ABSTRACT
The malignant pleural mesothelioma is kind of tumor that has close contact with theasbestos to oncolytic,and its attack is very strong.Because the reasons of it iS not obviously and always be found in the middle of late period,the present treatment plan dosnt have a satisfied effect.However oncolytic herpes simplex viruses and obliging platinum induction to oncolyti herpes simplex viruses that generate the GADD34 protein may have the relative specificity to themesothelioma cancer cell,therefore is a prospect ive treatment plan.
ABSTRACT
<p><b>BACKGROUND</b>To investigate the influence of tumor metastasis suppressor gene nm23-H1 on the activity of glycogen synthase kinase 3β (GSK-3β) in human high-metastasis large cell lung cancer cell line L9981.</p><p><b>METHODS</b>The levels of GSK-3β expression in cytoplasm and nucleus were determined with anti- GSK-3β antibody in human high-metastasis large cell lung cancer cell line L9981 (cell line with nm23-H1 gene deletion), L9981-nm23-H1 (cell line with nm23-H1 transfected) and L9981-pLXSN (cell line with vector transfected) by Western blot method. The activity of GSK-3β among those three cell lines was detected by immunoprecipitation and analysed by a radioactive isotope scintillation counter before and after treating with 20 mmol/L LiCl.</p><p><b>RESULTS</b>(1) The expression indensity of GSK-3β of cytoplasm and nucleus was (6 341±541) and (4 356±490) IOD in L9981-nm23-H1, (3 613±383) and (705±75) IOD in L9981-pLXSN, and (3 736±298) and (675±57) IOD in L9981, respectively. A high significance in GSK-3β expressive indensity of both cytoplasm and nucleus existed among L9981-nm23-H1, L9981-pLXSN and L9981 (P < 0.01); Multiple comparison: A highly significant difference was observed when L9981-nm23-H1 was compared with L9981-pLXSN or L9981 (P < 0.01), but no significant difference was observed between L9981-pLXSN and L9981 (P > 0.05). (2) The GSK-3β activity of cytoplasm and nucleus was (28 955±2 509) and (9 247±924) CPM in L9981-nm23-H1, (11 241±1 495) and (1 492±176) CPM in L9981-pLXSN, and (12 505±1 469) and (1 763±125) CPM in L9981, respectively. A highly significant difference in GSK-3β activity of both cytoplasm and nucleus existed among L9981-nm23-H1, L9981-pLXSN and L9981 (P < 0.01); Multiple comparison: the GSK-3β activity in L9981-nm23-H1 was significantly higher than that in L9981-pLXSN and L9981 (P < 0.01), but no significant difference was observed between the L9981-pLXSN and L9981 (P > 0.05). (3) After treatment with 20 mmol/L LiCl, the expressive indensity of GSK-3β of cytoplasm and nucleus was (4 718±549) and (3 823±350) IOD in L9981-nm23-H1, (2 030±155) and (217±15) IOD in L9981-pLXSN, and (2 164±151) and (224±19) IOD in L9981, respectively. No significant difference in GSK-3β expressive indensity existed between before and after treatment with LiCl in L9981-nm23-H1 (P > 0.05). However, the GSK-3β expressive indensity in cytoplasm and nucleus before treatment was remarkably higher than those after treatment in both L9981-pLXSN and L9981 (P < 0.05). (4) After treatment with 20 mmol/L LiCl, the GSK-3β activity in cytoplasm and nucleus was (11 099±1 112) and (3 748±215) CPM in L9981-nm23-H1, (4 447±430) and (1067±159) CPM in L9981, and (4 435±427) and (909±156) CPM in L9981-pLXSN, respectively. The GSK-3β activity both in cytoplasm and nucleus after treatment with LiCl was remarkably lower than that before treatment in L9981-nm23-H1, L9981-pLXSN and L9981 (P < 0.01 or P < 0.05).</p><p><b>CONCLUSIONS</b>(1) Transfection of nm23-H1 gene can significantly up-regulate the expression level and activity of GSK-3β in human high-metastasis large cell lung cancer cell line L9981; (2) LiCl can remarkably suppress the upregulation effects of nm23-H1 gene on GSK-3β activity in L9981 cell line; (3) The effects of nm23-H1 gene on suppressing the signal transduction of Wnt pathway might be carried out through upregulating GSK-3β expression and activity in human high-metastasis large cell lung cancer cell line L9981.</p>
ABSTRACT
