chemosensitivity of transplantable non-small cell bronchial rat tumours growing subcutaneously or in...

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039 13 040 SERUM LEVELS OF FERRITIN IN PATIENTS WITH LUNG CANCER (LC). D.Ferrigno, and GF.Buccheri, FCCP. 0. Carle Hospital of Chest Diseases, Cuneo, Italy. Using an immunoradiometric method, we measured the serum ferritin levels of 168 patients with newly diagnosed LC. Other 82 assays were obtained during their fol- low-up. Ferritin values at diagnosis were correlated with other 55 variables, con- taining clinical, functional, radiologi- cal, pathological, and staging data. In general, ferritin correlated best with the acute phase serum proteins and the ESR in particular (ROz.41, p<.001, Spearman rank test). Ferritin did not change signi- ficantly as a function of histotype, cli- nical stage, or "umber and type of metas- tases. It increased in parallel with the N factor (RO=.21, P<.Ol), the PS (RO=.26,p<.Ol), and the number of previous diseases (RO=.24, p<.Ol). There was no relation between ferritin and response to treatment (RO=.03). Patients with ferri- tin levels below the median had longer survival5 (9.2 vs.. 6.5 months, p=.o4, Mantel-Cox test). A Cox’s multivariate analysis, including 17 significant progno- stic factors, selected ferritin as the 4th IndeDendent variable. 041 THECULTIVATION OFHUMAN EMBRYO BRONCHO-EPITHELIA CELL (HEBE) TREATED WITH CARCINOGENS AND SEX HORMONES Du,Y.X. Gao,H.G. Jin,B. Zhan,D.J. Guangzhou Institute for Chemical Carcinogenesis 195,Dongfeng Rd.W.Guangzhou,510182,P.R.of China At least86% of lungcancer is klieved to be erwiromtal carcinogens induced, and thecelltype alscclosely related to carciwgens.Ihe~jorcelltype intmleis sqwmus celland in famleis aden cell that are the general phenmon in tile world, eventhough the existenceof environwntal carcinogens in all partof the wx-ldis quitedifferences. It w thatsex horm~nesntight be an intluence factor for thecelltypeoflung cancer. For studythe relationship between thecelltype and the sex horm3nes,HEBE&LlswareexposedtonYNAor B(a)Pwithorwi* out humn embryo liver microames,thencultured ina Il%M-Fl2 mediun, whichcontainstestoster~(~)or estralial (EST). The results show that allHE%ceIls of control groups will died in tw) weeksaftercu.ltured,the groupexposed to B(a)Pand treatedwithsex t0tmxles 'IEsandE3bothcanbe grown for llweks, however the lifespof ~cellsexpzxd toIl%JA and treated with sex hormxwswxe extended to15w&s (m) and 45weks (E3). F wtharmxe,~t only the transforrnrl focus, butalsosaneadenoidst~turecellscanbeseeninthe flask in the @-group. It suggested that estrodial might bean influence factor for indwing aden carcinam of lung. J&B. Qlen,J.K. Yi,F'. rkl,Y.X. kngzhou Research Institute for Qlenical Carcinogenesis Guangzhou M&Cal Collage, 195,Ibngfeng Rd. W. Guangzhou, 510182, Chiza Benzo(a)pyrene is one of widespread enviro~talcontaminants. in forming ultirrate carcinogen, wa)P mtbe metabolized by Mixed Function Oxidase after eplter body. lhe rnetabolites cari interact withcell DNAto produce B(a)P-mAadductaod thisnay be related to cellmalignance. Epideniological investigation also shownthatB(a)P is a majorassociated factor for humn 1% carxler. In thisarticle, the aerobic metabolism of B(a)Pby humn fetallung (Hn) micrcxxxz in vitrok~s studied.'Ihe microsane ~LS obtained franHFL by meansof differential centrifugation and incubated with B(a)Pin a metabolic system contaning G6-P, G&FTl and#-NADpat 37'Cfor lhr.The equal voluneofacetonewasaddedto quench the process of metatolisn. The rrdxturew extractedtticewith ethylacetate,and organic @we m collected. Triethylamine was added to stabli&metak&ites. The organic solvents was evaperatal underreduced pressure.The residue was solved inmethanolaodanalyzed by reverd-pbaseHPI.Cwitha SP 87cOsystem, Ekkmx 163 detector(m rm).A m(2T1X4.6 mn) CO~UITI )rBSuSedwithalineargradientof60_la)%~thanolin~~ata flewrateof 1.5mllmin.lheresults shownthattherrajor canpxents are diol-EaP and OH-Bep, suchas 9,1(Miol-E@; 7,B-diol-Bap; 4,F diol-PaP; 9-&&P and 3-C&I@, and asiallannunt is quinwF!aP. pnrmgthem, 9,lOand 7,8diol-Bap are mx-e easier to be oxidi& to diol-epoxid&kPwhichcan covalently bindto cellCWA. It *tad that B(a)P can be met&&& by ticrosuw of hwan fetallung.It might be of great referencevalueto explain the relationship between B(a)P and humn long cancer. 042 Chemosensitivity of transplantable non-small cell bronchial rat tumours growing subcutaneously or in the lung. D.W. van Bekkum, H.B. Kal, P.J.N. Meijnders and J. L. Noteboom, Institute of Applied Radiobiology and Immunology TNO, Rijswijk, The Netherlands. Five squamous cell carcinomas of varying grades of differentiation and two adenocaminomas were induced in the lungs of inbred rats by ionizing radiation and maintained by serial subcutaneous passage in syngeneic animals for between 11 and 75 passages at the time of this study. Responses of the tumours to a panel of cytostatic drugs were determined for tumours growing subcutaneously and for tumours from the same passage following implantation into the lung. The endpoint was growth delay as determined by direct measurements in the case of subcutaneously growing turnouts or by radiography in case of intrapulmonary implants. Consistent differences were observed within each tumour cell line between the two sites in that lung implants were always less responsive than flank implants. These findings suggest that responses of subcutaneously growing bronchi cancers are not predictive for tumours growing in the lung, in that flank implants can only be dependably used for excluding ineffective agents. This seems to be in accordance with the poor responses obtained with chemotherapeutic agents in human non- small cell cancers of the lung. An attempt was made to facilitate the measurement of responses of tumours that are smaller than required for volume measurements - that is of a size representative of small micrometastases -, several of our tumour lines were cultured in vitro and provided with a bacterial galactosidase marker by transfection with a retmviral vector containing the lac-Z gene. This marker allows a sensitive estimate of low tumour cell numbers. However, the tumourgenecity of these transfected cells was found to be much lower than that of the parent lines. The factors responsible for this interesting change are presently under investigation.

