allopurinol and Carcinoma--Squamous-Cell

Topics: Allopurinol; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Squamous Cell; Colonic Neoplasms; Cyclophosphamide; Dactinomycin; Diethylstilbestrol

Twenty-three patients with advanced inoperable squamous cell carcinoma of the esophagus were treated with aminothiadiazole (A-TD) 125 mg/m2 weekly plus allopurinol daily in a phase II cooperative group trial. No patients responded to treatment; 17 patients progressed, three showed stable disease, and three were unevaluable. There were no life-threatening hematologic or metabolic toxicities. The median survival from study entry was 5 months. A-TD is not active in advanced squamous cell carcinoma of the esophagus.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Evaluation; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Survival Rate; Thiadiazoles

Clinical and epidemiological findings have provided evidence supporting a role of free radicals in the etiology of cancer. Scavengers and inhibitors of free radical processes have been demonstrated to prevent or delay the neoplastic process.. Adenosine deaminase, xanthine oxidase, superoxide dismutase, and glutathione peroxidase activities and malondialdehyde levels were measured in the sera of 35 patients with head and neck cancers and were compared to those of healthy control subjects.. Serum adenosine deaminase activity was found to be significantly increased in the patient group (p<0.001). Compared to the control group, glutathione peroxidase and xanthine oxidase activities and malondialdehyde levels were slightly higher and serum superoxide dismutase activity was slightly lower in the patient group, with none reaching statistical significance.. The results indicate that serum adenosine deaminase activity may be helpful in the diagnosis and follow-up of head and neck cancers. Further studies with a larger cohort of patients are needed to clarify the exact mechanism of adenosine deaminase elevation.

Topics: Adenosine Deaminase; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Female; Glutathione Peroxidase; Head and Neck Neoplasms; Humans; Male; Malondialdehyde; Middle Aged; Predictive Value of Tests; Superoxide Dismutase; Xanthine Oxidase

The antitumor effect of oxygen radicals produced by hypoxanthine and xanthine oxidase reaction was studied in an experimental rabbit model. VX2 carcinomas were transplanted into rabbit hind legs. Hypoxanthine was administered continuously through the ear vein, while xanthine oxidase was administered simultaneously through the femoral artery. As a result, hypoxanthine and xanthine oxidase reacted only in the hind leg, and superoxide was produced in that area. The volume of the VX2 carcinoma was measured immediately prior to treatment and 7 days later. As an index of lipid peroxidation, thiobarbituric acid-reactive substances in the tumor tissue were measured 60 min following infusion of hypoxanthine and xanthine oxidase. Tumor growth was suppressed significantly by the hypoxanthine-xanthine oxidase reaction, and thiobarbituric acid-reactive substances in the tumor tissue infused with hypoxanthine and xanthine oxidase were significantly increased. In addition, the antitumor effect of the hypoxanthine and xanthine oxidase reaction was significantly inhibited by the administration of superoxide dismutase and catalase. Pathological examination showed that oxygen radicals produced by hypoxanthine and xanthine oxidase reaction were selectively more destructive for VX2 carcinoma tissue than muscle tissue surrounding the tumor region. These results suggest that oxygen radicals produced by hypoxanthine and xanthine oxidase reaction produce an anticancer effect and that the VX2 carcinoma used in this study was more sensitive to oxygen radicals than normal muscle tissue.

Topics: Animals; Carcinoma, Squamous Cell; Catalase; Cattle; Free Radical Scavengers; Humans; Hypoxanthine; Hypoxanthines; Male; Muscles; Papilloma; Rabbits; Recombinant Proteins; Superoxide Dismutase; Superoxides; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase

