83 results on '"Anjum, Sohail"'
Search Results
2. Urbanization, informal economy, and ecological footprint quality in South Asia
- Author
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Qayyum, Unbreen, Sabir, Samina, and Anjum, Sohail
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- 2021
- Full Text
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3. Expression and subcellular localization of Discoidin Domain Receptor 1 (DDR1) define prostate cancer aggressiveness
- Author
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R. Daniel Bonfil, Wei Chen, Semir Vranic, Anjum Sohail, Dongping Shi, Hyejeong Jang, Hyeong-Reh Kim, Marco Prunotto, and Rafael Fridman
- Subjects
DDR1 ,Prostate cancer ,Receptor tyrosine kinases ,Immunohistochemistry ,Prognostic markers ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Background The Discoidin Domain Receptor 1 (DDR1) is one of the two members of a unique family of receptor tyrosine kinase receptors that signal in response to collagen, which has been implicated in cancer progression. Here, we examined the expression of DDR1 in prostate cancer (PCa), and assessed its potential value as a prognostic marker, as a function of grade, stage and other clinicopathologic parameters. Methods We investigated the association between the expression level and subcellular localization of DDR1 protein and PCa aggressiveness by immunohistochemistry, using tissue microarrays (TMAs) encompassing 200 cases of PCa with various Gleason scores (GS) and pathologic stages with matched normal tissue, and a highly specific monoclonal antibody. Results DDR1 was found to be localized in the membrane, cytoplasm, and nuclear compartments of both normal and cancerous prostate epithelial cells. Analyses of DDR1 expression in low GS (≤ 7[3 + 4]) vs high GS (≥ 7[4 + 3]) tissues showed no differences in nuclear or cytoplasmic DDR1in either cancerous or adjacent normal tissue cores. However, relative to normal-matched tissue, the percentage of cases with higher membranous DDR1 expression was significantly lower in high vs. low GS cancers. Although nuclear localization of DDR1 was consistently detected in our tissue samples and also in cultured human PCa and normal prostate-derived cell lines, its presence in that site could not be associated with disease aggressiveness. No associations between DDR1 expression and overall survival or biochemical recurrence were found in this cohort of patients. Conclusion The data obtained through multivariate logistic regression model analysis suggest that the level of membranous DDR1 expression status may represent a potential biomarker of utility for better determination of PCa aggressiveness.
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- 2021
- Full Text
- View/download PDF
4. Armed conflict, militarization and ecological footprint: Empirical evidence from South Asia
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Qayyum, Unbreen, Anjum, Sohail, and Samina Sabir
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- 2021
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5. Analysis of efficacy of metformin in pregnant women with Polycystic Ovarian Syndrome (PCOS).
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Anjum, Sohail, Malik, Sarah Hafeez, Nadeem, Nighat, and Sulehria, Sohail Bashir
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GESTATIONAL diabetes , *PREGNANT women , *METFORMIN , *POLYCYSTIC ovary syndrome , *EXPERIMENTAL design - Abstract
Objective: To analyze of efficacy of metformin in pregnant women with POCS regarding occurrence of gestational diabetes mellitus. To analyze parity distribution for efficacy of metformin regarding occurrence of gestational diabetes mellitus in pregnant women with POCS. Study Design: Descriptive Cases Series. Setting: Sheikh Zaid Hospital, Lahore. Period: July 1, 2019 to December 31, 2019. Methods: Till delivery 200 pregnant ladies were followed up to see if they developed GDM or not. A pre-prepared form was used to record metformin efficacy frequency and GDM in pregnant ladies with PCOS. For efficacy and parity (qualitative variables), percentages and frequencies were got calculated using SPSS.16. Results: Thirty two (16%) women got '0' parity. Forty four (22%) got '1'parity. Fifty (25%) got '2' parity. Forty two (21%) got '3'parity.While thirty two women (16%) got '4' parity. Twenty two (78.57%) was efficacy for nulliparous patients. Thirty three (76.74%) was efficacy for primiparous patients. One hundred nine (84.50%) was efficacy for multiparous patients. Insignificant difference was noted as p was more than 0.05. In one hundred sixty six (83%) women metformin efficacy got achieved. Conclusion: Multiparous patients with PCOS showed relatively more efficacy (84.50%) of metformin against gestational diabetes mellitus while twenty five percent pregnant women with PCOS with a thorough use of metformin delivered two live neonates. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Organic acids in poultry industry: a review of nutritional advancements and health benefits
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Du, Hongxu, primary, Sarwar, Imran, additional, Ahmad, Sajjad, additional, Suheryani, Imran, additional, Anjum, Sohail, additional, Andlib, Shaista, additional, Kakar, Mohib Ullah, additional, and Arain, Muhammad Asif, additional
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- 2023
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7. Religion and economic development: new insights
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Qayyum, Unbreen, Anjum, Sohail, and Sabir, Samina
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- 2020
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8. Organic acids in poultry industry: a review of nutritional advancements and health benefits.
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Du, Hongxu, Sarwar, Imran, Ahmad, Sajjad, Suheryani, Imran, Anjum, Sohail, Andlib, Shaista, Kakar, Mohib Ullah, and Arain, Muhammad Asif
- Abstract
The discovery of antibiotics has been one of the greatest milestones in the field of medical science that has played a pivotal role in advancing the progress and performance of the livestock and poultry sector. Antibiotics have been used in poultry diets at sub-therapeutic doses for growth promotion and at therapeutic levels for disease treatment. Inappropriate and indiscriminate use of antimicrobials leads to antibiotic resistance and transmission of resistant genes either directly or through bacteria from animal feed, or the environment. In fact, numerous feed supplements have been proposed over the years as antibiotic alternatives, to improve the health status, welfare and productive performance of poultry birds. However, organic acids (OA) have emerged as a potential antibiotic replacement due to their antimicrobial nature. Although, OA are abundant in nature as conventional components of animal and plant tissues, whereas, few of them are produced by microbial fermentation in the hindgut of animals. Interestingly, supplementation of several types of OA such as formic acid, lactic acid, fumaric acid, butyric acid, citric acid and tartaric acid have been shown to significantly improve the health status and production performance of poultry birds. At the same time, OA have also been investigated for their multiple therapeutic effects on pathological disorders, as antimicrobial, antifungal, antiprotozoal, and anticoccidial agents. In addition, OA provide protection by improving the immune system, physiology and morphology of the gastrointestinal tract (GIT). The prime objective of the present review is to highlight the therapeutic potential and beneficial uses of OA as an alternative to antibiotics in the poultry industry. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Discoidin domain receptor 1 activation links extracellular matrix to podocyte lipotoxicity in Alport syndrome
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Jin-Ju Kim, Judith M. David, Sydney S. Wilbon, Javier V. Santos, Devang M. Patel, Anis Ahmad, Alla Mitrofanova, Xiaochen Liu, Shamroop K. Mallela, Gloria M. Ducasa, Mengyuan Ge, Alexis J. Sloan, Hassan Al-Ali, Marcia Boulina, Armando J. Mendez, Gabriel N. Contreras, Marco Prunotto, Anjum Sohail, Rafael Fridman, Jeffrey H. Miner, Sandra Merscher, and Alessia Fornoni
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Alport syndrome ,Discoidin domain receptor ,Podocyte lipotoxicity ,Glomerular basement membrane ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that is activated by collagens that is involved in the pathogenesis of fibrotic disorders. Interestingly, de novo production of the collagen type I (Col I) has been observed in Col4a3 knockout mice, a mouse model of Alport Syndrome (AS mice). Deletion of the DDR1 in AS mice was shown to improve survival and renal function. However, the mechanisms driving DDR1-dependent fibrosis remain largely unknown. Methods: Podocyte pDDR1 levels, Collagen and cluster of differentiation 36 (CD36) expression was analyzed by Real-time PCR and Western blot. Lipid droplet accumulation and content was determined using Bodipy staining and enzymatic analysis. CD36 and DDR1 interaction was determined by co-immunoprecipitation. Creatinine, BUN, albuminuria, lipid content, and histological and morphological assessment of kidneys harvested from AS mice treated with Ezetimibe and/or Ramipril or vehicle was performed. Findings: We demonstrate that Col I-mediated DDR1 activation induces CD36-mediated podocyte lipotoxic injury. We show that Ezetimibe interferes with the CD36/DDR1 interaction in vitro and prevents lipotoxicity in AS mice thus preserving renal function similarly to ramipril. Interpretation: Our study suggests that Col I/DDR1-mediated lipotoxicity contributes to renal failure in AS and that targeting this pathway may represent a new therapeutic strategy for patients with AS and with chronic kidney diseases (CKD) associated with Col4 mutations. Funding: This study is supported by the NIH grants R01DK117599, R01DK104753, R01CA227493, U54DK083912, UM1DK100846, U01DK116101, UL1TR000460 (Miami Clinical Translational Science Institute, National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities), F32DK115109, Hoffmann-La Roche and Alport Syndrome Foundation.
