63

Institut f~r Virusforschung, Deutsches Krebs- forschungszentrum, 6900 Heidelberg, Germany. Cancer 55: 1737-1740, 1985.

Twenty-four biopsy specimens from various histologic types of human carcinomas in the lung were analyzed for the presence of human papillomavirus (HPV) DNA. DNA from the indi- vidual specimens was tested for the presence of homologous sequences to HPV genotypes i, 2, 4, 8, 9, i0, ii, 13, 16 and 18. One ana- plastic carcinoma in the lung contained mul- tiple copies of DNA hybridizing under stringent conditions to HPV 16 DNA. The lat- ter DNA has been found to be frequently associated with human genital cancer (cer- vical, penile, and vilval cancer) and genital Howen's disease. The HPV 16 posi- tive lung tumor originated from a 61-year-old female patient who underwent hysterectomy due to cervical cancer 9 years earlier.

Dimethyl Sulfoxide Induces Expression of H-2 Antigens on Mouse Lung Carcinoma Cells. Bahler, D.W., Lord, E.M. Department of Microbiology and Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.J. Immunol. 134: 2790-2798, 1985.

The addition of dimethyl sulfoxide (DMSO) to cultures of line 1 carcinoma cells can increase the surface expression of H-2K and H-2D antigens at least 100-fold from bare- ly detectable initial levels, as determined by using specific monoclonal antibodies and flow cytometry. H-2 values stabilize approx- imately 1 wk after exposure to maximally inducing concentrations of DMSO (3% vol) at densities found on normal spleen cells. Increased expression of H-2 antigens is not the result of cell selection, it is specific in that expression of an unrelated surface protein decreases, and it is associ- ated with increased synthesis of these an- tigens as measured by incorporation of (sup 3sup, 5S)methionine. Additonal DMSO- induced changes in the growth, cycling, lectin binding, and antigenic properties of line 1 cells are consistent with increa- sed cell maturation. All changes are rever- sed when DMSO is removed. This system may facilitate study of products associated with differentiation that influence tumor cell malignancy.

Selective Cytotoxicity of SMI Monoclonal Antibody Towards Small Cell Carcinoma of the Lung. Bernal, S.D., Mabry, M., Stahel, R.A., et al. Division of Medicine and Medical Onco- logy, Dana-Farber, Cancer Institute and Harvard Medical School, Boston, MA 02115, U.S.A. Cancer Res. 45: 1026-1032, 1985.

A murine monoclonal antibody, SMI, is strongly reactive with the surface membrane

of small cell carcinoma of the lung (i).

SMI antibody is unreactive with most other

cancers and various normal tissues including bone marrow cells. We now find that SMI anti- body is selectively cytotoxic to small cell carcinoma (SCC) in vitro. The antibody is pre- sent in high titers in supernatant fluids or ascites obtained by i.p. injection of SMI hy- bridoma cells into pristaned BALC/c mice. The cytotoxic effect of the antibody is reduced to one-half maximal activity only at dilutions greater than 1:40,000. The efficiency of tumor cell lysis is greater enhanced by repeated treatments with antibody and complement. Using three treatments with antibody and complement, 99.9% of SCC cells are lysed, as determined by the chromium release. Similar efficiency of SCC cell kill was observed by clonogenic assays. SMI antibody produces no significant antibody- dependent lysis of cell lines derived from non- SCC lung carcinomas and leukemia cells. The result from chromium release assay and clono- genic assays also indicate that the effect of SMI antibody and complement on bone marrow cells is minimal and could be accounted for by the effect of complement alone.

A 5p Deletion in Small Cell Lung Carcinoma. Falor, W.H., Ward-Skinner, R., Wegryn, S. Cyto- genetics Laboratory, Akron City Hospital, Akron, OH 44309, U.S.A. Cancer Genet. Cytogenet. 16: 175-177, 1985.

A specific chromosomal abnormality (3p del) was found in direct preparations from three small cell carcinomas of the lung: one prima- ry tumor and two metastatic tumors in media- stinal lymph nodes. This lends support to Whang-Peng et al.'s (3) detection of the dele- tion in tissue cultures.

Urinary Hypoxanthine and Pseudouridine as Indi- cators of T~or Development in Mesothelioma- Transplanted Nude Mice. Buhl, L., Dragsholt, C., Svendsen, P., et al. Department of Pathology, Odense University Hos- pital, Odense, Denmark. Cancer Res. 45: 1159- 1162, 1985.

A human mesothelioma was heterotransplan- ted to nude mice, and the urinary excretions of hypoxanthine, xanthine, pseudourifline, oro- tic acid, 7-methylguanine, and l-methylhypo- xanthine have been followed before and after the tumor transplantation. The compounds were measured by means of isotachophoresis, which has been found a rapid and precise method. The tumor reached maximum size within 30 days, and at this time a significantly increased excre- tion of pseudouridine and hypoxanthine was ob- served. Tumor growth was stopped by chemothe- rapy (vincristine, cyclophosphamide, predniso- lone, and adriamycin), and corresponding to this, a decrease occurred in both pseudouridi- ne and hypoxanthine excretion tO normal values.

I,~nunoreactive Neuron-Specific Enolase, Bombe-

sin, and Chromogranin as Markers for Neuro-

64

endocrine lung t~ors.

