the anti-inflammatory effect of ALY688 in a sublethal LPS mouse model. In summary, a newly identified gene cluster signature is suitable for assessing the pharmacodynamic action of adiponectin or its mimetics in blood samples.
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- 2024
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4. Establishing a High-Quality Pediatric Cardiac Surgery Program in Post-Conflict Regions: A Model for Limited Resource Countries
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Youssef, Tammam, Bitar, Fouad, Alogla, Hassanain, El Khoury, Maya, Moukhaiber, Jihan, Alamin, Farah, AlHareth, Bassam, Gabriel, Cristoveanu Catalin, Youssef, Rana, Abouzahr, Labib, Abdul Sater, Zahi, and Bitar, Fadi
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- 2024
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5. The integration of ortho-plastic limb salvage teams in the humanitarian response to violence-related open tibial fractures: evaluating outcomes in the Gaza Strip
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Theresa Farhat, Krystel Moussally, Hasan Nahouli, Shahd Abu Hamad, Khulood Abul Qaraya, Zahi Abdul-Sater, Walaa G. El Sheikh, Nadine Jawad, Khouloud Al Sedawi, Mohammed Obaid, Hafez AbuKhoussa, Innocent Nyaruhirira, Hani Tamim, Shehan Hettiaratchy, Anthony M. J. Bull, and Ghassan Abu-Sittah
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Limb salvage ,Open tibial fracture ,Lower extremity ,War ,Conflict ,Gunshot wounds ,Special situations and conditions ,RC952-1245 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Limb salvage by ortho-plastic teams is the standard protocol for treating open tibial fractures in high-income countries, but there’s limited research on this in conflict settings like the Gaza Strip. This study assessed the clinical impact of gunshot-related open tibial fractures, compared patient management by orthopedic and ortho-plastic teams, and identified the risk factors for bone non-union in this context. Methods A retrospective review of medical records was conducted on Gaza Strip patients with gunshot-induced-open tibial fractures from March 2018 to October 2020. Data included patient demographics, treatments, and outcomes, with at least one year of follow-up. Primary outcomes were union, non-union, infection, and amputation. Results The study included 244 injured individuals, predominantly young adult males (99.2%) with nearly half (48.9%) having Gustilo-Anderson type IIIB fractures and more than half (66.8%) with over 1 cm of bone loss. Most patients required surgery, including rotational flaps and bone grafts with a median of 3 admissions and 9 surgeries. Ortho-plastic teams managed more severe muscle and skin injuries, cases with bone loss > 1 cm, and performed less debridement compared to other groups, though these differences were not statistically significant. Non-union occurred in 53% of the cases, with the ortho-plastic team having the highest rate at 63.6%. Infection rates were high (92.5%), but no significant differences in bone or infection outcomes were observed among the different groups. Logistic regression analysis identified bone loss > 1 cm, vascular injury, and the use of a definitive fixator at the first application as predictors of non-union. Conclusions This study highlights the severity and complexity of such injuries, emphasizing their significant impact on patients and the healthcare system. Ortho-plastic teams appeared to play a crucial role in managing severe cases. However, further research is still needed to enhance our understanding of how to effectively manage these injuries.
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- 2024
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6. Impaired autophagy flux contributes to enhanced ischemia reperfusion injury in the diabetic heart
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Jialing Tang, Nanyoung Yoon, Keith Dadson, Hye Kyoung Sung, Yubin Lei, Thanh Q. Dang, Wing Yan Chung, Saher Ahmed, Ali A. Abdul-Sater, Jun Wu, Ren-Ke Li, James Jonkman, Trevor McKee, Justin Grant, Jeffrey D. Peterson, and Gary Sweeney
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Autophagy ,cardiac remodeling ,cathepsin ,diabetes ,fluorescence molecular tomography ,ischemia-reperfusion ,Cytology ,QH573-671 - Abstract
ABSTRACTMyocardial ischemia/reperfusion (I/R) injury is exacerbated in diabetic individuals and animal models. We tested whether autophagy is an important cellular determinant of cell death. First, we utilized a cellular model of hypoxia reoxygenation (H/R) in H9c2 cells cultured in low or high glucose (HG) and tested cell death using flow cytometry to detect Annexin-V and propidium iodide, imaging cell viability ReadyProbe and lactate dehydrogenase release. We observed that cell death induced by H/R was enhanced by HG. Kinetic analysis of caspase-3 activity using a fluorescence reporter probe, stable expression of the VC3AI biosensor and western blotting indicated that H/R induced activation of caspase-3 was enhanced by HG. Temporal autophagy flux analysis using DapRed and DalGreen probes indicated an initial increase in response to H/R that was reduced upon prolonged (24h) R. HG suppressed this induction of autophagy. This was verified using LC3 HiBiT reporter assay, tandem-fluorescent LC3, and western blotting. Lysosomal cathepsin activity was also elevated at 6h and suppressed at 24h R. Autophagy-deficient cells were generated via CRISPR-mediated knockout of atg7 and the effect of combined HG and H/R treatment on caspase activation and cell death was elevated in comparison with wild type cells. We then performed coronary artery ligation surgery to induce ischemia, followed by reperfusion, in wild-type or streptozotocin (STZ)-induced hyperglycemic mice. Non-invasive 3-dimensional imaging using fluorescence molecular tomography combined with computerized tomography was employed to monitor spatio-temporal activation of cardiac autophagy and apoptosis. Upon systemic injection of a near infra-red cathepsin activatable probe we found that hyperglycemic mice had lower activity in the infarct region after I/R versus wild type. In parallel, we observed a higher extent of I/R-induced apoptosis, detected with an annexin-V probe, in hyperglycemic mice. Collectively, these results revealed that impaired autophagic flux in the presence of high glucose levels exacerbates I/R injury.Abbreviation: satg7, autophagy-related 7; FMT, fluorescence molecular tomography; HG, high glucose; H/R, hypoxia/reoxygenation; I/R, ischemia/reperfusion; LC3, MAP1LC3; N, normoxia; NG, normal glucose; NIR, near-infrared; p62, SQSTM1; STZ, streptozotocin.
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- 2024
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7. Characteristics of injuries during the 2006 Lebanon conflict: a three-center retrospective study of survivors, 16 years after the conflict
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Theresa Farhat, Hasan Nahouli, Marwan Hajjar, Zahi Abdul-Sater, Elsa Kobeissi, Marilyne Menassa, Bachar F. Chaya, Ahmad Elamine, Walaa G. El Sheikh, Hani Tamim, Shehan Hettiaratchy, and Ghassan Abu-Sittah
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war ,armed conflict ,war injuries ,disability ,Lebanon ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundArmed conflict injury is a growing public health concern, particularly in regions like the Middle East and North Africa (MENA). The protracted conflicts and political unrest in this region have led to a substantial number of injuries. Despite this, there is still limited understanding of the specific injury patterns stemming from conflicts, such as the 2006 Lebanon conflict. This study aimed to assess the characteristics and burdens of injuries resulting from this conflict, which occurred 16 years prior to this research.MethodsThis retrospective study analyzed data of individuals affected by the 2006 Lebanon conflict, across three tertiary care centers. Demographics, injuries, complications, injury management, and hospitalization expenses were extracted from medical records and analyzed using SPSS version 29.0. Categorical variables were presented as counts and proportions, and continuous variables as mean ± standard deviation (SD). Hospital comparisons utilized chi-square or Fisher’s exact tests for categorical variables, and one-way ANOVAs for continuous variables. Analysis was conducted from September to November 2023.ResultsAcross three hospitals, 341 patients were studied, comprising 73.6% males and 26.4% females. Among them, a notable proportion (57.3% males and 34.1% females) fell within the 18–39 age range. Children and adolescents under 18 years accounted for 15.9% of males and 25.9% of females. Blast-related injuries predominated, with 24.5% resulting from direct damage caused by explosive parts and 33.3% from blast wave forces. Extremity trauma occurred in 49.0% of patients, and head/neck trauma in 24.9%. Common injuries, including penetrating, musculoskeletal, and traumatic brain injuries affected 34.9%, 31.1, and 10.0% of patients, respectively. Wound repair, fracture treatment, and debridement were the most performed procedures on 15.5, 13.5 and 9.7% of the patients, respectively. The total cost of care was USD 692,711, largely covered by the Ministry of Public Health (95.9%).ConclusionConflict-related injuries significantly contribute to the global burden of disease. Therefore, there is a pressing need to improve national guidelines to prioritize life-threatening cases and potential long-term disabilities. Furthermore, enhancing electronic registry systems to collect clinical data on injured patients is essential for conducting research and better understanding the needs of conflict casualties.
