QUESTION: I have a patient with gastric cancer whose oncologist is saying HDIVC is contraindicated. What do you think?
ANSWER: This is one of those “WTF” statements… I hear Oncologists make these a lot and they never have data for them. The topic of Gastric CA and ASC is somewhat complicated by presence or absence of H. pylori and much data is on PO supplementation. If one considers the main MOA of HDIVC on Gastric CA cells they appear to be quite sensitive to H2O2 so IV IVC would be just fine and likely useful. (First two papers below)
- Yubin Maoa, b, Gang Songa, et.al. Hydrogen peroxide-induced apoptosis in human gastric carcinoma MGC803 cells. DOI: 10.1016/j.cellbi.2005.12.008
Abstract: Hydrogen peroxide (H2O2), a representative ROS, has been used to study the apoptosis of cancer cells to oxidative stress. In this study, we exploited the cellular and molecular mechanisms involved in H2O2-induced apoptosis in human gastric carcinoma MGC803 cells. Exposure of cells to H2O2 might cause significant viability loss and the increase in apoptotic rate. Treatment with 0.4 mmol/L H2O2 up-regulated Bax but down-regulated Bcl-2 in a time-dependent manner, while Bcl-xL expression remained unchanged. Our results also showed that the levels of Fas and Fas-L were increased, the pro-caspase-3 and pro-caspase-9 were down-regulated in H2O2-treated MGC803 cells. Under H2O2 stress, we found that the protein p53 also participated in MGC803 cells apoptosis. Taken together, the present study indicated that Fas-mediated cell surface death receptor pathway and mitochondria-mediated pathway may participate in regulating the MGC803 cells apoptosis under oxidative stress. - Gencer S1, Irmak Yazicioğlu MB. Differential response of gastric carcinoma MKN-45 and 23132/87 cells to H2O2 exposure. Turk J Gastroenterol. 2011;22(2):145-51. PMID: 2179655
Abstract: BACKGROUND/AIMS: Reactive oxygen species are involved in tumor progression but how they function is not well understood. In this study, we investigated and compared the effects of hydrogen peroxide on the survival, apoptosis, accumulation of oxidative stress, and matrix metalloprotein-7 gene expression on human gastric carcinoma MKN-45 and 23132/87 cells. METHODS: The cell lines were exposed to hydrogen peroxide in a dose- and time-dependent manner. The surviving cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The oxidative stress was analyzed by an oxidative stress marker, 2,7-dichlorofluorescein diacetate, under fluorescence microscope. The effect of oxidative stress on the apoptotic behavior, caspase-3 activity, and matrix metalloprotein-7 gene expressions of the cell lines were determined, respectively, by TUNEL, caspase-3 activity assay, and quantitative real-time polymerase chain reaction. RESULTS: Exposure of the gastric cancer cells to oxidative stress resulted in dose- and time-dependent decrease in the survival of the cell lines. While MKN-45 cells had oxidative stress, increased apoptosis with no caspase-3 activity, and increased matrix metalloprotein-7 expression following hydrogen peroxide exposure, 23132/87 cells showed none, with internal oxidative stress accumulation prior to hydrogen peroxide exposure. CONCLUSIONS: The two gastric cancer cell lines responded differently to oxidative stress conditions, and unlike in 23132/87 cells, matrix metalloprotein-7 gene expression was shown to be affected by external hydrogen peroxide in MKN-45 cells. - And-Oral Ascorbate / Gastric CA and H pylori: From : PMCID: PMC1773094
Background: Gastric juice vitamin C may be protective against gastric carcinogenesis but concentrations are significantly reduced by Helicobacter pylori infection. We investigated the in vitro effects of vitamin C at concentrations comparable with those found in gastric juice on gastric cancer cells and H pylori. Methods: Gastric cancer cell lines and various H pylori strains were treated with l-ascorbic acid for up to 72 hours. Cell viability, and protein and DNA synthesis were determined. Flow cytometry was used for assessment of H pylori adherence, cell cycle distribution, and apoptosis. H pylori growth and its haemagglutination activity were determined using viability count and microtitration assay. Results: Vitamin C induced a significant dose dependent growth inhibition of gastric AGS and MKN45 cells but this effect was significantly reduced at levels similar to those in gastric juice of H pylori infected patients (<50 μM). Although vitamin C had no obvious effect on H pylori growth, haemagglutination activity, or adherence ability to gastric AGS cells compared with untreated controls, it significantly enhanced H pylori associated apoptosis and induced cell cycle arrest in these cells. Conclusion: Vitamin C may inhibit gastric cancer cell growth and alter H pylori induced cell cycle events at concentrations comparable with those in gastric juice, but has no effect on H pylori growth or pathogenicity. However, the inhibitory effect on gastric cancer cells was lost at vitamin C concentrations found in patients withH pylori infection. - And in oral related ASC: Helicobactor pylori 2003, pp 195-203: “Chronic infection with Helicobacter pylori is now widely recognized to be a cause of gastric adenocarcinoma. Although a variety of factors are thought to be important in its aetiopathogenesis, the role of gastric juice vitamin C has recently attracted considerable attention from a number of research groups. There is increasing evidence to suggest that dietary vitamin C influences the risk of developing gastric cancer. High dietary intake of fresh fruit and vegetables, and diets rich in vitamin C, have been shown to protect against the development of gastric cancer; high vitamin C diets may reduce the relative risk by between 0.3 and 0.5.
