mercaptopurine and Liver-Neoplasms

Hepatosplenic T-cell lymphoma (HSTCL) is a rare form of peripheral T-cell lymphoma. It is associated with an aggressive clinical course, a poor response to conventional treatment, and an exceedingly high mortality rate. Recent reports suggest an excessive number of cases of HSTCL in young patients with Crohn's disease who are treated with thiopurines (azathioprine or 6-mercaptopurine [6-MP]) either in conjunction with or without agents that inhibit tumor necrosis factor-alpha (TNF-alpha). Herein, we describe the case of an 18-year-old man with Crohn's disease who developed HSTCL after 5 years of 6-MP treatment. He died 7 months after diagnosis from chemotherapy-refractory lymphoma. Through a literature review, we identified 28 cases of HSTCL in Crohn's patients. All patients were treated with azathioprine or 6-MP; 22 of 28 (79%) received concomitant treatment with infliximab, and 3 of these 22 patients later received treatment with adalimumab. The median age at diagnosis of HSTCL was 22 years (range, 12-40 years). The median survival for all patients was 8 months (range, 5 days-31+ months), with only 1 patient achieving remission. Additional research is needed to better understand the role of thiopurines and TNF-alpha inhibitors in promoting HSTCL and what can be done to prevent and treat this devastating malignancy in young patients with Crohn's disease.

Topics: Adalimumab; Adolescent; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Azathioprine; Crohn Disease; Fatal Outcome; Humans; Infliximab; Leukemia-Lymphoma, Adult T-Cell; Liver Neoplasms; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Male; Mercaptopurine; Splenic Neoplasms; Tumor Necrosis Factor-alpha

This article reviews the current literature and knowledge about hepatosplenic T-cell lymphoma (HSTCL), providing an overview of the clinical features, a description of its pathology and immunophenotypic traits in relation to other lymphomas. In addition, we explore the history of reported cases of hepatosplenic T-cell lymphoma in relation to the possible existence of a causal relationship between infliximab use and HSTCL. The treatments for HSTCL will be briefly addressed.. A comprehensive literature search using multiple databases was performed. Keyword search phrases including "lymphoma," "hepatosplenic T-cell lymphoma," "Inflammatory bowel disease," "6-mercaptopurine," and "infliximab" were used in various combinations. In addition references from published papers were reviewed as well.. There are over 200 reported cases of HSTCL. Only 22 cases of hepatosplenic T-cell lymphoma are associated with IBD treatment. Clinicians usually reserve immunomodulators and biologics for moderate to severe IBD cases. The ultimate goal of therapy is to control inflammation and therefore allow mucosal healing. IBD patients demonstrating mucosal healing are less likely to undergo surgery and experience complications related to their disease. We manipulate the immune system with corticosteroids, immunomodulators, and biologics, therefore causing bone marrow suppression. With bone marrow suppression, malignant degeneration may begin through selective uncontrolled cell proliferation, initiating HSTCL development in the genetically susceptible.. Hepatosplenic T-cell lymphoma is a rare disease, often with a poor outcome. With the increasing number of reported cases of HSTCL linked to the use of infliximab, adalimumab, and AZA/6-MP, there appears to be an undeniable association of HSTCL development with the use of these agents. This risk is unquantifiable. When considering the rarity of cases and the multiple complications with uncontrolled disease, however, the benefit of treatment far outweighs the risk.

Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal; Azathioprine; Humans; Immunophenotyping; Immunosuppression Therapy; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Liver Neoplasms; Lymphoma, T-Cell, Peripheral; Mercaptopurine; Splenic Neoplasms; Tumor Necrosis Factor-alpha

