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pressive factor was isolated by ion exchange chromatography using a gradient of 0.04 to 0.08 M NaCl solution, Gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the factor to have molecular weights of 98 kD and 102 kD, respectively. These results suggest that SCLC cells produce a potent immunosuppressive factor which may account for the immunedeficiency in SCLC patients.

Induction of cytokine messenger RNA and secretion in alveolar macrophages and blood monocytes from patients with long cancer receiving granutocyte-macrophage colony-stimulating factor ther- apy Thomassen MJ. Ahmad M, Bama BP, Antal J, Wicdemann HP. Meeker et al. Department ofPulmonary Disease, ClevelandClinic Foundation, 9500 EuclidAvenue, Cleveland, OH4419S-5038. Cancer Res 1991;51:857- 62.

Human granulocyte-macrophage colony-stimulating factor (GM- CSF) promotes the proliferation and differentiation of hematopoietic progenitor cells. Although preliminary data are available from clinical trials, the effect of GM-CSF on gene expression of immunocompetent cells in treated patients has not been studied. We previously demon- strated that in vitro treatment with GM-CSF also enhances maturation- related anti-tumor activities in mononuclear phagccytes. The purpose of the present study was to examine the effects of in viva recombinant GM-CSF therapy on alveolar macrophages and blood monocytes, to determine if these cells demonstrated differential expression of cytok- ine genes, cytokine production, and tumoricidal activity. Alveolar macrophages and blood monocytes were isolated from 13 patienta receiving a range of GM-CSF doses (60-250 pg/m%iay) by continuous infusion over a 2-week period. Both monocytes and macrophages were isolated prior to therapy and at day 10 of the infusion, Monocytes, in addition, were isolatedon day 3 of infusion. Results indicated that GM- CSF therapy enhanced expression of tumor necrosis factor, interleukin 1, and interleukin 6 mRNA in both monocytes and alveolar macroph- ages. Differential responses, however, were observed in cytokine secre- tion; monocytes demonstrated enhanced secretion of all three cytokines by day 3 of treatment, but alveolar macrophages showed only enhanced interleukin 6 secretion at&y IO. Monocyte tumoricidal activity after in vitro lipopolysaccharide stimulation was also significantly elevated by day 3 of treatment. but at day 10 activity was not statistically different from pretreatment values in either monccytes or alveolar macrophages. These data indicate that GM-CSF exerts striking time-dependent modulatory effects on gene expression and functional activities of monocytes and alveolar macrophages in viva, although the responses of the two cell types differ with respect to cytokine secretion.

Retention of activity by selected anthracyclines in a multidrug resistant human brge cell lung carcinoma line without P-glycopro- tein hyperexpression Coley HM, Workman P, Twentyman PR. MRC Clinical Oncology. MRC Centre, Hills Road, Cambridge CB2 ZQH. Br J Cancer 1991:63:351- 7.

A subline (COR-L23/R) of the human large cell lung cancer line COR-L23. derived by in viva exposure to doxontbicin, exhibits an unusual multidrug resistant (MDR) phenotype. This subline shows cross-resistance to daunorubicin, vincristine. colchicine and etoposide but does not express P-glycoprotein. Interestingly, COR-Ll2/R shows little or no resistance to a range of structurally-modified analogues of doxorubicin comprising 9-aIkyl and/or sugar modified anthracyclines. We have previously identified these same compounds as effective agents against P-glycoprotein-positive MDR cell lines. In contrast to typical MDRcelI lines, COR-LI2/R shows only minimal chemosensi- tisation by verapamil and no collateral sensitivity to verapamil. Com- pared to the parental cell line, COR-LlUR displays reduced accumula- tion of doxorubicin and daunorubicin. Accumulation defects were apparent only after 0.5- 1 h of incubation of cells with these agents. The rate of daunorubicin effhtx was shown to be enhanced by COR-Ll2IR and this efflux was demonstrated to be energy-dependent. The use of anthracyclines which retain activity in MDR cells thus appears to be a valid approach for the circumvention of MDR, not only in cells which

express P-glycoprotein, but also where defective drug accumulation is due to other mechanisms possibly involving an alternative multidrug transporter.

