Effect of Vitamin D Supplements on Relapse of Digestive Tract Cancer with Tumor Stromal Immune Response: A Secondary Analysis of the AMATERASU Randomized Clinical Trial.
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SUBMITTER: Akutsu T
PROVIDER: S-EPMC8470811 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceRandomized clinical trials of vitamin D supplementation for secondary prevention in patients with cancer are needed, given positive results of observational studies.ObjectiveTo determine whether postoperative vitamin D3 supplementation can improve survival of patients with digestive tract cancers overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels.Design, setting, and participantsThe AMATERASU trial, a randomized, double-blind, placebo-controlled trial conducted at a single university hospital in Japan. Enrollment began in January 2010 and follow-up was completed in February 2018. Patients aged 30 to 90 years with cancers of the digestive tract from the esophagus to the rectum, stages I to III, were recruited. Of 439 eligible patients, 15 declined and 7 were excluded after operation.InterventionsPatients were randomized to receive oral supplemental capsules of vitamin D (2000 IU/d; n = 251) or placebo (n = 166) from the first postoperative outpatient visit to until the end of the trial.Main outcomes and measuresThe primary outcome was relapse-free survival time to relapse or death. The secondary outcome was overall survival time to death due to any cause. Subgroups analyzed had baseline serum 25(OH)D levels of 0 to less than 20 ng/mL, 20 to 40 ng/mL, and greater than 40 ng/mL; because of small sample size for the highest-baseline-level group, interactions were tested only between the low- and middle-baseline-level groups.ResultsAll 417 randomized patients (mean age, 66 years; male, 66%; esophageal cancer, 10%; gastric cancer, 42%; colorectal cancer, 48%) were included in the analyses. There was 99.8% follow-up over a median 3.5 (interquartile range, 2.3-5.3) years, with maximal follow-up of 7.6 years. Relapse or death occurred in 50 patients (20%) randomized to vitamin D and 43 patients (26%) randomized to placebo. Death occurred in 37 (15%) in the vitamin D group and 25 (15%) in the placebo group. The 5-year relapse-free survival was 77% with vitamin D vs 69% with placebo (hazard ratio [HR] for relapse or death, 0.76; 95% CI, 0.50-1.14; P = .18). The 5-year overall survival in the vitamin D vs placebo groups was 82% vs 81% (HR for death, 0.95; 95% CI, 0.57-1.57; P = .83). In the subgroup of patients with baseline serum 25(OH)D levels between 20 and 40 ng/mL, the 5-year relapse-free survival was 85% with vitamin D vs 71% with placebo (HR for relapse or death, 0.46; 95% CI, 0.24-0.86; P = .02; P = .04 for interaction). Fractures occurred in 3 patients (1.3%) in the vitamin D group and 5 (3.4%) in the placebo group. Urinary stones occurred in 2 patients (0.9%) in the vitamin D group and 0 in the placebo group.Conclusions and relevanceAmong patients with digestive tract cancer, vitamin D supplementation, compared with placebo, did not result in significant improvement in relapse-free survival at 5 years.Trial registrationUMIN Identifier: UMIN000001977.
| S-EPMC6459116 | biostudies-literature
Project description:The stromal tumor microenvironment (TME) consists of immune cells, vascular and neural structures, cancer-associated fibroblasts (CAFs), as well as extracellular matrix (ECM), and favors immune escape mechanisms promoting the initiation and progression of digestive cancers. Numerous ECM proteins released by stromal and tumor cells are crucial in providing physical rigidity to the TME, though they are also key regulators of the immune response against cancer cells by interacting directly with immune cells or engaging with immune regulatory molecules. Here, we discuss current knowledge of stromal proteins in digestive cancers including pancreatic cancer, colorectal cancer, and gastric cancer, focusing on their functions in inhibiting tumor immunity and enabling drug resistance. Moreover, we will discuss the implication of stromal proteins as therapeutic targets to unleash efficient immunotherapy-based treatments.