6-Mercaptopurine (6-MCP) is an antiproliferative purine analog used in acute lymphoblastic leukemia, non-Hodgkin lymphoma, and inflammatory bowel disease (Crohn's disease, ulcerative colitis). Although 6-MCP has the great therapeutic potential for cancer and immunosuppressant-related diseases, 6-MCP is not readily soluble in water, presents a high first-pass effect, short half-life (0.5-1.5 h), and implies a low bioavailability (16%). On the contrary, solid lipid nanoparticles (SLNs) are prepared from solid lipids at room temperature and body temperature. In this study, SLNs were prepared w/o/w double emulsion-solvent evaporation method using Precirol ATO5 as matrix lipid. In the emulsion stabilization, surfactant (Tween 80) and polymeric stabilizer (polyvinyl alcohol [PVA]) were used. Two group formulations using Tween 80 and PVA were compared in terms of particle size, polydispersity index, zeta potential encapsulation efficiency%, and process yield%. Differential calorimetric analysis and release properties were examined for optimum formulation, and release kinetics were calculated. According to studies, sustained release was obtained with SLNs by the Korsmayer-Peppas kinetic model. The

Topics: Antineoplastic Agents; Emulsions; Humans; Lipids; Liver Neoplasms; Mercaptopurine; Nanoparticles; Polysorbates

Combination treatment with low-dose thiopurine and allopurinol (AP) has successfully been used in patients with inflammatory bowel disease with a so called skewed thiopurine metabolite profile. In red blood cells in vivo, it reduces the concentration of methylated metabolites and increases the concentration of the phosphorylated ones, which is associated with improved therapeutic efficacy. This study aimed to investigate the largely unknown mechanism of AP on thiopurine metabolism in cells with an active thiopurine metabolic pathway using HepG2 and HEK293 cells. Cells were treated with 6-mercaptopurine (6MP) and AP or its metabolite oxypurinol. The expression of genes known to be associated with thiopurine metabolism, and the concentration of thiopurine metabolites were analyzed. Gene expression levels were only affected by AP in the presence of 6MP. The addition of AP to 6MP affected the expression of in total 19 genes in the two cell lines. In both cell lines the expression of the transporter SLC29A2 was reduced by the combined treatment. Six regulated genes in HepG2 cells and 8 regulated genes in HEK293 cells were connected to networks with 18 and 35 genes, respectively, present at known susceptibility loci for inflammatory bowel disease, when analyzed using a protein-protein interaction database. The genes identified as regulated as well as the disease associated interacting genes represent new candidates for further investigation in the context of combination therapy with thiopurines and AP. However, no differences in absolute metabolite concentrations were observed between 6MP+AP or 6MP+oxypurinol vs. 6MP alone in either of the two cell lines. In conclusion; the effect of AP on gene expression levels requires the presence of 6MP, at least in vitro. Previously described AP-effects on metabolite concentrations observed in red blood cells in vivo could not be reproduced in our cell lines in vitro. AP's effects in relation to thiopurine metabolism are complex. The network-identified susceptibility genes represented biological processes mainly associated with purine nucleotide biosynthetic processes, lymphocyte proliferation, NF-KB activation, JAK-STAT signaling, and apoptotic signaling at oxidative stress.

Topics: Allopurinol; Antimetabolites; Carcinoma, Hepatocellular; Drug Therapy, Combination; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; HEK293 Cells; Humans; Liver Neoplasms; Mercaptopurine; Methyltransferases; Purines

Infliximab-induced hepatotoxicity is reported in several case studies involving patients with inflammatory bowel disease (IBD) and a direct hepatotoxic effect has been proposed.. The aim of this study was to determine the direct in vitro toxicity of infliximab. As a proof of principle the in vitro toxicity of thiopurines and methotrexate was also determined.. Cell survival curves and the half maximal inhibitory concentrations (IC(50)) were obtained after 24, 48 and 72 h of incubation in HepG2 cells with the IBD drugs azathioprine, 6-mercaptopurine, 6-thioguanine, methotrexate or infliximab by using the WST-1 cytotoxicity assay.. No in vitro hepatotoxicity in HepG2 cells was seen with infliximab, while concentration-dependent cytotoxicity was observed when HepG2 cells were incubated with increasing concentrations of azathioprine, 6-mercaptopurine and 6-thioguanine.. Infliximab alone or given in combination with azathioprine showed no direct hepatotoxic effect in vitro, indicating that the postulated direct hepatotoxicity of infliximab is unlikely.

