Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer
2
Abstracts/Lung Cancer 13 (1995) 81-104 Ca” rbd not a5ect the action potential production, whereas 5 iM TTX or subslttutton of Na* with cholineabolished rt. Action pMentiaIselicited rn the Ca”-free condition were reversibly blocked by 4 mM M&I, due to the Mn”-induced inhibition of voltage-dependent sodium currents (I(Na)) Therefore, Na’ channels, not Ca’* channels, underlie the excitability of SCLC cells. Whole-cell @a) was maximal with step- depolarizing stimulations to 0 mV, and reversed at +45 2 mV, tn accord with the p=dicted Nemst ectuilibrium pofential for a Na+-selective channel. i(Na) evoked by dep&izing test potentials (-60 to +40 mV) exhibited a transient time course and activation/ mactivation kinetics typical of neuronal excitable membranes; the plot oftbe Hodgkin-Huxley parameters. m() and ho. also revealed biophysical similarity between SCLC and neumnal Na’ channels The single channel current amplitude, the armsense-treated cells compared tith control-treated cells in NCI- H209. Togctkr with unique charaaeristia of the Llnyc gene. including: (a) a frequently amplified and overexpressed state in SCLC; and (b) very rcstictcd and low-level expression in human adult tissues. the present data indicate that L-myc is a good candidate for the target gene for antisenw DNA therapy based on molecular biological diagnosis in SCLC. as nuasured with the inside-out patch co&guration. was I .Opi at -20 mV with a slope conductance of 12. I pS. The autoantibodies implicated in the Lambert-Eaton myasthenic syndrome (L.ES), whtch are known to inhibit I(Ca) and I(Na) in bovine adrenal chmmaliin cells. also si8niticantly inhibited IlNa) in SCLC cells. These results indicate that (i)action po(endals in human SCLC cells nsult from the regenerative increase in voltage-gated Na* channel conductance: (ii) timdamental characteristics of SCLC Na’ channels are the same as the classical sodium channels found in a variety of excitable cells; and (iii) in some LES patients, SCLC Na’ channels are an additional target of the pathological IgG present in the patients’ sera Mechmims of MRP over-expression in four human lung-cancer cell lines and analysis of the MRP amplican Eiidems EWHM. De Haa M Ccco-Martin JM. Dttenheim CPE. Zaman &I. DawerseHG et al. &ision Uo/ecu/ar Biology Netherlands Cancer Insdtofe, Plesmanlaan 121, 1066 CYAmstenlam Int I Cancer l995;60:676-84. Some mtdtidrugresistant cell lines over-express Ihe gene encoding the multidrug-resistann-associaled protein f.MRP). In all all lines reported thus far, over-expression is assccialed with gene amplification. We have studied the predominant mechanisms of MRP over-expression in 4 human Iuwcanccr all lines that myer a range ofdntrrcsistance lewls, and we&e attalyzed the MRP ampli&. In th;SW-l573- derived. waklv resistant cell line 30.3M. h4RP mRNA IS elevated 3- fold in & &s&x of gene amplification. Run-on analysis shows that the increased MRP gene expression in this cell line is due lo trans- criptional activation. In the highly resistant GLC4/ADR and CO&L231 R cells. MRP gene amplification predominates, whereas rn the moderately resistant MOP& alls, geneamplification ISwmbmed with a mechanism nsulting in an additional increase in UK level of MRP mRNA. Fhtomsccnce in situ hybridiratron shows that, in the GLCU ADR cells. amplitied MRP xq!znces arc present both in double minute chromosomes (DM) and in homogeneously stainmg regions (HSR). By pulxd-field gel electrophoresis we show that the MRP-mntaining DM an I Mb in Icngtlt Chromosome-l6-specific repetitive sequences adjacent to the MRP gene arc also present in Ihe DM and HSR, campaliblc with the inwlvement of these sequences