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papillary tumors arose from the pulmonary acinus, invading the bron- chioles only as the tumors grew. Furthermore, a mixture of solid and papillary patterns within a single nodule did not represent a merging of two tumors butaprogression from thesolid tothepapillary form. By use of two rabbit antisera against mouse lung surfactant apoproteins found in normal alveolar type II cells, it was shown by the avidin-biotin peroxidase complex proccdurc, by the peroxidase-antiperoxidase tcch- nique, and by indirect immunofluorescence that both solid and papillary tumors contained these proteins that are specific markers for alveolar type II cells. With a rabbit anti-rat Clara cell antiserum, none of the tumors studied was immunoreactive while normal Clara cells were reactive. The nitroblue tetrazolium formazan stain for dehydrogenase enzymes, found particularly in Clara cells, did not reveal these enzymes in any lung tumors from either strain. Ultrastructurally, no typical features of the mature Clara cell were detected in papillary or other pulmonary neoplasms. However, all tumors showed characteristic alveolar type II cell structures such as various stages of Iamellar body formation, although these features were less well differentiated in the papillary tumors. Argentaffin densebodies, representing lysosomes and

immature forms of Iamellar bodies, were commonly observed in papil- lary tumors. Some features of the papillary tumors such as cell shape, high glycogcn content, and primary cilia were equivalent to those seen in pulmonary epithelial precursor cells during fetal development. With age, the papillary tumors became invasive, accumulated neutral lipids, and developed bizarre cleaved nuclei and lamehated nuclearpseudoin- elusions. In conclusion, the papillary lung tumors of the mouse, at least those induced transplacentally by N-nitrosoethylurea, constitute less well-differentiated or poorly differentiated alveolar type II cell adeno- mas or carcinomas with fetal morphological and biochemical proper- ties.

Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors. Papa MZ, Yang JC, Vetto JT, Shiloni E, Eisenthal A, Rosenberg S.A. Surgery Branch, National Cancer institute, Bethesda, MD 20892. Cancer Res 1988;48: 122-9.

We have evaluated the effects of chemotherapeutic agents on the toxicity and antitumor benefit of therapy of established murine tumors by high-dose interleukin 2 (IL-2). Cyclophosphamide (Cy), doxorubi- tin, and bischloroethylnitrosourea were given to normal mice prior to IL-2 administration to test the effects of these agents on IL-2-induced toxicity. Cy at doses of 100 mg/kg and 150 mg/kg completely protected mice from a 100% lethal dose of IL-2, and doses of 50 mg/kg and 150 mg/kgallowedtheadministrationofamedianof4Sand lO.Omoredoses of IL-2,respcctively, bcforedcath from IL-2 toxicity occurred. Doxoru- bicin at 8 mg/kg and bischlorocthylnitrosourea at 20 mg/kg did not impact on toxicity in IL-2 trcatcd mice. In mice bearing pulmonary metastases of the weakly immunogenic MCA-I05 sarcoma, IL-2 in- creased median survival time from 33 (no IL-2) to >60 days for all doses of IL-2 tested when combined with a single injection of Cy at 75 mg/kg (P < 0.002). Increasing doses of either Cy or IL-2 produced increasing benefits on survival which were always greater than either treatment alone. Thcsc effects of Cy and IL-2 were also seen in mice bearing the nonimmunogenic MCA-101 sarcoma and a murinc adenocarcmoma (MCA-38). Doxorubicin and bischlorocthylnitrosourea did not consis- tently enhance the effects of IL-2 treatment. Cy appears to reduce the yield of in viva gcncratcd lymphokine-activated killer cells, but these lymphokinc-activated killcrcclls are still lytic for fresh tumor targets in vitro.Thus,thcmcchanismofthc thissynergydoesnotappcarto involve stimulation of lymphokinc-activated killer cell activity, but may in part involve reduction of tumor burden by the chemotherapeutic agent, an increase in susceptibility of tumor to cellular immune Iysis, and/or a dccrcasc in suppressor ccl1 activity mediated by the chemotherapy.

