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20 067 068 BASIC FETOPROTEIN (BFP) IN PRIMARY LUNG CANCER Yukihisa Fujita, Takechika Goto, Tsuneo Fujii, Norihiro Hiramori, Takao Kida, Taichiro Arimoto, Yoshinobu Nakagaki, Mayuka Sakai, Yoshinobu Iwasaki, Katsuhiko Nishiyama*, Taizo Nakamura and Masao Nakagawa. Second Department of Medicine, *Second Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan BFP is a kind of oncofetal protein and an useful tumor marker for lung cancer. To investigate BFP in primary lung cancer cells, 21 surgically resected primary lung cancers were stained immunohistochemically by labelled streptoavidin-biotin method with polyclonal anti-BFP antibody. In 9 of 12 adenocarcinomas, 3 of 5 squamous cancers, 1 adenosquamous cancer, none of 2 large cell cancers and 1 small cell lung cancer, BFP was positively stained. From the view point of differentiation, well differentiated carcinomas, as well as poorly differentiated carcinomas were positive for BFP. The results indicate that BFP is expressed in a wide range of primary lung cancer, irrelevant to histologal types and the degree of differentiation. Radiation sensitivities in various anticancer drug resistant human lung cancer cell lines and mechanism of radioresistance in cis-Diamminedichlaroplatinum~IIl resistant lung cancer cell line Fumihiro Oshita, Yasuhiro Fujiyara and Nagahiro Saijo Pharmacology Division, National Cancer Center Research Institute, Tsukiji, 5-1-l. Chuo-ku, Tokyo, Japan To analyze the mechanism of cross-resistance between anticancer drugs and ionizing radiation, 6 drug resistant lung cancer cell lines and their parental cell lines were examined for radiosensitivity using a growth inhibition assay. The IDS,, and Do in PC-9/CDDP, Which was cisplatin resistant or PC-g, its parental adenocarcinoma cell lines of the lung, were 843f31.BcGy and 1.020~0.161Gy, or 509f13.3cGy (p=O.O004) and 0.551*0.129Gy (p=O.O353), respectively. These data show that PC-9/CDDP was radioresistant compared to PC-g. The radiosensitivities of cisplatin or CPT-11 resistant adenocarcinoma cull lines of the lung such as PC-7/CDDP, PC- 14,CDDP o: :'C-:/rPT, ". : “qi.‘ ..‘p _1 ,‘y‘ : .n ~ 1 cell lung cancer cell lines such as H69/CDDP or H69/VP were not significantly different from those of respective parental cell lines such as PC-J, PC-14 and H69. To analyze the mechanism of radioresistance in PC-9/CDDP, the amounts of induction and repair speed of single-strand breaks (ssb) or double-strand breaks (dsbl after irradiation were examined in PC-9 and PC-9/CDDP by an alkaline elution method. Although the repair of dsb were not different between PC-9 and PC- 9/CDDP, the induction of dsb in PC-9/CDDP was less than that in PC-g. The induction and repair of ssb were not different in each cell line. Intracellular glutathione (GSH) contents of PC-9 and PC-9/CDDP were 20.0i0.9nmol/mg protein and 63.5*8.5nmol/mg protein respectively. After depletion of GSH in PC-9/CDDP by treatment with 5Ow of buthionine sulfoximine (BSOI to the level of parental PC-g, the induction of dsb by irradiation became elevated to the same levels in BSO untreated PC-g, and PC-9/CDDP became to show the same levels of radiosensitivity in BSO untreated PC-g. Therefore, the elevated GSH content of PC-9/CDDP was thought to induce radioresistance in PC-O/CDDP. These data provide a basis for a clinical trial of radiotherapy with BSO against the locally advancedrecurrent lung cancerafter cisplatin treatment. 069 INHIBITORY EFFECTS UF/%CAHCITENE UN PHOLIFEMTIUN IN VITXO AND IWI'ASTASIS 1~4VIVd OF LUNG CAB&3 CEdS BT Lai,H Wang,l;Z Liu,E'H Jiao and H Yan. Beijing Thoracic Tumor Research Institute,P.H.China. We have investigated tne erf'ect of,@-carotene on cellular proliferation of human pulmonary carcinoma cell line PAA-801 and spontaneous lung metastasis of' murine lung adenocarcinoma L47y5 cell. C-carotene cause a dose-dependent innioition of proliferation of P!A-~01 cells,wrtn maximal innibition observed at concentration 20,uPl.its innibitory rate of colony forming at concentration of 5 ,ut? was around I&, 10,~M was 454, 209 was near li@&?he killing efficiency was related closely to its concentration but could not be enhanced by prolor&ing tne treating time from tl to 72 hrs. In the model of spontaneous lung metastasis 1*107 LA795 tumor cells were inJected subcutaneously. 'The primary tumor was resected on 10th day end metastatic lung lesion was counted on 30th day. Treatment was started immediately following the surgical excision. Mice received diets containing 0 or 250 m&/lcg of p-carotene. The average lesion number per lung in control andp-carotene groups were respectively 44.6 and 31.7. The inhibition rate was 2%. The result of second experiment showed that 35.1 and 18.1 and the inhibitory rate was 48%. The evaluation of the antitumor properties of p-carotene snould be continued. 070 In Vitro Induction of HLA-DR Antigen -- Expression in Human%ng?%Cancer Cell s ___- H. Kamma, T. Yazawa. H. Horiguchi. M. shiwa and T. Ogata. Dept. of Path01 ogy . uni versi ty of Tsukuba. Tsukuba. Japan. HLA-DR antigen is often demonstrated in lung cancers with lymphocytic infiltrates. An Jo vitro study was performed to induce -~ HLA-DR antigen in 10 lung cancer cell lines of various histologic types. Tumor ccl 1 s were cultured in the media containing recombinant Interferon-E (IFN-r) for 4 days. After washing out IFN-r. they were continued to culture in IFN-r-free media for 4 days. HLA-DR antigen el ici ted in the cytoplasm was examined by an immunoperoxidase method every day. Its expression on the cell-surface was al so conf i rmed usi ng i mmuno-f ruol ecence and immunoel ectron microscopic methods. HLA-DR antigen was induced in the cytoplasms of non-small cell cancer cells. while it was not elicited in small cell cancer ccl 1s except for one of variant type. After the intracytoplasmic induction, HLA-DR antigen was also expressed on the ccl l- surface though to a lesser extent than In the cytoplasm. HLA-DR antigen -positive tumor cells gradually increased till the 4th or 6th day. and then decreased. Its patterns and maximum positive rates varied among the cell types. It was revealed that HLA-DR antigen expression could be induced in lung cancer cells exceot for classic small cell cancer.

