432 Abstracts/Lung Cancer 11 (1994) 423-444

approaches. Recent studies havedetined several drug rasistant mechanisms in lung cancer and have suggested methods for preventing and reversing treatment resistance. Insight into the biology of lung cancer will allow theimprovementofcurrent approaches to the prevention, diagnosis, and treatment of this devastating disease.

Interleukin-1 production is defective in alveolar macrophages from patients with lung cancer McDonald CF. Senea-Ferrari S, AtkinsRC. Department ofRespiratoory Medicine, Heidelberg Repatriation Hospital, Banksia St., Heidelberg Kc. 3084. Cancer J 1994;7:25-31.

Aim. To determine whether interleukin-I (IL-l) production by pulmonary alveolar macrophages (PAM) is impaired in patients with lung cancer. Patients. Eleven untreated patients with bronchogenic carcinoma and ten control subjects, including seven without demonstrable pulmonary abnormality undergoing bronchoscopy for investigation of chronic cough or haemoptysis, and three normal volunteers. Interventions - Bronchoalveolar lavage (BAL) with subsequent measurement of IL-I. Measurements and main results - IL- 1 was measured by a thymocyte proliferation assay in PAM supematants after a four-hour incubation in the presence or absence of gamma interferon or endotoxin. Whereas IL- I was found in the unstimulated supematants from seven out of nine control subjects (1.25 f 0.5 units/lob PAM), it was present in the instimulated supematant of only one out of I I cancer subjects (0. I6 f 0.2unitsll06PAM)(pC0.05). Gammainterferonorendotoxinincreased IL-l in eight of nine control supematants. Small amounts of IL-l were measured in three of eight cancer supematants after endotoxin, and in four of nine cancer supematants after gamma interferon. Conclusions - IL-I is generally not produced by unstimulated alveolar macrophages from lung cancer patients, whereas it is produced in small amounts by those from control subjects. However, macrophages from some cancer patients can be induced to produce IL-I after activation with endotoxin or gamma interferon. The mechanism for the reduced IL-l production by cancer macrophages is unclear, but this difference does not appear to reflect the presence of inhibitors.

~53 mutations in primary human lung tumors and their metastaws Reichel MB, Ohgaki H, Petersen I, Kleihues P. Institute of Neuropathology, Uniwrsity Hospital, CH-8091 Zurich. Mol Carcinog 1994;9:105-9.

In a total of 26 primary human lung tumors and 60 metastases derived from them, exons 5-8 of the p53 tumor suppressor gene were analyzed by single-strand conformation polymorphism and subsequent direct DNA sequencing of amplified DNA. Mutational inactivation of the ~53 gene was identified in four of five squamous cell carcinomas, three of nine adenocarcinomas, and two of nine small-cell carcinomas, the overall incidence being 35%. Point mutations occurred at a similar incidence in exons 5-8, with a preference for G T transversions. In seven of nine cases (78 %), mutations were identical in the primary tumor and all of its metastases, indicating that in lung tumors, ~53 mutations usually precede metastasis and that hematogenic and lymphogenic dissemination of tumor cells to other tissue is not associated with a selection against ~53 inactivation. In one case, a kidney metastasis had the same mutation as the primary squamous cell carcinoma, whereas a liver metastasis had no mutation, indicating heterogeneity of the primary lung neoplasm and selective metastasis of mutated and nonmutated tumor cells to kidney and liver, respectively. Only in one liver metastasis was a mutation identified that was neither present in the primary lung tumor nor in a kidney metastasis, suggesting that occasionally P53 mutations occur after metastatic spread.

Oxidative DNA base damage and antioxidant enzyme activities in human lung cancer Jaruga P. Zastawnya T.H. Skokowski J. Dizdaroglu M. Olinski R. Chemical Science/Technol. Lab. National Inst. Standardr/Technol., Gaithersburg, MD 20899. Febs L&t 1994;341:59-64.

We have investigated levels of antioxidant enzymes and free radical- induced DNA base modifications in human cancerous lung tissue and in their cancer-free surrounding tissues. Various DNA base lesions in chromatin of lung tissues were measured by gas chromatography-mass spectmmetry. Activitiesofsupemxidediimutaqcatalaseandglutathione peroxidase were also measured in lung tissues. Higher levels of DNA lesionswereobsenedincanceroustissuesthanincancer-~~surrounding tissues. Antioxidant enyme levels were lower in cancerous tissues. The resultsindicateanassociationbehvcendecreasedactivitiesofantioxidant enzymes and increased levels of DNA lesions in cancerous tissues. Higher levels of DNA lesions suggest that free radical reactions may be increased in malignant tumor cells.

Differences of E-cadherin expression levels and patterns in human lung- Bohm M, Totzeck B, Wieland I. last Zellbiologie (Tumorforschung), Universitatsklinikxm, Virchowstrasse 173, D-451 22Ewen. Ann Hem&l 1994;68:81-3.

Fitly-two lung carcinomas obtained at surgical resection were examined by immunofluorescence for their expression levels and patterns of the calcium-dependent intercellular adhesion molecule E- cadherin. In well-differentiated squamous cell and adenocarcinomas expression of E-cadherin was confined to the lateral cell border, similar to theexpression level and pattern ofnormal lung tissue. The E-cadherin level was reduced and the expression pattern was spotty or diffuse in moderately and poorly differentiated squamous cell carcinomas and in small cell carcinomas of the lung. Also, most metastases resected had a reduced level and an altered pattern of E-cadherin expression. In contrast, no such correlation was found in adenocarcinomas of the lung. This indicates that different cellular mechanisms are responsible in the progression of squamous cell carcinomas versus adenocarcinomas of the lung.

Clinical assessment Evaluation of CYFRA 21-l as a new marker for non-small cell lung cancer Nikliaski J, Furman M, Chyczewska E, Chyczewski L, Rogowski F, Jamszewicz E et al. Department of Ihoracic Surgery, Medical School, 24a M. Sklodowska-Curie Street, 15-276 Bialystok. Eur J Cancer Prev 1994;3:227-30.

The levels of the new tumour marker CYFRA 21-l were assessed in I I5 patients with non-small cell lung cancer (NSCLC) and in 45 patients withnon-malignant lung disease. Increased IeveIsofCYFRAZl-I were observed in 47.8%. mostly in patients with squamous cell carcinoma (SCC; 69. I W). Serum CYFRA 21-l levels were correlated with the stage of SCC type. Positive CYFRA 21-l levels in patients with SCC werepresentin4O%ofstage1,61.1%ofstageII,and85.2%ofstage III. In addition, SCC patients who presented media&ml lymph nodes (N2) demonstrated higher serum CYFRA 21-l levels, compared with patients without media&al lymph nodes metastases (NO or Nl). With regard to tumour size, significant difference was observed between Tl, T2 and T3. The study also showed that the percentage of patients who survived I8 months with normal preoperative level of CYFRA 21-1 was higher compared with those patients with elevated preoperative levels of this marker, but the differences were not statistically significant.