Vitamin D3 and deconvoluting a rash
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA905668 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22414800.fastq.gz | Fastqsanger.gz | |||
| SRR22414801.fastq.gz | Fastqsanger.gz | |||
| SRR22414802.fastq.gz | Fastqsanger.gz | |||
| SRR22414803.fastq.gz | Fastqsanger.gz | |||
| SRR22414804.fastq.gz | Fastqsanger.gz |
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Project description:BACKGROUNDAdverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D3) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of healthy human adults, we investigated the clinical and molecular immunomodulatory effects of a single high dose of oral vitamin D3 on an experimentally induced chemical rash.METHODSSkin inflammation was induced with topical nitrogen mustard (NM) in 28 participants. Participant-specific inflammatory responses to NM alone were characterized using clinical measures, serum studies, and skin tissue analysis over the next week. All participants underwent repeat NM exposure to the opposite arm and then received placebo or 200,000 IU cholecalciferol intervention. The complete rash reaction was followed by multi-omic analysis, clinical measures, and serum studies over 6 weeks.RESULTSCholecalciferol mitigated acute inflammation in all participants and achieved 6 weeks of durable responses. Integrative analysis of skin and blood identified an unexpected divergence in response severity to NM, corroborated by systemic neutrophilia and significant histopathologic and clinical differences. Multi-omic and pathway analyses revealed a 3-biomarker signature (CCL20, CCL2, CXCL8) unique to exaggerated responders that is suppressed by cholecalciferol and implicates IL-17 signaling involvement.CONCLUSIONHigh-dose systemic cholecalciferol may be an effective treatment for severe reactions to topical chemotherapy. Our findings have broad implications for cholecalciferol as an antiinflammatory intervention against the development of exaggerated immune responses.TRIAL REGISTRATIONclinicaltrials.gov (NCT02968446).FUNDINGNIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)).
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Project description:This phase III trial studies how well vitamin D3 given with standard chemotherapy and bevacizumab works in treating patients with colorectal cancer that has spread to other parts of the body. Vitamin D3 helps the body use calcium and phosphorus to make strong bones and teeth. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, oxaliplatin, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as bevacizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving vitamin D3 with chemotherapy and bevacizumab may work better in shrinking or stabilizing colorectal cancer. It is not yet known whether giving high-dose vitamin D3 in addition to chemotherapy and bevacizumab would extend patients’ time without disease compared to the usual approach (chemotherapy and bevacizumab).
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