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- 2024
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8. Development of a non-invasive bioassay for adiponectin target engagement in mice
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Tang, Jialing, Lei, Yubin, Pignalosa, Angelica, Hsu, Henry H., Abdul-Sater, Ali A., and Sweeney, Gary
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- 2024
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9. A novel blood-based bioassay to monitor adiponectin signaling
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Lone, Abdul Hadee, Tang, Jialing, Pignalosa, Angelica, Hsu, Henry H., Abdul-Sater, Ali A., and Sweeney, Gary
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- 2024
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10. Ischemia‐induced cardiac dysfunction is exacerbated in adiponectin‐knockout mice due to impaired autophagy flux
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Hye Kyoung Sung, Jialing Tang, James Won Suk Jahng, Erfei Song, Yee Kwan Chan, Abdul Hadee Lone, Jeffrey Peterson, Ali Abdul‐Sater, and Gary Sweeney
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Therapeutics. Pharmacology ,RM1-950 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Strategies to enhance autophagy flux have been suggested to improve outcomes in cardiac ischemic models. We explored the role of adiponectin in mediating cardiac autophagy under ischemic conditions induced by permanent coronary artery ligation. We studied the molecular mechanisms underlying adiponectin's cardio‐protective effects in adiponectin knockout (Ad‐KO) compared with wild‐type (WT) mice subjected to ischemia by coronary artery ligation and H9c2 cardiomyocyte cell line exposed to hypoxia. Systemic infusion of a cathepsin‐B activatable near‐infrared probe as a biomarker for autophagy and detection via noninvasive three‐dimensional fluorescence molecular tomography combined with computerized tomography to quantitate temporal changes, indicated increased activity in the myocardium of WT mice after myocardial infarction which was attenuated in Ad‐KO. Seven days of ischemia increased myocardial adiponectin accumulation and elevated ULK1/AMPK phosphorylation and autophagy assessed by Western blotting for LC3 and p62, an outcome not observed in Ad‐KO mice. Cell death, assessed by TUNEL analysis and the ratio of Bcl‐2:Bax, plus cardiac dysfunction, measured using echocardiography with strain analysis, were exacerbated in Ad‐KO mice. Using cellular models, we observed that adiponectin stimulated autophagy flux in isolated primary adult cardiomyocytes and increased basal and hypoxia‐induced autophagy in H9c2 cells. Real‐time temporal analysis of caspase‐3/7 activation and caspase‐3 Western blot indicated that adiponectin suppressed activation by hypoxia. Hypoxia‐induced mitochondrial reactive oxygen species production and cell death were also attenuated by adiponectin. Importantly, the ability of adiponectin to reduce caspase‐3/7 activation and cell death was not observed in autophagy‐deficient cells generated by CRISPR‐mediated deletion of Atg7. Collectively, our data indicate that adiponectin acts in an autophagy‐dependent manner to attenuate cardiomyocyte caspase‐3/7 activation and cell death in response to hypoxia in vitro and ischemia in mice.
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- 2024
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11. Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with advanced non-small cell lung cancer
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Arun Rajan, Renee N Donahue, Jeffrey Schlom, James L Gulley, Elizabeth Lamping, Osama Rahma, Houssein Abdul Sater, Jennifer L Marté, Beatriz Walter-Rodriguez, Yulia Vugmeyster, Yo-Ting Tsai, Shania Bailey, Wiem Lassoued, Richy Agajanian, Andrew Weisman, Rena Ito, Masashi Sato, and Andreas Machl
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Bintrafusp alfa, a first-in-class bifunctional fusion protein targeting transforming growth factor-β (TGF-β) and programmed cell death ligand 1, has demonstrated encouraging efficacy as second-line treatment in patients with non-small cell lung cancer (NSCLC) in a dose expansion cohort of the phase 1, open-label clinical trial (NCT02517398). Here, we report the safety, efficacy, and biomarker analysis of bintrafusp alfa in a second expansion cohort of the same trial (biomarker cohort).Methods Patients with stage IIIb/IV NSCLC who were either immune checkpoint inhibitor (ICI)-naïve (n=18) or ICI-experienced (n=23) were enrolled. The primary endpoint was the best overall response. Paired biopsies (n=9/41) and peripheral blood (n=14/41) pretreatment and on-treatment were studied to determine the immunological effects of treatment and for associations with clinical activity.Results Per independent review committee assessment, objective responses were observed in the ICI-naïve group (overall response rate, 27.8%). No new or unexpected safety signals were identified. Circulating TGF-β levels were reduced (>97%; p
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- 2024
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12. Nod-like receptors in inflammatory arthritis
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Sahib Singh Madahar, Alita Gideon, and Ali A. Abdul-Sater
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Nod-like receptors ,Rheumatoid arthritis ,Psoriatic arthritis ,Gout ,Ankylosing spondylitis ,Pediatric arthritis ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Nod-like receptors (NLRs) are innate immune receptors that play a key role in sensing components from pathogens and from damaged cells or organelles. NLRs form signaling complexes that can lead to activation of transcription factors or effector caspases – by means of inflammasome activation –Inflammatory arthritis (IA) culminating in promoting inflammation. An increasing body of research supports the role of NLRs in driving pathogenesis of IA, a collection of diseases that include rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis, and pediatric arthritis. In this review, we briefly discuss the main drivers of IA diseases and dive into the evidence for – and against – various NLRs in driving these diseases. We also review the studies examining the use of NLR and inflammasome inhibitors as potential therapies for IA.
