azaserine and Neoplasms

A review of the clinical data on azaserine, DON, and azotomycin reveals that these agents have limited but definite antitumor activity. All three drugs are analogs of L-glutamine and contain a diazo group. They have been studied as single agents in a wide variety of human malignancies and have also been included in trials using combination chemotherapy. Most of these studies were performed early in the history of clinical trials and, therefore, the method of reporting results and the evaluation criteria were quite different from those in use today. A renewed interest in these agents has been triggered by the remarkable activity of DON and azotomycin against human tumor lines implanted into nude mice. On the basis of this activity and the clinical data we have compiled, we feel that new clinical trials with these agents are warranted.

Topics: Animals; Antineoplastic Agents; Azaserine; Azo Compounds; Colonic Neoplasms; Diazooxonorleucine; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Transplantation, Heterologous

Topics: Alkylating Agents; Allopurinol; Antibiotics, Antineoplastic; Antimetabolites; Antineoplastic Agents; Asparaginase; Azaserine; Azauridine; Bleomycin; Camptothecin; Carmustine; Cell Division; Cyclophosphamide; Cytarabine; Dactinomycin; Daunorubicin; Doxorubicin; Fluorouracil; Humans; Kinetics; Neoplasms; Nitrogen Mustard Compounds; Procarbazine; Triazines; Vincristine

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Asparaginase; Azaserine; Cell Division; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Disease Models, Animal; Drug Combinations; Humans; Kinetics; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Neoplasms; Prednisone; Remission, Spontaneous; RNA, Neoplasm; Vincristine

Topics: Adult; Aminobutyrates; Animals; Asparaginase; Azaserine; Azo Compounds; Child; Diazooxonorleucine; Drug Combinations; Drug Interactions; Glutamate-Ammonia Ligase; Glutaminase; Glutamine; Humans; Hydroxylysine; Leukemia; Leukemia L1210; Liver; Methionine Sulfoximine; Mice; Neoplasms; Rats; RNA, Transfer

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Azaguanine; Azaserine; Carcinoma, Ehrlich Tumor; DNA; DNA, Neoplasm; Floxuridine; Fluorouracil; Folic Acid; Glutamine; Leukemia L1210; Mercaptopurine; Methotrexate; Mitomycin; Neoplasms; Neoplasms, Experimental; Pharmacology; Purines; Puromycin; Pyrimidines; Research; RNA; RNA, Neoplasm; Thioguanine; Thiouracil

Topics: Alkylating Agents; Antineoplastic Agents; Azaserine; Dactinomycin; DNA; Drug Resistance; Drug Resistance, Microbial; Drug Tolerance; Folic Acid; Humans; Leucine; Metabolism; Mitomycin; Mitomycins; Neoplasms; Neoplasms, Experimental; Pharmacology; Purines; Pyrimidines; RNA; Steroids; Tissue Culture Techniques

Topics: Alkylating Agents; Antimetabolites; Antineoplastic Agents; Azaserine; Colchicine; Drug Resistance; Drug Resistance, Microbial; Folic Acid Antagonists; Guanidines; Humans; Leucine; Metabolism; Neoplasms; Neoplasms, Experimental; Pharmacology; Purines; Pyrimidines; Steroids; Tissue Culture Techniques

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Asparaginase; Azaserine; Cell Division; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Disease Models, Animal; Drug Combinations; Humans; Kinetics; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Neoplasms; Prednisone; Remission, Spontaneous; RNA, Neoplasm; Vincristine

Topics: Anemia; Asparaginase; Azaserine; Breast Neoplasms; Clinical Trials as Topic; Colonic Neoplasms; Drug Combinations; Humans; Hydroxyurea; Leukopenia; Lung Neoplasms; Melanoma; Neoplasms; Rectal Neoplasms; Remission, Spontaneous; Stereoisomerism; Stomach Neoplasms; Thrombocytopenia

Seven out of 31 (23%) human malignant tumor cell lines had no detectable methylthioadenosine phosphorylase activity (less than 0.001 nmol/min per mg of protein), assayed with 5'-chloroadenosine as substrate. The enzyme-deficient cell lines were derived from five leukemias, one melanoma, and one breast cancer. None of 16 cell lines of nonmalignant origin, derived from lymphocytes, fibroblasts, and epithelial cells, lacked the enzyme (range, 0.156-1.447 nmol/min per mg of protein). As detected by autoradiography, intact enzyme-positive cell lines normal immature bone marrow cells, and four specimens of malignant tumor cells incorporated the adenine moiety of 5'-chloroadenosine into nucleic acids; however, no enzyme-deficient cell lines used 5'-chloroadenosine. When both types of cell lines were cultured in a medium containing 0.4 microM methotrexate, 16 microM uridine, and 16 microM thymidine (or 10 microM azaserine alone), no cells grew. If methylthioadenosine was added to the same medium, only enzyme-positive cells increased in number; most enzyme-deficient cells were dead after 3 days. Thus, human malignant tumor cell lines naturally deficient in methylthioadenosine phosphorylase could be selectively killed when de novo purine synthesis was inhibited and methylthioadenosine was the only exogenous source of purines.

