Purging of small cell lung cancer cells from human bone marrow using ethiofos (WR-2721) and light-activated merocyanine 540 phototreatment MeaghcrRC,Rothman SA,PaulP, KobemaP. WillmerC, BauccoPA. Section of Developmenuzl Hematology, Department of Laboratory Ilemaiology, Cleveland Clinic Foundation. Cleveland, OH 44195- 5139. Cancer Rcs 1989;49:363741.

One IimItation of autologous bone marrow transplantation for pa- tients with cancer has been the presence of tumor cells m the bone marrow. Methods toeliminate tumor cells while preserving hematopoi- ctic stem cells have been sought. The present study was performed lo analy/.e the m wtro cffectivcncss of light-activated merocyanine 540 phototreatment (LAMP) and an aminothlol (ethiofos) as a marrow- purging rcgimcn for small cell lung cancer (SCLC). Two human SCLC ~elllincs(ATCCHTB-l19andHTB-l20)werecrcatedw~thLAMPand exposed to light for varying periods of time up to 120 min. LAMP reduced SCLC cell proliferation and colony formation in a light exposure-dependent manner; colony formation was nottotally inhibited untillightexpsureof 120mm wasuscd.Attbis lightexposure interval, multipotential hematopoietic progenitors, colony-forming units-gran- ulocytc. erythrold. macrophage, mcgakaryocyte (CFU-GEMM), were subsrantially reduced. In an attempttodiminish hcmatopoietic toxicity, SCLC cells were mcubated with cthiofos (formerly WR-2721) for 1 hour before LAMP. SCLCcolony formanon wascliminatedat hghtcxposure mtervals (90 min or less) which had mhlbltory effect on CFU-GEMM. EthiofosdidnolprotectCFIJ-GEMM fromLAMPmh~bit~onat120mm. Ethiofos alone had no effect on the SCLC or hcmatopoleuc cells. When normal bone marrow as contamnxated wth I or 5% SCLC cells, ethiofos plus6Omin ofLAMPelimmatcdSCLC ccllabut had noeffectonCFU- GEMM. The results suggest that cthlofos sensitized SCLC cells to LAMP: thus ethiofos-enhanced LAMP may be an effective method for removmg metastatic SCL.C cells from bone marrow used forautologous marrow’ transplantation after high dose chcmothcrapy.

Amplification of oncogenes in lung carcinoma grafted in nude mice Chauvm C. Jacrot M, Rmndel J ct al. Lahorulowe de Medecinr er Chlrurqlr Experrmenrulcs~~r Comparces,Departemrnrdr~Biophyslque. UFR de Medecuw de Grrnohlr. 78700 La 7’ronche. AntILancer Rcs 1989;9:449-5’.

Seven lung carcinomas wcrc grafted on nude rmce and continuously propagated as in vivo modelson which theamplification of9oncogenes (N-myc, v-erb A, v-abl, v-sis, c-myc, c-myb, v-Ha-ras, c-Kiras, and v- scr) was studied by Southern blot hybndizatlon. Only c-myc was amplified (20 copies) in an adcnocarcinoma. The presence of 2 bands at 9 kb and 6.6 kb in addition to the normal 12.7 kb in EcoRl digested DNAs wggested a polymorphism of the c-myc gene in this tumor. The other 8 oncogcnes were not ampllficd in this tumor. The 5 small cell lung carcinomas of this study did not show any ampllficatlon of any of the 9 oncopcnw tcstcd.

Neuropeptides elevate qtosolic calcium in small-cell lung cancer CIAIS

Mood) TW, Mahmoud S, Stalcy J, Fiskum G. Deparrmem ofBlochem- u~rj. (;eorxe U’ashin~ton l~nwers~ly, School of Medicine and Health Sclenc es. WashinKfon, DC _700?7 Ann New York Acad SCI 1988;551:280-:,.

Small-cell lung cancer tSCLC) IS a ncurocndocnne tumor which I\ cnnchcd m its neurocndocrmc propertIcs. SCLC cells have high level\ of neuronal cwymes and polypepude hormones mcludmg bombesin (BN)-ltke pcptldes and ncurotcnsin (NT). Upon secrctmn from the SCLC cells the neuropcptidcs may diffuse and bmd to receptors present on the cell surface. SCLC cells have receptors that bind BN and the structurally related ga\uin-rclwsmg pcptlde (GRP) with high affinity. Also. SCLC cells have receptors for NT, vasoactivc mtestmal polypep- tide I VIP). and somatostatm (SRIF). VIP and SRIF rcccptors interact

with adcnylatccyclase poswvcly and negauvely, rcspwtl~cly. BN-like peptidesstimulatephosphatidylinositol tumovcrand thzresultingmosl- 101-l ,4,Qrisphosphate released elevates cytosolic Cal’ Icvels. Here we investigated whether ncuropcptides alter the cytowl~: (‘a” levels m SCLC ccllc.

