ascorbic-acid and Carcinoma--Renal-Cell

Studies have showed that vitamin C intake is linked to renal cell carcinoma risk, however, the results were inconsistent. Hence, the present meta-analysis was to examine the association between vitamin C intake and RCC risk. We searched the published studies that reported the relationship between vitamin C intake and RCC risk using PubMed and Embase up to January 2015. Based on a fixed effects model, RR and the corresponding 95% CI were used to assess the pooled risk. 3 prospective cohort studies and 7 case-control studies were included. The overall RR (95% CI) of RCC for the highest vs. the lowest levels of vitamin C intake was 0.78(0.69,0.87). Little evidence of heterogeneity was found. In the subgroup analyses, we found an inverse association between vitamin C intake and RCC risk in the case-control studies but not in the prospective cohort studies. Additionally, this association between vitamin C intake and RCC risk was not differed by population distribution. Our study provides evidence that vitamin C intake is associated with a reduced RCC risk. However, our conclusion was just based on ten including studies, so more high-quality of case-control studies or cohort studies which report this topic are needed.

Topics: Ascorbic Acid; Carcinoma, Renal Cell; Dietary Supplements; Humans; Kidney Neoplasms; Public Health Surveillance; Publication Bias; Risk

Recent observational studies and meta-analyses have shown that vitamin C reduces cancer incidence and mortality, but the underlying mechanisms remain unclear. We conducted a comprehensive pan-cancer analysis and biological validation in clinical samples and animal tumor xenografts to understand its prognostic value and association with immune characteristics in various cancers.. We used the Cancer Genome Atlas gene expression data involving 5769 patients and 20 cancer types. Vitamin C index (VCI) was calculated using the expression of 11 genes known to genetically predict vitamin C levels, which were classified into high and low subgroups. The correlation between VCI and patient overall survival (OS), tumor mutational burden (TMB), microsatellite instability (MSI), and immune microenvironment was evaluated, using Kaplan-Meier analysis method and ESTIMATE (https://bioinformatics.mdanderson.org/estimate/). Clinical samples of breast cancer and normal tissues were used to validate the expression of VCI-related genes, and animal experiments were conducted to test the impact of vitamin C on colon cancer growth and immune cell infiltration.. Significant changes in expression of VCI-predicted genes were observed in multiple cancer types, especially in breast cancer. There was a correlation of VCI with prognosis in all samples (adjusted hazard ratio [AHR] = 0.87; 95% confidence interval [CI] = 0.78-0.98;. VCI is significantly correlated with OS and immunotypes in multiple cancers, and vitamin C might have therapeutic potential in colon cancer.

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Carcinoma, Renal Cell; Colonic Neoplasms; Female; Humans; Kidney Neoplasms; Lung Neoplasms; Mice; Rectal Neoplasms; Tumor Microenvironment; Vitamins

Exploring the regulatory mechanism of PD-L1 in renal cancer is one of the key strategies to improve the response of renal cancer patients to checkpoint blockade therapy. In this study, the synergistic effect of ascorbic acid (vitamin C) supplementation and the impact of TET2 depletion on anti-PD-L1 therapy were determined in xenograft model experiments. Lymphocyte infiltration and chemokine expression were determined using flow cytometry and qRT-PCR. To determine the downstream targets of TET2, we performed hMeDip-seq and RNA-seq analyses. The molecular mechanism was further confirmed by hMeDip-qPCR, MeDip-qPCR, bisulfite sequencing, Western blotting, qRT-PCR and xenograft model experiments

Topics: Ascorbic Acid; B7-H1 Antigen; Carcinoma, Renal Cell; Cell Line, Tumor; Chemokines; Cytokines; Dioxygenases; DNA-Binding Proteins; Enzyme Activation; Female; Humans; Immunotherapy; Kidney Neoplasms; Male