Topics: Analysis of Variance; Antibodies, Monoclonal; Azathioprine; Cell Survival; Dose-Response Relationship, Drug; Hep G2 Cells; Hepatoblastoma; Humans; In Vitro Techniques; Inflammatory Bowel Diseases; Infliximab; Liver Neoplasms; Mercaptopurine; Methotrexate; Sensitivity and Specificity; Thioguanine

Due to the increasing incidence of cancer, a leading cause of death worldwide, discovery of new therapeutic drugs is urgently needed. By screening for agents with low toxicity that selectively target cancer cells, we found that 6-[(1-naphthylmethyl) sulfanyl]-9H-purine (NMMP), a derivative of 6-mercaptopurine (6-MP), could reduce the viability of five human cancer cell lines. Further study suggested that NMMP inhibition of the proliferation of hepatocellular carcinoma (HepG2) cells was associated with G2/M phase cell cycle arrest, and reduced cyclin-dependent kinase (CDK) 4 and cyclin B1/D1 levels. In addition, NMMP induced cell apoptosis, as determined by TUNEL assay. Immunoblot analysis revealed that the expression of cleaved caspase-9 and caspase-3 as well as the ratio of Bax/Bcl-2 protein increased significantly. Overall, our results suggest that NMMP exerts anti-tumor activities through induction of G2/M phase arrest and mitochondria-dependent cell apoptosis, implicating its potential therapeutic value for the treatment of cancer.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Proliferation; Drug Screening Assays, Antitumor; G2 Phase Cell Cycle Checkpoints; Hep G2 Cells; Humans; Liver Neoplasms; M Phase Cell Cycle Checkpoints; Mercaptopurine

Topics: Adolescent; Antibodies, Monoclonal; Crohn Disease; Fatal Outcome; Female; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Infliximab; Liver Neoplasms; Lymphoma, T-Cell; Mercaptopurine; Splenic Neoplasms; Tumor Necrosis Factor-alpha

In a 64-year-old man who had been treated with prednisolone (PSL) and 6-mercaptopurine (6MP) for a long period, for ulcerative colitis (UC), hepatocellular carcinoma (HCC) was detected incidentally. The UC was in remission with these medications. After he had been taking these medications for about 8 years, HCC was detected by computed tomography (CT), done for the evaluation of an other disease. Blood chemistry examination results were normal, except that the protein induced by vitamin K antagonist (PIVKA)-II level was 7940 AU/ml. We performed resection of liver segment V. With comparative genomic hybridization, chromosomal aberrations were recognized; these were gains of 1q, 3ptel-21, 8p12, and 22q11.23-22q13.1. Generally, HCC is associated with hepatitis virus infection in most cases, but in this patient, the HCC was not related to hepatitis C virus (HCV) or HBV. It is presumed that this case was related to the immunosuppressive therapy for UC and was associated with the gains of 1q, 3p, and 8p.

Topics: Carcinoma, Hepatocellular; Chromosome Aberrations; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 8; Colitis, Ulcerative; Gene Amplification; Humans; Immunosuppressive Agents; In Situ Hybridization, Fluorescence; Karyotyping; Liver Neoplasms; Male; Mercaptopurine; Middle Aged; Nucleic Acid Hybridization; Tomography, X-Ray Computed

A 26-year-old man, diagnosed with acute myelogenous leukemia had multiple inflammatory pseudotumors (IPT) in the liver. The patient presented complete remission after remission induction therapy, and then showed right upper quadrant discomfort and intermittent fever. An ultrasonography disclosed multiple hypoechoic nodules in the liver. A biopsy of the nodules showed focal liver cell necrosis with scant inflammatory cells, compatible with IPT. After several courses of chemotherapy, the nodules in the liver increased. The second liver biopsy of the nodule showed fibrosis. Multiple IPTs in the liver should be distinguished from abscess and metastatic nodules.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Cytarabine; Daunorubicin; Diagnosis, Differential; Granuloma, Plasma Cell; Humans; Leukemia, Myeloid, Acute; Liver Abscess; Liver Diseases; Liver Neoplasms; Magnetic Resonance Imaging; Male; Mercaptopurine; Prednisolone; Tomography, X-Ray Computed

The modifying effects of an immunosuppressive agent, 6-mercaptopurine (6-MP), on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride (CCl4) or furfural were studied in male F344 rats. Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused immunosuppression, and significantly enhanced the induction of gamma-glutamyltranspeptidase (GGT)-positive foci and nodules in the CCl4 but not furfural case. Glutathione S-transferase P (GST-P)-positive preneoplastic lesions were not affected. Moreover, phenobarbital (PB) also enhanced the induction of GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis model, no promotion influence being exerted after treatment with the non-carcinogenic furfural. This study, therefore, suggests that 6-MP can enhance the induction of one type of preneoplastic foci and nodules and that essential differences exist between focal lesions arising in cirrhotic livers caused by CCl4 as opposed to furfural.

