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  • Articles  (6)
  • 1985-1989  (5)
  • 1980-1984  (1)
  • 1
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The antitumor and antimetastatic activities of a thymic factor, thymostimulin (TP-1), with or without cyclophosphamide (CPA) were examined in C57BL/6 mice inoculated with Lewis lung carcinoma (3LL). Tumor growth was followed by determining the tumor diameter after tumor implantation. TP-1 given to mice every 2 days after tumor implantation significantly inhibited tumor growth without affecting the survival rate. For induction of spontaneous pulmonary metastases, 3LL cells were implanted into the footpads of mice, and the implanted tumor was removed on day 9. The antimetastatic effect of TP-1 on pulmonary metastases after removal of the primary tumor was evaluated by counting the number of pulmonary surface nodules. TP-1 showed antimetastatic activity depending on its time of administration and dose. Combined therapy with TP-1 plus CPA significantly prolonged the survival of mice with pulmonary metastases. The cytolytic activities of spleen cells on 3LL cells were enhanced in mice treated with TP-1 and/or CPA and the cytolytic activity of nonadherent spleen cells, the T-cell population, was enhanced. The role of cytolytic spleen cells in inhibiting and preventing metastases was discussed.
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  • 2
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Spleen cells of C57BL/6N mice bearing lung metastases were induced to the cytotoxic state by subcutaneous injection of recombinant human interleukin-2 (IL-2) at a minimum dose of 5×104 U/mouse three times a day for 3 consecutive days. A single intraperitoneal injection of lentinan alone at concentrations of up to 10 mg/kg body weight did not render spleen cells cytotoxic to P-29 cells, but a combination of subthreshold doses of these agents (5×104 U/ml IL-2 and 5 mg/kg lentinan) induced significant in vivo lymphokine-activated killer activity in spleen cells of tumor-bearing mice. Similarly, spleen cells from mice treated i.p. with lentinan became cytotoxic on in vitro treatment with IL-2. The in vitro responsiveness of spleen cells to IL-2 was maximal 3 days after i.p. injection of lentinan. Synergism between IL-2 and lentinan was also observed in mice bearing spontaneous lung micrometastases: neither IL-2 (〈5×104 U/mouse) nor lentinan (〈2.5 mg/kg) alone had a therapeutic effect, but multiple injections of IL-2 with a single injection of lentinan resulted in significant inhibition of spontaneous pulmonary metastases. From these results we conclude that IL-2 and lentinan in combination are more effective than either one alone for inducing destruction of pulmonary metastases.
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  • 3
    ISSN: 1617-4623
    Keywords: Microbial protease ; Proenzyme ; Secretion ; Yeast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The aspartic protease gene of a zygomycete fungus Mucor pusillus was expressed in Saccharomyces cerevisiae under the control of the yeast GAL7 promoter. A putative preproenzyme with an NH2-terminal extension of 66 amino acids directed by the gene was processed in yeast cells and the mature enzyme, whose NH2-terminus was identical to that of the Mucor enzyme, was efficiently secreted into the medium at a concentration exceeding 150 mg/l. The enzyme secreted from the recombinant yeast was more glycosylated than the native Mucor enzyme but its enzymatic properties were almost identical with those of the native enzyme, which has been used as a milk coagulant in cheese manufacture.
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  • 4
    ISSN: 1520-6025
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 6
    ISSN: 1573-7233
    Keywords: metastasis ; tumor cell arrest ; coagulation ; fibrinolysis ; platelet ; host defense
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Most metastases in patients occur as a result of hematogenous dissemination of tumor cells (1–3). This process of metastasis is complex and consists of several steps, foremost of which is the arrest of circulating emboli in capillary beds and the formation of a thrombus at that site (4–5). Thrombus formation in the metastasis of human cancer was described first by Billroth in 1878. It was reported that the organization of tumor cell emboli, and the subsequent penetration of tumor cells into the capillary wall, was the first stage of metastasis. Since then, many investigations and observations have been made clinically as well as experimentally to clarify the process (or mechanisms) of tumor cell arrest and how to inhibit it. Coagulative and fibrinolytic pathways were believed to have a main role in thrombus formation (6, 7). However, other factors responsible for the relationship between tumor cells and the host must be also considered. Elegant and extensive studies by Fidler and Kripke (8) demonstrated that development of metastasis is not a random process, but a selection process of specialized subpopulations of highly metastatic cells within the primary tumors. Biochemical constituents and ionic properties on cell surfaces, deformability or locomotive activities of tumor cells, as well as thrombo-plastic-fibrinolytic activities, are also important factors determining the arrest patterns of circulating tumor cells. On the other hand, host defense factors against tumor cells in the bloodstream have been attracting much attention recently in tumor immunology. Host defense factors relating the arrest of tumor cells to the establishment of metastatic foci seemed difficult to define, since many studies showed contradictory data concerning the influence of immune response on tumor cell arrest (9, 10). Hemodynamic abnormality may also influence the arrest of tumor cells in the circulation (5). Hypercoagulability induced from host tissues is greatly associated with the arrest patterns (11, 12). Platelet activities might affect thrombus formation (7, 13). Nevertheless, exact explanations of the process or mechanisms inhibiting or enhancing the arrest of tumor cells after hematogenous dissemination have not been obtained. In any event, for cancer treatment, it is important to determine which substances inhibit the arrest of circulating tumor cells and how to prevent hematogenous metastasis. In this review, we will focus upon coagulative and fibrinolytic processes and then upon substances that inhibit the arrest of circulating tumor cells. Furthermore, some comments on the possible clinical applications of inhibitory substances for prevention of cancer metastasis are added.
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