108 Abstrrrcts / Lung Ctuwrr I6 (1996) 105-127

ferences between the mortality rates of each period studied. Lung can- cer mortality rates for males in Catalonia and Spain show relative in- crements of 4658% and 52.41%, respectively. In contrast, lung cancer mortality in countries such as England-Wales and SwitzerIand have decreased. Moreover, the O-44 year age group in Catalonia and Spain shows the absolute highest rates in the 1987-1989 period among all the countries analyzed. The marked contrast of the lung cancer mortality rate evolution in Catalonia and Spain compared with some other Euro- pean countries and the considerable increase of the mortality in younger age groups indicate the need to intensify lung cancer central measures.

Basic biology

Association between the ~21 codon 31 Al (arg) allele and lung cancer Sjalander A, Birgander R, Rannug A, Alexandrie AK, Tornling G, Beckman G. Department of Medical Genetics, Umea Univers$v, S- 90185 I/mea. Hum Hered 1996;46: 221-5.

In previous investigations p53 polymorphisms and haplotypes have been found to be associated with different types of cancer. In this paper the codon 3 1 polymorphism of the p53-inducible protein p2 1 was stud- ied in 144 Swedish lung cancer patients and two different control groups: 95 patients with chronic obstructive pulmonary disease (COPD) and 76 1 healthy controls. An increased frequency of the p2 1 codon 3 1 A 1 (arg) allele was found in lung cancer patients, especially in comparison with COPD patients @ = 0.004). There was a significantly increased frequency among lung cancer patients of individuals carrying the arg allele both in comparison with COPD controls (OR= 5.2, 95% CI l.S- 18.1) and healthy controls (OR = 1.7,95%CI = 1.0-2.9). The results of this and previous studies indicate that allehc variants of both ~53 and its effector protein p2 1 may have an intluence on lung cancer.

Modification of tumor suppressor gene expression and induc- tion of apoptosis in non-small cell lung cancer (NSCLC) with an adenovirus vector expressing wildtype ~53 and cisplatin Roth JA. Univ Texas MD Anderson Cancer Centes Dept Thoracic Car- diovascular Sut~ety, Houston, TX. Hum Gene Ther 1996;7: 1013-30.

Protocol: Clinical Protocol for Modification of Tumor Suppressor Gene Expression and Induction of Apoptosis in Non-Small Cell Lung Cancer (NSCLC) with an Adenovirus Vector Expressing Wildtype ~53 and Cisplatin. Study Chairman: Jack A. Roth, M.D. Patient Eligibility: Patients must have histologic proof of non-small cell lung cancer, Pa- tients must be either unresectable, unable to receive primary external beam radiation therapy, or have failed primary external beam radiation therapy, or have failed chemotherapy, Patients muat have either an en- dobronchial tumor accessible by the bronchoscope with some clinical evidence of bronchial obstruction, or advanced local-regional cancer which is unresectable. All patients must have a life expectancy of at least I2 weeks and must have a performance status of 5 2 (Zubrod scale, Appendix B). A tumor biopsy must show a ~53 mutation by sin- gle-strand conformation or sequence analysis. Patients will be tested for HIV prior to entry onto the protocol and must be HIV-negative, Patients must have adequate bone marrow function (defined as periph- eral absolute gramdocyte count of > 2,000/mniJ and platelet count of 1OO,OOO/rmn’), adequate liver function (bihrubin 5 1.5 mg/dl), and

adequate renal function (creatinine < 1.5 mg/dl). Treatment Plan (In- chide dose adjustment). The study will be done with two arms. It is not know what toxicities if any will be caused by the adenovirus. The first arm of the study will allow assessment of toxicities related only to the vector. Patients will receive one intratumor injection of AdSCMV-~53. The initial dose will be 10, plaque forming units (PFU). Following

completion of the first vector-alone group, a second phase will evalu AdSCMV-p53 and cisplatin administered conNrrently. Patients in A II will receive one course of cisplatin at 80 MgM2 on day 1 (which ( be given as an outpatient) followed by intratumor injection of AdSCN ~53 on day 4. Three patients will be entered at each dose level wit patients entered at the maximum tolerated or maximum attainable d (limitation imposed by production of the adenovirus) for each gro

The adenovirus dose will increase in one log,, increments from 10 to IO9 and half-log increments from IO9 to 10”. Patients entered i given dose level will not be eligible for dose escalation. The dose cisplatin will remain constant, Pretreatment and Treatment Evaluati Patients will have a CBC, platelet count, PT, PTT, SMA-12, elecl lytes, and a chest x-ray prior to each course of therapy. Serum will collected pre- and post-treatment for analysis of antibodies to adenc rus proteins. The endobronchial tumors will be photograpl bronchoscopically at the beginning of each course. Tumor meast ments are to be recorded before each course for all measurable tumc Fine needle aspirates or core biopsies will be obtained of accessl local tumor. For endobronchial tumors bronchoscopic tumor and r ma1 bronchial epithelial biopsies will be obtained prior lo the bet ning of each course. Tissue will be fixed immediately in 4% para-’ maldehyde and 0.5% gluteraldehyde at 4°C. This will permit exti tion of DNA and RNA and permit in situ hybridization, Biopsies ( be analyzed for incorporation of the transduced gene into the host nomic DNA and expression of the transduced gene at the RNA leve standard hybridization techniques following polymerase chain reacl and by in situ hybridization. All patients will be evaluable for respc and toxicity following one course of therapy. Miscellaneous lnfor tion: Not applicable. Statistical Considerations: Three patients wil entered at each dose level with 6 patients entered at the maximum erated or maximum attainable dose (limitations imposed by produc of the adenoviius). A maximum of 27 patients will be entered in intratumor group, respectively for each of the treatment gro (AdSCMV-p53 alone and Ad5CMV-p53 plus cisplatin). Objective! To determine the maximum tolerated dose of the wild-type ~53 adc virus vector given with and without cisplatin in patients with refrac non-small cell lung cancer. 2. To determine the qualitative and qua tative toxicity and reversibility of toxicity of this treatment approacl To document observed antitumor activity of this treatment approac

Significance of IL-ZR mRNA expression in patients with II cancer Wang Zx, Zhang CY, Chen WZ. Tumor Center: Xingiao Hospital, T Military Medical College. Chongqing. Chin J Clin Oncol 19%;23:i 6.

The human IL-2Ra cDNA probe was prepared to determine IL mRNA expression level in PBMC of 46 lung cancer patients. The suits showed that the IL-2R mRNA expression was closely associa with presence of tumor metastasis. The IL-2R mRNA expressio patients with no metastasis was signiticantly higher than that of 1 trol and metastatic groups, It was related to the histological classii tion of cancer and duration of disease. IL-2R mRNA expression 01 metastatic group was much lower than that of control group. It is gested thatthe patients had inununologic suppression in periods a tive &se of cellular activity IL-2R transcription. Serum TNF lev pat&s was not different in between the two patient group. It was sh that IL-2R mRNA expression level was closely related to the progr of cancer patients.

Detection of human papilloma virus (HPV) and K-ras m tions in hum8n lung carcinomas NoutsouA,KoffaM,ErgazakiM,SiafakasN’M, SpandidosDA.h