Serum thyrosinase in human lung carcinoma.

Compared to normal humans, lung carcinoma patients show increased tyrosinase activity. 7 serum enzymic fractions or carriers were present in the diseased state. Further, serum tyrosinase inhibitory factors generally were decreased in lung carcinoma patients compared to normal individuals.     

In vitro effects of melanocytolytic agents and other compounds upon dominant human melanoma tyrosinase activity

Summary The activity of dominant human melanoma tyrosinase isozyme was greatly decreased by certain reducing agents. The number and geometry of phenolic groups as well as free-SH group appear important for enzymic inhibition.This investigation was supported by U.S. Public Health Service Research Grant No. CA-12731-02 and CA-15991-01 from National Cancer Institute.     

Utilization ofd-tyrosine by vertebrate skin tyrosinase

Résumé Certaines espèces de vertébrés inférieurs convertissent lad-tyrosine radioactive en mélanine par la tyrosinase de la peau. On pense que l'utilisation normale de lad-tyrosine est importante pour la mélanogenèse intégumentale.

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This investigation was supported by U.S.P.H.S. Grant No. CA-07273-04 GM from the National Cancer Institute and White Laboratories, Inc.     

Integumental tyrosinase activity in amphibians

Résumé L'analyse radiométrique de tyrosinase intégumentale a démontré que les amphibiens sont les vertébrés les plus intéressants dans les études de mélanogenèse.

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This work was supported by U.S.P.H.S. Research grant No. CA-07273-04 GM from the National Cancer Institute and by White Laboratories, Inc.

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Contribution 179, Department of Biology.     

A simple procedure for removal of intra- and extra-tumoral macrophages from primary tumor cultures

Summary Improved growth of tumor cells in primary cell suspensions isolated from solid tumors can be achieved by addition of an antifungal agent, mycostatin, to the culture medium. Mycostatin inhibits the cytotoxicity of macrophages and also quickly detaches phagocytes without any apparent retardation of the growth of tumor cells. This method is particularly useful for obtaining cultures of lung tumor cells or cells from lung metastases of other tumors.This research was supported in part by grants CA-22839 and CA-28482 awarded by the National Cancer Institute, DHEW, USA. This is publication No. 406 from the Department of Basic and Clinical Immunology and Microbiology, Medical University of South Carolina.We thank Charles L. Smith for editorial assistance. Address correspondence to Y. Y., Department of Basic and Clinical Immunology and Microbiology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29403, USA.     

Induction of mouse hepatic ornithine decarboxylase by skin application of 12-0-tetradecanoylphorbol-13-acetate

Summary Topically applied 12-0-tetradecanoylphorbol-13-acetate on mouse skin was able to induce liver ornithine decarboxylase. Maximum induction occurred 10 h after a single application. Whereas no induction was noticeable at doses of 0.17 and 1.7 nmoles, 17 and 177 nmoles of 12-0-tetradecanoylphorbol-13-acetate caused about 30- and 57-fold increases respectively.This work was supported by NCI grants CA-09020, CA-07175 and P01-CA-22484.     

Structure of gap junctions in cultures of normal and neoplastic bladder epithelial cells

Summary Normal rat urinary bladder epithelial cells contain small subunit (PF-1) and large subunit (PF-2) gap junctions, whereas carcinoma cells only contain PF-1 gap junctions. The absence of PF-2 gap junctions, which are composed of larger connexons with slightly larger ionic channels, may contribute to altered metabolic coupling between urinary bladder carcinoma cells.Acknowledgments. The authors wish to thank Ms Denise Wiler and Mr William Leonard for expert technical assistance. This work was supported by funds from the National Cancer Institute, CA-25034, and in part by the Otho SA Sprague Memorial Institute.     

Glia maturation factor influences recovery from injury in neonatal rat brains

Summary Newborn rats were injured with a puncture wound in one cerebral hemisphere. Experimental animals were treated with three i.p. injections of Glia Maturation Factor (GMF) at daily intervals starting from the time of injury, whereas control littermates were treated with equivalent amounts of bovine serum albumin. At 25 days old the size of the cerebral cortex at the plane of injury was measured on representative brain sections. In control rats the injured side was 18% smaller than the normal side whereas in GMF-treated animals the difference was only 1%. The results suggest a possible regulatory role of GMF in promoting tissue recovery from brain damage.Acknowledgments. This work was supported by the following research grants to Dr Lim: Veterans Administration Merit Review Award and Clinical Investigatorship Award, National Science Foundation grant No.BNS-8308341 and National Cancer Institute grant No. CA-31796. We thank Marjorie Strabala for preparing the histological sections and Dr Peter A. Lachenbruch and John Tsuang for statistical analysis.     

