ascorbic-acid and Bone-Neoplasms

The relationship of vitamins to cancer is very complex. Three types of interactions are possible: the effect of vitamins on tumor growth, the effect of tumors on vitamin metabolism, and the effect of vitamins on chemical carcinogens and anti-tumor chemotherapeutic agents. The significance of vitamins with particular references to vitamins A,B-complex and C, in cancer has been reviewed.

Topics: Antineoplastic Agents; Ascorbic Acid; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Bronchial Neoplasms; Humans; Neoplasms; Nutritional Physiological Phenomena; Tryptophan; Vitamin A; Vitamin B Complex; Vitamin B Deficiency; Vitamins

To evaluate efficacy of oral antioxidant treatment given to patients before radiologic procedures in reducing x-ray-induced DNA damage.. There was a significantly higher number of gamma-H2AX foci/cell after ionization radiation in the control group compared with the antioxidant group (P = .009). There was no statistically significant difference in number of gamma-H2AX foci/cell before or after exposure in the antioxidant group; the number of gamma-H2AX foci/cell was statistically significantly higher (P = .009) in the control group after exposure to. In patients undergoing

Topics: Acetylcysteine; Administration, Oral; Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Bone Neoplasms; DNA Breaks, Double-Stranded; Drug Combinations; Histones; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Neoplasm Staging; Ontario; Oxidative Stress; Predictive Value of Tests; Prospective Studies; Radiation Injuries; Radiopharmaceuticals; Technetium Tc 99m Medronate; Thioctic Acid; Time Factors; Treatment Outcome

Vitamin C and iron are both important nutrients for humans and involved in several physiological processes. The biological activities of vitamin C and iron are based on their abilities to accept or donate electrons. Although vitamin C is well known as an excellent electron donor in physiological conditions, it also has pro-oxidant properties, especially with catalytic metal iron. Cancer cells have a higher iron requirement than normal cells, which allows pharmacological ascorbate to kill cancer cells selectively. In this study, we demonstrated that the levels of H

Topics: Ascorbic Acid; Bone Neoplasms; Cell Line, Tumor; Humans; Iron; Osteosarcoma; Oxidative Stress

Osteosarcoma (OS) is the most common malignant bone tumor and a leading cause of cancer-related deaths in children and adolescents. Current standard treatments for OS are a combination of preoperative chemotherapy, surgical resection, and adjuvant chemotherapy. Cisplatin is used as the standard chemotherapeutic for OS treatment, but it induces various adverse effects, limiting its clinical application. Improving treatment efficacy without increasing the cisplatin dosage is desirable. In the present study, we assessed the combined effect of ascorbate on cisplatin treatment using cultured human OS cells. Co-treatment with ascorbate induced greater suppression of OS cell but not nonmalignant cell proliferation. The chemosensitizing effect of ascorbate on cisplatin treatment was tightly linked to ROS production. Altered cellular redox state due to increased ROS production modified glycolysis and mitochondrial function in OS cells. In addition, OS cell sphere formation was markedly decreased, suggesting that ascorbate increased the treatment efficacy of cisplatin against stem-like cells in the cancer cell population. We also found that enhanced MYC signaling, ribosomal biogenesis, glycolysis, and mitochondrial respiration are key signatures in OS cells with cisplatin resistance. Furthermore, cisplatin resistance was reversed by ascorbate. Taken together, our findings provide a rationale for combining cisplatin with ascorbate in therapeutic strategies against OS.

