vitamin-b-12 and Pancreatic-Neoplasms

Nutrients involved in one-carbon metabolism may play a key role in pancreatic carcinogenesis. The aim of this study was to examine the association between pancreatic cancer risk and intake or blood levels of vitamins B6, B12 and methionine via meta-analysis.. A systematic search was performed in PubMed, Web of Knowledge and Chinese National Knowledge Infrastructure (CNKI) up to April 2020 to identify relevant studies. Risk estimates and their 95% confidence intervals (CIs) were retrieved from the studies and combined by a random-effect model.. A total of 18 studies were included in this meta-analysis on the association of vitamin B6, B12 and methionine with pancreatic cancer risk. The combined risk estimate (95% CI) of pancreatic cancer for the highest vs lowest category of vitamin B6 intake and blood pyridoxal 5'-phosphate (PLP, active form of vitamin B6) levels was 0.63 (0.48-0.79) and 0.65 (0.52-0.79), respectively. The results indicated a non-linear dose-response relationship between vitamin B6 intake and pancreatic risk. Linear dose-response relationship was found, and the risk of pancreatic cancer decreased by 9% for every 10 nmol/L increment in blood PLP levels. No significant association were found between pancreatic cancer risk and vitamin B12 intake, blood vitamin B12 levels, methionine intake and blood methionine levels.. Our study suggests that high intake of vitamin B6 and high concentration of blood PLP levels may be protective against the development of pancreatic cancer. Further research are warranted to confirm the results.

Topics: Diet; Folic Acid; Humans; Methionine; Pancreatic Neoplasms; Risk Factors; Vitamin B 12; Vitamin B 6

New drugs are clearly needed for the treatment of advanced pancreatic cancer, a disease refractory to most chemotherapy. Pemetrexed, a novel antifolate, inhibits thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. Pemetrexed is active against pancreatic cancer cell lines in vitro. Two partial responses in pancreatic cancer patients were observed in a phase I trial of pemetrexed. This led to a phase II trial of pemetrexed in patients with advanced pancreatic cancer. The objective response rate was 6%, 1-year survival rate was 28%, and the toxicities of therapy were mild. Pemetrexed is synergistic with gemcitabine in vitro. In a phase I trial, the pemetrexed/gemcitabine combination was broadly active and well tolerated. A phase II trial of this combination in 42 patients with advanced pancreatic cancer showed promising activity. A 520-patient international randomized phase III trial that compares the pemetrexed/gemcitabine combination with single-agent gemcitabine is currently accruing patients.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Deoxycytidine; Folic Acid; Folic Acid Antagonists; Gemcitabine; Glutamates; Guanine; Humans; Pancreatic Neoplasms; Pemetrexed; Thymidylate Synthase; Vitamin B 12

Phosphorylcholine and homocysteine have an important choleretic action and also potentiate exocrine pancreatic secretion by way of stimulation and a more effective preparation of the substrate against attack by lipolytic enzymes. The protection offered by pancreatic enzymes in the correction of the digestive insufficiency in the endoluminal stage is also known. An analysis was therefore made of the action of an association of phosphorylcholine homocysteine and digestive enzymes in cases of exocrine pancreatic insufficiency and primary or secondary malabsorption. This action was evaluated on the basis of the reduction of elimination of steatorrhoea. For this purpose, faecal lipids were determined with the method proposed by van de Kramer et al. The most significant results were obtained in cases where digestive insufficiency was most marked, where correction of the pancreatic enzyme deficiency and improved biliary function were particularly required.

Topics: Adolescent; Adult; Aged; Amylases; Celiac Disease; Cholagogues and Choleretics; Choline; Clinical Trials as Topic; Crohn Disease; Drug Combinations; Drug Evaluation; Female; Gastroenteritis; Homocysteine; Humans; Male; Middle Aged; Pancreatic Neoplasms; Pancreatitis; Pronase; Silicone Elastomers; Vitamin B 12; Whipple Disease