Nuclear DNA content, cytomorphologic features and clinical char- acteristics of small cell carcinoma of the lung. Abe S, Makimura S, Itabashi K, Kawakami Y. Department of internal Medicine, llokkaido University Faculty of Medicine, Hokkaido. Anal Quant Cytol Histol 1987;9:495-8.

The relationship bctwecn the cytomorphologic features, the nuclear DNA patterns and the clinical prognosis of patients with small ccl1 carcinoma of the lung was studied. In cases in the long-survival group (-24 months), bronchial brushing smears contained a relatively high frequency of nuclei with large irregular shapes and finely granular chromatin patterns, in comparison with patients in the short-survival group (-9 months); the correlation was not statistically significant, howcvcr. The incidence of cells with round or oval nuclei and finely granular chromatin patterns was higher in patients whose cells had hypcrdiploid DNA patterns than for patients whose cells had near- diploid patterns; again, the diffcrcnce was not statistically significant. Patients whose tumor cells had hyperdiploid DNA patterns had signifi- cantly shorter survival times than did patients whose tumor cells had near-diploid pattcms. These results indicate that (1) judging the nuclear DNA pattern from thecytomorphologic fcaturesofsmall cellcarcinoma is unrcliablc and (2) the nuclear DNA patterns are related to the clintcal prognosis of patients with small ccl1 carcinoma of the lung.

Expression of antigens associated with small cell carcinoma of the lung on hematopoietic progenitor cells. Ball ED, Kcefc KA, Colby E. Department of Medicine, Darfmouth Medical School. Ilanover. NII 03756. Cancer Res 1987;47:6556-9.

We have previously dcscribcd a panel of four monoclonal antibodies (MoAbs)reactivc withantigcnscxprcssedon tumorcellsfrom smallcell carcinoma of the lung (SCCL). These IgM MoAbs are cytotoxic to SCCL cells in the presence of complcmcnt and thus have potential as reagents for the removal of SCCL cells contaminating bone marrow autografts. Thercforc, we examined the cytotoxicity of these MoAbs against normal hematopoictic progenitor cells as a preliminary step toward their USC in clinical trials. In this paper we report the results of treating normal bone marrow and peripheral blood mononuclear cells with the four IgM MoAbs, as well as an IgG2a MoAb that we have rcccntly prcparcd against an SCCL cell line, DMS 406. Peripheral blood and bone marrow mononuclcarcclls were treated with the MoAbs alone orincombination, rn thcprcscncc ofrabbitcomplemcnt,and then plated intocolony-formingassays.Notably,onlyone MoAb.SCCL-I, hadany dcmonstrablc cytotoxicity against progenitor cells. This toxicity was limited to bone marrow burst-forming unit-crythroid and all classes of blood progcnrtor cells. A MoAb cocktail containing a combination of cithcr four or five MoAbs + complcmcnt spared most marrow progenitor cells. Thcsc studies extend the base of information regarding the cxprcssion of SCCL-associated antigens on hematopoietic cells and indicate that sclcctcd MoAbs may bc used safely for the removal of SCCL cells from autografts by complcmcnt-dependent lysis or other means.

High affmity binding of VIP to human lung cancer cell lines. Shaffcr MM, Carncy DN, Korman LY, Lebovic GS, Moody TW. Department of Biochemistry, The George Washington University School of Medicine and lleaith Sciences, Washington, DC 20037. Pcptides 1987;8: 1101.6.

The binding of ‘XI-VIP to human lung cancer cell lines was investi- gated. Radiolabclcd VIP bound to adenocarcinoma, squamous cell carcinoma, large ccl1 carcinoma and small cell lung cancer (SCLC) cell lines. As SCLC ccl1 line NCI-N592 bound radiolabeled VIP well, its binding was further charactcrizcd. ‘uI-VIP bound to membranes in a specific and time dcpcndcnt manner. lzI-VIPbound with high (Kd=0.8