in recombination wcnts underlying h4lW gene amphtication. Our results show that low levels of drug resistance may arise by tmnxriptional activatmn of the MRP gene, whereas at high levels of drug resistance amplificalmn of the MRP gene predominates, posslbly facilitated by the prwence of recombination-prone sequences Inhibition of proliferation by L-myc antisense DNA for the translational initiation site in human small cell lung cancer Dosaka-Akita H, Akie K. Hiroumi H. Kinoshita I. Kawakamr Y, Murakaml A. Fwsl Deparrnwnr of.WedKme. Hokkaido Unrversr~Sch of Bkdrcme. Norlh ,J, Wes, 7. .&to-ku. Sapporn 060. Cancer Res 1995;55 1559-64. We evaluated the antiprolifera0vc effect of L-myc antisense DNA m NCI- H209. a human small cell lung cancer (SCLC) cell line over- expressing the L- rnyc gene. The syntbetrc DNA used in the present study was oligodeoxynucleoside phospborothiaate, which showed rapid mcorpomtion into NC131209 cells and localized mainly m the cell nucleus and weakly in the cytoplasm. Tbc exposure of this cell line to L-mvc antisense DNA coverina the tnnslational initiation sile of L- myc proteins inhibited the s& proliferation in a dose-dependent seauence-.sccciIic manner. Funhemmre. the mowh inhibitton by this . antscn~ DNA was correlated with the level-of L- myc expression in three SCLC cell lines. NCI-H209, NCI-HS IO. and NCI-H82. In Western blot analysis, expression of the L-myc proteins was down-regulated in Mutations in the pl6(lNKJ)/MTSl/CDKN2, plS(INKdB)/ MTSZ, and pig genes in primary and metartatic lung cancer Okamoto A, Hussain SP, Hagiwara K, Spillare EA. Ruin MR. 1448-51. We exammed Ihe genomic status ofcychn&pmdent kinase-4 and -6 mlub~tors, pl6(INK4). pl5(INK4B). and ~18, I” 40 primary lung cancers and 31 metastatic lung cancers Alterations of the p16(INK4) gene were detected in 6 (2 wetirons and 4 homozygous deletions) of 22 metastat~ non-small cell lung cancers (NSCLCs: 27%). but none weredetected in 25 pnmay NSCLCs. 15 primarysmalloell lungcancers (SCLCs). or 9 metastatrc SCLCs. mdrcatin8 that mutation tn Ihe pl6(lNK4) gene IS a late event in NSCLC c&nogenesis Although three mtragenic mutationsofthc pIS(INK4B) gene were dctcctcd fin 25 prrmary NSCLCs (12%) and f,\e homozygous deletions of Ihe olS(INK4Bl eerie wcrc detected tn 22 NSCLCs 123%L no eenetx . _I I alteratiowofthepl5(INK4B) genewere foundin primary and metastauc SCLCs. The pl8 gene was wdd type tn these 7 I lung cancers. except I metastatic NSCLC whrch showed loss of hetcrwygowy We also esamincdaltcrat1onsofthcrthrcegennandespress~onofpl6(INK4) rn 21 human lung cancer cell hncs. Alteratmns of the plG(INK4) and plS(lNK4B) genes wcredetected I” 7l%ofthe NSCLC cell hnes (n = 14) and 50% of the NSCLC cell hncs (n = l4), rcspect~\cl>. but there were mane ,n the 7 SCLC cell hnes studwd No plR mutauons were dctcctedmthcsc21 cell hnes Thescraultr~nd~catethatbMhpl6lINK4~ andplS(INKJB)gene mutat,onsareasroc~rtcd~rth tumorprogrcsrmn ofa subset ofNSCLC. but not ofSCLC. and tbat plS(INK4B) mutatwns might also be an early event m the molecular pathogcncsrs of a subset or NSCLC Increased prevalence of K-w oncogene mutations in lung adenocarcinoma Mills NE, Fishman CL. Ram WN, Dubin N. Jacobson DR. Research Service IJI. New York VA. Hosmlal, 423 E. 23 St.. New York, NY 10010. Cancer Res l995;55 1444-7. Reported estimates of ras mutation prevalence in lung adeno- carcinomaof l5-24%maybcundexstimatesbecause oftbe insenatrnty of the assays used. We have devised a rapid, non-radioactive assay for ras mutations. which detects I mutant allcle/l0’ normal alleles and have used it to study DNA isolated from 53 lung tunwr samples (including 28 adenocarcinomas) previously analyzed by PCFUallele specific