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- 2021
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10. Discoidin Domain Receptors in Melanoma: Potential Therapeutic Targets to Overcome MAPK Inhibitor Resistance
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Coralie Reger de Moura, Marco Prunotto, Anjum Sohail, Maxime Battistella, Fanelie Jouenne, Daniel Marbach, Celeste Lebbé, Rafael Fridman, and Samia Mourah
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DDR1 ,melanoma ,drug resistance ,MAPK inhibitors ,therapeutic target ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Melanoma is a highly malignant skin cancer with high propensity to metastasize and develop drug resistance, making it a difficult cancer to treat. Current therapies targeting BRAF (V600) mutations are initially effective, but eventually tumors overcome drug sensitivity and reoccur. This process is accomplished in part by reactivating alternate signaling networks that reinstate melanoma proliferative and survival capacity, mostly through reprogramming of receptor tyrosine kinase (RTK) signaling. Evidence indicates that the discoidin domain receptors (DDRs), a set of RTKs that signal in response to collagen, are part of the kinome network that confer drug resistance. We previously reported that DDR1 is expressed in melanomas, where it can promote tumor malignancy in mouse models of melanoma, and thus, DDR1 could be a promising target to overcome drug resistance. In this review, we summarize the current knowledge on DDRs in melanoma and their implication for therapy, with emphasis in resistance to MAPK inhibitors.
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- 2020
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11. Estimating the effect of technological innovations on environmental degradation: empirical evidence from selected ASEAN and SAARC countries.
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Kiani, Taimoor Arif, Sabir, Samina, Qayyum, Unbreen, and Anjum, Sohail
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ENVIRONMENTAL degradation ,TECHNOLOGICAL innovations ,CLEAN energy investment ,EVIDENCE gaps ,ECOLOGICAL impact ,KUZNETS curve - Abstract
Over the last few decades, both South and Southeast Asian regions have witnessed noteworthy economic development but unfortunately could not manage to mitigate the looming threat of climate change. Several initiatives have been taken recently to achieve sustainable development goals via technological innovations and the adoption of renewable energy. Given this milieu, it becomes pertinent to examine how technological innovations have assisted the South Asian Association of Regional Cooperation and Association of Southeast Asian Nations to combat environmental challenges. To address the research gap, this study investigated the impact of technological innovations on environmental degradation for selected countries from 1991 to 2018. Due to the presence of cross-sectional dependence, we have applied the second generational panel unit root test and after the confirmation of long-run cointegration, the panel autoregressive distributed lag models based on the mean group, pool mean group, and augmented mean group techniques have been used to calculate the long and short-run estimates. The results indicate that technological innovations have a negative and significant impact on the ecological footprint in the long run but are insignificant in the short run for both South and Southeast Asian countries. The study also confirms the existence of the environmental Kuznets curve hypothesis in both regions. Based on findings, it is recommended for countries in these regions to pay serious attention to the adoption of cleaner technology and to increase investment in research and development activities geared at enhancing renewable energy consumption for the sustainability of the environment. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Discoidin Domain Receptor 1 (DDR1) Is Necessary for Tissue Homeostasis in Pancreatic Injury and Pathogenesis of Pancreatic Ductal Adenocarcinoma
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Anjum Sohail, Yaqing Zhang, Daniel Long, Jeanine M. Ruggeri, Janusz Franco-Barraza, Marina Pasca di Magliano, Rafael Fridman, Edna Cukierman, and Howard C. Crawford
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0301 basic medicine ,Acinar Cells ,Article ,Pathology and Forensic Medicine ,Collagen receptor ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Discoidin Domain Receptor 1 ,Cell Line, Tumor ,medicine ,Acinar cell ,Animals ,Homeostasis ,Humans ,Pancreas ,Tissue homeostasis ,Cell Proliferation ,Mice, Knockout ,DDR1 ,Chemistry ,medicine.disease ,Pancreatic Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,Tumor progression ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Pancreatitis ,Discoidin domain ,Carcinoma, Pancreatic Ductal ,Signal Transduction - Abstract
Pancreatic ductal adenocarcinoma (PDA) and chronic pancreatitis are characterized by a dense collagen-rich desmoplastic reaction. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagens that can regulate cell proliferation, migration, adhesion, and remodeling of the extracellular matrix. To address the role of DDR1 in PDA, Ddr1-null (Ddr-/-) mice were crossed with the KrasG12D/+; Trp53R172H/+; Ptf1aCre/+ (KPC) model of metastatic PDA. Ddr1-/-; KPC mice progress to differentiated PDA but resist progression to poorly differentiated cancer compared with KPC control mice. Strikingly, severe pancreatic atrophy accompanied tumor progression in Ddr1-/-; KPC mice. To further explore the effects of Ddr1 ablation, Ddr1-/- mice were crossed with the KrasG12D/+; Ptf1aCre/+ neoplasia model and subjected to cerulein-induced experimental pancreatitis. Similar to KPC mice, tissue atrophy was a hallmark of both neoplasia and pancreatitis models in the absence of Ddr1. Compared with controls, Ddr1-/- models had increased acinar cell dropout and reduced proliferation with no difference in apoptotic cell death between control and Ddr1-/- animals. In most models, organ atrophy was accompanied by increased fibrillar collagen deposition, suggesting a compensatory response in the absence of this collagen receptor. Overall, these data suggest that DDR1 regulates tissue homeostasis in the neoplastic and injured pancreas.
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- 2020
13. Expression and subcellular localization of Discoidin Domain Receptor 1 (DDR1) define prostate cancer aggressiveness
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Semir Vranic, Dongping Shi, Hyeong Reh Choi Kim, Wei Chen, Anjum Sohail, Rafael Fridman, Marco Prunotto, R. Daniel Bonfil, and Hyejeong Jang
- Subjects
Cancer Research ,Prostate Cancer Aggressiveness ,Receptor tyrosine kinase ,Prognostic markers ,Prostate cancer ,Receptor tyrosine kinases ,Genetics ,medicine ,DDR1 ,Receptor ,RC254-282 ,QH573-671 ,biology ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Subcellular localization ,Immunohistochemistry ,Biorepository ,Oncology ,Cancer research ,biology.protein ,Cytology ,Primary Research ,business ,Discoidin domain - Abstract
Background The Discoidin Domain Receptor 1 (DDR1) is one of the two members of a unique family of receptor tyrosine kinase receptors that signal in response to collagen, which has been implicated in cancer progression. Here, we examined the expression of DDR1 in prostate cancer (PCa), and assessed its potential value as a prognostic marker, as a function of grade, stage and other clinicopathologic parameters. Methods We investigated the association between the expression level and subcellular localization of DDR1 protein and PCa aggressiveness by immunohistochemistry, using tissue microarrays (TMAs) encompassing 200 cases of PCa with various Gleason scores (GS) and pathologic stages with matched normal tissue, and a highly specific monoclonal antibody. Results DDR1 was found to be localized in the membrane, cytoplasm, and nuclear compartments of both normal and cancerous prostate epithelial cells. Analyses of DDR1 expression in low GS (≤ 7[3 + 4]) vs high GS (≥ 7[4 + 3]) tissues showed no differences in nuclear or cytoplasmic DDR1in either cancerous or adjacent normal tissue cores. However, relative to normal-matched tissue, the percentage of cases with higher membranous DDR1 expression was significantly lower in high vs. low GS cancers. Although nuclear localization of DDR1 was consistently detected in our tissue samples and also in cultured human PCa and normal prostate-derived cell lines, its presence in that site could not be associated with disease aggressiveness. No associations between DDR1 expression and overall survival or biochemical recurrence were found in this cohort of patients. Conclusion The data obtained through multivariate logistic regression model analysis suggest that the level of membranous DDR1 expression status may represent a potential biomarker of utility for better determination of PCa aggressiveness.
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- 2021
14. Clustering, Spatial Distribution, and Phosphorylation of Discoidin Domain Receptors 1 and 2 in Response to Soluble Collagen I
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David A. Yeung, Ramesh K. Ganju, Carolyn Wang, Brent A. Weiss, Subhadip Das, Anjum Sohail, Andrew B. Herr, Nirvan Shanker, Jeanette L.C. Miller, Jack Wellmerling, Gunjan Agarwal, and Rafael Fridman
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macromolecular substances ,Collagen Type I ,Article ,Receptor tyrosine kinase ,Cell Line ,Tyrosine Phosphorylation Site ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Discoidin Domain Receptor 2 ,0302 clinical medicine ,Discoidin Domain Receptor 1 ,Structural Biology ,Animals ,Cluster Analysis ,Humans ,Phosphorylation ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,DDR1 ,Binding Sites ,biology ,Cell Membrane ,Receptor Protein-Tyrosine Kinases ,Tyrosine phosphorylation ,Fibrillogenesis ,3T3 Cells ,Recombinant Proteins ,Extracellular Matrix ,HEK293 Cells ,chemistry ,biology.protein ,Biophysics ,Tyrosine ,Receptor clustering ,030217 neurology & neurosurgery ,Discoidin domain ,Protein Binding ,Signal Transduction - Abstract
Discoidin domain receptors (DDR1 and DDR2) are receptor tyrosine kinases that signal in response to collagen. We had previously shown that collagen binding leads to clustering of DDR1b, a process partly mediated by its extracellular domain (ECD). In this study, we investigated (i) the impact of the oligomeric state of DDR2 ECD on collagen binding and fibrillogenesis, (ii) the effect of collagen binding on DDR2 clustering, and (iii) the spatial distribution and phosphorylation status of DDR1b and DDR2 after collagen stimulation. Studies were conducted using purified recombinant DDR2 ECD proteins in monomeric, dimeric or oligomeric state, and MC3T3-E1 cells expressing full-length DDR2-GFP or DDR1b-YFP. We show that the oligomeric form of DDR2 ECD displayed enhanced binding to collagen and inhibition of fibrillogenesis. Using atomic force and fluorescence microscopy, we demonstrate that unlike DDR1b, DDR2 ECD and DDR2-GFP do not undergo collagen-induced receptor clustering. However, after prolonged collagen stimulation, both DDR1b-YFP and DDR2-GFP formed filamentous structures consistent with spatial re-distribution of DDRs in cells. Immunocytochemistry revealed that while DDR1b clusters co-localized with non-fibrillar collagen, DDR1b/DDR2 filamentous structures associated with collagen fibrils. Antibodies against a tyrosine phosphorylation site in the intracellular juxtamembrane region of DDR1b displayed positive signals in both DDR1b clusters and filamentous structures. However, only the filamentous structures of both DDR1b and DDR2 co-localized with antibodies directed against tyrosine phosphorylation sites within the receptor kinase domain. Our results uncover key differences and similarities in the clustering abilities and spatial distribution of DDR1b and DDR2 and their impact on receptor phosphorylation.
