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  • 1
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: MO4 cell aggregates with a diameter of 0·3 mm produced invasive fibrosarcomas after s.c. implantation into the pinna of syngeneic mice. Histology of pinnae fixed 10 min to 5 days after implantation of an aggregate suggested that the tumour was produced by the cells that invaded during the first day, and that the cells remaining in the aggregate were eliminated by the reaction of the host. Before implantation we have pretreated MO4 cell aggregates with 1 μg/ml of the microtubule inhibitors Nocodazole (ND) and vincristine (VCR), known to inhibit both proliferation and invasion, and with 1 μg/ml 5-fluorouracil (5-FU), known to inhibit proliferation but not invasion. Tumorigenicity was significantly reduced after treatment with ND or VCR, as compared to treatment with 5-FU or to controls. Histology of pinnae fixed 10 min to 3 days after implantation showed absence or scarceness of invasive MO, cells after pretreatment with ND or VCR, in contrast with controls or with aggregates pretreated with 5-FU. The effect of ND, VCR and 5-FU on the growth of aggregates in culture on gyrotory shaker was reversible within 1 and 2 days respectively. After treatment with ND or VCR slight alterations in the function of the cytoplasmic microtubule complex remained visible during 3 days in cells migrating from an aggregate explanted on glass. Confrontation of pretreated aggregates with fragments of embryonic chick cardiac muscle in three-dimensional culture indicated that the anti-invasive effect of ND or VCR was reversible in vitro. We concluded that a delay of invasiveness caused by pretreatment with ND or VCR provided the host with the opportunity to eliminate MO4 cells implanted s.c. into the pinna.
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  • 3
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Metastatic tumor burden in the lung of C57BL/6 or BDF1 mice was quantitated by measuring DNA polymerase a activity in the lung of tumor-bearing animals. DNA polymerase activity in the lung increased time-dependently following the inoculation of Lewis lung carcinoma (s.c.) or B16 melanoma variant B16–B2 (i.v.). In the Lewis lung carcinoma system, the number of metastatic modules and the weight of lung also increased time-dependently. Results from the B16 melanoma showed that the increase in lung nodules occurred 10 to 20 days after i.v. inoculation of tumor cells. DNA polymerase activity increased significantly during this period. Because the lung nodules were very small there was no obvious concomitant increase in lung weight. Since no significant infiltration of host cells was observed in the lung in response to metastatic foci, the rise in DNA polymerase activity should be due to tumor cells and not to infiltrating host cells. When the metastasis of Lewis lung carcinoma was inhibited by adriamycin and cyclophosphamide, decrease in DNA polymerase activity in the lung occurred. These results indicate that the degree of tumor metastasis can be quantitated by measuring DNA polymerase activity.
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  • 4
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of brain implants of Walker 256 carcinosarcoma tumour cells on the integrity of the blood-brain barrier was examined in rats using labelled albumin, horseradish peroxidase and trypan blue. Barrier integrity was intact within 1 hour of implantation but was gradually reduced within the tumour after 3·5 days. This was related to alterations in the fine structure of the tumour capillaries. Dissociated tight junctions were apparent within the tumour centre, but no fenestrated endothelium or gap junctions were observed by electron microscopy.
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  • 5
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The murine melanoma subline B16-F1 of low brain- and lung-colonizing potential has been used to obtain brain-colonizing variant sublines by sequential selectionin vivo for their abilities to form brain meningeal tumors. After fourteen and fifteen selections in syngeneic C57BL/6 mice sublines B16-B14b and B16–B15b, respectively, were established in culture. These were then assayedin vivo by injection of single tumor cell suspensions into the tail vein (i.v.), left ventricle of the heart (i.c.) or left common carotid artery (i.a.), and the resulting tumors were examined histologically. Injection of subline B16-B14b or B16–B15b resulted in brain meningeal tumor formation in the dura mater and leptomeninges with invasion into underlying brain parenchyma and also some brain ventricular tumors at the sites of i.a. injection. Lung colonization ability remained in the brain-selected sublines, although it was remarkably reduced in i.a. tumor cell-injected animals. The brain meningeal tumors that formed were of three types: intravascular, nodular or infiltrative. Injection of tumor cells i.v. resulted mainly in the establishment of the intravascular type of brain meningeal tumors with eventual perivascular invasion, while injection i.a. or i.c. resulted mostly in nodular or infiltrative type brain meningeal tumors. The B16–B14b brain meningeal tumors formed were small (〈 1 mm in diameter) and usually non-pigmented, while B16–B15b tumors were generally large (up to 7mm in diameter) and pigmented. Host reactions towards B16–B14b and B16–B15b tumors at meningeal sites differed. The former B16 subline was characterized by extensive fibrosis with some immunocytic cell infiltration in and around the meningeal tumors, while the latter subline did not elicit such host reactions. In contrast, tumors in brain parenchyma failed to evoke observable host reactions, and there was little evidence of immunocyte cell infiltration or glial cell alterations.