<p><b>BACKGROUND</b>To explore the influences of nm23-H1 gene transfection and protein kinase C (PKC) inhibitor Calphostin C on PKC signal transduction pathway in human high-metastasis large cell lung cancer cell line L9981, and to evaluate the effects of nm23-H1 gene on translocation and activation in subcellular region.</p><p><b>METHODS</b>The translocation of PKC in subcellular region was observed in L9981 before and after nm23-H1 gene transfection and Calphostin C treatment by Laser scanning confocal microscope (LSCM) method.</p><p><b>RESULTS</b>PKC-α and PKC-βII were found to locate in different subcellular site in L9981 before and after nm23-H1 gene transfection. PKC-α and PKC-βII mainly located in nucleus and perinucleus in L9981 and L9981-pLXSN cell lines, which were in active status. PKC-α and PKC-βII mainly located in soluble cytosolic fraction in L9981-nm23-H1 cell line and were inactive status. PKC-α and PKC-βII mainly located in cytosolic fraction and were in inactive status in all the three cell lines after treatment with Calphostin C.</p><p><b>CONCLUSIONS</b>The results suggest that nm23-H1 gene might make PKC to translocate from nucleus and perinucleus to soluble cytosolic fraction in L9981 cell line. PKC inhibitor, Calphostin C, can also make PKC to translocate from nucleus and perinucleus to soluble cytosolic fraction in L9981, L9981-pLXSN cell lines. Both transfection of nm23-H1 gene and treatment with Calphostin C can suppress the PKC signal transduction in L9981 cell line.</p>
ABSTRACT
<p><b>BACKGROUND</b>To explore the effects of nm23-H1 gene transfection and forskolin on PKA activity in human high-metastasis large cell lung cancer cell line L9981.</p><p><b>METHODS</b>Three cell lines, primary human large cell lung cancer cell line (L9981), vector transfection cell line (L9981-pLXSN) and nm23-H1 gene transfection cell line (L9981-nm23-H1-pLXSN), were treated with PKA activator forskolin. The PKA activity at different time points after treatment with forskolin was detected in the three lung cancer cell lines by radioimmunological method with SignaTECT cAMP-dependent PKA assay system.</p><p><b>RESULTS</b>(1) Before forskolin treatment, the activity of PKA of L9981-nm23-H1-pLXSN was remarkably higher than those of L9981 and L9981-pLXSN (P < 0.01), but no significant difference in the PKA activity was observed between L9981 and L9981-pLXSN (P > 0.05). (2)The PKA activity was remarkably increased in all the three lung cancer cell lines after treatment with different concentration of forskolin (P < 0.01), and up to the highest level at the concentration of 100 μmol/L. It showed a dose-dependent relationship between the PKA activity and forskolin concentration; (3) The PKA activity in all the three cell lines was elevated to the highest level at 30 minutes after treatment with forskolin of 100 μmol/L, and it showed a time-dependent relationship between the PKA activity and action time of forskolin.</p><p><b>CONCLUSIONS</b>(1)Transfection of nm23-H1 gene can up-regulate the PKA activity of human high-metastasis large cell lung cancer cell line L9981, and its function as a tumor metastasis suppressor gene may be related to its effects on regulation of PKA signal transduction pathways; (2)Forskolin can remarkably up-regulate the PKA activity of L9981 cell line, and the elevation of PKA activity has a time-dependent and dose-dependent relation to forskolin.</p>
ABSTRACT
<p><b>BACKGROUND</b>To explore the possibility of targeting blockage of Wnt signal transduction pathway of nm23-H1 gene transfection in human high-metastatic large cell lung cancer cell line L9981, and to provide evidence to elucidate the signal conductive mechanism of nm23-H1 mediated tumor metastasis suppression.</p><p><b>METHODS</b>The expression of GSK-3β and β-catenin of Wnt signal pathway was detected in cytoplasm and nucleus in L9981 cell line with nm23-H1 deletion, L9981-pLXSN cell line transfected with vector and L9981-nm23-H1 cell line transfected with nm23-H1 gene by Western blot.</p><p><b>RESULTS</b>(1)GSK-3β expression in L9981-nm23-H1 cytoplasm (6 341±541) was significantly higher than those in L9981 (3 736±298) and L9981-pLXSN (3 613±383) cell lines ( P < 0.001); (2)GSK-3β expression in L9981-nm23-H1 nucleus (4 356±490) was significantly higher than those in L9981 (657±57) and L9981-pLXSN (705±75) cell lines ( P < 0.001); (3)β-catenin expression in L9981-nm23-H1 cytoplasm (3 649±118) was significantly higher than those in L9981 (1 401±31) and L9981-pLXSN (1 350±55) cell lines ( P < 0.001); (4)No statistical difference of the β-catenin expression in nucleus was observed among L9981-nm23-H1 (2 945±68), L9981 (2 604±23) and L9981-pLXSN (2 652±53)( P > 0.05); (5)No significant difference of GSK-3β or β-catenin expression in cytoplasm and nucleus was observed between L9981 and L9981-pLXSN ( P > 0.05).</p><p><b>CONCLUSIONS</b>(1)nm23-H1 gene can remarkably upregulate the expression of GSK-3β in cytoplasm and nucleus, and β-catenin expression in cytoplasm in L9981-nm23-H1 cell, but can not induce the nucleus accumulation of β-catenin. (2)Regulation of GSK-3β and β-catenin expression, and targeting blockage of Wnt signaling pathway may be one of molecular mechanisms that nm23-H1 contributes to play a vital role in the "Lung Cancer Metastasis Suppressive Cascade".</p>