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- 2024
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13. Cardioprotection by the adiponectin receptor agonist ALY688 in a preclinical mouse model of heart failure with reduced ejection fraction (HFrEF)
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Sungji Cho, Keith Dadson, Hye Kyoung Sung, Oyeronke Ayansola, Ali Mirzaesmaeili, Nina Noskovicova, Yimu Zhao, Krisco Cheung, Milica Radisic, Boris Hinz, Ali A. Abdul Sater, Henry H. Hsu, Gary D. Lopaschuk, and Gary Sweeney
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Adiponectin ,Heart failure ,Therapeutic ,Fibrosis ,Inflammation ,Metabolism ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Aims: Adiponectin has been shown to mediate cardioprotective effects and levels are typically reduced in patients with cardiometabolic disease. Hence, there has been intense interest in developing adiponectin-based therapeutics. The aim of this translational research study was to examine the functional significance of targeting adiponectin signaling with the adiponectin receptor agonist ALY688 in a mouse model of heart failure with reduced ejection fraction (HFrEF), and the mechanisms of cardiac remodeling leading to cardioprotection. Methods and results: Wild-type mice were subjected to transverse aortic constriction (TAC) to induce left ventricular pressure overload (PO), or sham surgery, with or without daily subcutaneous ALY688-SR administration. Temporal analysis of cardiac function was conducted via weekly echocardiography for 5 weeks and we observed that ALY688 attenuated the PO-induced dysfunction. ALY688 also reduced cardiac hypertrophic remodeling, assessed via LV mass, heart weight to body weight ratio, cardiomyocyte cross sectional area, ANP and BNP levels. ALY688 also attenuated PO-induced changes in myosin light and heavy chain expression. Collagen content and myofibroblast profile indicated that fibrosis was attenuated by ALY688 with TIMP1 and scleraxis/periostin identified as potential mechanistic contributors. ALY688 reduced PO-induced elevation in circulating cytokines including IL-5, IL-13 and IL-17, and the chemoattractants MCP-1, MIP-1β, MIP-1alpha and MIP-3α. Assessment of myocardial transcript levels indicated that ALY688 suppressed PO-induced elevations in IL-6, TLR-4 and IL-1β, collectively indicating anti-inflammatory effects. Targeted metabolomic profiling indicated that ALY688 increased fatty acid mobilization and oxidation, increased betaine and putrescine plus decreased sphingomyelin and lysophospholipids, a profile indicative of improved insulin sensitivity. Conclusion: These results indicate that the adiponectin mimetic peptide ALY688 reduced PO-induced fibrosis, hypertrophy, inflammation and metabolic dysfunction and represents a promising therapeutic approach for treating HFrEF in a clinical setting.
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- 2024
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14. Memory impairment in the D2.mdx mouse model of Duchenne muscular dystrophy is prevented by the adiponectin receptor agonist ALY688
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Catherine A. Bellissimo, Laura N. Castellani, Michael S. Finch, Mayoorey Murugathasan, Shivam Gandhi, Gary Sweeney, Ali A. Abdul‐Sater, Rebecca E. K. MacPherson, and Christopher G. R. Perry
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cognition ,Duchenne muscular dystrophy ,memory ,mitochondria ,Physiology ,QP1-981 - Abstract
Abstract Memory impairments have been well documented in people with Duchenne muscular dystrophy (DMD). However, the underlying mechanisms are poorly understood, and there is an unmet need to develop new therapies to treat this condition. Using a novel object recognition test, we show that recognition memory impairments in D2.mdx mice are completely prevented by daily treatment with the new adiponectin receptor agonist ALY688 from day 7 to 28 of age. In comparison to age‐matched wild‐type mice, untreated D2.mdx mice demonstrated lower hippocampal mitochondrial respiration (carbohydrate substrate), greater serum interleukin‐6 cytokine content and greater hippocampal total tau and Raptor protein contents. Each of these measures was partly or fully preserved after treatment with ALY688. Collectively, these results indicate that adiponectin receptor agonism improves recognition memory in young D2.mdx mice.
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- 2023
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15. Nod-like receptors in inflammatory arthritis
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Madahar, Sahib Singh, Gideon, Alita, and Abdul-Sater, Ali A.
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- 2024
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16. TRAF1 Deficiency in Macrophages Drives Exacerbated Joint Inflammation in Rheumatoid Arthritis
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Ali Mirzaesmaeili and Ali A. Abdul-Sater
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TRAF1 ,rheumatoid arthritis ,inflammation ,macrophages ,collagen antibody-induced arthritis ,Microbiology ,QR1-502 - Abstract
The tumor necrosis factor receptor-associated factor 1 (TRAF1) plays a key role in promoting lymphocyte survival, proliferation, and cytokine production. Recent evidence showed that TRAF1 plays opposing roles in monocytes and macrophages where it controls NF-κB activation and limits pro-inflammatory cytokine production as well as inflammasome-dependent IL-1β secretion. Importantly, TRAF1 polymorphisms have been strongly linked to an increased risk of rheumatoid arthritis (RA). However, whether and how TRAF1 contributes to RA pathogenesis is not fully understood. Moreover, investigating the role of TRAF1 in driving RA pathogenesis is complicated by its multifaceted and opposing roles in various immune cells. In this study, we subjected wildtype (WT) mice to the collagen antibody-induced arthritis (CAIA) model of RA and injected them intra-articularly with WT- or TRAF1-deficient macrophages. We show that mice injected with TRAF1-deficient macrophages exhibited significantly exacerbated joint inflammation, immune cell infiltration, and tissue damage compared to mice injected with WT macrophages. This study may lay the groundwork for novel therapies for RA that target TRAF1 in macrophages.
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- 2024
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17. Congenital heart disease research landscape in the Arab world: a 25-year bibliometric review
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Fouad Bitar, Mariam Arabi, Ziad Bulbul, Georges Nemer, Yehya Jassar, Fadi F. Bitar, and Zahi Abdul Sater
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research ,Arab countries ,limited resource countries ,developing and developed countries ,congenital heart disease ,pediatric cardiology ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundWhile research on congenital heart disease has been extensively conducted worldwide, comprehensive studies from developing countries and the Arab world remain scarce.AimThis study aims to perform a bibliometric review of research on congenital heart disease in the Arab world from 1997 to 2022.MethodsWe analyzed data from the Web of Science, encompassing various aspects such as topics, countries, research output, citations, authors, collaborations, and affiliations. This comprehensive science mapping analysis was done using the R statistical software's Bibliometrix Package.ResultsThe research output from Arab countries over the 25 years showed an average annual growth rate of 11.5%. However, Arab countries exhibited lower research productivity than the United States and Europe, with a 24-fold difference. There was substantial variation in research output among 22 Arab countries, with five countries contributing to 78% of the total publications. Most of the published research was clinical, with limited innovative contributions and a preference for regional journals. High-income Arab countries displayed higher research productivity and citation rates than their low-income developing counterparts. Despite being categorized as upper-middle-income, post-conflict countries exhibited low research productivity. About one-quarter of the published articles (26%) resulted from collaborative efforts among multiple countries, with the United States being the most frequent collaborator. Enhanced research productivity and impact output were strongly associated with increased international cooperation.ConclusionResearch productivity in the Arab region closely correlates with a country's GDP. Success hinges on governmental support, funding, international collaboration, and a clear research vision. These findings offer valuable insights for policymakers, educational institutions, and governments to strengthen research programs and nurture a research culture.
