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 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

Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience

Abstract In idiopathic thrombocytopenic purpura (ITP), corticosteroids have been widely recognized as the most appropriate first-line treatment, even if the best therapeutic approach is still a matter of debate. Recently, a single high-dose dexamethasone (HD-DXM) course was administered as first-line therapy in adult patients with ITP. In this paper we show the results of 2 prospective pilot studies (monocentric and multicentric, respectively) concerning the use of repeated pulses of HD-DXM in untreated ITP patients. In the monocenter study, 37 patients with severe ITP, age at least 20 years and no more than 65 years, were enrolled. HD-DXM was given in 4-day pulses every 28 days, for 6 cycles. Response rate was 89.2%; relapse-free survival (RFS) was 90% at 15 months; long-term responses, lasting for a median time of 26 months (range 6-77 months) were 25 of 37 (67.6%). In the multicenter study, 95 patients with severe ITP, age at least 2 years and no more than 70 years, were enrolled. HD-DXM was given in 4-day pulses every 14 days, for 4 cycles; 90 patients completed 4 cycles. Response rate (85.6%) was similar in patients classified by age (< 18 years, 36 of 42 = 85.7%; ≥ 18 years, 41 of 48 = 85.4%, P = not significant), with a statistically significant difference between the second and third cycle (75.8% vs 89%, P = .018). RFS at 15 months 81%; long-term responses, lasting for a median time of 8 months (range 4-24 months) were 67 of 90 (74.4%). In both studies, therapy was well tolerated. A schedule of 3 cycles of HD-DXM pulses will be compared with standard prednisone therapy (eg, 1 mg/kg per day) in the next randomized Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) trial

Brief Tale of a Bacteraemia by Rhodococcus equi, With Concomitant Lung Mass: What Came First, the Chicken or The Egg?

Rhodococcus equi is an uncommon Gram positive, variably acid-fast pathogen, that appears as hard to treat mostly owing to the establishment of intracellular niches. Lack of interpretive criteria for susceptibility testing may lead to under-reporting or overestimation of resistances, whereas knowledge about this pathogen’s clinical impact may be affected by erroneous phenotype-based characterization at a genus and species level

ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia

Abstract Extracellular signal-regulated kinase-1/2 (ERK1/2) is frequently found constitutively activated (p-ERK1/2) in hematopoietic diseases, suggesting a role in leukemogenesis. The aim of this study was to assess the expression and clinical role of p-ERK1/2 in adult acute lymphoblastic leukemia (ALL). In 131 primary samples from adult de novo ALL patients enrolled in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acute Linfoide (LAL) 2000 protocol and evaluated by flow cytometry, constitutive ERK1/2 activation was found in 34.5% of cases; these results were significantly associated with higher white blood cell (WBC) values (P = .013). In a multivariate analysis, p-ERK1/2 expression was an independent predictor of complete remission achievement (P = .027). Effective approaches toward MEK inhibition need to be explored in order to evaluate whether this may represent a new therapeutic strategy for adult ALL patients

Megadoses of Sodium Ascorbate Efficiently Kill HL60 Cells <i>in Vitro</i>: Comparison with Arsenic Trioxide

Arsenic Trioxide (ATO) is widely acknowledged as the treatment of choice for Acute Promyelocytic Leukemia (APL). It is a “two-sided” drug since it can induce differentiation or kill APL and other tumor cells according to the dosage. Part of the cytotoxic effects of ATO on APL cells is due to its pro-oxidant activity, a characteristic which ATO shares with a number of other compounds, including high doses of ascorbate (ASC). In a comparative investigation on the cy-totoxic effects of both ATO and ASC on HL60 (APL) cell lines, in vitro, we have been able to confirm the known cy-totoxic effects of ATO, but, more importantly, we have demonstrated that ASC is significantly more effective than ATO, in killing these cancer cells in vitro, when the concentrations are maintained within the millimolar (mM) range, i.e. the range of plasma concentrations at which ASC induces oxidative damage to tumor cells. Since these plasma lev- els can be reached only by the intravenous administration of high doses of ASC, we propose that intravenous high doses of ASC may represent a potentially revolutionary new approach in the management of APL

Catheter-Related Candidemia Caused by Candida lipolytica in a Patient Receiving Allogeneic Bone Marrow Transplantation

Candida lipolytica was recovered from the blood and the central venous catheter in a patient receiving allogeneic bone marrow transplantation. Two C. lipolytica strains from different geographical areas and the ATCC 9773 strain of C. lipolytica were used as controls. C. lipolytica was identified by standard methods. MICs indicated antifungal susceptibilities to amphotericin B, fluconazole, and itraconazole for all strains. In vitro testing and scanning electron microscopy showed that C. lipolytica was capable of producing large amounts of viscid slime material in glucose-containing solution, likely responsible for the ability of the yeast to adhere to catheter surfaces. Restriction fragment length polymorphisms revealed an identical profile for all clinical isolates, unrelated to those observed for the control strains. This finding suggested the absence of microevolutionary changes in the population of the infecting strain, despite the length of the sepsis and the potential selective pressure of amphotericin B, which had been administered to the patient for about 20 days. The genomic differences that emerged between the isolates and the control strains were indicative of a certain degree of genetic diversity between C. lipolytica isolates from different geographical areas

Haemopoietic reconstitution after autologous blood stem cell transplantation in patients with malignancies: A multicentre retrospective study

A retrospective study was undertaken to evaluate the efficacy of autologous blood stem cell transplantation (ABSCT) in terms of haemopoietic reconstitution after ablative chemotherapy or chemo-radiotherapy, 55 patients with malignancies, observed in four Italian institutions from January 1987 to June 1991, were eligible for evaluation. This series included 19 non- Hodgkin's lymphoma, 11 multiple myeloma, nine ovarian cancer, seven Hodgkin's disease, seven non-lymphocytic leukaemia, one acute lymphoblastic leukaemia, one neuroblastoma. 522 PBSC collections were performed on 55 patients. Following ABSCT, the rate of engraftment was positively related to the dose of CFU-GM infused and negatively to the presence of bone marrow involvement at conditioning, 48 patients out of 55 transplanted (87%) had rapid, complete and sustained engraftment. Three patients (5%) died of transplant-related complications. Considering that 60% of the patients in this series were in partial remission or in progressive disease at the time of ABSCT, we conclude that ABSCT is a safe approach for the use of ablative conditioning therapy in patients with a wide scope of malignancies, provided that a large number of CFU-GM have been collected after mobilizing treatment