target receptors androgen therapy has emerged as an effective tool for managing prostate cancer (PCa). However, the frequent occurrence of therapy resistance is a major challenge in the clinical management of the patient, as well as the molecular mechanisms behind resistance therapy is not yet fully understood.
In this study, we aimed to identify new targets for intervention with therapy resistance using gene expression analysis of PCa spheroids co-cultures in which the cells of PCa were grown in the presence of fibroblasts associated cancer (CAFS) and which had previously been shown to be reliable models for change antiandrogen resistance.Gene expression of co-culture spheroids (LNCaP and featured DuCaP together with the CAFS) identified by Illumina microarray profiles.
Real-time PCR, Western blotting, immunohistochemistry and cell viability tests in 2D and 3D cultures performed to validate the selected target expression in vitro and in vivo. cytokine profiles was conducted to analyze the CAF-conditioned medium.Gene co-culture expression analysis spheroids revealed that CAFS trigger a significant upregulation of cholesterol and steroid biosynthesis pathway in PCa cells. Cytokine profiling reveal a high number of pro-inflammatory factors, pro-migratory and pro-angiogenic in the supernatant CAF.
In particular, two genes, 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (HMGCS2) and aldo-keto reductase family 1 member C3 (AKR1C3), was significantly upregulated in PCa cells in co-culture with CAFS. Both enzymes also increased significantly in human PCa compared with benign tissue with AKR1C3 expression even associated with Gleason score and metastatic status. Inhibiting HMGCS2 and AKR1C3 resulted in a significant growth retardation of spheroids co-culture as well as a variety of castration and enzalutamide resistant cell lines in 2D and 3D cultures, underlining their alleged role in PCa.
Importantly, dual targeting cholesterol and steroid biosynthesis with simvastatin, commonly prescribed cholesterol synthesis inhibitors, and inhibitors to have the strongest growth inhibitory AKR1C3 effect.From our results we conclude that the CAFS induces upregulation of cholesterol and steroid biosynthesis in PCa cells, driving them to AR targeted therapy resistance. Hinder both paths with AKR1C3 inhibitor simvastatin and therefore may be a promising approach to overcome resistance to targeted therapies AR in PCa. Video abstract.

Role of Platelet-Derived Growth Factor (PDGF) in Asthma as an immunoregulatory Factor Mediates Airway Remodeling and Possible Pharmacological Target.
Asthma is a chronic disease of the respiratory system and heterogeneous, one of the most common lung diseases worldwide. The underlying pathology, the chronic inflammatory process and airway remodeling (AR), mediated by cells and cytokines.
Particularly interesting in this field is the platelet-derived growth factor (PDGF), one of the members of the family of human growth factors. In this article, the authors analyze the available data on the role of PDGF in asthma in experimental models and human studies. PDGF is expressed in the airway by a variety of cells contribute to the pathogenesis of asthma-mast cells, eosinophils and airway epithelial cells.
