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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Iranian Journal of Biotechnology
- نوع مقاله: Journal Article
- کلمات کلیدی: Surface functionalization,Drug Delivery,Hydrogels ,Biomedical applications,Nanodiamonds
- چکیده:
- چکیده انگلیسی: Context: The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Evidence Acquisition: Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, non-toxicity, photostability and facile surface functionalization properties. Results: There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. Conclusions: NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustained-release.
- انتشار مقاله: 28-05-1394
- نویسندگان: Shakeel Ahmed Ansari,Rukhsana Satar,Mohammad Alam Jafri,Mahmood Rasool,Waseem Ahmad,Syed Kashif Zaidi
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Chronic myeloid leukemia,tyrosine kinase inhibitors,Nilotinib,BCR-ABL Mutation
- چکیده:
- چکیده انگلیسی: Objective: BCR-ABL fusion oncogene is the hallmark of chronic myeloid leukemia (CML), causing genomic instability which leads to accumulation of mutations in BCR-ABL as well as other genes. BCR-ABL mutations are the cause of tyrosine kinase inhibitors (TKIs) resistance in CML. Recently, compound BCR-ABL mutations have been reported to resist all FDA approved TKIs. Therefore, finding novel compound BCR-ABL mutations can help and clinically manage CML. Therefore, our objective was to find out novel drug-resistant compound BCR-ABL mutations in CML and carry out their protein modelling studies. Methodology: Peripheral blood samples were collected from ten imatinib resistant CML patients receiving nilotinib treatment. BCR-ABL transcript mutations were investigated by employing capillary sequencing. Patient follow-up was carried out using European LeukemiaNet guidelines. Protein modeling studies were carried out for new compound mutations using PyMol to see the effects of mutations at structural level. Results: A novel compound mutation (K245N mutation along with G250W mutation) and previously known T351I utation was detected in two of the nilotinib resistance CML patients respectively while in the rest of 8 nilotinib responders, no resistant mutations were detected. Protein modelling studies indicated changes in BCR-ABL mutant protein which may have negatively impacted its binding with nilotinib leading to drug resistance. Conclusion: We report a novel nilotinib resistant BCR-ABL compound mutation (K245N along with G250W mutation) which impacts structural modification in BCR-ABL mutant protein leading to drug resistance. As compound mutations pose a new threat by causing resistance to all FDA approved tyrosine kinase inhibitors in BCR-ABL+ leukemias, our study opens a new direction for in vitro characterization of novel BCR-ABL compound mutations and their resistant to second generation and third generation TKIs.
- انتشار مقاله: 05-03-1399
- نویسندگان: Zafar Iqbal,Muhammad Absar,Amer Mahmood,Aamer Aleem,Mudassar Iqbal,Abid Jameel,Tanveer Akhtar,Sajjad Karim,Mahmood Rasool,Zeenat Mirza,Muhammad Khalid,Afia Muhammad Akram,Muhammad Farooq Sabar,Ahmad M Khalid,Khalid Aljarrah,Janhangir Iqbal,Muhammad Khalid,Ijaz H Shah,Nawaf Alanazi
- مشاهده