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Journal articles on the topic 'Anti-integrins therapies'

Author: Grafiati

Published: 11 March 2023

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1

Tabatabai, Ghazaleh, Jorg-Christian Tonn, Roger Stupp, and Michael Weller. "The Role of Integrins in Glioma Biology and Anti-Glioma Therapies." Current Pharmaceutical Design 17, no. 23 (2011): 2402–10. http://dx.doi.org/10.2174/138161211797249189.

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Khanna, Reena, Mahmoud H. Mosli, and Brian G. Feagan. "Anti-Integrins in Ulcerative Colitis and Crohn's Disease: What Is Their Place?" Digestive Diseases 34, no. 1-2 (2016): 153–59. http://dx.doi.org/10.1159/000443132.

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Background: Inflammatory bowel diseases (IBD) are a group of heterogeneous conditions, characterized by immune-mediated inflammation of the gastrointestinal tract. Traditionally, medical management of these disorders has been based on use of systemic immunosuppressives. The development of new drugs that selectively inhibit leukocyte trafficking to the gut has the potential to reduce inflammation and minimize systemic toxicities. Key Messages: In this article, we review the immunology of the gut and the mechanism of action these emerging therapies for IBD. Natalizumab, a monoclonal antibody to

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Yerramothu, Praveen. "New Therapies of Neovascular AMD—Beyond Anti-VEGFs." Vision 2, no. 3 (2018): 31. http://dx.doi.org/10.3390/vision2030031.

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Neovascular age-related macular degeneration (nAMD) is one of the leading causes of blindness among the aging population. The current treatment options for nAMD include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). However, standardized frequent administration of anti-VEGF injections only improves vision in approximately 30–40% of nAMD patients. Current therapies targeting nAMD pose a significant risk of retinal fibrosis and geographic atrophy (GA) development in nAMD patients. A need exists to develop new therapies to treat nAMD with effective and long-term a

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Garlatti, Valentina, Sara Lovisa, Silvio Danese, and Stefania Vetrano. "The Multiple Faces of Integrin–ECM Interactions in Inflammatory Bowel Disease." International Journal of Molecular Sciences 22, no. 19 (2021): 10439. http://dx.doi.org/10.3390/ijms221910439.

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Inflammatory Bowel Disease (IBD) comprises a series of chronic and relapsing intestinal diseases, with Crohn’s disease and ulcerative colitis being the most common. The abundant and uncontrolled deposition of extracellular matrix, namely fibrosis, is one of the major hallmarks of IBD and is responsible for the progressive narrowing and closure of the intestine, defined as stenosis. Although fibrosis is usually considered the product of chronic inflammation, the substantial failure of anti-inflammatory therapies to target and reduce fibrosis in IBD suggests that fibrosis might be sustained in a

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Yoo, Jun Hwan, Stefan Holubar, and Florian Rieder. "Fibrostenotic strictures in Crohn’s disease." Intestinal Research 18, no. 4 (2020): 379–401. http://dx.doi.org/10.5217/ir.2019.09148.

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The use of biologic agents including anti-tumor necrosis factor monoclonal antibodies followed by anti-integrins and anti-interleukins has drastically changed the treatment paradigm of Crohn’s disease (CD) by improving clinical symptoms and mucosal healing. However, up to 70% of CD patients still eventually undergo surgery mainly due to fibrostenotic strictures. There are no specific anti-fibrotic drugs yet. This review comprehensively addresses the mechanism, prediction, diagnosis and treatment of the fibrostenotic strictures in CD. We also introduce promising anti-fibrotic agents which may b

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Łasiñska, Izabela, and Jacek Mackiewicz. "Integrins as A New Target for Cancer Treatment." Anti-Cancer Agents in Medicinal Chemistry 19, no. 5 (2019): 580–86. http://dx.doi.org/10.2174/1871520618666181119103413.

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:Despite the great progress in the development of targeted therapies for different types of cancer utilizing monoclonal antibodies (e.g., cetuximab for colorectal cancer and head and neck cancer therapy), kinase inhibitors (e.g., sorafenib for kidney cancer and gastrointestinal stromal tumours therapy), and immunomodulatory treatments (e.g., nivolumab and pembrolizumab for melanoma therapy and lung cancer therapy), there is still a need to search for new, more effective treatments.:Integrins are responsible for intercellular adhesion and interaction with the cellular matrix. The function of in

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Dotan, Iris, Matthieu Allez, Silvio Danese, Mary Keir, Swati Tole, and Jacqueline McBride. "The role of integrins in the pathogenesis of inflammatory bowel disease: Approved and investigational anti‐integrin therapies." Medicinal Research Reviews 40, no. 1 (2019): 245–62. http://dx.doi.org/10.1002/med.21601.

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Sawada, Kenjiro, Chifumi Ohyagi-Hara, Tadashi Kimura, and Ken-ichirou Morishige. "Integrin Inhibitors as a Therapeutic Agent for Ovarian Cancer." Journal of Oncology 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/915140.

