To study the effect of anticancer drugs on the RESFunction, cyclophosphamide and 6-mercaptopurine were intramuscularly injected and evaluated the reticuloendotherial phagocytic activity by the carbon clearence method in rats. Experimental groups were subdivided by the dosage, into the small and large dosage groups, and by the duration of treatment, into the 1, 3, 5 days and 8days (3 days cessation after 5 days treatment) groups. The results obtained were as follow. 1. Cyclophosphamide-treated groups showed the splenic atrophy which was in proportion to duration of treatment. RES phagocytic activities seemed to be slightly increased in large groups, but to be within normal ranges in ranges in small dosage groups, which were normalized in the 8 days groups. 2. 6-Mercaptopurine-treated groups didn't show the hepatic and splenic alterations significantly. RES phagocytic activities were variably changed as in triphagic curve fashion in both small and large dosage subgroups of 1, 3, 5 days treated groups, which were normalized in the 8 days groups.
6-Mercaptopurine* ; Animals ; Atrophy ; Carbon ; Cyclophosphamide* ; Rats* ; Reference Values

Azathioprine is an imidazole derivative of 6-mercaptopurine and is well known for its role in T and B lymphocyte inhibition. These properties have made it useful in the treatment of organ transplant rejection, rheumatoid arthritis, and severe psoriasis. We studied the effects of low-dose azathioprine and acitretin combined therapy in 3 cases of refractory psoriasis. The patients had previously been treated with other systemic and topical therapies. Although they had received partial and temporary benefits, they were not controlled effectively. These patients were subsequently treated with azathioprine and acitretin. Azathioprine treatment (50-100 mg/day) in combination with acitretin (10 mg/day) showed marked improvement of recalcitrant psoriasis. There were no noticeable major side effects associated with this course of treatment. In conclusion, some cases of recalcitrant psoriasis may be effectively and safely controlled using low-dose of azathioprine and acitretin combined therapy.
6-Mercaptopurine ; Acitretin* ; Arthritis, Rheumatoid ; Azathioprine* ; Humans ; Lymphocytes ; Psoriasis* ; Transplants

BACKGROUND/AIMS: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD). METHODS: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing. RESULTS: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined. CONCLUSIONS: Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.
6-Mercaptopurine ; Asian Continental Ancestry Group* ; Azathioprine ; Clinical Coding ; Hair ; Humans ; Inflammatory Bowel Diseases* ; Leukopenia

Although pancreatitis is known as a common complication during the treatment of acute lymphoblastic leukemia, acute pancreatitis that's induced by 6-mercaptopurine or 6-thioguanine is very uncommon. We experienced the case of an 11-year-old boy with consecutive acute pancreatitis, and this was induced by 6-mercaptopurine and 6-thioguanine during maintenance chemotherapy of childhood acute lymphoblastic leukemia. We report here on this along with a review of the pertinent literature.
6-Mercaptopurine ; Child ; Humans ; Maintenance Chemotherapy ; Pancreatitis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Thioguanine

PURPOSE: We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant). Clinical and laboratory features during the first year of maintenance therapy were investigated. RESULTS: A total of 182 patients were included in the final analysis. There were five (2.7%), 46 (25.3%), and 131 (72.0%) patients in low-, intermediate-, and normal-activity groups, respectively. The lowest 6-mercaptopurine (6-MP) dose (mg/m2/day) was administered to the low-activity group (low-activity group 7.5 vs. intermediate-activity group 24.4 vs. normalactivity group 31.1, p < 0.01) from three months to a year after beginning maintenance therapy. The low-activity group experienced the longest duration of therapy interruption during the first year (low-activity group 169 days vs. intermediate-activity group 30 days vs. normal-activity group 16 days, p < 0.01). They also showed the lowest blood cell counts and had a longer duration of leukopenia (low-activity group 131 days vs. intermediate-activity group 92 days vs. normal-activity group 59 days, p < 0.01). 6-TGN level and its ratio to 6-MP dose were lowest in the low-activity group. CONCLUSION: NUDT15 variants cause hematopoietic toxicity with low 6-TGN levels. NUDT15 genotyping should be conducted before administering thiopurine, and dose adjustments require caution regardless of 6-TGN levels.
6-Mercaptopurine ; Blood Cell Count ; Child* ; Humans ; Leukemia ; Leukopenia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Thioguanine

A pediatric patient with combined primary thrombocytopenic purpura and acquired hemolytic anemia (Evans syndrome), whose condition did not respond to treatment with prednisolone, has enjoyed long-term remission following a period of treatment with 6-Mercaptopurine.
6-Mercaptopurine/therapeutic use* ; Anemia, Hemolytic, Autoimmune/drug therapy* ; Child ; Human ; Male ; Purpura, Thrombocytopenic/drug therapy* ; Syndrome

