vitamin-b-12 and Liver-Neoplasms

Topics: Animals; Antibody Formation; Carcinogens; Choline; Choline Deficiency; Diet; DNA; Folic Acid; Folic Acid Deficiency; Humans; Immunity, Cellular; Lipotropic Agents; Liver; Liver Neoplasms; Methionine; Methylation; Neoplasms; Neoplasms, Experimental; Pharmaceutical Preparations; Risk; Tetrahydrofolates; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Biological Transport; Blood Proteins; Carcinoma, Hepatocellular; Carrier Proteins; Chromatography, Gel; Chromatography, Ion Exchange; Electrophoresis; Granulocytes; Humans; Intrinsic Factor; Isoelectric Focusing; Kinetics; Liver Neoplasms; Molecular Weight; Transcobalamins; Vitamin B 12

Topics: Anemia, Macrocytic; Animals; Bacteria; Bone Marrow; Bone Marrow Cells; Carcinoma, Hepatocellular; Chemical Phenomena; Chemistry; DNA Replication; Enzyme Repression; Erythropoiesis; Escherichia coli; Humans; In Vitro Techniques; Kinetics; Liver; Liver Neoplasms; Microscopy, Phase-Contrast; Models, Chemical; Nucleotides; Oxidoreductases; Phosphorus Isotopes; Rats; RNA; Time Factors; Tritium; Vitamin B 12

Topics: Adenocarcinoma; alpha-Fetoproteins; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Vitamin B 12

Deficient intake of micronutrients involved in one-carbon metabolism (eg, choline, methionine, vitamin B

Topics: Carbon; Carcinoma, Hepatocellular; Diet; Dietary Supplements; Eating; Female; Folic Acid; Humans; Liver Neoplasms; Male; Methionine; Micronutrients; Middle Aged; Nutritional Status; Prospective Studies; Riboflavin; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Portal vein thrombosis (PVT) is a common complication of endstage hepatocellular carcinoma (HCC). The aim of our study was to evaluate the role of Homocysteine (Hcy) in HCC patient with PVT. Hcy is a sulphur amino-acid involved in two pathways, trans-sulphuration and remethylation, that involve vitamins B6, B12 and folates.. We recruited 54 patients with HCC and PVT, 60 patients with HCC and without PVT and 60 control subjects. We measured serum levels of Hcy, folate, vitamins B6 and B12.. The comparison between HCC patients with PVT versus HCC without PVT was shown that mean values of Hcy were 6.4 nmol/L (p<0.0073) higher, LDL cholesterol were 4.8 mg/dl (p<0.0079) lower, vitamin B6 were 4.6 nmol/L(p=0.0544) lower, vitamins B 12 were 22.1 pg/ml (p=0.0001) lower.. High serum levels of Hcy are an established thrombotic risk factor in the general population. We found significantly higher levels of Hcy in HCC patients with PVT versus both HCC patients without PVT and controls.

Topics: Adult; Aged; Biomarkers, Tumor; Budd-Chiari Syndrome; Carcinoma, Hepatocellular; Cholesterol, LDL; Female; Folic Acid; Homocysteine; Humans; Liver Neoplasms; Male; Middle Aged; Portal Vein; Prognosis; Vitamin B 12; Vitamin B 6

Liver metastatic disease is the main cause of death in colorectal cancer (CRC) patients. During metastatic spread of the disease an imbalance in the oxidative stress and inflammation plays a crucial role in tumor progression. In order to improve the efficacy of current therapies, new complementary therapeutic approaches are being analyzed including biologically active compounds with low side effects. The anti-inflammatory and anti-oxidant properties of Ocoxin® oral solution (OOS) prompt us to analyze its effect on the metastatic development of CRC to the liver. First, in vitro effect of OOS in tumor cell viability and migration was analyzed. Second, in vivo effect of different dosage patterns and concentrations in the development of hepatic metastasis was analyzed by intra-splenic inoculation of C26 colon carcinoma cells in Balb/c mice. Third, the expression of alpha smooth muscle actin, caspase-3 and Ki-67 expression was quantified by immunohistochemistry, then gene expression levels of inflammatory factors were measured by quantitative RT-PCR. According to our results, OOS reduced tumor cell viability and migration in vitro. Moreover, in vivo daily administration of OOS from the 7th day after tumor cell inoculation decreased the total area and size of metastatic foci in the liver. Furthermore, cell proliferation and fibroblast recruitment was decreased in tumor foci while a higher number of apoptotic cells were observed. Finally, RNA levels for the inflammatory mediators COX-2, IFNγ, IL1β, IL6 and TNFα were reduced in total liver. In conclusion, OOS reduced the metastatic development of colorectal cancer to the liver by increasing apoptosis, and decreasing tumor cell proliferation and fibroblast recruitment in the tumor foci, as well as the expression of inflammatory mediators in total liver. These results point out OOS as a potential supplement to be applied as complementary therapy for the treatment of liver metastasis from colorectal cancer.