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Ovarian cancer is a deadly disease, with a cure rate of only 30%. Despite aggressive treatments, relapse remains almost inevitable in patients with advanced-stage disease. In recent years, great progress has been made towards targeting integrins in cancer treatment, and clinical studies with various integrin inhibitors have demonstrated their effectiveness in blocking cancer progression. Given that the initial critical step of ovarian cancer metastasis is the attachment of cancer cells onto the peritoneum or omentum, in addition to the proven positive clinical results of anti-angiogenic therap

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Kustiati, Ulayatul, Suleyman Ergün, Srikanth Karnati, Dwi Aris Agung Nugrahaningsih, Dwi Liliek Kusindarta та Hevi Wihadmadyatami. "Ethanolic Extract of Ocimum sanctum Linn. Inhibits Cell Migration of Human Lung Adenocarcinoma Cells (A549) by Downregulation of Integrin αvβ3, α5β1, and VEGF". Scientia Pharmaceutica 90, № 4 (2022): 69. http://dx.doi.org/10.3390/scipharm90040069.

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Adenocarcinoma lung cancer is a type of non-small cell lung carcinoma (NSCLC), which accounts for 85% of lung cancer incidence globally. The therapies that are being applied, both conventional therapies and antibody-based treatments, are still found to have side effects. Several previous studies have demonstrated the ability of the ethanolic extract of Ocimum sanctum Linn. (EEOS) as an ethnomedicine with anti-tumor properties. The aim of this study was to determine the effect of Ocimum sanctum Linn. ethanolic extract in inhibiting the proliferation, angiogenesis, and migration of A549 cells (N

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Wehkamp, Jan, and Eduard F. Stange. "Recent advances and emerging therapies in the non-surgical management of ulcerative colitis." F1000Research 7 (August 7, 2018): 1207. http://dx.doi.org/10.12688/f1000research.15159.1.

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The so-called “biologicals” (monoclonal antibodies to various inflammatory targets like tumor necrosis factor or integrins) have revolutionized the treatment of inflammatory bowel diseases. In ulcerative colitis, they have an established role in inducing remission in steroid-refractory disease and, thereafter, maintaining remission with or without azathioprine. Nevertheless, their limitations are also obvious: lack of primary response or loss of response during maintenance as well as various, in part severe, side effects. The latter are less frequent in anti-integrin treatment, but efficacy, e

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Dormond, Olivier, and Curzio Rüegg. "Regulation of endothelial cell integrin function and angiogenesis by COX-2, cAMP and Protein Kinase A." Thrombosis and Haemostasis 90, no. 10 (2003): 577–85. http://dx.doi.org/10.1160/th03-03-0196.

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SummaryAngiogenesis, the development of new blood vessels from preexisting vessels, is a key step in tumor growth, invasion and metastasis formation. Inhibition of tumor angiogenesis is considered as an attractive approach to suppress cancer progression and spreading. Adhesion receptors of the integrin family promote tumor angiogenesis by mediating cell migration, proliferation and survival of angiogenic endothelial cells. Integrins up regulated and highly expressed on neovascular endothelial cells, such as αVβ3 and α5β1, have been considered as relevant targets for anti-angiogenic therapies.

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Furfaro, Federica, Ludovico Alfarone, Daniela Gilardi, et al. "TL1A: A New Potential Target in the Treatment of Inflammatory Bowel Disease." Current Drug Targets 22, no. 7 (2021): 760–69. http://dx.doi.org/10.2174/1389450122999210120205607.

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Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic inflammatory diseases of the gastrointestinal tract. In the last few years, the development of biological agents targeting cytokines and receptors involved in IBD pathogenesis has led to better outcomes and has improved the course of the disease. Despite their effectiveness, drugs such as tumor necrosis factor (TNF) inhibitors, anti-Interleukin-12/23 and anti-integrins, do not induce a response in about one-third of patients, and 40% of patients lose response over time. Therefore, more ef

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Mitsdoerffer, Meike, Giovanni Di Liberto, Sarah Dötsch, et al. "Formation and immunomodulatory function of meningeal B cell aggregates in progressive CNS autoimmunity." Brain 144, no. 6 (2021): 1697–710. http://dx.doi.org/10.1093/brain/awab093.

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Abstract Meningeal B lymphocyte aggregates have been described in autopsy material of patients with chronic multiple sclerosis. The presence of meningeal B cell aggregates has been correlated with worse disease. However, the functional role of these meningeal B cell aggregates is not understood. Here, we use a mouse model of multiple sclerosis, the spontaneous opticospinal encephalomyelitis model, which is built on the double transgenic expression of myelin oligodendrocyte glycoprotein-specific T-cell and B-cell receptors, to show that the formation of meningeal B cell aggregates is dependent

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Yang, Edward, Ann M. Arvin та Stefan L. Oliver. "Role for the αV Integrin Subunit in Varicella-Zoster Virus-Mediated Fusion and Infection". Journal of Virology 90, № 16 (2016): 7567–78. http://dx.doi.org/10.1128/jvi.00792-16.

