المؤلفون: Barisas, Derek A. G., Kabir, Ashraf Ul, Wu, Jun, Krchma, Karen, Kim, Minseo, Subramanian, Madhav, Zinselmeyer, Bernd H., Stewart, Colin L., Choi, Kyunghee

المساهمون: Bhandoola, Avinash, National Institutes of Health, Foundation for Barnes-Jewish Hospital

المصدر: PLOS Biology ; volume 21, issue 5, page e3001746 ; ISSN 1545-7885

الوصف: Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1α and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, respectively. IL-1α induced TNFα expression in splenic HSPCs, which then activated splenic niche activity, while LIF induced proliferation of splenic niche cells. IL-1α and LIF display cooperative effects in activating EMH and are both up-regulated in some human cancers. Together, these data expand avenues for developing niche-directed therapies and further exploring EMH accompanying inflammatory pathologies like cancer.

الإتاحة: https://doi.org/10.1371/journal.pbio.3001746Test

المؤلفون: Subramanian, Madhav, Kabir, Ashraf Ul, Barisas, Derek, Krchma, Karen, Choi, Kyunghee

المساهمون: National Institutes of Health, NHLBI, Siteman Cancer Center

المصدر: Cell Reports Medicine ; volume 4, issue 1, page 100896 ; ISSN 2666-3791

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology

الإتاحة: https://doi.org/10.1016/j.xcrm.2022.100896Test
https://api.elsevier.com/content/article/PII:S266637912200475X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S266637912200475X?httpAccept=text/plainTest

المؤلفون: Oladipupo, Sunday S., Kabir, Ashraf Ul, Smith, Craig, Choi, Kyunghee, Ornitz, David M.

المساهمون: U.S. Department of Health & Human Services | National Institutes of Health

المصدر: Scientific Reports ; volume 8, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: VEGF signaling through its tyrosine kinase receptor, VEGFR2 (FLK1), is critical for tumor angiogenesis. Previous studies have identified a critical gene dosage effect of VegfA in embryonic development and vessel homeostasis, neovascularization, and tumor growth, and potent inhibitors of VEGFR2 have been used to treat a variety of cancers. Inhibition of FGFR signaling has also been considered as an antiangiogenic approach to treat a variety of cancers. Inhibition of VEGFR2 with neutralizing antibodies or with pharmacological inhibitors of the VEGFR tyrosine kinase domain has at least short-term efficacy with some cancers; however, also affects vessel homeostasis, leading to adverse complications. We investigate gene dosage effects of Vegfr2 , Fgfr1 , and Fgfr2 in three independent mouse models of tumorigenesis: two-stage skin chemical carcinogenesis, and sub-cutaneous transplantation of B16F0 melanoma and Lewis Lung Carcinoma (LLC). Mice heterozygous for Vegfr2 display profound defects in supporting tumor growth and angiogenesis. Unexpectedly, additional deletion of endothelial Fgfr1 and Fgfr2 in Vegfr2 heterozygous mice shows similar tumor growth and angiogenesis as the Vegfr2 heterozygous mice. Notably, hematopoietic deletion of two alleles of Vegfr2 had minimal impact on tumor growth, with little effect on angiogenesis, reinforcing the importance of endothelial Vegfr2 heterozygosity. These studies reveal previously unrecognized Vegfr2 gene dosage effects in tumor angiogenesis and a lack of synergy between VEGFR2 and endothelial FGFR1/2 signaling during tumor growth.

