33

Camptotnecin sodium i~ the form of

polyphase liposme was studied in this paper, It is assumed that CS in liposo-

me-entrapped form might have more power- ful antitumor activity and less toxici- ty than free CS. The effects of poly- phase liposome of camptothecin sodium (PL-CSA) on the life cycle of Ehrlich ascites carcinoma cells in mice was stu- died by autoradiographic method. The Tc of the cells was found to be 39.2 hours.

The T G , T , TG2 , and T M were 8.6, 24.7, 4.3 an~ i.~ hours, respectively. The growth fraction was 0.84. The experimen- tal results showed that cells in S phase might be killed by PL-CSA 25 mg/kg. The mitotic index was also decreased ~ignifl- c~Dtly after the treatment. PL-CSA prevent- ed strongly the cells progression from S phase into M phase. By microscopic examination, most cells accumulated in GA phase exhibited remarkable morpholo- Z

glcal changes, such as swollen, vacuola- ted nuclei and karyorrhexis, etc. Five hours after the administration of PL-CSA the damaged cells in Go phase were about 9.5%. Under the action of PL-CSA, the syntheses of DNA in vivo was inhibited significantly. Experimental results in- dicate that PL-CSA is a non-specific agent on the carcinoma cells cycle and that cells in S, G 2 phase are sensitive to this drug.

Intratumoral Diversity of Phenot)~ie At- trabutes of Squamous Cell Lung Carcino- mas: Consequences for Biological Analysis. Olsson, L., Rahbek S~rensen, H. State University Hospital, Copenhagen, Denmark.

Cloned cell lines of squamous cell lung carcinomas were established in vitro and the phenotypic diversity analysed in re- spect to morphology, clonogenicity, anti- genicity, and tumorigenicity. A remark- able diversity was found in all parame- ters, including antigenicity that was studied by the use of monoclonal anti- bodies with specificity for common cell surface components (histocompatibility angivens) and for antigens with high tumor specificity.

In order to study the effect of chan- ges in gene activity and degree of cell maturation on the expression of the pheno- typic attributes analysed in this study, the cloned in vitro cell lines sere treat- ed with 5-azacytidine(5-azaC) in order to obtain gene activity and with phorbol ester (TPA) and retinoid acid (RA) in or- der to induce cell differentiation. 5-AzaC changed the cloning efficiency of the cell lines up to 80 times and could also

result in s~blines with both tumorigenic and metastatic activity in nude mice.

In contrast, TPA or RA treatment resulted

in loss of tumorigenicity in vivo and clonogenici- ty in vitro. These data thus indicate that the

amount of clonogenic/tumorigenic cells in such cell lines is determined by expression of a set of genes that in their expression seems regulated by the me- thylation pattern of the genome. The consequences for these aspects for attempts to identify genes in- volved in the tumorigenic behaviour of these cells are outlined.

Moreover, the generation of metastatic variants should permit application of molecular biology tech- nology to identify metastasis associated genes.

Expression of H~nan Lymphocite Antigens (HLA) in Human L~,g"- Cancer. . I Facchini I A., Mariani~, E., Mastrorill~ , M., Bragagl~a , R., Milanil, M., Villanacci , V., Ferrone , S., Gozzetti , G. i. Department of Surge- ry and Pathology, University of Bologna, Italy. 2. Department of Microbiology and Immunology, Val- halla University, New York, U.S.A.

The expression of three cytoplasmic membrane antigens (HLA, HLA-Dr, B2-microglobulin ) was inve- stigated in serial sections of twenty-one human lung cancers (non small cell lung cancer) using monoclonal antibodies and the Avidin-Biotin Perox- idase-Complex method.

The frequency of positive reactions and the relationship among these antigens were determined. Some of these antigenic expression seem to be re- lated to histological and cytological aspects of tumors and can provide important information about the prognosis and therapy.

Role of Tumor Associated Macrophages in Lung Can- cer Patients. Takeo, S., Yasumoto, K., Miyazaki, K., Kuda, T., Nagashima, A., Yaita, H., Furukawa, T., Nomoto, K. Second Department of Surgery, Kyushu University Medical SchooL, ~ka, Japan.

Content and antitumor activity of tumor as- sociated macrophages (TAM) were examined in 71 patients with resectable primary lung cancer.

TAM was obtained by plastic adherence follow- ing trypsinization of surgical specimens. The plastic adherent cells were identified as TAM more than 90% by nonspecific esterase staining and morpho- logical features,

Content of TAM was widely distributed from 0.1% to 17.3% of total viable cell counts. Patients having more than 2% of TAM content exhibited 4/29 (13.8%) of recurrence rate. On the other hand, those having less than 2% did 8/26 (30.8%). However, there was no significant difference between them.

Cytostatic activity of TAM was assessed by inhibition of DNA synthesis of allogenic lung can- cer cell line of QG-56, and was ranged from -56% to 81%. Although 7 of 15 patients showing less than 30% of cytostatic activity have recurrent diseases following surgical treatment, only one of 19 pa- tients showing more than 30% of it does. There was significant difference between them (P<0.005).

Thus, the assessment of antitumor activity of TAM (not content of TAM) may give prognostic

information of lung cancer patients.