Vitamin C Against Cancer

The selective anticancer properties of vitamin C are known since at least four decades. However, only recently in vitro studies have shown that vitamin C, in high enough concentrations, can efficiently and selectively kill a number of different human tumor cell lines, and these data have been confirmed in experimental animal tumor models. The first human clinical trials revealed that high doses of vitamin C administered by intravenous injection are not only very well tolerated but also substantially improve the quality of life of patients with clinically advanced cancer. However, the clinical evidence of the effectiveness of vitamin C in fighting off cancer is still controversial. The present chapter outlines the importance of vitamin C for a number of physiological functions, within the human body, and shows that there is a solid rationale for its use in the routine treatment of cancer, either alone or in combination with conventional treatment

The cure from nature: the extraordinary anticancer properties of Ascorbate (Vitamin C)

The anticancer properties of Vitamin C (ascorbic acid o sodium ascorbate) are known since at least four decades, However, being a cheap and "natural" product, Vitamin C is not patentable and therefore has never been developed as an anticancer molecule. Recent in vitro investigations have confirmed the extraordinary antitumor properties of high doses of Vitamin C (sodium ascorbate), particularly when administered by the intravenous route, and phase I/II randomized, controlled clinical trials have been started to verify its anticancer properties in vivo. Unfortunately, the controlled clinical trials performed so far, do not confirm the extraordinary results obtained with Vitamin C (sodium ascorbate) in vitro. However, this may depend on a number of different factors, such as the pharmaceutical preparation (Sodium ascorbate may be more suitable than buffered ascorbic acid), the schedule of administration (slow infusion better than rapid infusion), tumor tissue oxygenation (Cancer tissue oxygenation is lower that oxygenation of tumor cell lines, in vitro), etc., which deserve further in depth investigation. Even with these limitations, Vitamin C (sodium ascorbate) in high doses, administered by intravenous route, beyond being extremely effective in vitro, against a number of human tumor cell lines, is safe, has minimal contraindications, improves the quality of life of patients, and is highly selective for cancer cells. The Authors discuss these important aspects and suggest possible solutions to improve the in vivo anticancer effects of Vitamin C (sodium ascorbate)

High Doses of Ascorbate Kill Y79 Retinoblastoma Cells In vitro

Objectives: To tests the sensitivity of Y79 retinoblastoma cell lines to high doses of ascorbate, in vitro, and compare its effects with those of some chemotherapeutic agents routinely employed in the treatment of retinoblastoma. Methods: Y79 retinoblastoma cells have been exposed to increasing doses of either sodium ascorbate (SA) or Melphalan (MEL), to define a dose-response curve around the peak plasma concentrations reached by both chemicals when administered according to the existing therapeutic procedures and protocols. The assessment of cell number and viability was performed, before and after exposure, with both the manual (Trypan Blue Exclusion Test) and automated (flow cytometry) methods. Fluorescence microscopy and direct observation of cells in culture, with inverted microscope, were also performed. Results: Y79 cells are highly sensitive to the cytotoxic effect of SA, with cell viability reduced of over 90% in some experiments. As reported in the literature, this effect is directly cytotoxic and most probably mediated by acute oxidative stress on different cellular components. The same does not apply to Melphalan which, at the doses commonly used for therapeutic purposes, did not show any significant effect on cell viability, in vitro. Conclusion: To our knowledge, this is the first report showing that high doses of SA can actively kill retinoblastoma cells in vitro. While it is not surprising for SA, to show direct cytotoxic effect on tumor cells, the data reported herein represent the first evidence in favor of the possible clinical use of high doses of intravenous SA, to treat children affected by retinoblastoma. Given the many advantages of SA over the chemotherapeutic agents commonly employed to treat cancer (including its almost total absence of toxic or side effects, and its exclusive specificity for cancer cells), it is reasonable to assume, from the data reported herein, that the high doses of intravenous ascorbate, have the potential to represent a real revolution in the treatment of retinoblastoma

High Doses of Vitamin C and Leukemia: In Vitro Update

Vitamin C (ascorbic acid) is an essential nutrient with a number of beneficial effects on the human body. Although the majority of mammals can synthesize their own Vitamin C, humans and a few other species, do not produce it and depend on dietary sources for their Vitamin C supply. Among its many effects on cell function and metabolism, Vitamin C has shown, in vitro, a powerful anticancer effect against a number of human tumor cell lines, including myeloid leukemia. There are many different mechanistic explanations for the anticancer/anti-leukemic effects of Vitamin C and the aim of the present review is to illustrate these mechanisms, showing the results of some preliminary in vitro investigations, and outlining their potential clinical relevance

Differential expression of follistatin and FLRG in human breast proliferative disorders

<p>Abstract</p> <p>Background</p> <p>Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG) bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases.</p> <p>Methods</p> <p>Paraffin embedded specimens of normal breast (NB - n = 8); florid hyperplasia without atypia (FH - n = 17); fibroadenoma (FIB - n = 17); ductal carcinoma <it>in situ </it>(DCIS - n = 10) and infiltrating ductal carcinoma (IDC - n = 15) were processed for follistatin and FLRG immunohistochemistry and <it>in situ </it>hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively.</p> <p>Results</p> <p>Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed.</p> <p>Conclusion</p> <p>The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the present findings indicate that an increased FST and FLRG expression in breast proliferative diseases might counteract the anti-proliferative effects of activin in human breast cancer.</p