饮用咖啡与胰腺癌患病的Meta分析

目的 综合评价饮用咖啡因素与胰腺癌发生的相关性,进一步探讨胰腺癌的危险因素.方法 检索1970.01.01/2010.10.01国内外公开发表的有关人群饮用咖啡和胰腺癌发生的病例对照研究,制定纳入标准,采用Rev Man4.2软件对研究资料进行Meta分析,定量综合评价饮用咖啡与胰腺癌的关系.结果 共有15组病例-对照研究符合入选标准,累积胰腺癌病例共3 335例和正常对照者共15 064例.Meta分析显示,合并OR=1.08(95％ CI:0.88～1.31),(P=0.48),差异无统计学意义；男性组结果显示,OR和95％ CI为1.14(0.95-1.37),差距不具有统计学意义(P=0.15),女性组结果显示OR和95％CI为1.18(0.98-1.43),(P=0.09),由于P＜0.1,故属于边缘性显著差异.结论 女性胰腺癌患者中有饮用咖啡习惯与无饮用咖啡习惯的人相比,饮用咖啡的习惯可能会增加胰腺癌的发病风险.     

Induction of micronuclei in PHA-stimulated human lymphocyte cultures by therapeutic radiation

Summary Micronuclei frequency and percent of chromosome breaks increases significantly in adults whose thymus glands were irradiated in infancy and after irradiation of cancer patients.Acknowledgments. This work was supported by a grant, No. CA-14876, from the National Cancer Institute. Rita Giuliano gave valuable technical assistance.     

Species-specific differences in the mitogenic activity of heparin-binding growth factors in the sera of various mammals

Sera from different mammalian species displayed great differences in mitogenic activity, as measured by stimulation of DNA synthesis in BALB/c 3T3 cells (3T3 cells). Among the sera examined, fetal bovine serum was least active, and increasing activity was detected in calf serum, human serum, rat serum and mouse serum, in that order. Rat and mouse sera exhibited extremely high mitogenic activity with 3T3 cells, but when TIG-1 human fetal lung fibroblasts were used for the DNA assay instead, the activity levels of all of the sera were lower, and the differences between them were smaller. To determine the reasons for these differences, the heparin-binding growth factors in each serum were separated on a heparin affinity column. Five peaks of DNA-stimulating activity were obtained. Three of these were found in all sera examined, with both 3T3 cells and TIG-1 cells. Two other peaks were found only with 3T3 cells; one was peculiar to rat and mouse sera, with extremely high activity in the rat, and the other was specific to fetal serum. The dependence of the activity of these peaks on the cells used for the test was confirmed using normal rat lung fibroblasts and immortalized rat kidney cells. These findings adequately explain the species-specific differences in mitogenic activity of whole sera, and the variation in activity depending on the cells used for assay of DNA synthesis.     

Species-specific differences in the mitogenic activity of heparin-binding growth factors in the sera of various mammals.

Sera from different mammalian species displayed great differences in mitogenic activity, as measured by stimulation of DNA synthesis in BALB/c 3T3 cells (3T3 cells). Among the sera examined, fetal bovine serum was least active, and increasing activity was detected in calf serum, human serum, rat serum and mouse serum, in that order. Rat and mouse sera exhibited extremely high mitogenic activity with 3T3 cells, but when TIG-1 human fetal lung fibroblasts were used for the DNA assay instead, the activity levels of all of the sera were lower, and the differences between them were smaller. To determine the reasons for these differences, the heparin-binding growth factors in each serum were separated on a heparin affinity column. Five peaks of DNA-stimulating activity were obtained. Three of these were found in all sera examined, with both 3T3 cells and TIG-1 cells. Two other peaks were found only with 3T3 cells; one was peculiar to rat and mouse sera, with extremely high activity in the rat, and the other was specific to fetal serum. The dependence of the activity of these peaks on the cells used for the test was confirmed using normal rat lung fibroblasts and immortalized rat kidney cells. These findings adequately explain the species-specific differences in mitogenic activity of whole sera, and the variation in activity depending on the cells used for assay of DNA synthesis.     