Interleukin 4 (IL4) Antibody |
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20-abx173160 | Abbexa |
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20-abx173161 | Abbexa |
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20-abx173162 | Abbexa |
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20-abx173163 | Abbexa |
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20-abx173164 | Abbexa |
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20-abx173165 | Abbexa |
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20-abx177176 | Abbexa |
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Interleukin 4 (IL4) Antibody |
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20-abx177177 | Abbexa |
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Interleukin 4 (IL4) Antibody |
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abx148481-100ug | Abbexa | 100 ug | EUR 526.8 |
Interleukin 4 (IL4) Antibody |
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abx330739-100ul | Abbexa | 100 ul | EUR 510 |
Interleukin 4 (IL4) Antibody |
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abx032452-400ul | Abbexa | 400 ul | EUR 627.6 |
Interleukin 4 (IL4) Antibody |
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abx032452-80l | Abbexa | 80 µl | EUR 343.2 |
Interleukin 4 (IL4) Antibody |
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abx037033-100ug | Abbexa | 100 ug | EUR 469.2 |
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20-abx100944 | Abbexa |
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20-abx100945 | Abbexa |
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20-abx100947 | Abbexa |
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20-abx130732 | Abbexa |
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20-abx131748 | Abbexa |
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20-abx323730 | Abbexa |
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20-abx324014 | Abbexa |
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Interleukin 4 (IL4) Antibody |
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20-abx009115 | Abbexa |
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20-abx009116 | Abbexa |
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20-abx009117 | Abbexa |
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Interleukin 4 (IL4) Antibody |
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20-abx015093 | Abbexa |
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Dog Interleukin-4 (IL4) |
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1-CSB-EP011659DO | Cusabio |
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Description: Recombinant Dog Interleukin-4(IL4) expressed in E.coli |
Active Interleukin 4 (IL4) |
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4-APA077Hu01 | Cloud-Clone |
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Description: Recombinant Human Interleukin 4 expressed in: E.coli |
Active Interleukin 4 (IL4) |
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4-APA077Hu61 | Cloud-Clone |
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Description: Recombinant Human Interleukin 4 expressed in: 293F cell |
Active Interleukin 4 (IL4) |
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4-APA077Mu01 | Cloud-Clone |
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Description: Recombinant Mouse Interleukin 4 expressed in: E.coli |
Active Interleukin 4 (IL4) |
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4-APA077Ra01 | Cloud-Clone |
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Description: Recombinant Rat Interleukin 4 expressed in: Available from E.coli, Yeast, Baculovirus and Mammalian cells |
Human Interleukin-4 (IL4) |
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1-CSB-YP011659HU | Cusabio |
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Description: Recombinant Human Interleukin-4(IL4) expressed in Yeast |
Sheep Interleukin-4 (IL4) |
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1-CSB-YP011659SH | Cusabio |
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Description: Recombinant Sheep Interleukin-4(IL4) expressed in Yeast |
Human Interleukin-4 (IL4) |
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1-CSB-EP011659HUa0 | Cusabio |
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Description: Recombinant Human Interleukin-4(IL4) expressed in E.coli |
Sheep Interleukin-4 (IL4) |
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1-CSB-EP011659SH | Cusabio |
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Description: Recombinant Sheep Interleukin-4(IL4) expressed in E.coli |
Active Interleukin 4 (IL4) |
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RPU54749-100ug | Biomatik Corporation | 100ug | EUR 777.7 |
Active Interleukin 4 (IL4) |
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RPU54749-1mg | Biomatik Corporation | 1mg | EUR 3445 |
Active Interleukin 4 (IL4) |
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RPU54749-50ug | Biomatik Corporation | 50ug | EUR 624.8 |
Active Interleukin 4 (IL4) |
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RPU54828-100ug | Biomatik Corporation | 100ug | EUR 822.8 |
Active Interleukin 4 (IL4) |
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RPU54828-1mg | Biomatik Corporation | 1mg | EUR 3244.8 |
