IV Ascorbic Acid in Peritoneal Metastatic Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Glut3,Vitamin C,Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2349088 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Preclinical study has shown that human colorectal cancer cells harboring KRAS or BRAF mutations are selectively killed by high levels of ascorbic acid (AA). High dose of AA aslo impairs tumor growth in Apc/KRASG12D mutant mice. Previous phase Ⅰ studies have found that high dose iv AA is well tolerated in cancer patients.This protocol is a phase Ⅲ study of AA infusions combined with treatment with FOLFOX +/- bevacizumab versus treatment with FOLFOX +/- bevacizumab alone as first-line therapy in patients with recurrent or advanced colorectal cancer.
| 2230288 | ecrin-mdr-crc
Project description:Background: Clear guidelines for therapy of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-a monotherapy and high-dose ascorbic acid (AA) monotherapy in open clinical trials. However, there is no clear evidence to support the value of one of these specific treatment approaches, due to the lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-a treatment in the context of HAM/TSP. Principal Findings: Based on flow cytometry and thymidine incorporation, we demonstrated for the first time that high-dose AA displays superior antiproliferative and immunomodulatory effects over IFN-a in HAM/TSP PBMCs ex vivo. In addition, high-dose AA induces cell death in HTLV-1-infected T-cell lines in vitro. Microarray combined with Ingenuity Pathway Analysis revealed AA-induced modulation of genes associated with cell death and cell cycle. Conclusions: In comparison with IFN-a, high-dose AA is preferred as anti-HTLV-1 treatment in vitro, due to its superior cell death-inducing, antiproliferative and immunomodulatory effects. Considering the lack of treatment options, the mild in vivo side effects and the low cost price, high-dose AA should be further explored for its therapeutic potential in HAM/TSP treatment. In total, 15 samples were analyzed. One microarray experiment was performed, including triplicate samples for each treatment condition (untreated, IFN-a, 10 µg/ml ascorbic acid, 50 µg/ml ascorbic acid, 100 µg/ml ascorbic acid). Triplicate samples were obtained from three separate RNA experiments.
2012-06-13 | E-GEOD-34572 | biostudies-arrayexpress
Project description:This protocol is a phase I/II, study of ascorbic acid (AA) infusions combined with treatment with irinotecan versus treatment with irinotecan alone in patients with recurrent or advanced colorectal cancer who have failed at least one treatment regimen with a 5-FU based therapy. This study will be conducted as an amendment to Investigational New Drug # 77486.
| 2121689 | ecrin-mdr-crc
Project description:Reprogramming intermediates (pre-iPSCs) were subjected to control DMSO, ascorbic acid (AA), 2i ( MAP kinase inhibitor + GSKinhibitor) or AA+2i conditions to assess conversion to the iinduced pluripotent stem cell state (iPSC) after 10days.
2015-01-13 | GSE58836 | GEO
Project description:Various substances have been reported to enhance the cardiac differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Ascorbic Acid had a cardiogenic effect in mESC CGR8 cell line. Transcriptome of AA-treated CGR8 ESCs did not reveal any significant changes in gene expression as compared to untreated cells. We performed a global gene expression analysis to better understand the mechanism of Ascorbic acid-induced cardiac differentiation.
2015-05-21 | GSE54242 | GEO
Project description:Background: Clear guidelines for therapy of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-a monotherapy and high-dose ascorbic acid (AA) monotherapy in open clinical trials. However, there is no clear evidence to support the value of one of these specific treatment approaches, due to the lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-a treatment in the context of HAM/TSP. Principal Findings: Based on flow cytometry and thymidine incorporation, we demonstrated for the first time that high-dose AA displays superior antiproliferative and immunomodulatory effects over IFN-a in HAM/TSP PBMCs ex vivo. In addition, high-dose AA induces cell death in HTLV-1-infected T-cell lines in vitro. Microarray combined with Ingenuity Pathway Analysis revealed AA-induced modulation of genes associated with cell death and cell cycle. Conclusions: In comparison with IFN-a, high-dose AA is preferred as anti-HTLV-1 treatment in vitro, due to its superior cell death-inducing, antiproliferative and immunomodulatory effects. Considering the lack of treatment options, the mild in vivo side effects and the low cost price, high-dose AA should be further explored for its therapeutic potential in HAM/TSP treatment.