Topics: Antineoplastic Agents; Ascorbic Acid; Bone Neoplasms; Cell Line, Tumor; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Humans; Osteosarcoma; Oxidation-Reduction

The objective of this study is to understand the effect of sustained release of vitamin C from β-tricalcium phosphate (β-TCP) scaffold on proliferation, viability and differentiation of human fetal osteoblast cells (hFOB). The influence of pH, drug concentration, and presence of polymer on the sustained release of vitamin C from polycaprolactone (PCL) coated β-TCP scaffolds are studied. Prolonged and sustained release of vitamin C, over 60 days is observed in PCL coated β-TCP scaffolds compared to uncoated scaffolds. Presence of PCL helps to minimize the burst release of vitamin C from β-TCP scaffolds in the initial 24 h of release. To evaluate the osteogenic potential of vitamin C incorporated β-TCP scaffolds, osteoblast cells are cultured and cell morphology, proliferation, viability, and differentiation are assessed. Morphological characterization shows layer like osteoblast cell attachment in the presence of vitamin C compared to the control. MTT cell viability assay shows 2 folds increase in osteoblast cell density in the presence of vitamin C after 3,7 and 11 days of culture. Furthermore, increased ALP activity at 11 days of culture indicates the possible role of vitamin C on osteoblast differentiation. Additionally, a preliminary study shows vitamin C loaded scaffolds suppress osteosarcoma (MG-63) cell proliferation to 4 folds after 3 days compared to control. These results show a sustained release of vitamin C from PCL coated β-TCP scaffolds improve proliferation, viability, and differentiation of osteoblasts cell as well as mitigate osteosarcoma cell proliferation, suggesting its potential application as synthetic bone graft substitutes in tissue engineering application.

Topics: Ascorbic Acid; Bone Neoplasms; Calcium Phosphates; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Delayed-Action Preparations; Humans; Osteoblasts; Osteosarcoma

The aim of this study was to observe effects of ascorbic acid application on pain, performance status, and survival time in cancer patients. A retrospective cohort of 39 patients with bone metastases treated with radiotherapy was identified. All patients were radiotherapy-resistant. Fifteen patients who received chemotherapy, and 15 patients who received an infusion of 2.5 g ascorbic acid were included in the study. Nine control patients were treated with neither chemotherapy nor vitamin C. Eastern Cooperative Oncology Group Performance Status Scale and Visual Analog Scale were used to determine performance status and pain assessments. Survival time and rate in patients were defined. Statistical analyses were performed to compare the results of groups. Performance status was increased in 4 patients of vitamin C group and 1 patient of chemotherapy group, whereas performance status in control group was decreased. A median reduction of 50% in pain was observed among the patients in the vitamin C group. Median survival time was 10 mo in patients receiving ascorbic acid, whereas the chemotherapy and control groups had a median survival of 2 mo. Intravenous vitamin C application seems to reduce pain in patients in comparison to other patients who did not receive it. Patient performance status and survival rate were increased using vitamin C.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Bone Neoplasms; Dose-Response Relationship, Radiation; Female; Humans; Male; Middle Aged; Palliative Care; Radiotherapy; Retrospective Studies; Survival Rate

Osteosarcoma originates from mesenchymal stem cells with impaired bone differentiation. In the present study we investigated the effect of ascorbic acid (AsA) on osteogenic differentiation and apoptosis of the MG-63 osteosarcoma cell line.. We evaluated the expression of runt-related transcription factor-2 (RUNX2) and secreted phosphoprotein 1 (SPP1) genes by real-time Polymerase Chain Reaction (PCR) and of endogenous bone morphogenetic protein-2 (BMP2) and osteocalcin proteins by immunohistochemistry. We analyzed osteoblast maturation by phosphatase alkaline synthesis and calcium deposition, and apoptosis by (TUNEL) test and Annexin staining.. Our results showed that RUNX2 and SPP1 gene expression was increased in cells treated with low concentrations of AsA with respect to untreated cells. At higher concentrations, AsA induced apoptosis of osteosarcoma cells, possibly with the involvement of p21.. Our findings support the ability of AsA to induce both differentiation, by affecting the target involved in early and late phases of osteogenic maturation, and apoptosis in poorly-differentiated osteosarcoma cells.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Bone Morphogenetic Protein 2; Bone Neoplasms; Cell Differentiation; Cell Line, Tumor; Cell Lineage; Cell Survival; Core Binding Factor Alpha 1 Subunit; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Osteopontin; Osteosarcoma

