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An immunohistochemical study of cellular proliferation markers in CDDP resistant and sensitive tumors in non-small cell lung cancer
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047 BLOOD NEUTROPHILAND RONOCYTEFUNCTIONFOLLOUING CHEMOTHERAPYIN PllTIENTS VITH MALL CELL LUNG CANCER H S R HOSKERl Y SCOTT+ P KESTEVENt P A CORRISX Departmentsof RespiratoryiTedicine(l) and Haeaatology(*), Freenan Hospital,Neucastleupon Tyne NE7 7DN England, P cheniluminescence (CL) assay uas used to assess phagocytic functionduring cytotoxicchenotherapy(Cyclophosphaaide, Doxorubicin,Etoposide,Vincristinelin patients with small cell lung cancer,SIX patientsunderwentsequentialneutrophil(N) studiesbefore treatment(day 0) and on days 1, 3, IO, 21 and 42 followingchemotherapy,Eleven patientssimilarlyunderwent monocyte(If)studies,Luninol was the probe for N studies, lucigeninwas used for I!studiesand latex beads were used as the stimulus,There was a marked depressionof cell functionbetween cyclesof chemotherapywhich ras independentof cell numbers, 1axinalsuppressionoccured 10 days after chemotherapy,to 10-15X of pre-treatmentvalues (p(O,Olfor N studies,p(O,OOl for If studies),Cell functionreturnedtouardspre-treatmentlevels at the time of the second cycle of treatment(day 21). Functionat 42 days was also normal, ilonocytes, but not neutrophils,shoved 'overshoot'of CL responsesat 21 days and 42 days which was most narked in patients uho subsequentlymade a good responseto treatment,The degree of overshootat 42 days shoved a significantcorrelationuith survival (n=iO; r=0,78;p
SilALL CELL LUNG CANCER (SCLC) ANTIGENS ARE EXPRESSED DIFFEREl!TLY Ofi tlUt:All COfITIlILIOUS CUI.TUP,EDCE!.L LI!IES REPRESE'lTI!jGSCLC "CLASSIC," "VARIANT," AI:D CARCINOID PHENOTYPES.
m, A.ll.C., ATCHISON, R.II., AilD tiITCHELL, D.L. UNIVERSITY OF PITTSBURGH, GRADUATE SCHOOL OF PUBLIC HEALTH, PITTSBURGH, PEWYLVAI'IA, U.S.A. 152Gl A panel of 3C monoclonal antibodies (t;OABS), (mouse or rat) provided by the Second International !lorkshop on Small Cell Lung Cancer Antigens was tested by indirect immunofluorescence and flow cytometry using prototype cell lines [tICI-HG3 (SCLC "classic"), ilCI4417 ("variant"), IICI-H727 (carcinoid) (A.F. Gazdar et al. Bethesda, IiD2 as well as normal human peripheramod lymphocytes (PBL) and sea urchin coelomocytes [Koros, A.I;.C. Int. J. lieurosci. 48:161 (1383)]. All cells had some reactivity with s=e of the MOABS. There is however, differential expression of antigens amongst the prototype cell lines which may provide a useful method for phenotyping human Lund cancers. In contrast to our earlier observations of neuroendocrine cells, human natural killer cells, and sea urchin coelonocytes, fw (14/50) antigens identified by the present panel appear to be evolutionarily conserved. Those tlOABS which do not react with normal PBL should be tested further for possible utility as therapeutic agents in patients whose tumors have escaped conventional therapy.