Topics: Animals; Apoptosis; Ascorbic Acid; Caspase 3; Cell Proliferation; Colorectal Neoplasms; Folic Acid; Gene Expression Regulation, Neoplastic; Glycyrrhizic Acid; Humans; Ki-67 Antigen; Liver Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Pantothenic Acid; Plant Extracts; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Zinc; Zinc Sulfate

Folate and vitamin B12 involved in the one-carbon metabolism may play a key role in carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. The purpose of this study is to evaluate the association of plasma folate and vitamin B12 levels with HCC in a case-control study on 312 HCC patients and 325 cancer-free controls. Plasma concentrations of folate and vitamin B12 in all the subjects were measured by electrochemiluminescence immunoassay. Meanwhile, the information of HCC patients' clinical characteristics including tumor-node-metastasis (TNM) stage, tumor size and tumor markers were collected. The patients of HCC had significantly lower folate levels than those of controls; there was no significant difference in the mean of plasma vitamin B12 levels. We also observed an inverse association between the levels of plasma folate and HCC: the adjusted odds ratios (OR) (95% confidence intervals (CI)) of HCC from the highest to lowest quartile of folate were 0.30 (0.15-0.60), 0.33 (0.17-0.65), and 0.19 (0.09-0.38). Compared to the subjects in the lowest quartile of plasma vitamin B12, only the subjects in the highest quartile of vitamin B12 exhibited a significant positive relationship with HCC, the adjusted OR was 2.01 (95% CI, 1.02-3.98). HCC patients with Stage III and IV or bigger tumor size had lower folate and higher vitamin B12 levels. There was no significant difference in the mean plasma folate levels of the HCC cases in tumor markers status (AFP, CEA and CA19-9 levels), whereas patients with higher CEA or CA19-9 levels retained significantly more plasma vitamin B12 than those with normal-CEA or CA19-9 level. In conclusion, plasma folate and vitamin B12 levels could be associated with HCC, and might be used as predictors of clinical characteristics of HCC patients. However, further prospective studies are essential to confirm the observed results.

Topics: Adult; Aged; Biomarkers; Carcinoma, Hepatocellular; Case-Control Studies; Female; Folic Acid; Humans; Immunoassay; Liver Neoplasms; Luminescent Measurements; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Odds Ratio; Risk Factors; Vitamin B 12

Evidence is accumulating regarding a role of micronutrients in folate metabolism in cancer risk. We investigated the associations of plasma folate, vitamin B12, and homocysteine with upper gastrointestinal (GI) cancers in a population-based case-control study in Taixing City, China. With informed consent, we recruited cases with cancers of esophagus (n = 218), stomach (n = 206), and liver (n = 204), and one common healthy control group (n = 405). A standardized epidemiologic questionnaire was used in face-to-face interviews, and blood samples were collected during interviews. We observed an inverse association between plasma folate levels and liver cancer. The adjusted odds ratio (aOR) was 0.46 [95% confidence interval (CI) = 0.24-0.88] comparing individuals in the highest quartile to those in the lowest. We found a positive association between plasma vitamin B12 levels and all three cancers. The aORs for those in the highest quartile were 2.80 (95% CI = 1.51-5.18) for esophageal cancer, 2.17 (1.21-3.89) for stomach cancer, and 9.97 (4.82-20.60) for liver cancer, comparing to those in the lowest quartile. We further observed interaction between plasma folate and vitamin B12 on these cancers. Our data indicated associations between plasma folate and vitamin B12 with upper GI cancers in Chinese population. Further research is warranted considering the debate over the necessity of food fortification.

Topics: Adult; Aged; Case-Control Studies; China; Esophageal Neoplasms; Female; Folic Acid; Homocysteine; Humans; Liver Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Stomach Neoplasms; Surveys and Questionnaires; Vitamin B 12

The vitamin B12 (B12)-binding protein haptocorrin (HC) has proven to be a potentially useful biomarker in patients with fibrolamellar hepatocellular carcinoma (HCC). Little is known concerning the level of HC and other B12-related proteins in patients with HCC as compared to patients with other chronic liver diseases (CLDs) and healthy controls. We hypothesized that HC could be a biomarker of HCC.. To investigate levels of HC and B12-related proteins in HCC compared to CLDs and healthy controls.. We investigated two patient populations: A cross-sectional cohort of HCC patients (n = 130), CLD patients (n = 102) and healthy controls (n = 46) and a cohort of 38 HCC patients studied at baseline and 1, 4, and 12 weeks following ablative treatment. Patients were evaluated by standard biochemistry, Child-Pugh-score and Barcelona Clinic Liver Cancer (BCLC) classification. We analyzed total B12 by routine methods and HC, transcobalamin (TC), B12 saturated TC (holoTC), and the soluble cell surface receptor for holoTC (sCD320) by in-house enzyme-linked immunosorbent assay.. HC showed higher median (range) levels for both HCC (590 [290-5860]) and CLD patients (620 [310-4010]) compared to controls (460 [250-2020]) (p < 0.01). Total B12, TC, holoTC, and sCD320 showed elevated levels in both HCC and CLD compared to controls. Only holoTC changed following treatment, without a concurrent change in TC.. B12 and B12-related proteins (total B12, HC, TC, holoTC, and sCD320) show elevations in both HCC and CLD patients compared to controls, suggesting a relation to CLD in general rather than to primary liver cancer. Thus, HC is not useful as a biomarker for HCC.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Catheter Ablation; Chemoembolization, Therapeutic; Chronic Disease; Cross-Sectional Studies; Female; Humans; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Receptors, Cell Surface; Transcobalamins; Vitamin B 12

Elevated blood vitamin B(12) (VitB(12)) level has recently been identified as a prognostic indicator for advanced cancer patients. The predictive value of blood VitB(12) for survival of patients with hepatocellular carcinoma (HCC) remains unclear. Our objective was to examine the determinants of elevated serum VitB(12) levels and their associations with prognosis of patients with HCC. The cohort study included 90 HCC patients who were consecutively admitted to the Chi-Mei Hospital, Taiwan, from April 2005 to December 2006. Nutrition and clinical pathological data were collected. Serum VitB(12) levels were determined by radioimmunoassay. Survival curves were calculated by the Kaplan-Meier method. Multivariate analysis of outcome predictors was assessed by Cox regression. Elevated serum VitB(12) levels of HCC patients were associated with reduced levels of albumin, hemoglobin, red blood cells count, and glutamate-pyruvate transaminase (GPT) (P < 0.05). Serum VitB(12) levels were positively correlated with alpha-fetal protein (AFP) levels (r = 0.623, P = 0.001) and tumor size (r = 0.630, P = 0.001; Table 3). By univariate analysis, survival was significantly worse in patients with elevated serum AFP (> 200 mu g/l) and VitB(12) levels (> 1,500 ng/l; P < 0.05). In multivariate analysis, both elevated AFP (> 200 vs. < 20; HR 4.4; CI = 1.9-10.3, P = 0.001) and VitB(12) levels (> 699 vs. < or = 699; HR = 2.88; CI = 1.26-6.6, P = 0.012) were found to be favorable predictive factors for HCC survival. This study shows that the determinants of elevated serum VitB(12) levels in HCC patients were in association with malnourishment, liver injuries, and tumor progression. Elevated VitB(12) levels in concurrence with AFP levels serve as the prognostic factors predictive for poor survival of HCC patients.