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Page 1: Chemosensitivity of transplantable non-small cell bronchial rat tumours growing subcutaneously or in the lung

039 13

040

SERUM LEVELS OF FERRITIN IN PATIENTS WITH LUNG CANCER (LC).

D.Ferrigno, and GF.Buccheri, FCCP. 0. Carle Hospital of Chest Diseases, Cuneo, Italy.

Using an immunoradiometric method, we measured the serum ferritin levels of 168 patients with newly diagnosed LC. Other 82 assays were obtained during their fol- low-up. Ferritin values at diagnosis were correlated with other 55 variables, con- taining clinical, functional, radiologi- cal, pathological, and staging data. In general, ferritin correlated best with the acute phase serum proteins and the ESR in particular (ROz.41, p<.001, Spearman rank test). Ferritin did not change signi- ficantly as a function of histotype, cli- nical stage, or "umber and type of metas- tases. It increased in parallel with the N factor (RO=.21, P<.Ol), the PS (RO=.26,p<.Ol), and the number of previous diseases (RO=.24, p<.Ol). There was no relation between ferritin and response to treatment (RO=.03). Patients with ferri- tin levels below the median had longer survival5 (9.2 vs.. 6.5 months, p=.o4, Mantel-Cox test). A Cox’s multivariate analysis, including 17 significant progno- stic factors, selected ferritin as the 4th IndeDendent variable.

041

THECULTIVATION OFHUMAN EMBRYO BRONCHO-EPITHELIA CELL (HEBE) TREATED WITH CARCINOGENS AND SEX HORMONES

Du,Y.X. Gao,H.G. Jin,B. Zhan,D.J. Guangzhou Institute for Chemical Carcinogenesis 195,Dongfeng Rd.W.Guangzhou,510182,P.R.of China

