ascorbic-acid and Lymphoma--Non-Hodgkin

Arsenic trioxide (As(2)O(3)) has established clinical activity in acute promyelocytic leukaemia and has pre-clinical data suggesting activity in lymphoid malignancies. Cell death from As(2)O(3) may be the result of oxidative stress. Agents which deplete intracellular glutathione, such as ascorbic acid (AA), may potentiate arsenic-mediated apoptosis. This multi-institution phase II study investigated a novel dosing schedule of As(2)O(3) and AA in patients with relapsed or refractory lymphoid malignancies. Patients received As(2)O(3) 0.25 mg/kg iv and AA 1000 mg iv for five consecutive days during the first week of each cycle followed by twice weekly infusions during weeks 2-6. Cycles were repeated every 8 weeks. The primary end point was objective response. In a subset of patients, sequential levels of intracellular glutathione and measures of Bcl-2 and Bax gene expression were evaluated in peripheral blood mononuclear cells during treatment. Seventeen patients were enrolled between March 2002 and February 2004. The median age was 71, and the majority of enrolled patients had non-Hodgkin's lymphoma (12/17). Sixteen patients were evaluable, and one patient with mantle cell lymphoma achieved an unconfirmed complete response after five cycles of therapy for an overall response rate of 6%. The trial, which had been designed as a two-stage study, was closed after the first stage analysis due to lack of activity. Haematologic toxicities were the most commonly reported events in this heavily pre-treated population, and comprised the majority of grade 3 and 4 toxicities. Intracellular depletion of glutathione was not consistently observed during treatment. As(2)O(3) and AA in this novel dosing strategy was generally well tolerated but had limited activity in patients with relapsed and refractory lymphoid malignancies.

Topics: Adult; Aged; Aged, 80 and over; Arsenic Trioxide; Arsenicals; Ascorbic Acid; Female; Glutathione; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Lymphoma, Non-Hodgkin; Male; Middle Aged; Oxides; Safety

Incidence rates of non-Hodgkin's lymphoma (NHL) increased substantially in the United States and worldwide during the latter part of the 20(th) century, but little is known about the etiology of this condition. Antioxidant nutrients may reduce the risk of NHL by quenching free radicals, which may contribute to carcinogenesis by damaging DNA and lipid membranes. We examined the association of intake of vitamin A and antioxidant nutrients with risk of NHL and its major subtypes in 1,104 cases of NHL identified among 154,363 postmenopausal women followed for an average of 11 yr in the Women's Health Initiative. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Of all nutrients examined, only total vitamin A intake (from diet and supplements combined) was inversely associated with risk of NHL overall (multivariate adjusted HR for highest vs. lowest quartile 0.83, 95% CI 0.69-0.99), whereas total vitamin C intake was inversely associated with risk of diffuse large B-cell lymphoma (HR for highest vs. lowest quartile 0.69, 95% CI 0.49-0.98). Overall, this study provides some evidence of inverse associations of intake of total vitamin A and total vitamin C with the risk of NHL and diffuse lymphoma, respectively.

Topics: Aged; Antioxidants; Ascorbic Acid; Diet; Dietary Fats; Dietary Supplements; Estrogen Replacement Therapy; Female; Humans; Lymphoma, Non-Hodgkin; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; United States; Vitamin A; Vitamins; Women's Health