Maintenance of whole-body ascorbate levels and distribution is mediated via sodium-dependent vitamin C transporters (SVCTs). The kidney is one of a few organs that express both SVCT1 and SVCT2. Recent evidence suggests that accumulation of ascorbate may be different in tumour compared to normal tissue, but data on SVCT levels in tumours is sparse.. The role of the two SVCT isoforms in ascorbate uptake in renal cell carcinoma (RCC) was investigated in vitro and in clinical samples. In three human RCC cell lines, we investigated SVCT protein levels and cellular location in response to ascorbate supplementation and withdrawal. In clinical RCC samples (n=114), SVCT patterns of staining and protein levels were analysed and compared to ascorbate levels.. In cell culture, transporter levels and cellular location were not modified by ascorbate availability at any time up to 8h, although basal SVCT2 levels governed maximal ascorbate accumulation. In clinical samples, SVCT1 protein levels in papillary RCC (pRCC) were similar to matched normal renal cortex, but were increased in clear-cell RCC (ccRCC). Native SVCT2 (72 kDa) was significantly decreased in both pRCC and ccRCC tissues compared to cortex (p<0.01), whereas a modified form of SVCT2 (100 kDa) was significantly increased (p<0.001). There was no association between the transporters (SVCT1, native or modified SVCT2) and ascorbate concentrations in either normal or tumour tissues. SVCT1 and SVCT2 displayed diffuse cytoplasmic staining in both pRCC and ccRCC tumour cells, with cortex showing distinct membrane staining for SVCT1.. We observed a re-distribution of ascorbate transporters in tumour tissue compared to normal cortex and a shift from native to modified SVCT2 in cell culture and clinical samples. Data presented here show that SVCT protein levels do not appear to predict intracellular ascorbate accumulation in RCC.

Topics: Ascorbic Acid; Carcinoma, Renal Cell; Cell Line, Tumor; Humans; Kidney Neoplasms; Sodium-Coupled Vitamin C Transporters

The inhibition of 5-lipoxygenase (5-LO), the key enzyme for the biosynthesis of leukotrienes (LTs), has generated increasing enthusiasm as anti-inflammatory and antitumor strategies in recent years. Based on our previous studies, we synthesized a series of dihydroxycinnamic acid-based analogs that might be 5-LO inhibitors. LTs biosynthesis inhibition in HEK293 cells and polymorphonuclear leukocytes (PMNL) was measured and antitumor activities were investigated in Renal Cell Carcinoma (RCC). Results showed that the 2,5-dihydroxycinnamic acid phenethyl ester (10b) was the best 5-LO inhibitor and was 7-fold more potent than Zileuton (1), the only clinically approved 5-LO inhibitor. 2,5-Dihydroxy substitution was more favorable to 5-LO inhibition since compound 10b is twice as active as CAPE (2) which is a 3,4-dihydroxylcinnamic acid ester. Meanwhile, 10b reduced the cell viability of renal cancer cells  and was more selective toward RCC4 and 786.0 cells which are deficient for the Von Hippel-Lindau (VHL) tumor suppressor gene. As to the underlying cell-death mechanisms, 10b induced apoptosis in VHL-deficient RCC4 cells. Also, increases in LC3B and p62 expression suggest a blockage of the autophagic flux in RCC in response to 10b.

Topics: Antineoplastic Agents; Apoptosis; Arachidonate 5-Lipoxygenase; Carcinoma, Renal Cell; Cell Proliferation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Drug Discovery; Drug Screening Assays, Antitumor; HEK293 Cells; Humans; Kidney Neoplasms; Lipoxygenase Inhibitors; Molecular Structure; Neutrophils; Structure-Activity Relationship

Although clear cell renal cell carcinoma (ccRCC) has been shown to result in widespread aberrant cytosine methylation and loss of 5-hydroxymethylcytosine (5hmC), the prognostic impact and therapeutic targeting of this epigenetic aberrancy has not been fully explored. Analysis of 576 primary ccRCC samples demonstrated that loss of 5hmC was strongly associated with aggressive clinicopathologic features and was an independent adverse prognostic factor. Loss of 5hmC also predicted reduced progression-free survival after resection of nonmetastatic disease. The loss of 5hmC in ccRCC was not due to mutational or transcriptional inactivation of ten eleven translocation (TET) enzymes, but to their functional inactivation by l-2-hydroxyglutarate (L2HG), which was overexpressed due to the deletion and underexpression of L2HG dehydrogenase (L2HGDH). Ascorbic acid (AA) reduced methylation and restored genome-wide 5hmC levels via TET activation. Fluorescence quenching of the recombinant TET-2 protein was unaffected by L2HG in the presence of AA. Pharmacologic AA treatment led to reduced growth of ccRCC in vitro and reduced tumor growth in vivo, with increased intratumoral 5hmC. These data demonstrate that reduced 5hmC is associated with reduced survival in ccRCC and provide a preclinical rationale for exploring the therapeutic potential of high-dose AA in ccRCC.

