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large cell undifferentiated carcinoma (3 of 3 cell lines); adenosquamous carcinoma(lof2celllines);squamouscellcarcinoma(0of2celllines); adenocarcinoma (9 or 10 cell lines); bronchioloalveolar cell carcinoma (2 of 2 cell lines); and small cell carcinoma (1 of 9 cell lines). Using the mean levels of 9_,1 Ill-prostaglandin F,, prostaglandin F&I, prostaglandin D,, prostaglandin E,, thromboxane B, and 6-kem- prostaglandin F,(_) as an index of prostaglandin H (PGH) synthase activity, the disuibution in cell lines representative of the different histological classes of human lung tumors exhibiting PGH synthase activity exceeding mean values _ 2 pmol/106 cells was as follows: large cell undifferentiated carcinoma (3 of 3 cell lines), adenosquamous carcinoma (1 of 2 cell lines), adenocarcinoma (8 of 10 cell lines),
bronchioloalveolar cell carcinoma (2 of 2 cell lines) and small cell carcinoma (0 of 9 cell lines). Three different prostanoid species accu- mulated to mean levels _ 2 pmol/l@ cells. Prostaglandin E, levels exceeded 2 pmol/ltY cells in 14 of the 16 cell lines in which this prostanoid accumulated to detectable levels. Cumulative levels Of prostaglandin F2(_) exceeded 2 pmoI/l06 cells in 9 of the 15 cell lines in which prostaglandin F,C) reached detectable levels. Detectable levels of thromboxane B, were observed in five cell lines with throm- boxane B, accumulation exceeding 2 pmol/lO“ cells in two of the five celllines.9_,1 lB-prostaglandinF,and6-keto-prostaglandinF,(_)accu- mulated todetectablelevels in theculturemedium ofonecell line, while prostaglandin D, accumulation to detectable levels was observed in two cell lines. Stimulation of cultured human lung tumor cells exhibiting PGH synthase activity _ 2 pmol/106 cells in the presence of IO” M exogenous arachidonic acid resulted in a 2- to 4.fold increase in the accumulation of individual prostanoids, while the inclusion of a 10.’ M exogenous concentration of arachidonic acid failed to stimulate detect- able prostanoid production in human lung tumor cells in which PGH synthase activity was not previously expressed. The predominance of PGH synthase activity in cell lines derived fmm human non-small cell carcinomas of the lung suggest that prostanoid biosynthesis may be characteristic of tumor cells comprising certain histological subclasses of human non-small cell carcinomas of the lung, particularly adenocar- cinema, bronchioloalveolar cell carcinoma, large cell undifferentiated carcinoma, and possibly adenosquamous carcinoma.
Classification of lung cancer patients and controls by chromalogra- phy of modified nucleosides in serum. McEntire JE, Kuo KC, Smith ME et al. IMBIC Corporation, Columbia, MO 65201. Cancer Res. 1989;49: 1057-62.
A wide spectrum of modified nucleosides has been quantified by high-performance liquid chromatography in serum of 49 male lung cancerpatients, 35 patients with other cancers, and 48 patients hospita- ized for nonneoplastic diseases. Data for29 modified nucleoside peaks were normalized to an internal standard and analyzed by discriminant analysis and stepwise discriminant analysis. A model based on peaks selected by a stepwise discriminantprocedure correctly classified 79% of the cancer and 75% of the noncancer subjects. It also demonstrated 84% sensitivity and 79% specificity when comparing lung cancer to noncancer subjects, and 80% sensitivity and 55% specificity in compar- ing lung cancer to other cancers. The nucleoside peaks having the greatest influence on the models varied dependent on the subgroups compared, confirming the importance of quantifying a wide array of nucleosides. These data support and expand previous studies which reported the utility of measuring modified nucleoside levels in serum and show that precise measurement of an army of 29 modified nucleo- sldcs in serum by high-performance ltquid chromatography with UV scanning withsubsequentdatamodelingmayprovideaclinically useful approach topatientclassification indiagnosisandsubsequent therapeu- uc monitoring.
Killing lung cancer cells at cell-cycle phase by a new indium-lll- bleomycin complex. flou D-Y, Ordonez fV, Cross RI, Ross DD. Maruyama i’. Departmem ofRadiation Medicine, UniversifyofKenlucky MedicalCenter, Lexing- ion. KY40536 J Surg Oncol 1989;40:73-8.
