406 Abstracts/ Lung Cancer 10 (1994) 395-430

CNRS. Itwtitut Curie, 26 Rue d’lJlm, 75231 Paris Ceda 5. Int J Oncol 1993:2:621-S.

The analysis of oncogette expression may provide insights into the pathogen&s of small cell lung cancer (SCLC) and may help to predict clinical behavior. The expression of 8 oncogenes (c-myc, N-myc, L- myc, Ha-t-as. Ki-ms. N-ms, erbB-2. v-sis) was evaluated in small cell lung cancer (SCLC) xenognfts of tumor samples, recently transplanted, taken from 17 different patients. Eight ofthese 17 SCLC linesexpressed the L-myc oncogene and 2 SCLC lines expressed the c-myc oncogene. One SCLC line (SCLC63M) simultaneously expressed the L-myc and c-myc oncogenes. Ail SCLC lines examined bad almost similar high RNA levels of the Ki-ras oncogene, while the expression of Ha- and N- ras oncogenes was not always observed. The N-myc and v-sisoncogenes were c?xpressed in only one tumor and at a very weak level, and no transcript of the erbB-2 oncogene was observed in any of our I7 SCLC lines. These results indicate that oncogene expression in SCLC lines is heterogeneous, with the exception of the Ki-ras oncogene which is constantly overexpressed.

A novel small cell lung car&oma-specific DNA-binding activity related to tbe transaiption factor AP-1 Adsmkiewicz J, Behn M. Brusselbacb S. Havemann K. Muller R. Inst. Molekularbiologie/Tumorforsch., Philipps-Universirat, Emil- Mannkopff-Strasse 2, D-3550 Marburg. ht J Oncol 1993;2:503-12.

A novel TRE-binding protein complex was detected specifically in 12 out of 13 small cell lung carcinoma (SCLC) cell lines. This complex

complex present in all other carcinoma cell lines analysed. As shown by UV-crosslinking and South-Western blotting, the SCLC-specific complex contains a protein with an apparent M(r) > 100 kD, which is far bigger than all Fos and Jun proteins described lo date. In addition. the DNA- binding specificityofthiscomplax isdifferent fromthespecificityofthe ‘ubiquitous’ complex or a FosNun beterodimer.

Regulation of E-cadherin-mediated adhesion by muscarinic acetylcboline receptors in small cell lung carcinoma Williams CL, Hayes VY. Hummel AM, Tarara JE, Halsey TJ. Department of Immunology, Mayo Clinic, 842A Guggenheim Building, Rochester, MN55m5. J Cell Biol 1993;121:643-54.

We. present the tirst evidence that adhesion mediated by a member of the cadhsrin gene family can he regulated by a G protein-coupled receptor. We show that activating the M, muscarimc acetylcholine receptor (mAChR) rapidly induces E-cadherin-mediated adhesion in a small cell lung carcinoma (SCLC) cell line. This response is inhibited by E-cadberin antibodies, and does not occur in another SCLC call line which expresses functional mAChR but reduced levels of E-cadberin. Protein kinase C may be involved, since phorbol 12-myristare 13- acetate also induces E-cadberin-mediated aggregation. Immuno- tluorescence analyses indicate that mAChR activation does not grossly alter E-cadberin surface expression or localization at areas of cell-cell contac[. suggesting mAChR activation may increase E-cadherin binding activity. Our findings suggest that G protein-coupled receptors may regulate processes involving cadher&mediated adhesion, such as embryoorc development, nrumgenesis, and cancer metastasis.

Lymphocyte subseu in putients with lung cancer treated with tbiophospboric acid alkaloid derivatives from Chelidonium mqjus L. (Ukrain) Staniszwski A, Slesak B. Kolodziej J, HarlozimkaSxmyrka A. Nowicky JW. Dept of 7horacic Surgqv, Wroclaw Medical School, Grabis~oskz 105, PL 53 439 Wroclaw. Drugs Exp CIin Res 1992;18:Suppl. 63-7.