Topics: Aged; Alanine Transaminase; alpha-Fetoproteins; Analysis of Variance; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cohort Studies; Diet; Erythrocyte Count; Female; Hemoglobins; Humans; Life Style; Liver Neoplasms; Male; Middle Aged; Prognosis; Serum Albumin; Survival Rate; Vitamin B 12

Vitamins B12, B6, and folic acid converge at the homocysteine metabolic junction where they support the activities of two key enzymes involved in intracellular homocysteine management, methionine synthase (MS) and cystathionine beta-synthase. The molecular mechanism for the regulation of homocysteine metabolism by B12 supplementation has been investigated in this study. B12 supplementation does not alter mRNA or protein turnover rates but induces translational up-regulation of MS by shifting the mRNA from the ribonucleoprotein to the polysome pool. The B12-responsive element has been localized by deletion analysis using a reporter gene assay to a 70-bp region located at the 3' end of the 5'-untranslated region of the MS mRNA. The cellular consequence of the B12 response is a 2- and 3.5-fold increase in the flux of homocysteine through the MS-dependent transmethylation pathway in HepG2 and 293 cells, respectively. It is speculated that B12-induced up-regulation of MS may have evolved as an adaptive strategy for rapidly sequestering an essential and rare nutrient whose availability may have been limited in the evolutionary history of mammals, a problem that is exacerbated by the absence of this vitamin from the plant kingdom.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; 5' Untranslated Regions; Animals; Carcinoma, Hepatocellular; COS Cells; Gene Expression; Gene Expression Regulation, Enzymologic; Homocysteine; Humans; Kidney; Liver Neoplasms; Methylation; Nucleic Acid Conformation; Nutritional Physiological Phenomena; Polyribosomes; Protein Biosynthesis; RNA, Messenger; Tumor Cells, Cultured; Vitamin B 12

As we have reported previously, both DNA and tRNA become hypomethylated in livers of rats fed a cancer promoting, methyl-deficient diet (MDD) for as short a period as one week. Within the same period, activities of tRNA and DNA methyltransferases (MTases) increase and levels of mRNAs for several genes believed to have roles in growth regulation are altered. These diet-induced changes in nucleic acid methylation and gene expression increased in extent when MDD was fed continuously for four weeks. We also observed hypomethylation of specific CCGG sites within several genes for which mRNA levels were increased. These included c-myc, c-fos and c-Ha-ras. To investigate the reversibility of such diet-induced alterations in methylation and gene expression, animals were fed MDD for four weeks, after which a diet supplemented with adequate sources of methyl groups (CSD) was fed for 1-3 weeks. One to two weeks after the restoration of an adequate diet, the overall extent of methylation of tRNA and DNA from livers of these rats did not differ from that of tRNA and DNA from livers of age matched animals continually maintained on CSD. At the same time, activities of MTases in the liver dropped to normal values. Levels of mRNAs for all genes studied returned to control levels within three weeks after ending MDD feeding, although at different rates. In contrast, MDD-induced hypomethylation of some HpaII sites in c-myc, c-fos and c-Ha-ras genes persisted after 3 weeks refeeding of an adequate diet. These results, which demonstrate that most of the effects of MDD on the parameters we have studied occur rapidly and are essentially reversible, are consistent with the role of MDDs as promoters of hepatocarcinogenesis. However, the finding that unmethylated sites persist in genes that play a role in growth regulation suggests a mechanism by which intermittent or long term exposure to MDDs could result in heritable phenotypic changes in some hepatocytes that lead to hyperplasia and tumorigenesis.

Topics: Amino Acid Sequence; Animals; Choline; DNA; Folic Acid; Gene Expression Regulation, Neoplastic; Genes, fos; Genes, myc; Genes, ras; Liver; Liver Neoplasms; Male; Methionine; Methylation; Methyltransferases; Molecular Sequence Data; Rats; Rats, Inbred F344; RNA, Messenger; RNA, Transfer; Vitamin B 12

Topics: Adolescent; Biomarkers, Tumor; Biopsy; Carcinoma, Hepatocellular; Humans; Hyperplasia; Liver; Liver Neoplasms; Male; Neurotensin; Tomography, X-Ray Computed; Vitamin B 12

The known function of human transcobalamin II (TC II) is to transport cobalamin (Cbl) in the circulation to tissue receptors for TC II-Cbl. Several types of human cells synthesize apo (unsaturated) TC II and the present study was conducted in order to evaluate possible functions of this endogenous TC II. The approach consisted of a correlation between the abilities of cultured cells to produce apo TC II and to internalized Cbl when presented in the free form. The amount of apo TC II produced by six lines of cultured human cells ranged from abundant to nil. The amount of free Cbl internalized by these cells correlated directly with the capacity to produce apo TC II. The interactions between endogenous TC II and free Cbl took place either at the cell surface or in the medium surrounding the cell. It was also shown that cells in culture contain free Cbl and release free Cbl into the surrounding medium. Thus it was concluded that the apo TC II produced by human cells remains intact to interact with free Cbl and to participate in the cellular metabolism of Cbl.