oligonucleotide hybridization, which is less sensitive. We detected m&ions in I3 of 28 samples, including 7 not detected by PCP/alkle so&tic oliaonucleotide hybndwation. We also found ras mutations in.14 of 25 ~wicusly unstudied samples (56%). Our resuits indicate that the prevalence of K-ras codon I2 mutations in lung adenocarciwma is higherthan previously reported; thus, ras mutations may be more clinically use&l as molecular markers for lung cancer than has been appreciated. Neumlihromntosis type 2 (NF2) gene is somatically mutated in mesothelioma hut not in lung cancer Sekido Y. Pass HI. Bader S. Mew DN. Chnstman MF. Ca&r AF et al Smmons Cancer Centes Umrar.q v/ 7k,r SII Akdtcol (‘rr 5323 Horn Hrnes Bhd, Da//as. T.Y 75235-8590 Cancer Rcs l’J95.55 1227. 31. WC have found 16 or28 small cell lung carlccrs. I7 or3 I non-llmill cell lung cancers. 2 of 3 carano~ds. and I2 of I4 mcsothclmmas thal had chromosome 22 cymgenetrc abnormalmes To dctcrmme whether the neurofibromalosis type 2 (NF2) gcnc lccalcd on chromosome 22 partic@es m the oncogencsls ofthcsc mahgnanacs. WC studxd DNAs from lung cancer cell lines and mesothclmmas usmg Southern blot analysis and the srnglc-strand conformauon polymorphism (SSCP) techmque for mutations covcrmg 8 of the 16 known NF2 ewns WC
Transcript of Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer
Abstracts/Lung Cancer 13 (1995) 81-104
Ca” rbd not a5ect the action potential production, whereas 5 iM TTX or subslttutton of Na* with cholineabolished rt. Action pMentiaIselicited rn the Ca”-free condition were reversibly blocked by 4 mM M&I, due to the Mn”-induced inhibition of voltage-dependent sodium currents (I(Na)) Therefore, Na’ channels, not Ca’* channels, underlie the excitability of SCLC cells. Whole-cell @a) was maximal with step- depolarizing stimulations to 0 mV, and reversed at +45 2 mV, tn accord with the p=dicted Nemst ectuilibrium pofential for a Na+-selective channel. i(Na) evoked by dep&izing test potentials (-60 to +40 mV) exhibited a transient time course and activation/ mactivation kinetics typical of neuronal excitable membranes; the plot oftbe Hodgkin-Huxley parameters. m() and ho. also revealed biophysical similarity between SCLC and neumnal Na’ channels The single channel current amplitude,
the armsense-treated cells compared tith control-treated cells in NCI- H209. Togctkr with unique charaaeristia of the Llnyc gene. including: (a) a frequently amplified and overexpressed state in SCLC; and (b) very rcstictcd and low-level expression in human adult tissues. the present data indicate that L-myc is a good candidate for the target gene for antisenw DNA therapy based on molecular biological diagnosis in SCLC.
as nuasured with the inside-out patch co&guration. was I .O pi at -20 mV with a slope conductance of 12. I pS. The autoantibodies implicated in the Lambert-Eaton myasthenic syndrome (L.ES), whtch are known to inhibit I(Ca) and I(Na) in bovine adrenal chmmaliin cells. also si8niticantly inhibited IlNa) in SCLC cells. These results indicate that (i)action po(endals in human SCLC cells nsult from the regenerative increase in voltage-gated Na* channel conductance: (ii) timdamental characteristics of SCLC Na’ channels are the same as the classical sodium channels found in a variety of excitable cells; and (iii) in some LES patients, SCLC Na’ channels are an additional target of the pathological IgG present in the patients’ sera
Mechmims of MRP over-expression in four human lung-cancer cell lines and analysis of the MRP amplican Eiidems EWHM. De Haa M Ccco-Martin JM. Dttenheim CPE. Zaman &I. DawerseHG et al. &ision Uo/ecu/ar Biology Netherlands Cancer Insdtofe, Plesmanlaan 121, 1066 CYAmstenlam Int I Cancer l995;60:676-84.
