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Morris hepatoma 7794A was found to have its c-myc gene amplified 5- to 10-fold. The over-expression of c-myc was observed in all three hepatomas studied (Morris hepatomas 5123D, 7136A and 7794A), although in the first two instances the c-myc genes were not amplified. Over-expression or deregulation of c-myc seems to be a general phenomenon associated with hepatoma.

The organotropic effect of orally administered N-bis(2-hydroxypropyl)nitrosamine (DHPN) in male F344 rats was studied with respect to total dosage and length of observation period. DHPN was given at 5 dosages, a single intragastric intubation of 800 mg/kg body weight, or administration as a 0.2% solution in the drinking water for 4, 7, 14 or 21 days. Animals were killed at weeks 32, 40 and 48. Tumors were induced in the lung, thyroid, kidney and urinary bladder. High tumor incidence was demonstrated in the lung and thyroid. Dose-related increases in overall tumor incidences in these 4 organs were clearly shown but time-related increases at the 3 sacrifice time points were not clear. Histologically, the tumors were adenoma and adenocarcinoma of the lung and thyroid, renal cell tumor, nephroblastoma and transitional cell tumor of the kidney, and transitional cell papilloma of the urinary bladder.

The distribution of blood group ABH antigens, their precursor I(Ma) antigen, Lewis a antigen and monoclonal antibody-defined tumor-associated antigen CA 19-9 in gastric cancers and their surrounding non-neoplastic mucosa was studied by using immunohistochemical methods. ABH antigens were localized in the foveolar epithelium except for a few cases presumed to be non-secretors, but ABH antigens were lost focally from metaplastic mucosa. In contrast, Lewis a and I(Ma) antigens were present in the foveolar epithelium of non-secretors and metaplastic mucosa where ABH antigens were not detected. Gastric cancers also showed focal loss of ABH antigens and gain of Lewis a and I(Ma) antigens, and the cancer cells showed marked heterogeneity in antigen expression compared with non-neoplastic mucosa. Expression of incompatible blood group antigen (A-like antigen) reactive with monoclonal anti-A antibody was also detected in cancer cells of blood group O and B cases. CA 19-9 (sialylated-Lewis a) was detected in 62% of gastric cancers and in the restricted areas of gastric mucosa where Lewis a was positive.

Male Syrian golden hamsters were given 1.0% 2-tert- or 3-tert-butylated hydroxyanisole (BHA) or crude BHA for 1 to 4 weeks. The incidence of severe hyperplasia induced in the forestomach was high in the hamsters given 3-tert-BHA or crude BHA for 2 weeks or more, but was almost at the control level in those given 2-tert-BHA. Thus, the 3-tert isomer would appear to be responsible for the tumorigenicity of crude BHA.

Vincristine (VCR) combined with interferon (IFN)-beta suppressed H.Ep #2 cell proliferation more than additively, whereas 6-mercaptopurine combined with IFN-beta suppressed it less than additively. Factors associated with the more-than-additive effect were examined. The enhanced antiproliferation was achieved in HeLa cells as well as H.Ep #2 cells but not in Daudi or M-14 cells, indicating cell dependency of the enhancement. This enhancement was not dependent on the IFN species, including IFN-beta, IFN-alpha (leukocyte), and IFN-alpha (lymphoblastoid), although the cells were variably sensitive to these IFN species. In contrast, the enhance antiproliferation was critically dependent on the species of antineoplastic agents, and was selective to VCR and adriamycin among those tested under the present experimental conditions. The sequential exposure of H.Ep #2 cells to IFN and VCR induced the enhancement but exposure to VCR followed by IFN did not, suggesting that IFN-induced cell modification made the cells more sensitive to VCR. Either IFN or VCR was successfully replaced by colchicine, an antimicrotubule agent, but not by cytochalasin D, an antimicrofilament agent, suggesting the involvement of microtubule modification in the enhanced antiproliferation observed with IFN and VCR.

A monoclonal antibody, ST-4-39, was obtained by means of a unique immunization procedure using a gastric cancer xenograft as an immunogen. ST-4-39 reacted immunohistochemically with various cancers and a limited number of normal tissues. The antigen reactive with ST-4-39 was detected in sera of cancer patients, and possessed a molecular weight of greater than or equal to 1 X 10(6). The antigenic determinant was a sialyl-sugar residue different from sialyl-Lewis a recognized by NS 19-9.