Many anticancer drugs have been shown to produce superoxide anion (O2.-) and seem to involve O2.- in their mode of action. Ionizing radiation provokes the decomposition reaction of water, producing a variety of reactive oxygen species, including O2.-. The finding that cancer cells are generally low in SOD activity may offer a theoretical base for radiation therapy and chemotherapy. The purpose of this study was to examine the protective effect of intracellular SOD against cytotoxicity induced by O2.- or radiation and to investigate whether exogenous SOD can protect cells from O2.-(-) and radiation-induced cytotoxicity. For this purpose, xanthine (X) and xanthine oxidase (XOD) were employed as an O2.- (-)generating system, and a linear accelerator was used for ionizing radiation. Cytotoxicity against monolayer cancer cell lines and leukemic cell lines was estimated by measuring the release of lactate dehydrogenase from these cells. The results revealed that the resistibilites to X- and XOD-generated O2.- and radiation correlated with intracellular Cu. Zn-SOD levels and that exogenous SOD could only slightly reduce X- and XOD-induced cytotoxicity while having no influence on radiation-induced cytotoxicity. Thus, intracellular SOD may play a central role in protecting cancer cells against reactive oxygen species generated by anticancer drugs and radiation.

Topics: Carcinoma, Squamous Cell; Cell Line; Cell Survival; Dose-Response Relationship, Radiation; Humans; L-Lactate Dehydrogenase; Leukemia; Mouth Neoplasms; Superoxide Dismutase; Superoxides; Tumor Cells, Cultured; Xanthine; Xanthine Oxidase; Xanthines

We determined activities of adenosine deaminase (ADA), 5' nucleotidase (5NT), xanthine oxidase (XO), superoxide dismutase (Cu-Zn SOD), and catalase (CAT) enzymes in 15 human laryngeal tissues with well-differentiated squamous cell carcinomas, in 15 corresponding tumor-free adjacent tissues and in 7 normal laryngeal tissues. We found lower ADA and 5NT and higher XO, Cu-Zn SOD, and CAT activities in cancerous tissues than those in corresponding noncancerous ones. In the correlation analysis, we established one positive intercorrelation, which was between ADA activities of tumor tissues and noncancerous adjacent tissues. We also found some significant intracorrelations between enzyme activities of the tissues, all of which were positive in cancerous ones.

Topics: 5'-Nucleotidase; Adenosine Deaminase; Adult; Antioxidants; Carcinoma, Squamous Cell; Catalase; DNA; DNA, Neoplasm; Free Radicals; Humans; Laryngeal Neoplasms; Larynx; Male; Middle Aged; Superoxide Dismutase; Xanthine Oxidase

The activities of several enzymes involved in reactive oxygen production and detoxification were quantified in murine skin during the ontogeny of chemically induced skin cancer. Relative to solvent-treated controls, the specific activities of epidermal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were reduced approximately 45, approximately 60 and approximately 24% respectively, 24 h after the fourth or tenth topical application of 1 microgram of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal skin of SENCAR mice. The specific activity of epidermal xanthine oxidase (XO) increased approximately 350% during the same period. SOD and CAT specific activities in papillomas and carcinomas generated in an initiation-promotion protocol were approximately 15 and approximately 40% respectively of the activities measured in age-matched, non-treated mice. CAT and SOD activities were also significantly suppressed in the skin adjacent to the papillomas for several weeks following the cessation of TPA promotion, but eventually recovered to the levels measured in age-matched controls. XO specific activities in papillomas and squamous cell carcinomas (SCC) were approximately 85-350% greater than the activities determined in skin adjacent to the tumors. The increases in XO and the decreases in SOD and CAT activities measured in the tumors were independent of continued treatment with TPA, and thus characteristic of the tumor phenotype. GPX activities in papillomas were comparable to normal, untreated skin, but reduced approximately 22-41% in SCC. Collectively, these studies demonstrate that TPA orchestrates changes in the activities of several enzymes involved in reactive oxygen metabolism that are characteristic of the papilloma and SCC phenotype.

