Vitamin D Receptor-Mediated Stromal Reprogramming Suppresses Pancreatitis and Enhances Pancreatic Cancer Therapy
Mara H. Sherman1, Ruth T. Yu1, Dannielle D. Engle2, Ning Ding1, Annette R. Atkins1, Herve Tiriac2, Eric A. Collisson3, Frances Connor4, Terry Van Dyke5, Serguei Kozlov6, Philip Martin6, Tiffany W. Tseng1, David W. Dawson7, Timothy R. Donahue7, Atsushi Masamune8, Tooru Shimosegawa8, Minoti V. Apte9, Jeremy S. Wilson9, Beverly Ng10, 11, Sue Lynn Lau10, 12, 13, Jenny E. Gunton10, 11, 12, 13, Geoffrey M. Wahl1, Tony Hunter14, Jeffrey A. Drebin15, Peter J. O’Dwyer16, Christopher Liddle17, David A. Tuveson2, Michael Downes 1 downes@salk.edu , Ronald M. Evans1, 18,
Publisher wants $31.50 for the PDF – publisher also has a 3 minute low-tech video
- There have been hundreds of attempts to make a patentable synthetic vitamin D
- Calcipotriol has been used for Psoriasis – apparently since 1989
- It is about 1% as powerful as natural vitamin D and has a great many side affects
- This study shows calcipotriol to result in improved survival from chemotherapy
- No comment in abstract about the benefits of calcipotriol relative to vitamin D
- Review of this study - apparently done on MICE, not humans UT San Diego Sept 2014
- In May 2014 one of the authors got a $5 million grant to extend this synthetic vitamin D study to humans
- Note: the video mentions that natural vitamin D works with Pancratic Cancer too – but they do not state how well.
- Note: Dr. Salk prided himself on not patenting his polio vaccine, but Salk Institute has many synthetic Vitamin D patents
- Search VitaminDWiki for calcipotriol 70 items as of Sept 2014
- Search VitaminDWiki for calcipotriol AND pancreatic 59 items as of Dec 2015
- Cancer - Pancreatic category listing and associated searches
- All items in category Pancreatic Cancer and Vitamin D
57 items - All items in category Vitamin D Receptor
530 items - Vitamin D Receptor can be modulated with a new compound – Feb 2014 PS121912
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Highlights
•VDR is a master transcriptional regulator in pancreatic stellate cells
•VDR ligands suppress pancreatitis
•Stromal VDR activation overcomes chemotherapeutic drug resistance
•VDR ligand plus gemcitabine enhances survival in a PDA mouse modelThe poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy.
See also web
- Pancreatic Cancer Ecosystem and Vitamin D Huffingtonpost on same topic - Dec 2015
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