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- 2019
15. Ecology of House Crow (Corvus splendens) in Dir Lower, Khyber Pakhtunkhwa, Pakistan
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Anjum, Sohail, primary
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- 2021
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16. Cardiac autonomic neuropathy in children and adolescents with Type 1 diabetes mellitus: Prevalence and relation to duration and control of diabetes.
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Khan, Waqas Imran, primary, Arshad, Muhammad Sohail, additional, Anjum, Sidra, additional, and Anjum, Sohail, additional
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- 2020
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17. Ecology of House Crow (Corvus splendens) in Dir Lower, Khyber Pakhtunkhwa, Pakistan.
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Anjum, Sohail, Ahmad, Awais, Bibi, Farzana, and Ali, Hazrat
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House crow (Corvus splendens) is a native species of the Indian subcontinent. It shows greater tractability as it can easily adapt to new environment where food supply and garbage are found in abundance. Their intelligence is also acknowledged duly. They are also obligate to human presence. We can assume that “where there is human, there is house crow essentially”. The present article documents the ecology of this bird in Dir Lower, Khyber Pakhtunkhwa, Pakistan. The house crow population has reached a considerable size in the study area. The species has colonized both rural and urban areas and has dispersed throughout the study area. One of the most important factors for its population increase is the increased number of dumping sites in the area. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Road kills of vertebrate fauna in Dir Lower, Khyber Pakhtunkhwa, Pakistan
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Anjum, Sohail, primary, Ali, Hazrat, additional, Ahmad, Awais, additional, and Bibi, Farzana, additional
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- 2019
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19. Discoidin domain receptors: A promising target in melanoma
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Céleste Lebbé, Cécile Pagès, Fanélie Jouenne, Marie-Pierre Podgorniak, Samia Mourah, Coralie Reger de Moura, Sarra Mazouz Dorval, Maxime Battistella, Jean Paul Feugeas, Anjum Sohail, Suzanne Menashi, Anne Caudron, O. Marco, and Rafael Fridman
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0301 basic medicine ,medicine.drug_class ,Mice, Nude ,Apoptosis ,Dermatology ,General Biochemistry, Genetics and Molecular Biology ,Tyrosine-kinase inhibitor ,Receptor tyrosine kinase ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Discoidin Domain Receptor 1 ,Downregulation and upregulation ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Melanoma ,neoplasms ,Cell Proliferation ,Skin ,DDR1 ,biology ,Cancer ,Prognosis ,medicine.disease ,Xenograft Model Antitumor Assays ,Survival Rate ,030104 developmental biology ,Oncology ,Tumor progression ,Case-Control Studies ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Female ,Discoidin domain - Abstract
The discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase family that signals in response to collagen and that has been implicated in cancer progression. In the present study, we investigated the expression and role of DDR1 in human melanoma progression. Immunohistochemical staining of human melanoma specimens (n = 52) shows high DDR1 expression in melanoma lesions that correlates with poor prognosis. DDR1 expression was associated with the clinical characteristics of Clark level and ulceration and with BRAF mutations. Downregulation of DDR1 by small interfering RNA (siRNA) in vitro inhibited melanoma cells malignant properties, migration, invasion, and survival in several human melanoma cell lines. A DDR tyrosine kinase inhibitor (DDR1-IN-1) significantly inhibited melanoma cell proliferation in vitro, and ex vivo and in tumor xenografts, underlining the promising potential of DDR1 inhibition in melanoma.
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- 2019
20. Discoidin Domain Receptors, DDR1b and DDR2, Promote Tumour Growth within Collagen but DDR1b Suppresses Experimental Lung Metastasis in HT1080 Xenografts
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Seongho Kim, Mohamad Bouhamdan, Allen Saliganan, R. Daniel Bonfil, Anjum Sohail, Hyeong Reh Choi Kim, Rafael Fridman, Benjamin D. Wasinski, Marco Prunotto, and Lisa Polin
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Cancer microenvironment ,Lung Neoplasms ,Fibrillar Collagens ,Fibrosarcoma ,lcsh:Medicine ,Mice, Nude ,Stimulation ,Apoptosis ,Receptor tyrosine kinase ,Collagen Type I ,Article ,Mice ,Discoidin Domain Receptor 2 ,Stroma ,Discoidin Domain Receptor 1 ,medicine ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Animals ,Humans ,Phosphorylation ,lcsh:Science ,Receptor ,Cell Proliferation ,Hippo signaling pathway ,Multidisciplinary ,biology ,Chemistry ,lcsh:R ,medicine.disease ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,Cancer research ,biology.protein ,lcsh:Q ,HT1080 ,Female ,Discoidin domain ,Cell signalling - Abstract
The Discoidin Domain Receptors (DDRs) constitute a unique set of receptor tyrosine kinases that signal in response to collagen. Using an inducible expression system in human HT1080 fibrosarcoma cells, we investigated the role of DDR1b and DDR2 on primary tumour growth and experimental lung metastases. Neither DDR1b nor DDR2 expression altered tumour growth at the primary site. However, implantation of DDR1b- or DDR2-expressing HT1080 cells with collagen I significantly accelerated tumour growth rate, an effect that could not be observed with collagen I in the absence of DDR induction. Interestingly, DDR1b, but not DDR2, completely hindered the ability of HT1080 cells to form lung colonies after intravenous inoculation, suggesting a differential role for DDR1b in primary tumour growth and lung colonization. Analyses of tumour extracts revealed specific alterations in Hippo pathway core components, as a function of DDR and collagen expression, that were associated with stimulation of tumour growth by DDRs and collagen I. Collectively, these findings identified divergent effects of DDRs on primary tumour growth and experimental lung metastasis in the HT1080 xenograft model and highlight the critical role of fibrillar collagen and DDRs in supporting the growth of tumours thriving within a collagen-rich stroma.
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- 2019
21. Design and Analysis of a Novel Patch Antenna Array for 5G and Millimeter Wave Applications
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Anjum Sohail, Jamal Abdul Nasir, Hamid Khan, Usman Ali Khan, Nasir Saleem, and Muhammad Irfan Khattak
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Physics ,Optics ,business.industry ,K band ,Planar array ,Extremely high frequency ,Bandwidth (signal processing) ,Return loss ,Ka band ,business ,V band ,Antenna efficiency - Abstract
Multiband high gain antennas are the essence of future wireless communication networks. This paper presents a detailed investigation and design of 1×4 linear and 2×2 planar array antennas. Arrays are designed using Rogers RT/duroid5880 (lossy) substrate. Thickness, dielectric constant and tangent loss of the substrate are 0.508 mm, 2.2 and 0.0013 respectively. Both arrays are multiband antennas and have resonance frequencies in K band, Ka band and V band. The maximum and minimum gains of 14.22dB and 9.9dB are achieved at 44.8 GHz and 67.8 GHz using linear array. The highest gain of planar antenna is 12.34dB at 29GHz and lowest gain of 8.5 dB is obtained at 38GHz. Radiation efficiency of both antennas are in the range of 90% at all the resonance frequencies. Results of both arrays show that array with linear setup have better gain than array of planar setup whereas bandwidth and return loss of planar array is better than linear array.
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- 2019
22. Live cell measurements of interaction forces and binding kinetics between Discoidin Domain Receptor 1 (DDR1) and collagen I with atomic force microscopy
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Peter M. Hoffmann, Anwesha Sarkar, Kazuhiko Shinki, Jiayin Dong, Marco Prunotto, Anjum Sohail, and Rafael Fridman
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0301 basic medicine ,Cell type ,Integrin ,Biophysics ,Microscopy, Atomic Force ,Biochemistry ,Receptor tyrosine kinase ,Collagen Type I ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Discoidin Domain Receptor 1 ,Cell surface receptor ,Humans ,Receptor ,Molecular Biology ,DDR1 ,biology ,Chemistry ,Receptor–ligand kinetics ,Kinetics ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Discoidin domain - Abstract
Background Discoidin Domain Receptors (DDRs) are membrane-tethered proteins of the receptor tyrosine kinase family, which signal in response to collagen. DDR expression is associated with human diseases, including fibrosis and cancer. The role of DDRs in human pathogenesis is mediated by dysregulated receptor function in response to the collagenous milieu. Thus, understanding DDR-collagen interactions is important for developing novel therapeutic strategies against DDRs. Methods We developed a biophysical method to isolate and measure specific interactions between DDR1 and collagen in live cells at the single molecule level using atomic force microscopy. This new method is capable of providing density and kinetics of membrane receptors in live cells. Results We isolated DDR1-collagen interactions and quantified the association and dissociation rates of the DDR1-collagen I complex. We estimated separate binding probabilities of collagen I to DDR and integrin, and by combining kinetic and binding probability data, we were able to estimate the density of receptors in two cancer cell types. We also tested the viability of a DDR1 blocking antibody and determined its efficacy in suppressing DDR1-collagen binding. Conclusions The new method shows promise in quantifying receptor-ligand kinetics and receptor density on live cells. General significance The new approach is applicable to other receptor-ligand systems and allows the determination of critical parameters at the single cell/single molecule level – in particular, the direct determination of kinetic and density differences of receptors in different cell types. This capability should prove to be useful in cancer research and drug design.