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- 2024
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18. Long-term burden of war injuries among civilians in LMICs: case of the July 2006 war in Lebanon
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Elsa Kobeissi, Marilyne Menassa, Gladys Honein-AbouHaidar, Nassim El Achi, Zahi Abdul-Sater, Theresa Farhat, Dalia Al Mohtar, Marwan Hajjar, Rima A. Abdul-Khalek, Bachar F. Chaya, Ahmad Elamine, Shehan Hettiaratchy, and Ghassan Abu-Sittah
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armed conflict ,Lebanon ,long-term burden ,access to health care ,patient referral ,blast injuries ,Public aspects of medicine ,RA1-1270 - Abstract
IntroductionLebanon, a country located on the eastern shore of the Mediterranean Sea, is one of the world’s smaller sovereign states. In the past few decades, Lebanon endured a perpetual political turmoil and several armed conflicts. July 12, 2006, marked the start of a one-month war in Lebanon, which resulted in thousands of casualties. Little is known about the long-term consequences of war injuries inflicted on civilians during the July 2006 war.MethodsThe objectives of this paper were to identify and evaluate: 1- civilians’ access to healthcare and medicine under conditions of war; 2- the long-term socioeconomic burden on injured civilians; and 3- their quality of life more than a decade post-war. We adopted a mixed-method research design with an emphasis on the qualitative component. We conducted interviews with patients, collected clinical and financial data from hospital medical records, and administered a self-rated health questionnaire, the EQ-5D-5L. Simple descriptive statistics were calculated using Excel. NVivo 12® was used for data management and thematic analysis.ResultsWe conducted 25 interviews. Injured civilians were mostly males, average age of 27. The most common mechanism of injury was blast injury. Most patients underwent multiple surgeries as well as revision surgeries. The thematic analysis revealed three themes: 1- recall of the time of the incident, the thousand miles journey, and patients’ access to services; 2- post-trauma sequelae and services; and 3- long-term impact. Patients described the long-term burden including chronic pain, poor mobility, anxiety or depression, and limited activities of daily living.DiscussionCivilians injured during the July 2006 war described the traumatising events they endured during the war and the limited access to medical care during and post-war. Up until this study was conducted, affected civilians were still experiencing physical, psychological, and financial sequelae. Acknowledging the limitations of this study, which include a small sample size and recall bias, the findings underscore the necessity for the expansion of services catering to civilians injured during wartime.
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- 2023
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19. 587 Nivolumab increased vaccine induced T-cell infiltration in Prostate cancer
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James L Gulley, Ravi Madan, Jennifer Marte, Fatima Karzai, Amy Hankin, Houssein Abdul Sater, Manuk Manukyan, William Dahut, Shania Bailey, Wiem Lassoued, Michell Manu, Peter Pinto, Daniel Burnett, Kenneth Canubas, and Nikki William
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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20. 913 Tumor immune micro-environment (TIME) Atlas for prostate cancer bone metastasis
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James L Gulley, Jennifer Marte, Houssein Abdul Sater, Michael Xu, William Kelly, Wiem Lassoued, and Kenneth Canubas
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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21. Autophagy deficiency exacerbates iron overload induced reactive oxygen species production and apoptotic cell death in skeletal muscle cells
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Hye Kyoung Sung, Mayoorey Murugathasan, Ali A. Abdul-Sater, and Gary Sweeney
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Cytology ,QH573-671 - Abstract
Abstract Iron overload is associated with various pathological changes which contribute to metabolic syndrome, many of which have been proposed to occur via damaging tissue through an excessive amount of reactive oxygen species (ROS) production. In this study, we established a model of iron overload in L6 skeletal muscle cells and observed that iron enhanced cytochrome c release from depolarized mitochondria, assayed by immunofluorescent colocalization of cytochrome c with Tom20 and the use of JC-1, respectively. This subsequently elevated apoptosis, determined via use of a caspase-3/7 activatable fluorescent probe and western blotting for cleaved caspase-3. Using CellROX deep red and mBBr, we observed that iron increased generation of reactive oxygen species (ROS), and that pretreatment with the superoxide dismutase mimetic MnTBAP reduced ROS production and attenuated iron-induced intrinsic apoptosis and cell death. Furthermore, using MitoSox Red we observed that iron enhanced mROS and the mitochondria-targeted anti-oxidant SKQ1 reduced iron-induced ROS generation and cell death. Western blotting for LC3-II and P62 levels as well as immunofluorescent detection of autophagy flux with LC3B and P62 co-localization indicated that iron acutely (2–8 h) activated and later (12–24 h) attenuated autophagic flux. We used autophagy-deficient cell models generated by overexpressing a dominant-negative Atg5 mutant or CRISPR-mediated ATG7 knock out to test the functional significance of autophagy and observed that autophagy-deficiency exacerbated iron-induced ROS production and apoptosis. In conclusion, our study showed that high iron levels promoted ROS production, blunted the self-protective autophagy response and led to cell death in L6 skeletal muscle cells.
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- 2023
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22. Bayesian modeling of the impact of antibiotic resistance on the efficiency of MRSA decolonization.
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Fanni Ojala, Mohamad R Abdul Sater, Loren G Miller, James A McKinnell, Mary K Hayden, Susan S Huang, Yonatan H Grad, and Pekka Marttinen
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Biology (General) ,QH301-705.5 - Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity and mortality. Colonization by MRSA increases the risk of infection and transmission, underscoring the importance of decolonization efforts. However, success of these decolonization protocols varies, raising the possibility that some MRSA strains may be more persistent than others. Here, we studied how the persistence of MRSA colonization correlates with genomic presence of antibiotic resistance genes. Our analysis using a Bayesian mixed effects survival model found that genetic determinants of high-level resistance to mupirocin was strongly associated with failure of the decolonization protocol. However, we did not see a similar effect with genetic resistance to chlorhexidine or other antibiotics. Including strain-specific random effects improved the predictive performance, indicating that some strain characteristics other than resistance also contributed to persistence. Study subject-specific random effects did not improve the model. Our results highlight the need to consider the properties of the colonizing MRSA strain when deciding which treatments to include in the decolonization protocol.
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- 2023
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23. Cancer Research in Vulnerable Populations: A Call for Collaboration and Sustainability From MENAT Countries
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Marwan Tolba, Mac Skelton, Zahi Abdul Sater, Ibtihal Fadhil, Ali Al-Zahrani, Tezer Kutluk, Kamal Akbarov, Ali Taher, Richard Sullivan, and Layth Mula-Hussain
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
PURPOSECancer is a major burden across Middle East, North Africa, Türkiye (MENAT). Many MENAT countries experience multiple conflicts that compound vulnerabilities, but little research investigates the linkages between vulnerability and cancer research. This study examines the current level and the potential for cancer research among vulnerable populations in the MENAT region, aiming to provide direction toward developing a research agenda on the region's vulnerable populations.METHODSExpert-driven meetings were arranged among the 10 authors. After obtaining institutional review board approval, a self-administered online survey questionnaire was circulated to more than 500 cancer practitioners working in 22 MENAT countries.RESULTSTwo hundred sixteen cancer practitioners across the MENAT region responded. Fifty percent of the respondents identified clinical research in vulnerable patients with cancer as a significant issue; 21.8% reported previous research experience that included vulnerable populations, and 60% reported encountering vulnerable populations in their daily clinical practice. The main barriers to conducting research were lack of funding (60%), protected time (42%), and research training (35%). More than half of the respondents believed that wars/conflicts constituted an important source of vulnerability. The most vulnerable cancer populations were the elderly, palliative/terminally ill, those with concomitant mental health-related issues, those with other chronic illnesses, and socioeconomically deprived patients.CONCLUSIONResults support that a major effort is needed to improve cancer research among vulnerable cancer populations in the MENAT region. We call for interdisciplinary research that accounts for the region's unique, compounding, and cumulative forms of vulnerability. This cancer research agenda on different vulnerable populations must balance sociobehavioral studies that explore sociopolitical barriers to quality care and clinical studies that gauge and refine treatment protocols. Building a research agenda through collaboration and solidarity with international partners is prime time.