X-Ray induced phototherapy is highly sought after as it provides a deep tissue, synergistic method of treating cancers via standard-of-care radiotherapy. When this is combined with releasable chemotherapy agents, it can provide high target selectivity, with reduced off-target organ effects that limit current systemic therapies. We have recently developed a unique light-activated drug delivery system whereby the drug is conjugated to an alkylcobalamin scaffold. Alkylcobalamins are actively transported into cells by transcobalamin receptors (TCblR), which are overexpressed in a variety of cancer types. We hope to utilize this cobalamin scaffold technology for drug delivery in pancreatic adenocarcinoma (PDAC) cancer.. The ability of the cobalamin scaffold to selectively target PDAC was investigated by treating mice that had MIA PaCa-2 xenografts with an alkylcobalamin labeled with the fluorophore Bodipy650 (Bodipy650-cobalamin). The mice were imaged alive and organs as well as tumors were subsequently imaged ex vivo. In addition, we examined the potential of the cobalamin scaffold to deliver drugs to orthotopic pancreas MIA PaCa-2 tumors with Bodipy650-cobalamin. We determined the light dose required for release of cargo from the cobalamin scaffold by examining the fluorescence increase of Bodipy650-cobalamin in response to red light (650 nm). Finally, we probed the ability of the cobalamin scaffold to release cargo with increasing X-ray doses from a clinical linear accelerator.. We have found that Bodipy650-cobalamin was shown to localize in MIA PaCa-2 tumors, both in flank and orthotopic models. We quantified a light dose for red light release from the cobalamin scaffold that is within normal clinical doses required for photodynamic therapy. This derivative was also activated with clinical X-ray doses from a linear accelerator.. Tumor selectivity combined with fluorescence detection demonstrates the effectiveness of the vitamin B

Topics: Adenocarcinoma; Animals; Mice; Pancreatic Neoplasms; Photochemotherapy; Photosensitizing Agents; Vitamin B 12; X-Rays

Pancreatic carcinoma is one of the most aggressive cancers overcoming chemoresistance. Thus, novel compounds to complement the current antitumor agents are in need. Ocoxin oral solution (OOS) has proven antioxidant, anti-inflammatory, and antistromagenic properties. The aim of this study was to analyze the effect of OOS in an experimental pancreatic cancer model and its implication in stroma-related chemoresistance to paclitaxel and gemcitabine.. Murine pancreatic carcinoma 266-6 cells were treated with OOS to analyze cell cycle and to perform a mRNA comparative microarray study. Then the viability was assessed in combination with paclitaxel and/or gemcitabine. Chemoresistance induced by the medium taken from fibroblast cultures was also investigated on 6 human pancreatic carcinoma cell lines. Furthermore, an experimental model of pancreatic cancer was carried out to study the effect of OOS in vivo.. Ocoxin oral solution enhances the cytotoxic effect of paclitaxel and gemcitabine, while it ameliorates the chemoresistance induced by fibroblast-derived soluble factors in human pancreatic cancer cells. The OOS also promotes the regulation of the expression of genes that are altered in pancreatic carcinoma and slows down 266-6 cell pancreatic tumor development in vivo.. Ocoxin oral solution could be a potential complement to the chemotherapeutic drugs for pancreatic adenocarcinoma.

Topics: Adenocarcinoma; Administration, Oral; Animals; Antineoplastic Agents; Ascorbic Acid; Cell Cycle; Cell Line; Cell Line, Tumor; Cell Survival; Deoxycytidine; Drug Resistance, Neoplasm; Folic Acid; Gemcitabine; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Mice, Inbred C57BL; Neoplasms, Experimental; Paclitaxel; Pancreatic Neoplasms; Pantothenic Acid; Plant Extracts; Solutions; Vitamin B 12; Vitamin B 6; Zinc Sulfate

Folate, vitamin B. Cases (n = 150) were identified from all hospitals in the metropolitan areas of the Twin Cities and the Mayo Clinic, Minnesota. Controls (n = 459) were selected randomly from the general population and were frequency matched to cases by age, sex, and race. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for risk of pancreatic cancer in relation to intake of nutrients considered.. Dietary intake of folate was associated with a reduced pancreatic cancer risk [OR (95% CI) for quartile (Q) 4 vs. Q1: 0.31 (0.12-0.78)]. A composite score (range from 2 to 8), reflecting combined dietary intake of folate and vitamin B. Dietary folate intake was associated with a reduced pancreatic cancer risk, and this association became stronger when dietary intake of folate and vitamin B

Topics: Adult; Aged; Case-Control Studies; Diet; Dietary Supplements; DNA Methylation; Female; Folic Acid; Humans; Male; Methionine; Middle Aged; Minnesota; Odds Ratio; Pancreatic Neoplasms; Risk Factors; Vitamin B 12; Vitamin B 6

Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (± 1 year), date (± 1 year) and time (± 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate ≤ 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI=0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR=1.17, 95% CI=1.00-1.38) but not in women (OR=0.91, 95% CI=0.78-1.07; p for heterogeneity <0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.

