ascorbic-acid and Carcinoma--Ductal--Breast

The transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer.. In a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1α, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters.. HIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with decreased disease-free and disease-specific survival. Grade 1 tumors had higher ascorbate levels than did grade 2 or 3 tumors. Higher ascorbate levels were associated with less tumor necrosis, with lower HIF-1 pathway activity and with increased disease-free and disease-specific survival.. Our findings indicate that there is a direct correlation between intracellular ascorbate levels, activation of the HIF-1 pathway and patient survival in breast cancer. This is consistent with the known capacity of ascorbate to stimulate the activity of the regulatory HIF hydroxylases and suggests that optimisation of tumor ascorbate could have clinical benefit via modulation of the hypoxic response.

Topics: Antigens, Neoplasm; Ascorbic Acid; Breast Neoplasms; Carbonic Anhydrase IX; Carcinoma, Ductal, Breast; Cell Hypoxia; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Membrane Proteins; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins; Retrospective Studies; Survival Analysis; Up-Regulation; Vascular Endothelial Growth Factor A

The effects of vitamins E and E, beta-carotene and selenium on development of N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumours in hamsters were investigated. Dietary supplementation of vitamin C, alone as well as in combination with beta-carotene resulted in consistently lower numbers of advanced ductular lesions. The differences with the controls, however, did not reach the level of statistical significance. Beta-Carotene alone demonstrated no inhibitory effect on the development of (pre)neoplastic lesions in the pancreas. Vitamin E or Se, either alone or in combination, had no effect on the development of advanced ductular lesions in BOP-treated hamsters.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; beta Carotene; Body Weight; Carcinogens; Carcinoma, Ductal, Breast; Carotenoids; Cricetinae; Diet; Male; Mesocricetus; Nitrosamines; Organ Size; Pancreatic Neoplasms; Selenium; Vitamin E