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- 2018
23. Religion and economic development: new insights
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Qayyum, Unbreen, primary, Anjum, Sohail, additional, and Sabir, Samina, additional
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- 2019
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24. SCIENTIFIC RESEARCH
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Anjum, Sohail, primary and Mahboob, Usman, primary
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- 2018
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25. Challenges faced by marginalized communities such as transgenders in Pakistan
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Usman, Hassan Bin, primary, Rashid, Farah, additional, Atif, Iffat, additional, Hydrie, Muhammad Zafar, additional, Bin, Muhammad Waleed, additional, Muzaffar, Hafiz Zeeshan, additional, Rehman, Abdul, additional, Anjum, Sohail, additional, Mehroz, Muhammad Bin, additional, Haider, Ali, additional, Hassan, Ahmed, additional, and Shukar, Hassaan, additional
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- 2018
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26. Shedding of Discoidin Domain Receptor 1 by Membrane-type Matrix Metalloproteinases
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M. Margarida Bernardo, Kiran V. Mahasenan, Malika Kumarasiri, Rafael Fridman, Gregg B. Fields, Benjamin D. Wasinski, Hsueh Liang Fu, Rajeshwari R. Valiathan, Anjum Sohail, Shahriar Mobashery, Dorota Tokmina-Roszyk, Fu, Hsueh-Liang, Sohail, Anjum, Valiathan, Rajeshwari R, Wasinski, Benjamin D, Kumarasiri, Malika, Mahasenan, Kiran V, Bernardo, Margarida M, Tokmina-Roszyk, Dorota, Fields, Gregg B, Mobashery, Shahriar, and Fridman, Raphael
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collagen ,Amino Acid Motifs ,Receptor Protein-Tyrosine Kinases ,cell surface receptor ,Biology ,Biochemistry ,Receptor tyrosine kinase ,shedding ,Discoidin Domain Receptor 1 ,Cell surface receptor ,Cell Line, Tumor ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Collagenases ,Discoidin Domain Receptors ,Molecular Biology ,Matrix Metalloproteinase (MMP) ,DDR1 ,Cell Biology ,proteolytic enzymes ,Molecular biology ,Extracellular Matrix ,Protein Structure, Tertiary ,COS Cells ,Proteolysis ,Enzymology ,Collagenase ,biology.protein ,Female ,Discoidin domain-containing receptor 2 ,Signal transduction ,Discoidin domain ,medicine.drug - Abstract
The discoidin domain receptors (DDRs) are receptor tyrosine kinases that upon binding to collagens undergo receptor phosphorylation, which in turn activates signal transduction pathways that regulate cell-collagen interactions. We report here that collagen-dependent DDR1 activation is partly regulated by the proteolytic activity of the membrane-anchored collagenases, MT1-, MT2-, and MT3-matrix metalloproteinase (MMP). These collagenases cleave DDR1 and attenuate collagen I- and IV-induced receptor phosphorylation. This effect is not due to ligand degradation, as it proceeds even when the receptor is stimulated with collagenase-resistant collagen I (r/r) or with a triple-helical peptide harboring the DDR recognition motif in collagens. Moreover, the secreted collagenases MMP-1 and MMP-13 and the glycosylphosphatidylinositol-anchored membrane-type MMPs (MT4- and MT6-MMP) have no effect on DDR1 cleavage or activation. N-terminal sequencing of the MT1-MMP-mediated cleaved products and mutational analyses show that cleavage of DDR1 takes place within the extracellular juxtamembrane region, generating a membrane-anchored C-terminal fragment. Metalloproteinase inhibitor studies show that constitutive shedding of endogenous DDR1 in breast cancer HCC1806 cells is partly mediated by MT1-MMP, which also regulates collagen-induced receptor activation. Taken together, these data suggest a role for the collagenase of membrane-type MMPs in regulation of DDR1 cleavage and activation at the cell-matrix interface. Refereed/Peer-reviewed
- Published
- 2013
27. Posttranslational regulation of membrane type 1-matrix metalloproteinase (MT1-MMP) in mouse PTEN null prostate cancer cells: Enhanced surface expression and differential O-glycosylation of MT1-MMP
- Author
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Emilio P. Mottillo, Rafael Fridman, Yoon Ah Ham, Hyeong Reh Choi Kim, Anjum Sohail, Shihua Wang, Chong Jai Kim, Seaho Kim, Yong Q. Chen, Guri Tzivion, M. Katie Conley-LaComb, and Wei Huang
- Subjects
Male ,PTEN ,Glycosylation ,Cell ,Mice ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Cell Movement ,Tensin ,Mice, Knockout ,Enzyme Precursors ,0303 health sciences ,Prostate cancer ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,medicine.anatomical_structure ,Gelatinases ,030220 oncology & carcinogenesis ,Signal Transduction ,Genotype ,Immunoblotting ,Article ,03 medical and health sciences ,Cell Line, Tumor ,Matrix Metalloproteinase 14 ,medicine ,Animals ,Humans ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,Sirolimus ,Akt/PKB signaling pathway ,Gene Expression Profiling ,Cell Membrane ,PTEN Phosphohydrolase ,Prostatic Neoplasms ,Epithelial Cells ,Cell Biology ,Molecular biology ,Enzyme Activation ,Matrix metalloproteinases ,Cell culture ,Cancer cell ,biology.protein ,Cancer research ,Posttranslational modification ,Protein Processing, Post-Translational ,Proto-Oncogene Proteins c-akt - Abstract
Membrane type 1 (MT1)-matrix metalloproteinase (MT1-MMP) is a membrane-tethered MMP that has been shown to play a key role in promoting cancer cell invasion. MT1-MMP is highly expressed in bone metastasis of prostate cancer (PC) patients and promotes intraosseous tumor growth of PC cells in mice. The majority of metastatic prostate cancers harbor loss-of-function mutations or deletions of the tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome ten). However, the role of PTEN inactivation in MT1-MMP expression in PC cells has not been examined. In this study, prostate epithelial cell lines derived from mice that are either heterozygous (PTEN(+/-)) or homozygous (PTEN(-/-)) for PTEN deletion or harboring a wild-type PTEN (PTEN(+/+)) were used to investigate the expression of MT1-MMP. We found that biallelic loss of PTEN is associated with posttranslational regulation of MT1-MMP protein in mouse PC cells. PTEN(-/-) PC cells display higher levels of MT1-MMP at the cell surface when compared to PTEN(+/+) and PTEN(+/-) cells and consequently exhibited enhanced migratory and collagen-invasive activities. MT1-MMP displayed by PTEN(-/-) cells is differentially O-glycosylated and exhibits a slow rate of turnover. MT1-MMP expression in PTEN(-/-) cells is under control of the PI3K/AKT signaling pathway, as determined using pharmacological inhibitors. Interestingly, rapamycin, an mTOR inhibitor, upregulates MT1-MMP expression in PTEN(+/+) cells via PI3K activity. Collectively, these data in a mouse prostate cell system uncover for the first time a novel and complex relationship between PTEN loss-mediated PI3K/AKT activation and posttranslational regulation of MT1-MMP, which may play a role in PC progression.
- Published
- 2010
28. Abstract 1070: Discoidin domain receptor 1 (DDR1): A potential suppressor of prostate cancer progression
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Dongping Shi, Semir Vranic, Daniel S. M. Oliveira, Wei Chen, Anjum Sohail, Hyeong Reh Choi Kim, Benjamin D. Wasinski, Allen Saliganan, R. Daniel Bonfil, Hyejeong Jang, and Rafael Fridman
- Subjects
Cancer Research ,DDR1 ,Stromal cell ,biology ,medicine.disease ,Receptor tyrosine kinase ,Small hairpin RNA ,Prostate cancer ,Oncology ,Downregulation and upregulation ,biology.protein ,Cancer research ,medicine ,Receptor ,Discoidin domain - Abstract
Discoidin domain receptors DDR1 and DDR2 are the only receptor tyrosine kinases that bind to and signal in response to collagen. In cancer, DDRs have been shown to play a key role in mediating the crosstalk between tumor cells and the stromal collagen matrix. Because prostate cancer (PCa) preferentially metastasizes to bone, a collagen-rich microenvironment, we set out to investigate the role of DDR1 in intraosseous growth of PC3 cells, a human PCa cell line that expresses DDR1 but not DDR2. PC3 cells were engineered to express short hairpin RNAs (shRNAs) against DDR1, or a scrambled shRNA as a control. These cells were inoculated into the tibiae of male SCID mice, and then bone response and intraosseous tumor growth evaluated by X-ray and histomorphometry. Whereas no differences were observed in bone response (osteolytic lesions), downregulation of DDR1 in PC3 cells was associated with a significant increase in intraosseous tumor growth when compared to control PC3 cells (P Citation Format: R. Daniel Bonfil, Anjum Sohail, Semir Vranić, Daniel S. Oliveira, Dongping Shi, Wei Chen, Hyejeong Jang, Allen D. Saliganan, Benjamin D. Wasinski, Hyeong-Reh C. Kim, Rafael A. Fridman. Discoidin domain receptor 1 (DDR1): A potential suppressor of prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1070.
