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679 183 680 BRDNCHDALVSOLAR LAVAGE (BALI IN TRB DIAMOSIS OF BRoNCRIOLtOALVROLAR CAR- CINOMA G. Krag Jacobsen & N. Milman. Departments of Pathology and Pulmonary Medicine, Gentofte Hospital, University of Copenhagen, Denmark Bronchioloalveolarcarcinoma is located peri- pherally in the pulmonary parenchyma at the terminal bronchioles and alveoli and may present either as a localized tumor or as diffuse lesions. On chest X-ray the latter may show the pattern of diffuse interstitial pulmonary disease. In such cases it is often difficult to obtain the correct diagnosis. The frequency of positive findings atcytolo- gical examination of brush biopsies and bronchial washings is disappointinglylow and the same apply to transbronchial and per- cutaneous biopsies. We hereby present one case of our own and four cases previously reported, where BAL yielded the diagnosis. Thiough this presentation we intend to draw attention to the use of BAL as a tool in the diagnosis of bronchioloalveolar carcinoma, especially of the type that radiologically shows a diffuse distribution. 681 Magainln Analoguss Have Antitumor Activity Against Human Lung Cancer Cell Lines. Y.Ohsaki. G.E. Richardson, H-C. Chen, A.F. Gazdar and B.E. Johnson. NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889, U.S.A. Magainin peptides, originally isolated from African clawed frog skin, have been reported to inhibit growth of bacteria and fungi by interacting with their cell membrane. Recently, magainin analogues, magainin A (MA) and magainin G (MG), were synthe- sized, which are more potent against bacteria. In order to deter- mine the antitumor activity of MA and MO, we have tested them against six small cell lung cancer (SCLC) cell lines NCI-H82, 528, 678, 735, 841 and 889, which differ by more than 10 fold in their sensitivity to different chemotherapeutic agents, and four normal human fibroblast (NFB) cells Fe Sin, CCD39Sk, 43Sk and 27Sk. Semiautomated MTT assays of the six SCLC cell lines gave median IC50 values of 2.6 FM (range 0.49-9.30) for cisolatin. 2.5 uM (0.39-6.00) for VP-16, 138.8 nM (55.0- 450.0) for adiiamycin. Median IC50 of MA was 26.1 iglml (18.8-35.2) and that of MO was 28.8 W/ml (13.5-38.0). Despite a 10 fold difference sensitivity to standard chemothera- peutic agents, the IC50 of MA and MG differs less than 3 fold range. Median IC50 values lo the NFB cells of MA was 63.7 ug/m I (38.3-77.4) and that of MO was 89.0 pg/ml (74.9-105.9). The addition of MA 18.8 ug/ml reduced surviving cells to44.8%, MG 12.5 wrnl to 51.5% , VP-16 1 .O pM to 49.0% and cisplatln 1.48 uM to 59.2% in H878. Combined exposure to MA or MG plus VP-18 or cisplatin decreased surviving cells to 29.0% (26.1- 31.7). MA or MG may have additive effect with standard chemotherapeutic agents. Our data suggests that MA and MO have in vitro antitumor activity against SCLC cell lines. Department of Pulmonary Medicine, HelsinkiUniversity CentralHospital, Helsinki, Finland We have alreadyinvestigated, in 15 patientswith cancer,whether naturalor reambinant alpha-IF?? will enter the blood streamafter the inhalation of single escalating doses. Each patient inhaled1, 3, 6, 18, 60 and 120 MIU of naturalalpha-IFN(8 patients)or 18, 126 and 216 MIU of remmbinant alpha-IF??-2a (7 patients)via a dosimter-equipPea jet nebulizer, as single inhalations on separate days, HR, BP, tmpera- ture, PEF and subjective synptmm weremitoredto evaluatethe toxicityof these dosages. Measurable sermconcentraticms of IFNweredetected after inha- laticmof > 60 MIU of naturalalpha-IFN, whereas r+ ambinantZl@a-IFNwasbarely detectable in these- nnn, azxl then only after inhalation of doses > 126 MIU. Side-effects similartothcee seenafter-system- ic administration of IEN occurredafter inhalatim of both types of alpha-IFN: flushin?, fever,stuffy mse,headache andnausea. Inadditicm, bronchial obstructicnwas&served as anewand specificside- effectof inhaledalpha-IFN. We concluded that the pharmamkineticsof natural and reccm&inantalpha-IFN -me different. We are nmccnductinga similarstudywithgamm-IFN. We will also measure the concentration of aamna-IEN in the bronchoalveolar lavage fluid@AL fluid) after inhalation and investigate possible IF?+induced acti- vation of the alveolarmacrqhages and theblood ncnoqtes. We willreport the results of theseinves- tigatla. 682 SERUM LEVELS OF CA 130 IN PRIMARY LUNG CANCER TAKASHI YAMADA, ATSUHIKO SATO*, KIYOSHI SUZUKI, KAZUYUKI YAGI. JIN-ICHIROU AKIYAMA, YOSHIMITSU TAKASHIMA, MASAHARU NAGAYAMA*, JUN HASEGAWA* Shimada Municipal Hospital,*Hamamatsu University School of Medicine,Shizuoka,Japan We investigated serum levels of CAI 30 to evaluate the clinical usefulness. We studied 106 patients with primary lung cancer and 137 of normal subjects. Serum concentration of CA 130 was measured by RIA kit (Dai~chi radlo-isotope Inc. Japan). Serum levels of normal subiects(mean tSD) was 16.4t8.2 U/ml,and the normal range was 0 to 35 U/ml. In primary lunq cancer patients serum CA I30 level was 6 1.4t79.7 U/ml and the positive rate was 40.6%. According to hlstopathological type of lung cancer, each serum level and positive rate were, adenocarclnoma(n=Sl);82.5~99.8 U/ml, 50.9 W, squamous cell carcinoma (n=40);39.0+49.2 U/m1,25.0 %, small cell carclnoma(n=l0);49.9*54.7 U/m1,30.0 W. The CA 130 level and posltlve rate increased with advancing clinical stage (Stage I; 18.2+ 12.4 U/ml, 8.3 %, Stage 11;59.6i84.3 U/ml, 50.0 R, Stage llla;53.1+71.0 U/m1,33.3 W, Stage lllb;l07.2+86.0 U/ml, 83 3%, Stage lV;l27.0t 121.6 U/ml,71.4 XI. There was significant (P(O.05) difference between Stage I and lllb or IV. Therefore CA I30 may be useful for diagnosis of adenocarcinoma of the lung.