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ABSTRACTVaricella-zoster virus (VZV) is an alphaherpesvirus that causes varicella and herpes zoster. Membrane fusion is essential for VZV entry and the distinctive syncytium formation in VZV-infected skin and neuronal tissue. Herpesvirus fusion is mediated by a complex of glycoproteins gB and gH-gL, which are necessary and sufficient for VZV to induce membrane fusion. However, the cellular requirements of fusion are poorly understood. Integrins have been implicated to facilitate entry of several human herpesviruses, but their role in VZV entry has not yet been explored. To determine the involv

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Ager, Ann, H. Angharad Watson, Sophie C. Wehenkel, and Rebar N. Mohammed. "Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells." Biochemical Society Transactions 44, no. 2 (2016): 377–85. http://dx.doi.org/10.1042/bst20150254.

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The success of adoptive T-cell therapies for the treatment of cancer patients depends on transferred T-lymphocytes finding and infiltrating cancerous tissues. For intravenously transferred T-cells, this means leaving the bloodstream (extravasation) from tumour blood vessels. In inflamed tissues, a key event in extravasation is the capture, rolling and arrest of T-cells inside blood vessels which precedes transmigration across the vessel wall and entry into tissues. This depends on co-ordinated signalling of selectins, integrins and chemokine receptors on T-cells by their respective ligands whi

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Mair, Devin B., Heather M. Ames, and Rong Li. "Mechanisms of invasion and motility of high-grade gliomas in the brain." Molecular Biology of the Cell 29, no. 21 (2018): 2509–15. http://dx.doi.org/10.1091/mbc.e18-02-0123.

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High-grade gliomas are especially difficult tumors to treat due to their invasive behavior. This has led to extensive research focusing on arresting glioma cell migration. Cell migration involves the sensing of a migratory cue, followed by polarization in the direction of the cue, and reorganization of the actin cytoskeleton to allow for a protrusive leading edge and a contractile trailing edge. Transmission of these forces to produce motility also requires adhesive interactions of the cell with the extracellular microenvironment. In glioma cells, transmembrane receptors such as CD44 and integ

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Wang, Shizhen Emily. "The Functional Crosstalk between HER2 Tyrosine Kinase and TGF-β Signaling in Breast Cancer Malignancy". Journal of Signal Transduction 2011 (24 лютого 2011): 1–8. http://dx.doi.org/10.1155/2011/804236.

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Accumulating evidence indicates a functional crosstalk between the HER2 (ErbB2) tyrosine kinase and the TGF-β signaling mediated by its serine/threonine kinase receptors. In HER2-overexpressing breast cancer, this crosstalk results in increased cancer cell proliferation, survival and invasion, accelerated cancer progression and metastasis in animal models, and resistance to chemotherapy and HER2-targeted therapy. The transformed cellular context with constitutively active HER2 signaling, as a consequence of HER2 gene amplification or overexpression, converts TGF-β from a tumor suppressor to a

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18

Morris, Kenise, and Anne-Laure Papa. "Abstract A004: The role of calcium in metastatic progression." Cancer Research 83, no. 2_Supplement_2 (2023): A004. http://dx.doi.org/10.1158/1538-7445.metastasis22-a004.

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Abstract Calcium is essential to the structural stability of integrin proteins implicated in platelet–cancer cell interactions, namely integrins GPIIb/IIIa and avb3, which share a common beta subunit (Pelletier et al., J Biol Chem, 1996), (Zhang and Chen, Cell Adh Migr, 2012). Additionally, calcium is essential for ligand binding to these integrins (e.g., fibrinogen) that bridge platelets and cancer cells (Raborn et al., Biochemistry, 2011) and for the downstream signaling following mechanical and chemical stimulation in the integrin microenvironment (Michelson, Platelets, 2013). Platelet-canc

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Vetter, Marcel, and Markus F. Neurath. "Emerging oral targeted therapies in inflammatory bowel diseases: opportunities and challenges." Therapeutic Advances in Gastroenterology 10, no. 10 (2017): 773–90. http://dx.doi.org/10.1177/1756283x17727388.

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To improve quality of life and prevent long-term risks in patients with inflammatory bowel diseases (IBDs: Crohn’s disease, ulcerative colitis), it is essential to suppress inflammatory activity adequately. However, corticosteroids are only suitable for therapy of acute flares and the evidence for positive effects of immunosuppressive substances like azathioprine or 6-mercapropurine is mainly limited to maintenance of remission. In addition, only subgroups of patients benefit from biologicals targeting tumour necrosis factor α or α4β7 integrins. In summary, until now the disease activity is no

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Van Assche, Gert, and Paul Rutgeerts. "Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease." American Journal of Physiology-Gastrointestinal and Liver Physiology 288, no. 2 (2005): G169—G174. http://dx.doi.org/10.1152/ajpgi.00423.2004.

