scholarly journals Bronchopulmonary Dysplasia: Crosstalk Between PPARγ, WNT/β-Catenin and TGF-β Pathways; The Potential Therapeutic Role of PPARγ Agonists

2019 ◽  
Vol 7 ◽  
Author(s):  
Yves Lecarpentier ◽  
Elizabeth Gourrier ◽  
Vincent Gobert ◽  
Alexandre Vallée
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Therapeutic Role ◽  
Potential Therapeutic Role ◽  
Pparγ Agonists

In vitro studies reveal a potential therapeutic role of the combination of biguanides and statins for the treatment of prostate cancer

2018 ◽  
Author(s):  
Vicente Herrero-Aguayo ◽  
Juan M Jimenez-Vacas ◽  
Enrique Gomez-Gomez ◽  
Antonio J Leon-Gonzalez ◽  
Prudencio Saez-Martinez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
In Vitro Studies ◽  
Therapeutic Role ◽  
Potential Therapeutic Role

In Reply: Inhaled Nitric Oxide Trials: "Vive la différence!"

PEDIATRICS ◽  
1996 ◽  
Vol 97 (3) ◽  
pp. 438-439
Author(s):  
STEVEN H. ABMAN ◽  
JOHN P. KINSELLA
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Clinical Care ◽  
Inhaled Nitric Oxide ◽  
Multicenter Studies ◽  
Therapeutic Role ◽  
Inappropriate Use ◽  
Recent Commentary ◽  
Potential Therapeutic Role

Dr Davidson misinterprets our recent commentary on the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN) and potential therapeutic role of inhaled nitric oxide (I-NO) as suggesting the lack of a need for multiple studies that investigate different questions regarding its efficacy. In contrast, we clearly state that "multicenter studies play vital roles in improving clinical care, and the absence of such studies may lead to the inappropriate use of ineffective or harmful therapies."

scholarly journals The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer

2020 ◽  
Vol 20 ◽  
pp. 373-384 ◽  
Author(s):  
Huijuan Shi ◽  
Hui Li ◽  
Tiantian Zhen ◽  
Yu Dong ◽  
Xiaojuan Pei ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Role ◽  
Potential Therapeutic Role ◽  
Exosomal Microrna

Potential therapeutic role of statins in neurological disorders

2008 ◽  
Vol 8 (5) ◽  
pp. 827-837 ◽  
Author(s):  
Maurizio Bifulco ◽  
Anna Maria Malfitano ◽  
Giuseppe Marasco
Keyword(s):  
Neurological Disorders ◽  
Therapeutic Role ◽  
Potential Therapeutic Role

Potential Therapeutic Role of the Selective Adhesion Molecule (SAM) Inhibitor Natalizumab in Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1850-1850 ◽  
Author(s):  
Klaus Podar ◽  
Alexander Zimmerhackl ◽  
Ursula Hainz ◽  
Mariateresa Fulciniti ◽  
Sonia Vallet ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Adhesion Molecule ◽  
Research Funding ◽  
Therapeutic Role ◽  
Potential Therapeutic Role

Abstract Abstract 1850 Poster Board I-876 Multiple Myeloma (MM) is characterized by the clonal proliferation of malignant plasma cells in the bone marrow. Despite current therapeutic approach and prolongation of the median survival, new therapies are urgently needed. Integrins are cell surface receptors which mediate both cell-cell adhesion and cell-extracellular matrix (ECM) protein adhesion. beta1-integrins, including very-late antigen-4 (VLA-4;á4β1), are typically expressed on MM cells. In MM, VLA-4-mediated binding to ECMS and bone marrow stromal cells (BMSCs) confers protection against drug-induced apoptosis and triggers transcription and secretion of IL-6, the major MM growth and survival factor. In addition to up-regulation of cell surface-clustering, integrin activity can also be triggered by multiple agonists through ‘inside-out’ signaling, independent of changes in integrin expression levels. Importantly, VEGF-induced migration of MM cells on fibronectin is also associated with β1-integrin- and PI3-kinase- dependent PKC activation. Targeting VLA-4 is therefore of potential high therapeutic interest in MM. Indeed, an antibody against murine á4 induces inhibition of MM growth in a murine model. Natalizumab is a recombinant humanized IgG4 monoclonal antibody, which belongs to a new class of molecules known as selective adhesion molecule (SAM) inhibitors and binds to á4-integrin. Clinically, Natalizumab has demonstrated activity in patients with multiple sclerosis and Crohn's disease. Here we tested the potential therapeutic role of Natalizumab on MM cell survival, and migration in the BM microenvironment. VLA-4 is expressed by all MM cell lines investigated (NCIH929, RPMI8226, INA-6, MM.1S, and OPM2). Functionally, Natalizumab but not a control antibody, triggered dose-dependent inhibition of MM cell adhesion to fibronectin, BMSCs, and endothelial cells (ECs). Importantly, inhibition of adhesion to fibronectin, BMSCs, or ECs was observed in MM cells pretreated with Natalizumab. Moreover, inhibition of MM cell adhesion to fibronectin, BMSCs, or ECs was also observed when Natalizumab was added to already adherent MM cells. Taken together, Natalizumab decreases adhesion of non-adherent MM cells as well as binding of already adherent MM cells to non-cellular and cellular components of the microenvironment. Given the protective role of the microenvironment on MM cell survival, we next sought to evaluate the chemosensitizing activity of Natalizumab. Specifically, we investigated dose- and time- dependent effects of Natalizumab, alone and when combined with conventional and novel therapies, on MM cells. Our results show that Natalizumab alone did not inhibit growth or survival of MM cells when cultured without components of the microenvironment. However, Natalizumab enhanced sensitivity of tumor cells to both bortezomib and dexamethasone in MM-BMSC and, MM-EC co-cultures. These data indicate a potential role of Natalizumab in bortezomib- and dexamethasone-containing treatment regimens including MPV. Moreover, Natalizumab decreases IL-6 and VEGF secretion triggered in MM-BMSC co-cultures. Consequently, angiogenesis triggered by supernatants of Natalizumab- treated MM-BMSC co-cultures was inhibited. Moreover, Natalizumab blocked MM cell migration on fibronectin triggered by both VEGF and IGF-1. Finally, our previous results implicate an PKC signaling in MM cell migration on fibronectin, and our current results show that Natalizumab inhibits phosphorylation of á4 integrins and PKC induced by co-stimulation with VEGF/ fibronectin, IGF-1/ fibronectin, and patient serum. Taken together, our data indicate a potential therapeutic role of Natalizumab in MM. Ongoing studies evaluating the effect of Natalizumab in a SCID-hu murine model of MM will also be reported. Disclosures: Podar: Biogen Idec: Research Funding. Off Label Use: natalizumab, integrin inhibitor. Zimmerhackl:Biogen Idec: Research Funding. Olsen:Biogen Idec: Employment.

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