• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.310-322
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• 2000

Background : Phospholipase C(PLC) plays an important role in cellular signal transduction and is thought to be critical in cellular growth, differentiation and transformation of certain malignancies. Two second messengers produced from the enzymatic action of PLC are diacylglycerol (DAG) and inositol 1, 4, 5-trisphosphate (IP3). These two second messengers are important in down stream signal activation of protein kinase C and intracellular calcium elevation. In addition, functional domains of the PLC isozymes, such as Src homology 2 (SH2) domain, Src homology 3 (SH3) domain, and pleckstrin homology (PH) domain play crucial roles in protein translocation, lipid membrane modificailon and intracellular memrane trafficking which occur during various mitogenic processes. We have previously reported the presence of PLC-${\gamma}1$, ${\gamma}2$, ${\beta}1$, ${\beta}3$, and ${\delta}1$ isozymes in normal human lung tissue and tyrosine-kinase-independent activation of phospholipase C-${\gamma}$ isozymes by tau protein and AHNAK. We had also found that the expression of AHNAK protein was markedly increased in various mstologic types of lung can∞r tissues as compared to the normallungs. However, the report concerning expression of various PLC isozymes in lung canærs and other lung diseases is lacking. Therefore, in this study we examined the expression of PLC isozymes in the paired surgical specimens taken from lung cancer patients. Methods : Surgically resected lung cancer tissue samples taken from thirty seven patients and their paired normal control lungs from the same patients, The expression of various PLC isozymes were studied. Western blot analysis of the tissue extracts for the PLC isozymes and immunohistochemistry was performed on typical samples for localization of the isozyme. Results : In 16 of 18 squamous cell carcinomas, the expression of PLC-${\gamma}1$ was increased. PLC-${\gamma}1$ was also found to be increased in all of 15 adenocarcinoma patients. In most of the non-small cell lung cancer tissues we had examined, expression of PLC-${\delta}1$ was decreased. However, the expression of PLC-${\delta}1$ was markedly increased in 3 adenocarcinomas and 3 squamous carcinomas. Although the numbers were small, in all 4 cases of small cell lung cancer tissues, the expression of PLC-${\delta}1$ was nearly absent. Conclusion : We found increased expression of PLC-${\gamma}1$ isozyme in lung cancer tissues. Results of this study, taken together with our earlier findings of AHNAK protein-a putative PLD-${\gamma}$, activator-over-expression, and the changes observed in PLC-${\delta}1$ in primary human lung cancers may provide a possible insight into the derranged calcium-inositol signaling pathways leading to the lung malignancies.

• Proceedings of the Ginseng society Conference
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• 1980.09a
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• pp.87-113
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• 1980

