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RAS–MAPK–MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1
Park, Jeehye,Al-Ramahi, Ismael,Tan, Qiumin,Mollema, Nissa,Diaz-Garcia, Javier R.,Gallego-Flores, Tatiana,Lu, Hsiang-Chih,Lagalwar, Sarita,Duvick, Lisa,Kang, Hyojin,Lee, Yoontae,Jafar-Nejad, Paymaan,Sa Nature Publishing Group, a division of Macmillan P 2013 Nature Vol.498 No.7454
Many neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and polyglutamine diseases, share a common pathogenic mechanism: the abnormal accumulation of disease-causing proteins, due to either the mutant protein’s resistance to degradation or overexpression of the wild-type protein. We have developed a strategy to identify therapeutic entry points for such neurodegenerative disorders by screening for genetic networks that influence the levels of disease-driving proteins. We applied this approach, which integrates parallel cell-based and Drosophila genetic screens, to spinocerebellar ataxia type 1 (SCA1), a disease caused by expansion of a polyglutamine tract in ataxin 1 (ATXN1). Our approach revealed that downregulation of several components of the RAS–MAPK–MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice. Importantly, pharmacological inhibitors of components of this pathway also decrease ATXN1 levels, suggesting that these components represent new therapeutic targets in mitigating SCA1. Collectively, these data reveal new therapeutic entry points for SCA1 and provide a proof-of-principle for tackling other classes of intractable neurodegenerative diseases.
Khader, Jamal K.,Al-Mousa, Abdelatif M.,Mohamad, Issa A.,Abuhijlih, Ramiz A.,Al-Khatib, Sondos A.,Alnsour, Anoud Z.,Asha, Wafa A.,Ramahi, Shada W.,Hosni, Ali A.,Abuhijla, Fawzi J. The Korean Society for Radiation Oncology 2019 Radiation Oncology Journal Vol.37 No.1
Purpose: The quality assurance (QA) chart rounds are multidisciplinary meetings to review radiation therapy (RT) treatment plans. This study focus on describing the changes in RT management based on QA round reviews in a single institution. Materials and Methods: After 9 full years of implementation, a retrospective review of all patients whose charts passed through departmental QA chart rounds from 2007 to 2015. The reviewed cases were presented for RT plan review; subcategorized based on decision in QA rounds into: approved, minor modifications or major modifications. Major modification defined as any substantial change which required patient re-simulation or re-planning prior to commencement of RT. Minor modification included treatment plan changes which didn't necessarily require RT re-planning. Results: Overall 7,149 RT treatment plans for different anatomical sites were reviewed at QA rounds. From these treatment plans, 6,654 (93%) were approved, 144 (2%) required minor modifications, while 351 (5%) required major modifications. Major modification included changes in: selected RT dose (96/351, 27%), target volume definition (127/351, 36%), organs-at-risk contouring (10/351, 3%), dose volume objectives/constraints criteria (90/351, 26%), and intent of treatment (28/351, 8%). The RT plans which required major modification according to the tumor subtype were as follows: head and neck (104/904, 12%), thoracic (12/199, 6%), gastrointestinal (33/687,5%), skin (5/106, 5%), genitourinary (16/359, 4%), breast (104/2387, 4%), central nervous system (36/846, 4%), sarcoma (11/277, 4%), pediatric (7/251, 3%), lymphoma (10/423, 2%), gynecological tumors (2/359, 1%), and others (11/351, 3%). Conclusion: Multi-disciplinary standardized QA chart rounds provide a comprehensive and an influential method on RT plans and/or treatment decisions.
Influence of physical factors on tablet splitting, weight and content uniformity of atenolol tablets
Abdel Naser Zaid,Rowa’ Al-Ramahi,Abeer Abu Ghoush,Numan Malkieh,Maher Kharoaf 한국약제학회 2012 Journal of Pharmaceutical Investigation Vol.42 No.5
Tablet splitting is widely practiced worldwide. Several studies have considered weight variation of split tablets as a mean of estimating drug content uniformity but the analysis of their drug content and physical factors that may affect splitting are limited. The aim of this study is to evaluate the impact of manufacturing parameters and splitting on content and weight uniformity of atenolol tablets. Atenolol tablets (100 and 50 mg) were prepared under the same manufacturing conditions and using the same excipients. The obtained tablets were checked for hardness, weight, and disintegration. The weight and the content of the two strength atenolol tablets after splitting into two halves were evaluated. Atenolol tablets (100 mg)showed higher values of hardness, disintegration time and diameter than atenolol tablets (50 mg). Atenolol tablets (100 mg) passed both weight and content uniformity while atenolol tablets (50 mg) failed these tests. Half tablet weight appears to be directly correlated with its drug content. Manufacturers should investigate physical factors such as tablet hardness, diameter, and disintegration time that may play an important role in achieving both weight and content uniformity in the resultant tablet halves.
Fawzi J. Abuhijla, MD, MSc,Abdelatif M. Al-Mousa,Issa A. Mohamad,Ramiz A. Abuhijlih,Sondos A. Al-Khatib,Anoud Z. Alnsour,Wafa A. Asha,Shada W. Ramahi,Ali A. Hosni,Fawzi J. Abuhijla 대한방사선종양학회 2019 Radiation Oncology Journal Vol.37 No.1
Purpose: The quality assurance (QA) chart rounds are multidisciplinary meetings to review radiation therapy (RT) treatment plans. This study focus on describing the changes in RT management based on QA round reviews in a single institution. Materials and Methods: After 9 full years of implementation, a retrospective review of all patients whose charts passed through departmental QA chart rounds from 2007 to 2015. The reviewed cases were presented for RT plan review; subcategorized based on decision in QA rounds into: approved, minor modifications or major modifications. Major modification defined as any substantial change which required patient re-simulation or re-planning prior to commencement of RT. Minor modification included treatment plan changes which didn’t necessarily require RT re-planning. Results: Overall 7,149 RT treatment plans for different anatomical sites were reviewed at QA rounds. From these treatment plans, 6,654 (93%) were approved, 144 (2%) required minor modifications, while 351 (5%) required major modifications. Major modification included changes in: selected RT dose (96/351, 27%), target volume definition (127/351, 36%), organs-at-risk contouring (10/351, 3%), dose volume objectives/constraints criteria (90/351, 26%), and intent of treatment (28/351, 8%). The RT plans which required major modification according to the tumor subtype were as follows: head and neck (104/904, 12%), thoracic (12/199, 6%), gastrointestinal (33/687,5%), skin (5/106, 5%), genitourinary (16/359, 4%), breast (104/2387, 4%), central nervous system (36/846, 4%), sarcoma (11/277, 4%), pediatric (7/251, 3%), lymphoma (10/423, 2%), gynecological tumors (2/359, 1%), and others (11/351, 3%). Conclusion: Multi-disciplinary standardized QA chart rounds provide a comprehensive and an influential method on RT plans and/ or treatment decisions.