Said, J.W., Vimadalal, S., Nash, G., et al. Division of Anatomic Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, U.S.A. Hum. Pathol. 16: 236-240, 1985.

Sixty-four lung tumors were evaluated for the presence of immunDreactive neuron-spe- cific enolase (NSE), bombesin (Bn), and chromogranin (Cg) to assess their value as markers for neuroendocrine cells in the hi- stologic diagnosis of pulmonary neoplasms. Staining was correlated with the presence and density of neurosecretory granules (num- ber of neurosecretory granules per unit cytoplasmic cross-sectional area) as deter- mined by planimetry on electron micrographs. The cytoplasmic density of neurosecretory granules was significantly greater in the carcinoid tumors than in the small cell car- cinomas (P < 0.001). Neuron-specific eno- lase was localized in all of the neuroen- docrine granule-bearing tumors but was also present in 57 per cent of the nonneuroendo- crine carcinomas. Bombesin was present in 68 per cent of the neuroendocrine tumors and in less than 1 per cent of the nonneuro- endocrine tumors. Staining for the Cg ap- peared to correlate with the density of neu- roendocrine granules, with staining in car- cinoid tumors but no staining in small cell anaplastic carcinomas. A panel of antibodies may be required for the reliable indentifi- cation of neuroendocrine lung tumors by im- munohistochemical techniques.

Assay for the Determination of H~nan Carci- noma Cells in Circulating Blood. Schwartz, R., Walk, A., Toomes, H., Schirr- macher, V. Institut f6r Immunologie und Genetik, Deutsches Krebsforschungszentrum, D-6900 Heidelberg, Germany. J. Cancer Res. Clin. Oncol. 109: 122-129, 1985.

Methods have been developed in an in vitro system (i) of assessing the number of disseminated tumor cells in peripheral blood and (2) of enriching tumor cells from peripheral blood samples for further characterization. Cells from three human carcinoma lines (El4, ChaGo, and LEDWiDr) were mixed with leukocytes from normal individuals in various ratios. The p~opor- tions of tumor cells were determined by a quantitative assay using sup 3H-thymidine, sup 3H-leucine, and sup 3H-galactose incor- poration. Determination of tumor cell pro- portions with this method was most accu- rate in the range of 5xl0sup 4 to 5-10sup 3 tumor cells mixed with a constant number (5xl0sup 5) of lymphocytes. It was possible to separate sup 7sup 5Se-labeled tumor cells from sup 5sup iCr-labeled blood leu- kocytes by centrifugation in isopyknic Percoll density gradients. These cells were mixed at different ratios and subjected to

Percoll gradient centrifugation. By this

approach as few as 5xl0sup 3 tumor cells could

by identified in the presence of 5xl0sup 7 leu- kocytes, representing a ratio in i:i0,000. Percoll centrifugation did not damage the tumor cells. In blood cells from two lung cancer pa- tients with lung metastases the incorporation of sup 3H-thymidine and sup 3H-galactose was significantly enhanced compared with that in blood cells from patients with primary lung tumors and in cells from normal individuals. The difference became even more apparent when metabolically-labeled blood cells were subse- quently separated by Percoll gradient centri- fugation.

Further Studies on the Differences in Cyto- toxicity of Human Peripheral Blood Monocytes and Bronchoalveolar Macrophages for Cultured Human Lung Cells. Swinburne, S., Morre, M., Cole, P. Host Defence Unit, Department of Medicine, Cardiothoracic Institute, Brompton Hospital, London, United Kingdom. Cancer Immunol. Immunother. 19: 62-67, 1985.

Previously reported differences between the cytostatic activity of human peripheral blood monocytes (PBM) and bronchoalveolar macropha- ges (BAM) for cultured human lung tumor cells have been further investigated. The differen- ces are both quantitative and qualitative and are shown not to be due to the respective me- thods of purification. There was a varying contribution of cytolysis to the cytostasis detected by the sup 7sup 5selenomethionine post-labeling assay used. Bronchoalveolar ma- crophages were cytolytic when tested at both low and high E: T ratios but PBM were only cy- tolytic at the low E : T radio. A variable de- pendence upon soluble cytostatic factor(s) was suggested, and there was evidence of heteroge- neity in the factors released by the two po- pulations. Cytostatic factor production by both populations appeared to be under similar regulatory constraints. In vitro maturation of PBM altered their cytostatic dose-response cur- ve to one resembling that previously reported for BAM. It was also shown that sera from poor-prognosis lung tumor patients, which sup- pressed the in vitro maturation of PBM, also suppressed the in vitro cytostatic activity of PBM for cultured human lung tumor cells.

Establishment and Characterization of Cell Lines from H~nan Small Cell and Large Cell

Carcinoma of the Lung. Bergh, J., Nilsson, K., Ekman, R., Giovanelle, B. Laboratory of Tumor Biology, Department of Pathology, University of Uppsala, S-751 85 Uppsala, Sweden. Acta Pathol. Microbiol. Immunol Scand., Sect. A Pathol. 93: 133-147, 1985.

Five new small cell carcinomas (SCC) cell lines and a large cell carcinoma (LCC) cell line were established from human lung cancers. The SCC cell lines had, as a group, common phenotypic properties which distinguished them from non-SCC cell lines. However, the