A rabbit lymphoid cell line transformed by human T-cell leukemia virus (HTLV) was inoculated into the peritoneal cavity of six newborn hamsters treated by antilymphocyte serum. All of them developed lethal tumors two weeks after implantation. The tumor cells were chromosomally of rabbit type, and harbored HTLV and HTLV antigens.

Sodium chloride, saccharin sodium, phenobarbital sodium and aspirin were tested for tumor-promoting activity in the glandular stomach of rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) coupled with administration of a high salt diet. Male outbred Wistar rats were given MNNG in the drinking water (100 mg/liter) for 8 weeks, and during this period they were fed on diet supplemented with 10% sodium chloride. Thereafter, they were divided into 5 groups and fed on the basal diet or one of various diets supplemented with 10% sodium chloride, 5% saccharin, 0.05% phenobarbital or 1% aspirin until the end of the experiment. All animals were killed at the 40th experimental week for necropsy and histological examination. The incidence of adenocarcinoma was increased in the group given sodium chloride following initiation by MNNG and sodium chloride as compared with the group given MNNG and sodium chloride initiation only, but not significantly. However, the incidence of preneoplastic hyperplasia was significantly increased in this group. Saccharin also enhanced the development of adenocarcinomas of the glandular stomach. The results indicated that dietary administration of sodium chloride or saccharin after MNNG tends to promote tumor development. Phenobarbital or aspirin did not enhance tumor development, aspirin in fact rather showing a tendency to decrease the tumor incidence.

A human cancer cell line (ZK-1) has been established from a well-differentiated squamous cell carcinoma of the tongue. The cytokeratin polypeptides pattern of ZK-1 cells consists of four major polypeptides with molecular weights between 46 and 58 kilodaltons (kd). Antibodies raised against the purified 58 kd cytokeratin filament from cultured ZK-1 cells were shown to be specific by one- and two-dimensional polyacrylamide gel electrophoresis, immunofluorescence, and immunoelectron microscopy. Immunoprecipitation studies showed that the antibody reacted mainly with the 58 kd cytokeratin. The distribution of the 58 kd cytokeratin in both sparse and confluent cultures was analyzed by the indirect immunofluorescence technique. In both cases, it appeared that fibrillar arrays extended throughout the cytoplasm running over the nucleus and toward cell-to-cell boundaries. Thick bundles of filaments were seen in confluent cultures, especially in large and flattened keratinized cells. Characteristically, reactions were also seen in the intercellular boundaries, appearing as "dots." Electron microscopy using immunoperoxidase techniques indicated that the 58 kd cytokeratin was localized in tonofilaments, tonofilaments attached to desmosomes, desmosomal plaques and membrane-coating granules.

beta-Glucuronidase from human lung neoplasms of various histological types and from uninvolved tissues was studied. A significant elevation of beta-glucuronidase activity was observed in adenocarcinoma and squamous cell carcinoma of the lung as compared with the corresponding uninvolved tissues (P less than 0.01). Saccharo-1,4-lactone, a strong inhibitor of the enzyme, exhibited a substantially greater stabilizing effect on the adenocarcinoma enzyme than on the other enzymes. However, removal of the carbohydrate moiety from the adenocarcinoma enzyme by treatment with endo-beta-N-acetylglucosamidase H (endoglycosidase H) brought about a decrease in the stabilizing effect. Tumor beta-glucuronidase showed considerable negative charge heterogeneity in the pI range from 4.2 to 6.2 in isoelectric focusing on polyacrylamide gel. Upon treatment with exogenous alkaline phosphatase or endoglycosidase H, the heterogenous variant forms of the tumor enzyme appeared to partly or completely lose their negative charge and to be converted into forms similar to those of the normal lung enzyme. These data strongly suggest that the variants are highly phosphorylated on the oligosaccharide chains of the enzyme. An experiment on the labelling of beta-glucuronidase with [32P]-phosphoric acid provided further evidence that the acidic variants found in lung cancers are extensively phosphorylated forms of the enzyme.