Some mtdtidrugresistant cell lines over-express Ihe gene encoding the multidrug-resistann-associaled protein f.MRP). In all all lines reported thus far, over-expression is assccialed with gene amplification. We have studied the predominant mechanisms of MRP over-expression in 4 human Iuwcanccr all lines that myer a range ofdntrrcsistance lewls, and we&e attalyzed the MRP ampli&. In th;SW-l573- derived. waklv resistant cell line 30.3M. h4RP mRNA IS elevated 3- fold in & &s&x of gene amplification. Run-on analysis shows that the increased MRP gene expression in this cell line is due lo trans- criptional activation. In the highly resistant GLC4/ADR and CO&L231 R cells. MRP gene amplification predominates, whereas rn the moderately resistant MOP& alls, geneamplification IS wmbmed with a mechanism nsulting in an additional increase in UK level of MRP mRNA. Fhtomsccnce in situ hybridiratron shows that, in the GLCU ADR cells. amplitied MRP xq!znces arc present both in double minute chromosomes (DM) and in homogeneously stainmg regions (HSR). By pulxd-field gel electrophoresis we show that the MRP-mntaining DM an I Mb in Icngtlt Chromosome-l6-specific repetitive sequences adjacent to the MRP gene arc also present in Ihe DM and HSR, campaliblc with the inwlvement of these sequences in recombination wcnts underlying h4lW gene amphtication. Our results show that low levels of drug resistance may arise by tmnxriptional activatmn of the MRP gene, whereas at high levels of drug resistance amplificalmn of the MRP gene predominates, posslbly facilitated by the prwence of recombination-prone sequences
Inhibition of proliferation by L-myc antisense DNA for the translational initiation site in human small cell lung cancer Dosaka-Akita H, Akie K. Hiroumi H. Kinoshita I. Kawakamr Y, Murakaml A. Fwsl Deparrnwnr of.WedKme. Hokkaido Unrversr~Sch of Bkdrcme. Norlh ,J, Wes, 7. .&to-ku. Sapporn 060. Cancer Res 1995;55 1559-64.
We evaluated the antiprolifera0vc effect of L-myc antisense DNA m NCI- H209. a human small cell lung cancer (SCLC) cell line over- expressing the L- rnyc gene. The syntbetrc DNA used in the present study was oligodeoxynucleoside phospborothiaate, which showed rapid mcorpomtion into NC131209 cells and localized mainly m the cell nucleus and weakly in the cytoplasm. Tbc exposure of this cell line to L-mvc antisense DNA coverina the tnnslational initiation sile of L- myc proteins inhibited the s& proliferation in a dose-dependent seauence-.sccciIic manner. Funhemmre. the mowh inhibitton by this . antscn~ DNA was correlated with the level-of L- myc expression in three SCLC cell lines. NCI-H209, NCI-HS IO. and NCI-H82. In Western blot analysis, expression of the L-myc proteins was down-regulated in
Mutations in the pl6(lNKJ)/MTSl/CDKN2, plS(INKdB)/ MTSZ, and pig genes in primary and metartatic lung cancer Okamoto A, Hussain SP, Hagiwara K, Spillare EA. Ruin MR.
1448-51. We exammed Ihe genomic status ofcychn&pmdent kinase-4 and
-6 mlub~tors, pl6(INK4). pl5(INK4B). and ~18, I” 40 primary lung cancers and 31 metastatic lung cancers Alterations of the p16(INK4) gene were detected in 6 (2 wetirons and 4 homozygous deletions) of 22 metastat~ non-small cell lung cancers (NSCLCs: 27%). but none weredetected in 25 pnmay NSCLCs. 15 primarysmalloell lungcancers (SCLCs). or 9 metastatrc SCLCs. mdrcatin8 that mutation tn Ihe pl6(lNK4) gene IS a late event in NSCLC c&nogenesis Although three mtragenic mutationsofthc pIS(INK4B) gene were dctcctcd fin 25 prrmary NSCLCs (12%) and f,\e homozygous deletions of Ihe olS(INK4Bl eerie wcrc detected tn 22 NSCLCs 123%L no eenetx . _I I
alteratiowofthepl5(INK4B) genewere foundin primary and metastauc SCLCs. The pl8 gene was wdd type tn these 7 I lung cancers. except I metastatic NSCLC whrch showed loss of hetcrwygowy We also esamincdaltcrat1onsofthcrthrcegennandespress~onofpl6(INK4) rn 21 human lung cancer cell hncs. Alteratmns of the plG(INK4) and plS(lNK4B) genes wcredetected I” 7l%ofthe NSCLC cell hnes (n = 14) and 50% of the NSCLC cell hncs (n = l4), rcspect~\cl>. but there
were mane ,n the 7 SCLC cell hnes studwd No plR mutauons were dctcctedmthcsc21 cell hnes Thescraultr~nd~catethatbMhpl6lINK4~ andplS(INKJB)gene mutat,onsareasroc~rtcd~rth tumorprogrcsrmn ofa subset ofNSCLC. but not ofSCLC. and tbat plS(INK4B) mutatwns might also be an early event m the molecular pathogcncsrs of a subset or NSCLC
Increased prevalence of K-w oncogene mutations in lung adenocarcinoma Mills NE, Fishman CL. Ram WN, Dubin N. Jacobson DR. Research Service IJI. New York VA. Hosmlal, 423 E. 23 St.. New York, NY 10010. Cancer Res l995;55 1444-7.
