Male Wistar rats that had received a low dose of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium taurocholate showed a significantly higher incidence of hyperplastic and neoplastic lesions in the stomach mucosa than did the MNNG-treated controls. The result suggested an enhancing effect of taurocholate in stomach tumorigenesis.

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B-cell lines which showed predominantly surface IgA κ immunoglobulins were established from each of seven adult T-cell leukemia (ATL) patients. ATL virus proviral DNA was found in five of the lines. Though the chromosomal analysis of the B-cell lines yielded normal results, fresh leukemic T-cells showed chromosome abnormalities.

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A new human monocytoid leukemic cell line, CTV-1, was established from a patient with relapsed acute monoblastic leukemia. The characteristics of this cell line were evaluated by morphologic and cytochemical analyses, electron-microscopy, chromosome study, surface marker analysis and a study of differentiation potential with tumor-promoting agents.

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The effect of dietary carbohydrate (CHO) level on liver carcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) was investigated in male Wistar rats. In the first experiment, three groups of 30 rats were maintained on liquid diets, which differed only in the level of CHO (sucrose); high-CHO (14.04g/day), medium-CHO (9.72g/day) and low-CHO (3.64g/day). Half of the animals from each group were given 3'-Me-ADB added to their diet at the level of 10mg/day/rat for 20 weeks, the remainder being maintained as carcinogen-free controls. Final body and liver weights of control rats decreased with decreasing dietary level of CHO, while carcinogen treatment increased the liver/body weight ratio with decreasing CHO level. Quantitative analysis showed that the number and area of liver tumors per unit area of liver sections increased with decreasing dietary sucrose level. Hepatocellular carcinomas were only observed in rats placed on the low-CHO diet (4 out of 15 rats). In the second experiment, where rats were given 3'-Me-DAB in a semisynthetic powder diet for 16 weeks, the number and area of γ-glutamyltranspeptidase-positive foci were significantly higher in the low-CHO diet group, with decreasing values being associated with increase in sucrose level in the diet. Thus, the present experiments clearly showed that lowered CHO intake enhanced, whereas high intake reduced, 3'-Me-DAB liver carcinogenesis in rats.

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The effects on primary human skin fibroblasts of the structurally unrelated tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin B were compared with those of epidermal growth factor (EGF) and the non-promoting derivative 4-O-methyl TPA (4-O-MeTPA) by means of two-dimensional gel electrophoresis. Both TPA and teleocidin B caused a marked increase in the synthesis of two polypeptides with molecular weights of 44 kilodaltons (p44) and 55 kilodaltons (p55). P55 was complexed in cell lysates by antiactin antibody and was shown to be a component of the cytoskeleton. P44 migrated very near to actin, but was shown not to be a variant form of actin. No such specific increase in polypeptide synthesis was observed following treatment with either EGF or 4-O-MeTPA, suggesting that the increase in synthesis of p44 and p55 is specific to TPA and teleocidin, both agents with strong promoting activities.

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Hormonal regulation of plasminogen activator in rat mammary tumor induced by 7, 12-dimethylbenz[a]anthracene (DMBA) was studied both in vivo and in vitro. Plasminogen activator activity in DMBA-induced tumor (DMBA-tumor) was markedly decreased by ovariectomy, and recovered in a dose-dependent fashion upon estradiol administration, reaching a maximal level at 12hr. This estrogen-stimulated production of the enzyme was prevented by actinomycin D, cycloheximide, and tamoxifen, indicating that in DMBA-tumor, estrogen might regulate de novo synthesis of plasminogen activator at a transcriptional level via an estrogen receptor system. Furthermore, DMBA-tumor cells in primary culture displayed similar estrogen-dependency toward the production of the enzyme without any cell proliferation. This indicates that the action of estrogen is mediated neither by cell division nor by prolactin, another hormone pastulated to be responsible for the development and growth of DMBA-tumor. Taken together, the present results have led to support the view that the primary function of estrogen is to induce plasminogen activator, which is probably essential to maintain the malignant state of DMBA-tumor.