Topics: Carcinoma, Hepatocellular; Cell Line; Cells, Cultured; Fibroblasts; Humans; Liver Neoplasms; Receptors, Cell Surface; Transcobalamins; Tumor Cells, Cultured; Vitamin B 12

Topics: Anemia; Biological Assay; Humans; Liver Neoplasms; Myeloproliferative Disorders; Pancreatitis; Radioisotope Dilution Technique; Reference Values; Vitamin B 12; Vitamin B 12 Deficiency

The serum unsaturated vitamin B12-binding capacity (UBBC), unsaturated transcobalamin (UTC) I, UTC II, UTC III levels, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activities and bilirubin concentration were estimated in 61 patients with liver diseases (31 with hepatoma, 30 with viral hepatitis). The levels of serum cobalamin, UTC I, UTC III, UBBC, alanine and aspartate aminotransferases, and bilirubin were raised in both hepatoma and viral hepatitis patients. Serum UTC II was reduced in both conditions. Alkaline phosphatase activity was significantly increased in hepatoma. Four significant correlations were observed among these parameters in the hepatoma patients while only one significant correlation was observed in viral hepatitis.

Topics: Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Carcinoma, Hepatocellular; Female; Hepatitis, Viral, Human; Humans; Liver Neoplasms; Male; Middle Aged; Protein Binding; Transcobalamins; Vitamin B 12

Elevated Serum B12 levels were found at diagnosis in five of eleven patients with primary hepatocellular carcinoma. During chemotherapy either with CB3717 or VP16 the serum B12 rose dramatically, in one case reaching levels ten times the upper limit of normal. However, the serum LD activities did not change in parallel with the serum B12 levels suggesting that there was little necrosis of the tumour or the liver. With two out of five patients with other types of cancer the serum B12 levels also increased but less markedly. This data seems to suggest that the serum B12 level may not be as good a tumour marker for hepatocellular carcinoma as has been suggested and indeed may be influenced by the chemotherapeutic agent.

Topics: Adult; Aged; alpha-Fetoproteins; Carcinoma, Hepatocellular; Female; Folic Acid; Follow-Up Studies; Humans; L-Lactate Dehydrogenase; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Quinazolines; Vitamin B 12

A case of pleomorphic hepatocellular carcinoma with biochemical characteristics similar to those of fibrolamellar carcinoma is described. During chemotherapy there was a marked disorder of vitamin B12 metabolism.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Combined Modality Therapy; Doxorubicin; Etoposide; Female; Folic Acid; Humans; Liver Neoplasms; Neurotensin; Quinazolines; Vitamin B 12

A 12 year old girl with a localised fibrolamellar hepatoma had a raised serum unsaturated vitamin B12 binding capacity (UBBC) and transcobalamin I (TCI) prior to complete resection and chemotherapy. Regular clinical and radiological follow-up detected no recurrence of her disease, but the UBBC and TCI slowly rose. Local recurrence and pulmonary metastases became detectable 2 1/2 years after diagnosis, 18 months after the UBBC and TCI level became elevated. Measurement of UBBC and TCI can help in the early detection of recurrence long before there is clinical or radiological evidence of recurrent fibrolamellar hepatoma.

Topics: Carcinoma, Hepatocellular; Child; Female; Humans; Liver Neoplasms; Transcobalamins; Vitamin B 12

Sera from 242 South African blacks with hepatocellular carcinoma were assayed for unsaturated vitamin B12 binding capacity (UBBC) and vitamin B12 activity. Six patients were younger than 20 years of age, and 24% were younger than 30 years of age. Eighty-four percent of the patients had a slightly raised UBBC and 86% had a slightly elevated vitamin B12 value, but in no patient was an exceptionally high UBBC present. Serum UBBC and vitamin B12 were not higher in younger patients, and raised UBBC values were not related to serum alpha-fetoprotein values. Serum UBBC and vitamin B12 concentrations were not significantly different in patients with and without coexisting cirrhosis. In none of the patients with a UBBC above 3000 pg/ml was the fibrolamellar variant of hepatocellular carcinoma present. The authors conclude that South African blacks with hepatocellular carcinoma do not secrete an abnormal vitamin B12 binding protein.

Topics: Adolescent; Adult; Aged; alpha-Fetoproteins; Black People; Blood; Carcinoma, Hepatocellular; Child; Female; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Receptors, Drug; South Africa; Vitamin B 12

The binding, internalization, processing and release of labeled cyanocobalamin (CN[57Co]Cbl) bound to human transcobalamin II (TC II) were studied in HepG2 cells, a line of hepatocytes derived from a human hepatoma. The cells bound the TC II-Cbl by specific, high affinity receptors. Within the cell, the CN-Cbl was promptly freed from TC II and the CN-Cbl converted to more active forms including adenosyl Cbl (AdoCbl) and methyl Cbl (MeCbl). Whereas free labeled Cbl was still present at 72 hours after entry, the cells also bound Cbl to an intracellular binder (ICB) presumed to represent the holo enzymes dependent on Cbl. At levels of TC II that saturated the receptors for TC II-Cbl, much of the Cbl entering the cells remained free and was converted to AdoCbl. Under these circumstances the cells released free Cbl, mostly AdoCbl. Human R type binders of Cbl, which are glycoproteins and some having a terminal galactose, were bound by the HepG2 cells. The binding was characteristic of the receptor system responsive to a terminal galactose, or asialoglycoproteins, but was inconsistent and of low affinity. Cbl bound to R binder was internalized and converted to coenzyme forms of Cbl, but the process was much less effective than when the Cbl entered via the TC II receptor system. It was concluded that the receptors for R-Cbl were unlikely to contribute to the physiologic transport of Cbl in man, but may function in some yet unknown way.