At least 86% of lung cancer is klieved to be erwiromtal carcinogens induced, and thecelltype alsc closely related to carciwgens.Ihe~jorcelltype intmleis sqwmus cell and in famleis aden cell that are the general phenmon in tile world, even though the existenceof environwntal carcinogens in all part of the wx-ld is quite differences. It w that sex horm~nesntight be an intluence factor for thecelltypeoflung cancer. For study the relationship between thecelltype and the sex

horm3nes,HEBE&LlswareexposedtonYNAor B(a)Pwithorwi* out humn embryo liver microames, thencultured ina Il%M-Fl2 mediun, whichcontainstestoster~(~)or estralial (EST). The results show that allHE%ceIls of control groups will

died in tw) weeks after cu.ltured,the group exposed to B(a)P and treatedwithsex t0tmxles 'IEsandE3bothcanbe grown for llweks, however the lifespof ~cellsexpzxd toIl%JA and treated with sex hormxwswxe extended to15w&s (m) and 45weks (E3). F wtharmxe,~t only the transforrnrl focus, butalsosaneadenoidst~turecellscanbeseeninthe flask in the @-group. It suggested that estrodial might bean influence factor for indwing aden carcinam of lung.

J&B. Qlen,J.K. Yi,F'. rkl,Y.X. kngzhou Research Institute for Qlenical Carcinogenesis Guangzhou M&Cal Collage, 195, Ibngfeng Rd. W. Guangzhou, 510182, Chiza

Benzo(a)pyrene is one of widespread enviro~talcontaminants. in forming ultirrate carcinogen, wa)P mtbe metabolized by Mixed Function Oxidase after eplter body. lhe rnetabolites cari interact withcell DNAto produce B(a)P-mAadductaod thisnay be related to cell malignance. Epideniological investigation also shown that B(a)P is a major associated factor for humn 1% carxler. In this article, the aerobic metabolism of B(a)P by humn fetal lung (Hn) micrcxxxz in vitro k~s studied.'Ihe microsane ~LS obtained fran HFL by means of differential centrifugation and incubated with B(a)P in a metabolic system contaning G6-P, G&FTl and#-NADp at 37'C for lhr. The equal voluneof acetonewasaddedto quench the process of metatolisn. The rrdxturew extractedtticewith ethylacetate,and organic @we m collected. Triethylamine was added to stabli&metak&ites. The organic solvents was evaperatal under reduced pressure. The residue was solved inmethanolaod analyzed by reverd-pbaseHPI.Cwitha SP 87cO system, Ekkmx 163 detector(m rm). A m(2T1X4.6 mn) CO~UITI )rBSuSedwithalineargradientof60_la)%~thanolin~~ata flew rate of 1.5mllmin.lhe results shown thattherrajor canpxents are diol-EaP and OH-Bep, such as 9,1(Miol-E@; 7,B-diol-Bap; 4,F diol-PaP; 9-&&P and 3-C&I@, and asiallannunt is quinwF!aP. pnrmg them, 9,lO and 7,8diol-Bap are mx-e easier to be oxidi& to diol-epoxid&kP which can covalently bind to cell CWA. It *tad that B(a)P can be met&&& by ticrosuw of hwan fetal lung. It might be of great reference value to explain the relationship between B(a)P and humn long cancer.

042

Chemosensitivity of transplantable non-small cell bronchial rat tumours growing subcutaneously or in the lung. D.W. van Bekkum, H.B. Kal, P.J.N. Meijnders and J. L.

Noteboom, Institute of Applied Radiobiology and Immunology TNO, Rijswijk, The Netherlands. Five squamous cell carcinomas of varying grades of differentiation and two adenocaminomas were induced in the lungs of inbred rats by ionizing radiation and maintained by serial subcutaneous passage in syngeneic animals for between 11 and 75 passages at the time of this study. Responses of the tumours to a panel of cytostatic drugs were determined for tumours growing subcutaneously and for tumours from the same passage following implantation into the lung. The endpoint was growth delay as determined by direct measurements in the case of subcutaneously growing turnouts or by radiography in case of intrapulmonary implants. Consistent differences were observed within each tumour cell line between the two sites in that lung implants were always less responsive than flank implants. These findings suggest that responses of subcutaneously growing bronchi cancers are not predictive for tumours growing in the lung, in that flank implants can only be dependably used for excluding ineffective agents. This seems to be in accordance with the poor responses obtained with chemotherapeutic agents in human non- small cell cancers of the lung. An attempt was made to facilitate the measurement of responses of tumours that are smaller than required for volume measurements - that is of a size representative of small micrometastases -, several of our tumour lines were cultured in vitro and provided with a bacterial galactosidase marker by transfection with a retmviral vector containing the lac-Z gene. This marker allows a sensitive estimate of low tumour cell numbers. However, the tumourgenecity of these transfected cells was found to be much lower than that of the parent lines. The factors responsible for this interesting change are presently under investigation.