Topics: Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride; Drug Synergism; Furaldehyde; gamma-Glutamyltransferase; Glutathione Transferase; Liver; Liver Cirrhosis, Experimental; Liver Neoplasms; Male; Mercaptopurine; Phenobarbital; Precancerous Conditions; Rats; Rats, Inbred F344

Acute myeloblastic leukemia (AML) was diagnosed in a 54-year-old male who had been known to carry a chronic hepatitis B surface antigen (HBsAg) from June, 1983. Prompt remission was achieved with combination chemotherapy of BHAC-DMP. Follow-up maintenance and an intensification of this chemotherapy had been given for five years. He was readmitted to our hospital in March, 1988 because a mass was detected in the right lobe of the liver by ultrasonography. His serum alpha fetoprotein (AFP) level was found to be 180.1 ng/ml, and was diagnosed as having a hepatocellular carcinoma though there was no evidence of liver cirrhosis. A curative right hepatectomy was performed in May, 1988 after transcatheter arterial embolization and portal embolization. After resection of the tumor, the AFP level decreased to 10.7 ng/ml and no HbsAg was detected in the serum.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Combined Modality Therapy; Cytarabine; Daunorubicin; Embolization, Therapeutic; Hepatectomy; Hepatitis B Surface Antigens; Humans; Leukemia, Myeloid, Acute; Liver Neoplasms; Male; Mercaptopurine; Middle Aged; Neoplasms, Multiple Primary; Prednisolone; Remission Induction

Hepatocellular carcinoma (HCC) occurred in a 28-year-old woman treated for acute lymphocytic leukemia (ALL) with methotrexate (MTX) and 6-mercaptopurine (6-MP), off all therapy for 15 years, who was also heterozygous for alpha-1 antitrypsin (alpha-1 AT) deficiency. MTXD is responsible for the development of HCC in this patient. The literature concerning the incidence of HCC in patients treated with MTX and 6-MP and in alpha-1 antitrypsin deficiencies is reviewed.

Topics: Adult; alpha 1-Antitrypsin; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Female; Humans; Leukemia, Lymphoid; Liver Cirrhosis; Liver Neoplasms; Mercaptopurine; Methotrexate; Neoplasm Proteins; Neoplasms, Multiple Primary

A patient, a 46-year-old female, with a malignant thymoma spreading to the extrathoracic region is described. She underwent a thoracotomy and received radiation therapy, but the myasthenic symptoms did not disappear. A metastatic thymoma of the right mandibula was removed 9 months after thoracotomy. Further examination revealed metastatic thymomas of the bone and liver. After the operation the patient received combination chemotherapy (vincristine, cyclophosphamide, 6-mercaptopurine, prednisone) and remained asymptomatic for 31 months. She was found to have a metastatic thymoma in the occipital lobe of the brain 3.5 years after thoracotomy, and died from infection of the lung. Distant metastases and chemotherapy in malignant thymoma are reviewed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Cyclophosphamide; Female; Humans; Liver Neoplasms; Mandibular Neoplasms; Mercaptopurine; Middle Aged; Neoplasm Metastasis; Prednisone; Thymoma; Thymus Neoplasms; Vincristine

The inoculation of a mixture of drugs and guinea pig hepatoma cells (line-10) induced tumor-specific immunity in about 20% of guinea pigs. When guinea pigs with established intradermal tumors were given various drugs ip, no cures were observed; in contrast, multiple intralesional injections of actinomycin D, 1,3-bis(2-chlorethyl)-1-nitrosourea, adriamycin, mitomycin C, and melphalan were effective in curing animals of their intradermal tumors at a time when there were tumor cells in the draining lymph nodes; dimethyl-triazenoimidazole carboxamide, methotrexate, 5-fluorouracil, and 6-mercaptopurine were not effective. More than 80% of the cured animals were immune to rechallenge with 10(6) line-10 tumor cells.

