vitamin-b-12 and Carcinoma--Squamous-Cell

Previous studies have found associations between one-carbon metabolism nutrients and risk of several cancers, but little is known regarding upper gastrointestinal tract (UGI) cancer. We analyzed prediagnostic serum concentrations of several one-carbon metabolism nutrients (vitamin B12, folate, vitamin B6, riboflavin and homocysteine) in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers, which was undertaken in Finland between 1985 and 1988. We conducted a nested case-control study including 127 noncardia gastric adenocarcinoma (NCGA), 41 esophagogastric junctional adenocarcinoma and 60 esophageal squamous cell carcinoma incident cases identified within ATBC. Controls were matched to cases on age, date of serum collection and follow-up time. One-carbon nutrient concentrations were measured in fasting serum samples collected at baseline (up to 17 years prior to cancer diagnosis). Odds ratios and 95% confidence intervals (CI) were calculated using conditional logistic regression. Lower prediagnostic vitamin B12 concentrations at baseline were associated with a 5.8-fold increased risk of NCGA (95% CI = 2.7-12.6 for lowest compared to highest quartile, p-trend <0.001). This association remained in participants who developed cancer more than 10 years after blood collection, and after restricting the analysis to participants with clinically normal serum vitamin B12 (>300 pmol/L). In contrast, pepsinogen I, a known serologic marker of gastric atrophy, was not associated with NCGA in this population. As vitamin B12 absorption requires intact gastric mucosa to produce acid and intrinsic factor, our findings suggest vitamin B12 as a possible serologic marker for the atrophic gastritis that precedes NCGA, one more strongly associated with subsequent NCGA than pepsinogen.

Topics: Aged; alpha-Tocopherol; beta Carotene; Carcinoma, Squamous Cell; Case-Control Studies; Dietary Supplements; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Finland; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Prospective Studies; Riboflavin; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC).. This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles.. Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy.. Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted.

Topics: Adult; Aged; Aminopterin; Carcinoma, Squamous Cell; Disease Progression; Female; Folic Acid; Folic Acid Antagonists; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Squamous Cell Carcinoma of Head and Neck; Vitamin B 12; Vitamin B Complex; Young Adult

Pralatrexate is an antifolate designed for preferential tumor cell uptake and accumulation and received accelerated Food and Drug Administration approval in relapsed/refractory peripheral T-cell lymphoma. Pralatrexate 135 to 150 mg/m(2) every 2 weeks without vitamin supplementation was active in non-small cell lung cancer (NSCLC) although mucositis was dose limiting. This phase 1 study evaluated the safety of higher pralatrexate doses with vitamin supplementation to minimize toxicities.. Patients with stage IIIB/IV NSCLC received pralatrexate 150 to 325 mg/m(2) every 2 weeks with folic acid and vitamin B12 supplementation. Outcomes measured included adverse events (AEs), pharmacokinetics, and radiologic response.. Thirty-nine patients were treated for a median of two cycles (range 1-16+). Common treatment-related grade 3 and 4 AEs by dose (≤190 mg/m(2) and >190 mg/m(2)) included mucositis (33 and 40%) and fatigue (11 and 17%). Treatment-related serious AE (SAE) rates for doses ≤190 and >190 mg/m(2) were 0 and 20%, respectively. The response rate was 10% (95% confidence interval: 1-20%), including two patients with complete response (26+ and 32+ months) and two with partial response. Serum pralatrexate concentrations increased dose dependently up to 230 mg/m(2).. Pralatrexate with vitamin supplementation was safely administered to patients with previously treated NSCLC, and durable responses were observed. The recommended starting dose for phase 2 is 190 mg/m(2). A similar safety profile was observed in patients treated at 230 mg/m(2), although a higher serious AE rate was evident. Mucositis remains the dose-limiting toxicity of pralatrexate, and this study failed to demonstrate that vitamin supplementation prevents mucositis and failed to identify clinical predictors of mucositis. Individualized dose-modification strategies and prospective mucositis management will be necessary in future trials.