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  • 6
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Brain organ cells were cultured on cellulose polyacetate and other substrates in order to investigate metastatic tumor cell invasion in vitro. The cultures consisted of small pieces (approximately 1 × 3 mm) of neonatal mouse cerebrum or cerebellum tissue. Brain tissue pieces were allowed to attach to the substrates and were then cultured for 14–15 days in roller tubes. Cellulose polyacetate was found to be the best substrate for the attachment of brain tissue, and it eliminated some of the undesirable tissue movements that occurred using other substrates. Also, the invasion assays were the most reproducible using this tissue support. In culture, both cerebrum and cerebellum tissue achieved stable structures by 14 days, but the neurons and astrocytes in these tissues continued to exhibit structural changes such as extension of cellular processes. Murine B16 melanoma cells selected in vivo 15 times for brain colonization bound rapidly to and invaded brain tissue, infiltrating deep into the tissue within 4 hours and displacing the entire tissue by 5 days. Many of the B16 tumor cells extended pseudopodia and filopodia during invasion, suggesting that their tissue infiltration was an active invasive process. However, some B16 cells remained spherical in shape with numerous surface microvilli, but these same tumor cells also moved into the brain tissue. Brain tissue attached to cellulose polyacetate appeared to be the most useful system for elucidating the invasive interactions of malignant cells with brain tissues in vitro.
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  • 7
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The effect of inicarone (L7035), a potent fibrinolytic, alone or in combination, was investigated on spontaneously metastasizing Lewis lung carcinoma (implanted intramuscularly) to verify whether it could prevent the formation of metastases. After intraperitoneal and oral administration, inicarone did not show any cytotoxicity since the survival of animals was not prolonged. Its activity was compared to that of warfarin, an anticoagulant: both drugs were inactive when administered in curative treatment and inicarone even enhanced the number of lung metastases. When administered in combination with cyclophosphamide, an antiproliferative agent, inicarone did not induce any synergism or antagonism, but this combination did not inhibit tumour growth or metastasis spreading. Moreover, when inicarone was combined with a potent antimetastatic agent, Nocodazole, it was shown to be in competition with the latter agent and totally overshadowed its activity; since inicarone had no antimetastatic effect, the number of metastases rose dramatically.
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  • 8
    ISSN: 1573-7276
    Keywords: breast cancer ; axillary nodes ; tumour area ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The tumour-load in the axilla of breast cancer patients is classically measured from the number of tumour-bearing nodes present, which is then used to assess prognosis. This preliminary morphometric study on 73 cases of breast carcinoma for which standardized axillary dissection specimens were available shows that the total tumour load, measured from the sum of the tumour area (cm2) in hilar nodal sections, gives a redistribution of the patients; one that may provide better prognostic information in particular in women with a high tumour load. In those with four or more nodes involved the actual number is said to give little prognostic discrimination at 4 years post-operatively, as was demonstrated in this series. In contrast, using data from the same patients, the risk of death by this time increased steadily with increasing tumour area.
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  • 9
    ISSN: 1573-7276
    Keywords: doubling time ; genetic variability ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The contribution of both non-inherited (stochastic, random, environmental, and other non-inherited influences) and inherited factors (genetic and inherited epigenetic factors) to the variability of spontaneous lung metastasis formation in over 100 metastatic lines from each of three murine tumors was measured. The contribution of inherited and genetic sources of variability to metastasis formation was significantly greater than 0 in all cases, but only in the lines of sarcoma SANH was it the major influence on metastatic variability. In the sarcoma SA4020 and hepatocarcinoma HCA-l lines, non-inherited factors accounted for the majority of the variation in spontaneous lung metastasis formation. A similar situation was also observed in the variability of the tumors with respect to the diameter doubling time. In conclusion, both non-inherited and genetic/inherited factors significantly influenced the formation of spontaneous metastases in the tumors examined. The significance of this finding for the cloning of metastatic genes is discussed.
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  • 10
    ISSN: 1573-7276
    Keywords: human ; hematogenous ; metastatic patterns
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: An attempt is made to clarify some general concepts of hematogenous metastatic patterns in humans, by the use of autopsy data. The significance and problems associated with ‘false negative’ reports are assessed. By the use of metastatic efficiency indices in which the incidence of specific target organ involvement is related to organ blood-flow, ‘seed-and-soil’ effects are discriminated from the effects of differential cancer cell delivery. An analysis of autopsy data from cases with a history of colorectal carcinoma is used to illustrate the importance of metastasis from metastases in the genesis of hematogenous metastatic patterns in humans.
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