1.Expression and clinical significance of SIRT-1 and NF-κB in non-small cell lung cancer
Zhongxiu JIANG ; Yang LIU ; Ning LI ; Xiaoying QI ; Xiaoye ZHANG
Journal of International Oncology 2015;(7):504-507
Objective To investigate the expression and clinical significance of silent mating type information regulation 2 homolog-1(SIRT-1)and nuclear factor-κB(NF-κB)in non-small cell lung cancer (NSCLC). Methods The expressions of SIRT-1 and NF-κB were evaluated by immunohistochemistry in 108 selected cases of primary NSCLC and 48 samples of para-carcinoma normal tissue. The relationships of the expressions of SIRT-1 and NF-κB and clinical pathological features were analyzed,respectively. Results Immunohistochemical results showed that the positive expression rates of SIRT-1 and NF-κB in NSCLC tissue were 90. 7%(98 / 108)and 94. 4%(102 / 108),respectively,significantly higher than those in normal lung tissue 4. 2%(2 / 48),16. 7%(8 / 48),χ2 = 108. 237,P = 0. 000;χ2 = 96. 683,P = 0. 000,and the expre-ssion of SIRT-1 and NF-κB showed a positive correlation(r = 0. 480,P = 0. 001). There were significant posi-tive correlations between the expression of SIRT-1 and tumor size(r = 0. 227,P = 0. 018),TNM stage(r =0. 298,P = 0. 002)and lymph node metastasis(r = 0. 280,P = 0. 003),and there was negative correlation between the expression of SIRT-1 and differentiation(r = - 0. 300,P = 0. 002),and there were no correlation between the expression of SIRT-1 and sex,age and histological type in NSCLC tissues. There were significant positive correlation between the expression of NF-κB and TNM stage(r = 0. 256,P = 0. 009)and lymph node metastasis(r = 0. 261,P = 0. 006),and there was negative correlation between the expression of NF-κB and differentiation(r = - 0. 235,P = 0. 013),and there were no correlation between the expression of NF-κB and sex,age,histological type and tumor size in NSCLC tissues. Conclusion The positive expression rates of SIRT-1 and NF-κB in NSCLC tissue are significantly higher than those in normal lung tissue,and they are rela-ted to TNM stage,lymph node metastasis and differentiation,and the former is also related to tumor size. High expression of SIRT-1 and NF-κB may play important roles in the occurrence and development of NSCLC.
2.Establishment of a mouse model of orthotopic Lewis lung cancer
Ning LI ; Xiaoye ZHANG ; Zhongxiu JIANG ; Yang LIU ; Xuejiao LI
Acta Laboratorium Animalis Scientia Sinica 2014;(5):79-83
Objective To establish a mouse model of orthotopic Lewis lung carcinoma using Matrigel, to evaluate the tumor growth and metastasis, and to provide a more stable mouse model of orthotopic lung cancer, which is more similar to human lung cancer.Methods Logarithmic phase of cultured Lewis lung cancer cells were suspended in Matrigel, vac-cinated into the left lung of inbred C57BL/6 mice.Five mice were killed on the 4th, 7th, 10th, 13th, and 16th days, re-spectively, and to observe the median survival, tumor formation rate, tumor growth, and metastasis.Pathological changes of the mouse lung, liver, kidney and spleen were examined.Results In 5 mice killed on the 7th postoperative day, small tumor nodules were observed on the lung in three mice and no tumor was visible by gross inspection in the other two mice, but small tumor nodules were observed under the microscope.For all the mice killed on the 10th postoperative day, tumors were visible to the naked eye on the lung of all the five mice.On the 13th day, orthotopic tumor was observed on the lung with bloody pleural effusion and pleural metastasis in all the five mice.On the 25th day, in addition to the pleural metasta-sis, one mouse had pericardial metastasis and renal metastasis.The survival periods of the 5 mice were 17 d, 20 d, 22 d, 22 d, and 25 d, respectively, with a median survival period of 21.2 d (17-25 d), and the tumor formation rate was 100%.Conclusions Mouse models of orthotopic Lewis lung carcinoma is successfully established using injection of tumor cells suspended in Matrigel.This model is more similar to the growth of human lung cancer, with good stability, high tumor formation rate and characteristics of distant metastasis, therefore, is worthy of further application.
3.Effect evaluation of chymotrypsin and danshen mixture to treat moist skin damage caused by radiotherapy
Rongqing LI ; Daiqi JIANG ; Zhongxiu HAN ; Zhongmin TANG
Chinese Journal of Practical Nursing 2012;(34):43-45
Objective To observe the curative effect of chymotrypsin and danshen mixture treatment to moist skin damage caused by radiotherapy.Methods 90 NPC patients who underwent radiotherapy plus concurrent chemotherapy were randomized into the observation group(46 cases)and the control group(44 cases).Patients in the observation group received external application of chymotrypsin and danshen mixture;while patients in the control group received laser irradiation treatment.The healing progress of skin injury of two groups was observed and compared.Results Time of detumescence,pain relieving,itching and healing of the observation group was shorter than the control group.Nursing effect for level 2 & 3 radiation-induced skin injury in the observation group was better than the control group.Conclusions Chymotrypsin and danshen mixture has a great nursing efficacy on radiation-induced skin injury.It should be used in the early stage.