Chromosome alterations in 21 non-small cell lung carcinomas Miura I, Siegfried JM, Resau J, Keller SM, Zhou J-Y, Testa JR. Fox Chase Cancer Center, 7701 B&v&e Ave., Philadelphia, PA 19111. Genes Chromosomes Cancer 1990:2:328-38.

Cytogenetic analysis was performed on 16 primary tumors, 2 effu- sions, and 3 cell lines from 21 patients with non-small cell lung cancer (NSCLC). In 20 patients specimens were obtained prior to initiating cytotoxictherapy.Ertensiveclonalchromosomealterationswerefound in all cases. The most frequent numerical changes werepolysomy 7 and polysomy 20 (each seen in 12 specimens). In addition, tumor cells from another six cases exhibited partial trisomy 7, with the shortest region of overlap(SRO)at7pll-pl3.Reat~angementsofchmmosomes I, 3,6,8, 11, 15, 17, and 19 were each observed in nine or more tumors. Breakpoints were clustered at several chromosomal sites, including Ip13,3pl3,15pll-q1l,l7pll,andl9ql3.Recurrentlossrnvolvinglp, 3p,6q, 1 Ip, 15p, 17p,and 19q wereeach seen inat IeasteightcasesThe SRO of 3p losses was at band 3~21. Double minute chromosomes were found in three tumors. Overall, our findings indicate that even though karyotypes in newly diagnosed NSCLC are very complex, recurrent cytogenetic changes can be identified. The high incidence of loss of 17p (14 of21 specimens) appears to be compatible with reports implicating the TP53 gene (at band 17~13) as a frequent site for genetic alteration in lung cancer. Moreover, the recurrence of loss of 3p (12 cases) and I 1 p (10 casea) is also consistent with recent molecular evidence. The existence of other “hot spots” for cytogenetic change, particularly those involving specific regions on chromosomes 7, 15, and 19, war- rants further molecular investigation of these sites in NSCLC.

[Des-Met”]bombesin analogues function as small cell lung cancer bombesin receptor antagonists Staley J, Coy D, Taylor JE, Kim S, Moody TW. GWU Biochemistry Department, 2300 Eye St. N.W., Washington, DC 20037. Peptides 1991:12:145-9.

A series ofbombesin (BN) analogues lacking the C-terminal methion- ine at the 14 position were evaluated as BN receptor antagonists. ID- Phe”]BN(6-13)amide inhibited specific ‘=I-GRP binding to lung cancer cell line NCI-H720 with an IC,, value of 12 nM. In contrast, [D- Phe’]BN(6-13)propylamide. butylamide and methylester were more potent with IC,, values of 3,5 and 5 nM whereas [D-Phe6,Sta”]BN(6- 13)amide was less potent with an IC,, value of 180 nM. [D-Phe6]BN(6- 13)propylamide antagonized the ability of BN to elevate cytosolic Ca”, whereas [D-Phe6]BN(6-13)butyIamide was a partial agonist. In a small cell lung cancer (SCLC) growth assay, [D-Phe6]BN(6-13)propylamide inhibited colony formation. In summary, BN analogues which lack a C- terminal methionine may function as useful SCLC BN receptor antago- nists.

Nearoteosin may function as a regulatory peptide in small cell lung cancer Davis TP, Crowell S, McInturff B, Louis R, Gillespie T. Department of Pharmacology, University ofArizona College ofMedicine. Tucson. AZ 85724. Peptides 1991;12:17-23.