050
049 A new dlfferentlatlon marker for small-cell lung cancer (SCLC) cell Ilnea: a compound wlth r_ enolaae antlgen but wlthout enxym actMty. T.A.W. Splinter, C. Vsrkoelen, M. Vlaetuln, A. v.d. Gaaat. Dspt. of Medlcal Oncology Unlveralty Hoapltal Dljkxlgt, Rottsrdam, The Netherlands. Recently we rsported that a linear correlation existed between the doubling-tlme of SCLC-cell Ilnea and both thslr Intracelllular content of yanolaae Immunoreacthrlty and r_enolaae enzymeaotlvtly (Proc. AACR 31; 7, 1990). Furthsr experlmsnta showed that yanolaas ImmunoreactMty wlthout enxyme4ctMty could be detected at 3 Ievsb, which differed 1, 4 and 20 fold and dletlngubhed 3 claaaea of call Ilnea. Wlthln each claae of cell Ilnaa both 74noleee Immunoreactlvlty and enzyme-actlvlty wsrs Ilnearly correlated wlth the doubllngtlmo durlng sxponentlal growth. Immunoblottlng experlmenta with rabbit-antlbodlee agalnet yy4nolaee oould not detect a compound wlth a different siectrophoratlc moblllty than -f-fanolaae In-any of the 3 claeeee. Synohrenlzatlon experlw rhowad that a tranalent slgnlflcant Increaee of 74nolaea ImmunoreactMty occured In tho early Glphaae. The compound wlth 74nolaae antlgen but wlthout enzyme sctMty Is found In eerum of SCLC-patlsnte, but not In thelr erythocytea, and In cerebroaplnal fluld of healthy IndMduab. Thb obeewatlon aeema to explatn the confuelon about ths of 74nolaee Immunoreactlvlty. a-lty Charactertxatlon and Inveetlgatlon of the mgulatlon of praduotlon of thla compound will provide knowledge about difbrentiatlon of SCLC. Furthrmom meawemsnl ot ths compound In serum of SCLC-patlenta may be more speclflc, mom eenaltlve and of a hlgher prognoetlc vakm.
An immunohistochemical study of cellular proliferation markers in CDDP resistant and sensitive tumors in non-small cell lung cancer First Department of Surgery, Tokai University, School of Medicine, Kanapawa, JAPAN. Jun-ichi Ogawa, Shunsuke Yamada, Hiroshi Inoue, Akira Shohtsu To examine the relationship between chemosensitivities to cisplatin (CDDP) and expression of cellular proliferation markers, immunohistochemical studies have been performed in 33 resected non-small cell lung cancer patients, using monoclonal antibodies against proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR) and erbB-2. Sensitivities to CDDP were evaluated according to the changes of flow cytometric DNA patterns of cancer cells, such as accumulation of G2M and/or S phases, after culture of single cell suspensions with CDDP. Eiaht oatients were sensitive and 25 were reiistant to CDDP. As a result CDDP resistant cells showed hiqher expression of PCNA and EGFR, although there wa; no difference of erbB-2 expression. Also the frequencies of the aneuoloid cases in the DNA histoqrams were higher'in the resistant group. In-conclusion COOP resistant group was assumed to have more actively proliferating cells than the sensitive group.
047 BLOOD NEUTROPHILAND RONOCYTEFUNCTIONFOLLOUING CHEMOTHERAPYIN PllTIENTS VITH MALL CELL LUNG CANCER H S R HOSKERl Y SCOTT+ P KESTEVENt P A CORRISX Departmentsof RespiratoryiTedicine(l) and Haeaatology(*), Freenan Hospital,Neucastleupon Tyne NE7 7DN England, P cheniluminescence (CL) assay uas used to assess phagocytic functionduring cytotoxicchenotherapy(Cyclophosphaaide, Doxorubicin,Etoposide,Vincristinelin patients with small cell lung cancer,SIX patientsunderwentsequentialneutrophil(N) studiesbefore treatment(day 0) and on days 1, 3, IO, 21 and 42 followingchemotherapy,Eleven patientssimilarlyunderwent monocyte(If)studies,Luninol was the probe for N studies, lucigeninwas used for I!studiesand latex beads were used as the stimulus,There was a marked depressionof cell functionbetween cyclesof chemotherapywhich ras independentof cell numbers, 1axinalsuppressionoccured 10 days after chemotherapy,to 10-15X of pre-treatmentvalues (p(O,Olfor N studies,p(O,OOl for If studies),Cell functionreturnedtouardspre-treatmentlevels at the time of the second cycle of treatment(day 21). Functionat 42 days was also normal, ilonocytes, but not neutrophils,shoved 'overshoot'of CL responsesat 21 days and 42 days which was most narked in patients uho subsequentlymade a good responseto treatment,The degree of overshootat 42 days shoved a significantcorrelationuith survival (n=iO; r=0,78;p
SilALL CELL LUNG CANCER (SCLC) ANTIGENS ARE EXPRESSED DIFFEREl!TLY Ofi tlUt:All COfITIlILIOUS CUI.TUP,EDCE!.L LI!IES REPRESE'lTI!jGSCLC "CLASSIC," "VARIANT," AI:D CARCINOID PHENOTYPES.