Topics: Asialoglycoprotein Receptor; Carcinoma, Hepatocellular; Cell Line; Cobalt Radioisotopes; Cobamides; Galactose; Glycoproteins; Humans; Liver Neoplasms; Receptors, Immunologic; Time Factors; Transcobalamins; Vitamin B 12

Serum neurotensin concentrations were supranormal in 5 out of 20 patients with carcinoma of the liver. Liver specimens from 4 of these 5 patients demonstrated features typical of fibrolamellar carcinoma. Neurotensin may be suitable as a tumour marker for fibrolamellar carcinoma and may be useful for the detection of recurrences after treatment.

Topics: alpha-Fetoproteins; Carcinoma, Hepatocellular; Diagnosis, Differential; Embolization, Therapeutic; Humans; Liver; Liver Neoplasms; Neurotensin; Prognosis; Vitamin B 12

Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Methods; Vitamin B 12

Of 37 patients with histologically verified hepatocellular carcinoma (HCC) from Bangkok, Thailand, 34 had raised values of plasma cobalamin, and 1 presented with a markedly increased value of plasma transcobalamin I (TC I). One patient with clinical malignancy of the liver, not proven histologically to be HCC, had a raised plasma cobalamin value and a markedly increased value of TC I. From our own studies and from studies in the literature we find circumstantial evidence that TC I occasionally is produced by the malignant liver cells in HCC.

Topics: Adolescent; Adult; Aged; Carcinoma; Female; Humans; Liver Neoplasms; Male; Middle Aged; Thailand; Transcobalamins; Vitamin B 12

Ten (9.3%) of 107 patients with hepatocellular carcinoma had considerably increased serum unsaturated vitamin B12 binding capacity. All 10 were young (mean 12 years), had no serum alpha-fetoprotein, and no underlying cirrhosis; all had a longer survival compared with patients without increased serum unsaturated vitamin B12 binding capacity in the study. Seven of the 10 patients had fibrolamellar hepatocellular carcinoma, a recently recognised histological variant, which was found in only one young patient without increased serum unsaturated vitamin B12 binding capacity and no alpha-fetoprotein among the remaining 97. This high degree of correlation between increased serum unsaturated vitamin B12 binding capacity and fibrolamellar hepatocellular carcinoma has not been reported before. Increased serum unsaturated vitamin B12 binding capacity may be of considerable help in diagnosis, prognosis, and monitoring treatment of this well-defined group of patients with hepatocellular carcinoma but no alpha-fetoprotein.

Topics: Adolescent; Adult; Aged; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Vitamin B 12

Topics: Carcinoma, Hepatocellular; Carrier Proteins; Fibroma; Gallbladder Neoplasms; Hemangioma, Cavernous; Humans; Lipoma; Liver Neoplasms; Male; Middle Aged; Neoplasms, Multiple Primary; Stomach Neoplasms; Vitamin B 12

Topics: Blood Proteins; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Transcobalamins; Vitamin B 12

Grossly raised levels of tumour related vitamin B12 binding protein, reflected by rises in serum vitamin B12 and unsaturated vitamin B12 binding capacity (UBBC), were found in three of 44 patients with hepatocellular carcinoma. All three were HBsAg negative and had normal serum alpha fetoprotein levels. The patients did not have underlying cirrhosis and the tumours contained characteristic intracellular inclusions. In the first patient the UBBC level fell during a partial remission induced by adriamycin therapy and in the second patient UBBC levels rose with progression of her disease. In the third patient serum B12 binding protein levels fell after tumour resection. Assay and subsequent monitoring of serum vitamin B12 and UBCC may prove valuable in the assessment and follow-up of some patients with hepatocellular carcinoma whose alpha fetoprotein levels are normal.

Topics: Adolescent; Adult; alpha-Fetoproteins; Blood Proteins; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Transcobalamins; Vitamin B 12

36% of a total of chronic liver patients suffered from anaemia and 50.5% of patients affected with liver cirrhosis. In most cases the anaemias were normochrome and hypochrome or hyperchrome only in some cases. In analyzing possible single factors the reductions of vitamin B12 absorption could be made probable by means of the Schilling test and sometimes a folic acid deficiency in macrocyte anaemia with normal vitamin B12 absorption by determining the folic acid content in the serum and by successes of test treatment 82% of patients with liver cirrhosis showed a latent or manifest haemolysis. However, it was only in 1/3 of the patients with liver cirrhosis that the spleen turned out to be the place of an increased degradation of erythrocytes. In some cases an increased erythrocytoclasia into the liver could be identified. Predominantly, however, an increased degradation of erythrocytes in the total RHS had to be assumed. Twice an ineffective erythropoiesis could be found by ferrokinetic examinations. As a whole ferrokinetic examinations cannot be interpreted easily, because their static and dynamic values of iron transport in the plasma volume of liver patients will undergo considerable changes. Patients with disturbances of haematopoiesis and with haemolysis remaining in the latent stage may develop a manifest anaemia because of the influence of additional factors, such as increase of the plasma volume at lowered haematocrit value or microbleedings. The cause of anaemia cannot be concluded with sufficient probability from the type of anaemia; in a single case all pathogenetic factors will rather have to be analyzed. Therapeutic possibilities for hepatogenous anaemia of complex genesis are discussed.

