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The present study deals with the influence of presensitization with tumor antigens via the intragastric route on the development of syngeneic tumor-specific immunity. Tumor-specific T cell-mediated immunity could be induced in C3H/He mice by intradermal inoculation of syngeneic X5563 tumor cells, followed by the surgical resection of the tumor 7 days later (immunization procedure). However, when the mice were presensitized intragastrically (ig) with 10(8) X-irradiated (10,000 R) tumor cells for four consecutive days, these mice failed to show in vivo protective immunity even after the above immunization procedure. Winn assays performed with spleen cells from mice presensitized ig with X5563 tumor cells revealed that ig-induced suppression was specific for the tumor antigen used for the presensitization, and that suppressor cell activity was not detected in the induction or implementation of in vivo tumor-specific effector cell activity. It was also demonstrated that such unresponsiveness was accompanied by failure to develop delayed-type hypersensitivity and cytotoxic T cell responses to X5563 tumor antigens. These results are discussed in the light of the effect of presensitization with tumor antigens via inappropriate routes on the subsequent induction of in vivo tumor-specific immunity and in relation to the tumor escape mechanism which could occur in gastrointestinal cancers.

With the aim of establishing a topical chemotherapy against stomach carcinoma, 5-fluorouracil (5-FU) emulsion (oil/water type) for injection has been developed. The drug distribution was analyzed by 5-FU bioassay and radiographic examination of soft parts, for which radiopaque Lipiodol was employed in an oil phase. In order to examine local toxicity, tissue retention, and transfer to lymph nodes of 5-FU emulsion, the drug was administered perorally to rats and injected intramurally through the gastric serosa into laparotomized dogs. Following this series of experiments, which gave satisfactory results, the time courses of drug concentration in the gastric wall and regional lymph nodes were studied as a pre-clinical trial, by applying endoscopic intramural injection of 5-FU emulsion or solution in dogs. The anti-metastatic and anti-neoplastic effects of 5-FU emulsion were investigated in an experimental model of lymph node metastasis in mice. The emulsion was more effective in subduing metastasis and tumor growth than the solution, and the effectiveness of the former was further augmented by the use of repeated injections rather than a single injection. This method of endoscopic injection of 5-FU emulsion should be of great value as a local therapeutic measure against stomach carcinoma itself as well as against metastatic lesions in the lymph nodes.

A 10-year prospective cohort study was made of 495 male hepatitis B surface antigen (HBsAg) carriers aged over 40 at entry. The observed/expected mortality rate ratio of primary liver cancer (PLC) was 10.40, based on the general population in Japan. The annual incidence rate of PLC (including 2 survivals) was 365/100,000 person-years. All histologically confirmed cases of PLC were hepatocellular carcinoma (HCC). The chronic HBsAg carrier state is suggested to be a risk factor of HCC.

A potent interferon (IFN) inducer, 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP), induced hyporeactivity in mice, and so IFN induced by subsequently administered ABPP was reduced even 120 hr after the first administration of ABPP. This hyporeactivity was counteracted by the injection of IFN (10,000 IU or more) 3 hr before the subsequent administrations of ABPP. Since the injection of more than 5,000 IU/mouse of IFN 3 hr before an administration of ABPP enhanced the circulating IFN titer, the priming effect in vivo by IFN may result in the reduction of hyporeactivity. Administrations of ABPP (200 mg/kg or 500 mg/kg) at intervals of 2 days and the injection of IFN (25,000 IU/mouse) 3 hr before each administration of ABPP to neuroblastoma-bearing A/J mice reduced the mortality and completely cured 40% of the mice in each combined therapy group. These results suggest that the combined use of the IFN inducer with IFN may be available for patients with neoplasm or viral infection.

