Abstracts/Lung Cancer 12 (199s) 113-160 125

Thcortgta of isocbnunosomcs and their si&fruance ht tumorigcnesis of human lung cancer Fu S-B, Li P, Feng X-L, Liu C-X, Liu Q-Z. Laboratory ofMedical Genetics, Department of Biology, Harbin Medical Universify, Harbin 150086 Cancer Gent Cytogenet 1994;74: 120-2. Isoehromosomca related to chromosomes I, $6.8, and 9 were frequently nbservcd in 23 cases of lung cancer. Their existence in tumor cells might he nonrandom Premtue eentmmere sepanuion (PCS) was found in the PGT-13 1 cell line of a lung cancer. It is suggested that PCS may play a role in the formation of isochromoromes in lung cancer.

Expression of the glutatbione S-transferases in human lung carcinoma Guo S-C. Department of Pathology, Generat Hospital, Beijing Command ofPL4, Beijing. Chin J Clin Gncol 1994;21:271-2. The content of glutathione S-transterases (GST) were immunohisto- chemically analyzed in 84 cases of human lung carcinoma of various histological types and compared with that of 23 cases of pulmonary non-cancerous lesions. Acid GST were demonstrated in squamous cell carcinomas, adenocarcinomas, adenosquamous carcinomas, stnmll cell carcinomas, carcinoid tumors at rates of 93.5%, 66.7%. 83.3% 7.1%, 18.2% respectively, but seldom presented in non-cancerous lesions. However, basic, neutral and non-acid GST were seldom presented in both carcinomas and non-cancerous lesions. The results indicated that acid GST may be a useful marker for squamous cell carcinoma, adeno- carcinoma and adenosquamous carcinoma in distinguishing from non- cancerous lesion.

A rncc-spceific genetic polymorphism in the CYPlAl gene is not associated with lung Cancer in African Americans Kelsey KT, Wtencke JK, Spitz MR Lab for Molecular Epidemiology. Dept of Epidemiol and Biostatistics, University of California, San Francisco, CA 94143. Carcinogenesis 1994;15:1121-4. In a case-control study, we tested the hypothesis that a previously described African American-specific polymorphism in an intron 3’ to the coding region of the CYPlAl gene was associated with the occurrence of lung cancer. The study population included 72 African Americans with newly diagnosed, untreated lung cancer who presented to collaborating clinicians at the University of Texas M.D.Anderson Cancer Center and from county, community and Veterans Administration hospitals in the Houston metropolitan area. ControIs were 97 African Americans, frequency-matched on gender and age, recruited from wmnmnity centers, churches, cancer screening programs and from among hospital employees. The prevalence of the variant CYPlAl genotype did not mer between the cases and controls. The odds ratio for individuals with one or more copies of the variant allele was 0.64 [95%contidencc interval (CI) 0.3-1.41. Overall, 20.7% ofthe population had one or more variant alleles; the prevalence in cases was 16.7% and in controls it was 23.7%. Two individuals with the homozygous variant genotype were controls while one individual with lung cancer was found to have the homoaygous variant genotype. The lack of an association between genotype and lung cancer persisted after subgroup analysis for lifetime cigarette smoking history and tumor histology was performed. The sample size of this study is sufficient to detect odds ratios of three or greater; associations of this magnitude are similar to those reported in studies of a different polymorphism in the same region ofthe CYPlAl gene in Japanese. Thus, it is tutlikely that this polymorphism is associated with sizable risks for tobaao-induced lung cancer in this population subgroup.

Be-asswsmeot of acidic glycmphiaptipids in smalkell- hmg-canccr tissues and cell Iinca Gnewuch C, Jaques G, Havemann K, Wiegandt H. Inst. Phystologische Chemie, Abt. Hamatol./lmmunol./Onkol., Philipps-Universitat, Karl- van-Frisch-Str 1, D-35033Marbwg. Int J Cancer 1994;57:Suppl. 8: 125 6. The occurrence of tumor-associated glycosphingolipids (GSLs) has been dccumentedin avarietyofcancer tissues@akomori, 1984,1985,1989). In the case of small-cell lung cancer (SCLC), the monosialoganglioside WFuc-IPNeuAc-Gg,Cer (Put-GMl; short notations of gangliosides were according to Svennerholm, 1963) first described from bovine liver (Wiegandt, 1973). was found to be a unique tumor-associated GSL (Nilsson et al., 1984). It is present in up to 900/a of all SCLC cases as compared with 25% tiequency in non-SCLC, and no occurrence in normal lung (Btezicka et al., 1989,1992). Thus, FucGMl may represent a suitable target antigen for immunotherapy of SCLC, and successlid experiments have been performed showing tumor-cell killing by monoclonal antibodies (MAbs) against Fuc-GMl, both in vitro and, in a mouse model, in viva (Brezicka et al., 1991). However, an effective tumor vaccination in humans would require this antigen to be expressed hy the primary tumor and also by all metasmsea. The co-expression of Fuc-GM1 has already been repotted in primary tumors and in most but not all metastams of SCLC (Hanqing et al., 1986, Nilsson et al., 1986; Brezicka et al., 1989). In view of the signiticance this ganglioside may have for possible immunotherapcutical approaches to SCLC and of the difticulty io obtaining a sutEcient number of samples for analysis, a re- asaemment ofFuc-GMl expression was made in SCLC primary tumors and their metastases, as well as in established SCLC cell lines. In addition, the possible pmsence of such gangliosidea, that might help to urplain the selective tetanus-toxin binding of SCLC cells (Critchley et al., 1986; Henmnns et al., 1989) was investigated. Finally. the typical owurrence of sulfatide in all SCLC tissues and cell lines could be eat&w.

Characterization of somatostatin receptors and gtuwth inhibition by the somatostatin anabpe BIM23014 in small ccl1 hmg carcinoma xenograftz SCLC-6 Prevost G, Bourgeois Y, Mormont C. Lerrant Y, Veber N, Poupon ME Thomas F. Ipsen-Biotech, 24 rue Erlange,: 75781 Paris Cedex 16. Life Sci 199455: 155-62. Human small cell lung cancer (SCLC) is a neuroendocrine tumour with a very poor prognostic, Receptors for somatostatin-14 and its synthetic analogne BIM23014 (Lanrcotide) were characterized in 3 human SCLC xenografts (SCLC6, SCLC-t0 and SCLC-75) transplanted in nude mice. The binding activity of both iodinated Iigands wns tested by C-TOSS-

linking assay. One major complex of 57kDa was identified by both ligands in all 3 tumours. Two other minor complexes were only detected by the natural l&and: 90kDa in all 3 tumours and 70kDa in 2 out of the 3 tumorus (SCLC-6 and SCLC-75). Analysed by Northern hybridization, the expression of the gene encoding for the receptor subtype I was detected in all 3 tumours whereas the expression of the receptor subtype II was only detected in 2 out of the 3 tumours (SCLC-6 and SCLC-75). No receptor subtype HI transcript was observed. The relative quantification of the detected messengers and of the cross-linked complexes determined by densitomehy suggested that SCLC-6 contained a large amount of somatostatin receptors. SCLC-6 growing in nude mice was used to evaluate the antiproliferative effect of BIM23014. BIM23014 (250 ig, b.i.d. for 5 days)signi6cantlyinhibitedtumorgrowtb and had an additive effect with cis-platinum (1.5 m&/day for 2 days) when given concomitantly. Wues of the relative tumour volume as compared to control were: BlM23014 alone 57%, cis-platinum alone 57% and BlM23014 + cis-platinum: 78%. These experimental data