2012-06-14 | GSE34572 | GEO
Project description:Various substances have been reported to enhance the cardiac differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Ascorbic Acid had a cardiogenic effect in mESC CGR8 cell line. Transcriptome of AA-treated CGR8 ESCs did not reveal any significant changes in gene expression as compared to untreated cells. We performed a global gene expression analysis to better understand the mechanism of Ascorbic acid-induced cardiac differentiation. Differentiating murine embryonic stem cells from CGR cell line were selected at stages of Day 0 (undifferentiated cells), Day 2, Day 3 and Day 5 of differentiation for RNA extraction and hybridization on Affymetrix microarray chip. Samples were collected in 3 biological replicate and were either treated with Ascorbic acid or nontreated (control group). Only those samples were processed for further analysis in which we were able to confirm that AA significantly enhanced cardiac differentiation efficiency at later stages (day 8 and 12) of differentiation by assessing the number of beating EBs in control and AA-treated groups. Cardiac efficiency was evaluated later on this study. But samples that were analyzed by microarray analysis was limited till Day 5. We did not perform whole genome study for these later days of differentiation ( day 8 or 12).
2015-05-21 | E-GEOD-54242 | biostudies-arrayexpress
Project description:Objective: Insights about differences in tumor vasculature and how it reacts to VEGF inhibition is limited, but nevertheless of major relevance to anti-angiogenic therapy. In this study we therefore characterize the effect of bevacizumab combined with chemoradiotherapy (CRT), and explore molecular and genetic markers for response prediction to this combination treatment. Material and Methods: In an academic multicentric randomized phase II study, patients with advanced rectal cancer have been treated with bevacizumab (5mg/kg) in combination with capecitabine (1650mg/m2/day) and radiotherapy (45Gy; 1.8Gy/day) with (50mg/m2) or without oxaliplatin prior to surgery. Of 59 patients, tumor tissue and blood samples were collected before treatment and after the first loading dose of bevacizumab but before CRT (week 3). First, cDNA micro-arrays were performed on the biopsies to investigate differences in gene expression of tumors from patients with and without a pathological complete response (pCR) before start of treatment and to identify biological processes affected by bevacizumab delivery. The paraffin embedded tissue was stained for blood vessels (CD31/CD34) combined with α-SMA (pericytes) and CA-IX (hypoxia). To explore candidate blood-based biomarkers ELISA’s were performed for PDGF-AA, PDGF-BB, THBS-1, IL-8, CYR61 and Ang-2. The expression of all markers was correlated with the pathological response of the patients. Results: Differences in tumoral gene expression are observed between patients with and without a pCR, with the first response group presenting a more angiogenic phenotype before start of treatment and changes in angiogenic processes after bevacizumab delivery. One dose of bevacizumab leads to a decrease in the number of pericyte covered blood vessels, a decrease in circulating PDGF-AA, PDGF-BB and Thrombospondin-1. Patients showing a pCR having less pericyte covered blood vessels, more hypoxia, and less circulating PDGF-BB compared to patients who did not have a pCR after bevacizumab treatment with chemoradiation and bevacizumab. Conclusions: The translational data demonstrate that tumors with an angiogenic expression profile respond better to bevacizumab combined with CRT and points towards a possible role for PDGF, CA-IX and pericyte covered blood vessels for the early response prediction to this treatment. Our findings suggest a role for mural cell recruitment and vessel maturation for the susceptibility of the tumor vasculature to bevacizumab treatment. Further validation of our biological observations and hypothesis generating data in randomized trials is needed.
2016-08-02 | GSE60331 | GEO
Project description:Recent studies show vitamin C (VitC) pro-oxidant properties at high pharmacological concentrations which favor repurposing VitC as an anti-cancer therapeutic agent. However, redox-based anticancer properties of different forms of VitC are yet partially understood. We examined the difference between the reduced and oxidized forms of VitC, ascorbic acid (AA) and dehydroascorbic acid (DHA), in terms of cytotoxicity and redox mechanisms toward breast cancer cells. Our data showed that AA displays higher cytotoxicity towards triple-negative breast cancer (TNBC) cell lines in vitro than DHA. AA has a similar cytotoxicity on non-TNBC breast cancer cells with much less effect on noncancerous cell lines. Using MDA-MB-231, a representative TNBC cell line, we observed that cellular redox-state alterations conditioned AA- and DHA-induced cytotoxicity. Hydrogen peroxide (H2O2) accumulation extracellularly and in different intracellular compartments, and to a less degree, induced intracellular GSH oxidation, played a key role in AA-induced cytotoxicity. In contrast, DHA affected GSH oxidation and thus had less cytotoxicity. Furthermore, different cytotoxicity is observed among breast cancer cell lines. Bioinformatics analysis and biological experiments showed that peroxiredoxin 1 (PRDX1) expression levels correlates with AA differential cytotoxicity in breast cancer cells. A “redoxome” proteomics approach revealed that AA treatment altered the redox state of key antioxidant enzymes (PRDX 1-3) and a number of cysteines-containing proteins including many nucleic acid binding proteins and proteins involved in RNA, DNA and energetic processes. We showed that cell cycle progression delay and translation inhibition are parts of the underlying mechanisms for AA-induced cytotoxicity.
2019-08-16 | PXD013833 | Pride