386 Abstracts / Lung Cancer 15 (1996) 381-399

or controls at 1 imoVL or 10 ImobL concentrations for 4 or 10 days. Cellular proliferation was measured by tritiated thymidine uptake. Flow cytometry was used to quantitate oncoprotein expression. Intranuclear ASODN uptake was documented by fluoresceine-tagged ASODNs. Results. Fluoresceine-tagged ASODNs were readily taken up by all cell lines. c-myc, as well as b&Z and ~53 ASODNs, were found to inhibit proliferation ofall cell lines significantly compared with controls, most notably in line AS49 (40.1% f 7.1% of control, p = 0.000 with c-myc ASODN). Antisense c-myc reduced c-myc protein by as much as 7 1.3% in A427. although protein levels were only minimally reduced in the viable cells of the other lines. Conclusions. c-myc ASODNs inhibit proliferation of non-small cell lung cancer cell lines as well as reduce c-myc protein expression. Antisense bcl-2 and ~53 also cause similar growth inhibition. These results suggest a critical role for activation of these oncogena in the growth of cultured lung cancer cells. Furthermore. the efficacy and rapid cellular uptake of ASODNs support the potential role of antisense targeting of oncogene expression for pharmacologic control of non-small cell lung cancer,

The effect of 3’-deorysdenosine N1-oxide on growth in vitro and in vivo on Ehrlich ascites tumor and on a human squamous lung cell carcinoma xenograft in nude mice Ramlov Svendsen K. Overgaard-Hansen K. FrederiJtsen S. Spang- Thomsen M. Dept. Medical Biochemistry/Genetics. Bichemistry Laboratory B, University of Copenhagen, Copenhagen. Cancer Invest 19%;14:19-24.

The effect of 3’deoxyadenosine Ni-oxide (3’dANO) on Ehrlich ascites tumor and a human squamous lung cell carcinoma was investigated. The 3’dANO concentration that inhibited the cell growth 50% (IC,,,) in Ehrlich ascites tumor cells in vitro was 0.15 r&f, and the killing efficiency concentration (concentration of the dnig that kills all cells) was 1 mM. By simultaneous administration of 3’dANO and the adenosine deaminase inhibitor erythro-9-(2-hydroxyI-3-nonyl) adenine (EHNA), the IC,, of 3’dANO was unchanged, but the killing efficiency concentration of 3’dANO was reduced to 0.3 mM. When mice bearing Ehrlich ascites tumor were treated i.p. with 3’dANO doses of 200 mp/ kg daily for 4 days, the mean increased life span (JJS) was 200%. 3’- dAN0 in combination with EJJNA did not further increase the life span of tlte tumor-bearing mice. The specific growth delay (SGD) of the Ehrlich tumor and of a human squamous lung cell carcinoma growing subcutaneously in 3’dANO-treated mice were calculated from Gomperts tumor growth curves. The Ehrlich tumor-bearing mice received 3’dANO i.p. at doses of 250 mgikg daily for 4 days, and the nude mice bearing human carcinoma received 3’-dANO i.p. at doses of 225 mg/kg daily for 5days. The SGD for the investigated tumors were calculated to be 1.0 and I. 1. respectively.

Pathology

A dinicopathologic study of resected Casey of adenosquamous carcinoma of the lung Shimiztt J, Oda M. Hayashi Y, Nonomura A, Watanabe Y. Department ofSutge!y, Kanazawa University&h. ofMedicine, 13-1 Takara-machi, Konozowo 920. Chest 1996;109:989-94.

Adenosquamous carcinoma of the lung is an uncommon form of the lung cancer. Owing to the infrequent occurrence of this disease, no series reported to date (and to our knowledge) has been of adequate size for definitive statistical analysis. In this study, survival curves and

background factors affecting prognosis in those with resected adenosquamous carcinoma of the lung were reviewed. In the period from 1973 to 1994, a total of 1,284 patients with primary lung cancer, including 44 cases (3.4%) of adenosquamous carcinoma, were su@aJly treated in our department. The cumulative 5-year postoperative survive

rate, for all eases of adenosquamous carcinoma of the lung, was 18.5%. When the survival rates were compared by histologic type, tlte outcomes ofpatients with adenosquamous carcinoma were statistically worse than

for patients with squamous cell carcinoma and adenocarcinoma, owing to the highly aggressive pathologic stage of adenosquamous carcinoma. The background factors most closely associated with the survival rate in those with adenosquamous carcinoma, using Cox’s proportional hazard model, were gender and the degree of nodal involvement. Five- year sunivaJ was obtained in seven patients as follows: TJNOMO in one patient, T2NOMO in three, TZNIMO in two, and T3NOMO in one, Of these seven patients, all had received complete resections, and five were NO cases. Although our series is small, this study suggests that adenoszJuamous carcinoma of the lung is an aggressive tumor that grows rapidly.

Inversely correlated expression of p16 and Rb protein in non- small cell lung cancers: An immunohistochemical study Sakaguchi M. Fujii Y, Hirabayashi H, Yoon H-E, Komoto Y, Oue T et al. 1. Department of .SuTety Osaka University Medical School, 2-2 Yomadaoka, Suita, Osaka 565. Int J Cancer 1996;65:442-5.

Cdk4-mediated phosphorylation ofRb protein is inhibited by ~16, a product of a possible tumor suppressor gene. We examined the expression of pl6 and Rb protein by means of immunohistochemistry in 6 I non-small cell lung cancers and have demonstrated an inverse relationship between the expression of ~16 and Rb protein: 28130 specimens that did not stain for pl6 stained for Rb and 21/3 1 p16- positive specimens did not stain for Rb. Only I of the pl6-negative specimens had a mutation of exon 2 of the CDKNZ gene. Our results indirectly support the theory that pl6 expression is negatively regulated by the functional Rb protein.

Observer variability in histopathological reporting of non-small Cell lung carcinoma on bmnchial biopsy specimens Burnett RA, Howatson SR, Lang S, Lee FD, Lessells AM, McLaren I&I et al. University of Glasgow. Department of Pathology, Western In/irmav, Glasgow GlI 6NI: J Clin Pathol 199649: 130-3.

Aims - To evaluate the ability of histopathologists to sub-classify non-small cell lung carcinomas on bronchial biopsy material using the current World Health Organisation (WHO) classification. Methods - Twelve hi&pathologists each reviewed 100 randomly selected bronchial biopsy specimens which had originally been reported as showing non- small cell lung carcinoma. For each case, two sections were circulated. one stained by haematoxylin and eosin and the other by a standard method for mucin (alcian blue/pericxlic acid Schiff). The participants were allowed to indicate their degree of confidence in their classification of each case. A standard proforma was completed and the results were analysed using kappa statistics. Results - Where the participants were confident in their classitication, they were actually quite good at sub- classifying the non-small cell carcinoma sections (kappa = 0 7 I, standard error = 0.058). Overall, however, the results were only fair (kappa = 0.39, standard error = 0.034). Conclusions - The majority of non-small cell lung carcinomas can be correctly categorised on adequate bronchial biopsy material. Where a confident diagnosis was made, both squamous carcinoma (kappa = 0.73) and adenocarcinoma (kappa = 0.83) were well recognised.