The action mechanism of antibody-dependent macrophage-mediated cytotoxicity (ADMC) induced by OK-432 against MM2 carcinoma cells was examined. Adherent peritoneal exudate cells (adherent PEC) harvested from mice 4 days after intraperitoneal injection of OK-432 exhibited potent cytotoxic activity against MM2 cells in the presence of anti-serum obtained from tumor-free mice which had survived over 60 days following treatment with OK-432 and resisted rechallenge with MM2 cells. The cytotoxic activity of the adherent PEC was not abolished by treatment with anti-Thy-1.2 and complement, and there were no differences in ADMC between adherent PEC from BALB/c mice and those from athymic BALB/c (nu/nu) mice. Further, ADMC activity was shown not only against MM2 cells, but also against other allogeneic tumor cells, such as MOPC-11 plasmacytoma cells. On the other hand, the effective factor(s) in anti-serum to MM2 cells was eliminated by passage through a protein A-Sepharose CL-4B affinity column. The action mechanism of ADMC caused by the adherent PEC and anti-serum to MM2 cells is discussed.

Transfusion of 15 ml of blood from a rhesus monkey seropositive for human T-cell leukemia virus (HTLV) antigens to an anti-HTLV negative rhesus monkey resulted in the seroconversion of the recipient after five weeks. Cultured peripheral lymphocytes from the seroconverted monkey expressed HTLV antigens and type C virus particles.

Leukemia cells from patients with acute myeloid leukemia in relapse were treated with various inducers of differentiation of human myeloid leukemia cell lines. Leukemia cells in primary culture from most, but not all, patients underwent morphological, cytochemical and biochemical changes after treatment with inducers of differentiation such as 12-O-tetradecanoylphorbol-13-acetate (TPA), retinoic acid, actinomycin D, aclarubicin, and alkyl lysophospholipid. The most effective inducer varied from specimen to specimen. Leukemia cells from patients in relapse were compared with those from untreated patients. The responsiveness to TPA of leukemia cells from patients in relapse was similar to that of leukemia cells from untreated patients. However, retinoic acid or actinomycin D resistance was more frequently observed in leukemia cells from patients in relapse than in those from patients before initial therapy. This is the first report to indicate that leukemic cells from relapsed patients who are resistant to cytotoxic chemotherapeutic drugs can be induced to differentiate into mature cells by appropriate inducers. However, the responsiveness to inducers of leukemia cells from patients in relapse is not the same as that of leukemia cells before therapy.

Spontaneous metastasis of highly metastatic variants, B16 melanoma BL-6 and colon adenocarcinoma 26 NL-22, was examined. Tumor cells were inoculated into the right front footpad and the original tumors were removed by amputation of the forelimb at an appropriate time after tumor inoculation. Spontaneous lymph node and lung metastases occurred with B16 BL-6 and spontaneous lung metastasis occurred with NL-22. Analysis of the time-dependent formation of lymph node and lung metastases of BL-6 indicated that lung metastasis could be formed after the lymph node metastasis. Metastasis is influenced by the mouse strain, and both inbred and F1 hybrid mice of syngeneic origin could be used as host animals. By using these metastatic variants, two spontaneous metastasis systems were established. In order to evaluate the systems, the effects of 5-fluorouracil (5-FU) and adriamycin (ADM) were examined. 5-FU was effective against the metastases of both tumors, and ADM was moderately effective against B16 BL-6 metastasis.

The aggregating properties of murine melanoma cell lines with low metastatic potential (B16-F1) and high metastatic potential (B16-F10 and B16-BL6) were compared. All three types of cells were found to possess Ca2+-dependent and Ca2+-independent intrinsic mechanisms for cell adhesion, though the extent of reaggregation varied in each mechanism. After trypsin treatment at around 1 microgram/ml, F10 and BL6 cells reaggregated in the presence of 1mM Ca2+ to a greater degree than F1 cells. F10 and BL6 cells were also more aggregative than F1 cells after dissociation with collagenase. The apparent adhesiveness of the cells was found to be dependent on both the manner of cell preparation for reaggregation and on the presence of external Ca2+ or serum factors. The results are discussed in relation to the mechanisms of tumor cell arrest with emphasis on the effect of extracellular factors on cell adhesiveness.

The mutagenic compound 2-amino-3-methylimidazo[4,5-f]quinoline, originally isolated from broiled sardines and also present in cooked beef and beef extract, is being tested for carcinogenicity in F344 rats of both sexes. High incidences of tumors of the Zymbal gland, colon, small intestine and liver in males have been observed in the first 300 days of the experiment.