Topics: Adult; Aged; Alcohol Drinking; Body Mass Index; Case-Control Studies; Cotinine; Diabetes Complications; DNA-Binding Proteins; Europe; Female; Flavin Mononucleotide; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Logistic Models; Male; Methionine; Middle Aged; Odds Ratio; Pancreatic Neoplasms; Prospective Studies; Pyridoxal Phosphate; Riboflavin; Risk Factors; Sex Factors; Smoking; Transcription Factors; Vitamin B 12; Vitamin B Complex

Folate and other methyl-group nutrients may play a key role in pancreatic carcinogenesis through their effects on DNA integrity. We examined the association between pancreatic cancer and intake of folate, vitamins B(6), B(12) and methionine in a large population-based case-control study.. Risk factor data were collected during in-person interviews with 532 pancreatic cancer cases diagnosed in 1995-1999 and 1,701 frequency-matched controls in the San Francisco Bay Area. Dietary history and supplement use were obtained using a semi-quantitative food-frequency questionnaire developed at Harvard University. Adjusted unconditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) as estimates of the relative risk.. Total folate intake was inversely associated with pancreatic cancer (5th vs. 1st quintile: OR = 0.67, 95% CI = 0.48-0.93, p (trend) = 0.04). Increased vitamin B(12) from food was positively associated with pancreatic cancer although risk estimates for quintiles 3-5 were similar (5th vs. 1st quintile: OR = 1.9, 95% CI = 1.3-2.6, p (trend) = 0.001). Intake of vitamin B(6) or methionine was not associated with pancreatic cancer risk.. Our study provided some support for an inverse association between folate intake and pancreatic cancer risk. The increased pancreatic cancer risk with vitamin B(12) intake from food warrants further investigation.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Case-Control Studies; Diet Surveys; Eating; Female; Folic Acid; Humans; Male; Methionine; Micronutrients; Middle Aged; Pancreatic Neoplasms; Population; Risk Factors; Vitamin B 12; Vitamin B 6; Young Adult

Folate deficiency induces DNA breaks and may alter cellular capacity for mutation and epigenetic methylation. Few studies have examined the influence of one-carbon nutrients on pancreatic cancer risk, although recent studies suggest a potential protective effect for one-carbon nutrients from food sources, but not from supplements. We conducted a prospective nested case-control study to examine plasma concentrations of folate, vitamin B6 [whose main circulating form is pyridoxal-5'-phosphate (PLP)], vitamin B12, and homocysteine in relationship to pancreatic cancer, using four large prospective cohorts. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. All statistical tests were two sided. Among 208 cases and 623 controls, we observed no association between folate, PLP, vitamin B12, or homocysteine and pancreatic cancer risk. Comparing the highest to lowest quartiles of plasma concentration, the ORs were 1.20 (95% CI, 0.76-1.91) for folate, 0.80 (95% CI, 0.51-1.25) for B6, 0.91 (95% CI, 0.57-1.46) for B12, and 1.43 (95% CI, 0.90-2.28) for homocysteine. In analyses restricted to nonusers of multivitamins, we observe a modest inverse trend between folate, PLP, and B12 and pancreatic cancer risk. In contrast, no such inverse associations were observed among study subjects who reported multivitamin supplement use. Among all participants, plasma levels of folate, B6, B12, and homocysteine were not associated with a significant reduction in the risk of pancreatic cancer. Among participants who obtain these factors exclusively through dietary sources, there may be an inverse relation between circulating folate, B6, and B12 and risk.

Topics: Adult; Case-Control Studies; Cohort Studies; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Pancreatic Neoplasms; Risk Factors; Vitamin B 12; Vitamin B 6

Few risk factors for pancreatic cancer have been identified, with age and cigarette smoking being the most consistent. The protective effect associated with consumption of fruits and vegetables-the major dietary sources of folate-is suggestive of a role for factors influencing cellular methylation reactions; however, to our knowledge, no study has investigated this relationship. Whether biochemical indicators of methyl-group availability are associated with exocrine pancreatic cancer risk was the focus of this investigation.. We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29133 male Finnish smokers aged 50-69 years. One hundred twenty-six subjects with incident exocrine pancreatic cancer were matched by date of baseline blood draw (+/-30 days), study center, age (+/-5 years), trial intervention group, and completion of dietary history to 247 control subjects, who were alive and free from cancer at the time the case subjects were diagnosed. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined by use of conditional logistic regression. Reported P values are two-tailed.. Serum folate and pyridoxal-5'-phosphate (PLP) concentrations showed statistically significant inverse dose-response relationships with pancreatic cancer risk, with the highest serum tertiles having approximately half the risk of the lowest (folate: OR = 0.45; 95% CI = 0.24-0.82; P for trend = .009, and PLP: OR = 0.48; 95% CI = 0.26-0.88; P for trend = .02). An increased pancreatic cancer risk was also observed with greater exposure to cigarettes (e.g., pack-years [number of packs smoked per day x number of years of smoking], highest versus lowest quartile: OR = 2.13; 95% CI = 1.13-3.99; P for trend = .04).. These results support the hypothesis that maintaining adequate folate and pyridoxine status may reduce the risk of pancreatic cancer and confirm the risk previously associated with cigarette smoking.