Inflammatory cells and cytokines production in chalazia

Purpose Aim of the present study was to localize the different types of inflammatory cells and cytokines in chalazion lesions to determine the sequence of events in cellular reaction. Methods Fifty four chalazia surgically removed by excision were fixed in Bouin’s solution and imbedded in paraffin. For immunohistochemical studies we used CD68, CD3, CD4, CD8, CD45RO, lactoferrin antibodies to detect respectively macrophages, T cells, T helper, T cytotoxic, mature activated T lymphocytes and neutrophils. For detection of cytokines we used IFN gamma and TNF alpha antibodies. The EnVision peroxidase detection system were used and the immmunoreactivity was visualized with diaminobenzidine. Results Large numbers of macrophages infiltrated the stroma around the alveoli and the glandular tissue of the chalazion lesions. Lower numbers of the neutrophils were found with similar distribution to macrophages. CD3(+) lymphocytes also accumulated in large numbers in the stroma, around the glands, and in the areas of granulomatous inflammation indicating an association with macrophages and neutrophils. Within the T-cell population, numerous CD8(+) cells, fewer CD4(+) cells, many CD45RO(+) cells were present. Positivity for IFN-gamma and TNF-alpha was showed in granulomatous areas and near vessels. Conclusion These cells play a significant role in the formation of the chalazion lesion. Neutrophils might be recruited into granulomatous lesions from the blood and may subsequently promote inflammatory cells accumulation both by direct cell to cell interactions and through the interaction of cytokines. The presence of IFN-gamma and TNF alpha suggests that these cytokines play a paracrine role in chalazion inflammatio

Glucocorticoid receptors in human peripheral blood mononuclear cells in relation to explosive performance in elite handball players

Ten handball players, members of the Italian National Team (aged 20–25 years), were studied in two sessions corresponding to different performance levels. The first session occurred one week after the end of the regular season of the Italian Handball ederation: it corresponded to the beginning of the training cycle for the European Handball Championship. The second session occurred ten weeks after the first session. During this period, training consisted of 3 weeks of active recovery and 7 weeks of increasing workload. For each session, jumping performances (maximal height in a single jump, average mechanical power for a 15-s set of consecutive jumps) were evaluated. Venous blood samples were collected in resting conditions immediately before jumping performances to assess cortisol and testosterone plasma concentrations and glucocorticoid receptors (GcR) binding capacity and affinity in peripheral blood mononuclear cells (PBMCs). All the parameters, except GcR binding affinity, increased in the second session. The trends of variation in jumping performances, steroid hormone levels and GcR binding capacity were similar. For testosterone, this agrees with the hypothesis that an adequate level of this hormone is a prerequisite for improvement in explosive performances. For cortisol, higher GcR binding capacity after 10 weeks of training (with respect to initial values) indicated an upregulation of GcR concomitant with the increase in hormone levels and performances. These findings suggest that the adaptation to training, confirmed by the improvement in performance, is characterized by a high value of GcR binding capacity and that it is mediated, among other factors, by the hormone levels and up-regulation of the receptors

Megadoses of Ascorbate as a New Chemotherapeutic Approach in Uveal Melanoma: A Preliminary In Vitro Investigation

Background: Despite the more recent advances, there is still no effective systemic therapy for Uveal Melanoma (UM). However, a better understanding of the role of oxidative stress in cancer, has more recently led to a completely new approach to the systemic therapy of cancer, and modulators of the oxidative balance, such as sodium ascorbate (ASC) or arsenic trioxide (ATO), have already entered advanced phases of preclinical and clinical development. Since high doses of ASC have already demonstrated a strong cytotoxic effect on different human cancer cell lines, we have undertaken the present investigation in order to test the sensitivity of OCM1 and C918 uveal melanoma (UM) cell lines to high doses of ASC, in vitro, as compared to ATO, a pro-oxidant drug which has already undergone extensive in vitro and pre-clinical investigation in UM. Methods: Both OCM1 and C918 UM cell lines have been exposed to increasing doses of either ASC or ATO, to build a dose-response curve around the peak plasma concentrations reached by both chemicals. The assessment of cell count and viability was performed with flow cytometry. Results: Both OCM1 and C918 UM cell lines are highly sensitive to ASC in the range of millimolar (mM) concentrations which can be usually reached by the intravenous injection of high doses of the compound. ATO at the dosages used in this study, never reached the LC50. When the exposure to ASC was reduced to two hours, it still had significant effects on survival of both OCM1 and C918 UM cells. Conclusions: This report shows that ASC is highly cytotoxic for both OCM1 and C918 UM cells, when used in high, pro-oxidant doses. To our knowledge, this is the first report showing that UM cells can be efficiently killed, in vitro, with high doses of ASC