Reported estimates of ras mutation prevalence in lung adeno- carcinomaof l5-24%maybcundexstimatesbecause oftbe insenatrnty of the assays used. We have devised a rapid, non-radioactive assay for ras mutations. which detects I mutant allcle/l0’ normal alleles and have used it to study DNA isolated from 53 lung tunwr samples (including 28 adenocarcinomas) previously analyzed by PCFUallele specific oligonucleotide hybridization, which is less sensitive. We detected m&ions in I3 of 28 samples, including 7 not detected by PCP/alkle so&tic oliaonucleotide hybndwation. We also found ras mutations in.14 of 25 ~wicusly unstudied samples (56%). Our resuits indicate that the prevalence of K-ras codon I2 mutations in lung adenocarciwma is higherthan previously reported; thus, ras mutations may be more clinically use&l as molecular markers for lung cancer than has been appreciated.
Neumlihromntosis type 2 (NF2) gene is somatically mutated in mesothelioma hut not in lung cancer Sekido Y. Pass HI. Bader S. Mew DN. Chnstman MF. Ca&r AF et al Smmons Cancer Centes Umrar.q v/ 7k,r SII Akdtcol (‘rr 5323 Horn Hrnes Bhd, Da//as. T . Y 75235-8590 Cancer Rcs l’J95.55 1227. 31.
WC have found 16 or28 small cell lung carlccrs. I7 or3 I non-llmill cell lung cancers. 2 of 3 carano~ds. and I2 of I4 mcsothclmmas thal had chromosome 22 cymgenetrc abnormalmes To dctcrmme whether the neurofibromalosis type 2 (NF2) gcnc lccalcd on chromosome 22 partic@es m the oncogencsls ofthcsc mahgnanacs. WC studxd DNAs from lung cancer cell lines and mesothclmmas usmg Southern blot analysis and the srnglc-strand conformauon polymorphism (SSCP) techmque for mutations covcrmg 8 of the 16 known NF2 ewns WC
Abstmcts/Lung Cancer 13 (1995) 81-104
detected 7 mutatvx~s in 17 mcsolhchomas (41%) nnlnn Ihc ccdmg regton of NE but none III 75 lung cancer cell lmcs (3X small ccl1 lung cancers. 34 non-small cell lung cancers. and 3 carcmmds) Thcsc mulalmns were found to bc somatic when normal lrssw uas aadablc for testing Four mcsothclioma ccl1 hncs had rclan\cl) large delcwns (-10-50 khbascs) mtbcNF2 gcnedncnabk~ Soulhcrn blot anal>srs Two mcsothehoma cell hncs had nonsense mulanons a, codons 57 and 341, respectively Anolhcr mcsolhclionla obaamcdasa spccmle~r dlrcctl! from a palrent. had a IO-base pmr mrcrodclcuon from nuclcoc~dc llWI4 10 nucleonde 1013 causing a framcshrn mutatron Thcsc rcsuI,s suggcs, that the NFZ gene parlrcrpalcs rn the oncogcncrw III a subscl of mcsothchomas bu, no, III lung cancers
Transforming growth factor il, as Y pmgnosfic faclur in pulmunrr’! ndenocrrvinoma Takanam~ I. lmamura T . HashrrumcT. K,kucb K. Yamanwlo Y. Kodarra S Rrs, Depa,0nenr o/Suge~. Te,@o ~~n,vcrs,!v oj,\fed,c,nr. II-l Kogo 2.Chome, Ilaha.sh+ku. 7b@o 173 J Chn Palhol 1994.47 109R- I IO0
Arm -Tocvalualc lkcflicacyofvansformll~ggmuth fanorD (TCF- 0) for the prognosis of pulmonary adenocaranoma .tLlhadv - TCF-0 was detcctcd immunohis~ochcnncally uung the awdm-bwun-pcrovdasc complex tcchmque m rcscctcd pulmonary adcnocarcmomas irom 88 pa,& Resulrs-- Of the 88 pat&. 39 were TGF-O negau\e and 45 TGF-0 msitrve The 8ve war survwl ra,c was 56% for ,hc TGF-O negalivf and 16% for the ‘fGF-0 pornwe group Conclusions - TGF-O can bc used as a progncmic factor m pulmonar) adcnoclrcmorna
New short-chain analogs of l substance-P antagonist inhibit proliferation of human small-cell lung-cancer ceils in vitro and in viva Omu A. Schren 1. Nagy 1. Bathe L. Schon 1. Nyekr PG. Bmchenml Department, Nat Kormyt Ins, TBC/Pubw~nologv POE 1. H-1529 Budapest. In, 1 Cancer 1995:6@82-7