In vitro induction of HLA-DR antigen expression in human lung cancer cells

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067 068

BASIC FETOPROTEIN (BFP) IN PRIMARY LUNG CANCER

Yukihisa Fujita, Takechika Goto, Tsuneo Fujii, Norihiro Hiramori, Takao Kida, Taichiro Arimoto, Yoshinobu Nakagaki, Mayuka Sakai, Yoshinobu Iwasaki, Katsuhiko Nishiyama*, Taizo Nakamura and Masao Nakagawa. Second Department of Medicine, *Second Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

BFP is a kind of oncofetal protein and an useful tumor marker for lung cancer. To investigate BFP in primary lung cancer cells, 21 surgically resected primary lung cancers were stained immunohistochemically by labelled streptoavidin-biotin method with polyclonal anti-BFP antibody. In 9 of 12 adenocarcinomas, 3 of 5 squamous cancers, 1 adenosquamous cancer, none of 2 large cell cancers and 1 small cell lung cancer, BFP was positively stained. From the view point of differentiation, well differentiated carcinomas, as well as poorly differentiated carcinomas were positive for BFP. The results indicate that BFP is expressed in a wide range of primary lung cancer, irrelevant to histologal types and the degree of differentiation.

Radiation sensitivities in various anticancer drug resistant human lung cancer cell lines and mechanism of radioresistance in cis-Diamminedichlaroplatinum~IIl resistant lung cancer cell line