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Page 1: Serum levels of CA 130 in primary lung cancer

679

183

680

BRDNCHDALVSOLAR LAVAGE (BALI IN TRB DIAMOSIS OF BRoNCRIOLtOALVROLAR CAR- CINOMA

G. Krag Jacobsen & N. Milman. Departments of Pathology and Pulmonary Medicine, Gentofte Hospital, University of Copenhagen, Denmark

Bronchioloalveolar carcinoma is located peri- pherally in the pulmonary parenchyma at the terminal bronchioles and alveoli and may present either as a localized tumor or as diffuse lesions. On chest X-ray the latter may show the pattern of diffuse interstitial pulmonary disease. In such cases it is often difficult to obtain the correct diagnosis. The frequency of positive findings atcytolo- gical examination of brush biopsies and bronchial washings is disappointingly low and the same apply to transbronchial and per- cutaneous biopsies. We hereby present one case of our own and four cases previously reported, where BAL yielded the diagnosis. Thiough this presentation we intend to draw attention to the use of BAL as a tool in the diagnosis of bronchioloalveolar carcinoma, especially of the type that radiologically shows a diffuse distribution.

681

Magainln Analoguss Have Antitumor Activity Against Human Lung Cancer Cell Lines. Y.Ohsaki. G.E. Richardson, H-C. Chen, A.F. Gazdar and B.E.

