132 Abstracts/Lung Cancer IO (1993) 123-150

complexp~ttemof~drconsistentwithei~~~complexg~estruc~n co&oing maoy exoos or- the p-ce of P family of closely related gales.

MolecuIor clmmchization of a Iafge homozygols deletion in the small cell hmg cancw ceJl line U2@2& A strategy for cloning the putative tumor suppressor *au Latif P, Tory K, Modi WS, Grszisno SL, Gamble G. Douglss I e( al. Lubomta~ of Immunobiology. NCI-FCRDC, Fredmick MD 21702- 1201. Genes Cbmmommea Cancer 1992$:119-27.

Homozygoas deletions sre inst-tsl in the detection and cloning of tumor suppressor genes. We report the isolatioo nod characteriutiooofRnew~l~ypmbssssavltiagosubmi-pic homozygw deletion detected io the DNA of the small cell lung caocer (SCLC) cell line u2020. The probes were selected From P large coll~tioa,coveriogthe~ttirelsngtbofchromosome3withaoestirmted avenge spacing of 100-150 kb. Bwed on the number of probes in the deletioo end the probe density, the size of the U2020 submicroscopic deletion was estimated to be io the noge of 4-7 megnbases. Among the deletedloci, 17shmvedccmsavotiwacrosaspecifs,pmbeblyrepresenting potential coding gene sequences. By genetic and physical mapping of s large randomly chose~~ lkction of the deleted probes, we detined the location of the U2020 deletion within chromosome baod 3~12. Our cloning strategy is based on oarrowing the region of interest by elimioatiig probes that retaio hetemaygosity in SCLC samples, thus selecting for probes in the region of commoo loss.

iung hanours, are d&&able in prein&ive lesions of the Soodaresao V, Geoly SP, Huleton P, Rodd R, Sinha G, Bleeheo NM et sl. Medical Research Council, Clin. Ondqy/Radiothmqxul Unit. Hi& Road, Cambridge CBZ 2QH. Oafogeae 1X%7:1989-97.

Bronchial epithelial dysplasia is believed to precede invasive s+amoos cell carciooma of the lung. Six paixed dysplesia nod hamour samples were distinguished kistologicelly io secticms of formal&fixed paraff~n-embedded lung tissue from patients with long caocer. Additionally, ssmples of dysplastic braachisl epitheliam wereobtained from p&ients without lung htmaws. Microdisswtion of the anstsined sections provided dysplastic nod tomour samples from which DNA was prepared for comparisoo with the ptients constihltiooal genotype, using polymerase &ii rasctioo-based restriction fragmmt leagth polymorphism analysis. All six samples of Nmow nod the paired edjaceot samples of bronchial dysplssia showed loss of heterozygosity (LOH) st loci on the short srm of chromosome 3. Five of the six cases showed iavolvemeot of the p53 gene ss assessed by LOH nt the AccII site within the gene, sad by immanoffsctivity to CM-l. 011 aatihady which rec0gnizes the mutsted form of the p53 protein in psmflin- embedded msterisI. Of the dysplastic sunpies, obtsimxl from pstients without invssive tumows. sll three. showed LOH st 3p; one sample showed LOH at the A&I paIym.xphic Iotas within the ~53 gene, and snotk sample, winformative st this locus, stsined positively with this sntibady. These results indicate thst somstic genetic &sages are present in preinvssive lesions in the bronchus.

Antitwnoralactivilyoftamln+nmmb@esana~ll~elll~ cancerx~Rela~pwithhombainreaptorapprssion ThomasF. A~eloF. AotoioeE. JacrotM.Po~h4.F. IpscnBioscah. 30 rue Cambmn~~, 75015 Park Cancer Rea 1992;52: 4872-7.

Gsstrin releasing peptide (GRP), the humso hamologue of bombeeia (BN), is m subxxine growth f&tar for smell cell hmg caocer (SCLC)oells.Thesynthetico~~‘-aLcUcdskMdSL (BIM 26182) cod [D-~-Lcu”~NH~~“]~(6-14)N~ (~1~26189)~dotsot~~~/~~m~~tsf1heprolifentiollof3T3 sadntpncrascelIs. TbeeffectoftbwsnsIoguesontbepr0lifersti~ offourSCU:cslll~(SCU:6,SCLC41,SCU:75,SCU:74R)~ tsszedinvitro~iavivo.TwooftheseSCU:Lines(SCLC41Mnnd SCLC 75) hd nxeptma far BNWRP sad expressed the prsprooRp mRNA. BIM 26182 sod BIM 26189 inhibited [‘Hlthymidine