Topics: Adult; Anemia; Chronic Disease; Erythrocyte Count; Erythrocyte Volume; Folic Acid; Hematocrit; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Neoplasm Metastasis; Vitamin B 12

The influence of dietary protein content and dietary vitamin B12 supplement on the hepatotoxicity and carcinogenicity of aflatoxin in rat liver was studied. In animals fed a low-protein diet, aflatoxin induced extensive toxic and carcinogenic effects. Cirrhosis was significantly prevented to a certain level by vitamin B12 administration, but the incidence of cholangiofibrosis and hyperplastic nodules was unchanged. No toxic effect was observed in animals receiving high-protein diet with no vitamin B12 supplement in this study (33 weeks). Only one rat bearing a hepatoma was observed in this group. However, hepatoma and hyperplastic nodules were found in the group receiving high-protein diet plus vitamin B12. Cholangiofibrosis and cirrhosis were not observed in the high-protein group regardless of vitamin B12 administration.

Topics: Aflatoxins; Animals; Carcinoma, Hepatocellular; Dietary Proteins; Hyperplasia; Liver; Liver Cirrhosis, Experimental; Liver Neoplasms; Male; Neoplasms, Experimental; Rats; Vitamin B 12

A serum B12-binding protein with increased sialic acid content (termed hepatoma B12-binding protein) that causes elevations of serum B12 and unsaturated B12-binding capacity has been found in some patients with hepatocellular carcinoma (hepatoma). We now report another patient with hepatoma with initial near-normal, unsaturated B12-binding capacity that increased 400-fold as the disease progressed and then fell 50% with response to chemotherapy. A perfusate of the tumor in the liver had 5 times more B12-binding protein than did the serum and was immunologically the same as the serum hepatoma B12-binding protein isolated from previous cases. A cell line derived from hepatoma produced significant amounts of B12-binding protein similar to hepatoma B12-binding protein, whereas cell lines from normal liver and other neoplasia did not. The hepatoma sera, perfusate, and media from the hepatoma cell line contained elevated sialyltransferase activity. These data suggest that some hepatomas produce increased hypersialylated B12-binding protein that is cleared slowly from the plasma and accumulates there as hepatoma B12-binding protein.

Topics: Adolescent; Alpha-Globulins; Beta-Globulins; Carcinoma, Hepatocellular; Carrier Proteins; Cell Line; Humans; Liver Neoplasms; Male; Neoplasm Proteins; Sialyltransferases; Vitamin B 12

The distribution of cobalamin cofactors was investigated in the livers and tumors of rats bearing transplanted Morris 7777 or 7800 hepatomas, in the livers of rats treated with the hepatocarcinogen diethylnitrosamine, and in normal rats. There was a significant increase in the proportion of methylcobalamin both in livers and tumors from rat bearing the hepatomas 7777 and 7800 compared to the proportion of methylcobalamin in the livers of normal rats. The total cobalamin content of the hepatomas was significantly lower than that of host or control livers. Similarly, the total cobalamin content of the livers from the tumor-bearing rats was less than that in control animals. The administration to rats of an acute dose of diethylnitrosamine led to an 84% increase in the hepatic concentration of methylcobalamin. Chronic administration of diethylnitrosamine slightly increased the hepatic methylcobalamin concentration, but this was not statistically significant. Liver weight was reduced, and the hepatic content of total cobalamin fell to 55% of that in control animals.

Topics: Animals; Carcinoma, Hepatocellular; Cobamides; Diethylnitrosamine; Female; Liver; Liver Neoplasms; Neoplasms, Experimental; Nitrosamines; Rats; Vitamin B 12

Serum vitamin B12, folic acid, vitamin B12 and folic acid binding protein concentration were determined in 31 patients with primary carcinoma of the liver. Serum vitamin B12 level was found to be higher in 16 of 31 (52%) patients with carcinoma of the liver and the mean value was also significantly higher than that of the control group. There was no significant difference between the mean values of serum UBBC of these 2 groups. TCI and TCIII increased while TCII decreased considerably in the patient group. Serum folate level in patients with primary carcinoma of the liver was significantly lower than that of the control group. About 39% of these patients had serum folate level lower than the lowest value of the control group. Serum FABP in the former group was also significantly higher than that of the latter group.

Topics: Adult; Aged; Carcinoma; Carrier Proteins; Folic Acid; Humans; Liver Neoplasms; Middle Aged; Vitamin B 12

One hundred and thirty-nine patients with non-hematologic malignancy were studied to define the incidence of vitamin B12-related abnormalities and correlate them with clinical findings. Based on vitamin B12-binding patterns, the following relatively distinct groups were defined: (A) 50% had normal results; (B) 6% had very high transcobalamin (TC) I and vitamin B12 levels as reported in isolated instances previously: most had hepatic metastases and early death, and all had definite metastatic disease; (C) 11% had high vitamin B12 levels with little or no unsaturated TC I elevation: most also had hepatic and other metastases and early death; (D) 23% had high vitamin B12-binding capacity with normal TC I and vitamin B12 levels: there were no distinguishing features for this group other than an increased proportion of black patients; and (E) 10% had low vitamin B12 levels, in many cases not associated with vitamin B12 deficiency or other known causes of low serum levels. Thus, high serum vitamin B12 level, with or without unsaturated TC I elevation, usually implies a poor prognosis in a patient with cancer. However, while most such patients have hepatic and other metastases, hepatic involvement was not universal nor did most patients with hepatic disease have high vitamin B12 levels. High serum TC I thus is not always due to increased granulocytic proliferation or to hepatic tumor, and alternative mechanisms for TC I accumulation should be sought.