Non-Hodgkin lymphoma (NHL) is the fifth most common cancer in the U.S. and few causes have been identified. Genetic association studies may help identify environmental risk factors and enhance our understanding of disease mechanisms.. 768 coding and haplotype tagging SNPs in 146 genes were examined using Illumina GoldenGate technology in a large population-based case-control study of NHL in the San Francisco Bay Area (1,292 cases 1,375 controls are included here). Statistical analyses were restricted to HIV- participants of white non-Hispanic origin. Genes involved in steroidogenesis, immune function, cell signaling, sunlight exposure, xenobiotic metabolism/oxidative stress, energy balance, and uptake and metabolism of cholesterol, folate and vitamin C were investigated. Sixteen SNPs in eight pathways and nine haplotypes were associated with NHL after correction for multiple testing at the adjusted q<0.10 level. Eight SNPs were tested in an independent case-control study of lymphoma in Germany (494 NHL cases and 494 matched controls). Novel associations with common variants in estrogen receptor 1 (ESR1) and in the vitamin C receptor and matrix metalloproteinase gene families were observed. Four ESR1 SNPs were associated with follicular lymphoma (FL) in the U.S. study, with rs3020314 remaining associated with reduced risk of FL after multiple testing adjustments [odds ratio (OR) = 0.42, 95% confidence interval (CI) = 0.23-0.77) and replication in the German study (OR = 0.24, 95% CI = 0.06-0.94). Several SNPs and haplotypes in the matrix metalloproteinase-3 (MMP3) and MMP9 genes and in the vitamin C receptor genes, solute carrier family 23 member 1 (SLC23A1) and SLC23A2, showed associations with NHL risk.. Our findings suggest a role for estrogen, vitamin C and matrix metalloproteinases in the pathogenesis of NHL that will require further validation.

Topics: Ascorbic Acid; Case-Control Studies; Environment; Estrogen Receptor alpha; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Lymphoma, Non-Hodgkin; Male; Matrix Metalloproteinases; Models, Genetic; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Risk Factors

To investigate and analyze changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy.. Thirty-seven patients with head and neck tumors, who received 40-70 Gy of irradiation to all major salivary glands, were analyzed. The weights of saliva secreted for 10 minutes at rest, and for 5 minutes with vitamin C stimulation, were measured. The salivary gland function was defined by the weight of saliva.. With vitamin C stimulation, the weight of saliva in patients whose doses were < or =50 Gy, was significantly higher than that of patients whose doses were > or = 58 Gy (2.48 +/- 0.33 g vs. 0.73 +/- 0.18 g, P = 0.0003). When doses administered to salivary glands were < or =50 Gy, the stimulated saliva secretion recovered over time, after irradiation. However, when the doses of irradiation were > or = 58 Gy, there was no recovery in saliva secretion even after a few years. Multiple regression analysis showed that age and chemotherapy may not affect salivary gland function even years after radiotherapy.. When salivary glands were irradiated with doses < or =50 Gy, gradual recovery of salivary gland function was observed over time, whereas there was no significant recovery when the irradiation dose was >58 Gy.

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Radiotherapy Dosage; Saliva; Salivary Glands

The authors examined use of individual supplements of vitamins A, C, and E only and multivitamins in relation to risk of non-Hodgkin's lymphoma in prospective cohorts of 88,410 women in the Nurses' Health Study (1980-1996), with 261 incident cases during 16 years of follow-up, and of 47,336 men in the Health Professionals Follow-Up Study (1986-1996), with 111 incident cases during 10 years of follow-up. Multivitamin use was associated with a higher risk of non-Hodgkin's lymphoma among women but not among men; the multivariate relative risks for long-term duration (10 or more years) were 1.48 (95% confidence interval (CI): 1.01, 2.16) for women and 0.85 (95% CI: 0.45, 1.58) for men. The pooled multivariate relative risk from the two cohorts was 1.18 (95% CI: 0.70, 2.02). Use of individual supplements of vitamins A, C, and E only was not associated with risk among men. An increased risk associated with the use of individual supplements of vitamins A, C, and E only among women appeared to be secondary to the use of multivitamins by the same persons. Because an elevated risk among multivitamin users was not observed consistently in the two cohorts and the pooled data were not significant, the elevated risk among women may be the result of chance.

Topics: Adult; Age Distribution; Aged; Antioxidants; Ascorbic Acid; Female; Health Surveys; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Nurses; Prospective Studies; Risk; Sex Distribution; Surveys and Questionnaires; United States; Vitamin A; Vitamin E