Johnson. NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889, U.S.A. Magainin peptides, originally isolated from African clawed frog skin, have been reported to inhibit growth of bacteria and fungi by interacting with their cell membrane. Recently, magainin analogues, magainin A (MA) and magainin G (MG), were synthe- sized, which are more potent against bacteria. In order to deter- mine the antitumor activity of MA and MO, we have tested them against six small cell lung cancer (SCLC) cell lines NCI-H82, 528, 678, 735, 841 and 889, which differ by more than 10 fold in their sensitivity to different chemotherapeutic agents, and four normal human fibroblast (NFB) cells Fe Sin, CCD39Sk, 43Sk and 27Sk. Semiautomated MTT assays of the six SCLC cell lines gave median IC50 values of 2.6 FM (range 0.49-9.30) for cisolatin. 2.5 uM (0.39-6.00) for VP-16, 138.8 nM (55.0- 450.0) for adiiamycin. Median IC50 of MA was 26.1 iglml (18.8-35.2) and that of MO was 28.8 W/ml (13.5-38.0). Despite a 10 fold difference sensitivity to standard chemothera- peutic agents, the IC50 of MA and MG differs less than 3 fold range. Median IC50 values lo the NFB cells of MA was 63.7 ug/m I (38.3-77.4) and that of MO was 89.0 pg/ml (74.9-105.9). The addition of MA 18.8 ug/ml reduced surviving cells to 44.8%, MG 12.5 wrnl to 51.5% , VP-16 1 .O pM to 49.0% and cisplatln 1.48 uM to 59.2% in H878. Combined exposure to MA or MG plus VP-18 or cisplatin decreased surviving cells to 29.0% (26.1- 31.7). MA or MG may have additive effect with standard chemotherapeutic agents. Our data suggests that MA and MO have in vitro antitumor activity against SCLC cell lines.

Department of Pulmonary Medicine, Helsinki University Central Hospital, Helsinki, Finland

We have already investigated, in 15 patients with cancer, whether natural or reambinant alpha-IF?? will enter the blood stream after the inhalation of single escalating doses. Each patient inhaled 1, 3, 6, 18, 60 and 120 MIU of natural alpha-IFN (8 patients) or 18, 126 and 216 MIU of remmbinant alpha-IF??-2a (7 patients) via a dosimter-equipPea jet nebulizer, as single inhalations on separate days, HR, BP, tmpera- ture, PEF and subjective synptmm weremitoredto evaluate the toxicity of these dosages. Measurable sermconcentraticms of IFNweredetected after inha- laticm of > 60 MIU of natural alpha-IFN, whereas r+ ambinantZl@a-IFNwasbarely detectable in these- nnn, azxl then only after inhalation of doses > 126 MIU. Side-effects similar tothcee seenafter-system- ic administration of IEN occurred after inhalatim of both types of alpha-IFN: flushin?, fever, stuffy mse,headache andnausea. Inadditicm, bronchial obstructicnwas &served as anewand specific side- effect of inhaled alpha-IFN. We concluded that the pharmamkinetics of natural and reccm&inantalpha-IFN -me different. We are nmccnductinga similar studywithgamm-IFN. We will also measure the concentration of aamna-IEN in the bronchoalveolar lavage fluid @AL fluid) after inhalation and investigate possible IF?+induced acti- vation of the alveolarmacrqhages and theblood ncnoqtes. We will report the results of these inves- tigatla.

682

SERUM LEVELS OF CA 130 IN PRIMARY LUNG CANCER TAKASHI YAMADA, ATSUHIKO SATO*, KIYOSHI SUZUKI, KAZUYUKI YAGI. JIN-ICHIROU AKIYAMA, YOSHIMITSU TAKASHIMA, MASAHARU NAGAYAMA*, JUN HASEGAWA* Shimada Municipal Hospital,*Hamamatsu University School of Medicine,Shizuoka,Japan We investigated serum levels of CAI 30 to evaluate the

clinical usefulness. We studied 106 patients with primary lung cancer and 137 of normal subjects. Serum concentration of CA 130 was measured by RIA kit (Dai~chi radlo-isotope Inc. Japan). Serum levels of normal subiects(mean tSD) was 16.4t8.2 U/ml,and the normal range was 0 to 35 U/ml. In primary lunq cancer patients serum CA I30 level was 6 1.4t79.7 U/ml and the positive rate was 40.6%. According to hlstopathological type of lung cancer, each serum level and positive rate were, adenocarclnoma(n=Sl);82.5~99.8 U/ml, 50.9 W, squamous cell carcinoma (n=40);39.0+49.2 U/m1,25.0 %, small cell carclnoma(n=l0);49.9*54.7 U/m1,30.0 W. The CA 130 level and posltlve rate increased with advancing clinical stage (Stage I; 18.2+ 12.4 U/ml, 8.3 %, Stage 11;59.6i84.3 U/ml, 50.0 R, Stage llla;53.1+71.0 U/m1,33.3 W, Stage lllb;l07.2+86.0 U/ml, 83 3%, Stage lV;l27.0t 121.6 U/ml,71.4 XI. There was significant (P(O.05) difference between Stage I and lllb or IV. Therefore CA I30 may be useful for diagnosis of adenocarcinoma of the lung.