Topics: Black People; Blood Proteins; Carrier Proteins; Female; Humans; Liver Neoplasms; Male; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Prognosis; Transcobalamins; Vitamin B 12

Topics: Carcinoma, Hepatocellular; Female; Humans; Liver Diseases; Liver Neoplasms; Male; Pregnancy; Transcobalamins; Vitamin B 12

The effects of high dietary levels of lipotropes on the carcinogenic activity of diethylnitrosamine (DENA) in rats were studied. All animals given DENA, with or without a dietary supplement, developed hepatocellular carcinomas. The mean survival times of all groups of rats dying with hepatocellular carcinomas after DENA treatment were determined. Choline, betaine, and folic acid consistently exerted no significant effect on those mean survival times. In rats receiving approximately equal to 2 mg DENA/day, methionine administration led to a slight but significant increase in the mean survival time of the carcinogen-treated rats, whereas vitamin B12 significantly lowered the survival time; neither substance altered the mean survival times of those treated with only 1.0 mg DENA/day. On the other hand, ethanolamine decreased the mean survival times of rats given 1.0 mg DENA daily, but had no effect on animals receiving 2 ml/day of carcinogen. Dimethylthetin (sulfur analogue of betaine), methotrexate, lecithin, and cephalin exerted no effect on the carcinogenic activity of DENA. The administration of dimethylthetin and betaine along with DENA led to markedly increased liver weights in animals dying of hepatocellular carcinomas, when compared to liver weights of animals treated with DENA alone.

Topics: Animals; Betaine; Carcinogens; Carcinoma, Hepatocellular; Choline; Diet; Ethanolamines; Folic Acid; Lipotropic Agents; Liver; Liver Neoplasms; Methionine; Methotrexate; Neoplasms, Experimental; Nitrosamines; Organ Size; Phosphatidylcholines; Phosphatidylethanolamines; Rats; Vitamin B 12

High levels of a novel vitamin B12-binding protein (hepatoma B12 BP) have been observed recently in plasma obtained from three adolescent patients with hepatocellular carcinoma. This protein has now been isolated in homogeneous form from the plasma and pleural fluid of two of these patients by the use of affinity chromatography with vitamin B12-Sepharose. The hepatoma B12 BP belongs to the R-type group of B12-binding proteins and is essentially indistinguishable from the recently isolated human milk and saliva R-type proteins in terms of: (a) immunologic properties based on immunodiffusion and immunoprecipitation assays; (b) amino acid composition; (c) molecular weight based on amino acid and carbohydrate content; and (d) absorption spectra. Both hepatoma B12 BPs contain more sialic acid and less fucose than the milk and saliva B12 BPs. All four proteins contain similar amounts of galactose, mannose, galactosamine, and glucosamine. Differences in sialic acid content appear to account for the differences in electrophoretic mobility that were observed among the four proteins. Differences in total carbohydrate content appear to account for the differences in apparent molecular weight that were observed with both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor tissue from one of the patients contained 10 times as much R-type protein as did normal liver tissue from the same patient. This suggests, although it does not prove, that synthesis by the tumor is the cause of the high levels of R-type protein found in the plasma of certain patients with hepatocellular carcinoma. Plasma survival studies performed with rabbits indicate that the hepatoma B12 BP has a prolonged plasma survival and suggests that his parameter is also of importance.

Topics: Aged; Carcinoma, Hepatocellular; Carrier Proteins; Female; Humans; Liver; Liver Neoplasms; Neoplasm Proteins; Vitamin B 12

A cobalamin-binding protein has been purified by affinity chromatography from plasma of a patient with hepatoma and a 10,000-fold increase in the concentration of the plasma cobalamin-binding capacity. The protein behaved as normal transcobalamin I in gel filtration, agar gel electrophoresis, immunoelectrophoresis, precipitation by ammonium sulphate, and cobalamin-binding studies. The protein contained 38 per cent carbohydrate, and the relative molecular mass based on amino acid and carbohydrate analyses was 69,000. The molar absorption coefficient of cyanocobalamin bound to the protein was determined to be 36,000 at 362 nm. On amino acid sequencing, one amino terminal was found, and the first 13 residues were determined as Glu-Ile-Ser/Cys-Glu-Val-Ser/Cys-Glu-Glu-Asx-Tyr-Ile-Arg-Leu/Ile.

Topics: Amino Acid Sequence; Amino Acids; Carbohydrates; Carcinoma, Hepatocellular; Carrier Proteins; Chromatography, Affinity; Electrophoresis, Agar Gel; Humans; Immunoelectrophoresis; Liver Neoplasms; Molecular Weight; Protein Binding; Transcobalamins; Vitamin B 12

Elevation of transcobalamin I and serum vitamin B12 levels has usually been associated with increased granulocytic proliferation, such as occurs in chronic myelogenous leukemia. Two patients with metastatic cancer had extremely high serum vitamin B12 and transcobalamin I levels--greater than those seen in even the most intense granulocytic proliferation--that were not explainable by leukocytosis. The subjects' serum vitamin B12 levels were 18,750 and 21,221 pg per milliliter (normal, 471 plus or minus 174 pg per milliliter, mean plus or minus S.D.) and unsaturated vitamin B12 binding capacity 158,750 and 5,400 pg per milliliter (normal, 1153 plus or minus 313 pg per milliliter) respectively. The abnormally elevated serum binder was shown to be identical with transcobalamin balamin I in every respect. Levels of transcobalamin II and serum third binder were normal. The cause of the binder abnormality is unknown, but factors other than granulocyte proliferation may control or contribute to the production or accumulation of transcobalamin I.