Topics: 5-Methylcytosine; Adult; Alcohol Oxidoreductases; Animals; Ascorbic Acid; Carcinoma, Renal Cell; Cell Line, Tumor; Female; Gene Deletion; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Male; Mice

Loss of 5-hydroxymethylcytosine (5hmC) occurs frequently in a wide variety of tumours, including clear-cell renal cell carcinoma (ccRCC). It remains unknown, however, whether the restoration of 5hmC patterns in tumours could have therapeutic efficacy. Here, we used sodium L-ascorbate (vitamin C, AsANa) and the oxidation-resistant form L-ascorbic acid 2-phosphate sesquimagnesium (APM) for the restoration of 5hmC patterns in ccRCC cells. At physiological concentrations, both show anti-tumour efficacy during long-term treatment

Topics: 5-Methylcytosine; Animals; Ascorbic Acid; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Proliferation; Dioxygenases; DNA-Binding Proteins; Enhancer Elements, Genetic; Humans; Kidney Neoplasms; Mice; Proto-Oncogene Proteins; Transcriptome; Xenograft Model Antitumor Assays

Renal cell carcinoma (RCC) is the eighth leading cancer among women in incidence and commonly is diagnosed at a more advanced stage. Oxidative stress has been considered to play an important role in the pathogenesis of RCC. Various dietary micronutrients have antioxidant properties, including carotenoids and vitamins C and E; thus, diets rich in these nutrients have been evaluated in relation to RCC prevention. The objective of this study was to explore the correlation between antioxidant micronutrients and the risk of RCC.. In total, 96,196 postmenopausal women who enrolled in the Women's Health Initiative (WHI) between 1993 and 1998 and were followed through July 2013 were included in this analysis. Dietary micronutrient intake was estimated from the baseline WHI food frequency questionnaire, and data on supplement use were collected using an interview-based inventory procedure. RCC cases were ascertained from follow-up surveys and were centrally adjudicated. The risks for RCC associated with intake of α-carotene, β-carotene, β-cryptoxanthin, lutein plus zeaxanthin, lycopene, vitamin C, and vitamin E were analyzed using Cox proportional hazards regression adjusted for confounders.. Two hundred forty women with RCC were identified during follow-up. Lycopene intake was inversely associated with RCC risk (P = .015); compared with the lowest quartile of lycopene intake, the highest quartile of intake was associated with a 39% lower risk of RCC (hazard ratio, 0.61; 95% confidence interval, 0.39-0.97). No other micronutrient was significantly associated with RCC risk.. The current results suggest that further investigation into the correlation between lycopene intake and the risk of RCC is warranted.

Topics: Aged; Antioxidants; Ascorbic Acid; Carcinoma, Renal Cell; Carotenoids; Clinical Trials as Topic; Cryptoxanthins; Dietary Supplements; Female; Follow-Up Studies; Humans; Kidney Neoplasms; Lutein; Lycopene; Micronutrients; Middle Aged; Multicenter Studies as Topic; Odds Ratio; Postmenopause; Proportional Hazards Models; Treatment Outcome; Vitamin E; Women's Health; Zeaxanthins

