Effect Modification of Vitamin D Supplementation by Histopathological Characteristics on Survival of Patients with Digestive Tract Cancer: Post Hoc Analysis of the AMATERASU Randomized Clinical Trial

Yonaga, Hideyuki; Okada, Shinya; Akutsu, Taisuke; Ohdaira, Hironori; Suzuki, Yutaka; Urashima, Mitsuyoshi

doi:10.3390/nu11102547

Cited by 14 publications

(19 citation statements)

References 22 publications

(38 reference statements)

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“…Thus, VDR may be a possible prognostic biomarker in patients. Furthermore, several findings support that vitamin D supplementation contributes to favorable prognosis (Ng et al, 2019;Urashima et al, 2019;Yonaga et al, 2019), especially the prognosis improvement compared to those with treatment alone (Wesselink et al, 2020).…”

Section: Vitamin D Metabolism and Epidemiologymentioning

confidence: 87%

Immune Response: A Missed Opportunity Between Vitamin D and Radiotherapy

Liu

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Radiotherapy (RT) is a mainstay treatment in several types of cancer and acts by mediating various forms of cancer cell death, although it is still a large challenge to enhance therapy efficacy. Radiation resistance represents the main cause of cancer progression, therefore, overcoming treatment resistance is now the greatest challenge for clinicians. Increasing evidence indicates that immune response plays a role in reprogramming the radiation-induced tumor microenvironment (TME). Intriguingly, radiation-induced immunosuppression possibly overwhelms the ability of immune system to ablate tumor cells. This induces an immune equilibrium, which, we hypothesize, is an opportunity for radiosensitizers to make actions. Vitamin D has been reported to act in synergistic with RT by potentiating antiproliferative effect induced by therapeutics. Additionally, vitamin D can also regulate the TME and may even lead to immunostimulation by blocking immunosuppression following radiation. Previous reviews have focused on vitamin D metabolism and epidemiological trials, however, the synergistic effect of vitamin D and existing therapies remains unknown. This review summarizes vitamin D mediated radiosensitization, radiation immunity, and vitamin D-regulated TME, which may contribute to more successful vitamin D-adjuvant radiotherapy.

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Section: Vitamin D Metabolism and Epidemiologymentioning

confidence: 87%

Immune Response: A Missed Opportunity Between Vitamin D and Radiotherapy

Liu

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…Yonaga et al performed a post hoc analysis of the AMATERAS study, namely participants were divided based on histopathological characteristic into the following subgroups: squamous cell carcinoma; adenocarcinoma well differentiated, moderately differentiated or poorly differentiated. They found that postoperative oral vitamin D supplementation improved OS and PFS in the subgroup of patients with poorly differentiated gastrointestinal adenocarcinoma, but not in the remaining subgroups [ 227 ]. Interestingly, a post hoc analysis of AMATERAS study conducted by Akutsu et al in which participants were stratified based on p53 protein, vitamin D receptor and Ki-67 expression levels in tumor samples demonstrated that daily 2000 IU vitamin D supplementation significantly improved PFS and a non-significant 10% longer 5-year OS in the subgroup of patients with p53 positive tumors [ 228 ].…”

Section: What Do We Know So Far About Vitamin D In Cancer Prevention and Prognosis From Clinical Trials?mentioning

confidence: 99%

Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?

Gabryanczyk

Klimczak

Szymczak-Pajor

et al. 2021

IJMS

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There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.

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“…Up to now, there are several reports exploring the association between vitamin D and cancer risk, especially in CRC ( Urashima et al, 2019 ; Yonaga et al, 2019 ; Amrein et al, 2020 ). 1α,25-dihydroxyvitamin D 3 (VD 3 , also known as calcitriol), activated by binding to nuclear vitamin D receptor (VDR) in the genomic way, displays its wide-ranging effects on a variety of cancers ( Jeon and Shin, 2018 ; Carlberg and Munoz, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Enhances Radiosensitivity of Colorectal Cancer by Reversing Epithelial-Mesenchymal Transition

Wang

Liu

et al. 2021

Front. Cell Dev. Biol.

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Colorectal cancer (CRC) is often resistant to conventional therapies. Previous studies have reported the anticancer effects of vitamin D in several cancers, its role in radiotherapy (RT) remains unknown. We found that 1α, 25-dihydroxyvitamin D3 (VD3), the biologically active form of vitamin D, had antitumor effect on CRC and sensitized CRC cells to ionizing radiation (IR). VD3 demonstrated synergistic effect in combination with IR, which were detected by colony formation and cell proliferation assay. Radiosensitivity restoration induced by VD3 was associated with a series of phenotypes, including apoptosis, autophagy, and epithelial-mesenchymal transition (EMT). Using proteomics, “regulation of cell migration” and “cadherin” were found to be obviously enriched GO terms. Moreover, cystatin D and plasminogen activator inhibitor-1 (PAI-1), the differentially expressed proteins, were associated with EMT. Next, we confirmed the contributions of these two genes in enhancing IR sensitivity of CRC cells upon inhibition of EMT. As determined by proteomics, the mechanism underlying such sensitivity involved partially block of JAK/STAT3 signaling pathway. Furthermore, VD3 also elicited sensitization to RT in xenograft CRC models without additional toxicity. Our study revealed that VD3 was able to act in synergy with IR both in vitro and in vivo and could also confer radiosensitivity by regulating EMT, thereby providing a novel insight for elevating the efficacy of therapeutic regimens.

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Effect Modification of Vitamin D Supplementation by Histopathological Characteristics on Survival of Patients with Digestive Tract Cancer: Post Hoc Analysis of the AMATERASU Randomized Clinical Trial

Cited by 14 publications

References 22 publications

Immune Response: A Missed Opportunity Between Vitamin D and Radiotherapy

Immune Response: A Missed Opportunity Between Vitamin D and Radiotherapy

Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?

Vitamin D Enhances Radiosensitivity of Colorectal Cancer by Reversing Epithelial-Mesenchymal Transition

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