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  • 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: 1613-9674
    Keywords: Radiation therapy ; Bone metastases ; Head and neck cancer ; Pain relief
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the efficacy of radiation therapy for pain relief of bone metastases from head and neck cancer, a total of 22 patients with head and neck cancer with 30 metastatic bone lesions treated by radiation therapy at the Cancer Institute Hospital were analyzed. These patients were given a dose of 20 to 50 Gy in 10 to 25 fractions using liniac X-ray or electron beam and were divided into two groups. Group A consisted of 10 patients with tongue cancer (tongue cancer group), and group B consisted of 12 patients other than with tongue cancer (non-tongue cancer group). In group A, of the 6 metastatic lesions treated with over 30 Gy, 17% achieved CR (complete pain relief for more than 3 months), 33% showed PR (over 50% extent pain relief), and 50% NC. While, in group B, of the 17 lesions 35% showed Cr, 53% PR and 12% NC. There was a significant difference in the response rate (50% vs 88%, P〈0.01) of pain relief between the osseous metastases from tongue cancer group and the non-tongue cancer group, although further prospective studies are necessary to elucidate the radiosensitivity of bone metastases in terms of the histologic difference in head and neck cancer patients.
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  • 4
    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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  • 5
    ISSN: 1432-1335
    Keywords: Bone metastasis markers ; Bone metastasis ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The efficacy and cost/performance benefit of radionuclide bone scintigraphy in monitoring metastatic bone activity remain controversial. Recently developed bone metabolic markers are expected to play an additional role in the diagnosis of bone metastasis. We measured osteoclastic and osteoblastic markers in 267 patients with breast cancer (100 with bone metastasis), 38 patients with prostatic cancer (25 with bone metastasis), 50 patients with lung cancer (12 with bone metastasis) and 33 patients with miscellaneous cancers (13 with bone metastasis) and compared the values in the presence and absence of bone metastasis. Bone metabolic markers, both osteoclastic and osteoblastic, increased significantly in patients with bone metastasis. In breast cancer (bone metastasis is mostly of the mixed type), osteoclastic markers were good in detecting bone metastasis. In prostatic cancer (bone metastasis is mostly osteoblastic), osteoclastic and osteoblastic markers were equally effective in detecting bone metastasis. In lung cancer (bone metastasis is mostly osteolytic), osteoclastic markers were elevated preferentially in bone metastasis. Over all, osteoclastic markers were more sensitive in the diagnosis of bone metastasis, and among osteoclastic markers, serum pyridionoline-cross-linked carboxyterminal telopeptide was the most efficient in both specificity (91.0%) and sensitivity (48.6%) for detecting bone metastasis.
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  • 6
    ISSN: 1573-5079
    Keywords: electron donors and acceptors ; Mn-incorporation ; N2-inhibition and O2-stimulation ; O2-evolution ; photoreactivation ; and Tris-washed chloroplasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The inactivated O2-evolving center of Tris-washed chloroplasts was reactivated by DCPIP-treatment and photoreactivation in the presence of Mn2+, Ca2+, DTT and weak light. Many electron donors (Asc and reduced DCPIP, etc.) were found to be suitable substitutes for DTT. By studying the anaerobic inhibition of the reactivation, the electron acceptors O2, NADP+, etc. were also found to be essential factors in photoreactivation. Weak light stimulated the chloroplast electron transport from the above-mentioned electron donors to the electron acceptor and effected the photoreactivation. More than 280 electrons were transported to NADP+ in the anaerobic photoreactivation of one unit of an O2-evolving center with 400 Chl. Electron transport in the reactivation was inhibited by omitting DTT or Mn2+ ion, and by adding DCMU. The photoreactivated chloroplasts incorporated about 2 Mn by 400 Chl. Omission of DTT in the reactivation caused chloroplasts in the weak light to bind large amounts of excess Mn.