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Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but α4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological as

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Walsh, Garry M., Alexander J. Robinson, and Ping Wu. "Recent Developments in Targeting Eosinophil Accumulation as a Novel Therapeutic Approach for Asthma." Open Allergy Journal 1, no. 1 (2008): 35–41. http://dx.doi.org/10.2174/1874838400801010035.

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Current therapies for asthma are aimed at controlling disease symptoms and for the majority of patients inhaled glucocorticoid anti-inflammatory therapy is both effective and well-tolerated. However, concerns remain about the adverse effects of glucocorticoids while a subset of asthmatic patients remains symptomatic despite optimal treatment thereby creating a clear unmet medical need. There is considerable evidence that implicates eosinophils as important effector cells and immunomodulators in the inflammation characteristic of asthma. Numerous in vitro and animal studies have demonstrated es

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Khamessi, Oussema, Hazem Ben Mabrouk, Selim Kamoun, Chaima Hkimi, Kais Ghedira, and Riadh Kharrat. "The First Snake Venom KTS/Disintegrins-Integrin Interactions Using Bioinformatics Approaches." Molecules 28, no. 1 (2022): 325. http://dx.doi.org/10.3390/molecules28010325.

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Snake venom contains a number of active molecules that have been shown to possess high anti-tumor activities; disintegrins are an excellent example among these. Their ability to interact and bind with integrins suggests that they could be very valuable molecules for the development of new cancer therapeutic approaches. However, in the absence of a clear Lysine-Threonine-Serine (KTS) Disintegrins Integrin interaction model, the exact compound features behind it are still unknown. In this study, we investigated the structural characteristics of three KTS-disintegrins and the interaction mechanis

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Kawamoto, Eiji, Nodoka Nago, Takayuki Okamoto та ін. "The Lectin-Like Domain of Thrombomodulin Inhibits β1 Integrin-Dependent Binding of Human Breast Cancer-Derived Cell Lines to Fibronectin". Biomedicines 9, № 2 (2021): 162. http://dx.doi.org/10.3390/biomedicines9020162.

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Thrombomodulin is a molecule with anti-coagulant and anti-inflammatory properties. Recently, thrombomodulin was reported to be able to bind extracellular matrix proteins, such as fibronectin and collagen; however, whether thrombomodulin regulates the binding of human breast cancer-derived cell lines to the extracellular matrix remains unknown. To investigate this, we created an extracellular domain of thrombomodulin, TMD123-Fc, or domain deletion TM-Fc proteins (TM domain 12-Fc, TM domain 23-Fc) and examined their bindings to fibronectin in vitro by ELISA. The lectin-like domain of thrombomodu

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Johnston, B., T. B. Issekutz, and P. Kubes. "The alpha 4-integrin supports leukocyte rolling and adhesion in chronically inflamed postcapillary venules in vivo." Journal of Experimental Medicine 183, no. 5 (1996): 1995–2006. http://dx.doi.org/10.1084/jem.183.5.1995.

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A role for the alpha 4-integrin (alpha 4 beta 1 or alpha 4 beta 7), has been implicated in the recruitment of peripheral blood mononuclear cells (PBMCs) to sites of inflammation. However, the adhesive interactions (i.e., tethering, rolling, and adhesion) mediated by the alpha 4-integrin have not been characterized in vivo. The objective of this study was to establish a model wherein postcapillary venules were chronically inflamed, and then use intravital microscopy to identify the adhesive interactions mediated by the alpha 4-integrin in vivo. Between 4 and 20 d after immunization with Mycobac

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Scanlon, C. S., E. A. Van Tubergen, R. C. Inglehart, and N. J. D’Silva. "Biomarkers of Epithelial-Mesenchymal Transition in Squamous Cell Carcinoma." Journal of Dental Research 92, no. 2 (2012): 114–21. http://dx.doi.org/10.1177/0022034512467352.

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An understanding of the process by which tumor cells destroy the basement membrane of the surface epithelium, invade, and metastasize is essential to the development of novel treatment of head and neck squamous cell carcinoma (HNSCC). In recent years, there has been increased interest in the role of epithelial-mesenchymal transition (EMT) in invasion. EMT is a process that describes the development of motile, mesenchymal-like cells from non-motile parent epithelial cells. There are 3 known types of EMT that mediate development, wound healing, and carcinogenesis. This review summarizes studies

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Huang, Jianmei, Jianming Huang, and Guonan Zhang. "Insights into the Role of Sialylation in Cancer Metastasis, Immunity, and Therapeutic Opportunity." Cancers 14, no. 23 (2022): 5840. http://dx.doi.org/10.3390/cancers14235840.