الإتاحة: https://doi.org/10.1038/s41598-018-33037-2Test
https://www.nature.com/articles/s41598-018-33037-2.pdfTest
https://www.nature.com/articles/s41598-018-33037-2Test

المؤلفون: Samad, Mehdi Bin, Mohsin, Md. Nurul Absar Bin, Razu, Bodiul Alam, Hossain, Mohammad Tashnim, Mahzabeen, Sinayat, Unnoor, Naziat, Muna, Ishrat Aklima, Akhter, Farjana, Kabir, Ashraf Ul, Hannan, J. M A

مصطلحات موضوعية: [6]-Gingerol, Leprdb/db mice, Type 2 diabetes, GLP-1, Rab27a, GLUT4, Glycogen synthase 1, Rab8, Rab10

الوصف: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0Test/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0Test/) applies to the data made available in this article, unless otherwise stated. ; Abstract Background [6]-Gingerol, a major component of Zingiber officinale, was previously reported to ameliorate hyperglycemia in type 2 diabetic mice. Endocrine signaling is involved in insulin secretion and is perturbed in db/db Type-2 diabetic mice. [6]-Gingerol was reported to restore the disrupted endocrine signaling in rodents. In this current study on Leprdb/db diabetic mice, we investigated the involvement of endocrine pathway in the insulin secretagogue activity of [6]-Gingerol and the mechanism(s) through which [6]-Gingerol ameliorates hyperglycemia. Methods Leprdb/db type 2 diabetic mice were orally administered a daily dose of [6]-Gingerol (200mg/kg) for 28days. We measured the plasma levels of different endocrine hormones in fasting and fed conditions. GLP-1 levels were modulated using pharmacological approaches, and cAMP/PKA pathway for insulin secretion was assessed by qRT-PCR and ELISA in isolated pancreatic islets. Total skeletal muscle and its membrane fractions were used to measure glycogen synthase 1 level and Glut4 expression and protein levels. Results 4-weeks treatment of [6]-Gingerol dramatically increased glucose-stimulated insulin secretion and improved glucose tolerance. Plasma GLP-1 was found to be significantly elevated in the treated mice. Pharmacological intervention of GLP-1 levels regulated the effect of [6]-Gingerol on insulin secretion. Mechanistically, [6]-Gingerol treatment upregulated and activated cAMP, ...

العلاقة: BMC Complementary and Alternative Medicine, 17(1):395; https://hdl.handle.net/10371/137261Test

الإتاحة: https://doi.org/10.1186/s12906-017-1903-0Test
https://hdl.handle.net/10371/137261Test

المؤلفون: Kabir, Ashraf Ul, Samad, Mehdi Bin, Ahmed, Arif, Jahan, Mohammad Rajib, Akhter, Farjana, Tasnim, Jinat, Hasan, S. M. Nageeb, Sayfe, Sania Sarker, Hannan, J. M. A.

المساهمون: Miele, Claudia

المصدر: PLOS ONE ; volume 10, issue 2, page e0116546 ; ISSN 1932-6203

الإتاحة: https://doi.org/10.1371/journal.pone.0116546Test

المؤلفون: Kabir, Ashraf Ul

المصدر: Arts & Sciences Electronic Theses and Dissertations

مصطلحات موضوعية: Angiogenesis, Etv2, Immunotherapy, Myct1, Tumor microenvironment, Vascular normalization, Allergy and Immunology, Immunology and Infectious Disease, Medical Immunology, Molecular Biology, Oncology

الوصف: Angiogenesis is a critical determinant of neoplastic growth and metastatic spread. As such, anti-angiogenic approaches have long been tried to throttle down tumor progression. However, current anti-angiogenic treatments so far have produced modest clinical benefits. Further in-depth research has provided rationales behind these disappointing and apparent perplexing clinical outcomes. It is now established that VEGF (vascular endothelial growth factor) and other prominent current angiogenic targets are neither specific to the vascular system nor the pathological conditions explaining the sub-optimal angiogenic control following the existing treatments. This suggests that anti-angiogenesis could still be a viable strategy for cancer patients should there are targets exclusive for tumor angiogenesis. The goal for my Ph.D. dissertation has been to identify novel angiogenic targets and their mechanism(s) of action in controlling tumor angiogenesis and growth.In aim 1, I have demonstrated that ETS transcription factor Etv2, which is critical for the endothelial and hematopoietic development exclusively in the developmental phase but stays silent in the adult phase, is reactivated in the endothelium of both the human cancers and mouse models of tumors. Etv2 deficiency renders the tumor vasculature similar to normal vessels and reduces tumor growth. Oxidative stress in the tumor environment is likely the driver to initiate Etv2 expression in the endothelial cells. Despite being a promising and exclusive target for tumor angiogenesis, it is challenging to utilize Etv2 as a therapeutic target because transcription factors are generally considered non-druggable. To address this, in aim 2, I have identified Myct1, a direct downstream target of Etv2, as a novel and endothelial-specific angiogenic gene. MYCT1 is a cell membrane-localized protein that makes it targetable by antibody-mediated approaches. Myct1 deficient endothelial cells lose migratory angiogenic phenotype in vitro and demonstrate normalized vascular functions ...