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Carmustine; Dacarbazine; Dactinomycin; Doxorubicin; Drug Therapy, Combination; Fluorouracil; Graft Rejection; Guinea Pigs; Injections; Injections, Intraperitoneal; Liver Neoplasms; Melphalan; Mercaptopurine; Methotrexate; Mitomycins; Neoplasm Transplantation; Neoplasms, Experimental

Topics: Animals; Antimetabolites; Biological Transport; Carcinoma, Hepatocellular; Cell Division; Cells, Cultured; Isopentenyladenosine; Leukemia L1210; Liver Neoplasms; Mercaptopurine; Neoplasms, Experimental; Nucleosides; Nucleotides; Rats; Ribonucleotides

Two chemically induced, antigenically distinct guinea pig hepatoma cell lines, line 1 and line 10, which are resistant to killing by rabbit anti-Forssman or specific antitumor antibody and complement, can be rendered susceptible when the cells are pretreated with metabolic inhibitors and drugs commonly used for the treatment of cancer patients. The effect appears within 7 hr after initial contact with the inhibitors and is dependent on temperature and on inhibitor concentration; the effect is reversible within 7 hr, and the process of reversion is also temperature dependent. Not all preparations of tumor cells were rendered susceptible following treatment with inhibitors. In some cases, susceptibility to killing by complement was observed with anti-Forssman antibody but not antitumor antibody. No clear correlation between known metabolic inhibitory activity of the inhibitors and conversion to the sensitive state could be made. The results suggest that properties of nucleated cells, which are under metabolic control, play an important role in the killing efficiency of antibody and complement.

Topics: Animals; Antibodies, Neoplasm; Antigen-Antibody Reactions; Antineoplastic Agents; Azacitidine; Carcinoma, Hepatocellular; Cells, Cultured; Complement System Proteins; Cyclophosphamide; Cytarabine; Dactinomycin; Doxorubicin; Fluorouracil; Guinea Pigs; Hydroxyurea; Liver Neoplasms; Mercaptopurine; Methotrexate; Mitomycins; Neoplasms, Experimental; Puromycin; Vincristine

Survival period of rats bearing ascites hepatoma, AH-60C, which was less sensitive to bis (3-methylsulfonyloxypropyl)amine (864-T) and 6-mercaptopurine each alone, was prolonged by the combined treatment with these two agents. Two or 3 rats in groups of 12 animals each survived over 60 days by this combined therapy beginning from day 0. In AH-109A, which was insensitive to 6-mercaptopurine, the group treated with this combination did not survive longer than that with 864-T alone.

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Drug Therapy, Combination; Injections, Intraperitoneal; Liver Neoplasms; Mercaptopurine; Mesylates; Neoplasms, Experimental; Nitrogen Mustard Compounds; Rats; Tosyl Compounds

A malignant hepatoma occurred in a 12-year-old girl who eight years previously had developed an acute lymphoblastic leukaemia which for eight years had been in complete haematological remission. Fourteen months after the last re-induction treatment period had been discontinued, but while on methotrexate and 6-mercaptopurine maintenance, a hepatocellular liver carcinoma developed of which the patient died after a fulminating course, still in complete haematological remission. As far as is known, no direct carcinogenic effect can be ascribed to the two antimetabolites, but it must be assumed that these two drugs, taken by the patient for over seven years, led to cirrhosis of the liver whose malignant transformation was significantly influenced by the immunosuppressive effects of methotrexate and 6-mercaptopurine, given as maintenance therapy according to protocol 02 LA 64, Paris.

