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with lung cancer TAA. Furthermore, the factor blocked the ability of lymphocytes from lung cancer patients to recognize lung cancer TAA. Both the factor from lung cancer serum and from theoligoclonal T-cells were absorbed on a lung cancer-associated antigen-coupled immuno- sorbent column. On FPLC-gel filtration the desorbed fractions from the immunosorbent column from both sources showed activity in the same molecular weight range, 70-90 kD. Heteroantisera raised against the factor from serum and against the factor from the oligoclonal T-cell supematant bound about the same portion of lymphocytes from lung cancer patients as measured by immunofluorescence, while only a minor fraction of cells from patients with unrelated cancers and from healthy persons were labelled on incubation with the antisera. These results support the hypothesis that an antigen-specific factor found in serum of cancer patients is produced by antigen-stimulated T-cells, possibly of the CD8 phenotype. This putative antigen-specific suppres- sor factor and the tumor antigen-reactive lymphocytes of the patient seem to share similar idiotopes.

myc Family gene abnormality in lung cancers and its relation to xenotransplantability. Gemma A, Nakajima T, Shiraishi M et al P athology Division, Nufionul Cancer Center Research Insriture, Chuo-ku, Tokyo 104. Cancer Rcs 1988;48:6025-8.

In order to study the relationship between tumor transplantability to the nude mouse and abnormality of the myc family genes (c-myc, N- myc, L-myc) in human primary lung cancers, 32 various lung cancers were analyzed for abnormality of the myc family genes by Southern blot hybridization, and were transplanted S.C. into nude mice. Southern blot analysisshowedthatfournon-smaI1cellcarcinomasandthreesmallceIl carcinomas had amplifiedc-myc and L-myc genes,respectively. Allelic deletion of the L-myc gene was observed in seven cancers, of which two also had an additional band of the c-myc gene or amplification of the L- myc gene. No abnormality of the N-myc gene was observed in this series. Of 13 cancers with abnormality of the myc family genes, 1 I, including all tumors with myc gene amplification, were transplantable to nude mice. Of 19 tumors without any abnormalities of the myc family genes, however, only five were transplantable to nude mice (P c 0.005). These results indicate that abnormality of the myc family genes, especially gene amplification, might promote tumorigenic ability in xenotransplantation of lung cancers and this phenomenon might be closely related to the function of the myc gene.

Oocogene expression detected by in situ hybridization in human primary lung cancer. Lee JH, Lee DH, Park SS, Seok SE, Lee JD. Department of Medicine, Hanyang Universify School ofMedicine, Seoul. Chest 1988;94: 1046-9.

By meansof in situ hybridization using biotinylated oncogeneprobes and the immunohistochemical reaction of avidin-biotin complex-alka- line phosphatase with substrate, we investigated expresson of c-myc oncogene in the formalin-fixed,paraffin-embedded tissue sections from seven patients with squamous cell carcinoma (six cases) and small cell carcinoma (one case) of primary lung origin. The expression of c-myc oncogcne was greatly enhanced in ah cases studied, with individual and cell-to-cell variation. In contrast, all of the specimens incubated with deoxyribonuclease after the standard pretreatment with ribonucleaseT1 were negative for the expression of c-myc oncogene. The in situ hybridization permitsestimation of a heterogeneous amplification ofc- myc oncogcne that may bc related to secondary alterations occurring during the progression of the malignant lung tumors.

A23187 and protein kinase C activators stimulate pbosphatidyli- nositol metabolism and prostaglandin synthesis in a human lung cancer cell line. Rapuano BE, Bockman RS. Division ofEndocrinology. Cornell Vniver- sity Medical College, Hospital for Special Surgery, New York, NY tOO.21. Biochem Biophys Res Commun 1988:156:644-52.

Activation of cell phospholipase. release of arachidonic acid and stimulation of prostaglandin synthesis were studied ma newly described human tumor cell line (Lu-65). In the Lu-65 tumor cell line, thecalcium ionophore A23 187 (2 ??M) caused a 100% increase in the release of ‘H- arachidonic acid and a 7-fold increase in the synthesis of prostaglandin E,. I-oleoyl,-2-acetyl-glycerol (100 ??M) increased arachidonate re- lease and prostaglandin E, synthesis by 100%. A23187 and the protein kinase C activators, 1.2.dioctanoyl-glycerol and I-oleoyl,-2-acetyl- glycerol, decreased the specific radioactivity of ‘H-arachidonate in phosphatidylinositol by 37% and 57%. respectively. The effects of A23187 were blocked in Ca*‘-free media or in the presence of the phospholipase A, inhibitor, p-bromophenacyl bromide, while those of I-oleoyl,-Zacetyl- glycerol were not. The data provide evidence in a human tumor cell line for calcium/phospholipase AZ-dependent and independent pathways for arachidonic acid release, both of which preferentially hydrolyze phosphatidylinositol.

Insulin-like growth factor-l can mediate autocrine proliferation of human small lung cancer cell lines in vitro. Nakanishi Y, Mulshine JL, Kasprzyk PG et al. National Cancer Insti- tute-Navy Medical Oncology Branch. Division of Cancer Treatment. Belhesdu. MD 20814. J Clin Invest 1988:82:354-9.

The effect of insulin-like growth factor I (IGF-I) on growth of small cell lung cancer (SCLC) cell lines was studied. Western blot analysis of whole cell lysates of cell lines NCI-H345 and NCI-N4 17 demonstrated the presence of a 16.kD band consistent with an IGF-I precursor molecule. Scatchard plot analysis of cell line NCI-H345 using ‘“I- labeled IGF-I demonstrated two high affinity specific binding sites (K(d) 1.3 and4.0 nM with maxima1 rate (B(max)) 200 and 500 fmol/mg protein, respectively). The exogenous addition of IGF-I. IGF-II. or insulin resulted in marked proliferation of human SCLC cells as evaluated using an in vitro growth assay. These peptides stimulate the growth of SCLC cell lines NCl-H82, NCI-H209, NCI-H345, and NCI- N417. The concentration of IGF-1 producing maximal SCLC cell growth was IO-lOO-fold less than that of insulin or IGF-II, whereas the maximal growth stimulated by the optimal concentration of these peptidcs were similar. An MAb that specifically binds to the IGF-I receptor (but not to the insulin receptor) mediates a dose-dependent inhibition of cell growth in basal media as well as IGF-I, IGF-II, or insulin-supplemented media. The IGF-I receptor thus appears to be the common pathway for the mitogenic activity by IGF-I, IGF-II, and insulin for human SCLC cell lines. The demonstration of an IGF-I precursor molecule, specific IGF-I receptor binding, IGF-I-mediated growth stimulation, and inhibition of basal cell growth by an MAbtothe IGF-I rcccptor suggests that an IGF-I-like molecule can function in vitro as an autocrine growth factor for human SCLC cell lines.

Transferrin synthesis by small cell lung cancer cells acts as an autocrine regulator of cellular proliferation. Vostrejs M, Moran PL, Scligman PA. Division ofHemnfology, Univer- sity of Colorado Health Sciences Center, Denver. CO 80262. J Clin Invest 1988;82:331-9.

Since transfcrrin is required for cellular proliferation, we investigated