Topics: Adenocarcinoma; Aged; Aminopterin; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Dietary Supplements; Female; Folic Acid; Folic Acid Antagonists; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Prognosis; Tissue Distribution; Vitamin B 12; Vitamin B Complex

We examined the efficacy of enzastaurin plus pemetrexed as second-line therapy in patients with advanced (stage IIIA/B or IV) non-small cell lung cancer in a double-blinded, randomized, phase II study.. Patients received pemetrexed 500 mg/m intravenously on day 1 of 21-day cycles (day 8 in cycle 1) plus oral enzastaurin (250 mg two times per day; combination arm) or placebo (pemetrexed arm). Both arms received supplementation with vitamin B12, folic acid, and dexamethasone. An interim analysis was conducted to determine whether efficacy would warrant a phase III study.. The interim analysis showed no evidence of improved progression-free survival with enzastaurin. At final analysis (N = 160, 80 in each arm), baseline characteristics were well balanced. There was no significant difference in progression-free survival (3.0 months, p = 0.544) or overall survival (9.6 months in combination arm and 7.4 months in pemetrexed arm, p = 0.171). Drug-related serious adverse events included cerebrovascular accident, palpitations, and renal failure (n = 1, each) in combination arm and neutropenic sepsis, thrombocytopenia, and panniculitis (n = 1, each) in pemetrexed arm. Nonhematologic drug-related grade 3/4 toxicities were similar in both arms. Grade 3/4 hematologic toxicities were higher with the combination, specifically leukopenia (6.3% versus 0%), neutropenia (15.2% versus 5.0%), and thrombocytopenia (8.9% versus 1.3%). Of the 26 deaths reported on-study or within 30 days of discontinuation (10 in combination arm and 16 in pemetrexed arm), none were drug related.. The combination regimen of enzastaurin and pemetrexed is well tolerated but does not improve efficacy over pemetrexed and placebo as second-line treatment of unselected patients with advanced non-small cell lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Double-Blind Method; Female; Folic Acid; Glutamates; Guanine; Humans; Indoles; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Pemetrexed; Prognosis; Salvage Therapy; Survival Rate; Vitamin B 12

Elevated succinyl-CoA and cobalamin levels were associated with high-grade squamous intraepithelial lesions.

Topics: Anus Neoplasms; Biomarkers; Carcinoma, Squamous Cell; Early Detection of Cancer; Humans; Papillomavirus Infections; Vitamin B 12

B vitamins play an essential role in DNA synthesis and methylation, and may protect against oesophageal and gastric cancers. In this case-cohort study, subjects were enrolled from the General Population Nutrition Intervention Trial in Linxian, China. Subjects included 498 oesophageal squamous cell carcinomas (OSCCs), 255 gastric cardia adenocarcinomas (GCAs), and an age- and sex-matched sub-cohort of 947 individuals. Baseline serum riboflavin, pyridoxal phosphate (PLP), folate, vitamin B12, and flavin mononucleotide (FMN) were measured for all subjects. We estimated the associations with Cox proportional hazard models, with adjustment for potential confounders. Compared to those in the lowest quartile of serum riboflavin, those in the highest had a 44% lower risk of OSCC (HR: 0.56, 95% CI: 0.41 to 0.75). Serum vitamin B12 as a continuous variable was observed to be significantly inversely associated with OSCC (HR: 0.95, 95% CI: 0.89 to 1.01, P for score test = 0.041). Higher serum FMN levels were significantly associated with increased risk of OSCC (HR: 1.08, 95% CI: 1.01 to 1.16) and GCA (HR: 1.09, 95% CI: 1.00 to 1.20). Our study prompted that B vitamins have the potential role as chemopreventive agents for upper gastrointestinal cancers.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Squamous Cell; Cardia; China; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Flavin Mononucleotide; Folic Acid; Humans; Male; Middle Aged; Niacin; Proportional Hazards Models; Prospective Studies; Pyridoxal Phosphate; Riboflavin; Stomach Neoplasms; Vitamin B 12; Vitamin B Complex

Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis. Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer.. We prospectively examined the association between self-reported intakes of folate, methionine, vitamin B6, and vitamin B12 and gastric and esophageal cancer in 492,293 men and women.. We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate (relative risk (95% confidence interval): Q1 vs Q3, 1.91 (1.17, 3.10)), but no association with high intake. Folate intake was not associated with esophageal adenocarcinoma, gastric cardia adenocarcinoma, or non-cardia gastric adenocarcinoma. The intakes of methionine, vitamin B6, and vitamin B12 were not associated with esophageal and gastric cancer.. Low intake of folate was associated with increased risk of esophageal squamous cell carcinoma.