- Published
- 2018
29. Abstract 4499: Determining the role of discoidin domain receptors 1 and 2 in the pathogenesis of pancreatic ductal adenocarcinoma
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Jeanine M. Ruggeri, Christopher J. Halbrook, Howard C. Crawford, Rafael Fridman, and Anjum Sohail
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Pathogenesis ,Cancer Research ,Pancreatic ductal adenocarcinoma ,Oncology ,Cancer research ,Biology ,Receptor ,Discoidin domain - Abstract
Pancreatic ductal adenocarcinoma (PDA) is an aggressive and devastating cancer often characterized by an intense collagen-rich, fibrotic response. In the presence of an oncogenic Kras mutation, the pancreas undergoes an initial morphological event in which normal acinar cells transdifferentiate into a ductal-like phenotype in a process called acinar-ductal metaplasia (ADM). ADM advances into pre-cancerous lesions, followed by a subsequent replacement of epithelium with a collagen-dense stromal reaction as PDA progresses. Discoidin domain receptors, DDR1 and DDR2, are a unique family of tyrosine receptor kinases that bind to collagen and activate downstream cellular responses that affect cell proliferation, migration, and adhesion. Our preliminary data shows that during Kras-induced ADM in vitro DDR1 is downregulated and is accompanied by an upregulation of DDR2 expression. Immunohistochemistry on human tissue microarrays reveals DDR1 is expressed in normal epithelia and pre-neoplastic lesions, but downregulated during advanced PDA. Conversely, DDR2 is upregulated in metaplastic lesions and advanced carcinoma as well as in the stroma at all stages of progression, suggesting DDRs may play a differential role throughout the PDA. DDR1 is expressed in epithelial cells and associated with disease states such as fibrosis and various cancers, including PDA. To study the role of DDR1 in pancreatitis, a known risk factor of PDA, we used DDR1-null mice (DDR1-/-) with our cerulein-induced pancreatitis protocol. DDR1 ablation induces tissue damage and impairs recovery from extended cerulein treatment. To understand the role of DDR1 in tumorigenesis, we mated DDR1-/- mice in the KrasG12D/+; Ptf1aCre/+ (KC model) of pancreatic neoplasia. The absence of DDR1 in the KC model does not inhibit nor delay tumorigenesis, however, pancreata are smaller with less differentiated morphology than wild-type KC animals. In contrast, DDR2 is expressed in mesenchymal cells and has been implicated in EMT, cell proliferation, tumor invasion, and required for metastasis in breast cancer, however, its significance in PDA remains unknown. Our preliminary data shows DDR2 co-stains with neuroendocrine positive cells within neoplastic lesions that are associated with poor patient survival. To further investigate the role of DDR2 in tumor progression we have successfully mated a conditional, global DDR2 knockout mouse (DDR2fl/fl; β-actinCreERT2) with our novel KrasFSF-G12D/+;p53FRT/+ ;Ptf1a-FlpO/+ (KPF) aggressive PDA mouse model. Collectively, the results from these studies will help determine the role of DDRs throughout the initiation and progression of PDA and help define a potential point of regulation at the interface between the epithelial-stromal interactions. Citation Format: Jeanine Ruggeri, Christopher Halbrook, Anjum Sohail, Rafael Fridman, Howard Crawford. Determining the role of discoidin domain receptors 1 and 2 in the pathogenesis of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4499.
- Published
- 2018
30. Abstract 2135: Complex roles of discoidin domain receptors (DDRs) in tumor growth and experimental metastasis: role of collagen I in DDR-mediated tumor growth
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Marco Prunotto, Lisa Polin, Benjamin D. Wasinski, Anjum Sohail, Sayed Nabi, Mohamad Bouhamdan, Hyeong Reh Choi Kim, R. Daniel Bonfil, Rafael Fridman, Allen-Dexter Saliganan, and Seongho Kim
- Subjects
Cancer Research ,DDR1 ,Cancer ,Biology ,medicine.disease ,Receptor tyrosine kinase ,Metastasis ,Oncology ,medicine ,Cancer research ,biology.protein ,HT1080 ,Fibrosarcoma ,Receptor ,Discoidin domain - Abstract
DDR1 and DDR2 constitute a unique set of receptor tyrosine kinases that signal in response to collagen. Evidence indicates that DDRs play key roles in cancer progression. However, a comparison of the effects of DDR1 and DDR2 on tumor growth and metastasis within the same cellular context has not been done. To accomplish this goal, we developed a doxycycline (DOX) regulated system (Tet-Off) to express human DDR1b or DDR2 in the human HT1080 fibrosarcoma cell line. The cells were then examined for their ability to form subcutaneous (s.c.) tumors, or experimental lung metastases after intravenous (i.v.) injection in SCID mice. To induce or repress DDR expression in vivo, mice were fed a regular diet or a diet with DOX, respectively. Because collagen I (COL I) is a ligand for both DDR1 and DDR2, a set of mice were inoculated s.c. with HT1080 cells suspended in COL I with or without DDR induction in –DOX and +DOX mice, respectively. Growth of s.c. tumors was evaluated by measuring tumor volumes and lung metastases were quantitated by Alu qPCR and histological examination. In the absence of COL I, expression of either DDR1b or DDR2 had no impact on s.c. tumor growth rate, when compared to cells without DDR induction (+DOX). However, in the presence of COL I, tumor growth rates were significantly higher only in HT1080 cells with induced expression of DDR1b or DDR2 (p Citation Format: Benjamin D. Wasinski, R. Daniel Bonfil, Anjum Sohail, Seong Ho Kim, Lisa Polin, Allen-Dexter Saliganan, Mohamad Bouhamdan, Sayed Nabi, Hyeong-Reh C. Kim, Marco Prunotto, Rafael A. Fridman. Complex roles of discoidin domain receptors (DDRs) in tumor growth and experimental metastasis: role of collagen I in DDR-mediated tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2135.
- Published
- 2018
31. MT6-MMP is present in lipid rafts and faces inward in living human PMNs but translocates to the cell surface during neutrophil apoptosis
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Carl Fortin, Patrick P. McDonald, Rafael Fridman, Tamas Fulop, Qing Sun, and Anjum Sohail
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Matrix Metalloproteinases, Membrane-Associated ,Neutrophils ,Immunoblotting ,Immunology ,Apoptosis ,chemical and pharmacologic phenomena ,Biology ,Granulocyte ,Matrix metalloproteinase ,GPI-Linked Proteins ,Membrane Microdomains ,medicine ,Humans ,Immunology and Allergy ,Macrophage ,Secretion ,Lipid raft ,Cells, Cultured ,Tissue Inhibitor of Metalloproteinase-2 ,Microscopy, Confocal ,Endoplasmic reticulum ,Proteolytic enzymes ,Chemotaxis ,General Medicine ,Cell biology ,Protein Transport ,medicine.anatomical_structure ,Original Research Papers - Abstract
Polymorphonuclear neutrophils (PMNs) are the first line of defense against invading organisms in humans; in addition, PMNs contribute to the linking of innate and adaptive immunity. To fulfill their biological behavior, PMNs utilize an arsenal of proteolytic enzymes, including members of the matrix metalloproteinase family of zinc-dependent endopeptidases. PMNs express high levels of MT6-MMP (MMP-25), a glycosyl-phosphatidylinositol-anchored MMP, that belongs to the subfamily of membrane-anchored matrix metalloproteinases. Due to the paucity of information on MT6-MMP in primary cells, we set to investigate the localization and potential function of MT6-MMP in human PMNs. We found that MT6-MMP is present in the membrane, granules and nuclear/endoplasmic reticulum/Golgi fractions of PMNs where it is displayed as a disulfide-linked homodimer of 120 kDa. Stimulation of PMNs resulted in secretion of active MT6-MMP into the supernatants. Membrane-bound MT6-MMP, conversely, is located in the lipid rafts of resting PMNs and stimulation does not alter this location. In addition, TIMP-2, a natural inhibitor of MT6-MMP, does not co-localize with it in the lipid rafts. Interestingly, living PMNs do not display MT6-MMP on the cell surface. However, induction of apoptosis induces MT6-MMP relocation on PMNs' cell surface. Our studies suggest that metalloproteinases may play a role in respiratory burst and IL-8 secretion, but not chemotaxis or granulocyte macrophage colony-stimulating factor-induced survival. Collectively, these results provide new insights on the role of MT6-MMP in the physiology of human PMNs.