The authors evaluated the association between use of individual supplements of vitamins A, C, and E only and multivitamins and fatal non-Hodgkin's lymphoma in a large prospective mortality study of US men and women. During 14 years of follow-up (1982-1996), 1,571 non-Hodgkin's lymphoma deaths among 508,351 men and 1,398 non-Hodgkin's lymphoma deaths among 676,306 women were documented. Long-term regular use of individual supplements of vitamins A, C, and E only and multivitamins was unrelated to fatal non-Hodgkin's lymphoma among either men or women. The multivariate relative risks for men who used supplements for 10 or more years were 1.03 (95% confidence interval (CI): 0.54, 2.00) for vitamin A supplements, 1.04 (95% CI: 0.78, 1.39) for vitamin C supplements, 1.06 (95% CI: 0.74, 1.51) for vitamin E supplements, and 1.14 (95% CI: 0.92, 1.40) for multivitamins. The multivariate relative risks for women who used supplements for 10 or more years were 1.40 (95% CI: 0.77, 2.54) for vitamin A supplements, 1.19 (95% CI: 0.89, 1.60) for vitamin C supplements, 1.27 (95% CI: 0.87, 1.84) for vitamin E supplements, and 1.21 (95% CI: 0.98, 1.50) for multivitamins. All associations became weaker when vitamin supplements were mutually adjusted. These findings do not support an important relation between long-term regular use of individual supplements of vitamins A, C, and E only and multivitamins and fatal non-Hodgkin's lymphoma.

Topics: Age Distribution; Antioxidants; Ascorbic Acid; Female; Health Surveys; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prospective Studies; Sex Distribution; United States; Vitamin A; Vitamin E

Little is known about dietary factors and non-Hodgkin's lymphoma (NHL) risk, although high intakes of animal protein and milk have been associated with NHL in two previous studies. As part of a population-based case-control study of agricultural and other risk factors for NHL in eastern Nebraska (USA), we examined the self- and proxy-reported frequency of consumption of 30 food items by 385 White men and women with NHL and 1,432 controls. Animal protein intake was not associated significantly with the risk of NHL, however, there was a nonsignificantly elevated risk of NHL among men with high milk consumption. Vitamin C, carotene, citrus fruit, and dark green vegetable intakes were inversely significantly related to the risk of NHL for men, but not for women. Among men, the odds ratios for the highest quartiles of both vitamin C and carotene intake were 0.6 (95% confidence intervals = 0.3-1.0). There were no meaningful differences in the associations of nutrient intakes and NHL risk between B- and T-cell lymphomas and histologic types. Risks for low intakes of vitamin C and carotene were greater among men and women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives.

Topics: Adult; Aged; Animal Population Groups; Animals; Ascorbic Acid; Carotenoids; Case-Control Studies; Citrus; Diet; Dietary Proteins; Female; Food; Humans; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Male; Middle Aged; Milk; Nebraska; Population Surveillance; Risk Factors; Sex Factors; Vegetables; White People

In 1975, we reported the remarkable case of a 42-year-old man with histologically proven widely disseminated reticulum cell sarcoma who, in a remarkably short time, appeared to enjoy not one, but two, complete spontaneous regressions of his fatal illness. Both these regressions coincided exactly in time with intravenous high-dose ascorbate administration, and it seemed reasonable to conclude that this unconventional therapy must have been responsible for his excellent responses. For those interested in spontaneous regressions of cancer and the possible mechanisms, we now report his subsequent progress some 17 years later.

Topics: Adenocarcinoma; Ascorbic Acid; Dose-Response Relationship, Drug; Humans; Lymphoma, Non-Hodgkin; Middle Aged; Neoplasm Regression, Spontaneous; Thyroid Neoplasms

A new malignant human T-cell line-labelled PFI-285-has been isolated from a boy with malignant lymphoma. Morphologically, the cells had characteristics of malignant lymphoid cells. The cells presented surface antigens as early cortical lymphocytes and proliferated non-adherently as single cells, independent of T-cell growth factor (IL-2), in liquid culture. The cells had undetectable levels of receptors for IL-2, were not clonogenic in soft agar, but did form tumors in nude mice. Their establishment and continuous growth in vitro was dependent on the number of cells inoculated and on the growth medium used. Cytogenetic alteration, HTLV-1 or reverse transcriptase activity were not detected. The production of known T-cell derived lymphokines such as IL-2, B-cell growth factor(s), alpha-interferon or granulocyte/macrophage colony stimulating or inhibiting factor(s) was not detected. The cells had 5-8% natural killer (NK)-cell activity against NK-cell sensitive target cells (K562) and were not sensitive for NK cells. A most unusual characteristic was the pronounced sensitivity of the cells to ascorbic acid. Concentrations down to 50 mumol/l killed the cells within hours.