Osteosarcoma (OS) is a highly aggressive bone cancer affecting children and young adults. Growing evidence connects the invasive potential of OS cells with their ability to form invadopodia (structures specialized in extracellular matrix proteolysis).. In this study, we tested the hypothesis that commonly used in vitro stimulators of mineralization limit the invadopodia formation in OS cells. Here we examined the invasive potential of human osteoblast-like cells (Saos-2) and osteolytic-like (143B) OS cells treated with the stimulators of mineralization (ascorbic acid and B-glycerophosphate) and observed a significant difference in response of the tested cells to the treatment. In contrast to 143B cells, osteoblast-like cells developed a mineralization phenotype that was accompanied by a decreased proliferation rate, prolongation of the cell cycle progression and apoptosis. On the other hand, stimulators of mineralization limited osteolytic-like OS cell invasiveness into collagen matrix. We are the first to evidence the ability of 143B cells to degrade extracellular matrix to be driven by invadopodia. Herein, we show that this ability of osteolytic-like cells in vitro is limited by stimulators of mineralization.. Our study demonstrates that mineralization competency determines the invasive potential of cancer cells. A better understanding of the molecular mechanisms by which stimulators of mineralization regulate and execute invadopodia formation would reveal novel clinical targets for treating osteosarcoma.

Topics: Ascorbic Acid; Bone Neoplasms; Calcification, Physiologic; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Surface Extensions; Cell Survival; Collagen Type I; Glycerophosphates; Humans; Neoplasm Invasiveness; Osteosarcoma; Phenotype; Proteolysis

To further understand the synergistic mechanism of As2O3 and asscorbic acid (AA) in human osteosarcoma MG-63 cells by systems biology analysis.. Human osteosarcoma MG-63 cells were treated by As2O3 (1 µmol/L), AA (62.5 µmol/L) and combined drugs (1 µmol/L As2O3 plus 62.5 µmol/L AA). Dynamic morphological characteristics were recorded by Cell-IQ system, and growth rate was calculated. Illumina beadchip assay was used to analyze the differential expression genes in different groups. Synergic effects on differential expression genes (DEGs) were analyzed by mixture linear model and singular value decomposition model. KEGG pathway annotations and GO enrichment analysis were performed to figure out the pathways involved in the synergic effects.. We captured 1987 differential expression genes in combined therapy MG-63 cells. FAT1 gene was significantly upregulated in all three groups, which is a promising drug target as an important tumor suppressor analogue; meanwhile, HIST1H2BD gene was markedly downregulated in the As2O3 monotherapy group and the combined therapy group, which was found to be upregulated in prostatic cancer. These two genes might play critical roles in synergetic effects of AA and As2O3, although the exact mechanism needs further investigation. KEGG pathway analysis showed many DEGs were related with tight junction, and GO analysis also indicated that DEGs in the combined therapy cells gathered in occluding junction, apical junction complex, cell junction, and tight junction.. AA potentiates the efficacy of As2O3 in MG-63 cells. Systems biology analysis showed the synergic effect on the DEGs.

Topics: Antineoplastic Agents; Apoptosis; Arsenic Trioxide; Arsenicals; Ascorbic Acid; Bone Neoplasms; Cell Line, Tumor; Drug Synergism; Drug Therapy, Combination; Humans; Osteosarcoma; Oxides; Systems Biology

Immunotherapy has become an attractive new strategy in the treatment of cancer. The laboratory and clinical study of cancer immunotherapy is rapidly advancing. However, in the clinical setting, the results of cancer immunotherapy are mixed. We therefore contend that cancer immunotherapy should be customized to each patient individually based on their immune status and propose an integrative immunotherapy approach with second-generation group-specific component macrophage activating factor (GcMAF)-containing human serum.. The standard protocol of our integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily.. By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy was remarkably effective.. The results of our integrative immunotherapy seem hopeful. We also plan to conduct a comparative clinical study.>

