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SELECTIVE REACTIVITY OF CIBr YONOCLONAL ANTIBODIES (ILlAL) WITH LUNG CARCINOMA CELLS Pereira. A.. Pllkington, G.R., Dempsey, P.J.. Whitehead. R.Ii.l and Jose, D.-G. Peter Mac- Callum Cancer Institute and ’ Ludwig Insti- tute for Cancer Research, Melbourne, 3000.

A series of MAb was produced to the human breast cell line PMC42. Extensive testing of these MAb by immunohistochemis- try, immunofluorescence and immunoprecipita- tlon of labelled lysates on fresh tumours and cell lines has demonstrated these antibodies to react with molecules expressed on cells of epithelial and myoepithelial origin ranging In molecular weight (Mr) between 38 - 165 kDa. Differences in reactivity of the CIBr antibodies between foetal and adult tissues are evident suggesting expression of the corresponding antigens at different stages of differentiation in several epithelial tis- sues. Variable expression of the CIBr anti- gens was observed in malignant lung tissues and in some cases a correlation was evident between antigen expression and morphological subtype. Testing of the CIBr MAb has demon- strated CIBr7, CIBrl2, CIBrl7 and CIBrl8 to react with small cell Ca lung and all CIBr MAb to react with adeno and squamous cell Ca lung. Reactivity of CIBr9 and CIBr13 were hence specific for large cell carcinomas. Further analysis may reveal association of some of these antigens with clinical parame- ters such as response or survival.

olFFERENr ENERGY METASOIJBM INlWOSMAUCELL LUNG CANCER @Ct_CI SUBf’OPUlAllONS EXAMINED BY ~PMAGNmCRizSOt&JCE SPEcTRoscow (MRS) AND BlOCHEMlCAl ANMYSfS IN WV0 AND IN Vl?RO.

C. Kristensen, P.E.G. Kristjansen, M. Spang-Thomsen, B. Quistorff. Dept. of Oncology, The Finsen Institute, Institute of Pathological Anatomy, and NMR-center, University of Copenhagen, Denmark.

The two SCLC tumor lines, CPH SCCL 54A and 548, are originally derived from the same patient tumor. In spite of similar morphology and growth characteristics, they respond differently to therapy. The G, phase DNA content of 54A is twice as high as that of 548. The energy metaboliim of 54A and 548 was studied by “P-MRS and biochemical anafysis in vivo and in vitro. Xenografts on nude mice were used as the in viva tumor model, while for in vitro MRS the cells were retained in perifused agarose gel threads in a 2.5 cm hollow plastic sphere. A significantly higher ATP/P, ratio in 54A than in 548 was demonstrated by both methods, thus indicating that this metabolic difference is an intrinsic quality of the tumor cells and not caused by stromal factors as e.g. oxygen supply. Biochemical analysis of freeze-clamped tumor extracts and extracts of cell cultures corroborated the MRS results and the difference in ATP/P, ratio was found to be caused exclusively by a diierence in the cellular ATP level in 54A and 548. Phosphocreatine was found in small amounts in the xenografts but not in the pure in vitro cell cultures, which indicated that the phcsphocreatine content of the solid tumors was of stromal origin. The combined methodology of thii study provides a means for non-invasive analysis of the energy metabolism in tumor lines as well as a distinction between metabolic proponies of tumor cells and solid tumors including their stromal components.

;g Nuclear A- cancer subtvoes J.L.V. Broers, ‘H. Kuijpers, F.C.S. Ramaekers, Dept. of

Molecular Cell Biology, Univer&y of Limburg, P.O. Box 616,62&l MD Maastricht, The Netherlands.

Lamins belong to the family of intermediate filament proteins and make up a fibrillary network that constitutes the nuclear lamina. It has been well-established that lamins A and C (A-type lamins), but not B-type lamins are differentially expressed during embryogenesis, being absent in undifferentiated cells and the earliest stages of development.

We have examined 20 small cell lung cancer (SCLC) and 10 non- XLC cell lines for their lamln expression patterns, using different monoclonal antibodies in immunocytochemistry and immunoblotting experiments. Non-SCLC cell lines were positive with both B-type and A-type lamin antibodies, while SCLC cell lines were in general positive with B-type lamin antibodies but negative for A-type lamins. These data were confirmed by Northern blotting experiments using a cDNA probe hybridizing to lamin A and lamin C mRNA. Similar observations were made in freshly frozen lung tumor specimens of SCLC and non-SCLC, showing that most SCLC did not express A-type lamins. In contrast, non-SCLC did contain both A- type and B-type lamins.The applicability of lamin antibodies in lung cancer diagnosis as well as the biological importance of this phenomenon will be further discussed.

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Sensitivity to adriamycin of two sets of small cell lung cancer (SCLC) cell lines from indiiual patients

Lone Nergard Petersen, Svend A. Engelholm & Mogens Spang- Thomsen. institute of Pathological Anatomy, University of Copenhagen, Frederik V’s Vej 11, DK-2100 Copenhagen, Denmark.

Two sets of SCLC cell lines, each derived from individual patients, were tested for sensitivity to adriamycin (ADM) using the clonogenic assay. GLC 14, 16 & 19 were established from a patient prior to treatment, after combination chemo- therapy, and following additional radiotherapy, respectively. GLC 26 & 26 were established from another patient before and after treatment, respectively. The semi-log survival curves of the lines had an initial shoulder representing the repair capacity for ADM sublethal damage (DJ followed by exponential cell kill, the slope (DJ representing the cellular sensitivity to ADM. The pre-treatment derived tumors, GLC 14 and 26 had smaller DO, i.e. were more sensitive than their “treated” counterparts (Table). Furthermore, GLC 16 & 19 showed a pronounced increase in 0, compared to GLC 14, whereas no difference was found in D, between GLC 26 and 28. The results seem to reflect the development of chemoresistance in the patients, and the sensitivity analysis further detailed the changes with respect to D, and 0,.

GLC14 GLCl6 QLCW QLC28 QLC28

DO 13 37 28 14 34

Dq 13 47 35 33 32

Addamycin dou ot 0, and 0, am &ml x10’