Good Vitamin D receptor reduced bladder cancer and cisplatin deaths

Vitamin D3 enhances the response to cisplatin in bladder cancer through VDR and TAp73 signaling crosstalk

Cancer Medicine: 10 April 2019 https://doi.org/10.1002/cam4.2119

Brittany L. Bunch Yingyu Ma Kristopher Attwood Lauren Amable Wei Luo Carl Morrison Khurshid A. Guru Anna Woloszynska‐Read … See all authors

* Urinary Bladder Cancer survival is associated with vitamin D receptor: 14 months vs 53 months – Oct 2015* Bladder cancer modifiable risk factors include low vitamin D – meta-analysis March 2016* Bladder cancer 60 percent less likely if have high vitamin D – meta-analysis Dec 2015* * Cancer - Bladder category listing has items along with related searches* 51diseases were strongly associated with Vitamin D Receptor as of March 2019* Overview Cancer-Colon and vitamin D has the following Colon Cancer Prevention** chart Items in both categories Cancer - Bladder and Vitamin D Receptor are listed here: {category}Chemotherapy and Cisplatin* Chemotherapy (cisplatin) and vitamin D synergistically stop stomach cancer – Feb 2014* Chemotheraphy not work as well with low Vitamin D (colon cancer this time) – Aug 2018* Similar to the Bladder Cancer study on this page* Chemotherapy and vitamin D - many studies cisplatin is mentioned several times--- 1. Items in both categories Vitamin D Receptor and Cancer{category} 1. Vitamin D Receptor had the following - April 2019| | || --- | --- || Risk
increase | Cancer || 4.6 | Breast Cancer 16.9 X another study || 3.1 | Colon Cancer survival || 2.7 | Gastric Cancer || 2.4 | Lung Cancer || 1.6 | Prostate Cancer while black |Vitamin D Receptor table shows what compensates for low VDR activation{include}

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Background

Vitamin D3 (VitD) deficiency is linked to increased incidence and worse survival in bladder cancer (BCa). In addition to cystectomy, patients are treated with cisplatin‐based chemotherapy, however 30%‐50% of patients do not benefit from this treatment. The effects of VitD deficiency on response to chemotherapy remain unknown.

Methods

To test effects of VitD supplementation on the response to cisplatin we analyzed patient serum VitD levels and correlated that with survival. In vivo, VitD deficient mice were treated with cisplatin, with or without pretreatment with the active VitD metabolite, 1,25 dihydroxyvitamin D3 (1,25D3). Lastly, using BCa cell lines, T24 and RT‐112, the mechanism of action of 1,25D3 and cisplatin combination treatment was determined by apoptosis assays, as well as western blot and RT‐PCR.

Results

In this study, we determined that low serum 25 hydroxyvitamin D3 (25D3) levels was significantly associated with worse response to cisplatin. Pretreating deficient mice with 1,25D3, reduced tumor volume compared to cisplatin monotherapy. In vitro, 1,25D3 pretreatment increased the apoptotic response to cisplatin. 1,25D3 pretreatment increased expression of TAp73 and its pro‐apoptotic targets, in a VDR dependent manner. VDR and its transcriptional targets were induced after 1,25D3 treatment and further increased after the combination of 1,25D3 and cisplatin in a TAp73 dependent manner.

Conclusions: Our data suggest that VitD deficiency could be a biomarker for poor response to cisplatin, and pretreating with VitD can increase the apoptotic response to cisplatin through VDR and TAp73 signaling crosstalk.