Topics: Carcinoma, Hepatocellular; Child; Female; Humans; Leukemia, Lymphoid; Liver Cirrhosis; Liver Neoplasms; Mercaptopurine; Methotrexate; Remission, Spontaneous; Time Factors

The effect of hydrocortisone on blood-borne tumor metastasis was studied in an i.v. inoculation experiment with Ehrlich hypotetraploid clone 1, Ehrlich hypotetraploid stock, and Ehrlich hyperdiploid stock tumors. The administration of hydrocortisone before tumor inoculation resulted in increased tumor take, reduced mean survival time of mice, and concentration of tumor metastasis in a specific organ (i.e., lung metastasis for Ehrlich hypotetraploid clone 1 tumor, and liver metastasis for Ehrlich hypotetraploid stock and Ehrlich hyperdiploid stock tumors). Enhancement of tumor metastasis, as induced by hydrocortisone pretreatment, was not reproduced by the administration of 6-mercaptopurine, testosterone, or estradiol. The progress of tumor death in hydrocortisone-conditioned mice was not affected by either heparin or dextran sulfate. This indicated that the effect of hydrocortisone on tumor metastasis was independent of the effect of these agents on immune reaction or blood coagulation. In the tracer experiment with 125-I-labeled tumor cells, hydrocortisone pretreatment significantly increased over the control the intrapulmonary retention of Ehrlich hypotetraploid clone 1 tumor cells from 1 through 72 hr after tumor inoculation, the time lag required for the establishment of metastatic foci in the lung. The arrest of Ehrlich hypotetraploid stock and Ehrlich hyperdiploid stock tumors in the liver was also temporarily increased by hydrocortisone pretreatment. No correlation was found between tumor cell size and differential distribution of metastatic tumors with 3 Ehrlich tumors. An attempt was made to use this blood-borne metastasis system for chemotherapeutic study. Administration of cyclophosphamide gave rise to a significant prolongation of survival time and often to complete prevention of tumor metastasis in hydrocortisone-conditioned mice.

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Line; Cyclophosphamide; Dextrans; Estradiol; Female; Heparin; Hydrocortisone; Injections, Intravenous; Liver Neoplasms; Lung Neoplasms; Mercaptopurine; Mice; Mice, Inbred ICR; Neoplasm Metastasis; Neoplastic Cells, Circulating; Stimulation, Chemical; Testosterone; Time Factors

Topics: Animals; Benzopyrenes; Carcinoma, Hepatocellular; Cell Fusion; Cell Line; Chromosomes; Clone Cells; Dexamethasone; Drug Resistance; Enzyme Induction; Fibroblasts; Hybrid Cells; Karyotyping; Liver Neoplasms; Mercaptopurine; Mice; Mixed Function Oxygenases; Neoplasms, Experimental; Parainfluenza Virus 1, Human; Rats; Tyrosine Transaminase

Topics: Abdominal Neoplasms; Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Gallbladder Neoplasms; Hodgkin Disease; Humans; Kidney Neoplasms; Liver Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Mercaptopurine; Middle Aged; Pancreatic Neoplasms; Prednisolone; Rectal Neoplasms; Stomach Neoplasms; Ultrasonography; Vincristine

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Hepatocellular; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Guanosine; Liver Neoplasms; Mercaptopurine; Methionine; Neoplasms, Experimental; Nitriles; Pyrimidines; Pyrroles; Ribonucleosides; RNA, Neoplasm; RNA, Ribosomal; Tritium; Uridine

Topics: Alkaline Phosphatase; Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Drug Resistance; Female; Liver Neoplasms; Mercaptopurine; Mice; Neoplasms, Experimental; Rats; Ribonucleoside Diphosphate Reductase; Sarcoma 180; Structure-Activity Relationship; Thiosemicarbazones

Topics: Adenosine Triphosphate; Animals; Bone Marrow; Carcinoma, Hepatocellular; Cattle; Cell Line; Cell-Free System; Chromatography, DEAE-Cellulose; Cytarabine; Cytidine; Deoxyribonucleosides; Dithiothreitol; Guanosine; Humans; Isoenzymes; Kinetics; Leukemia L1210; Liver Neoplasms; Lymphoma, Non-Hodgkin; Magnesium; Mercaptopurine; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred DBA; Phosphotransferases

Topics: Adenocarcinoma; Animals; Chromatography, Paper; Electrophoresis; Glucosyltransferases; L Cells; Leukemia L1210; Liver Neoplasms; Mercaptopurine; Methylation; Mice; Neoplasms, Experimental; Nucleosides; Nucleotides; Purines; Sulfur Isotopes

