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Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis.

Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis.
Posted by Frank

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.

Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis.
Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis.

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.

Chicken Interleukin 4 (IL4) ELISA Kit

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EUR 622

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Description: A sandwich quantitative ELISA assay kit for detection of Canine Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

Chicken Interleukin 4 (IL4) ELISA Kit

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EUR 454
Description: A sandwich quantitative ELISA assay kit for detection of Chicken Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

Chicken Interleukin 4 (IL4) ELISA Kit

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EUR 587
Description: A sandwich quantitative ELISA assay kit for detection of Chicken Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

Equine Interleukin 4 (IL4) ELISA Kit

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EUR 503
Description: A sandwich quantitative ELISA assay kit for detection of Equine Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

Equine Interleukin 4 (IL4) ELISA Kit

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EUR 654
Description: A sandwich quantitative ELISA assay kit for detection of Equine Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

Human Interleukin 4 (IL4) ELISA Kit

DLR-IL4-Hu-48T 48T
EUR 312
Description: A sandwich quantitative ELISA assay kit for detection of Human Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

Human Interleukin 4 (IL4) ELISA Kit

DLR-IL4-Hu-96T 96T
EUR 392
Description: A sandwich quantitative ELISA assay kit for detection of Human Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

Mouse Interleukin 4 (IL4) ELISA Kit

DLR-IL4-Mu-48T 48T
EUR 435
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Mouse Interleukin 4 (IL4) ELISA Kit

DLR-IL4-Mu-96T 96T
EUR 561
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

Porcine Interleukin 4 (IL4) ELISA Kit

DLR-IL4-p-48T 48T
EUR 493
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

Porcine Interleukin 4 (IL4) ELISA Kit

DLR-IL4-p-96T 96T
EUR 641
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

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Description: A sandwich quantitative ELISA assay kit for detection of Rat Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

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Description: A sandwich quantitative ELISA assay kit for detection of Monkey Interleukin 4 (IL4) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.

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Porcine Interleukin 4 (IL4) ELISA Kit

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Human Interleukin-4 (IL4)

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  • EUR 430.00
  • EUR 234.00
  • EUR 1508.00
  • EUR 642.00
  • EUR 1009.00
  • EUR 291.00
  • 100ug
  • 10ug
  • 1MG
  • 200ug
  • 500ug
  • 50ug
Description: Recombinant Human Interleukin-4(IL4) expressed in Yeast

Sheep Interleukin-4 (IL4)

1-CSB-YP011659SH
  • EUR 679.00
  • EUR 335.00
  • EUR 2172.00
  • EUR 1051.00
  • EUR 1442.00
  • EUR 435.00
  • 100ug
  • 10ug
  • 1MG
  • 200ug
  • 500ug
  • 50ug
Description: Recombinant Sheep Interleukin-4(IL4) expressed in Yeast

Recombinant Interleukin 4 (IL4)

4-RPA077Ca01
  • EUR 548.00
  • EUR 250.00
  • EUR 1780.00
  • EUR 660.00
  • EUR 1220.00
  • EUR 430.00
  • EUR 4300.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Dog Interleukin 4 expressed in: E.coli

Recombinant Interleukin 4 (IL4)

4-RPA077Ga01
  • EUR 510.37
  • EUR 239.00
  • EUR 1638.88
  • EUR 612.96
  • EUR 1125.92
  • EUR 404.00
  • EUR 3947.20
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Chicken Interleukin 4 expressed in: E.coli

Recombinant Interleukin 4 (IL4)

4-RPA077Hu02
  • EUR 535.46
  • EUR 246.00
  • EUR 1732.96
  • EUR 644.32
  • EUR 1188.64
  • EUR 421.00
  • EUR 4182.40
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Human Interleukin 4 expressed in: E.coli

Recombinant Interleukin 4 (IL4)

4-RPA077Mu01
  • EUR 503.20
  • EUR 238.00
  • EUR 1612.00
  • EUR 604.00
  • EUR 1108.00
  • EUR 400.00
  • EUR 3880.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Mouse Interleukin 4 expressed in: E.coli

Recombinant Interleukin 4 (IL4)

4-RPA077Po01
  • EUR 574.88
  • EUR 257.00
  • EUR 1880.80
  • EUR 693.60
  • EUR 1287.20
  • EUR 448.00
  • EUR 4552.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Pig Interleukin 4 expressed in: E.coli

Recombinant Interleukin 4 (IL4)

4-RPA077Ra01
  • EUR 504.99
  • EUR 238.00
  • EUR 1618.72
  • EUR 606.24
  • EUR 1112.48
  • EUR 401.00
  • EUR 3896.80
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Rat Interleukin 4 expressed in: E.coli

Recombinant Interleukin 4 (IL4)

4-RPA077Rb01
  • EUR 548.00
  • EUR 250.00
  • EUR 1780.00
  • EUR 660.00
  • EUR 1220.00
  • EUR 430.00
  • EUR 4300.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Rabbit Interleukin 4 expressed in: E.coli

Dog Interleukin-4 (IL4)

1-CSB-EP011659DO
  • EUR 611.00
  • EUR 309.00
  • EUR 1827.00
  • EUR 939.00
  • EUR 1218.00
  • EUR 397.00
  • 100ug
  • 10ug
  • 1MG
  • 200ug
  • 500ug
  • 50ug
Description: Recombinant Dog Interleukin-4(IL4) expressed in E.coli

Human Interleukin-4 (IL4)

1-CSB-EP011659HUa0
  • EUR 380.00
  • EUR 214.00
  • EUR 1309.00
  • EUR 560.00
  • EUR 873.00
  • EUR 262.00
  • 100ug
  • 10ug
  • 1MG
  • 200ug
  • 500ug
  • 50ug
Description: Recombinant Human Interleukin-4(IL4) expressed in E.coli

Sheep Interleukin-4 (IL4)

1-CSB-EP011659SH
  • EUR 611.00
  • EUR 309.00
  • EUR 1827.00
  • EUR 939.00
  • EUR 1218.00
  • EUR 397.00
  • 100ug
  • 10ug
  • 1MG
  • 200ug
  • 500ug
  • 50ug
Description: Recombinant Sheep Interleukin-4(IL4) expressed in E.coli

Active Interleukin 4 (IL4)

4-APA077Hu01
  • EUR 665.38
  • EUR 281.00
  • EUR 2220.16
  • EUR 806.72
  • EUR 1513.44
  • EUR 508.00
  • EUR 5400.40
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Human Interleukin 4 expressed in: E.coli

Active Interleukin 4 (IL4)

4-APA077Hu61
  • EUR 782.75
  • EUR 313.00
  • EUR 2660.32
  • EUR 953.44
  • EUR 1806.88
  • EUR 587.00
  • EUR 6500.80
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Human Interleukin 4 expressed in: 293F cell

Active Interleukin 4 (IL4)

4-APA077Mu01
  • EUR 651.04
  • EUR 277.00
  • EUR 2166.40
  • EUR 788.80
  • EUR 1477.60
  • EUR 499.00
  • EUR 5266.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Mouse Interleukin 4 expressed in: E.coli

Active Interleukin 4 (IL4)

4-APA077Ra01
  • EUR 829.34
  • EUR 325.00
  • EUR 2835.04
  • EUR 1011.68
  • EUR 1923.36
  • EUR 618.00
  • EUR 6937.60
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Rat Interleukin 4 expressed in: Available from E.coli, Yeast, Baculovirus and Mammalian cells

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.

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