m, A.ll.C., ATCHISON, R.II., AilD tiITCHELL, D.L. UNIVERSITY OF PITTSBURGH, GRADUATE SCHOOL OF PUBLIC HEALTH, PITTSBURGH, PEWYLVAI'IA, U.S.A. 152Gl A panel of 3C monoclonal antibodies (t;OABS), (mouse or rat) provided by the Second International !lorkshop on Small Cell Lung Cancer Antigens was tested by indirect immunofluorescence and flow cytometry using prototype cell lines [tICI-HG3 (SCLC "classic"), ilCI4417 ("variant"), IICI-H727 (carcinoid) (A.F. Gazdar et al. Bethesda, IiD2 as well as normal human peripheramod lymphocytes (PBL) and sea urchin coelomocytes [Koros, A.I;.C. Int. J. lieurosci. 48:161 (1383)]. All cells had some reactivity with s=e of the MOABS. There is however, differential expression of antigens amongst the prototype cell lines which may provide a useful method for phenotyping human Lund cancers. In contrast to our earlier observations of neuroendocrine cells, human natural killer cells, and sea urchin coelonocytes, fw (14/50) antigens identified by the present panel appear to be evolutionarily conserved. Those tlOABS which do not react with normal PBL should be tested further for possible utility as therapeutic agents in patients whose tumors have escaped conventional therapy.
050
049 A new dlfferentlatlon marker for small-cell lung cancer (SCLC) cell Ilnea: a compound wlth r_ enolaae antlgen but wlthout enxym actMty. T.A.W. Splinter, C. Vsrkoelen, M. Vlaetuln, A. v.d. Gaaat. Dspt. of Medlcal Oncology Unlveralty Hoapltal Dljkxlgt, Rottsrdam, The Netherlands. Recently we rsported that a linear correlation existed between the doubling-tlme of SCLC-cell Ilnea and both thslr Intracelllular content of yanolaae Immunoreacthrlty and r_enolaae enzymeaotlvtly (Proc. AACR 31; 7, 1990). Furthsr experlmsnta showed that yanolaas ImmunoreactMty wlthout enxyme4ctMty could be detected at 3 Ievsb, which differed 1, 4 and 20 fold and dletlngubhed 3 claaaea of call Ilnea. Wlthln each claae of cell Ilnaa both 74noleee Immunoreactlvlty and enzyme-actlvlty wsrs Ilnearly correlated wlth the doubllngtlmo durlng sxponentlal growth. Immunoblottlng experlmenta with rabbit-antlbodlee agalnet yy4nolaee oould not detect a compound wlth a different siectrophoratlc moblllty than -f-fanolaae In-any of the 3 claeeee. Synohrenlzatlon experlw rhowad that a tranalent slgnlflcant Increaee of 74nolaea ImmunoreactMty occured In tho early Glphaae. The compound wlth 74nolaae antlgen but wlthout enzyme sctMty Is found In eerum of SCLC-patlsnte, but not In thelr erythocytea, and In cerebroaplnal fluld of healthy IndMduab. Thb obeewatlon aeema to explatn the confuelon about ths of 74nolaee Immunoreactlvlty. a-lty Charactertxatlon and Inveetlgatlon of the mgulatlon of praduotlon of thla compound will provide knowledge about difbrentiatlon of SCLC. Furthrmom meawemsnl ot ths compound In serum of SCLC-patlenta may be more speclflc, mom eenaltlve and of a hlgher prognoetlc vakm.
An immunohistochemical study of cellular proliferation markers in CDDP resistant and sensitive tumors in non-small cell lung cancer First Department of Surgery, Tokai University, School of Medicine, Kanapawa, JAPAN. Jun-ichi Ogawa, Shunsuke Yamada, Hiroshi Inoue, Akira Shohtsu To examine the relationship between chemosensitivities to cisplatin (CDDP) and expression of cellular proliferation markers, immunohistochemical studies have been performed in 33 resected non-small cell lung cancer patients, using monoclonal antibodies against proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR) and erbB-2. Sensitivities to CDDP were evaluated according to the changes of flow cytometric DNA patterns of cancer cells, such as accumulation of G2M and/or S phases, after culture of single cell suspensions with CDDP. Eiaht oatients were sensitive and 25 were reiistant to CDDP. As a result CDDP resistant cells showed hiqher expression of PCNA and EGFR, although there wa; no difference of erbB-2 expression. Also the frequencies of the aneuoloid cases in the DNA histoqrams were higher'in the resistant group. In-conclusion COOP resistant group was assumed to have more actively proliferating cells than the sensitive group.