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- 2023
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24. Cancer Care During War and Conflict
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Sayed, Rola El, Abdul-Sater, Zahi, Mukherji, Deborah, Al-Shamsi, Humaid O., editor, Abu-Gheida, Ibrahim H., editor, Iqbal, Faryal, editor, and Al-Awadhi, Aydah, editor
- Published
- 2022
- Full Text
- View/download PDF
25. Autophagy deficiency exacerbates iron overload induced reactive oxygen species production and apoptotic cell death in skeletal muscle cells
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Sung, Hye Kyoung, Murugathasan, Mayoorey, Abdul-Sater, Ali A., and Sweeney, Gary
- Published
- 2023
- Full Text
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26. War and oncology: cancer care in five Iraqi provinces impacted by the ISIL conflict
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Mac Skelton, Ahmed Khalid Al-Mash'hadani, Zahi Abdul-Sater, Mohammed Saleem, Saad Alsaad, Marwa Kahtan, Ahmed Hazim Al-Samarai, Ahmed Moyed Al-Bakir, and Layth Mula-Hussain
- Subjects
cancer ,oncology ,conflict ,Iraq war ,Mosul ,Islamic State ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
War and cancer have been intertwined in Iraq for over three decades, a country where the legacies and ongoing impacts of conflict have been commonly associated with both increased cancer rates as well as the deterioration of cancer care. Most recently, the Islamic State of Iraq and the Levant (ISIL) violently occupied large portions of the country’s central and northern provinces between 2014 and 2017, causing devastating impacts on public cancer centers across central and northern Iraq. Focusing on the five Iraqi provinces previously under full or partial ISIL occupation, this article examines the immediate and long-term impacts of war on cancer care across three periods (before, during, and after the ISIL conflict). As there is little published data on oncology in these local contexts, the paper relies primarily upon the qualitative interviews and lived experience of oncologists serving in the five provinces studied. A political economy lens is applied to interpret the results, particularly the data related to progress in oncology reconstruction. It is argued that conflict generates immediate and long-term shifts in political and economic conditions that, in turn, shape the rebuilding of oncology infrastructure. The documentation of the destruction and reconstruction of local oncology systems is intended to benefit the next generation of cancer care practitioners in the Middle East and other conflict-affected regions areas in their efforts to adapt to conflict and rebuild from the legacies of war.
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- 2023
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- View/download PDF
27. Characteristics of injuries during the 2006 Lebanon conflict: a three-center retrospective study of survivors, 16 years after the conflict
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Farhat, Theresa, primary, Nahouli, Hasan, additional, Hajjar, Marwan, additional, Abdul-Sater, Zahi, additional, Kobeissi, Elsa, additional, Menassa, Marilyne, additional, Chaya, Bachar F., additional, Elamine, Ahmad, additional, El Sheikh, Walaa G., additional, Tamim, Hani, additional, Hettiaratchy, Shehan, additional, and Abu-Sittah, Ghassan, additional
- Published
- 2024
- Full Text
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28. TRAF1 Deficiency in Macrophages Drives Exacerbated Joint Inflammation in Rheumatoid Arthritis
- Author
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Mirzaesmaeili, Ali, primary and Abdul-Sater, Ali A., additional
- Published
- 2024
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- View/download PDF
29. Dicer regulates activation of the NLRP3 inflammasome.
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Ojcius, David M, Jafari, Ardavan, Yeruva, Laxmi, Schindler, Christian W, and Abdul-Sater, Ali A
- Subjects
Cells ,Cultured ,Macrophages ,Animals ,Mice ,Transgenic ,Mice ,Ribonuclease III ,DNA-Binding Proteins ,MicroRNAs ,Computational Biology ,Signal Transduction ,Gene Expression Regulation ,Up-Regulation ,DEAD-box RNA Helicases ,Immunity ,Innate ,Inflammasomes ,Primary Cell Culture ,NLR Family ,Pyrin Domain-Containing 3 Protein ,Cells ,Cultured ,Immunity ,Innate ,Transgenic ,NLR Family ,Pyrin Domain-Containing 3 Protein ,General Science & Technology - Abstract
Inflammation plays a critical role in initiation of adaptive immunity, pathogen clearance and tissue repair. Interleukin (IL)-1β is a potent pro-inflammatory cytokine and therefore its production is tightly regulated: its secretion requires the assembly of a macromolecular protein complex, termed the inflammasome. Aberrant activation of the inflammasome has been linked to debilitating human diseases including chronic inflammatory and autoimmune diseases. Thus, there is a great interest in understanding how inflammasomes are regulated. Here we show that Dicer, an enzyme necessary for the production of mature micro-RNAs (miRNAs), is required for optimal activation of NLRP3 inflammasomes in bone marrow macrophages. Our data indicate that miRNAs may play an important role in promoting inflammasome activation.
- Published
- 2019
30. The state of cancer research in fragile and conflict-affected settings in the Middle East and North Africa Region: A bibliometric analysis
- Author
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Zahi Abdul Sater, Theresa Farhat, Mohamed N. Elsayed, Yara Youssef, Marium Husain, Malak Kaddoura, Lubna Jaber, Deborah Mukherji, and Ali Taher
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cancer research ,bibliometric ,conflict settings ,Arab world ,MENA region ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundCancer represents a disproportionate burden in LMICs, especially conflict-affected countries in the MENA region. Research output on cancer fails to match the growing burden in the region. This bibliometric study aims to examine the status and trends of cancer research in fragile and conflict-affected settings in the MENA region from 2000 to 2021, while also incorporating economic and demographic indicators as additional factors of analysis.MethodsThe Web of Science databases were searched for publications related to cancer research in Iraq, Lebanon, Libya, Palestine, Syria, and Yemen from January 1, 2000, to December 31, 2021. The retrieved publications were screened based on preset eligibility criteria and the final list was analyzed using the Bibliometrix Package in R to generate the annual scientific production and citations, journals, institutions, authors, collaborations, keywords, and title co-occurrence. Each country’s annual scientific production was analyzed against its annual GDP per capita.ResultsA total of 4,280 documents met the inclusion criteria in this research. The annual number of publications revealed a significant increase over the past 20 years. These publications were mostly published in international journals that had impact factors rated in the 3rd or 4th quartiles. The overall contribution of researchers from Fragile and Conflict-Affected Settings (FCS) to cancer research was 6.5% of the MENA cancer research productivity, despite comprising around 23% of the total MENA region’s population. Lebanon had the highest publication productivity at the country level, followed by Iraq and Syria. GDP per capita was not significantly correlated with cancer research across the countries under investigation. At the institutional level, the American University of Beirut was the most prolific institution and had the highest number of collaborations and the widest range of cooperative partners. Most first authors were male researchers. There is an interest in cancer expression, prevalence, diagnosis, and management in terms of commonly researched topics.ConclusionThis study underscores the need for a concerted effort to improve cancer research outcomes in FCS, which can be achieved through targeted research, increased investment in research infrastructure and capacity-building initiatives, and greater regional and global collaboration.