Topics: Carcinoma, Squamous Cell; Cohort Studies; Diet; Esophageal Neoplasms; Female; Folic Acid; Humans; Male; Methionine; Middle Aged; Risk; Stomach Neoplasms; United States; Vitamin B 12; Vitamin B 6

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy with neurological disorder which incidence is relatively rare. Since the discovery of the ADAMTS 13 in 1996 and the changes in the treatment (plasma exchanges and rituximab), the prognosis of the TTP has considerably improved. We report the case of a 60-year-old man with a refractory TTP. The subsequent discovery of an epiglottis neoplasia and its treatment saved the patient.

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal, Murine-Derived; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Epiglottis; Fluorouracil; Humans; Laryngeal Neoplasms; Male; Middle Aged; Plasma Exchange; Plasmapheresis; Platelet Count; Purpura, Thrombotic Thrombocytopenic; Rituximab; Taxoids; Vitamin B 12; Vitamins

Diet is associated with cancer prognosis, including head and neck cancer (HNC), and has been hypothesized to influence epigenetic state by determining the availability of functional groups involved in the modification of DNA and histone proteins. The goal of this study was to describe the association between pretreatment diet and HNC tumor DNA methylation. Information on usual pretreatment food and nutrient intake was estimated via food frequency questionnaire (FFQ) on 49 HNC cases. Tumor DNA methylation patterns were assessed using the Illumina Goldengate Methylation Cancer Panel. First, a methylation score, the sum of individual hypermethylated tumor suppressor associated CpG sites, was calculated and associated with dietary intake of micronutrients involved in one-carbon metabolism and antioxidant activity, and food groups abundant in these nutrients. Second, gene specific analyses using linear modeling with empirical Bayesian variance estimation were conducted to identify if methylation at individual CpG sites was associated with diet. All models were controlled for age, sex, smoking, alcohol and HPV status. Individuals reporting in the highest quartile of folate, vitamin B12 and vitamin A intake, compared with those in the lowest quartile, showed significantly less tumor suppressor gene methylation, as did patients reporting the highest cruciferous vegetable intake. Gene specific analyses identified differential associations between DNA methylation and vitamin B12 and vitamin A intake when stratifying by HPV status. These preliminary results suggest that intake of folate, vitamin A and vitamin B12 may be associated with the tumor DNA methylation profile in HNC and enhance tumor suppression.

Topics: Adult; Aged; Carcinoma, Squamous Cell; CpG Islands; Diet; Diet Surveys; DNA Methylation; Female; Genes, Tumor Suppressor; Head and Neck Neoplasms; Humans; Male; Middle Aged; Squamous Cell Carcinoma of Head and Neck; Vitamin A; Vitamin B 12; Vitamins

Metabolic changes in head and neck carcinogenesis are often non-specifically correlated with carcinomas. The study of metabolic disorders can improve the understanding of tumourigenesis at the cellular level. This study was designed to evaluate the role of serum homocysteine, folate, and vitamin B(12) levels in the pathogenesis of laryngeal squamous cell cancer (LSCC) by measuring serum levels in 60 consecutive untreated patients with LSCC and 60 controls (30 smokers and 30 non-smokers). Compared with smoker and non-smoker control groups, significantly lower levels of vitamin B(12) were found in patients with LSCC. Folate levels in patients with LSCC were also significantly lower than in the smoker and non-smoker control groups. There were no significant differences in the homocysteine levels between these three groups. Metabolic alterations in vitamin B(12) and folate levels, particularly hypofolataemia, could be associated with the development of LSCC, although further research is required to confirm their roles definitively.