Chemical synthesis of a hexadecapeptide segment of ubiquitin that activates adenylate cyclase and induces lymphocytes to differentiate

Summary A hexadecapeptide corresponding to positions 59–74 of ubiquitin was synthesized and purified. The peptide was characterized by its mobility in TLC and electrophoresis, amino acid sequence and composition, and molar rotation. The peptide possessed approximately 40% activity compared with native ubiquitin in each of 3 biological assays in vitro: a) thymocyte induction, b) B cell induction and c) elevation of intracellular cyclic AMP levels in sarcoma 180 cells.Acknowledgments. We thank Dr Geoffrey Tregear for helpful suggestions for the synthesis strategy, Dr Jim Burton for guidance with the methods for establishing peptide purity, and Ronald King, Miriam Miller, Jeanette Dilley and Linda Townley for excellent technical assistance. This work was supported by U.S. Public Health Service Grants CA-08748, CA-16889, CA-08415, CA-17085 and AI-12487, and by NCI Contract CB-53868.     

The in vitro characterization of the inhibition of mouse brain protein kinase-C by retinoids and their receptors

Summary The mechanism of the in vitro inhibition of Ca²⁺-, phosphatidylserine-dependent protein kinase C (PK-C)² by the purifiedholo (ligand-saturated) forms of cellular retinol-binding protein (cRBP) and cellular retinoic acid-binding protein (cRABP) was studied. We report here that i) the PK-C-inhibitory action ofholo-cRBP andholo-cRABP is due to their respective ligands, all-trans-retinol and all-trans-retinoic acid; ii) the reduced phosphorylation of theholo-retinoid-binding proteins and brain cytosolic proteins is not the result of a retinoid-induced soluble phosphatase or protease activity; iii) retinoids reduce PK-C affinity for calcium and phosphatidylserine in vitro; and iv) the structure-function activity of the retinoids and the specific interaction of these effect of retinoids on plasma membrane-associated PK-C activity pays a significant role in defining the early epigenetic aspects of PK-C-dependent tumor promotion and may be a physiological mechanism by which retinoids induce terminal differentiation in cell types that do not express soluble retinoid-binding proteins.We would like to thank Dr L.M. De Luca (NIH, USA) for his contribution of retinylphosphate, Dr H.N. Bhagavan (Hoffmann-La Roche) for his contribution of the arotinoids, and Merrill-Dow Corp. for their contribution of difluoromethylornithine. This work was supported by NIH Grants CA-34968, CA-07175, CA-22484, and CA-09020.     

Transplantation of brain tissue in the brain of adult rats

Summary Brain tissues obtained from rat embryos were transplanted in the forebrain and/or cerebellum of the adult rats. The transplants survived, grew and achieved normal cellular and cytoarchitectural differentiation. They had become anatomically integrated with the host brain. The animals did not show any obviously detectable abnormal behavior or pathology of the brain. The transplants survived as long as the animals did suggesting that they had become a part and parcel of the host brain.Supported by research grants NS-08817 and CA-14650 from N.I.H.     

Velocity sedimentation of tumor cells: A comparison of methods

Summary Tumor cells isolated from a murine fibrosarcoma were grown in primary culture for two days and then separated on a basis of size by velocity sedimentation. Centrifugal elutriation and STAPUT methods were compared for their ability to isolate biophysically unique tumor subpopulations. The isolated cell fractions were assayed for cell number, incorporation of triatiated thymidine and Coulter volume. Both methods were comparable with regard to ability to separate tumor cells on a basis of size. Elutriation had the advantage of speed but required sophisticated equipment. The STAPUT method was less expensive but required somewhat longer times for separation.Supported in part by NIH-NCI grants No. CA-06294 and CA-18628.     

Inhibition of sensitized leukocyte's in vitro reactivity by circulating immune complexes in prostate cancer

Circulating immune complexes in the sera of patients with confirmed histological diagnosis of carcinoma of the prostate, were found to interfere in the sensitized leukocyte's in vitro reactivity to prostate cancer associated antigen as evaluated by tube leukocyte adherence inhibition assay, thereby suggesting an inhibitory role of such serum factors in host's anti tumor cell mediated immune responses.