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- 2023
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31. SIK2 kinase synthetic lethality is driven by spindle assembly defects in FANCA‐deficient cells
- Author
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Ka‐Kui Chan, Zahi Abdul‐Sater, Aditya Sheth, Dana K. Mitchell, Richa Sharma, Donna M. Edwards, Ying He, Grzegorz Nalepa, Steven D. Rhodes, D. Wade Clapp, and Elizabeth A. Sierra Potchanant
- Subjects
cancer ,Fanconi anemia pathway ,SIK2 ,spindle assembly checkpoint ,synthetic lethality ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The Fanconi anemia (FA) pathway safeguards genomic stability through cell cycle regulation and DNA damage repair. The canonical tumor suppressive role of FA proteins in the repair of DNA damage during interphase is well established, but their function in mitosis is incompletely understood. Here, we performed a kinome‐wide synthetic lethality screen in FANCA−/− fibroblasts, which revealed multiple mitotic kinases as necessary for survival of FANCA‐deficient cells. Among these kinases, we identified the depletion of the centrosome kinase SIK2 as synthetic lethal upon loss of FANCA. We found that FANCA colocalizes with SIK2 at multiple mitotic structures and regulates the activity of SIK2 at centrosomes. Furthermore, we found that loss of FANCA exacerbates cell cycle defects induced by pharmacological inhibition of SIK2, including impaired G2‐M transition, delayed mitotic progression, and cytokinesis failure. In addition, we showed that inhibition of SIK2 abrogates nocodazole‐induced prometaphase arrest, suggesting a novel role for SIK2 in the spindle assembly checkpoint. Together, these findings demonstrate that FANCA‐deficient cells are dependent upon SIK2 for survival, supporting a preclinical rationale for targeting of SIK2 in FA‐disrupted cancers.
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- 2022
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32. Responding to the Humanitarian Crisis in Gaza: Damned if You do… Damned if You don’t!
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Theresa Farhat, Sarah Ibrahim, Zahi Abdul-Sater, and Ghassan Abu-Sittah
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gaza ,siege ,humanitarian ,crisis ,emergency ,war ,palestine ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Palestine, since 1948, has endured frequent military occupations and uprisings, intifadas, in a limited geographic area that has resulted in one of the worst humanitarian crises. The prolonged nature of this military occupation has created a biosphere of war that is uninhabitable, whereby Palestinians suffer from physical, psychological, and social wounds. Israel also imposed restrictive measures in Gaza, making it difficult for Palestinians to obtain permits to work and travel throughout Palestine. Israel continued to intensify the restrictions on Gaza, reaching a blockade on the Gaza Strip, which cut off Palestinians from Jerusalem, where hospitals, banks, and vital services are found. This form of permanent siege resulted in a surge in the unemployment rate, poverty, and poor nutritional and wellbeing status. The siege also resulted in the largest open-air prison, as people became stuck between an incomplete life and the absence of total death. The major challenge is that humanitarian interventions, in the case of Gaza, are ineffective, as they are part of the siege framework. This is because any humanitarian aid meant for Gaza needs to be approved by Israel. Thus, when the emergency becomes chronic and humanitarian interventions become part of the siege framework, how can Gaza rebuild its health capacity in a permanent emergency, and to what extent can the humanitarian sector make a change?
- Published
- 2023
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33. Copper infused fabric attenuates inflammation in macrophages.
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Safoura Zangiabadi, Khalil P Chamoun, Khang Nguyen, Yitian Tang, Gary Sweeney, and Ali A Abdul-Sater
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Medicine ,Science - Abstract
While inflammation is an important immune response for protection from infections, excessive or prolonged inflammation can lead to a variety of debilitating diseases including skin disease, diabetes, heart disease, stroke, autoimmune diseases and cancer. Inflammation is a graded response that is typically initiated when resident macrophages sense the presence of pathogens or damage in the tissue and produce inflammatory cytokines and chemokines to kill the pathogen, clear debris and dead tissue, and initiate tissue repair. Here we show that copper-infused fabrics can prevent inflammation by blocking the production of inflammatory cytokines from macrophages after being exposed to LPS, a component of bacterial cell wall. Mechanistically, we show that copper-infused fabrics can significantly reduce the NF-κB and IRF3 activation in LPS-stimulated macrophages. Given the importance of excessive inflammation in diabetes, we show that copper can reduce insulin resistance mediated by inflammatory cytokines in muscle cells. Our data show that copper infused fabrics may be useful to reduce excessive inflammation in macrophages and improve insulin sensitivity in skeletal muscles.
- Published
- 2023
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34. Cancer Registration in the Middle East, North Africa, and Turkey: Scope and Challenges
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Zahi Abdul-Sater, Ali Shamseddine, Ali Taher, Fouad Fouad, Ghassan Abu-Sitta, Ibtihal Fadhil, Raya Saab, Richard Sullivan, Salim M. Adib, Shadi Saleh, and Deborah Mukherji
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
PURPOSENational cancer control strategies have been identified as essential tools for reducing and managing the growing burden of cancer in low- and middle-income countries. Cancer registration is an instrumental component of any cancer control strategy, providing the data to inform effective cancer policy. In the Middle East, North Africa, and Turkey (MENAT) region, cancer registration varies immensely and faces multifaceted challenges including protracted conflict. This study investigates and maps out the present capacities and outputs of cancer registration in the MENAT region and identifies thematic barriers facing implementation and utilization of cancer registry data.MATERIALS AND METHODSWe used a self-administered online survey with open and close-ended questions targeting national and institutional cancer registry managers in the MENAT countries.RESULTSRegistry managers from 19 MENAT countries reported the presence of 97 population-based, 48 hospital-based, and 24 pathology-based registries. Most population-based registries were well- or partially developed. Lack of accurate death records, complete medical records, and communication between stakeholders and deficiencies in trained personnel were critical challenges that were more severe in active conflict zones and neighboring conflict-affected regions. Cancer registration challenges included weak health infrastructure, absence of legislation mandating cancer registration, and disruption of cancer registration because of active conflict and loss of funding. Refugee host countries, such as Lebanon, Turkey, and Jordan, also reported conflict-related challenges including refugee mobility and lack of accurate data on forced migrants.CONCLUSIONThis study provides a much-needed understanding of the current landscape and contextual challenges affecting cancer registration in the MENAT. These data are important for identifying areas on which to focus regional capacity-strengthening initiatives.
- Published
- 2021
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35. Cancer registration in the Middle East, North Africa, and Turkey (MENAT) region: A tale of conflict, challenges, and opportunities
- Author
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Zahi Abdul-Sater, Deborah Mukherji, Salim M. Adib, Ali Shamseddine, Ghassan Abu-Sitta, Ibtihal Fadhil, Richard Sullivan, Amal Al Omari, Shadi Saleh, and Ali Taher
- Subjects
cancer registration data ,cancer control ,population based cancer registries (PBCRs) ,cancer surveillance ,Middle East & North Africa (MENA) ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cancer registration is a core component of national and regional cancer control strategies. In the Middle East, North-Africa and Turkey (MENAT) region, capacity and resources for cancer registration is variable and shaped by multiple contextual challenges. This viewpoint maps out practical recommendations around cancer registration, in an attempt to inform cancer control planning, policy, and implementation. The recommendations laid out in this viewpoint are informed by the discussions held at the Initiative for Cancer Registration in the MENAT (ICRIM) virtual workshop, which convened registry managers, policy makers, and international agencies from 19 countries in the MENAT region. The discussions were distilled in four categories of recommendations, revolving around cancer registration procedures, collaborative governance, putting cancer registration on the map, and capacity building. This viewpoint provides a much-needed mapping of practical recommendations around cancer registration, informed by direct key stakeholders in the region. These practical recommendations offer a road map for policy making, cancer control planning, and future regional capacity strengthening initiatives.