We report here a case of drug-induced acute pancreatitis proved by elimination and single, low dose challenge test in a child with Crohn disease. A 14-year-old boy with moderate/severe Crohn disease was admitted due to high fever and severe epigastric pain during administration of mesalazine and azathioprine. Blood test and abdominal ultrasonography revealed acute pancreatitis. After discontinuance of the medication and supportive care, the symptoms and laboratory findings improved. A single, low dose challenge test was done to confirm the relationship of the adverse drug reaction and acute pancreatitis, and to discriminate the responsible drug. Azathioprine and 6-mercaptopurine showed positive responses, and mesalazine showed a negative response. We introduce the method of single, low dose challenge test and its interpretation for drug-induced pancreatitis.
6-Mercaptopurine ; Azathioprine ; Child ; Crohn Disease ; Drug Toxicity ; Fever ; Hematologic Tests ; Humans ; Inflammatory Bowel Diseases ; Mesalamine ; Pancreatitis

Etoposide is a semi-synthetic podophyllotoxin that binds to microtubular proteins to inhibit cell division. It has been used extensively in the treatment of both solid and hematologic malignancies. Chemotherapy-induced acral erythema is a distinctive syndrome of painful, symmetric, well-defined swelling and erythema of the palms and soles seen in patients receiving high-dose chemotherapy. It occurs most commonly with fluorouracil, doxorubicin, and especially cytosine arabinoside. Although etoposide, mercaptopurine and methotrexate have also been implicated. Here we report a case of acral erythema induced by etoposide in a 15-year-old child with neuroblastoma.
6-Mercaptopurine ; Adolescent ; Cell Division ; Child ; Cytarabine ; Doxorubicin ; Erythema ; Etoposide ; Fluorouracil ; Hand-Foot Syndrome ; Hematologic Neoplasms ; Humans ; Methotrexate ; Podophyllotoxin ; Proteins

Immunosuppressive agents and biological agents are widely used for therapy in patients with inflammatory bowel disease (IBD). However, these therapies may be associated with an increased risk of malignancy. There is evidence that exposure of the therapeutic agents such as thiopurine and anti-tumor necrosis factor for IBD is associated with an increased risk of lymphoproliferative disorders, skin cancers, or uterine cervical cancers. This article reviews the malignancies associated with the use of immunosuppressive agents and biological agents in IBD.
6-Mercaptopurine ; Azathioprine ; Biological Factors* ; Humans ; Immunologic Factors* ; Immunosuppressive Agents ; Inflammatory Bowel Diseases* ; Lymphoproliferative Disorders ; Necrosis ; Skin Neoplasms ; Tumor Necrosis Factor-alpha ; Uterine Cervical Neoplasms

PURPOSE: Taxol (Paclitaxel) is a new generation of chemotherapeutic drug proven to be effective in the treatment of many cancers. In this study, to further demonstrate the differential effect of the tumor suppressor gene, p53, on the Taxol-induced apoptosis in osteogenic sarcoma cell lines, we used p53-defected SaOS2 cells and wild type p53-expressed U2OS cells. MATERIALS AND METHODS: The cell viability was measured by the XTT assay. To examine whether the differential expressions of p53, in U2OS and SaOS2 cells, were associated with Taxol-induced apoptosis, DNA fragmentation assays were performed on both cytosolic and genomic DNA. Since the cleavage of poly (ADP-ribose) polymerase (PARP) is primarily responsible for apoptosis, the cleavage of PARP, and the expression of cyclin B1, polo-like kinase, Bax, Bcl-xL, Bcl-2 in U2OS and SaOS2 cells were compared by Western blot analyses. RESULTS: The cell viability of the p53-defected SaOS2 cells was markedly decreased with Taxol treatment. Whereas, the cell viabilities due to 6-mercaptopurine and adriamycin were no different between the U2OS and SaOS2 cells. Treatment with Taxol induced a ladder- like pattern of DNA fragments, which is a biochemical hallmark of apoptosis, consisting of multiples of approximately 180-200 base pairs, in a dose-dependent manner in the SaOS2 cells, but insignificantly with the U2OS cells. When the cells were treated with Taxol, the 89 kDa cleavage product of PARP clearly appeared as a function of time in the SaOS2 cells, but not in the U2OS cells. The Taxol-induced apoptosis in p53 defected-osteogenic sarcoma cells was associated with the PARP cleavage as a result of the increased activity of caspase 3, and the high expressions of cyclin B1 and PLK. Bax, as a proapoptotic factor, was increased in the SaOS2cells, but the Bcl-xL and Bcl-2 were decreased when the cells were exposed to 10miceoM Taxol. CONCLUSION: From these results, it was concluded that p53-defected SaOS2 cells are much more sensitive to Taxol-induced apoptosis than p53-expressed U2OS cells.
6-Mercaptopurine ; Apoptosis* ; Base Pairing ; Blotting, Western ; Caspase 3 ; Cell Line ; Cell Survival ; Cyclin B1 ; Cytosol ; DNA ; DNA Fragmentation ; Doxorubicin ; Genes, Tumor Suppressor ; Osteosarcoma* ; Paclitaxel ; Phosphotransferases ; Sarcoma