This experiment was carried out to evaluate the effects of Korean ginseng extract on carcinogenesis induced by various chemical carcinogens. Red ginseng extract was used for this study and was administered orally to the experimental animals. Carcinogens that were injected in subscapsular region of ICR newborn mice within 24 hours after birth were 9,10-dimethyl-1,2-benzan-thracene (DMBA), urethane, N-2-fluorenylacetamide(AAF), aflatoxin $B_1$ and tobacco smoke condensate. N -methyl-N -nitroso-N'-nitroguani-dine(MNNG) was injected subcutaneously at the back of wistar rats. Experimental animals were autopsied in immediately after being sacrificed. All major organs were examined grossly and weighted. After fixation histopathological preparations were made for microscopical study. Following results were obtained. In DMBA group sacrificed at the 26th week after the treatment with DMBA, the incidence of lung adenoma was $77\%$ and the average number of the tumor was 17. However, in DMBA combined with red ginseng group, the incidence was $78\%$ and the average number of lung adenoma was 14.1. This indicates that ginseng extract had no effect on the incidence of lung adenoma but decreased the average number of lung adenoma by $17\%.$ In DMBA group sacrificed at the 48th week after the injection of DMBA, the lung adenoma incidence was $88\%.$ The average diameter of the largest lung adenoma was 3.5 cm, the incidence of diffuse pulmonary infiltration was $18\%$ and the average lung weight of male experimental mice was $528.2{\pm}469.1\;gm.$ On the other hand, in DMBA combined with red ginseng group sacrificed at the 48th week, the incidence of lung adenoma was $96\%.$ The average diameter of the largest adenoma was 2.7 cm, the incidence of diffuse pulmonary infiltration was $7\%$ and the average lung weight of male mice was $418.0{\pm}520\;gm.$ These observations show that ginseng extract did not have any inhibitory effect on the incidence of lung adenoma but decreased the average diameter of the largest lung adenoma by $23\%,$ the incidence of duffuse pulmonary infiltration by $63\%$ and the average lung weight of male experimental mice by $21\%.$ From these results we have found that the prolonged administration with ginseng extract showed no inhibitory effect on the incidence of adenoma but it had the inhibitory effect on the proliferation of lung adenomas induced by DMBA. In urethane group sacrificed at the 28th week after the injection of urethane, the incidence of lung adenoma was $94\%$ and the average number of lung adenoma was 8.6. In urethane combined with red ginseng group, the. incidence of lung adenoma was $73\%$ and the average number of adenoma was 6.0. These results indicate that there were $22\%$ decrease of the lung adenoma incidence and $31\%$ decrease of the average number of adenoma in urethane combined with red ginseng group. And in urethane group sacrificed at the 50th week, the incidence of lung adenoma was $98\%$ and the incidence of diffuse pulmonary infiltration was $14\%$. In urethane combined with ginseng group the incidence of lung adenoma was $85\%$ and the incidence of diffuse pulmonary infiltration was $12\%$. Therefore the ginseng administration resulted in $15\%$ decrease of the lung adenoma incidence and $14\%$ decrease of the diffuse pulmonary infiltration incidence. From these results we knew that the prolonged administration with ginseng extract inhibited the incidence and also the proliferation of the lung adenoma induced by urethane. Lung adenoma and hepatoma were induced in the experimental mice sacrificed at the 68th week but not in the experimental mice sacrificed at the 28th week after the injection of AAF. In AAF group sacrificed at the 68th week after the injection of AAF the incidence of lung adenoma was $18\%$ and the incidence of hepatoma was $27\%$. And in AAF combined with ginseng group the lung adenoma incidence was $12\%$ and the hepatoma incidence was $37\%$. So the ginseng seemed to decrease the lung adenoma incidence by AAF, but we were unable to conclude the significant inhibitory effect of the ginseng extract on the incidence of lung adenoma by AAF because the above incidence of lung adenoma were similar to that of control group which was $11\%$. And these experimental data revealed that ginseng extract didn't have any inhibitory effect on the incidence of hepatoma induced by AAF. In aflatoxin $B_1$ group sacrificed at the 56th week, the incidence of lung adenoma was $24\%$ and hepatoma was $11\%$. However in aflatoxin $B_1$ combined with ginseng group the incidence of lung adenoma was $17\%$ and hepatoma was $3\%$ These results indicate that there were $29\%$ decrease of the lung adenoma incidence and $75\%$ decrease of the hepatoma incidence in aflatoxin $B_1$ combined with ginseng group. In tobacco smoke condensate experimental group sacrificed at 67th week, no tumors were induced except just a few lung adenoma. The lung adenoma incidence both in tobacco smoke condensate group and in tobacco smoke condensate combined with ginseng group was $8\%$. And this incidence rate was similar to that of control group. These results indicate that the injection of 320 ug tobacco smoke condensate per ICR newborn mouse was unable to induce lung adenoma in our experiments. In MNNG group sacrificed at the 27th week the tumor incidence was $38.5\%$ and in MNNG combined with ginseng extract group was $37\%$. In MNNG group for investigation of the life span of tumor bearing rats the tumor incidence was $93\%$ and the average life span of tumor bearing rats was 318 days. And in MNNG combined with ginseng extract group the tumor incidence was $96\%$ and the average life span was 337 days. Tumor induced by MNNG was almost sarcoma. This indicates that there was no inhibitory effect of ginseng extract on the tumor incidence, but the extract prolonged the average life span of tumor bearing rats by approximately 19 days.