Fumihiro Oshita, Yasuhiro Fujiyara and Nagahiro Saijo Pharmacology Division, National Cancer Center Research Institute, Tsukiji, 5-1-l. Chuo-ku, Tokyo, Japan To analyze the mechanism of cross-resistance between anticancer drugs and ionizing radiation, 6 drug resistant lung cancer cell lines and their parental cell lines were examined for radiosensitivity using a growth inhibition assay. The IDS,, and Do in PC-9/CDDP, Which was cisplatin resistant or PC-g, its parental adenocarcinoma cell lines of the lung, were 843f31.BcGy and 1.020~0.161Gy, or 509f13.3cGy (p=O.O004) and 0.551*0.129Gy (p=O.O353), respectively. These data show that PC-9/CDDP was radioresistant compared to PC-g. The radiosensitivities of cisplatin or CPT-11 resistant adenocarcinoma cull lines of the lung such as PC-7/CDDP, PC- 14,CDDP o: :'C-:/rPT, ". : “qi.‘ ..‘p _1 ,‘y‘: .n ~ 1 cell lung cancer cell lines such as H69/CDDP or H69/VP were not significantly different from those of respective parental cell lines such as PC-J, PC-14 and H69. To analyze the mechanism of radioresistance in PC-9/CDDP, the amounts of induction and repair speed of single-strand breaks (ssb) or double-strand breaks (dsbl after irradiation were examined in PC-9 and PC-9/CDDP by an alkaline elution method. Although the repair of dsb were not different between PC-9 and PC- 9/CDDP, the induction of dsb in PC-9/CDDP was less than that in PC-g. The induction and repair of ssb were not different in each cell line. Intracellular glutathione (GSH) contents of PC-9 and PC-9/CDDP were 20.0i0.9nmol/mg protein and 63.5*8.5nmol/mg protein respectively. After depletion of GSH in PC-9/CDDP by treatment with 5Ow of buthionine sulfoximine (BSOI to the level of parental PC-g, the induction of dsb by irradiation became elevated to the same levels in BSO untreated PC-g, and PC-9/CDDP became to show the same levels of radiosensitivity in BSO untreated PC-g. Therefore, the elevated GSH content of PC-9/CDDP was thought to induce radioresistance in PC-O/CDDP. These data provide a basis for a clinical trial of radiotherapy with BSO against the locally advanced recurrent lung cancer after cisplatin treatment.

069

INHIBITORY EFFECTS UF/%CAHCITENE UN PHOLIFEMTIUN IN VITXO AND IWI'ASTASIS 1~4 VIVd OF LUNG CAB&3 CEdS

BT Lai,H Wang,l;Z Liu,E'H Jiao and H Yan. Beijing Thoracic Tumor Research Institute,P.H.China. We have investigated tne erf'ect of,@-carotene on cellular proliferation of human pulmonary carcinoma cell line PAA-801 and spontaneous lung metastasis of' murine lung adenocarcinoma L47y5 cell. C-carotene cause a dose-dependent innioition of proliferation of P!A-~01 cells,wrtn maximal innibition observed at concentration 20,uPl.its innibitory rate of colony forming at concentration of 5 ,ut? was around I&, 10,~M was 454, 209 was near li@&?he killing efficiency was related closely to its concentration but could not be enhanced by prolor&ing tne treating time from tl to 72 hrs. In the model of spontaneous lung metastasis 1*107 LA795 tumor cells were inJected subcutaneously. 'The primary tumor was resected on 10th day end metastatic lung lesion was counted on 30th day. Treatment was started immediately following the surgical excision. Mice received diets containing 0 or 250 m&/lcg of p-carotene. The average lesion number per lung in control andp-carotene groups were respectively 44.6 and 31.7. The inhibition rate was 2%. The result of second experiment showed that 35.1 and 18.1 and the inhibitory rate was 48%. The evaluation of the antitumor properties of p-carotene snould be continued.

070

In Vitro Induction of HLA-DR Antigen -- Expression in Human%ng?%Cancer Cell s ___-

H. Kamma, T. Yazawa. H. Horiguchi. M. shiwa and T. Ogata. Dept. of Path01 ogy . uni versi ty of Tsukuba. Tsukuba. Japan.

HLA-DR antigen is often demonstrated in lung cancers with lymphocytic infiltrates. An Jo vitro study was performed to induce -~ HLA-DR antigen in 10 lung cancer cell lines of various histologic types. Tumor ccl 1 s were cultured in the media containing recombinant Interferon-E (IFN-r) for 4 days. After washing out IFN-r. they were continued to culture in IFN-r-free media for 4 days. HLA-DR antigen el ici ted in the cytoplasm was examined by an immunoperoxidase method every day. Its expression on the cell-surface was al so conf i rmed usi ng i mmuno-f ruol ecence and immunoel ectron microscopic methods.

HLA-DR antigen was induced in the cytoplasms of non-small cell cancer cells. while it was not elicited in small cell cancer ccl 1s except for one of variant type. After the intracytoplasmic induction, HLA-DR antigen was also expressed on the ccl l- surface though to a lesser extent than In the cytoplasm. HLA-DR antigen -positive tumor cells gradually increased till the 4th or 6th day. and then decreased. Its patterns and maximum positive rates varied among the cell types. It was revealed that HLA-DR antigen expression could be induced in lung cancer cells exceot for classic small cell cancer.