Topics: Aged; Biomarkers, Tumor; Case-Control Studies; Folic Acid; Fruit; Homocysteine; Humans; Logistic Models; Male; Methylation; Middle Aged; Odds Ratio; Pancreatic Neoplasms; Pyridoxine; Risk; Smoking; Vegetables; Vitamin B 12

Because of the importance of homocysteine thiolactone metabolism in the growth of normal tissues, and because of abnormal metabolism of homocysteine thiolactone in malignant cells, N-substituted derivatives of homocysteine thiolactone were synthesized and assayed for antineoplastic and anticarcinogenic activities. A single dose of 2.5 mg/kg of the synthetic derivative, N-homocysteine thiolactonyl retinamido cobalamin, injected directly into subcutaneous human pancreatic adenocarcinoma neoplasms in athymic mice, caused 50% inhibition of growth without evidence of toxicity. The findings suggest a novel approach to counteracting the growth of malignant neoplasms and support the hypothesis of a deficiency of an N-homocysteine thiolactonyl derivative in malignant cells.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cell Division; Homocysteine; Humans; Male; Mice; Mice, Nude; Neoplasms, Experimental; Pancreatic Neoplasms; Tumor Cells, Cultured; Vitamin B 12

Topics: Achlorhydria; Adenoma, Islet Cell; Blood Glucose; Calcium; Dehydration; Diarrhea; Gastric Juice; Gastrointestinal Hormones; Humans; Hypokalemia; Pancreatic Juice; Pancreatic Neoplasms; Syndrome; Vitamin B 12

Topics: Adolescent; Adult; Female; Humans; Intestinal Absorption; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatin; Vitamin B 12; Whole-Body Counting

New tests and test methods aid in the diagnosis of pancreatic disorders. Pancreatic carcinoma, especially, may have an improved prognosis with earlier detection as a result of refinements in arteriography, cytology, pancreatic radioisotopic scanning, and endoscopic retrograde cholangiopancreatography. Acute pancreatitis results most commonly from alcoholism, biliary tract disease, and trauma. Management is directed primarily at decreasing pancreatic exocrine secretion. Surgery is usually best avoided in the acute phase. Chronic pancreatitis is most often a result of recurrent attacks of acute pancreatitis. Diabetes and malassimilation become manifest as pancreatic destruction progresses. Management consists of replacement of pancreatic enzymes and diet supplements. Once chronic pancreatitis is established, surgery can only be directed at complications of the disease. Pancreatic ascites is usually associated with a break in the pancreatic ductal system. Ascites caused by trauma responds well to surgical intervention, but the alcoholic type is less amenable to treatment.

Topics: Acute Disease; Alcoholism; Antacids; Ascites; Carcinoembryonic Antigen; Cholangiography; Chronic Disease; Cysts; Diabetes Mellitus; Diet Therapy; Endoscopy; Gastrointestinal Hemorrhage; Humans; Metabolic Diseases; Methionine; Pancreatic Diseases; Pancreatic Juice; Pancreatic Neoplasms; Pancreatin; Pancreatitis; Prognosis; Selenium; Ultrasonics; Vitamin B 12

Topics: Adenoma, Islet Cell; Bicarbonates; Celiac Disease; Diarrhea; Duodenum; Feces; Female; Gastric Juice; Humans; Hyperplasia; Hypokalemia; Intestinal Secretions; Malabsorption Syndromes; Middle Aged; Pancreas; Pancreatic Neoplasms; Pancreatitis; Potassium; Precancerous Conditions; Vitamin B 12

Topics: Abdominal Neoplasms; Adolescent; Adult; Aged; Breast Neoplasms; Carcinoma; Child; Cobalt Isotopes; Female; Gastric Juice; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Hodgkin Disease; Humans; Intestinal Mucosa; Iodine Isotopes; Leiomyosarcoma; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Male; Mesothelioma; Methods; Middle Aged; Neuroblastoma; Pancreatic Neoplasms; Povidone; Radiation Effects; Radioisotope Teletherapy; Splenic Neoplasms; Time Factors; Triolein; Vitamin B 12