Insertion of the v-Ha-ras oncogene induces differentiation of calci- tonin-producing human small cell lung cancer Mabry M, Nakagawa T, Baylm S, Pcttcngdl 0. Sorenson G, Nelkin B. Johns Hopkins Oncology Cenler, Balrrmore. MD -111 iI J Clin Invest 1989;84:194-9.

Human small ccl1 lung cancers (SCLC) and ccl1 lmes denvcd therefrom are phenotypically hetcrogcncou\ concerning neuroendo- wine differentiation. Unhke most SC1.C tumor’; and cell lines that express poorly diffcrentlated ncuroendocrinc ph’cnotyps, the SCLC cell lint DMS 53 exhibits mature endocrmc difltircntlation features, mcludmg unusually high cxprcssion ol the gcnc for the pcptidc hormone, calcitonm (CT). WC now rcp)rt that mwductwn of the viral Harvey ras (v-ras(H)) oncogcnc mm DMS 51 cells wa retrowal Infection. with resultant conslltutivc w.prc\wm, resulL\ m increased features of neuroendocrmc dlffcrcntwwn. 7-10 d after infection the cells demonstrated altered morphology, Increased (‘7‘ secretion, in- crcascd CT gene expression, markedly dnnnushcd cc11ular prolifcra- uon, and nearly abohshcd mcthylccllulose chmmg efflclency This response of DMS 53 cells to v-r&s(H) I\ unhkc the tumor progrcsswn cffcctswc have previously ohw-vcd mother SCIX‘ Imcs. Slgmficantly, the diffcrentlauon response that follow\ cxprcwon of the virally mtroduccd v-ras(H) oncogcnc m DMS 5 3 ccl]\ 13 hlm;lar to that 01. ncoplasuc ncurocndocrmc ccl] lines dcrlvcd from adrenal phctrhro- mocytes and thyroid C cells. The cllccts 01 constitutlvc was(H) cxpreslon m DMS S3 SCLC cells and other ncurocndocrmc cell Imes wggcst an mlportant role for ra\( H) or rclatcd gcrlc’\ 111 n~wrocndwzrme d~ffcrcntiation.

Lack of correlation between levels of MHC cla&\ I antigen and susceptibility to lysis of small cellular lung carcinoma 6CL.C) by natural killer cells Stam NJ, Kast WM, Voordouw AC ct ill f)eparrrwrll of Cellular Biochemrsi~, Nelherlands Cancer In.~i~rute. lOti (2’ 4m~terdam J lmmunol 1989;142:4113-7.

Small cellular lung carcinoma (SC1.C) cell lmes .ire su.scept:ble lo lysis by NK cells. SCLC. normally negauvc fbr mHC class I Ag. were rendered positive for HLA-A and -B AR hy two mcthtxls: treatment with IFN-gamma or uansfccwn with HLA ila\\ I gcncs. I~xposure to IFN gamma mduccd high Icvcls of class I Ag and rcduccd susccptibdity to NK-mcdlatcd lysls. However. transfccuon w&h clthcr IHLA-A2. HLA- B27,orHL.A-B27~1thO,mtl~dnotrcs~1It~nr~du~ecisu~cel~t~h~lit} toNK cells. These transfcctants cxprcbscd amounts 01 HL.A ( la\s I Ag Lompa- rahlc to those m IFN-gamma-trcatcd, unuan~fcctcd ccl]>. Translectlon with the U,m gent or plasmld alone ncllhcr Inlluenccl! Icvcls of hurfacc class I Ag nor rcsultcd m rcduccd auwcpt~b~ht> LO I wk hq Nk cells. Thuh, Ihccffc~t~oflFN-~nmrna~,n Yli w\icpt~h~lrt! % an hcdlwriated from the mductwn of ~I:I\\ I Ag.

Karyotypic evolution of a human undifferentiated large cell carci- noma of the lung in tissue culture Burholt DR, Shackncy SE, Kcttcrcr DM st al. ~~c~ntrf Cc,// Blologyand Generws Lahorolory. Alleghenv-Smgt,r R(~rc~nrr 11 In: ‘IIUIP. Pirt.+urqh. PA l5212. Cancer Rc\ lYUY:3Y:3355-61.

Serial cytogenetic studlcs wcrc pcrlwmzd on a cell Imc derwcd from a pleural cffusmn from a patlent wth undll’fcrermated large cell carcinoma of the lung. The lmtlal \amplc had a broad range of chromosome numhcrs per cell. with a hypodIploI,dip,eudtdlplold stem hnc and a hypotcuaplold sldclmc. A scqucnce cclnsl\ting of a doublmg 01. chromosome number per cell foiiowcd hy chromosome loss was