Lymphocyte subsets were evaluated in nine men (aged 42-68 years,

mea0 57 years) with histologically proven lung cancer, previously untreated. Lymphocyte. s&populations were quantified by iamuno- tluorescence using monoclonal antibodies against total T-cells, T-helper and T-suppressor cells. In addition, the percentage of NK cells and the belperlsuppnssor (H/S) ratio were evaluated. The n&ber of B-cells was determined by surface immunoglobulin immunofluorescence. ChelidoaiummsjusL.@ceparationUkraio)wasPpplialasaaintravenws injection every three days. One course consisted of 10 applications of IOmg each. All immunological tests were performed before and after drug administration. The treatment was generally well tolerated. T’he results showed an increase in the proponion of total T-cells, and a significant decrease in the percentage of T-suppressor cells. The normalization of the H/S ratio was also noted. However, there were no signs of activation of NK, T-helper and B-cells. The restoration of cellular immunity was accompanied by an improvement in the clinical course of the disease. This effect was particularly pronounced in patients who responded lo Further chemotherapy. Objective tumour regression (CR + PR) was seen in 44.4% of treated patients. Four out of nine patients (44.4 %) died of progressive disease during the course of this study. it is coacludd that Ukraii can be immunologically effective in lung cancer patients and can improve human cellular response.

In vitro characterization of lung cancers by the w of ‘H nuclear magnetic resonancespectroscopy of tk~~~tractsand dkriminant factor analysis Hanaoh H, Yosbioka Y, Ito I, Niitu K, Yasuda N. Deportment of Radioiogy, School of Medicine, Kyorin Universiry, 6-20-2. Shinkmva. Mitaka, Tokyo 181. Magn Resoa Med 1993;29:436-40.

Using proton magnetic resonance spectroscopy (‘H MRS) spectra were obtained in vitro from extmcts of four types of lung cancer (squamous cell, adenocarcinoma. large cell, small cell) and oormal lung. The hydrophilic phase of the chlomform/methanol-water extracts yielded several distinct peaks. Among them the peak areas for cholines. creatines, glycine, and alanine, and their ratios were calculated and used as parameters to characterizedifferent lung tissues. The ratios, cbolines/ alanineandglycineialanine, weresignificantly(P < 0.001 to P < 0.05) higher for the normal lung than lung cancers. Creatmesiglycine and creatinas/cholines generally provided good discnmination (P < 0.001 to P < 0.05) between any two types of lung cancer. When data were tirtber analy& by discriminant factor analysis, there was 81.5 to 90.7% accuracy in predictmg between normal lung and each cancer type, or among the four types of lung cancer. These results suggested that ‘H MRS might be useful as an adjunct modality in the differential diagnosis of lung cancers.

The molecular biology of lung cancer pathogen&s Minna JD. Simmons Cancer Center. University of Texas SW Medical Crr., S323 Harry Hines Blvd. Dallas. Ix 75235-8590. Chest 1993: 103:Suppl. 449S-56s.

Lung cancers exhibit multiple genetic lesions including mutations activating the dominant cellular pmto-oncogenes as well as those inactivating the recessive or ‘tumor suppressor’ genes. Candidate Nmor suppressorgenes include those onchromosoms Ip. lq, 3~14.3~21.3. 3~2.5 (VHL gene), 5q21 (APUMCC genecluster). 9~21-22 (interferon genecluster), 1 lp, 13q (rbgene), 16~24. and 17~ (~53 gene). Mutations inp53 inactivate& transcriptionalactivity, whilereplacementofawild- type ~53 in lung cancer cells inhibits growth and tumorigenicity suggesting that p53 acts as a master growth regulatory switch. Lung cancer cells exhibit several positive autocrine growth factor loops and express nicotine receptors which could timcoction as Nmor promotmg systems. In addition. they express a negative autocrine loop mvolving opioids and their receptors which is reversed by mcotine acting through