mercaptopurine and Colonic-Neoplasms

Topics: Age Factors; Breast Neoplasms; Cell Movement; Clinical Enzyme Tests; Colonic Neoplasms; Cytarabine; Diagnosis, Differential; Doxorubicin; Drug Combinations; Drug Evaluation; Drug Evaluation, Preclinical; Fluorouracil; Humans; Kinetics; Leukemia; Mercaptopurine; Methods; Methotrexate; Models, Chemical; Neoplasms; Prognosis; Sarcoma; Testosterone; Thioguanine

6-Mercaptopurine (6-MP) is a cycle specific antineoplastic agent with a short serum half-life following bolus administration, providing a rationale for continuous infusional administration of the parenteral formulation. 22 patients received 38 courses of 14 day 6-MP infusion. The maximum tolerated dose (MTD) was 35 mg/m2/day (total dose per 14 day cycle 490 mg/m2) with cycles repeated at 28 days. Toxicities included transient hyperbilirubinaemia, leucopenia and thrombocytopenia. 13 evaluable patients with advanced colon cancer resistant to 5-fluorouracil with or without leucovorin received infusional 6-MP at the MTD as part of the phase II study analysis, but no objective responses were observed. Phase II studies in previously untreated patients and longer infusion durations are being evaluated.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Colonic Neoplasms; Humans; Infusions, Intravenous; Mercaptopurine; Middle Aged

Topics: Adenocarcinoma; Anemia; Bone Marrow Diseases; Carcinoma, Squamous Cell; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Colonic Neoplasms; Humans; Leukopenia; Lung Neoplasms; Mercaptopurine; Nausea; Neoplasms; Rectal Neoplasms; Stomach Neoplasms; Thrombocytopenia; Vomiting

Topics: Adolescent; Antibiotics, Antineoplastic; Child; Child, Preschool; Clinical Trials as Topic; Colonic Neoplasms; Cyclophosphamide; Drug Combinations; Evaluation Studies as Topic; Female; Fluorouracil; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Colonic Neoplasms; Colonic Polyps; Cytarabine; Daunorubicin; Doxorubicin; Female; Humans; Idarubicin; Indoles; Kidney Neoplasms; Leukemia, Promyelocytic, Acute; Lung Neoplasms; Male; Mercaptopurine; Methotrexate; Middle Aged; Neoplasms, Second Primary; Pyrroles; Remission Induction; Sunitinib; Time Factors; Tretinoin

We investigated possible mechanisms of the antitumor action of gamma-(9H-purine-6-yl) thiomethyl L-glutamate (6-MPG), a water-soluble derivative of 6-MP. In the double grafted tumor system, BALB/c mice were inoculated intradermally with 10(6) cells of MethA fibrosarcoma at the right inguinal region on day 0 (the primary tumor) and later with 3 x 10(6) cells at the left on day 10 (the secondary tumor). Intraperitoneal administration of 6-MPG at a dose of 100 mg/kg/day from day 3 through 7 completely prevented growth of the secondary tumor. 6-MPG showed no effect on growth of colon 26 adenocarcinoma cells inoculated in place of the secondary MethA cells (antigen specificity). 6-MPG did not inhibit the secondary MethA growth in the BALB/c (nu/nu) mouse. The inhibitory effect of 6-MPG on the secondary tumor growth was diminished by prior treatment of the primed animals with cyclosporin A and anti-Thy antibody. Spleen cells from the tumor-bearing mice treated with 6-MPG showed a tumor-neutralizing activity (Winn assay). Treatment of the spleen cells with anti-CD8 antibody plus complement diminished the tumor-neutralizing effect but that with anti-CD4 antibody plus complement did not, indicating that CD8-positive cells are responsible for potentiation of the tumor immunity. These results suggest that the antitumor effect of 6-MPG against the secondary tumor is elicited by augmenting tumor specific T-cell production.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Animals; Antineoplastic Agents; Cell Division; Colonic Neoplasms; Cyclosporine; Drug Interactions; Fibrosarcoma; Immunosuppressive Agents; Male; Mercaptopurine; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Phenotype; Solubility; Spleen; T-Lymphocytes; Water

In an attempt to improve the effectiveness and bioavailability of 6-mercaptopurine, various kinds of water-soluble analogues, such as 6-S-aminoacyloxymethyl mercaptopurine derivatives (3a--m) and 6-S,9-disubstituted derivates (7a,b and 9a,b), were synthesized. These compounds were evaluated for activity to augment antitumor immunity by using a double grated tumor system. Antitumor activities against solid tumors (sarcoma 180 and colon 26) were also evaluated. Many compounds exhibited potent activities in both test systems. In particular, the aminopropionate derivative (3a) and the L-glutamate derivative (3f) showed significant enhancement of antitumor immunity together with potent antitumor activities.

Topics: Animals; Antineoplastic Agents; Colonic Neoplasms; Fibrosarcoma; Magnetic Resonance Spectroscopy; Mercaptopurine; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Sarcoma; Solubility; Water

Topics: Adult; Azathioprine; Carcinoma; Colonic Neoplasms; Crohn Disease; Humans; Mercaptopurine

Several aromatic seleno lactones have been synthesized and shown to possess significant inhibitory activity against human colon tumor-8r cells in culture at concentrations lower than 1 mM. Although all of the compounds tested were found to be active, 5-hydroxy-3-[(phenylseleno)methyl]hydrocoumarinoctanoate (3d) and 5-hydroxy-3-[(phenylseleno)methyl]hydrocoumarindecanoate (3e) were found to be the most effective in inhibiting cell growth. In situ formation of the corresponding alpha-methylene lactones is postulated to account for the cytotoxic activity in this class of compounds.

Topics: Antineoplastic Agents; Cell Line; Cell Survival; Colonic Neoplasms; Coumarins; Humans; Indicators and Reagents; Magnetic Resonance Spectroscopy; Selenium; Structure-Activity Relationship

We present a case of primary colonic plasmacytoma associated with acute myelogenous leukemia in a 32-year-old man. The neoplastic plasma cells revealed monoclonal lambda-light chains in the cytoplasm using immunoperoxidase techniques. Histochemical and electron microscopic findings are described with a review of the literature.

Topics: Adult; Colon; Colonic Neoplasms; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Plasmacytoma; Prednisolone

Topics: Antineoplastic Agents; Breast Neoplasms; Colonic Neoplasms; Cytarabine; Female; Fluorouracil; Humans; Lung Neoplasms; Mercaptopurine; Methotrexate; Neoplasms; Prognosis; Time Factors

Topics: Antigen-Antibody Reactions; Biomedical Research; Blood Group Antigens; Breast Neoplasms; Colonic Neoplasms; Escherichia coli; Francisella tularensis; gamma-Globulins; Humans; Melanoma; Mercaptopurine; Neoplasms; Pharmacology; Placebos; Skin Tests; Skin Transplantation; Transplantation Immunology