Topics: Adenosine; Azaserine; Breast Neoplasms; Cell Line; Cell Survival; Humans; Leukemia; Melanoma; Methotrexate; Neoplasms; Pentosyltransferases; Purine-Nucleoside Phosphorylase; Thionucleosides

Rats have been fed for up to 2 years with either raw soya flour or control diets of heated soya flour or rat chow not containing soya flour. In addition, the rats received weekly injections of either a weak pancreatic carcinogen (azaserine) or control injection of saline. We found that rats fed a diet of raw soya flour and given weekly injections of azaserine developed benign and malignant neoplasms of the pancreas earlier in life and much more frequently than rats given raw soya flour alone, whereas azaserine alone in the dose used in this study did not produce pancreatic cancer. We conclude that raw soya flour sensitizes the pancreas to the action of azaserine.

Topics: Animals; Azaserine; Drug Interactions; Glycine max; Male; Neoplasms; Organ Size; Pancreas; Pancreatic Neoplasms; Rats; Rats, Inbred Strains

There is evidence to suggest that the extra nuclear cell constituents are the part of the cell which contains all the biochemical mechanisms responsible for implementing all cell functions. These functions include control of cell division, growth, response to injury, replacement of effete cells, maintenance of anatomical and spatial cellular relations and specific cellular function and structure. The energy to perform these functions is derived from the aerobic metabolism of glucose. The energy required for nuclear division appears to be wholly or partly derived from the anaerobic metabolism of glucose. Ethyl alcohol interferes with the aerobic metabolic pathways and thus disrupts or diminishes all aerobically activated cell functions. The speed of all activities motivated by aerobic glycolysis can be increased by appropriate electrical stimulations delivered from any of a range of electromagnetic radiation frequencies tested. In addition to the stimulant effect on aerobic metabolic processes, 434 MHz can stimulate the anaerobic glucose metabolism of cancer with consequent stimulation of cancer growth rate. 434 MHz appears to deliver energy to the anaerobic cancer metabolism by causing a resonance phenomenon amongst one or more of the substrates which comprise the first few stages of glycolysis. This phenomenon permits the selective delivery of electromagnetic radiation energy to cancer cells which, if sufficiently intense, causes injury to cancer cells without harm to the normal cells except when the latter are in the phase of anaerobic metabolism which occurs at some stage of the mitotic cycle. Streptokinase, ethanol and glucose analogues increase the lethal effects on cancers undergoing therapy with 434 MHz radiation and observations of such responses suggest a theoretical basis to explain the rare spontaneous remissions of human cancer. Cancer appears to protect its glucose supplies by elevating the blood glucose levels above normal and by some mechanism which reduces the effectiveness of the body's control of its fasting glucose level. The serum fibrinogen level rises when cancer involves the abdominal viscerae, particularly the liver. A raised serum fibrinogen level appears to be a direct indication that the liver must be included in the treatment regime if longer survival is desired. If the level cannot be corrected then death of that individual appears assured.

Topics: Adult; Aged; Azaserine; Cell Division; Cytoplasm; Electromagnetic Phenomena; Ethanol; Female; Fibrinogen; Hexoses; Hot Temperature; Humans; Insulin; Male; Middle Aged; Mitosis; Neoplasms; Streptokinase; Wound Healing

Topics: Animals; Antineoplastic Agents; Azaserine; Azo Compounds; Diazooxonorleucine; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leukemia, Experimental; Mice; Neoplasms

Topics: Animals; Antibiotics, Antineoplastic; Azaserine; Bleomycin; Chlortetracycline; Cycloheximide; Dactinomycin; Dog Diseases; Dogs; Fatty Acids, Unsaturated; Leucomycins; Mitomycins; Neoplasms; Oleandomycin; Olivomycins; Oxytetracycline; Streptozocin

Topics: Adolescent; Adult; Aged; Asparaginase; Azaserine; Burkitt Lymphoma; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Child; Drug Hypersensitivity; Escherichia coli; Female; Humans; Leukemia, Lymphoid; Leukopenia; Lymphoma, Non-Hodgkin; Lymphopenia; Male; Mercaptopurine; Methotrexate; Middle Aged; Neoplasms; Pancreatitis; Thrombocytopenia