Neurotensin (NT) has been postulated to act as a modulatory agent in the central nervous system. Besides its presence in mammalian brain, NT is produced by small cell carcinoma of the lung (SCLC) and cell lines derived from these tumors. Receptors have also been character- ized in some SCLC cell lines leading to the suggestion that NT could regulate the growth of SCLC in an autocrine fashion similar to bomb- esin/GRP. Previously, we had reported that a 10 nM dose of NT and NT@-13). but not NT(l-8). elevated cytosolic Ca2*, indicating that SCLC NT receptors may use Ca2* as a second messenger. Using intact SCLC cells we report that time-course incubations with NT lead to the formation of the amino-terminal fragment NT(l-8) and small amounts of the C-terminal fragment NT(9- 13). These fragments are formed by

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metalloendopeptidase 3.4.24.15 cleaving enzyme at the Arti-Arg9 bond of NT. Significant levels of soluble 3.4.24.15 (IO-17 nmoles/mg Pr/min) are present in SCLC cell lines. Using the in vitro clonogenic assay we tested the effect of 0.5,5.0 and 10.0 nM doses of NT, NT(l- 8) and NT(8-13) on SCLC clonal growth. NT and the C-terminal fragment NT(8-13) stimulated colony formation whereas the N-termi- nal fragment did not In summary, NT may function as a regulatory peptide in SCLC through the formation of peptide fragments.

NMR spectroscopy analysis of phosphorus metabolites and teffect of adriamycin on these metabolite- levels in an adriamycin-sensitive and -resistant human small cell lung carcinoma cell line De Jong S, Mulder NH, De Vries EGE, Robillard GT. Deparfmenr of Internal Medicine. Universiry Hospiral, Oostersingel 59, 9713 EZ Groningen. Br J Cancer 1991;63:205-12.

“P nuclear magnetic resonance (NMR) spectra of cells and of cell extracts revealed high levels of phosptmrylcholine (FC) and phosphocreat- ine (PCr) in an adriamycin-resistant human small cell lung carcinoma cell line (GLC,/ADR) and the adriamycin-sensitive parental cell line (GLC& PCr levels in extracts of GLC,/ADR were increased compared to extracts of GLC,. We estimated that 11% of the total intracellular ATP is not bound to Mgz* in both cell lines. This value corresponded to an intracellular free Mgz+ of 0.30 mM. The effects of different adriamy- tin concentrations, 0.05.1 and 30 pM for GLC, and 1.30 and 200 pM for GLC,/ADR, on the phosphorus metabolite levels in continuously perfused cells were monitored. Significant differences between GLC, and GLCJADR included: (a) a strong increase in the BATP level in the presence of 30 pM adriimycin in GLC, only, followed by a fast decrease after 5 h of perfusion. (b) a less dramatic increase in the PC level in GLC,/ADR and an unchanged ATP level in the presence of increasing adriamycin concentrations. (c) an increased GPC level in GLCjADR in the presence of adriamycin. The changes in PC and GPC levels in the presence of adriamycin suggested that the phospholipid turnover was increased in GLC/ADR and could be stimulated in the presence of adriamycin. In both cell lines, PCr levels decreased faster than the ATP levels after adriamycin treatment. Thus, biochemical markers for adriamycin resistance can be detected with NMR spectros- copy. However, more studies are necessary to obtain parameters to distinguish drug-sensitive from drug-resistant tnmours in patients by NMR spectroscopy.

Pathology

The value of anticarcinoembryonic antigen, human milk factor globulin, and antikeratin antibodies in differentiating mesotheli- oma from lung carcinoma Joglekar VM, Oliver D, Harris M. Deparment ofPathology, Furness General Hospiral, Dalton &we. Barrow-in-Furness, Cumbria LA14 4LF. Br J Ind Med 1991;48:34-7.

