Borna disease virus (BDV) can induce severe neurological disorder in Lewis rats and MRL mice. Antiviral CD8 T cells have been shown to be the mediators of disease in these animals. To define molecules involved in the disease process, we performed infection studies in MRL mice lacking either interferon-gamma, a functional Fas/FasL system, chemokine receptor CXCR3, or inducible NO synthase. We further used transgenic MRL mice expressing interferon-gamma-inducible, T cell-attracting chemokine CXCL10 in brain astrocytes. After intracerebral infection with BDV, wild-type and mutant mice developed CD8 T cell responses and neurological disease at similar frequency and with similar kinetics, suggesting that these factors are not required for initiation and maintenance of the immunopathological process. Similarly, the course of disease could not be altered by treating infected MRL mice or Lewis rats with the drug L-N(6)-(1-iminoethyl)-lysine (L-NIL) that specifically blocks the activity of the inducible NO synthase. We therefore have excluded a number of important factors that have been demonstrated to be crucial in the pathogenesis of a broad number of pathologic conditions. Thus, BDV-induced disease may not result from the action of a single dominant T cell-dependent effector molecule. Disease rather reflects a combined influence of several as yet undefined factors from CD8 T cells.

Despite recent progress in different treatment modalities, colorectal cancer remains a leading cause of cancer-related death, highlighting the need to further develop novel treatment strategies. In this context, over recent decades, several experimental studies have demonstrated that high doses of vitamin C provide anti-cancer benefits in various colorectal cancer models. Intravenous administrations of vitamin C are necessary to reach these high concentrations in tumors. Tumors harboring KRAS or BRAF mutations or driven by the HIF1α signaling pathway are particularly sensitive to high-dose vitamin C. In addition, high doses of vitamin C increase the efficacy of other treatments when used in combination, including chemotherapies, targeted therapies, and immunotherapies. Whilst results of experimental studies were promising, their translation into clinical protocols has been disappointing. So far, very few clinical data support the anti-cancer benefits of vitamin C in colorectal cancer patients. This lack of success highlights the need to ameliorate the selection of patients based on biomarkers and to refine treatment protocols to achieve high-dose vitamin C in tumors. In this review, we analyze in vitro and in vivo studies that investigated the effect of vitamin C in colorectal cancer cells and point out the anti-cancer mechanisms of vitamin C. We further examine clinical trials that tested vitamin C in colorectal cancer patients and address several points that still need to be investigated in order to fully define the role of vitamin C in the treatment of colorectal cancer.