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- 2010
32. Identification and Role of the Homodimerization Interface of the Glycosylphosphatidylinositol-anchored Membrane Type 6 Matrix Metalloproteinase (MMP25)
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Anjum Sohail, Huiren Zhao, Seaho Kim, Shahriar Mobashery, Qing Sun, Rafael Fridman, and Qicun Shi
- Subjects
Matrix Metalloproteinases, Membrane-Associated ,Glycosylphosphatidylinositols ,Neutrophils ,Cellular differentiation ,medicine.medical_treatment ,HL-60 Cells ,Peptide ,Matrix metalloproteinase ,GPI-Linked Proteins ,Biochemistry ,Cell membrane ,Membrane Microdomains ,Cell Line, Tumor ,medicine ,Humans ,Cysteine ,Disulfides ,Molecular Biology ,Lipid raft ,chemistry.chemical_classification ,Protease ,Enzyme Catalysis and Regulation ,Chemistry ,Cell Membrane ,Computational Biology ,Cell Differentiation ,Cell Biology ,Lipids ,medicine.anatomical_structure ,Cell culture ,Mutagenesis, Site-Directed ,Biophysics ,Dimerization - Abstract
The membrane type (MT) 6 matrix metalloproteinase (MMP) (MMP25) is a glycosylphosphatidylinositol-anchored matrix metalloproteinase (MMP) that is highly expressed in leukocytes and in some cancer tissues. We previously showed that natural MT6-MMP is expressed on the cell surface as a major reduction-sensitive form of Mr 120, likely representing enzyme homodimers held by disulfide bridges. Among the membrane type-MMPs, the stem region of MT6-MMP contains three cysteine residues at positions 530, 532, and 534 which may contribute to dimerization. A systematic site-directed mutagenesis study of the Cys residues in the stem region shows that Cys532 is involved in MT6-MMP dimerization by forming an intermolecular disulfide bond. The mutagenesis data also suggest that Cys530 and Cys534 form an intramolecular disulfide bond. The experimental observations on cysteines were also investigated by computational studies of the stem peptide, which validate these proposals. Dimerization is not essential for transport of MT6-MMP to the cell surface, partitioning into lipid rafts or cleavage of α-1-proteinase inhibitor. However, monomeric forms of MT6-MMP exhibited enhanced autolysis and metalloprotease-dependent degradation. Collectively, these studies establish the stem region of MT6-MMP as the dimerization interface, an event whose outcome imparts protease stability to the protein.
- Published
- 2008
33. MT4-(MMP17) and MT6-MMP (MMP25), A unique set of membrane-anchored matrix metalloproteinases: properties and expression in cancer
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Anjum Sohail, Huiren Zhao, Jin Ah Cho, M. Margarida Bernardo, Qing Sun, and Rafael Fridman
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Cancer Research ,Proteases ,Matrix Metalloproteinases, Membrane-Associated ,Cell Membrane ,Cell ,Matrix Metalloproteinase 17 ,Biology ,Matrix metalloproteinase ,GPI-Linked Proteins ,Article ,Cell biology ,Cell membrane ,Extracellular matrix ,B vitamins ,medicine.anatomical_structure ,Oncology ,Biochemistry ,Neoplasms ,medicine ,Animals ,Humans ,lipids (amino acids, peptides, and proteins) ,Lipid raft ,Function (biology) - Abstract
The process of cancer progression involves the action of multiple proteolytic systems, among which the family of matrix metalloproteinases (MMPs) play a pivotal role. The MMPs evolved to accomplish their proteolytic tasks in multiple cellular and tissue microenvironments including lipid rafts by incorporation and deletions of specific structural domains. The membrane type-MMPs (MT-MMPs) incorporated membrane anchoring domains that display these proteases at the cell surface, and thus they are optimal pericellular proteolytic machines. Two members of the MT-MMP subfamily, MMP-17 (MT4-MMP) and MMP-25 (MT6-MMP), are anchored to the plasma membrane via a glycosyl-phosphatidyl inositol (GPI) anchor, which confers these enzymes a unique set of regulatory and functional mechanisms that separates them from the rest of the MMP family. Discovered almost a decade ago, the body of work on GPI-MT-MMPs today is still surprisingly limited when compared to other MT-MMPs. However, new evidence shows that the GPI-MT-MMPs are highly expressed in human cancer, where they are associated with progression. Accumulating biochemical and functional evidence also highlights their distinct properties. In this review, we summarize the structural, biochemical, and biological properties of GPI-MT-MMPs and present an overview of their expression and role in cancer. We further discuss the potential implications of GPI-anchoring for enzyme function. Finally, we comment on the new scientific challenges that lie ahead to better understand the function and role in cancer of these intriguing but yet unique MMPs.
- Published
- 2008
34. SAR Studies of Exosite-Binding Substrate-Selective Inhibitors of A Disintegrin And Metalloprotease 17 (ADAM17) and Application as Selective in Vitro Probes
- Author
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Anna M. Knapinska, Richard A. Houghten, Gregg B. Fields, Travis LaVoi, Marc Giulianotti, Lyndsay Smith, Andreas Ludwig, Rafael Fridman, Dmitriy Minond, Daniela Dreymüller, Vladislav S. Golubkov, and Anjum Sohail
- Subjects
CHO Cells ,ADAM17 Protein ,In Vitro Techniques ,Article ,Cell Line ,Substrate Specificity ,Structure-Activity Relationship ,Cricetulus ,In vivo ,Cricetinae ,Drug Discovery ,Disintegrin ,Structure–activity relationship ,Animals ,Humans ,chemistry.chemical_classification ,biology ,Drug discovery ,Biological activity ,ADAM Proteins ,In vitro ,Enzyme ,Biochemistry ,chemistry ,Molecular Probes ,biology.protein ,Molecular Medicine - Abstract
ADAM17 is implicated in several debilitating diseases. However, drug discovery efforts targeting ADAM17 have failed due to the utilization of zinc-binding inhibitors. We previously reported discovery of highly selective nonzinc-binding exosite-targeting inhibitors of ADAM17 that exhibited not only enzyme isoform selectivity but synthetic substrate selectivity as well ( J. Biol. Chem. 2013, 288, 22871). As a result of SAR studies presented herein, we obtained several highly selective ADAM17 inhibitors, six of which were further characterized in biochemical and cell-based assays. Lead compounds exhibited low cellular toxicity and high potency and selectivity for ADAM17. In addition, several of the leads inhibited ADAM17 in a substrate-selective manner, which has not been previously documented for inhibitors of the ADAM family. These findings suggest that targeting exosites of ADAM17 can be used to obtain highly desirable substrate-selective inhibitors. Additionally, current inhibitors can be used as probes of biological activity of ADAM17 in various in vitro and, potentially, in vivo systems.
- Published
- 2015
35. SCIENTIFIC RESEARCH; KNOWLEDGE AND ATTITUDES OF MEDICAL STUDENTS TOWARDS SCIENTIFIC RESEARCH.
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Anjum, Sohail and Mahboob, Usman
- Subjects
- *
MEDICAL students , *MEDICAL education , *STUDENT attitudes - Abstract
Objectives: The primary objective of our study is to assess the existing level knowledge and attitudes towards scientific research amongst medical students of a medical college in Lahore. Study Design: Quantitative descriptive questionnaire-based survey. Period: June to September 2017 on fourth year and final year students of MBBS. Setting: Medical College in Lahore. Methods: After informed consent and briefing, the questionnaire was distributed to the participants. The collected data was analyzed using SPSS. Results: A total of 200 students were contacted out of which 102 responded (response rate51%). The result showed that the knowledge assessment score of final year was lower than fourth year but the difference was not statistically significant. The knowledge was low in both the groups. Attitude score was slightly higher in 4th year as compared to 5th year. Conclusion: The study indicated less knowledge but positive attitude of medical students towards scientific research. Moreover, the culture of research needs to be developed in our undergraduate medical education. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
36. Mismatch Repair in Methylated DNA
- Author
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Xing Zhang, Anjum Sohail, Ashok S. Bhagwat, Chen Qiu, Xiaodong Cheng, and Peiying Wu
- Subjects
biology ,HMG-box ,Cell Biology ,DNA-binding domain ,Biochemistry ,Molecular biology ,MBD4 ,AP endonuclease ,Methyl-CpG-binding domain ,DNA glycosylase ,biology.protein ,Protein–DNA interaction ,Molecular Biology ,Binding domain - Abstract
MBD4 is a member of the methyl-CpG-binding protein family. It contains two DNA binding domains, an amino-proximal methyl-CpG binding domain (MBD) and a C-terminal mismatch-specific glycosylase domain. Limited in vitro proteolysis of mouse MBD4 yields two stable fragments: a 139-residue fragment including the MBD, and the other 155-residue fragment including the glycosylase domain. Here we show that the latter fragment is active as a glycosylase on a DNA duplex containing a G:T mismatch within a CpG sequence context. The crystal structure confirmed the C-terminal domain is a member of the helix-hairpin-helix DNA glycosylase superfamily. The MBD4 active site is situated in a cleft that likely orients and binds DNA. Modeling studies suggest the mismatched target nucleotide will be flipped out into the active site where candidate residues for catalysis and substrate specificity are present.
- Published
- 2003
37. Protection of DNA by α/β-Type Small, Acid-Soluble Proteins from Bacillus subtilis Spores Against Cytosine Deamination
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Pradeep Divvela, Peter Setlow, Ashok S. Bhagwat, Christopher S. Hayes, and Anjum Sohail
- Subjects
DNA, Bacterial ,Spores, Bacterial ,biology ,DNA damage ,Deamination ,Sigma Factor ,Uracil ,Bacillus subtilis ,biology.organism_classification ,Biochemistry ,Molecular biology ,DNA-Binding Proteins ,Cytosine ,Kinetics ,Restriction enzyme ,chemistry.chemical_compound ,Bacterial Proteins ,chemistry ,Restriction digest ,DNA ,DNA Damage ,Transcription Factors - Abstract
Spores of Bacillus subtilis contain high levels of proteins, termed alpha/beta-type small, acid-soluble proteins (SASP), that protect the spore's DNA against different types of DNA damage. We tested one such protein, SspC, and two of its variants for their ability to protect plasmid DNA against hydrolytic deamination of cytosine to uracil. If unrepaired, such damage to DNA causes C to T mutations. We found that one SspC variant, SspC(Delta 11-D13K), protected DNA against cytosine deamination at two different temperatures (45 and 70 degrees C) and pH values (5.2 and 7.9), reducing the rate of deamination by as much as 10-fold. At 70 degrees C, pH 7.9, the wild-type SspC and its variant, SspC(Delta 11), provided little protection against deamination but were effective in protecting DNA at 45 degrees C, pH 7.9. Parallel studies of the abilities of these proteins to protect DNA against restriction digestion revealed that there was a good correlation between the abilities of the proteins to protect against restriction endonucleases and reductions in cytosine deaminations. These results show that the binding of SspC variants to DNA can prevent attack on DNA bases by water and suggest a new general mechanism by which DNA-binding proteins in cells may be able to protect chromosomes from endogenous and exogenous reactive chemicals by excluding them from the vicinity of DNA.
