Metastatic tumor burden in the lung of C57BL/6 or BDF1 mice was quantitated by measuring DNA polymerase alpha 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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PubMedDate not supplied

Growth stimulating activity of lung extract on lung-colonizing colon 26 clones and its partial characterization.

The effects of lung tissue extract on the cell growth of eight colon 26 tumor clones, four highly and four poorly lung-colonizing clones, were examined in vitro. Addition of lung extract to serum-free medium stimulated the growth of all four of the highly lung-colonizing clones and one of the poorly lung-colonizing clones, but it had minimal effect on the other three poorly lung-colonizing clones. These results indicate that the lung extract contains a growth stimulating activity; it selectively stimulated some of the colon 26 clones including highly lung-colonizing ones. The growth stimulating activity was not dialyzable, was partially destroyed by heating at 56 degrees C or 80 degrees C for 30 min and completely destroyed by trypsin. These results suggest that the activity resides in a protein. Gel filtration chromatography of lung extract on Sephacryl S-200 revealed that the active component was eluted in a molecular weight range of 90,000-120,000.

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PubMedDate not supplied

Development of lymphosarcoma lines with high metastatic ability to lymph nodes and visceral organs in BALB/c mice.

A metastatic tumor population was isolated in BALB/c mice during routine s.c. passage of the colon 26 adenocarcinoma. The tumor metastasized to lymph nodes, liver, spleen, ovary and kidney. A primary culture established from the s.c. growing tumor was composed of both adherent and nonadherent cells. These two cell types were successfully separated from the primary culture and designated CMS (suspension cells) and CMA (adherent cells). The CMS and CMA cell lines are morphologically distinct in culture; however both formed similar histopathologic tumors when inoculated s.c. Furthermore, both tumor lines showed identical metastatic patterns in BALB/c mice with involvement of lymph node, liver, spleen, ovary and kidney. CMS and CMA expressed T-antigen as revealed by FITC-labeled-anti-Thy 1.2 antibody. Chromosome analysis and morphologic studies by light and electron microscopy indicated that the present metastatic lines have no relationship with the colon 26 adenocarcinoma and seem to be non-thymic T-cell lymphosarcomas which developed spontaneously in BALB/c mice.

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PubMedDate not supplied

Immunohistochemical investigation of thymidylate synthase in cervical cancer.

We prepared a polyclonal antibody against recombinant human thymidylate synthase (TS) to evaluate its use in immunohistochemical analysis. Formalin-fixed, paraffin-embedded sections of specimens of cervical tissue were prepared from 35 patients with cervical cancer. The TS immunoreactivity was studied by employing the peroxidase-labeled antibody method with our prepared antibody. At the same time, the TS activity was determined with the 5-fluoro-2'-deoxyuridylate (FdUMP)-TS-binding assay in fresh-frozen specimens of these cervical cancers. We observed a positive correlation (r = 0.658) between the degree of TS immunoreactivity and the TS activity in the binding assay of 9 patients with grade 4 (strongly positive) TS immunoreactivity, while 7 patients (78%) exhibited a TS activity of 5 pmol/g tissue or greater. Nine patients with a TS immunoreactivity of grade 1 (negative to weakly positive) showed a TS activity <5 pmol/g tissue. The difference between the two groups was statistically significant (p < 0.01). TS expression was easily detected by the immunohistochemical technique which will allow the assessment of the relationship between TS activity and patient outcome.

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PubMedDate not supplied

Comparative microscopic study on response of Ehrlich carcinoma to BNCT vs. chemo- and radiotherapy.

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