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Sialylation is an enzymatic process that covalently attaches sialic acids to glycoproteins and glycolipids and terminates them by creating sialic acid-containing glycans (sialoglycans). Sialoglycans, usually located in the outmost layers of cells, play crucial biological roles, notably in tumor transformation, growth, metastasis, and immune evasion. Thus, a deeper comprehension of sialylation in cancer will help to facilitate the development of innovative cancer therapies. Cancer sialylation-related articles have consistently increased over the last four years. The primary subjects of these st

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Monasterio, Carmen, Annette Schmitt-Gräff, Matthias Pohl, et al. "Fatal ulcerative enteritis of the small intestine in a patient with ulcerative colitis treated with vedolizumab." Zeitschrift für Gastroenterologie 55, no. 10 (2017): 1014–20. http://dx.doi.org/10.1055/s-0043-111805.

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AbstractVedolizumab (VDZ) inhibits α4β7 integrins and is used to target intestinal immune responses in patients with inflammatory bowel disease, which is considered to be relatively safe. Here we report on a fatal complication following VDZ administration. A 64-year-old female patient with ulcerative colitis (UC) refractory to tumor necrosis factor inhibitors was treated with VDZ. One week after the second VDZ infusion, she was admitted to hospital with severe diarrhea and systemic inflammatory response syndrome (SIRS). Blood stream infections were ruled out, and endoscopy revealed extensive u

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Eddy, Allison. "Serine proteases, inhibitors and receptors in renal fibrosis." Thrombosis and Haemostasis 101, no. 04 (2009): 656–64. http://dx.doi.org/10.1160/th08-12-0779.

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SummaryChronic kidney disease (CKD) is estimated to affect one in eight adults. Their kidney function progressively deteriorates as inflammatory and fibrotic processes damage nephrons. New therapies to prevent renal functional decline must build on basic research studies that identify critical cellular and molecular mediators. Plasminogen activator inhibitor-1 (PAI-1), a potent fibrosis-promoting glycoprotein, is one promising candidate. Absent from normal kidneys, PAI-1 is frequently expressed in injured kidneys. Studies in genetically engineered mice have demonstrated its potency as a pro-fi

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Stuve, Olaf, Geert R. A. M. D'Haens, Walter Reinisch, et al. "Anti-MAdCAM-1 therapy does not affect immune surveillance in the central nervous system." Journal of Immunology 196, no. 1_Supplement (2016): 139.6. http://dx.doi.org/10.4049/jimmunol.196.supp.139.6.

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Abstract Background Blocking integrins can be associated with an increased risk of progressive multifocal encephalopathy (PML). MAdCAM-1 is an adhesion molecule that is not constitutively expressed in healthy CNS and considered mostly gut-selective. However, MAdCAM-1 is upregulated in choroid plexus epithelium during experimental autoimmune encephalomyelitis (EAE. PF-00547659 is a fully human mAb that is highly selective for MAdCAM-1. The purpose of this study was to investigate its effect on cellular elements of immune surveillance in the CNS and blood of patients with Crohn’s disease (CD). M

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Li, Yi, Jianping Chen, Andrew A. Bolinger, et al. "Target-Based Small Molecule Drug Discovery Towards Novel Therapeutics for Inflammatory Bowel Diseases." Inflammatory Bowel Diseases 27, Supplement_2 (2021): S38—S62. http://dx.doi.org/10.1093/ibd/izab190.

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Abstract Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a class of severe and chronic diseases of the gastrointestinal (GI) tract with recurrent symptoms and significant morbidity. Long-term persistence of chronic inflammation in IBD is a major contributing factor to neoplastic transformation and the development of colitis-associated colorectal cancer. Conversely, persistence of transmural inflammation in CD is associated with formation of fibrosing strictures, resulting in substantial morbidity. The recent introduction of biological response m

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Carlos, TM, and JM Harlan. "Leukocyte-endothelial adhesion molecules." Blood 84, no. 7 (1994): 2068–101. http://dx.doi.org/10.1182/blood.v84.7.2068.2068.

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Abstract In the 9 years since the last review on leukocyte and endothelial interactions was published in this journal many of the critical structures involved in leukocyte adherence to and migration across endothelium have been elucidated. With the advent of cell and molecular biology approaches, investigations have progressed from the early descriptions by intravital microscopy and histology, to functional and immunologic characterization of adhesion molecules, and now to the development of genetically deficient animals and the first phase I trial of “anti-adhesion” therapy in humans. The mol

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Carlos, TM, and JM Harlan. "Leukocyte-endothelial adhesion molecules." Blood 84, no. 7 (1994): 2068–101. http://dx.doi.org/10.1182/blood.v84.7.2068.bloodjournal8472068.

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In the 9 years since the last review on leukocyte and endothelial interactions was published in this journal many of the critical structures involved in leukocyte adherence to and migration across endothelium have been elucidated. With the advent of cell and molecular biology approaches, investigations have progressed from the early descriptions by intravital microscopy and histology, to functional and immunologic characterization of adhesion molecules, and now to the development of genetically deficient animals and the first phase I trial of “anti-adhesion” therapy in humans. The molecular cl

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Tabe, Yoko, Linhua Jin, Gordon B. Mills, Yuko Tsutsumi-Ishii, Michael Andreeff, and Marina Konopleva. "Mesenchymal Stem Cells Promote Survival of Leukemic Cells Via Integrin-Linked Kinase (ILK)-Dependent Akt and STAT3 Activation: Implications for Leukemia Therapy." Blood 104, no. 11 (2004): 3377. http://dx.doi.org/10.1182/blood.v104.11.3377.3377.