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Azaserine; Carcinoma, Squamous Cell; Chelating Agents; Cortisone; Leucine; Mercaptopurine; Mice; Neoplasms; Neoplasms, Experimental; Rats; Research; Sarcoma 180; Streptomycin; Thioguanine; Transplantation

Topics: Adenocarcinoma; Antineoplastic Agents; Aspergillus; Azaserine; Carcinoma, Bronchogenic; Chick Embryo; Glycine; Mercaptopurine; Neoplasms; Neoplasms, Experimental; Puromycin; Pyrroles; Research; Saccharomyces; Tissue Culture Techniques; Triethylenemelamine

Topics: Alkylating Agents; Animals; Antimetabolites; Antineoplastic Agents; Ascites; Azaserine; Carcinoma, Ehrlich Tumor; Cyclophosphamide; Fluorouracil; Leukemia L1210; Leukemia, Experimental; Methotrexate; Mice; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Pharmacology; Research; Thioguanine; Thiotepa; Toxicology

Topics: Adrenal Cortex Hormones; Azaserine; Busulfan; Diagnosis, Differential; Drug Therapy; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Liver; Lymph Nodes; Mercaptopurine; Neoplasms; Pathology; Spleen

Topics: Adenocarcinoma; Alopecia; Antineoplastic Agents; Azaserine; Carcinoma, Squamous Cell; Diarrhea; Drug Eruptions; Drug Therapy; Geriatrics; Guanine; Leukopenia; Nausea; Neoplasms; Stomatitis; Thioguanine; Thrombocytopenia; Toxicology

Topics: Animals; Antineoplastic Agents; Azaserine; Mice; Neoplasms; Pharmacology; Purines; Research; Sarcoma 180

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Autoradiography; Azaserine; Azo Compounds; Carbon Isotopes; Formates; Metabolism; Mice; Neoplasms; Neoplasms, Experimental; Neoplasms, Plasma Cell; Nucleic Acids; Nucleotides; Pharmacology; Purines; Research

Topics: Antineoplastic Agents; Ascites; Azaserine; Ethidium; Humans; Neoplasms; Quinolines; Trypanocidal Agents

Topics: Animals; Ascites; Azaserine; Azoles; Carcinoma, Ehrlich Tumor; Humans; Mercaptopurine; Neoplasms; Neoplasms, Experimental; Pyrimidines; Serine; Thioguanine

Topics: Antineoplastic Agents; Ascites; Azaserine; Neoplasms; Purines

Topics: Animals; Antineoplastic Agents; Azaserine; Carcinoma, Hepatocellular; Liver Neoplasms; Neoplasms; Purines; Sarcoma; Sarcoma 180

Topics: Antineoplastic Agents; Azaserine; beta-Alanine; Humans; Neoplasms

Topics: Antineoplastic Agents; Ascites; Azaserine; Diazooxonorleucine; Leucine; Neoplasms; Serine

Topics: Antineoplastic Agents; Azaserine; Diazooxonorleucine; Leucine; Neoplasms; Serine

Topics: Animals; Antineoplastic Agents; Azaserine; Biochemical Phenomena; Carcinoma, Ehrlich Tumor; Diploidy; Leucine; Neoplasms; RNA

Topics: Antineoplastic Agents; Azaserine; Encephalomyelitis; Lymphocytes; Neoplasms; Plasma Cells; Serine

Topics: Amides; Animals; Antimetabolites; Antineoplastic Agents; Azaserine; Formamides; Leucine; Mice; Neoplasms; Neoplasms, Experimental; Serine

Topics: Animals; Antineoplastic Agents; Azaserine; Carcinoma, Ehrlich Tumor; Deoxyribose; DNA; Neoplasms; Nucleic Acids; Proteins; Serine

Topics: Antineoplastic Agents; Ascites; Azaserine; Biological Transport, Active; Carcinoma; Diazooxonorleucine; Leucine; Neoplasms; Serine

Topics: Animals; Anti-Bacterial Agents; Ascites; Azaserine; Carcinoma, Ehrlich Tumor; Mercaptopurine; Neoplasms; Purines

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Antineoplastic Agents; Azaserine; Dermatologic Agents; Neoplasms; Serine

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azaserine; Dermatologic Agents; Neoplasms; Neoplasms, Experimental; Serine

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azaserine; Carbohydrate Metabolism; Carbohydrates; In Vitro Techniques; Neoplasms; Sarcoma, Experimental; Serine

Topics: Animals; Azaserine; Biological Phenomena; Mice; Neoplasms; Neoplasms, Experimental; Physiological Phenomena; Rats; Serine

Topics: Animals; Azaserine; Mice; Neoplasms; Sarcoma 180; Sarcoma, Experimental; Serine

Topics: Anti-Bacterial Agents; Azaserine; Neoplasms; Serine