Topics: Carcinoma, Squamous Cell; Case-Control Studies; Demography; Folic Acid; Homocysteine; Humans; Laryngeal Neoplasms; Middle Aged; Vitamin B 12

The authors evaluated serum levels of folate, homocysteine, and vitamin B(12) in patients with head and neck squamous cell carcinoma (HNSCC) and in patients with laryngeal leukoplakia, a well known preneoplastic lesion.. One hundred forty-four consecutive, untreated patients with HNSCC and 40 consecutive, untreated patients with laryngeal leukoplakia were enrolled in the Department of Otolaryngology at the authors' institution. Data from those patients were compared with data from one control group, which included 90 smokers, and from another control group, which included 120 nonsmokers. Serum levels of homocysteine, folate, and vitamin B(12) were measured by an automated immunoassay method based on fluorescence polarization immunoassay technology.. Comparing groups by Student-Newman-Keuls test, serum folate levels were significantly lower in patients with HNSCC and in patients with laryngeal leukoplakia compared with serum folate levels in both the smoker control group and the nonsmoker control group. Serum homocysteine levels in patients with HNSCC were significantly higher compared with homocysteine levels both in the smoker and nonsmoker control groups and in patients with laryngeal leukoplakia. There were no statistically significant differences between groups in serum vitamin B(12) levels.. A role for folate deficiency as a risk factor in head and neck carcinogenesis is plausible. A chemoprevention protocol with folate is both feasible and ethically correct and is in progress at the authors' institution. Homocysteine levels in patients with HNSCC probably are affected largely by the HNSCC phenotype. An accumulation of homocysteine may reveal a genetic defect, which, theoretically, may be a target for pharmacologic therapy, for example, with antifolic drugs.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Female; Folic Acid; Head and Neck Neoplasms; Homocysteine; Humans; Laryngeal Neoplasms; Leukoplakia; Male; Middle Aged; Prognosis; Reference Values; Risk Assessment; Sensitivity and Specificity; Vitamin B 12

We measured the concentrations of folate and vitamin B-12 in paired tissue samples of squamous cell cancer (SCC) and adjacent grossly normal-appearing uninvolved bronchial mucosa (from which SCC developed and also "at risk" of developing SCC) of the lung in 12 subjects to determine the involvement of these vitamins in 1) lung carcinogenesis and 2) global DNA methylation. The folate concentrations were significantly lower in SCCs than in uninvolved tissues (p = 0.03). The vitamin B-12 concentrations were also significantly lower in SCCs than in uninvolved tissues (p = 0.02). The radiolabeled methyl incorporation (inversely related to the degree of in vivo DNA methylation) was significantly higher in SCCs than in uninvolved tissues (p < 0.0001). The correlation between folate and radiolabeled methyl incorporation was inverse and statistically significant in SCCs (p = 0.03). The correlation between vitamin B-12 and radiolabeled methyl incorporation also was inverse and statistically significant in SCCs (p = 0.009). The relationship between tissue vitamin B-12 and DNA methylation was minimal in uninvolved tissues. The relationship between folate and DNA methylation, however, was inverse in uninvolved tissues. In the multiple regression models that included both vitamins, only folate was inversely associated with radiolabeled methyl incorporation in uninvolved and cancerous tissues. These results suggested that folate might be the limiting vitamin for proper DNA methylation in SCC as well as in tissues at risk of developing SCC. Several possible mechanisms of folate deficiency, including inactivation of the vitamin by exposure to carcinogens of cigarette smoke and underexpression or absence of folate receptor in SCCs and associated premalignant lesions, are discussed in light of these findings.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA Methylation; Folic Acid; Folic Acid Deficiency; Humans; Lung Neoplasms; Middle Aged; Smoking; Statistics as Topic; Vitamin B 12; Vitamin B 12 Deficiency