Active Interleukin 4 (IL4) |
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RPU54828-50ug | Biomatik Corporation | 50ug | EUR 499.2 |
Active Interleukin 4 (IL4) |
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RPU55470-100ug | Biomatik Corporation | 100ug | EUR 973.5 |
Active Interleukin 4 (IL4) |
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RPU55470-1mg | Biomatik Corporation | 1mg | EUR 3837.6 |
Active Interleukin 4 (IL4) |
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RPU55470-50ug | Biomatik Corporation | 50ug | EUR 590.4 |
Active Interleukin 4 (IL4) |
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RPU55471-100ug | Biomatik Corporation | 100ug | EUR 1013.1 |
Active Interleukin 4 (IL4) |
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RPU55471-1mg | Biomatik Corporation | 1mg | EUR 5079.1 |
Active Interleukin 4 (IL4) |
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RPU55471-50ug | Biomatik Corporation | 50ug | EUR 781.5 |
Active Interleukin 4 (IL4) |
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RPU56354-100ug | Biomatik Corporation | 100ug | EUR 1282.6 |
Active Interleukin 4 (IL4) |
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RPU56354-1mg | Biomatik Corporation | 1mg | EUR 5054.4 |
Active Interleukin 4 (IL4) |
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RPU56354-50ug | Biomatik Corporation | 50ug | EUR 777.6 |
Active Interleukin 4 (IL4) |
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RPU56358-100ug | Biomatik Corporation | 100ug | EUR 1013.1 |
Active Interleukin 4 (IL4) |
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RPU56358-1mg | Biomatik Corporation | 1mg | EUR 5079.1 |
Active Interleukin 4 (IL4) |
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RPU56358-50ug | Biomatik Corporation | 50ug | EUR 781.5 |
Interleukin 4 (IL4) Antibody (PE) |
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20-abx200974 | Abbexa |
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20-abx270921 | Abbexa |
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20-abx109098 | Abbexa |
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Interleukin 4 (IL4) Antibody (RPE) |
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abx413390-100tests | Abbexa | 100 tests | EUR 994.8 |
Eukaryotic Interleukin 4 (IL4) |
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4-EPA077Hu61 | Cloud-Clone |
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Description: Recombinant Human Interleukin 4 expressed in: 293F cell |
Eukaryotic Interleukin 4 (IL4) |
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4-EPA077Mu61 | Cloud-Clone |
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Description: Recombinant Mouse Interleukin 4 expressed in: 293F cell |
Eukaryotic Interleukin 4 (IL4) |
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4-EPA077Ra61 | Cloud-Clone |
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Description: Recombinant Rat Interleukin 4 expressed in: 293F cell |
Eukaryotic Interleukin 4 (IL4) |
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RPU54769-100ug | Biomatik Corporation | 100ug | EUR 815.1 |
Eukaryotic Interleukin 4 (IL4) |
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RPU54769-1mg | Biomatik Corporation | 1mg | EUR 3614 |
Eukaryotic Interleukin 4 (IL4) |
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RPU54769-50ug | Biomatik Corporation | 50ug | EUR 655.6 |
Eukaryotic Interleukin 4 (IL4) |
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RPU54798-100ug | Biomatik Corporation | 100ug | EUR 862.4 |
Eukaryotic Interleukin 4 (IL4) |
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RPU54798-1mg | Biomatik Corporation | 1mg | EUR 3822 |
Eukaryotic Interleukin 4 (IL4) |
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RPU54798-50ug | Biomatik Corporation | 50ug | EUR 693 |
Eukaryotic Interleukin 4 (IL4) |
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RPU54799-100ug | Biomatik Corporation | 100ug | EUR 864.6 |
Eukaryotic Interleukin 4 (IL4) |
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RPU54799-1mg | Biomatik Corporation | 1mg | EUR 3832.4 |
Eukaryotic Interleukin 4 (IL4) |
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RPU54799-50ug | Biomatik Corporation | 50ug | EUR 695.2 |
Eukaryotic Interleukin 4 (IL4) |
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RPU59271-100ug | Biomatik Corporation | 100ug | EUR 1254 |
Eukaryotic Interleukin 4 (IL4) |
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RPU59271-1mg | Biomatik Corporation | 1mg | EUR 5557.5 |
Eukaryotic Interleukin 4 (IL4) |
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RPU59271-50ug | Biomatik Corporation | 50ug | EUR 836 |
Interleukin 4 (IL4) Antibody (FITC) |
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20-abx314854 | Abbexa |
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20-abx200973 | Abbexa |
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20-abx270457 | Abbexa |
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20-abx270530 | Abbexa |
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20-abx107010 | Abbexa |
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Interleukin 4 (IL4) Antibody Pair |
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20-abx370094 | Abbexa |