Monoclonal anticarcinoembryonic antigen (antiCEA), human milk factor globulin (HMFG2), and antikeratin antibodies were assessed for their value in the differential diagnosis of pleural mesothelioma (53 cases) and carcinoma of the lung (60 cases) in material from necropsies. In 40 of the cases pleural biopsies were also studied in the same manner. AntiCEA was found to be the best discriminating antibody for most types of mesothelioma; HMFG2 was slightly less valuable but a useful additional tool. Antikeratin was the least useful. For both antiCEA and HMFG2 antibodies, however, the proportion of carcinomas staining was smaller than in previous studies and this, combined with the positive staining of some mesotheliomas, reduces the value of the reactions in the individual case. Medical panels adjudicating compen- sation claims should not use these reactions as the sole criteria in deciding the origin of the mmours in these cases.

Clinical assessment

Digital gangrene in small cell lung cancer: Response to aspirin treatment Arrowsmith JE, Woodbead MA, Bevan DH, Nanson EM, Cummin ARCDepartment of Thoracic Medicine, St George’s Hospital, London SW1 7 OQT. Thorax 1991:46:63-4.

A patient who had a small cell lung cancer complicated by symmet- rical peripheral gangrene, secondary to spontaneous platelet aggrega- tion, improved dramatically after starting aspirin treatment

Lung cancer in patients younger than 40 years of age Jubelirer SJ. Wilson RA. Charleston Area Medical Center, 3200 Mac- Corkle Avenue, SE, Charlesron, wV25304. Cancer 1991;67:1436-8.

The records of 52 patients younger than 40 years of age who had bronchogenic carcinoma diagnosed between 1965 and 1985 were reviewed. The preponderance of adenocarcinoma (54%), the lower male-female ratio in this age group compared with patients age 40 or older @I), the importance of cigarette smoking as a causative factor (80% of patients), the long mean duration of symptoms (5 months), and the high incidence of advanced stage at diagnosis (77% Stages III and IV) in these patients are findings similar to those reported in other published series. There was no significant difference in resectability (23% versus 19%), median survival length (5.3 months versus 6.9 months), median survival length of patients who had surgical resection (10.5 months versus 10.8 months), and 5-year survival rate (11.5% versus6.3%) in thesepatientscompared with arandomly selected group of 260 patients with lung cancer who were age 40 or older.

Intravascular bronchoalveolar tumor Prats MS, Caliz C. Sancho FJ. Comudella R. Department off’neumol- ogy. Hospital de la Sla. Creu, Barcelona. Respiration 1990; 57~395-7.

We report the case of a young woman presenting productive cough and artbralgia in the left ankle. Chest radiography revealed multiple bilateral pulmonary nodules and abdominal echography and computer- ized axial tomography demonstrated various hepatic nodules. Defini- tive diagnosis of an intravascular bronchoalveolar tumor was reached by an open pulmonary biopsy. Liver involvement was confirmed by laparoscopy and biopsy.

Sputum occult blood screening for lung cancer: Stage II screening of 14,431 subjects Qin D-X, Li J-Y, Sun L-Q, Gu M, Wang G-S, Cong J-W, Wang J-Z. Depanmenl of Cancer Prevenrion and Detecrion, Cancer Insrirute, Chinese Academy of Medical Sciences, Beijing 100021. Cancer 1991;67:1960-3.

Sputum occult blood screening (SOBS) for lung cancer was per- formed in outpatients with suspected lung cancer. A total of 1011 patients were seen. Among them,604 patients were found to benegative for SOBS, and 407 were found to be positive. The false-negative rate was 3.97% (24 of 604), and the opposite positive rate was 19.65% (80 of 407). A total of 14.43 1 normal subjects over 40 years of age were screened by SOBS. In the series, 1942 specimens were found to be positive. Among the 1942 patients. 31 were found to have definite cancer cells.

Bronchualveolar carcinoma: Factors affecting survival Daly RC, Trastek VF, Pairolem PC, Murtaugh PA, Huang M-S, Allen MS et al. Mayo Clinic, 200 First St, SW, Rochester, MN 55905. Ann Thorac Surg 1991;51:368-77.

One hundred thirty-four consecutive patients (65 men and 69 women)