Human smallccll lung-cancer cells (SCLC) produce and sccrelc gasbin-rcJeasingpide (GRP). the mammalian equivalent of bomb&n (BN). There is some cvidaa to suggest that GRP is an autocrine regulator of SCLC all gmwh. In the search for potent BN antagonisls. several substance-P (SP) analogs were found ,o inhabit the growth of SCLC cells. WC found that a known showchain SP antagonia, pHOPA- DTrp-Phe-DTrp-La-La-~ (NY3238). inhibits Ihe binding of “‘I- Tyr’-BN on Swiss 3T3 ccl1 line expressing BN recep(ors. as well as the pmlifcralion of NCI-H69 SCLC alls In lhrs study we lested several analogs of NY3238 and we found that NY3521 and NY3460 arc more effectwe m ,nlnb,tmn ofproliferatwn of SCLC cells but less potent in inhrbilmn of binding of “‘I-Ty+BN on Swiss 3T3 cells than NY3238. Furlhennorc, we de(glcd spccdic bindmg of mdiolabcllcd NY3238 cvcn below I nM on NC&H69 cells that could have been inhibiled by SP and NY346OralhcrlhanbyBN. Inadditiontothereinv,vonudics.NY3460 proved 10 be effective in inhibiting the growth of NCI-H69 SCLC xenografb in nude mice in viva These analogs of NY3238 could be promising (herapeulic &gents m Ihe treatment of SCLC
Clonal dominance behveen subpopulations of mixed small cell lung cancer xenoprafts implanted ectopicllly in nu& mice Aaba K. Vindclw LL, Spang=Thornscn M. Univ. Ins,. ofP&ologrcal An,,,o,,ry, “~ivc,s,,y of Copenhagen. Fmdmk Vb !&J I I . DK-2100 Copenhagen. Eur J Cancer Part A Gcn Top 1995;3 L:222-9.
Clonalcvolution dncoplasticausduringsolidtumourgrauth leads to the cmcrgcncc of new ,umour cell subpop&dions with diverging phenc+ypiccharaEtrrinicrwhich mayaltuthckbatiourofamaligMnt discasc Cellular mtcmction was studied in mixed xenogr& in nude mice and during in vitro gmwh of twu sets of small cell lung cancer (SCLC) subuouulatmns f54A. 54B and NYH. NYHZ). The tumour ccl1 lines d&r& in cell&DNA content enabling flow cylomelric DNA analysis (FCM) to be used 10 monilor changes in the fraclional compm~tlon of the mixed all populations. The progeny clone 54B was found 10 dominate the parent 54A clone when grown as mixed subctrmeous xemgrafts in nude mia, whereas no dominance was exerted during in vitro growth. The in viva dominance add not be explained by diffcrcnccs in growth kinetics between the two tumour cell bnes, and the interaction was not dependent on 548 being in excess
in mixed turnours. The dominance was dependent on close ,n wvo contact as no remofe e&cl on the growth of 54A was found when ,hc dominating 54B cells wrc graving in the opposite flank of tunwur- bearing mice. Irradiation inactivated 548 alls were unable lo exert the dominating effect. indicating that the interaction required viable and pmlifcraling cells. Clone1 dombumcc was not found in mixed NYH- NYHZ tutnours indicating that Ihe dominance mechanism(s) may not always te operational between subpptdatiotu in hdcrogencous hunours Recognition of interaction between lumour cell populatwns may result in a belter understanding of the bcbwiow of hc,cmgcnwus human malignancies.
lmmunohistochemical locdiation of cytochrume P450 3A in human pulmonary carcinomas and normal bronchial tissue Kivisto KT, Frilz P, Linder A. Frxdel G. Bcaunc P, Krocmer HK Porhologrsches InsNfuI. Robe,,-Bosh-Kr~“kenhrrus. Auerbochslrosse 110, D-70376Slu,tgar, Hismchem Cell Biol 1995;103:25-9.