The combination of hydroxocobalamin (vitamin B12b) and ascorbic acid (vitamin C) can cause the death of tumor cells at the concentrations of the components at which they are nontoxic when administered separately. This cytotoxic action on epidermoid human larynx carcinoma cells HEp-2 in vitro is shown to be due to the hydrogen peroxide generated by the combination of vitamins B12b and C. The drop in the glutathione level preceding cell death was found to be the result of combined action of the vitamins. It is supposed that the induction of cell death by combined action of vitamins B12b and C is connected to the damage of the cell redox system.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Cell Division; Drug Synergism; Glutathione; Humans; Hydrogen Peroxide; Laryngeal Neoplasms; Oxidation-Reduction; Tumor Cells, Cultured; Vitamin B 12

Twenty-two cases of early squamous cell carcinoma of the arytenoid cartilage staged as T1 according to the 1983 American Joint Committee for Cancer Staging Classification system were reviewed. Eighteen percent of the patients showed no symptoms. In the remaining 82%, the main presenting symptom was pain in the form of sore throat, odynophagia, or otalgia. Radiotherapy and partial laryngeal surgery were the options retained for the treatment of the larynx. A "watch and wait" policy or preventive treatment of the ipsilateral jugulocarotid lymph nodes were the treatment options retained for the neck. Significant differences were noted in terms of local and nodal recurrence between the two programs. Results indicate that partial laryngeal surgery with total arytenoidectomy and preventive treatment of the neck appear to be advisable for this particular type of primary lesion.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Arytenoid Cartilage; Carcinoma, Squamous Cell; Cisplatin; Cobalt Radioisotopes; Female; Fluorouracil; Follow-Up Studies; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Laryngectomy; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Radiotherapy Dosage; Radiotherapy, High-Energy; Survival Rate; Treatment Outcome; Vitamin B 12

Functions of the stomach placed in the posterior mediastinum after esophagectomy were studied in 20 esophageal carcinoma patients. Seven were long-term survivors who lived more than 5 years after operation, and five of them showed normal fasting serum gastrin levels and good or fair gastric acid secretion. Of 13 patients who had their operations within 3 years before the study, 11 showed high fasting serum gastrin levels and poor gastric acid secretion. The hepatobiliary and alimentary scintigrams with double isotopes demonstrated a time lag between the excretion of the food from the stomach and the excretion of bile into the bowels, regardless of the postoperative periods. Absorption of vitamin B12 was normal in patients who lived more than 2 years after operation. The intraluminal pressure and pH studies in long-term survivors showed that our operative technique, the posterior invagination esophagogastrostomy, was effective in preventing a gastroesophageal reflux in the anastomosis.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagogastric Junction; Esophagoscopy; Esophagus; Female; Gastric Acid; Gastric Emptying; Gastrins; Humans; Intestinal Absorption; Liver; Male; Middle Aged; Radionuclide Imaging; Stomach; Thorax; Vitamin B 12

The authors, after a short introduction of physiopathology, report on 17 patients who underwent a total (10 cases) or a subtotal (7 cases) gastrectomy for cancer at various times and then submitted to hemochromocytometric test and Schilling test modified by Katz and Bell. On the bases of information given by the tests, some clinical and therapeutic considerations are made.

Topics: Carcinoma, Squamous Cell; Female; Gastrectomy; Humans; Malabsorption Syndromes; Male; Schilling Test; Stomach Neoplasms; Vitamin B 12

Topics: Administration, Oral; Aged; Anemia, Macrocytic; Bronchial Neoplasms; Carcinoma, Squamous Cell; Folic Acid; Folic Acid Deficiency; Humans; Injections, Intramuscular; Male; Vitamin B 12

Topics: Carbon Isotopes; Carcinoma, Squamous Cell; Culture Techniques; Homocysteine; Humans; Laryngeal Neoplasms; Ligases; Methionine; Quaternary Ammonium Compounds; Radioisotopes; Sulfates; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Blood Chemical Analysis; Bronchi; Bronchial Neoplasms; Carcinoma, Squamous Cell; Celiac Disease; Feces; Fluids and Secretions; Folic Acid; Folic Acid Deficiency; Humans; Hypokalemia; Hypoproteinemia; Jejunum; Lipid Metabolism; Malabsorption Syndromes; Pathology; Urine; Vitamin B 12