| S-EPMC7795083 | biostudies-literature
Project description:BackgroundThe effect of vitamin D supplementation on postural muscles of the trunk is of particular interest because low 25-hydroxyvitamin D [25(OH) D] levels are associated with decreased postural balance and increased risk of falls. Understanding the role of vitamin D supplementation plays in trunk muscle function of older adults is necessary, as this is a potentially modifiable factor to improve postural muscle function and decrease the risk of falling of older adults. The objective of this randomized controlled trial was to evaluate the effect of 12 months of vitamin D supplementation compared with placebo, on morphology and function of the trunk muscles of adults aged 50 to 79 years with low serum 25(OH) D levels.MethodsThis was a secondary analysis of a randomized, placebo-controlled, and double-blind clinical trial conducted between June 2010 and December 2013 in Tasmania, Australia. The clinical trial was registered with the Australian New Zealand clinical trial registration agency, ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN 12610000495022. Participants were aged 50-79 years with ongoing symptoms of knee osteoarthritis and with low serum [25(OH) D] (12.5 to 60 nmol/L, 5.2 to 24 ng/mL). Participants were randomly assigned to either monthly 50 000 IU oral vitamin D3 (n = 104) or an identical placebo (n = 113) for 24 months as per clinical trial protocol. The primary outcomes in this pre-specified secondary analysis were between-group differences in change in size of rectus abdominis, transversus abdominis, internal oblique, external oblique, and lumbar multifidus muscles and function (assessed by change in thickness on contraction) of these muscles (excepting rectus abdominis) from baseline to 12 months. Muscle size was assessed using ultrasound imaging.ResultsOf 217 participants (mean age 63 years, 48% women), 186 (85.7%) completed the study. There were no significant between-group differences in change in size or function of the abdominal or multifidus muscles after 12 months of vitamin D supplementation.ConclusionsA monthly dose of 50 000 IU of vitamin D3 alone for 12 months does not affect the size or ability to contract trunk muscles of independent community-dwelling older adults with symptomatic knee osteoarthritis and low serum 25(OH) D levels regardless of body mass index status or degree of vitamin D deficiency. An effect of vitamin D supplementation on other aspects of trunk muscle function such as strength, power, or physical function cannot be ruled out.
| S-EPMC6438333 | biostudies-literature
Project description:BackgroundThe Women's Health Initiative (WHI) randomized clinical trial (RCT) of calcium plus vitamin D (CaD) supplements found a 17% excess in urinary tract stone incidence in the supplemented group. This study evaluated whether this risk is modified by participant characteristics.ObjectiveWe examined the correlates of urinary tract stone occurrence in the CaD arm of the WHI trial.DesignWe analyzed an RCT involving 36,282 postmenopausal women aged 50-79 y from 40 WHI centers: 18,176 women received 500 mg calcium carbonate plus 200 IU vitamin D(3) twice daily (1000 mg and 400 IU daily, respectively), and 18,106 women received a matching placebo for an average of 7.0 y. The incidence of urinary tract stones was determined.ResultsThe incidence of self-reported clinically diagnosed urinary tract stones was more common in the active CaD medication group than in the placebo group (hazard ratio: 1.17; 95% CI: 1.02, 1.34): 449 women in the CaD group and 381 women in the placebo group reported a stone during the trial. The rates of self-reported stones did not differ between various demographic, anthropomorphic, dietary, and other hypothesized risk factors according to randomization assignment. Neither the total calcium intake nor the use of calcium supplements at baseline was associated with the risk of stones. In sensitivity analyses that censored participants who were below 80% adherence, the findings were similar.ConclusionsDaily supplementation with CaD for 7 y was associated with an increase in the number of self-reported urinary tract stones. These findings have implications for CaD supplement use. This trial was registered with the WHI at clinicaltrials.gov as NCT00000611.
| S-EPMC3127502 | biostudies-literature
Project description:ImportanceEpidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways.ObjectiveTo follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index.Design, setting, and participantsVITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline. Randomization took place from November 2011 through March 2014, and study medication ended on December 31, 2017. Data for this secondary analysis were analyzed from November 1, 2011, to December 31, 2017.InterventionsVitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d) supplements.Main outcomes and measuresFor the present analysis, the primary outcome was a composite incidence of metastatic and fatal invasive total cancer, because the main VITAL study showed a possible reduction in fatal cancer with vitamin D supplementation and effect modification by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for total cancer incidence reduction for individuals with normal BMI, but not for individuals with overweight or obesity. Secondary analyses included examination of BMI (<25, 25 to < 30, and ≥30) as effect modifiers of the observed associations.ResultsAmong 25 871 randomized VITAL participants (51% female; mean [SD] age, 67.1 [7.1] years), 1617 were diagnosed with invasive cancer over a median intervention period of 5.3 years (range, 3.8-6.1 years). As previously reported, no significant differences for cancer incidence by treatment arm were observed. However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D compared with placebo (226 of 12 927 assigned to vitamin D [1.7%] and 274 of 12 944 assigned to placebo [2.1%]; HR, 0.83 [95% CI, 0.69-0.99]; P = .04). When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR, 0.62 [95% CI, 0.45-0.86]) but not among those with overweight or obesity (BMI 25-<30: HR, 0.89 [95% CI, 0.68-1.17]; BMI≥30: HR, 1.05 [95% CI, 0.74-1.49]) (P = .03 for interaction by BMI).Conclusions and relevanceIn this randomized clinical trial, supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight.Trial registrationClinicalTrials.gov Identifier: NCT01169259.