- Published
- 2002
38. Discoidin domain receptors: unique receptor tyrosine kinases in collagen-mediated signaling
- Author
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Rajeshwari R. Valiathan, Richard Arkwright, Hsueh Liang Fu, Malika Kumarasiri, Kiran V. Mahasenan, Gunjan Agarwal, Rafael Fridman, Shahriar Mobashery, Cosmin Mihai, Paul H. Huang, Anjum Sohail, Fu, Hsueh-Liang, Valiathan, Rajeshwari R, Arkwright, Richard, Sohail, Anjum, Mihai, Cosmin, Kumarasiri, Malika, Mahasenan, Kiran V, Mobashery, Shahriar, Huang, Paul, Agarwal, Gunjan, and Fridman, Rafael
- Subjects
Models, Molecular ,collagen ,tyrosine protein kinase (tyrosine kinase) ,extracellular matrix ,Receptor Protein-Tyrosine Kinases ,Molecular Conformation ,Biology ,Ligands ,Biochemistry ,Receptor tyrosine kinase ,Mice ,Animals ,Humans ,Phosphotyrosine ,Receptor ,Discoidin Domain Receptors ,Molecular Biology ,DDR1 ,phosphotyrosine signaling ,Kinase ,Minireviews ,protease ,Cell Biology ,Endocytosis ,Extracellular Matrix ,Protein Structure, Tertiary ,Cell biology ,Kinetics ,Gene Expression Regulation ,Receptors, Mitogen ,biology.protein ,Collagen ,Discoidin domain-containing receptor 2 ,Signal transduction ,Discoidin domain ,signal transduction ,Peptide Hydrolases ,Signal Transduction - Abstract
The discoidin domain receptors (DDRs) are receptor tyrosine kinases that recognize collagens as their ligands. DDRs display unique structural features and distinctive activation kinetics, which set them apart from other members of the kinase superfamily. DDRs regulate cell-collagen interactions in normal and pathological conditions and thus are emerging as major sensors of collagen matrices and potential novel therapeutic targets. New structural and biological information has shed light on the molecular mechanisms that regulate DDR signaling, turnover, and function. This minireview provides an overview of these areas of DDR research with the goal of fostering further investigation of these intriguing and unique receptors. Refereed/Peer-reviewed
- Published
- 2013
39. Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography
- Author
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Marta, Toth, Anjum, Sohail, and Rafael, Fridman
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Octoxynol ,Gelatin ,Humans ,Matrix Metalloproteinase 2 ,Electrophoresis, Polyacrylamide Gel ,Neoplasm Invasiveness ,Matrix Metalloproteinase 1 ,Neoplasm Metastasis ,Cell Line ,Enzyme Assays ,Polyethylene Glycols - Abstract
Gelatin zymography is a simple yet powerful method to detect proteolytic enzymes capable of degrading gelatin from various biological sources. It is particularly useful for the assessment of two key members of the matrix metalloproteinase family, MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their potent gelatin-degrading activity. This polyacrylamide gel electrophoresis-based method can provide a reliable assessment of the type of gelatinase, relative amount, and activation status (latent, compared with active enzyme forms) in cultured cells, tissues, and biological fluids. The method can be used to investigate factors that regulate gelatinase expression and modulate zymogen activation in experimental systems. The system provides information on the pattern of gelatinase expression and activation in human cancer tissues and how this relates to cancer progression. Interpretation of the data obtained in gelatin zymography requires a thorough understanding of the principles and pitfalls of the technique; this is particularly important when evaluating enzyme levels and the presence of active gelatinase species. If properly used, gelatin zymography is an excellent tool for the study of gelatinases in biological systems.
- Published
- 2012
40. Assessment of Gelatinases (MMP-2 and MMP-9) by Gelatin Zymography
- Author
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Marta Toth, Anjum Sohail, and Rafael Fridman
- Subjects
Gelatinases ,food.ingredient ,food ,Biochemistry ,Chemistry ,Zymogen activation ,Gelatin Zymography ,Gelatinase A ,Proteolytic enzymes ,Gelatinase ,Matrix metalloproteinase ,Gelatin - Abstract
Gelatin zymography is a simple yet powerful method to detect proteolytic enzymes capable of degrading gelatin from various biological sources. It is particularly useful for the assessment of two key members of the matrix metalloproteinase family, MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their potent gelatin-degrading activity. This polyacrylamide gel electrophoresis-based method can provide a reliable assessment of the type of gelatinase, relative amount, and activation status (latent, compared with active enzyme forms) in cultured cells, tissues, and biological fluids. The method can be used to investigate factors that regulate gelatinase expression and modulate zymogen activation in experimental systems. The system provides information on the pattern of gelatinase expression and activation in human cancer tissues and how this relates to cancer progression. Interpretation of the data obtained in gelatin zymography requires a thorough understanding of the principles and pitfalls of the technique; this is particularly important when evaluating enzyme levels and the presence of active gelatinase species. If properly used, gelatin zymography is an excellent tool for the study of gelatinases in biological systems.
- Published
- 2012
41. Characterization of the dimerization interface of membrane type 4 (MT4)-matrix metalloproteinase
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Shahriar Mobashery, Rafael Fridman, Scott Merriman, Qicun Shi, Anjum Sohail, Marta Marco, and Huiren Zhao
- Subjects
Glycosylation ,Matrix Metalloproteinases, Membrane-Associated ,Population ,Cell ,Biology ,Molecular Dynamics Simulation ,Biochemistry ,Serine ,chemistry.chemical_compound ,Dogs ,Membrane Microdomains ,Enzyme Stability ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Cysteine ,education ,Molecular Biology ,Lipid raft ,Matrigel ,education.field_of_study ,Cell migration ,Cell Biology ,Tunicamycin ,Isoenzymes ,medicine.anatomical_structure ,chemistry ,Biophysics ,Enzymology ,Mutant Proteins ,Protein Multimerization ,Peptides - Abstract
MT4-MMP (MMP17) belongs to a unique subset of membrane type-matrix metalloproteinases that are anchored to the cell surface via a glycosylphosphatidylinositol moiety. However, little is known about its biochemical properties. Here, we report that MT4-MMP is displayed on the cell surface as a mixed population of monomeric, dimeric, and oligomeric forms. Sucrose gradient fractionation demonstrated that these forms of MT4-MMP are all present in lipid rafts. Mutational and computational analyses revealed that Cys(564), which is present within the stem region, mediates MT4-MMP homodimerization by forming a disulfide bond. Substitution of Cys(564) results in a more rapid MT4-MMP turnover, when compared with the wild-type enzyme, consistent with a role for dimerization in protein stability. Expression of MT4-MMP in Madin-Darby canine kidney cells enhanced cell migration and invasion of Matrigel, a process that requires catalytic activity. However, a serine substitution at Cys(564) did not reduce MT4-MMP-stimulated cell invasion of Matrigel suggesting that homodimerization is not required for this process. Deglycosylation studies showed that MT4-MMP is modified by N-glycosylation. Moreover, inhibition of N-glycosylation by tunicamycin diminished the extent of MT4-MMP dimerization suggesting that N-glycans may confer stability to the dimeric form. Taken together, the data presented here provide a new insight into the characteristics of MT4-MMP and highlight the common and distinct properties of the glycosylphosphatidylinositol-anchored membrane type-matrix metalloproteinases.
- Published
- 2011
42. MMP25 (MT6-MMP) Is Highly Expressed in Human Colon Cancer, Promotes Tumor Growth, and Exhibits Unique Biochemical Properties*§
- Author
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Christopher R. Weber, Jerrold R. Turner, Marta Toth, M. Margarida Bernardo, Anjum Sohail, Qing Sun, Huiren Zhao, and Rafael Fridman
- Subjects
Cell division ,Matrix Metalloproteinases, Membrane-Associated ,Colorectal cancer ,Glycosylphosphatidylinositols ,Cell ,Molecular Sequence Data ,Matrix metalloproteinase ,Biology ,Adenocarcinoma ,GPI-Linked Proteins ,Transfection ,Biochemistry ,Article ,Gene Expression Regulation, Enzymologic ,Catalytic Domain ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Tissue Inhibitor of Metalloproteinase-2 ,Tissue Inhibitor of Metalloproteinase-1 ,Cancer ,Epithelial Cells ,Cell Biology ,Haplorhini ,medicine.disease ,Molecular biology ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Cell culture ,Colonic Neoplasms ,Colorectal Neoplasms ,Cell Division - Abstract
MMP25 (MT6-MMP) is one of the two glycosylphosphatidylinositol-anchored matrix metalloproteinases (MMPs) that have been suggested to play a role in pericellular proteolysis. However, its role in cancer is unknown, and its biochemical properties are not well established. Here we found a marked increase in MT6-MMP expression within in situ dysplasia and invasive cancer in 61 samples of human colon cancer. Expression of MT6-MMP in HCT-116 human colon cancer cells promoted tumori-genesis in nude mice. Histologically, the MT6-MMP-expressing tumors demonstrated an infiltrative leading edge in contrast to a rounded leading edge in vector control tumors. Biochemical and biosynthesis analyses revealed that MT6-MMP displayed on the cell surface exists as a major form of 120 kDa that likely represents enzyme homodimers linked by disulfide bonds. Upon reduction, a single 57-kDa active MT6-MMP was detected. Interestingly, neither membrane-anchored nor phosphatidylinositol-specific phospholipase C-released MT6-MMPs were found to be associated with tissue inhibitor of metalloproteinases (TIMPs) and did not activate pro-gelatinases (pro-MMP-2 and pro-MMP-9) even in the presence of exogenous TIMP-2 or TIMP-1. A catalytic domain of MT6-MMP was inhibited preferentially by TIMP-1 (K(i) = 0.2 nm) over TIMP-2 (K(i) = 2.0 nm), because of a slower association rate. These results show that MT6-MMP may play a role in colon cancer and exhibit unique biochemical and structural properties that may regulate proteolytic function at the cell surface.