وصف الملف: application/pdf

العلاقة: https://openscholarship.wustl.edu/art_sci_etds/2432Test; https://openscholarship.wustl.edu/cgi/viewcontent.cgi?article=3483&context=art_sci_etdsTest

الإتاحة: https://openscholarship.wustl.edu/art_sci_etds/2432Test
https://openscholarship.wustl.edu/cgi/viewcontent.cgi?article=3483&context=art_sci_etdsTest

المؤلفون: Kabir, Ashraf Ul, Subramanian, Madhav, Lee, Dong Hun, Wang, Xiaoli, Krchma, Karen, Wu, Jun, Naismith, Teri, Halabi, Carmen M., Kim, Ju Young, Pulous, Fadi E., Petrich, Brian G., Kim, Suhyun, Park, Hae-Chul, Hanson, Phyllis I., Pan, Hua, Wickline, Samuel A., Fremont, Daved H., Park, Changwon, Choi, Kyunghee

المساهمون: National Institutes of Health, NIH Office of the Director, Children’s Healthcare of Atlanta

المصدر: Science Translational Medicine ; volume 13, issue 583 ; ISSN 1946-6234 1946-6242

الوصف: Myct1 inhibition controls tumor angiogenesis, remodels tumor immunity, and improves immunotherapy outcomes in mouse tumor models.

الإتاحة: https://doi.org/10.1126/scitranslmed.abb6731Test

المؤلفون: Kabir, Ashraf Ul, Samad, Mehdi Bin, D’Costa, Ninadh Malrina, Akhter, Farjana, Ahmed, Arif, Hannan, JMA

المصدر: BMC Complementary and Alternative Medicine ; volume 14, issue 1 ; ISSN 1472-6882

مصطلحات موضوعية: Complementary and alternative medicine, General Medicine

الإتاحة: https://doi.org/10.1186/1472-6882-14-31Test

المؤلفون: Samad, Mehdi Bin, Hasan, Md Nazmul, Banarjee, Sudipta, Rahman, Mizanur, Raihan, Sabbir, Banti, Faika Laz, Sayfe, Sania Sarker, Hasan, S.M. Nageeb, Akhter, Farjana, Kabir, Ashraf Ul, Hannan, J.M.A.

المساهمون: North South University

المصدر: Biomedicine & Pharmacotherapy ; volume 95, page 513-519 ; ISSN 0753-3322

مصطلحات موضوعية: Pharmacology, General Medicine

الإتاحة: https://doi.org/10.1016/j.biopha.2017.08.113Test
https://api.elsevier.com/content/article/PII:S0753332217337071?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0753332217337071?httpAccept=text/plainTest

المؤلفون: Kabir, Ashraf-ul, Samad, MehdiBin, Hannan, JuardarMohammad, D′Costa, NinadhMalrina

المصدر: Journal of Basic and Clinical Pharmacy ; volume 3, issue 4, page 336 ; ISSN 0976-0105

مصطلحات موضوعية: General Medicine

الإتاحة: https://doi.org/10.4103/0976-0105.105335Test