Topics: Aged; Ascorbic Acid; Bone Neoplasms; Cell- and Tissue-Based Therapy; Combined Modality Therapy; Female; Humans; Immunotherapy; Injections, Intramuscular; Injections, Subcutaneous; Liver Neoplasms; Lung Neoplasms; Macrophage-Activating Factors; Male; Prognosis; Prostatic Neoplasms; Thioctic Acid; Thymus Neoplasms; Vitamin D-Binding Protein

Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. In the present study, we evaluated the oxidative status and antioxidant defense in patients with prostate cancer (PCa) taking into consideration: treatment, Gleason score and bone metastasis. For this, we measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasma and erythrocyte thiol levels and serum vitamin C and E concentration. This study was performed on 55 patients with PCa and 55 healthy men. TBARS levels and serum protein carbonylation were higher in PCa patients than in controls and altered levels of antioxidants were found in these patients. CAT activity was decreased and SOD activity was higher in PCa patients when compared with controls. Non-protein thiol levels were increased, however, serum vitamin C and vitamin E content were reduced in PCa patients when compared with controls. In addition, different parameters analyzed in PCa patients based on metastasis, treatment and Gleason score showed changes in oxidative stress biomarkers and antioxidant defenses. These findings may indicate an imbalance in the oxidant/antioxidant status, supporting the idea that oxidative stress plays a role in PCa, moreover, the oxidative profile appear to be modified by bone metastasis, treatment and Gleason score.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Ascorbic Acid; Bone Neoplasms; Catalase; Cyproterone Acetate; Erythrocytes; Goserelin; Humans; Lipid Peroxidation; Male; Middle Aged; Neoplasm Grading; Oxidative Stress; Prostatic Neoplasms; Protein Carbonylation; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

During breast cancer metastasis to bone, tumor cells home to bone marrow, likely targeting the stem cell niche, and stimulate osteoclasts, which mediate osteolysis required for tumor expansion. Although osteoblasts contribute to the regulation of the hematopoietic stem cell niche and control osteoclastogenesis through production of proresorptive cytokine RANKL (receptor activator of NF-κB ligand), their role in cancer metastases to bone is not fully understood. C57BL/6J mouse bone marrow cells were treated for 3-12 days with ascorbic acid (50 μg/ml) in the presence or absence of 10% medium conditioned by breast carcinoma cells MDA-MB-231, 4T1, or MCF7. Treatment with cancer-derived factors resulted in a sustained 40-60% decrease in osteoblast differentiation markers, compared with treatment with ascorbic acid alone, and induced an osteoclastogenic change in the RANKL/osteoprotegerin ratio. Importantly, exposure of bone cells to breast cancer-derived factors stimulated the subsequent attachment of cancer cells to immature osteoblasts. Inhibition of γ-secretase using pharmacological inhibitors DAPT and Compound E completely reversed cancer-induced osteoclastogenesis as well as cancer-induced enhancement of cancer cell attachment, identifying γ-secretase activity as a key mediator of these effects. Thus, we have uncovered osteoblasts as critical intermediary of premetastatic signaling by breast cancer cells and pinpointed γ-secretase as a robust target for developing therapeutics potentially capable of reducing both homing and progression of cancer metastases to bone.