- Published
- 2022
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36. Editorial: The innate immune system in rheumatoid arthritis
- Author
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Zhu Chen, Javier Leceta, Ali A. Abdul-Sater, and Mario Delgado
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arthritis ,rheumatoid ,innate immunity ,inflammation ,osteoclast ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2022
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37. Bibliometric analysis of focal therapy in prostate cancer research
- Author
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Shahait, Mohammed, primary, Ibrahim, Sarah, additional, Baqain, Laith, additional, and Abdul‐Sater, Zahi, additional
- Published
- 2024
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38. Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with advanced non-small cell lung cancer
- Author
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Rajan, Arun, primary, Abdul Sater, Houssein, additional, Rahma, Osama, additional, Agajanian, Richy, additional, Lassoued, Wiem, additional, Marté, Jennifer L, additional, Tsai, Yo-Ting, additional, Donahue, Renee N, additional, Lamping, Elizabeth, additional, Bailey, Shania, additional, Weisman, Andrew, additional, Walter-Rodriguez, Beatriz, additional, Ito, Rena, additional, Vugmeyster, Yulia, additional, Sato, Masashi, additional, Machl, Andreas, additional, Schlom, Jeffrey, additional, and Gulley, James L, additional
- Published
- 2024
- Full Text
- View/download PDF
39. Detection of ASC Oligomerization by Western Blotting
- Author
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Zangiabadi, Safoura, primary, Akram, Ali, additional, and Abdul-Sater, Ali A., additional
- Published
- 2022
- Full Text
- View/download PDF
40. Measurement of Inflammasome-Induced Mitochondrial Dysfunction by Flow Cytometry
- Author
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Thasan, Mayoorey M., primary and Abdul-Sater, Ali A., additional
- Published
- 2022
- Full Text
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41. Innate immunity drives pathogenesis of rheumatoid arthritis
- Author
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Maria I. Edilova, Ali Akram, and Ali A. Abdul-Sater
- Subjects
Innate immune system ,Rheumatoid arthritis ,Inflammation ,Cytokines ,Toll-like receptors ,Inflammasomes ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Rheumatoid arthritis (RA) is an autoimmune disease affecting ∼1% of the general population. This disease is characterized by persistent articular inflammation and joint damage driven by the proliferating synovial tissue fibroblasts as well as neutrophil, monocyte and lymphocyte trafficking into the synovium. The factors leading to RA pathogenesis remain poorly elucidated although genetic and environmental factors have been proposed to be the main contributors to RA. The majority of the early studies focused on the role of lymphocytes and adaptive immune responses in RA. However, in the past two decades, emerging studies showed that the innate immune system plays a critical role in the onset and progression of RA pathogenesis. Various innate immune cells including monocytes, macrophages and dendritic cells are involved in inflammatory responses seen in RA patients as well as in driving the activation of the adaptive immune system, which plays a major role in the later stages of the disease. Here we focus the discussion on the role of different innate immune cells and components in initiation and progression of RA. New therapeutic approaches targeting different inflammatory pathways and innate immune cells will be highlighted here. Recent emergence and the significant roles of innate lymphoid cells and inflammasomes will be also discussed.
- Published
- 2021
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42. TRAF1 Deficiency in Macrophages Drives Exacerbated Joint Inflammation in Rheumatoid Arthritis.
- Author
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Mirzaesmaeili, Ali and Abdul-Sater, Ali A.
- Subjects
- *
TUMOR necrosis factors , *RHEUMATOID arthritis , *MACROPHAGES , *MONOCYTES , *ARTHRITIS - Abstract
The tumor necrosis factor receptor-associated factor 1 (TRAF1) plays a key role in promoting lymphocyte survival, proliferation, and cytokine production. Recent evidence showed that TRAF1 plays opposing roles in monocytes and macrophages where it controls NF-κB activation and limits pro-inflammatory cytokine production as well as inflammasome-dependent IL-1β secretion. Importantly, TRAF1 polymorphisms have been strongly linked to an increased risk of rheumatoid arthritis (RA). However, whether and how TRAF1 contributes to RA pathogenesis is not fully understood. Moreover, investigating the role of TRAF1 in driving RA pathogenesis is complicated by its multifaceted and opposing roles in various immune cells. In this study, we subjected wildtype (WT) mice to the collagen antibody-induced arthritis (CAIA) model of RA and injected them intra-articularly with WT- or TRAF1-deficient macrophages. We show that mice injected with TRAF1-deficient macrophages exhibited significantly exacerbated joint inflammation, immune cell infiltration, and tissue damage compared to mice injected with WT macrophages. This study may lay the groundwork for novel therapies for RA that target TRAF1 in macrophages. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
43. Similitude of Scaled and Full Scale Linkages
- Author
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Laudahn, Simon, Sviberg, Magnus, Wiesenfeld, Lukas, Haberl, Franz, Haidl, Johannes, Abdul-Sater, Kassim, Irlinger, Franz, Ceccarelli, Marco, Series Editor, Corves, Burkhard, Advisory Editor, Takeda, Yukio, Advisory Editor, Wenger, Philippe, editor, and Hüsing, Mathias, editor
- Published
- 2019
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44. High rates of advanced prostate cancer in the Middle East: Analysis from a tertiary care center
- Author
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Marilyne Daher, Talar Telvizian, Christelle Dagher, Zahi Abdul-Sater, Sarah Abdel Massih, Alissar EL Chediak, Maya Charafeddine, Mohammed Shahait, Raafat Alameddine, Sally Temraz, Fady Geara, Bassem Youssef, Albert El Hajj, Rami Nasr, Wassim Wazzan, Muhammad Bulbul, Raja Khauli, Ali Shamseddine, and Deborah Mukherji
- Subjects
cancer staging ,middle east ,prostate cancer ,prostate neoplasm ,tumor staging ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Objectives: Prostate cancer incidence is increasing in the Middle East (ME); however, the data of stage at the diagnosis and treatment outcomes are lacking. In developed countries, the incidence of de novo metastatic prostate cancer ranges between 4% and 14%. We hypothesized that the rates of presentation with advanced disease are significantly higher in the ME based on clinical observation. This study aims to examine the stage at the presentation of patients with prostate cancer at a large tertiary center in the ME. Methods: After Institutional Review Board approval, we identified the patients diagnosed with prostate adenocarcinoma and presented to a tertiary care center between January 2010 and July 2015. Clinical, demographic, and pathological characteristics were abstracted. Patients with advanced disease were stratified according to tumor volume based on definitions from practice changing clinical trials. Descriptive and Kaplan–Meier survival analysis was used. Results: A total of 559 patients were identified, with a median age at the diagnosis of 65 years and an age range of 39–94 years. Median prostate-specific antigen (PSA) at the presentation was 10 ng/ml, and almost a quarter of the men (23%) presented with metastatic disease. The most common site of metastasis was the bone (34/89, 38%). High-volume metastasis was present in 30.3%, 9%, and 5.2% of the cohort based on STAMPEDE, CHAARTED, and LATITUDE trial criteria, respectively. Conclusion: This is the first report showing the high proportion of men from ME presenting with de novo metastasis. This could be due to many factors, including the highly variable access to specialist multidisciplinary management, lack of awareness, and lack of PSA screening in the region. There is a clear need to raise the awareness about prostate cancer screening and early detection and to address the rising burden of advanced prostate cancer affecting men in the ME region.