Topics: Adolescent; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Ascorbic Acid; Cell Line; Cell Membrane; Cell Nucleus; Chromosome Banding; Clone Cells; Culture Techniques; Cytotoxicity, Immunologic; Humans; Karyotyping; Killer Cells, Natural; Lymphoma, Non-Hodgkin; Male; Mice; Mice, Nude; Microscopy, Electron; Microscopy, Electron, Scanning; Neoplasm Transplantation; T-Lymphocytes; Transplantation, Heterologous; Tumor Cells, Cultured

The possible inhibitory effect of vitamin C (sodium ascorbate) on metastases from two transplantable murine tumors was studied. The first murine tumor, colon carcinoma CA-51, was subcutaneously transplanted into male Balb/c mice. Immediately after tumor implantation, the mice were given either 1.0% sodium ascorbate or tap water. Subcutaneous tumors were surgically removed from one half of the animals in each group when the tumors reached a size of 1.5 cm. Results indicated no differences in survival, in the number of mice with metastases, or in the size of metastases between treated and untreated groups. The second murine tumor, lymphosarcoma 6C3HED, was subcutaneously implanted into C3H male and female mice. Sodium ascorbate (1.0% or 3.0%) was administered as above, but surgery was not performed. Again, no significant differences in the number of mice with metastases were observed between treated and untreated groups, with the exception of brain and regional lymph node metastases (enhanced, in males, by ascorbate).

Topics: Animals; Ascorbic Acid; Carcinoma; Colonic Neoplasms; Female; Lymphoma, Non-Hodgkin; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Neoplasm Metastasis; Neoplasms, Experimental

Topics: Ascorbic Acid; Female; Homogentisic Acid; Humans; Lactates; Lymphoma, Non-Hodgkin; Male; Phenylpropionates; Phenylpyruvic Acids; Time Factors; Tyrosine

The response of a patient with histologically proven reticulum cell sarcoma to no treatment other than large doses of ascorbic acid is described. At the time of first diagnosis, the disease was widely disseminated, and a very dramatic regression of all parameters of disease activity was induced by the continuous administration of large doses of ascorbic acid. Reduction in dosage some months later coincided with reactivation of the disease process. The reinstitution of regular high-dose ascorbic acid therapy induced a second complete remission. The case report is illustrated by serial radiographs. The significance of the therapeutic response is briefly discussed in relation to general schemes of cancer management.

Topics: Adult; Ascorbic Acid; Humans; Lymphoma, Non-Hodgkin; Male; Radiography

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Epinephrine; Flavonoids; Lymphoma, Non-Hodgkin; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Norepinephrine; Rats; Sarcoma 180

Topics: Adenocarcinoma, Papillary; Ascorbic Acid; Female; Hemangioendothelioma; Humans; Lymphoma, Non-Hodgkin; Male; Sarcoma; Thyroid Neoplasms

This series presents further evidence for an association between reticulosis of the intestine and steatorrhoea. Although some patients have a definite past history of gluten enteropathy, it seems likely that in certain patients the reticulosis itself is the primary cause of the steatorrhoea.

Topics: Ascorbic Acid; Blood Transfusion; Body Weight; Bone Marrow Examination; Celiac Disease; Diet; Diet Therapy; Fats; Feces; Folic Acid; Humans; Intestinal Neoplasms; Intestinal Perforation; Intestine, Small; Iron; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Nandrolone; Neomycin; Neoplasms; Pathology; Prednisone; Sarcoma; Steatorrhea; Surgical Procedures, Operative; Vitamin A; Vitamin B 12; Vitamin B Complex; Vitamins; Water-Electrolyte Balance

Topics: Animals; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Liver; Liver Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Metabolism; Mice; Microsomes; Microsomes, Liver; Neoplasms; Neoplasms, Experimental; Oxidoreductases; Research

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Ascorbic Acid; Histamine; Lymphoma; Lymphoma, Non-Hodgkin; Sarcoma; Vitamins