intxrporetioaintotheDNAofSCLC41celIs, stimuIsted[‘H]thymidioe incorporstion ia SCLC 6, sad hsd no effed 011 the two other ceII lines. The SCLC implpnted 6.c. in nude mice were treskd with either BIM 26182orBIM26189.B1M26182sndB1M26189inje&dstthedow of5Og hvices dny (s.c.) smuadthe tumor for 10 to21 daysdelsyedthe growthofSCLC4l~ofSCU:75.ThsmuimPleffectwssobeerved duria8 the tmatment period, sftez which the tumors regrew, suggesting P cytaststic effect of these peptides. No inhibitory effect of the peptik on SCLC 74R or SCLC 6 growth wss observed. These dsts suggest thst GRP~~o~sts~sbletoinhibittheinvitro~dinvivogrowthofBNl GRP receptors-positive SCLC.

pathology

Relationship of the queuine content of transfer rihonocleic acids to histopathological grading and survival in human lung cancer Hung B-S, WuR-T, Chico K-Y. Graduaie CIinicalMedicinelnrrirutr, National Yang-Ming Maiical College, Taipei. CsmcerRes 1992;52:46%- 4700.

To elucidste the significance of tRNA hypomodified with queuine to the grade of msligmmcies in hamso solid tumors, the smmmt of tRNA lwinn rmanosine ia tke of aaeuosine wss dekermined in humsa Iunn

residue for [‘H]gumine. The reaction is catslyzed by guniae:queuine tRNA tmnsglycceylsse. Tots1 tRNA wss extrscted tium 23 different lung cancer specimens sad the precursor of iseacceptor tRNA thst contains gusnine instead of qaeaine in the first or wobble position of the saticodon [(Q-)tRNA] content wss determined. In 12 csses the (Q-)- tRNA W&F determined in normsI lung tissues ss well. In each individas1, the (Q-)tRNA content in Ian8 cancer- tissue wss higher thsn that of the normsl lung tissue. The (Q-)tRNA content wss not correlated to the swgicopsthologicsl stsging of the pstients but wss highly correlsted to the histopsth0Iogical clsssitication of the tumors. The smounts of (Q)tRNAwere1.75*0.67(SD),2.36 *0.89,3.77 f 1.39,5.18* 2.32.imd7.65 f 1.34pmol/~,innonnal,weU,~ly,moderately toworlv. andwcwlvdiffe~tisted tumors. Thediffereacefmmnormsl

(P < O.OS).‘In 10 pstieots with (Q-)tRNA high& thk 3.5 p&I/q,, their caacers relapsed snd only 2 were. alive P&X 4 years. In 11 pstieats with (Q-)tRNA less thsa 3.5 pmol/~& in their lung wxx tissues, 7 patients were still alive witbout sny evidence of diseese, 3 were dead, sod I hsd recurrence of disease. These results, tsk together with other previous studies, suggest thst P decreased queuesine content of tRNA may be P general feahlre. of neoplssms and may be usefal for grading msIigmmcy snd perhaps also for the prediction of survival in human lung cancer-.

Preferential expression of immunoreactire fucosyl-ide in sdemxwci- of the long YsmsdaH, IshihwH. KitsgswsH, KwsbstsY, ItaysmsS, Sugwsrs 1. Lkpamnent ofPathology, Saimma Medical Cam. Saitama Medical School, 1981 Tsujih-aho. Kamodn. Kawagoe, Saitm 350. Cancer Res 1992;52:4408-12.

The expressian of fuwsylwemide (PC47H sntigea) in 97 lung cancers sad 4 extmpaImmwy sq-as cell cnrcinamss was exsmined with the use of. novel monoclaml antibody, PC47H. rsognizing fucasylcsrpmidcspsifi~ly.Tbsobselvsdv~stioninfucosyl~de wntexd wss wt on tlw degra, of gIemhdsr differentistion in &s~~~&~rmofthcIuag. FawsylcemmidewssbandaatIyexprwed in well differeatisted sden~tcinoms of the tang sad pc&y expressed inpcmrlydiffetm~ti sdemwcinonr. Samesqusmaas cell CprciIlOmaS of the lung reacted with this monacIonsI antibody wakIy, but the reection wss aated only st the periphery of the epithelisl sheets. Extnpulmoosry sq-us ceII urcinoms snd smsll cell cnrcinomss did not nrct with monoclonsl sntiboay PC47H. Intexestingly. lsrge cell

which lccumdstd in the c&&xn. At the uItmst&tursI level,