- Published
- 2007
43. MT1-MMP shedding involves an ADAM and is independent of its localization in lipid rafts
- Author
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Anjum Sohail, Shahriar Mobashery, Rafael Fridman, and Marta Toth
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Metalloproteinase ,Protease ,medicine.medical_treatment ,Cell ,Cell Membrane ,Biophysics ,Wild type ,Cell Biology ,Matrix metalloproteinase ,Biology ,Biochemistry ,Cell biology ,ADAM Proteins ,medicine.anatomical_structure ,Membrane Microdomains ,Ectodomain ,Cell Line, Tumor ,medicine ,Matrix Metalloproteinase 14 ,Animals ,Humans ,HT1080 ,Protease Inhibitors ,Molecular Biology ,Lipid raft - Abstract
The membrane type 1-matrix metalloproteinase (MT1-MMP) is a membrane-anchored protease that its entire ectodomain is shed from the cell surface. Here we show that in HT1080 cells MT1-MMP is shed as two soluble forms of approximately 52 and approximately 50kDa. Analyses in purified HT1080 plasma membranes show that release of these species is a two-step time-dependent process that is mediated by integral membrane metalloprotease(s). Differential sensitivity to TIMP-3 inhibition of the shedding process suggests that the second cleavage step leading to the formation of the 50-kDa soluble species is mediated by an ADAM. We also show that shedding of MT1-MMP is independent of its partition into lipid rafts because both wild type and glycosylphosphatidylinositol (GPI)-anchored MT1-MMP are shed. These studies provide new insights into the process of MT1-MMP ectodomain shedding, which may regulate pericellular proteolysis.
- Published
- 2006
44. Perceptions of house officers working in hospitals of Lahore about joining the field of anaesthesiology as a career.
- Author
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Anjum, Sohail and Mahboob, Usman
- Published
- 2016
45. Synthesis and molecular characterization of chitosan based polyurethane elastomers using aromatic diisocyanate
- Author
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Zia, Khalid Mahmood, primary, Anjum, Sohail, additional, Zuber, Mohammad, additional, Mujahid, Muhammad, additional, and Jamil, Tahir, additional
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- 2014
- Full Text
- View/download PDF
46. Synthesis and characterization of siloxane-based polyurethane elastomers using hexamethylene diisocyanate
- Author
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Zia, Khalid Mahmood, primary, Ahmad, Aftab, additional, Anjum, Sohail, additional, Zuber, Mohammad, additional, and Anjum, Muhammad Naveed, additional
- Published
- 2014
- Full Text
- View/download PDF
47. Human activation-induced cytidine deaminase causes transcription-dependent, strand-biased C to U deaminations
- Author
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Asad Ullah, Joanna Klapacz, Anjum Sohail, Mala Samaranayake, and Ashok S. Bhagwat
- Subjects
Transcription, Genetic ,Molecular Sequence Data ,Somatic hypermutation ,chemistry.chemical_compound ,Cytosine ,Plasmid ,Cytidine Deaminase ,Genetics ,Activation-induced (cytidine) deaminase ,Escherichia coli ,Humans ,Gene conversion ,Uracil ,Gene ,biology ,Base Sequence ,Cytidine deaminase ,DNA ,Articles ,Molecular biology ,chemistry ,Deamination ,Mutation ,biology.protein - Abstract
Activation-induced cytidine deaminase (AID) is required for the maturation of antibodies in higher vertebrates, where it promotes somatic hypermutation (SHM), class switch recombination and gene conversion. While it is known that SHM requires high levels of transcription of the target genes, it is unclear whether this is because AID targets transcribed genes. We show here that the human AID promotes C to T mutations in Escherichia coli which are stimulated by transcription. The mutations are strand-biased and occur preferentially in the non-transcribed strand of the target gene. Human AID purified from E.coli is active without prior treatment with a ribonuclease and deaminates cytosines in plasmid DNA in vitro. Further, the action of this enzyme is greatly stimulated by the transcription of the target gene in a strand-dependent fashion. These results confirm the prediction that AID may act directly on DNA and show that it can act on transcribing DNA in the absence of specialized DNA structures such as R-loops. It suggests that AID may be recruited to variable genes through transcription without the assistance of other proteins and that the strand bias in SHM may be caused by the preference of AID for the non-transcribed strand.
- Published
- 2003
48. Mismatch repair in methylated DNA. Structure and activity of the mismatch-specific thymine glycosylase domain of methyl-CpG-binding protein MBD4
- Author
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Peiying, Wu, Chen, Qiu, Anjum, Sohail, Xing, Zhang, Ashok S, Bhagwat, and Xiaodong, Cheng
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Deoxyribonuclease (Pyrimidine Dimer) ,Mice ,Endodeoxyribonucleases ,DNA Repair ,Base Pair Mismatch ,Protein Conformation ,Molecular Sequence Data ,Animals ,Amino Acid Sequence ,DNA Methylation ,Article ,Protein Structure, Tertiary - Abstract
MBD4 is a member of the methyl-CpG-binding protein family. It contains two DNA binding domains, an amino-proximal methyl-CpG binding domain (MBD) and a C-terminal mismatch-specific glycosylase domain. Limited in vitro proteolysis of mouse MBD4 yields two stable fragments: a 139-residue fragment including the MBD, and the other 155-residue fragment including the glycosylase domain. Here we show that the latter fragment is active as a glycosylase on a DNA duplex containing a G:T mismatch within a CpG sequence context. The crystal structure confirmed the C-terminal domain is a member of the helix-hairpin-helix DNA glycosylase superfamily. The MBD4 active site is situated in a cleft that likely orients and binds DNA. Modeling studies suggest the mismatched target nucleotide will be flipped out into the active site where candidate residues for catalysis and substrate specificity are present.
- Published
- 2002
49. Management of parotid tumor.
- Author
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Atiq-ur-Rehman, Sheikh, Masood, Umair, Ahmad, Fayyaz, yar, Ahmad, and Ansari, Anjum Sohail
- Subjects
PAROTID gland tumors ,PAROTIDECTOMY ,EPIDERMOID cancers of mucous membranes ,SURGICAL complications ,HISTOPATHOLOGY ,TUMOR treatment - Abstract
Objective: To describe the clinical & pathological presentations and treatment options of parotid swelling in adult patients. Design: Descriptive case series study. Place and Duration of Study: Surgical units of Bahawal Victoria Hospital Bahawalpur, from August 2010 to July 2015. Subjects and Methods: All patients of either sex & age above 20 years presented with parotid swelling to surgical units were included in the study. Clinical presentations, preoperative investigations, operative procedure, histopathology report, postoperative complications and further management (radiotherapy & chemotherapy) given were recorded. Results: 65 patients presented with parotid swelling. Commonest presentation was a painless lump over the parotid region in 83.07% & painful lump 16.93% patients. Majority of tumours were benign (pleomorphic adenoma 83.07%). Malignant tumours were mucoepidermoid carcinoma 7.05%, adenoid cystic carcinoma 4.61% & acinic cell carcinoma 5.26%. Conclusion: Benign tumours (pleomorphic adenoma) are the commonest tumour in adult patients. Superficial parotidectomy is the operation for benign tumours & total conservative parotidectomy for malignant tumours. [ABSTRACT FROM AUTHOR]
- Published
- 2016
50. Synthesis and characterization of siloxane-based polyurethane elastomers using hexamethylene diisocyanate.
- Author
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Zia, Khalid Mahmood, Ahmad, Aftab, Anjum, Sohail, Zuber, Mohammad, and Anjum, Muhammad Naveed
- Subjects
POLYURETHANES ,CHEMICAL synthesis ,HEXAMETHYLENE diisocyanate ,POLYBUTADIENE ,ELASTOMERS ,POLYDIMETHYLSILOXANE - Abstract
The present research work was performed to study the properties of siloxane-based polyurethane (SPU) elastomers using aliphatic diisocyanate. SPU samples constituting of hexamethylene diisocyanate, hydroxyl-terminated polybutadiene, and polydimethylsiloxane (PDMS) were synthesized by two-step polymerization technique. Molecular engineering and surface characterization were carried out, and the outcome of the results was discussed. The conventional spectroscopic characterization of the synthesized samples using Fourier transform infrared spectroscopy confirms the existence of the proposed SPU structure. Surface properties of the synthesized material were studied determining the percentage of water absorption and equilibrium of the degree of swelling. It was found that by increasing the mole ratio of PDMS, the synthesized PU samples showed hydrophobic behavior while placing them in water and in dimethylsulfoxide solvent. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
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