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  • 7
    ISSN: 1573-5079
    Keywords: chloroplasts ; cytochrome b-559 ; oxygen evolution ; photoreactivation ; Photosystem II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Restoration of a high potential (HP) form of cytochrome b-559 (Cyt b-559) from a low potential (LP) form was the primary process in the reconstitution of O2-evolving center during the photoreactivation of Tris-inactivated chloroplasts. In normal chloroplasts, about 0.5 to 0.7 mol of Cyt b-559 was present in the HP form per 400 chlorophyll molecules. However, the HP form was converted to the LP form when the O2-evolving center was inactivated by 0.8 M alkaline Tris-washing (pH 9.1). The inactivation was reversible and both the Cyt b-559 HP form and the O2-evolving activity were restored by incubating the inactivated chloroplasts with weak light, Mn2+, Ca2+ and an electron donor (photoreactivation). The recovery of the HP form preceded the recovery of O2-evolving activity. 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB) did not inhibit the recovery of the HP form. Thus, the recovery of Cyt b-559 HP form was the primary reaction in the photoreactivation, which was stimulated by the light-induced redox reaction of the PS-II core center.
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  • 8
    ISSN: 1573-5117
    Keywords: continuous culture ; high density culture ; marine rotifers ; Brachionus rotundiformis ; Brachionus plicatilis ; mass production ; nutritionalimprovement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In order to improve culture stability, as well as to reduce labor andspace for mass production of the marine rotifer Brachionus, an automaticcontinuous culture system has been developed for practical use. The systemconsists of a filtration unit, a culture unit and a harvest unit. In thissystem, filtered water and food are continuously supplied into a rotiferculture tank at a pre-determined rate, and the same amount of culture wateris transferred into a harvest tank to obtain rotifers at a significantbiomass. B. rotundiformis (so-called S-type) and B. plicatilis (so-calledL-type) were successfully mass-produced from the system, under regulatedconditions of 30 °C (for S-type) or 24°C (for L-type), 20 ppt diluted sea water and totaldarkness. As food for rotifers, commercially available concentrated freshwater Chlorella vulgaris was used. The dilution rate was adjusted to0.6–0.7 d−1 for S-type rotifer and 0.25d−1 for L-type rotifer, respectively. The average productionwas about 2.1 billion rotifers d−1 from a 1-m3S-type continuous culture in which high rotifer densities ranging from 3000to 6000 ind. ml−1 were maintained. On the other hand, about0.17 billion rotifers d−1 on average were obtained from a500-liter L-type culture, with densities ranging from 1100 to 2200 ind.ml−1. The longest duration for a continuous culture was over110 days. Furthermore, experiments utilizing five enrichment techniquesindicate that rotifers from the continuous culture system can easily benutritionally enriched in the same manner as those from common batch culturesystems.
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  • 9
    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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  • 10
    ISSN: 1437-7772
    Keywords: bisphosphonate ; bone metastasis ; breast cancer ; osteoclast activity ; bone scintigraphy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background Bisphosphonates are powerful inhibitors of osteoclast-mediated bone resorption. They are effective in the treatment of Paget's disease of the bone, tumor-associated hypercalcemia, and osteoporosis. They are also used to treat metastatic bone disease. YM-175 is a new highly potent bisphosphonate. Bisphosphonates are also used as radiopharmaceuticals in bone scintigraphy. The data remain unclear as to whether or not the administration of large amounts of bisphosphonate interferes with the bone scintigraphy process. Methods We have treated 8 patients with bone metastases from breast cancer with 10 mg IV, once a week for 5 weeks. The monitoring of bone pain, laboratory analysis with bone metabolic markers, and bone imaging including x-ray and bone scintigraphy, was performed for 8 weeks. A quantitative method was employed to evaluate serial bone scintigraphy. Results Bone pain improved in 5 out of 8 cases at 2 and 4 weeks post-treatment without serious adverse effects, but the duration of pain relief was short. Markers of osteoclast activity were decreased significantly to a minimum at 2 weeks. No significant changes were shown in markers of osteoblast activity or in serum calcium levels. Intact parathyroid hormone (PTH) was elevated at 2 and 4 weeks. It appears that YM-175 suppressed osteoclast activity, however, its effect was negated by a PTH elevation response. No changes were detected in either x-ray findings or serial bone scintigraphy by use of visual images and quantitative methods. Conclusion YM-175, a new bisphosphonate, was a safe and promising drug for the treatment of metastatic bone pain from breast cancer. Osteoclast activity was suppressed by bisphosphonate treatment, but, the PTH response negated the osteoclast suppression. Furthermore, YM-175 treatment did not alter bone scintigraphic images.
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