tretinoin and 4-(carboethoxyphenyl)retinamide

Since 1984, mass screening for cancer has been carried out in the realgar and tin mines, high incidence areas of lung cancer. Certain epidemical characteristics were found in precancerous lesion of lung cancer. Chemopreventive treatment were carried out by giving R1 [N-(p-ethoxycarbophenyl) retinamide] & R2 [N-(p-carboxyphenyl) retinamide]-retinoids synthesized by the Institute of Materia Medica, Chinese Academy of Medical Sciences. A prospective randomized double-blind control trial on the subjects with moderate or severe atypical hyperplasia cells in the sputum was conducted. Thirty-seven patients were treated by R1 (50 mg/d, p. o; total dose: 18.25 g/yr/case). In view of the absorption of R2 being better than R1, R2 (20 mg/d, p. o; total dose: 3.6/g/6mos/case) was given to 52 patients instead of R1. Patients in the control group were treated by riboflavin (50 mg/d, p. o.). The results showed that general status of the patients was improved. IgA and IgM in the serum were increased and the arsenic skin lesions were relieved after the treatment with R1 and R2. As compared with the control group, the incidence of lung cancer was 1:4 and mean degree of hyperplasia in the sputum dropped. It is suggested that these drugs are safe and effective in the chemoprevention of lung cancer. It is worth for further study.

Topics: Antineoplastic Agents; Arsenic; Clinical Trials as Topic; Double-Blind Method; Humans; Lung Neoplasms; Mining; Occupational Diseases; Precancerous Conditions; Random Allocation; Retinoids; Tin; Tretinoin

Two new retinoic acid esters and retinamides synthesized in China, N-(4-ethoxycarbophenyl)retinamide (RI) and N-(4-carboxyphenyl)retinamide (RII), significantly inhibited carcinogenesis induced in the epithelium of the forestomach of mice by N-nitrososarcosine ethyl ester. RI also markedly inhibited carcinogenesis induced in the epithelium of the oesophagus and forestomach in rats by this ester. No sign of hypervitaminosis was noticed with doses as high as six times the therapeutic dose. RI also inhibited precancerous and cancerous lesions in the nasal cavity and nasopharynx and oesophagus of rats induced by dinitrosopiperazine. In a malignant oesophageal epithelial cell line from rats, RE25-3, established in our laboratory, RI and RII inhibited mitosis, proliferation rate, chromosomal aberrations and incorporation of 3H-thymidine into DNA. The ability to form colonies on agar plates was also inhibited by these two compounds.

Topics: Animals; Antineoplastic Agents; Carcinogens; Esophageal Neoplasms; Female; Mice; Nitrosamines; Rats; Rats, Inbred Strains; Stomach Neoplasms; Tretinoin; Tumor Cells, Cultured

Topics: Animals; Antineoplastic Agents; Nasal Cavity; Nasopharyngeal Neoplasms; Nitrosamines; Nose Neoplasms; Precancerous Conditions; Rats; Rats, Inbred Strains; Tretinoin

Topics: Animals; Antigen-Presenting Cells; Diterpenes; Female; Male; Mice; Retinyl Esters; T-Lymphocytes, Cytotoxic; Tretinoin; Vitamin A

Carcinogenic and promoting effects of RRME as isolated from the pickled vegetables in Linxian County, a high incidence area of esophageal cancer, were studied in mice and rats. RRME alone did not cause tumor in the forestomach of mice and esophagus of rats. When the mice were intubated with a single dose of nitroso-sarcosine-ethylester (NSEE), the incidence of the forestomach carcinoma was only 9.5%. However, when the mice were given gastric doses of RRME after one single dose of NSEE, the incidence was increased to 41.0%. In rats, the tumor incidence was 5.3% in nitroso-methylbenzylamine (NMBzA) group, while in NMBzA kRME group, it was 20.7%. In rats intubated with NSEE for 7 times, no carcinoma appeared in esophageal epithelium; while followed by gastric doses of RRME, the incidence of esophagus carcinoma increased up to 63.2%. The experimental results show that RRME has distinct promoting effect on the process of cocarcinogenesis initiated by NSEE and NMBzA in the forestomach of mice and esophagus of rats, but without carcinogenic effect itself. Retinamide (RI) and massive dose of vitamin C showed an obviously inhibitory effect on promoting action of RRME in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Dimethylnitrosamine; Esophageal Neoplasms; Female; Mice; Nitroso Compounds; Rats; Rats, Inbred Strains; Stomach Neoplasms; Tretinoin

Topics: Antineoplastic Agents; Cell Differentiation; Cell Line; Dimethyl Sulfoxide; Humans; Leukemia, Myeloid, Acute; Macrophage-1 Antigen; Nitroblue Tetrazolium; Receptors, Complement; Tretinoin

Topics: Animals; Antineoplastic Agents; Dogs; Etretinate; Isotretinoin; Male; Mice; Rats; Tretinoin; Vitamin A