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Abstract The β integrins play an important role in the cell-to-cell interactions, which trigger intracellular signal transduction pathways. Integrin-linked kinase (ILK) has been shown to directly interact with β integrins and phosphorylate Akt, which promotes cell survival. On the other hand, PI3K/Akt and JAK/STAT signaling pathways are also recognized as potent anti-apoptotic mediators activated by ligation of growth factor receptors. We have previously demonstrated that stroma cells protect acute promyelocytic leukemic (APL) cells from apoptosis (Tabe, Blood103:1815–1822, 2004). Here, we inv

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Lee, J., G. Kim, J. C. Kim, J. H. Park, C. Han, and M. Kim. "P098 Novel drug candidate for the treatment of Inflammatory Bowel Disease with unique mechanisms of action." Journal of Crohn's and Colitis 17, Supplement_1 (2023): i261. http://dx.doi.org/10.1093/ecco-jcc/jjac190.0228.

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Abstract Background Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation and severe dysfunction of the gastrointestinal tract. Despite significant improvements in therapeutic agents targeting IBD, many subjects with IBD fail to achieve recovery or do not respond to current medication. Moreover, current therapy has been limited to the management of inflammation, while almost no progress has been made in the development of anti-fibrotic therapies for IBD. NEXEL's novel protein NP-011, targeting αVβ3 and αVβ5 integrins and phosphatidylserine, has shown anti-inflammatory and a

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Berghoff, Anna Sophie, Orsolya Rajky, Frank Winkler, et al. "Evaluation of invasion patterns and their correlation with integrin alphavbeta expression in brain metastases of solid cancers." Journal of Clinical Oncology 31, no. 15_suppl (2013): 2059. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.2059.

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2059 Background: Understanding the pathobiology of brain metastases (BM) could guide the establishment of new targeted therapies. Methods: We collected 57 autopsy specimens of BM (primary tumor: 27 lung cancer, 6 breast cancer, 8 melanoma, 1 kidney cancer, 2 colorectal cancer, 13 other) and histologically evaluated the patterns of invasion into the surrounding brain parenchyma. Expression of the following integrins was evaluated using immunohistochemistry: with novel antibodies for αv subunit, αvβ3, αvβ5, αvβ6 and αvβ8 integrin. Results: We observed three main invasion patterns: well-demarcate

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Hsieh, Yao-Te, Eun Ji Gang, Halvard Bonig, Ronald J. Biediger, Peter Vanderslice, and Yong-Mi Kim. "The Small Molecule Inhibitor of VLA4 TBC3486 Sensitizes Resistant ALL to Chemotherapy." Blood 120, no. 21 (2012): 1500. http://dx.doi.org/10.1182/blood.v120.21.1500.1500.

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Abstract Abstract 1500 Significant progress notwithstanding, drug resistant acute lymphoblastic leukemia (ALL) remains a therapeutic challenge, as well as acute and long-term off-target toxicity of anti-ALL therapies can be dose-limiting or debilitating. Therefore, the development of more targeted therapies is desirable. We recently provided evidence that chemotherapy resistance of ALL cells can be partly overcome by interfering with the function of VLA4, the alpha4beta1 integrin, in vivo. In those studies, we used the anti-functional antibody Natalizumab. We extended our studies to an alterna

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De Lorenzo, Emanuele, Serena Pillozzi, Marika Masselli, Olivia Crociani, Andrea Becchetti, and Annarosa Arcangeli. "Potassium Channels as Novel Pharmacological Targets in Acute Myeloid Leukemia." Blood 112, no. 11 (2008): 4034. http://dx.doi.org/10.1182/blood.v112.11.4034.4034.

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Abstract Targeted therapies are considerably changing the treatment and prognosis of hematologic malignancies. The progressive elucidation of the molecular mechanisms that regulate establishment and progression of tumours is leading to more specific and efficacious pharmacological approaches. In this picture, ion channels represent a relatively unexpected, but very promising players. In particular hERG1 channel expression is altered in many primary leukemias and frequently turn out to exert pleiotropic effects on cancer cell physiology, interaction with the external matrix and stimulation of a

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Nimmanapalli, Ramadevi, Elvira Gerbino, William S. Dalton, and Melissa Alsina. "Adhesion of 8226 Myeloma Cell Lines Induces over Expression of HSP70 and its Inhibition Reverses CAM-DR and Acquired Drug Resistance in Multiple Myeloma." Blood 104, no. 11 (2004): 636. http://dx.doi.org/10.1182/blood.v104.11.636.636.