Although several conventional therapeutic options for advanced renal cell carcinoma (RCC) are currently available, the unsatisfactory outcomes demand establishing more effective interventions. D-fraction (PDF), a bioactive proteoglucan of Maitake mushroom, demonstrates anticancer and immunomodulatory activities, which are also shown to be potentiated by vitamin C (VC). We thus hypothesized that a combination of PDF and VC (PDF + VC) could be an alternative approach to more effectively inhibit the growth of RCC.. We examined the dose-dependent effects of PDF + VC on RCC cell viability and also performed biochemical assays to explore the growth regulatory mechanism.. Human RCC, ACHN cell line, was employed and exposed to varying concentrations of PDF or VC and their combinations. Cell viability at specified times was determined by MTT assay. Lipid peroxidation assay, cell cycle analysis, and Western blot analysis were also performed.. PDF or VC alone led to the significant reduction in cell viability at 72 hours with PDF >500 µg/mL and VC ≥300 µM. When various combinations of PDF and VC were tested, the combination of the ineffective concentrations of PDF (300 µg/mL) and VC (200 µM) resulted in ~90% cell death in 24 hours. Lipid peroxidation assay then indicated significantly (~2.5 fold) elevated oxidative stress with this PDF + VC. Cell cycle analysis also indicated a G1 cell cycle arrest following a 6-hour PDF + VC treatment. Western blots further revealed a downregulation of Bcl2, an upregulation of Bax, and proteolytic activation of PARP (poly[ADP-ribose] polymerase) in PDF + VC-treated cells, indicating induction of apoptosis.. The present study demonstrates that the combination of PDF and VC can become highly cytotoxic, inducing severe cell death in ACHN cells. This cytotoxic mechanism appears to be primarily attributed to oxidative stress, accompanied by a G1 cell cycle arrest. Such cell death induced by PDF + VC could be more likely linked to apoptosis, as indicated by the modulation of apoptosis regulators (Bcl2, Bax, and PARP). Therefore, as PDF and VC may work synergistically to induce apoptotic cell death, they may have clinical implications in an alternative, improved therapeutic modality for advanced RCC.

Topics: Ascorbic Acid; Carcinoma, Renal Cell; Cell Death; Cell Proliferation; Cell Survival; Drug Combinations; Drug Evaluation, Preclinical; Drug Synergism; Grifola; Humans; Kidney Neoplasms; Oxidative Stress; Plant Extracts; Tumor Cells, Cultured

In industrialized countries, increasing concentrations of harmful trace elements in the human environment increases their concentration in the organs, which in turn may be responsible for the growth of cancer including cancer of the kidney. Trace elements by increasing the concentration of active free radicals damage cell DNA, and in a consequence increase the risk of carcinogenesis. The aim of this study was to determine concentrations of biochemical markers providing an increase in the concentration of free radicals in the cell kidney cancer and renal cortical tissue, from which it originates and to attempt correlation of these markers with the concentration of carcinogenic trace elements identified in these same tissues using spectral analysis of PIXE (Proton induced X-Ray Emmision).. Of the 12 kidneys removed because of renal cell carcinoma clippings taken from the parenchyma of the kidney and kidney tumor, and then the concentration of markers of oxidative stress such as malonic dialdehyd (MDA), reduced form and oxidized glutathione and 1-ascorbic acid of the tissue. The concentration of elements was made by means of physical methods of analysis of multielemental PIXE (Proton Induced X-Ray Emission) in tumor tissue and kidney tissue of renal cortical tumor unchanged.. Malonic dialdehyd concentrations (MDA), reduced and oxidized forms of glutathione and 1-ascorbic acid were successively 2.11, 1.23, 0.84 and 2.25 microg/g for tissue kidney tumor and subsequently one, 58, 0.99, 0.58 and 2.3 microg/g in the kidney cortex from which the tumor originates. Demonstrated significant differences in MDA concentrations (p < 0.01) and the oxidized form of glutathione (p < 0.05). In the analysis of correlation between the concentrations of markers of the concentrations of elements are carcinogenic by IARC (International Agency for Research on Cancer) showed significant increase in the concentration of 1-ascorbic acid with increasing concentrations of lead in kidney tumor tissue. In the renal cortex increased concentrations of MDA and oxidized forms of glutathione was significantly correlated with increased levels of selenium.. By markers of oxidative stress has been shown indirectly to increased metabolism of oxygen free radicals in kidney tumor tissue compared to kidney cortex tissue from which it derives. At the same time was selected markers concentration dependence of the concentration of the elements considered by the IARC human carcinogens. Confirmation of these results on a larger group of patients may become a contribution to the study of substances that protect the kidney against carcinogens storage elements or substances that reduce oxidative stress in the kidney.