- Published
- 2021
- Full Text
- View/download PDF
45. High-Cost Cancer Treatment Across Borders in Conflict Zones: Experience of Iraqi Patients in Lebanon
- Author
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Mac Skelton, Raafat Alameddine, Omran Saifi, Miza Hammoud, Maya Zorkot, Marilyne Daher, Maya Charafeddine, Sally Temraz, Ali Shamseddine, Layth Mula-Hussain, Mohammed Saleem, Kazim F. Namiq, Omar Dewachi, Ghassan Abu Sitta, Zahi Abdul-Sater, Talar Telvizian, Walid Faraj, and Deborah Mukherji
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
PURPOSE Conflict-induced cross-border travel for medical treatment is commonly observed in the Middle East. There has been little research conducted on the financial impact this has on patients with cancer or on how cancer centers can adapt their services to meet the needs of this population. This study examines the experience of Iraqi patients seeking care in Lebanon, aiming to understand the social and financial contexts of conflict-related cross-border travel for cancer diagnosis and treatment. PATIENTS AND METHODS After institutional review board approval, 60 Iraqi patients and caregivers seeking cancer care at a major tertiary referral center in Lebanon were interviewed. RESULTS Fifty-four respondents (90%) reported high levels of financial distress. Patients relied on the sale of possessions (48%), the sale of homes (30%), and vast networks to raise funds for treatment. Thematic analysis revealed several key drivers for undergoing cross-border treatment, including the conflict-driven exodus of Iraqi oncology specialists; the destruction of hospitals or road blockages; referrals by Iraqi physicians to Lebanese hospitals; the geographic proximity of Lebanon; and the lack of diagnostic equipment, radiotherapy machines, and reliable provision of chemotherapy in Iraqi hospitals. CONCLUSION As a phenomenon distinct from medical tourism, conflict-related deficiencies in health care at home force patients with limited financial resources to undergo cancer treatment in neighboring countries. We highlight the importance of shared decision making and consider the unique socioeconomic status of this population of patients when planning treatment.
- Published
- 2020
- Full Text
- View/download PDF
46. Antimicrobial resistance and the Iraq wars: armed conflict as an underinvestigated pathway with growing significance
- Author
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Anthony Rizk, Omar Dewachi, Vinh Kim Nguyen, Antoine Abou Fayad, Samya El Sayed, Malak Kaddoura, Nadine K Jawad, Adel Al-Attar, and Zahy Abdul Sater
- Subjects
Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Published
- 2022
- Full Text
- View/download PDF
47. Danger signals, inflammasomes, and the intricate intracellular lives of chlamydiae.
- Author
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Pettengill, Matthew A, Abdul-Sater, Ali, Coutinho-Silva, Robson, and Ojcius, David M
- Subjects
Humans ,Chlamydiaceae Infections ,Signal Transduction ,Inflammasomes ,Chlamydia ,Immunology ,Infection ,Inflammation ,Innate immunity - Abstract
Chlamydiae are obligate intracellular bacterial pathogens, and as such are sensitive to alterations in the cellular physiology of their hosts. Chlamydial infections often cause pathologic consequences due to prolonged localized inflammation. Considerable advances have been made in the last few years regarding our understanding of how two key inflammation-associated signaling pathways influence the biology of Chlamydia infections: inflammation regulating purinergic signaling pathways significantly impact intracellular chlamydial development, and inflammasome activation modulates both chlamydial growth and infection mediated pro-inflammatory cytokine production. We review here elements of both pathways, presenting the latest developments contributing to our understanding of how chlamydial infections are influenced by inflammasomes and purinergic signaling.
- Published
- 2016
48. The slow-release adiponectin analogue ALY688-SR modifies early-stage disease development in the D2.mdx mouse model of Duchenne muscular dystrophy
- Author
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Bellissimo, Catherine A., primary, Gandhi, Shivam, additional, Castellani, Laura N, additional, Murugathasan, Mayoorey, additional, Delfinis, Luca J, additional, Thuhan, Arshdeep, additional, Garibotti, Madison C., additional, Seo, Yeji, additional, Rebalka, Irena A, additional, Hsu, Henry H, additional, Sweeney, Gary, additional, Hawke, Thomas J., additional, Abdul-Sater, Ali A., additional, and Perry, Christopher G.R., additional
- Published
- 2023
- Full Text
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49. Long-term burden of war injuries among civilians in LMICs: case of the July 2006 war in Lebanon
- Author
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Kobeissi, Elsa, primary, Menassa, Marilyne, additional, Honein-AbouHaidar, Gladys, additional, El Achi, Nassim, additional, Abdul-Sater, Zahi, additional, Farhat, Theresa, additional, Al Mohtar, Dalia, additional, Hajjar, Marwan, additional, Abdul-Khalek, Rima A., additional, Chaya, Bachar F., additional, Elamine, Ahmad, additional, Hettiaratchy, Shehan, additional, and Abu-Sittah, Ghassan, additional
- Published
- 2023
- Full Text
- View/download PDF
50. Mitotic Errors Promote Genomic Instability and Leukemia in a Novel Mouse Model of Fanconi Anemia
- Author
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Donna M. Edwards, Dana K. Mitchell, Zahi Abdul-Sater, Ka-Kui Chan, Zejin Sun, Aditya Sheth, Ying He, Li Jiang, Jin Yuan, Richa Sharma, Magdalena Czader, Pei-Ju Chin, Yie Liu, Guillermo de Cárcer, Grzegorz Nalepa, Hal E. Broxmeyer, D. Wade Clapp, and Elizabeth A. Sierra Potchanant
- Subjects
Fanconi anemia ,leukemia ,spindle assembly checkpoint ,genomic instability ,FANCC ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Fanconi anemia (FA) is a disease of genomic instability and cancer. In addition to DNA damage repair, FA pathway proteins are now known to be critical for maintaining faithful chromosome segregation during mitosis. While impaired DNA damage repair has been studied extensively in FA-associated carcinogenesis in vivo, the oncogenic contribution of mitotic abnormalities secondary to FA pathway deficiency remains incompletely understood. To examine the role of mitotic dysregulation in FA pathway deficient malignancies, we genetically exacerbated the baseline mitotic defect in Fancc-/- mice by introducing heterozygosity of the key spindle assembly checkpoint regulator Mad2. Fancc-/-;Mad2+/- mice were viable, but died from acute myeloid leukemia (AML), thus recapitulating the high risk of myeloid malignancies in FA patients better than Fancc-/-mice. We utilized hematopoietic stem cell transplantation to propagate Fancc-/-; Mad2+/- AML in irradiated healthy mice to model FANCC-deficient AMLs arising in the non-FA population. Compared to cells from Fancc-/- mice, those from Fancc-/-;Mad2+/- mice demonstrated an increase in mitotic errors but equivalent DNA cross-linker hypersensitivity, indicating that the cancer phenotype of Fancc-/-;Mad2+/- mice results from error-prone cell division and not exacerbation of the DNA damage repair defect. We found that FANCC enhances targeting of endogenous MAD2 to prometaphase kinetochores, suggesting a mechanism for how FANCC-dependent regulation of the spindle assembly checkpoint prevents chromosome mis-segregation. Whole-exome sequencing revealed similarities between human FA-associated myelodysplastic syndrome (MDS)/AML and the AML that developed in Fancc-/-; Mad2+/- mice. Together, these data illuminate the role of mitotic dysregulation in FA-pathway deficient malignancies in vivo, show how FANCC adjusts the spindle assembly checkpoint rheostat by regulating MAD2 kinetochore targeting in cell cycle-dependent manner, and establish two new mouse models for preclinical studies of AML.
- Published
- 2021
- Full Text
- View/download PDF
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