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Abstract Multiple myeloma (MM) is characterized by the clonal proliferation of malignant plasma cells that accumulate preferentially in the bone marrow. In spite of high-dose chemotherapy and novel targeted therapies, myeloma remains to be an incurable disease due to emergence of drug resistance. Therefore, identification of mechanisms involved in drug resistance are essential to develop new and more effective targeted therapies. Heat shock proteins (HSPs) are a super family of highly conserved proteins, which are induced in plant, yeast, bacterial and mammalian cells in response to an array o

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Weidow, Brandy L., Jacqueline Vidosh, and John P. Biggerstaff. "The Role of Soluble Fibrin and Fibrin Inhibitory Peptides in Cancer Metastasis." Blood 108, no. 11 (2006): 5200. http://dx.doi.org/10.1182/blood.v108.11.5200.5200.

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Abstract Circulating soluble fibrin (sFn) is a marker for ongoing disseminated intravascular coagulation and may have prognostic significance, especially in metastatic cancers. Anti-coagulant therapies have been effective in reducing metastasis in several cancers, but with increased risk of bleeding. The authors have previously demonstrated that soluble fibrin (sFn), which is elevated in many cancer patients, enhances metastasis in an experimental model, and increases platelet/tumor cell adherence by cross-linking platelet aIIbb3 to tumor cell CD54 (a receptor for two of the leukocyte b2 integ

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Greenfield, Katharine, Saloomeh Mokhtari, Melissa Haug, Christopher D. Porada, and Graca Almeida-Porada. "Identification and Phenotypic Characterization of a Subpopulation of Acute Myelogenous Leukemia (AML) Cells with Increased Plastic Adherence." Blood 120, no. 21 (2012): 2556. http://dx.doi.org/10.1182/blood.v120.21.2556.2556.

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Abstract Abstract 2556 The high incidence of relapse in acute myelogenous leukemia (AML) patients has been attributed to the existence of a small population of leukemic stem cells (LSC) that current therapies are unable to eradicate. LSC, in similarity to normal hematopoietic stem cells (HSC), are able to engraft, self-renew, and interact with cells within the bone marrow (BM) niche. During leukemogenesis, changes within the BM microenvironment promote LSC survival and expansion, and shelter leukemic cells from chemotherapy. Therefore, displacing these cells from the BM niches prior to chemoth

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Blaess, J., J. Walther, J. E. Gottenberg, J. Sibilia, L. Arnaud, and R. Felten. "AB0332 IMMUNOSUPPRESSIVE AND IMMONOMODULATING AGENTS IN RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW OF CLINICAL TRIALS AND THEIR CURRENT DEVELOPMENT STAGE." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1464.1–1465. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1124.

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Background:Rheumatoid arthritis (RA) is the most frequent chronic inflammatory diseases with an incidence of 0.5% to 1%. Therapeutic arsenal of RA has continuously expanded in recent years with the recent therapeutic progress with the arrival of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), biological (bDMARDs) and targeted synthetic (tsDMARDs), JAK inhibitors. However, there are still some unmet needs for patients who do not achieve remission and who continue to worsen despite treatments. Of note, only approximately 40% of patients are ACR70 responders, in most ran

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McQueen, Teresa, Yoko Tabe, Marina Konopleva, and Michael Andreeff. "Inhibition of PI3K or Integrin-Linked Kinase (ILK) Target Primary AML Cells within the Bone Marrow Microenvironment in the In Vitro Co-Culture System." Blood 108, no. 11 (2006): 1903. http://dx.doi.org/10.1182/blood.v108.11.1903.1903.

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Abstract In hematological malignancies, there are reciprocal interactions between leukemic cells and cells of the bone marrow microenvironment such as marrow stromal cells (MSC). It is proposed that specific niches within the bone marrow microenvironment provide a sanctuary for subpopulations of leukemic cells to evade chemotherapy-induced death, and we indeed demonstrated that MSC protect primary AML cells from Ara-C induced apoptosis in vitro (Konopleva, Leukemia 2002). Integrin-linked kinase (ILK) has been shown to directly interact with β integrins and phosphorylate AKT in a PI3-kinase(PI3

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Blunt, Matthew D., Jack Parnell, Marta Larrayoz, et al. "The Syk\Jak Inhibitor Cerdulatinib (PRT062070) Shows Promising Preclinical Activity in Chronic Lymphocytic Leukemia By Antagonising B Cell Receptor and Microenvironmental Signalling." Blood 126, no. 23 (2015): 1716. http://dx.doi.org/10.1182/blood.v126.23.1716.1716.

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Abstract The emergence of B cell receptor (BCR) kinase inhibitors has proved effective for the treatment of a number of B-cell malignancies including chronic lymphocytic leukemia (CLL). BTK and PI3K inhibitors have clear efficacy in suppressing tumor progression but have not been curative. A number of patients have developed resistance to these drugs following mutation of the BTK or PLCγ2 gene. Whilst, other patients are unable to tolerate these drugs due to adverse events or progress whilst on therapy for unknown reasons. Thus the development of novel drugs which are still effective once othe

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Roth, Patrick. "The role of integrins in glioma biology and anti-glioma therapies." SpringerPlus 4, S1 (2015). http://dx.doi.org/10.1186/2193-1801-4-s1-l12.