Topics: Ascorbic Acid; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Glutathione; Humans; Kidney Neoplasms; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Trace Elements

Previous epidemiologic studies that have examined the relationship between renal cell carcinoma (RCC) risk and intakes of plant foods and antioxidant nutrients have yielded inconsistent results. We therefore examined the associations between intakes of fruit, vegetables, carotenoids, flavonoids, vitamin E and vitamin C and RCC risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort. At baseline, 27,062 male Finnish smokers aged 50-69 years completed a 276-item dietary questionnaire that included questions on frequency of consumption and portion size. During up to 19 years of follow-up, 255 men developed RCC. Cox proportional hazards models were utilized to estimate relative risks (RR) and 95% confidence intervals (CI). Despite a large range in intake, no association was observed between fruit, vegetables or antioxidant nutrients and RCC risk. For example, multivariate RRs and 95% CIs for the highest versus the lowest quartile of intake were 0.79 (0.55-1.14), 1.23 (0.85-1.79), 1.09 (0.74-1.60), 0.83 (0.57-1.21), 1.09 (0.73-1.64) and 0.99 (0.67-1.46) for fruit, vegetables, total carotenoids, total flavonoids, total vitamin E and vitamin C, respectively (all p values for trend > 0.05). Our results indicate that diet may not play a large role in the etiology of RCC in male smokers, although further examination of these associations in nonsmokers, women and diverse racial populations is warranted.

Topics: Aged; Antioxidants; Ascorbic Acid; Carcinoma, Renal Cell; Carotenoids; Diet; Finland; Flavonoids; Fruit; Humans; Liver Neoplasms; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires; Vegetables; Vitamin E

Advanced renal cell carcinoma (RCC) frequently develops skeletal metastasis and is highly resistant to conventional therapies. We hypothesized that the osteocalcin (OC) promoter may be a promising gene delivery system for RCC targeted gene therapy because osteotropic tumors gain osteomimetic properties and thrive in the new environment by exhibiting a bone-like gene expression profile. Human OC (hOC) expression is highly regulated by vitamins and hormone. In the present study, we tested the feasibility of vitamin-regulatable hOC promoter for RCC-specific transcriptional targeting, and examined the anti-tumor effect of vitamins C and D₃ with hOC-based adenoviral vectors towards RCC.. Real-time reverse transcriptase-polymerase chain reaction measured OC expression induced by vitamins C and D₃, either alone or in combination, in RCC and normal human renal epithelial cells (HRE). The RCC-cytotoxic effects of concomitant vitamins and hOC promoter-based adenoviral vectors, Ad-hOC-TK and Ad-hOC-E1, were evaluated in both cell culture and a xenograft murine model.. We found that high doses of vitamin C induced H₂O₂-dependent apoptosis in RCC but not HRE. Treatment of RCC cells with combined vitamins C and D₃ treatment significantly increased OC promoter activity compared to single reagent treatment. Combined vitamin therapy reduced tumor size (85%) and complete tumor regression occurred in 38% of mice co-administrated Ad-hOC-E1.. The results obtained in the present study demonstrate that vitamins C and D₃ synergized with the anti-tumor effects of therapeutic genes driven by hOC promoter through direct cytotoxicity as well as transcriptional targeting. This combined gene therapy provides a promising modality for advanced RCC targeted therapy.

Topics: Adenoviridae; Animals; Ascorbic Acid; Carcinoma, Renal Cell; Cell Line, Tumor; Genetic Therapy; Genetic Vectors; Humans; Kidney Neoplasms; Male; Mice; Mice, Knockout; Mice, Nude; Osteocalcin; Promoter Regions, Genetic; Transcription, Genetic; Tumor Cells, Cultured; Vitamin D; Xenograft Model Antitumor Assays

The study examines the association between dietary intake of vitamin C, E, and carotenoids and the risk of renal cell carcinoma (RCC).. Between 1994 and 1997 in 8 Canadian provinces, mailed questionnaires were completed by 1,138 incident, histologically confirmed cases of RCC and 5,039 population controls, including information on socio-economic status, lifestyle habits and diet. A 69-item food frequency questionnaire provided data on eating habits 2 years before data collection. Odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression.. Dietary intake of beta-carotene and lutein/zeaxanthin was inversely associated with the risk of RCC. The ORs for the highest versus the lowest quartile were 0.74 (95% CI, 0.59-0.92) and 0.77 (95% CI, 0.62-0.95), respectively. The significant inverse association with beta-carotene and lutein/zeaxanthin was more pronounced in women, and in overweight or obese subjects. The relation of lutein/zeaxanthin to RCC was stronger in ever smokers. No clear association was observed with vitamin C and E, beta-cryptozanthin, and lycopene.. The findings provide evidence that a diet rich in beta-carotene and lutein/zeaxanthin may play a role in RCC prevention.