Topics: Adenoma, Bile Duct; Africa, Eastern; Alanine Transaminase; Antineoplastic Agents; Aspartate Aminotransferases; Black People; Blood Proteins; Carcinoma, Hepatocellular; Clinical Enzyme Tests; Cyclophosphamide; Cytarabine; Dactinomycin; Fluorouracil; gamma-Globulins; Humans; Hydroxyurea; Liver Neoplasms; Male; Mercaptopurine; Methotrexate; Mitomycins; Nitrogen Mustard Compounds; Prednisone; Prognosis; South Africa; Vincristine

Topics: Animals; Body Weight; Carcinoma, Hepatocellular; DNA; DNA, Neoplasm; Glucokinase; Glucose; Hepatectomy; Hexokinase; Hydroxyurea; Liver Glycogen; Liver Neoplasms; Liver Regeneration; Male; Mercaptopurine; Neoplasms, Experimental; Organ Size; Phosphofructokinase-1; Rats; Thymidine; Time Factors; Tritium

Topics: Adenine; Animals; Chemical Phenomena; Chemistry; Female; Granuloma; Guanine; Injections, Subcutaneous; Liver Neoplasms; Male; Mercaptopurine; Neoplasms, Experimental; Oxides; Purines; Rats; Xanthines

Topics: Agar; Animals; Anti-Bacterial Agents; Antineoplastic Agents; Ascites; Carcinoma, Hepatocellular; Clone Cells; Culture Techniques; Diffusion; Liver Neoplasms; Mercaptopurine; Methods; Mitomycins; Neoplasms, Experimental; Nitrogen Mustard Compounds; Rats; Thiotepa

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Ascites; Carcinoma, Hepatocellular; Cobalt Isotopes; Colchicine; Cyclophosphamide; Dactinomycin; Female; Glycogen; Liver Neoplasms; Mechlorethamine; Mercaptopurine; Mitomycins; Neoplasm Transplantation; Neoplasms, Experimental; Oligosaccharides; Rats; Sarcoma, Yoshida

Topics: Agglutination Tests; Antigens; Blood Group Antigens; Blood Platelets; Erythrocytes; Female; Gallbladder Neoplasms; Hemagglutination Tests; Humans; Liver Neoplasms; Mercaptopurine; Middle Aged; Neoplasm Metastasis; Prednisone

Topics: Adult; Angiotensin II; Animals; Bile Duct Neoplasms; Biliary Tract Diseases; Blood Pressure; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chloramphenicol; Endopeptidases; Erythromycin; Female; Gout; Hepatitis; Humans; Hypertension; Liver; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Liver Neoplasms; Male; Mercaptopurine; Middle Aged; Nephrotic Syndrome; Rats

Topics: Antibodies; Autoantibodies; Blood Group Incompatibility; Humans; Hydrocortisone; Isoantibodies; Liver Neoplasms; Male; Mercaptopurine; Methotrexate; Middle Aged; Neoplasm Metastasis; Thymus Neoplasms

Topics: Adenine; Animals; Carcinoma, Hepatocellular; Guanine; Liver Neoplasms; Mercaptopurine; Neoplasms; Neoplasms, Experimental; Oxides; Rats; Xanthines

Topics: Antineoplastic Agents; Child; Chlorambucil; Cyclophosphamide; Drug Therapy; Ganglioneuroma; Gastrointestinal Diseases; Hodgkin Disease; Leukemia; Leukemia, Myeloid; Liver Neoplasms; Lymphoma; Mechlorethamine; Mercaptopurine; Methotrexate; Neoplasms; Pathology; Radiation Injuries; Stomach; Toxicology; Vinblastine; Vincristine; Wilms Tumor

Topics: Animals; Antineoplastic Agents; Antioxidants; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Leukemia; Leukemia, Experimental; Liver Neoplasms; Mercaptopurine; Neoplasm Proteins; Neoplasms, Experimental; Pharmacology; Proteins; Rats; Research

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azaguanine; Azaserine; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; DNA; DNA, Neoplasm; Fluorouracil; Idoxuridine; Liver Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Nucleosides; Nucleotides; Purines; Research; RNA; RNA, Neoplasm; Sarcoma 180; Thioguanine; Uracil Mustard