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Al-Bawardy, Badr, Raina Shivashankar, and Deborah D. Proctor. "Novel and Emerging Therapies for Inflammatory Bowel Disease." Frontiers in Pharmacology 12 (April 14, 2021). http://dx.doi.org/10.3389/fphar.2021.651415.

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Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s disease are chronic, relapsing and remitting disorders of intestinal inflammation with potential systemic manifestations. Despite the availability of current biologics, such as anti-tumor necrosis factor (anti-TNF), anti-integrins, anti-interleukins and small molecules such as tofacitinib, the rates of primary and secondary treatment failure remain high in IBD. This highlights the importance of continued development of new therapeutic targets and modifications of existing ones to improve the treatment response rates and t

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Leal, Raquel F., and Azucena Salas. "Adhesion Molecules as a Therapeutic Target in IBD." EMJ Gastroenterology, December 16, 2013, 62–73. http://dx.doi.org/10.33590/emjgastroenterol/10314457.

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Recruitment of circulating leukocytes to areas of inflammation is a key process in the pathophysiology of inflammatory bowel diseases, including ulcerative colitis (UC). This is a finely regulated multistep process in which specialised adhesion and signalling molecules mediate a series of sequential steps. Following activation, integrins expressed on the surface of leukocytes become the key mediators of firm adhesion and emigration through interaction with immunoglobulin superfamily molecules expressed on the vascular endothelium. The anti α4 antibody natalizumab has shown efficacy in inducing

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Reddy, Emily C., Guangheng Zhu, Pingguo Chen, et al. "Abstract 54: PSI Domain of ß3 Integrin Has Endogenous Thiol Isomerase Function and is a Novel Antithrombotic Therapeutic Target." Arteriosclerosis, Thrombosis, and Vascular Biology 34, suppl_1 (2014). http://dx.doi.org/10.1161/atvb.34.suppl_1.54.

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Integrin αIIbβ3 plays a critical role in platelet aggregation and adhesion, key events in hemostasis and thrombosis. Integrin activation involves complex signalling events that lead to conformational changes exposing ligand-binding sites; however, mechanisms underlying integrin activation remain poorly understood. The β subunit contains a PSI domain that is highly conserved across integrins and species, though its function is unknown. Integrin β subunits are cysteine-rich and endogenous thiol isomerase activity in integrin β3 has been reported. The PSI domain contains two CXXC sequences, the a

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Lightner, Amy L., Zeji Du, Timothy E. Peterson, et al. "Commonly Used Immunosuppressives Affect Mesenchymal Stem Cell Viability and Function: Should We Rethinking Clinical Trial Inclusion and Exclusion Criteria?" Crohn's & Colitis 360 1, no. 3 (2019). http://dx.doi.org/10.1093/crocol/otz025.

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Abstract Background Clinical trials utilizing mesenchymal stem cells (MCSs) for the treatment of perianal Crohn disease are expanding. Most enrolled Crohn patients are being actively treated with corticosteroids, immunomodulators, and biologic therapy for their luminal and perianal disease at the time of enrollment and treatment. Aim We sought to broaden the understanding of the effect of corticosteroids, immunomodulators, and biologic therapy on the viability and function of MCSs. This information is important for tailoring inclusion and exclusion criteria of clinical trials. Methods Human ad

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Caron, Bénédicte, William J. Sandborn, Remo Panaccione, et al. "Efficacy of Pharmacological Agents for Ulcerative Proctitis: A Systematic Literature Review." Journal of Crohn's and Colitis, November 30, 2021. http://dx.doi.org/10.1093/ecco-jcc/jjab218.

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Abstract Background Ulcerative proctitis is a common and often highly symptomatic form of inflammatory bowel disease. We performed a systematic review to assess the efficacy of different therapies in the management of patients with ulcerative proctitis. Methods We identified randomized controlled trials in adults with ulcerative proctitis treated with oral or topical therapies for induction of response or remission, or prevention of relapse. Results A total of 32 randomized controlled trials were included [27 induction/2839 participants, five maintenance/334 participants]. Follow-up varied fro

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Kruk, Linus, Attila Braun, Erika Cosset, Thomas Gudermann, and Elmina Mammadova-Bach. "Galectin functions in cancer-associated inflammation and thrombosis." Frontiers in Cardiovascular Medicine 10 (February 17, 2023). http://dx.doi.org/10.3389/fcvm.2023.1052959.

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Galectins are carbohydrate-binding proteins that regulate many cellular functions including proliferation, adhesion, migration, and phagocytosis. Increasing experimental and clinical evidence indicates that galectins influence many steps of cancer development by inducing the recruitment of immune cells to the inflammatory sites and modulating the effector function of neutrophils, monocytes, and lymphocytes. Recent studies described that different isoforms of galectins can induce platelet adhesion, aggregation, and granule release through the interaction with platelet-specific glycoproteins and

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