The efficacy of killing small cell lung cancer (SCLC) cells at the G,,
S and G,-M phase of the cell-cycle by a new “LIn-bleomycin complex (“‘In-BLMC) was investigated. SCLC cells (N417, H526, H209) were synchronized by double thymidine block and assessed by DNA content with flow cytometry, and the period for the maximal accumulation of cellsinS,G,,orG,-Mphasewasdete~ined.Dellsindifferentcellcycle phases wereexposed toO.91. NaCI, BLM, or”‘ln-BLMC for 1 hourand observed for colony formation. The survival of H526 cells treated with “‘ln-BLMC was 71% (for enriched S phase), 46% (G,), and 31% (G,- M). For N417 cells, it was 25% (S), 20% (G,), and 8% (G,-M) forILLIn- BLMCand lS%(S),33%(G,),and lO%(G,-M)forBLM.Theseresults indicated that SCLC cells in G,-M were most sensitive and those in S phase were least sensitive to”‘In-BLMC; cells m G, phase were the least sensitive to BLM.
Immunohxalisation and imaging of small cell cancer xenografts by the IgGZa monoclonal antibody SWAll. Smith A, WaibelR,WesteraG, Martin A, Zimmerman AT, StahelRA. Division of Oncology, Department of Medicine, Universiq Hospital, CH-8091 Zurich. Br J Cancer 1989:59:174-g.
We describe here a mtuine monoclonal antibody of the IgG2a isotype which was generated against the SW2 human small cell carcinoma cell line. The antibody, SWAll, was shown to bind to a partially defined antigen preferentially expressed on cell lines of small cell carcinoma origin. In vitro binding studies revealed 6.1x l@ antigeneic sites on the SW2 cell line and the K(a) to be 1.2~10~ M I, Following injection into micebearing l-2cm3SW2xenogr&,SWA11 showedstrongselective accumulation in the small cell heterotransplants with a tumour to blood ratio of 7.5:1 at day 4. Other tumour to organ ratios were simdarly high at 19:1, 22:1 and 12:l for liver, kidney and spleen respectively. The absoluteamountofSWA1 I which localised was 10.5% oftotal injected material per gram tumour at day 2 and this level did not markedly decrease by day 4. The high ability of SWAll to local& to SCC xenografts was confirmed by external gamma scintigmphy. The poten- tialapplicationofSWAI1 asamodel system form v~voradimmmuoth- erapy is discussed.
The genetic basis of susceptibility to lung tumors in mice.
Malkinson AM. School ofPharmacy. Universiiy of Colorado. Boulder. CO 80309. Toxicology 1989;54:‘241-71.
Thisis theftrstinaseriesofreview articlesdescribmg thecurrentstate of research on mouse lung tumorigenesis. The system is valuable as a biological model for studying stages of tumor development and the mteraction ofgenetic and environmental factors which dispose towards neoplasia. Additionally, these tumors are analogous to hronchiolo- alveolar cancer in man. Three pulmonary adenoma susceptibility (Pas) genes regulate susceptibility; 1 of these is the proto-oncogene, K-ras2. Candidates for the other 2 genes include the H-2 histocompatibility locus and genes which regulate the basal proliferative rate of the cells from which these tumors arise. Tumor development is favored by a depressed immune system, immature age, and decreased levels of circulating corticostemne.
Increased levelsof vaccenic acid in bronchogenic carcinoma tissue. Lawson N, Husband D, McGuigan J, Waston DCT. Colhns FJ, Pandov HI. Deparlment of Clinical Chemiswy, East Birmingham Ifoospiial. Birmingham B9 XT. Ann Chn B&hem 1989;26:125-31.
Employing capillary gas liquid chromatography the levels of palmitic, palmitoleic, stearic, oleic, cis-vaccenic, linoleic, arachidontc and docosahexaenoic acids were measured in lung ttssue and lung tumours from 28 patients undergoing surgery for bronchogenic carci- noma. There were significant increases in the majority of fatty acids m tumotu tissuecompared to normal tissue when theresult wereexpressed in absolute units. However, when the relative changes in fatty acid concentration were studied, the most consistent findings were a signifi- cant rise m vaccenic acid and a fall in palmitic acid in tumour tissue compared to normal tissue. This change in the vaccenic: palmitic acid
ralio may reflect specific changes in fatty acid metabohsm in broncho- genie carcinoma tissue involving a *gD-9 desaturase.