| S-EPMC7675103 | biostudies-literature
Project description:Analysis of gene expression in skin of rats subjected to electron irradiation and the effect of vitamin A supplements. Keywords: other
2003-03-20 | GSE284 | GEO
Project description:BackgroundThe present study investigated the expression, mutation, and methylation profile of PNN and its prognostic value in digestive tract cancers. The disparities in signaling pathways and the immune landscape in colon adenocarcinoma (COAD) based on PNN expression were specifically explored.MethodsThe expression, mutation, methylation levels of PNN, and survival data in esophageal cancer, gastric adenocarcinoma, COAD, and rectal adenocarcinoma were evaluated using several bioinformatic databases. Gene Ontology (GO) enrichment analysis and gene set enrichment analysis (GSEA) were performed to investigate the enriched biological functions and pathways in COAD. Several acknowledged bioinformatic algorithms were employed to assess the correlation between PNN expression and the tumor immune landscape in COAD.ResultsPNN was upregulated and remarkably related to tumor stage in digestive tract cancers. High expression of PNN was positively associated with poor progression-free survival and overall survival time, specifically in COAD. PNN expression was identified as an independent prognostic factor in COAD. GO and GSEA analyses revealed that PNN participates in multiple biological processes underlying carcinogenicity in COAD. Further investigation showed that PNN expression was significantly associated with tumor-infiltrating immune cells, immune cell functions, and several immune checkpoints in COAD. The PNN low expression group had a lower tumor immune dysfunction and exclusion (TIDE) score and a higher immunophenoscore (IPS), indicating a better response to immunotherapy.ConclusionPNN was highly expressed in digestive tract cancers and could act as an independent prognostic factor and a response predictor for immunotherapy in COAD.
| S-EPMC8993647 | biostudies-literature
Project description:Cancers of the digestive tract are among the most prevalent types of cancer. These types of cancers are often diagnosed at a late stage, which results in a poor prognosis. Currently, many biomedical studies focus on the role of ion channels, in particular transient receptor potential (TRP) channels, in cancer pathophysiology. TRP channels show mostly non-selective permeability to monovalent and divalent cations. TRP channels are often dysregulated in digestive tract cancers, which can result in alterations of cancer hallmark functions, such as enhanced proliferation, migration, invasion and the inability to induce apoptosis. Therefore, TRP channels could serve as potential diagnostic biomarkers. Moreover, TRP channels are mostly expressed on the cell surface and ion channel targeting drugs do not need to enter the cell, making them attractive candidate drug targets. In this review, we summarize the current knowledge about TRP channels in connection to digestive tract cancers (oral cancer, esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer) and give an outlook on the potential of TRP channels as cancer biomarkers or therapeutic targets.
| S-EPMC7084354 | biostudies-literature
Project description:1. The carbohydrase activities of homogenates of mucosa from the abomasum, small intestine, caecum and colon, and of the pancreas of cattle were studied. 2. The disaccharidase activities were located mainly in the small intestine and showed a non-uniform pattern of distribution along the small intestine; trehalase activity was highest in the proximal part, lactase and cellobiase activities were highest in the proximal and middle parts and maltase activity was highest in the distal part. 3. The intestinal lactase and cellobiase activities were highest in the young calf and decreased with age, whereas the intestinal maltase and trehalase activities, which were very low compared with the lactase activity, did not change with age. 4. No intestinal sucrase or palatinase activity was detected in the calf or in the adult cow. 5. Homogenates of intestinal mucosa also exhibited amylase and dextranase activity. 6. Homogenates of the pancreas possessed a strong amylase activity and a weak maltase activity. The maltase activity did not change with age, whereas the amylase activity increased with age. 7. No marked differences were observed between the carbohydrase activities of calves fed solely on milk and those of calves given a concentrate-hay diet from 6 weeks of age.
| S-EPMC1198890 | biostudies-other
Project description:Rhodnius prolixus, Panstrongylus megistus, Triatoma infestans, and Dipetalogaster maxima are all triatomines and potential vectors of the protozoan Trypanosoma cruzi responsible for human Chagas' disease. Considering that the T. cruzi's cycle occurs inside the triatomine digestive tract (TDT), the analysis of the TDT protein profile is an essential step to understand TDT physiology during T. cruzi infection. To characterize the protein profile of TDT of D. maxima, P. megistus, R. prolixus, and T. infestans, a shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was applied in this report. Most proteins were found to be closely related to metabolic pathways such as gluconeogenesis/glycolysis, citrate cycle, fatty acid metabolism, oxidative phosphorylation, but also to the immune system. We annotated this new proteome contribution gathering it with those previously published in accordance with Gene Ontology and KEGG. Enzymes were classified in terms of class, acceptor, and function, while the proteins from the immune system were annotated by reference to the pathways of humoral response, cell cycle regulation, Toll, IMD, JNK, Jak-STAT, and MAPK, as available from the Insect Innate Immunity Database (IIID). These pathways were further subclassified in recognition, signaling, response, coagulation, melanization and none. Finally, phylogenetic affinities and gene expression of annexins were investigated for understanding their role in the protection and homeostasis of intestinal epithelial cells against the inflammation.
| S-EPMC7755933 | biostudies-literature