Topics: Adult; Aged; Ascorbic Acid; Canada; Carcinoma, Renal Cell; Carotenoids; Case-Control Studies; Diet; Eating; Feeding Behavior; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Registries; Risk Factors; Social Class; Vitamin E; Young Adult

An Ethiopian girl 14 years and 11 months of age presented with bilateral transcervical hip fractures. Workup revealed severe vitamins D and C deficiencies with secondary hyperparathyroidism. Imaging studies showed bilateral radiolucent metaphyseal bands with multiple lytic lesions in long bones. A mass in the right flank was found to be renal cell carcinoma (RCC). Currently, 9 months postsurgery and supplemental therapy, the patient is fully ambulatory and free of pain. This first report of asymptomatic RCC in severely vitamin D deficient child highlights the relation of RCC to vitamin D deficiency and emphasizes the importance of careful evaluation of these children.

Topics: Adolescent; Ascorbic Acid; Carcinoma, Renal Cell; Combined Modality Therapy; Female; Femoral Neck Fractures; Functional Laterality; Humans; Kidney Neoplasms; Tomography, X-Ray Computed; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Early clinical studies showed that high-dose vitamin C, given by intravenous and oral routes, may improve symptoms and prolong life in patients with terminal cancer. Double-blind placebo-controlled studies of oral vitamin C therapy showed no benefit. Recent evidence shows that oral administration of the maximum tolerated dose of vitamin C (18 g/d) produces peak plasma concentrations of only 220 micromol/L, whereas intravenous administration of the same dose produces plasma concentrations about 25-fold higher. Larger doses (50-100 g) given intravenously may result in plasma concentrations of about 14,000 micromol/L. At concentrations above 1000 micromol/L, vitamin C is toxic to some cancer cells but not to normal cells in vitro. We found 3 well-documented cases of advanced cancers, confirmed by histopathologic review, where patients had unexpectedly long survival times after receiving high-dose intravenous vitamin C therapy. We examined clinical details of each case in accordance with National Cancer Institute (NCI) Best Case Series guidelines. Tumour pathology was verified by pathologists at the NCI who were unaware of diagnosis or treatment. In light of recent clinical pharmacokinetic findings and in vitro evidence of anti-tumour mechanisms, these case reports indicate that the role of high-dose intravenous vitamin C therapy in cancer treatment should be reassessed.

Topics: Aged; Ascorbic Acid; Carcinoma, Renal Cell; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Kidney Neoplasms; Lymphoma, B-Cell; Male; Middle Aged; Survival Analysis; Treatment Outcome; Urinary Bladder Neoplasms; Vitamins

Five-year survival is limited to 60% in renal cancer patients at diagnosis. Due to the cancer's resistance to conventional treatments and associated high morbidity, we investigated the antimetastatic effects of a specific nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid and green tea extract on human renal adenocarcinoma cell line 786-0 by measuring: cell proliferation, modulation of MMP-2 and -9 secretion, and cancer cell invasive potential. Human renal cancer cell line 786-0 (ATCC) was grown in RPMI medium in 24-well tissue culture plates. At near confluence, the cells were treated with NM, dissolved in media, and tested at 0, 10, 50, 100, 500 and 1000 microg/ml in triplicate at each dose. Cells were also treated with PMA 200 ng/ml to study enhanced MMP-9 activity. Cell proliferation was evaluated by MTT assay, MMP secretion by gelatinase zymography, and invasion through Matrigel. Zymography demonstrated MMP-2 and MMP-9 secretion by uninduced renal cancer cells with enhanced MMP-9 induced by PMA (200 ng/ml) treatment. NM inhibited the secretion of both MMPs in a dose-dependent fashion with virtual total inhibition of MMP-2 at 500-microg/ml concentration and MMP-9 at 100 microg/ml. The invasion of renal cancer cells through Matrigel was totally inhibited (p=0.0001) by NM at 1000 microg/ml concentration. Our results support a potential role for the nutrient mixture tested in the treatment of renal cell carcinoma, by inhibition of MMP-2 and MMP-9 secretion and invasion.