Topics: Administration, Topical; Animals; Carcinoma, Squamous Cell; Catalase; Female; Glutathione Peroxidase; Mice; Mice, Inbred Strains; Oxygen; Papilloma; Phenotype; Skin; Skin Neoplasms; Superoxide Dismutase; Tetradecanoylphorbol Acetate; Xanthine Dehydrogenase; Xanthine Oxidase

Topics: Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Evaluation; Esophageal Neoplasms; Fluorouracil; Humans; Middle Aged

The combination of cisplatin (100 mg/m2) and 5-fluorouracil (5-FU) by continuous infusion (1 g/m2/day for 5 days) has been reported to produce a high response rate as neoadjuvant therapy for advanced squamous cell head and neck cancer. We sought to improve the response rate by increasing the dose of 5-FU to 1.5 g/m2/day and 2.0 g/m2/day with allopurinol modulation to reduce toxicity. The overall response rate in the 30 patients who received three courses of chemotherapy was 100% with a 50% complete response (CR) rate. A 50% CR rate was observed in patients with T3 (six of 12) and N3 (four of eight) disease. Six patients (four with CR) did not complete subsequent treatment as planned. Seven of 11 (63.6%) chemotherapy complete responders and three of 12 (25%) partial responders (one lost to follow-up) who received all planned treatment are free of disease. The major toxicity encountered was stomatitis (severe in 32%) followed by leukopenia. The maximum tolerated dose of 5-FU in this combination with allopurinol protection was 1.5 g/m2/day. Cisplatin plus high dose 5-FU does not appear to be associated with a higher CR rate than that reported with conventional doses of 5-FU and is more toxic.

Topics: Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Evaluation; Fluorouracil; Head and Neck Neoplasms; Humans; Middle Aged; Neoplasm Staging

Forty patients with advanced squamous cell carcinoma of the esophagus were treated with a combination of cisplatin, 5-FU (by continuous 5-day infusion), and allopurinol; 37 are evaluable for response. Thirteen remissions (35%) were obtained, including three complete and ten partial, with a median duration of 9 months. After chemotherapy, seven responding patients underwent a surgical procedure, which was radical in four. The most frequent side effects were nausea and vomiting. This regimen is effective and can be included in a multimodality approach.

Topics: Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Evaluation; Esophageal Neoplasms; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Palliative Care

Allopurinol has been shown to ameliorate the myelotoxicity of 5-fluorouracil (5-FU) given as an infusion. To study the potential effectiveness of allopurinol in modifying the toxicity of 5-FU given as a bolus, 8 adult patients with metastatic malignancies were given 11 courses of bolus 5-FU with allopurinol. Allopurinol was administered at a dose of 900 mg/day orally beginning a week prior to the 5-FU therapy and continued a week after the last dose of 5-FU was administered. Three patients received a total of 5 courses of 600 mg/m2 of 5-FU via bolus injection for 4 consecutive days every 28 days. Six patients were given 6 courses of 800 mg/m2 of 5-FU via bolus injection in the same schedule. Gastrointestinal toxicity was mild and no significant neurotoxicity was documented. However, severe myelosuppression occurred at the 800 mg/m2 dosage which led to marked leukopenia in 5 of the 6 patient courses and thrombocytopenia in 1. Gram-negative sepsis developed in 3 of the leukopenic patients with 2 resultant deaths. Allopurinol does not appear to allow clinically significant dose escalation of bolus 5-FU given on this schedule.

Topics: Adenocarcinoma; Adult; Allopurinol; Carcinoma, Squamous Cell; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Gallbladder Neoplasms; Gastrointestinal Diseases; Hematologic Diseases; Humans; Lung Neoplasms; Neoplasm Metastasis; Rectal Neoplasms

Topics: Adolescent; Adult; Allopurinol; Antineoplastic Agents; Azathioprine; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cyclophosphamide; Facial Neoplasms; Female; Hand; Humans; Immunosuppressive Agents; Keratoacanthoma; Keratosis; Kidney Transplantation; Leg; Lip Neoplasms; Male; Middle Aged; Nose Neoplasms; Postoperative Complications; Skin Neoplasms; Transplantation, Homologous

Topics: Allopurinol; Carcinoma, Squamous Cell; Cell Line; Humans; Mass Spectrometry; Optical Rotation; Spectrum Analysis; Sulfhydryl Compounds; Ultraviolet Rays