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20-abx370134 | Abbexa |
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Interleukin 4 (IL4) Antibody Pair |
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20-abx370305 | Abbexa |
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Interleukin 4 (IL4) Antibody Pair |
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20-abx370499 | Abbexa |
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Interleukin 4 (IL4) Antibody Pair |
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20-abx370653 | Abbexa |
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Interleukin 4 (IL4) Antibody (FITC) |
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20-abx107681 | Abbexa |
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Interleukin 4 (IL4) Antibody (FITC) |
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20-abx274591 | Abbexa |
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Recombinant Interleukin 4 (IL4) |
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4-RPA077Ca01 | Cloud-Clone |
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Description: Recombinant Dog Interleukin 4 expressed in: E.coli |
Recombinant Interleukin 4 (IL4) |
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4-RPA077Ga01 | Cloud-Clone |
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Description: Recombinant Chicken Interleukin 4 expressed in: E.coli |
Recombinant Interleukin 4 (IL4) |
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4-RPA077Hu02 | Cloud-Clone |
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Description: Recombinant Human Interleukin 4 expressed in: E.coli |
Recombinant Interleukin 4 (IL4) |
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4-RPA077Mu01 | Cloud-Clone |
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Description: Recombinant Mouse Interleukin 4 expressed in: E.coli |
Recombinant Interleukin 4 (IL4) |
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4-RPA077Po01 | Cloud-Clone |
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Description: Recombinant Pig Interleukin 4 expressed in: E.coli |
Recombinant Interleukin 4 (IL4) |
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4-RPA077Ra01 | Cloud-Clone |
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Description: Recombinant Rat Interleukin 4 expressed in: E.coli |
Recombinant Interleukin 4 (IL4) |
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4-RPA077Rb01 | Cloud-Clone |
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Description: Recombinant Rabbit Interleukin 4 expressed in: E.coli |
Recombinant Interleukin 4 (IL4) |
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RPU42303-100ug | Biomatik Corporation | 100ug | EUR 653.4 |
Recombinant Interleukin 4 (IL4) |
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RPU42303-1mg | Biomatik Corporation | 1mg | EUR 2893.8 |
Recombinant Interleukin 4 (IL4) |
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RPU42303-50ug | Biomatik Corporation | 50ug | EUR 524.7 |
Recombinant Interleukin 4 (IL4) |
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RPU42304-100ug | Biomatik Corporation | 100ug | EUR 556.6 |
Recombinant Interleukin 4 (IL4) |
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RPU42304-1mg | Biomatik Corporation | 1mg | EUR 2467.4 |
Recombinant Interleukin 4 (IL4) |
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RPU42304-50ug | Biomatik Corporation | 50ug | EUR 447.7 |
Recombinant Interleukin 4 (IL4) |
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RPU42305-100ug | Biomatik Corporation | 100ug | EUR 616 |
Recombinant Interleukin 4 (IL4) |
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RPU42305-1mg | Biomatik Corporation | 1mg | EUR 2730 |
Recombinant Interleukin 4 (IL4) |
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RPU42305-50ug | Biomatik Corporation | 50ug | EUR 495 |
Recombinant Interleukin 4 (IL4) |
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RPU54429-100ug | Biomatik Corporation | 100ug | EUR 599.5 |
Recombinant Interleukin 4 (IL4) |
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RPU54429-1mg | Biomatik Corporation | 1mg | EUR 2653.3 |
Recombinant Interleukin 4 (IL4) |
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RPU54429-50ug | Biomatik Corporation | 50ug | EUR 480.7 |
Recombinant Interleukin 4 (IL4) |
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RPU54583-100ug | Biomatik Corporation | 100ug | EUR 616 |
Recombinant Interleukin 4 (IL4) |
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RPU54583-1mg | Biomatik Corporation | 1mg | EUR 2730 |
Recombinant Interleukin 4 (IL4) |
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RPU54583-50ug | Biomatik Corporation | 50ug | EUR 495 |
Recombinant Interleukin 4 (IL4) |
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RPU53482-100ug | Biomatik Corporation | 100ug | EUR 554.4 |
The study confirms the thesis that this factor is also secreted by these cells in the course of asthma. The main effect of PDGF in the bronchus is the proliferation of airway smooth muscle cells (ASM) ASM to epithelial cell migration and enhanced collagen synthesis by pulmonary fibroblasts. AR importance in asthma is a well recognized and new therapies should also aim to manage it, perhaps targeting PDGFRs.