Topics: Amyloid Precursor Protein Secretases; Animals; Antigens, Differentiation; Antioxidants; Ascorbic Acid; Benzodiazepinones; Bone Marrow Cells; Bone Neoplasms; Breast Neoplasms; Cell Differentiation; Cell Line, Tumor; Culture Media, Conditioned; Female; Humans; Mammary Neoplasms, Animal; Mice; Neoplasm Metastasis; Osteoblasts; Osteoclasts; Osteoprotegerin; RANK Ligand; Signal Transduction

Enhanced supplementation with certain naturally occurring nutrients and vitamins has been associated with a reduction in occurrence and progression of human cancer. The exact mechanisms of this action are still under investigation. Extracellular matrix (ECM) plays a key role in the development of cancer. Therefore, we studied whether nutrients could exert anticancer effects through alteration of ECM biological properties. Confluent cultures of normal human dermal fibroblasts were allowed to produce and deposit ECM during a 7 d incubation period in the presence of tested compounds. Subsequently, fibroblasts were removed and the growth rates of freshly placed cultures of human osteosarcoma cells (lines U2-OS, MMNG, or SK.ES1) on pre-formed ECM were assayed in plain cell growth medium. In addition, ECM was deposited by fibroblasts on the upper surface of a porous plastic membrane and the subsequent migration of osteosarcoma cells to the other side was assayed in non-supplemented medium. The results demonstrated that the ECM produced by normal fibroblasts treated with a mixture of ascorbic acid, lysine, proline, arginine, cysteine, and green tea polyphenols significantly reduced the growth rate and invasive activity of osteosarcoma cells in contrast to the non-supplemented control. The changes in ECM properties were accompanied by significant changes in ECM protein and glycosaminoglycan composition as assayed immunochemically. We conclude that anticancer effects of nutrients involve beneficial changes in ECM biological properties. The role of ECM components in ECM-dependent regulation of tumor cell activities is discussed.

Topics: Amino Acids; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Bone Neoplasms; Camellia sinensis; Cell Line, Tumor; Cell Proliferation; Collagen; Extracellular Matrix; Fibroblasts; Humans; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Osteosarcoma; Plant Extracts

Current treatment of osteosarcoma is associated with poor prognosis, especially due to the increased risk of developing other cancers with chemotherapy. Therefore, new, safe and effective treatment strategies are needed. We investigated the effect of a unique mixture of nutrients containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate (EGCG) on human osteosarcoma cell lines U-2OS, MNNG-HOS, and Ewing's sarcoma SK-ES-1 by measuring: cell proliferation, expression of matrix metalloproteinase-2 (MMP-2), MMP-9, and invasive and angiogenesis potential. Cell proliferation was evaluated by MTT assay, matrix metalloproteinases (MMP) expression by gelatinase zymography, VEGF expression by ELISA, and invasion through Matrigel. Cells were also treated with phorbol 12-myristate 13-acetate (PMA) to study enhanced MMP and VEGF expression. The invasion of osteosarcoma U-2OS and MNNG-HOS cells through Matrigel was significantly reduced in a dose-dependent fashion, with 100% inhibition of invasion of U-2OS cells at 100 microg/ml, and MNNG cells at 50 microg/ml concentration of the synergistically acting nutrient mixture. Ewing's sarcoma SK-ES-1 cells were not invasive. Nutrient synergy (NS) exhibited a dose response antiproliferative effect on osteosarcoma U-2OS cells, reaching 67% at 1000 microg/ml of NS; no significant suppression of cell proliferation was seen with MNNG or Ewing's sarcoma cells. Zymography showed dose-dependent inhibition of MMP secretion by all three cell lines in the presence of NS. VEGF secretion by U-2OS cells was completely blocked at 500 microg/ml of NS. Our results suggest NS is an excellent candidate for therapeutic use in the treatment of osteosarcoma, by inhibiting cancer cell invasion, and secretion of MMPs and VEGF, all critical parameters for cancer control and prevention.