The cytochrome P450 (CW) enzymes metabolize drugs and olher xenobiotics in liver and alsc in some earahepatic tissues. We have studzd the expression and localization of CYF’3A in primary lung lum~tus and normal lung tissue from the same patients. Thiny-two patients undcgoing pardal or total lung rescctwn for therapy of primary pulmonary carcinoma were inch&cd in lhis study Immunohismchcnucal staining for CYP3A was pcrfonncd wilh a modification of the ABC lahniquc. Eightofthe 32 cascsofprbnarypulmonarycarcinomashmved expression of CYPSA. In 12 of the 32 cases of normal tissue. ,he seronwwus glands were posn,vc for CYP3A. The bronchial epilhebum was positive for CYP3A in I I cases. We obscwcd no conelation beween CYP3A expression in tutnwr tissue and that in serotnucow glands or bmnchialepithclium Wemncludc1hatCYP3Aisprcscnt inbothnornml and cancerous lung tissue. Our findings suggest, however. no co- expression of CYP3A in lung cancer.
Investigation of grow kinetics in non-small lung cancer in relation to bcl-2 oncopn expnssion Vermes I, Van Den Bcmh FAJTM. Van Dcr Sluijs Uxr G. Gmsc WFA. Ollhuis FMFG. Haane;C. Klinmch Chmiscb ioboromrium. Mrdisch Swctrum Twente. Poslbus 50000, 7500 KA Enschcde Ned Tiidrhr Klin Chem 1995:20:38-43.
Expression of ,he bcl-2 oncogcne has been described to bc a prog- nostic marker in non-small cell lung cancer (NSCLC) demonstrated by a longer 5-years survival rate B&&c bcl-2 expression was found 10 prevent apopwsis in follicular lymphomas and hematopoielx cell lines, we wondered if lhe c~prcssion of bcl-2 rn NSCLC would Imply a distincl ncoplan~c mechanism. m which nunor growh II the result ofdiminished cell loss and no, the consequence of mcrcased cell prcduaion. To invertigate ,o what ewn, the mpnxsmn ofbcl-2 m NSCLC really affects the growth lanetics oflhesc tumor cells. we inlend 10 measure in tumor spximens ofNSCLC p&rents the cxlcnl ofbcl-2 expressron m relatmn topmlifcratmn andapcptarcirrdices These indrccs. related lothecx~en, ofbcl-2 expression. wdl possrbly prowde the answer to the hypothcrw that b&2 eprcssmn in NSCLC rmphes a drstinct tumor biology ofbcl- 2 protein positive lung cancers compared IobcI-2 protern negatweones
Changes in expression of neural cell adhesion molecule and
desmoplakin associated with phcnotypic transitions in cloned cell lines from a non-small cell lung carcinamn Wright-Perkins S. Daniel MR. Walker C. Clorlerbrtdge Comer Research Trusr. J.K Douglas Cancer Researrh Lob., Clarterbndge H~~prlo/, Bebington. W& L63 41,‘. In, 1 Oncol 1995;6: 617-23. -
I Ff and I F’f vanant A clonal cell lines. both derived from the same neuroendocrrne posrtwe. undillcremiated large cell lung carcinoma. shaved ddferences m Iheir morphology, DNA conlent, presence of desmosnmes and expression of NCAM and desmoplakm Colonies ofcells which morphologically resembled I F’f variant A cells arosc In cultures oftk 1 Ff clocal line followirw prolonacd cullwation. Such transilmns in cloned cells of NSCLC ori& havenot previously been reported Tlw lransnmn was arsocmtcd wrth incrcascd expression of dcsmoplakm and downregulauon of NCAM A converse transition of I PT vanant A cells 10 I PT-like cells wld not bc demonstrated