Topics: Antineoplastic Combined Chemotherapy Protocols; Arginine; Ascorbic Acid; Camellia sinensis; Carcinoma, Renal Cell; Cell Growth Processes; Cell Line, Tumor; Collagen; Drug Combinations; Gelatinases; Humans; Kidney Neoplasms; Laminin; Lysine; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Plant Extracts; Proline; Proteoglycans

Fruits and vegetables rich in antioxidants have been proposed to reduce the risk of renal cell cancer. However, few prospective studies have examined the intakes of fruits, vegetables, and antioxidant vitamins in relation to the risk of renal cell cancer.. We prospectively examined the associations between the intakes of fruits, vegetables, vitamins A, C, and E, and carotenoids and risk of renal cell cancer in women and men. We followed 88,759 women in the Nurses' Health Study from 1980 to 2000, and 47,828 men in the Health Professionals Follow-up Study from 1986 to 2000. We assessed dietary intake every 2 to 4 years using a validated semiquantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate study-specific multivariate relative risks (RR), which were pooled using a random effects model.. A total of 248 (132 women and 116 men) incident renal cell cancer cases were ascertained during 2,316,525 person-years of follow-up. The consumption of fruits and vegetables was associated with a decreased risk of renal cell cancer in men (multivariate RR, 0.45; 95% CI, 0.25-0.81, for >or=6 servings of fruit and vegetable intake/d versus <3 servings/d; P test for trend = 0.02), but not in women (multivariate RR, 1.17; 95% CI, 0.66-2.07, for the same contrast; P test for trend = 0.25; P test for between-studies heterogeneity = 0.02). Intakes of vitamins A and C from food and carotenoids were inversely associated with the risk of renal cell cancer in men only, but we cannot exclude the possibility that this was due to other factors in fruit and vegetables. No clear association was observed for vitamin E in women or men.. Fruit and vegetable consumption may reduce the risk of renal cell cancer in men.

Topics: Adult; Antioxidants; Ascorbic Acid; Carcinoma, Renal Cell; Carotenoids; Diet Records; Female; Fruit; Health Surveys; Humans; Middle Aged; Prospective Studies; Risk Assessment; Sex Factors; United States; Vegetables; Vitamin A; Vitamin E; Vitamins

The intensity of ascorbate-dependent free radical oxidation of endogenous lipids in malignant tumor tissue of human kidneys was studied. The LPO induction period was markedly increased in renal-cell carcinoma and malignant mesenchymal tumors compared to normal renal cortex. The content of alpha-tocopherol in cancer tissue lipids was considerably (7-fold) increased compared to that in normal renal cortex, which explains high antioxidant activity of these carcinomas. A less pronounced increase in the content of alpha -tocopherol in lipids of malignant mesenchymal tumors compared to the cortex (2-fold) can also contribute to their LPO resistance.

Topics: Adult; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Carcinoma, Renal Cell; Fatty Acids, Unsaturated; Female; Free Radicals; Humans; Kidney Cortex; Kidney Neoplasms; Kinetics; Lipid Metabolism; Lipid Peroxidation; Male; Mesoderm; Middle Aged; Time Factors

Oral administration of ochratoxin A to young weanling mice (Mus musculus) caused several haematological changes and induced hepatoma and renal carcinoma. Concurrent administration of berry and leaf juice of the common grape (Vitis vinifera) to mice together with ochratoxin A significantly reduced the hepatic and renal damage caused by ingestion of this mycotoxin. None of the animals receiving berry/leaf juice of V. vinifera showed the formation of hepatorenal carcinoma whereas 25% of animals receiving only ochratoxin A developed well differentiated renal carcinoma and hepatic lesions.

Topics: Animals; Antidotes; Ascorbic Acid; Carcinogens; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Kidney Neoplasms; Liver Neoplasms; Mice; Ochratoxins; Plant Leaves; Rosales; Thiamine