Topics: Arginine; Ascorbic Acid; Bone Neoplasms; Catechin; Cell Proliferation; Dose-Response Relationship, Drug; Humans; Lysine; Matrix Metalloproteinases; Neovascularization, Pathologic; Nutritional Physiological Phenomena; Osteosarcoma; Proline; Sarcoma, Ewing; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

The biosynthesis of type VI collagen was studied in human glioblastoma cell line, U-87 MG. The effects of ascorbic acid on type VI collagen synthesis and secretion were investigated. After ascorbic acid treatment, type VI collagen in cell layers increased from 4.48% in control to 6.63% in the ascorbic acid treated cultures, an increase of 48%. The effect of ascorbic acid on type VI collagen synthesized by glioblastoma cells was lower than that reported for osteosarcoma cells (Engvall et al., 1986). The reason for these differences is still under investigation. The function of type VI collagen in glioblastoma cells is still unknown. We utilized the collagen gel system to elucidate the possible roles of type VI collagen in glioblastoma cells in vitro. Glioblastoma cells in collagen gels showed a stellate shape with long, branched processes in all directions. The strong positive reactivity of type VI collagen detected on cell bodies and cell processes by anti-type VI collagen antibody indicated that this specific collagen was associated with cell surfaces and processes, without releasing or diffusing into the gels. Type VI collagen was directly involved in the cell process extension. When living cells were treated with anti-type VI collagen antibody, a variation of cell morphology was observed. Instead of a stellate shape with processes, cells formed clusters without or with very short processes. These data suggest that type VI collagen, synthesized and secreted by glioblastoma cells, may play a role in tumor cell adhesion and spreading, and enhance cell process extension, penetration, and invasion into collagen gels.

Topics: Antibodies; Artificial Organs; Ascorbic Acid; Bone Neoplasms; Brain Neoplasms; Cell Adhesion; Cell Membrane; Cell Shape; Cell Surface Extensions; Collagen Type VI; Extracellular Matrix; Gels; Glioblastoma; Humans; Models, Biological; Neoplasm Invasiveness; Osteosarcoma; Up-Regulation

Present evidence suggests that a high fat intake may be one of the factors in the aetiology of breast cancer. Patients with breast cancer may show an increased requirement for thiamin particularly when treated with 5-fluorouracil, and a number of metabolic disturbances in which ascorbic acid may play a central role.

Topics: Animals; Ascorbic Acid; Bone Neoplasms; Breast Neoplasms; Calcium; Dietary Fats; Feeding Behavior; Female; Fluorouracil; Humans; Hydroxyproline; Lipase; Lipids; Mammary Neoplasms, Experimental; Mice; Neoplasm Metastasis; Rats; Thiamine Deficiency; Thiamine Pyrophosphate

Of one hundred and twenty-six patients with Gardner's syndrome, 60% showed soft tissue tumors, 32% showed osteomatosis, 67% polyposis, and 20% the complete triad. Bowel cancer developed in 32% of the patients. The frequency of other diseases in these patients showed fibrous tumors in 8%, and two patients with cancer of the ampulla of Vater; otherwise the diseases seen did not show any major variation from what might be expected for the group at risk. Laboratory evaluation has included the demonstration of increased fecal cholesterol and primary bile acids in these patients. The recommended surgical treatment is colectomy and ileorectal anastomosis at a measured 12 cm level. This level of ileorectal anastomosis may be vital in giving a regression of rectal polyps, which was seen in 15 to 17 patients so treated. The conversion of an ileosigmoid to an ileorectal anastomosis resulted in polyp regression in one patient. The oral administration of ascorbic acid gave polyp regression in seven of 10 patients. There may be a possible relationship of fecal coprostanol and cholesterol levels and polyp regression.

Topics: Adolescent; Adult; Ascorbic Acid; Bone Neoplasms; Child; Colectomy; Colon, Sigmoid; Female; Follow-Up Studies; Humans; Ileum; Intestinal Polyps; Male; Rectal Diseases; Rectum; Soft Tissue Neoplasms; Syndrome

Topics: Ascorbic Acid; Bone Neoplasms; Breast Neoplasms; Female; Humans; Hydroxyproline; Leukocytes; Male; Neoplasm Metastasis; Time Factors

Topics: Adenocarcinoma; Ascorbic Acid; Bone Neoplasms; Breast Neoplasms; Humans; Neoplasm Metastasis