Topics: Adenocarcinoma; Aged; Animals; Blood Proteins; Carcinoma; Carrier Proteins; Cell Division; Chromatography, DEAE-Cellulose; Chromatography, Gel; Cobalt Radioisotopes; Colonic Neoplasms; Female; Granulocytes; Humans; Immune Sera; Leukemia, Myeloid; Leukocyte Count; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Protein Binding; Rabbits; Radioligand Assay; Saliva; Stomach Neoplasms; Vitamin B 12

Topics: Adolescent; Animals; Antibodies; Blood Proteins; Carcinoma, Hepatocellular; Centrifugation, Density Gradient; Child; Chromatography, DEAE-Cellulose; Chromatography, Gel; Cobalt Radioisotopes; Cobamides; Electrophoresis, Polyacrylamide Gel; HeLa Cells; Humans; Leukemia; Leukemia, Myeloid; Leukocytes; Liver Neoplasms; Neuraminidase; Protein Binding; Rabbits; Saliva; Vitamin B 12

Topics: Adolescent; Adult; Alpha-Globulins; Beta-Globulins; Carcinoma, Hepatocellular; Child, Preschool; Chromatography, DEAE-Cellulose; Chromatography, Gel; Cobalt Radioisotopes; Female; gamma-Globulins; Humans; Infant; Leukemia, Myeloid; Leukocyte Count; Liver Neoplasms; Macroglobulins; Male; Neoplasm Proteins; Protein Binding; Serum Globulins; Vitamin B 12

Topics: Ammonia-Lyases; Animals; Carcinoma, Hepatocellular; Choline; Choline Deficiency; Diet; Histidine Ammonia-Lyase; Hydro-Lyases; Liver; Liver Neoplasms; Male; Methionine; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Time Factors; Urocanate Hydratase; Vitamin B 12

Topics: Adenine; Animals; Carcinoma 256, Walker; Carcinoma, Hepatocellular; Choline; Diet; FIGLU Test; Folic Acid; Folic Acid Deficiency; Formates; Glycine; Guanine; Liver Neoplasms; Male; Methionine; Neoplasms, Experimental; Rats; Serine; Thymidine; Vitamin B 12

Topics: Chronic Disease; Fatty Liver; Hepatitis; Humans; Intestinal Absorption; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Radioimmunoassay; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Alpha-Globulins; Beta-Globulins; Blood Proteins; Child, Preschool; Chronic Disease; Female; Fever of Unknown Origin; Hodgkin Disease; Humans; Infections; Leukocyte Count; Leukocytosis; Liver Neoplasms; Lymphoma; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Protein Binding; Splenectomy; Vitamin B 12

Topics: Animals; Carcinoma, Hepatocellular; Choline Deficiency; Fatty Liver; Folic Acid; Homocystine; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Methionine; Methylation; Neoplasms, Experimental; Nutrition Disorders; Rats; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Cobalt Isotopes; Gold Colloid, Radioactive; Humans; Iodine Radioisotopes; Liver; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Methods; Radioisotope Dilution Technique; Radionuclide Imaging; Rose Bengal; Vitamin B 12

Topics: Animals; Diet; Fetal Proteins; Folic Acid; Haplorhini; Liver Neoplasms; Pyridoxine; Tryptophan; Vitamin B 12; Vitamin B 6 Deficiency

Topics: Acute Disease; Chronic Disease; Coenzymes; Folic Acid; Hepatitis; Histidine; Humans; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Liver Neoplasms; Male; Middle Aged; Vitamin B 12

Topics: Aflatoxins; Animals; Autoradiography; Body Weight; Choline; Diet; DNA; Hyperplasia; Kidney; Lipids; Lipotropic Agents; Liver; Liver Neoplasms; Male; Methionine; Rats; Thymidine; Tritium; Vitamin B 12

Topics: Adrenal Gland Neoplasms; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver Neoplasms; Male; Mandelic Acids; Neoplasm Metastasis; Neuroblastoma; Prognosis; Skin Neoplasms; Vitamin B 12

Topics: Aged; Female; Hemangiosarcoma; Humans; Infant; Liver Neoplasms; Male; Neoplasm Metastasis; Neuroblastoma; Skin Neoplasms; Vitamin B 12

Topics: Adolescent; Biopsy; Blood Chemical Analysis; Folic Acid; Geriatrics; Lactococcus lactis; Liver; Liver Diseases; Liver Neoplasms; Metabolism; Streptococcus; Vitamin B 12

Topics: Breast Neoplasms; Cyclophosphamide; Drug Therapy, Combination; Fluorouracil; Hepatomegaly; Humans; Liver Neoplasms; Methotrexate; Neoplasm Metastasis; Neoplasms; Prednisone; Testosterone; Thiotepa; Toxicology; Vitamin B 12

Topics: Blood; Chemical and Drug Induced Liver Injury; Chlorpromazine; Cholangitis; Diagnosis; Hepatitis; Hepatitis A; Humans; Jaundice; Jaundice, Obstructive; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Monoamine Oxidase Inhibitors; Prognosis; Vitamin B 12

Topics: Abdominal Neoplasms; Antineoplastic Agents; Carcinoma, Hepatocellular; Child; Cyclophosphamide; Female; Fibrosarcoma; Granulosa Cell Tumor; Humans; Infant; Leiomyoma; Liver Neoplasms; Neoplasms; Neuroblastoma; Ovarian Neoplasms; Surgical Procedures, Operative; Teratoma; Vitamin B 12; Wilms Tumor

Topics: Carcinogenesis; Carcinoma, Hepatocellular; Chick Embryo; Embryo, Mammalian; Embryo, Nonmammalian; Hepatectomy; Liver; Liver Extracts; Liver Neoplasms; Neoplasms; Rats; Research; Tissue Culture Techniques; Vitamin B 12; Yeasts

Topics: Animals; Carcinogens; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Neoplasms, Experimental; Neoplasms; p-Dimethylaminoazobenzene; Rats; Riboflavin; Vitamin B 12

Topics: Animals; Carcinoma, Hepatocellular; Encephalomyelitis; Liver Neoplasms; Neoplasms; Rats; Vitamin B 12

Topics: Hematinics; Humans; Liver Neoplasms; Vitamin B 12; Vitamins

Topics: Animals; Carcinoma; Humans; Liver Neoplasms; Neoplasms, Experimental; Vitamin B 12