ABSTRACT
<p><b>BACKGROUND</b>To investigate the role of curative and palliative surgical treatment of lung cancer with video-assisted thoracoscopic surgery (VATS).</p><p><b>METHODS</b>Forty-three patients with lung cancer were prescribed operations with VATS, which included 5 cases of stage IA, 14 cases of IB, 1 case of IIA, 4 cases of IIB, 7 cases of IIIA, 6 cases of T4-IIIB and 6 cases of IV. The 7 patients of stage IIIA were previously staged as N0 before operation, but reevaluated as N2-IIIA after operation. There were 3 cases of malignant pleural effusion and 3 cases of pleural implantation in stage IIIB cases. There were 2 cases of cardiac tamponade, 1 case of solitary brain metastasis, and 3 cases of ipsilateral or contralateral solitary lung metastasis in cases of stage IV. The main methods of operation performed included lobectomy in 36 cases, wedge resection in 5 cases, and pericardial opening in 2 cases. Systemly mediastinal lymph node dissections were performed in 36 cases. Concurrent contralateral pulmonary wedge resections were performed in 2 cases of contralateral solitary lung metastasis. Malignant pleural effusions were prescribed resection of implantation nodules, electrocautery and pleurodesis.</p><p><b>RESULTS</b>There was no perioperative death or bronchial leak. Five cases suffered lung infection, and 2 cases occurred with incision infection. Malignant pleural effusion in the 3 cases was controlled satisfactorily. Two cases of pericardial opening died in 4 months and 8 months after operation respectively. The other patients were alive till present. Postoperative hospital stay was 5-15 days with average of 7.4 days, except of two cases of pericardial opening.</p><p><b>CONCLUSIONS</b>VATS is an alternative way for complete resection of early stage lung cancer. It is technically feasible to dissect mediastinal lymph node for accidental N2 lung cancer. VATS has significant advantage in concurrent bilateral pulmonary resection. The palliative operation of malignant pleural effusion and cardiac tamponade by VATS can markedly improve the quality of life of patients.</p>
ABSTRACT
<p><b>BACKGROUND</b>To explore the effects of transfection of nm23-H1 gene on expression of β-catenin and phospho-β-catenin in human high-metastatic large cell lung cancer line L9981, and to provide evidence to elucidate the molecular mechanism of nm23-H1 mediated tumor metastatic suppression.</p><p><b>METHODS</b>To determine whether nm23-H1 contributes to cytoplasm and nuclear β-catenin and phospho-β-catenin expression, the expression level of β-catenin and phospho-β-catenin in cytoplasm and nucleus was detected in human high-metastatic large cell lung carcinoma cell lines including primary cell line L9981 with nm23-H1 gene deletion, L9981-nm23-H1 transfected with nm23-H1 gene, and L9981-pLXSN transfected with vector by Western blot.</p><p><b>RESULTS</b>(1)β-catenin expression in L9981-nm23-H1 cytoplasm (IOD) (3 649±118) was significantly higher than that in L9981 (1 401±31) and L9981-pLXSN (1 350±55) cell lines (P < 0.001);(2)There was no statistical diffe-rence of the β-catenin expression in nucleus among L9981-nm23-H1 (2 945±68), L9981 (2 604±23) and L9981-pLXSN (2 652±53) cell lines (P > 0.05);(3)Phospho-β-cetenin expression of cytoplasm in L9981-nm23-H1 cell line (3 123±102) was significantly lower than that in L9981 (4 362±131) and L9981-pLXSN ( 4 500 ±117) cell lines (P < 0.001);(4)Phospho-β-catenin expression of nucleus in L9981-nm23-H1 (5 136±112) was significantly higher than that in L9981 (2 666±116) and L9981-pLXSN (2 661±66) cell lines (P < 0.001);(5)There was no statistical difference of β-catenin or phospho-β-catenin expression in cytoplasm and nucleus between L9981 and L9981-pLXSN cell lines (P > 0.05).</p><p><b>CONCLUSIONS</b>(1)nm23-H1 gene transfection can remarkably upregulates the expression of cytoplasm β-catenin in human high-metastatic large cell lung cancer cell line L9981, but do not induce the nucleus accumulation of β-catenin; (2)Transfection of nm23-H1 gene can significantly upregulate the expression of phospho-β-catenin in nucleus and remarkably downregulate the expression of phospho-β-catenin in cytoplasm of L9981; (3)Regulation of the expression of the key modecule, β-catenin, in Wnt signal pathway might be the important melecular mechanisms which nm23-H1 gene controls "Lung Cancer Metastatic Suppresive Cascade" and reverves cancer metastasis in L9981.</p>