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A subline of human KB cells that was resistant to 1-β-D-arabinofuranosylcytosine (ara-C) was established by continuous exposure of the cells to increasing concentrations of ara-C. Thirteen resistant clones were isolated from the resistant subline (KB/ara-C). KB/ara-C showed 1, 300-fold higher resistance than the parent KB cells to ara-C; the most resistant clones, clones 7 and 10, showed 1, 330-fold higher resistance. In the absence of ara-C, the resistance of the parent KB/ara-C cells was stable for at least 14 weeks, whereas that of clone 7 was stable for 10 weeks, but was slightly less after 14 weeks. The ara-C kinase and ara-C deaminase activities of the 13 clones and the cellular uptake of ara-C by several clones were measured. In general the clones showed decreased deoxycytidine kinase activity and decreased cellular uptake of ara-C. Most clones had higher cytidine deaminase activity than KB cells, but some had activity similar to that of the KB cells. A clear inverse relationship was found between the ara-C sensitivity of the clones and their kinase activity, but not their deaminase activity or their ara-C uptake. These results clearly demonstrate that a major mechanism of ara-C resistance of these human KB cells was a decrease in the activity of the ara-C activating enzyme deoxycytidine kinase. The parent KB/ara-C cells showed no clear cross-resistance to various antitumor agents other than an ara-C derivative, including metabolic inhibitors, alkylating agents, DNA binders and mitotic spindle poisons.

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Isoelectric focusing profiles of ferritins isolated from livers of anemic rats and 3'-methyl-4-dimethylaminoazobenzene-induced hepatomas were more acidic than their normal counterparts, and exhibited patterns similar to those of heart ferritin. Iron administration induced a shift to more basic components for the normal and tumor ferritins. The isoferritin patterns reflected the subunit populations of the protein, as the more acidic components had greater proportions of H-type subunits and iron induced an increase in L subunits with concomitant increases in more basic isoferritins. For both normal and malignant tissues there was a direct correlation between iron content of the tissue and subunit composition. The apparently unique isoferritin patterns in the tumor tissue may, therefore, be ascribed primarily to the lower iron contents.

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Flow cytometric (FCM) analysis of tumor antigen TA-4 was made on cervical cells from 24 patients with squamous cell carcinoma of the uterine cervix and from 22 patients without cancer by using an indirect immunofluorescence staining technique. Cellular TA-4 content was much greater in cancer cells than in non-malignant cells. In all cases of squamous cell carcinoma, FCM histograms showed a broad but conspicuous peak with higher fluorescence intensity, whereas such a fluorescence pattern as seen in malignant cases was not detected in 21 non-malignant subjects whose cells had low levels of the antigen. It would be possible to identify and sort cancer cells on the basis of cellular TA-4 content. Therefore, FCM analysis of TA-4 may provide the basis of a prescreening method for cervical cancer detection.

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The effects of ¹³¹I-labeled syngeneic mouse monoclonal anti-melanoma antibodies on tumor growth in vivo were investigated. The injection of unlabeled antibody had little effect on tumor growth, whereas the anti-tumor activity was considerably increased when the antibody was conjugated with ¹³¹I and also when a mixture of two different radiolabeled monoclonal antibodies with distinct specificities was used. The anti-tumor effects of the radiolabeled antibody were transient but significant under the present experimental conditions: melanoma growth was completely inhibited for about 10 days or more after the antibody treatment, but resumed thereafter. Possible mechanisms of escape of the tumor from the therapy with radiolabeled monoclonal anti-tumor antibody are discussed.

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The effect of Sarcophaga lectin on mouse macrophage-like cell line J774.1 was studied. It was found that this lectin induced significant morphological changes and stimulated glucose consumption of J774.1 cells. A similar effect was observed when bacterial lipopolysaccharide was added to the culture medium. However, although cells treated with lipopolysaccharide were not cytotoxic to allogeneic tumor cells, those treated with Sarcophaga lectin were found to acquire cytotoxicity. The physiological significance of Sarcophaga lectin is discussed from the viewpoint of comparative immunology.

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An in vitro double soft agar technique was used to culture 91 human urologic tumors including 37 renal cell, 40 uroepithelial, 7 prostatic and 7 testicular cancers. Cells from 31 of 37 renal, 32 of 40 uroepithelial, 3 of 7 prostatic and 4 of 7 testicular cancer specimens grew to the extent that they could be used in chemosensitivity testing in soft agar (_??_30 colonies per control plate). With this assay system, a very high growth rate (70/91; 77%) was obtained. The in vitro response rates of _??_10% were noted with mitomycin C, 5-fluorouracil, cisplatin, bleomycin and vincristine in renal cell cancers, and with vincristine and cisplatin in uroepithelial cancers. Drug sensitivity studies showed that the rates of in vitro sensitivity of uroepithelial cancers were close to those obtained in general clinical experience, while the rates of in vitro sensitivity of renal cell cancers were considerably higher than the rates found clinically. It is concluded from this study that in vitro chemosensitivity testing by clonogenic assay is likely to be a useful tool in the treatment of urologic cancers, but that a simple definition of sensitivity cannot be applied for all types of tumors.

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