4.Expression and Clinical Significance of Sir2-related Enzymes-1 in Colorectal Cancer
Xiaoying QI ; Zhongxiu JIANG ; Yang LIU ; Ning LI ; Xiaoye ZHANG
Journal of China Medical University 2015;(7):606-609,613
Objective To investigate the expression and clinical significance of Sir2?related enzymes?1(SIRT1)in colorectal cancer. Methods The expression of SIRT1 was evaluated by immunohistochemistry in 86 selected cases of primary Colorectal cancer and 30 samples of normal rectum tissues besided carcinoma. The relationship of the expression and clinical pathological features were analyzed. Results The positive expression rate of SIRT1 in Colorectal cancer tissue was 88.4%,and significantly higher than in normal rectum tissue besided carcinoma(P<0.001). There were no correlation between the expression of SIRT1 and sex,age and tumor diameter,and significant positive correlation between the expression of SIRT1 and TNM stage (P<0.05),lymph node metastasis(P<0.05),infiltrating depth(P<0.05),and negagtive correlation between the expression of SIRT1 and tumor differentiation(P<0.05). Conclusion The positive expression rate of SIRT1 in colorectal cancer tissue was significantly higher than in normal rectum tissue besided carcinoma and intimate correlation with tumor differentiation,TNM stage,lymph node metastasis and Infiltrat?ing depth. Conclusion SIRT1 may be an important assistance gene to diagnose and judge prognosis,and may improve diagnostic rate and auxiliari?ly judge prognosis as a important Colorectal cancer marker.
5.Comparison of pharmacodynamics between different batches of recombinant decoy receptor innovative drug RC28-E1 and RC28-E2 in retinal angiogenesis and neovascularization and its mechanism
Zhongxiu GU ; Jing JIANG ; Min HUANG ; Mianmian WU ; Fang GUO ; Shenjun LI ; Jianmin FANG ; Shaozhen ZHAO ; Yan ZHANG
Chinese Journal of Experimental Ophthalmology 2018;36(8):581-589
Objective To compare the pharmacodynamics between different batches of recombinant decoy receptor innovative drug RC28-E1 and RC28-E2 in retinal angiogenesis and neovascularization,and analyze its mechanism.Methods Sixty postnatal Day 4 (P4) C57BL/6J mice were randomly divided into normal control group,vascular endothelial growth factor (VEGF)+fibroblast growth factor 2 (FGF2) group,VEGF+FGF2+RC28-E1 group,VEGF+FGF2+RC28-E2 group,VEGF+FGF2+conbercept group and VEGF+FGF2+FGF trap group by using a random number table,with 10 mice in each group.The mouse retinal explant culture system was established,and stimulated with the corresponding factors and drugs prepared in the starving culture media.The normal controls were treated with the starving media.Then the retinal explants were stained with Isolectin B4 and imaged.The number of filopodia per vascular length was quantified.In addition,ninety-six P7 C57BL/6J mice were randomly divided into normal control group,oxygen-induced retinopathy (OIR) model control group,OIR + RC28-E1 group,OIR + RC28-E2 group,OIR+conbercept group and OIR+FGF trap group by using a random number table,with 16 mice in each group.The normal controls were raised under normoxia for 10 days,and the rest of the groups were raised under hyperoxia for 5 days,then returned to normoxia for another 5 days.On P17,the retinas were isolated and stained with Isolectin B4.The stained retinas were mountedon the slides and photographed.The relative vessel obliteration and neovascularization in retina were analyzed with computer software.Then the protein levels of VEGF and FGF2 were examined by Western blot in the retinas of each group in the OIR experiment.Finally,in the RF/6A cells stimulated with VEGF and FGF2,the activities of the signaling pathways,including MEK-extracellular regulated protein kinases (Erk),protein kinase C (PKC) and protein kinase B (Akt) pathways,were examined by Western blot.All experimental procedures were evaluated and approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (SYXK 2009-0001),and were in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.Results The results of retinal explant cultures showed that the numbers of filopodia per vascular length in VEGF + FGF2 + RC28-E1,VEGF + FGF2 + RC28-E2,VEGF + FGF2 + conbcrcept,and VEGF+FGF2+FGF trap groups were all significantly less than that in the VEGF+FGF2 group (all at P < 0.001).The filopodia number in retinal vascular front in RC28-E1 group was similar to that in the RC28-E2 group (P =0.15),whereas the filopodia numbers in both groups were significantly decreased as compared to those in VEGF+ FGF2+conbercept group and VEGF+FGF2+FGF trap group (all at P<0.001).The results from the OIR mouse model showed that the relative vessel obliteration area in OIR model control group was dramatically higher than those in the drug intervention groups (all at P<0.05).There was no statistical significance in the relative vessel obliteration area between OIR+RC28-E1 group and OIR+RC28-E2 group (P =0.17),while the obliteration areas in both RC28-E-intervened groups were significantly lower than those in the OIR+conbercept group and OIR+FGF trap group (all at P<0.05).The relative neovascular pixels in the intervention groups were significantly lower than those in the OIR model control group (all at P<0.001).The neovascular pixels in OIR+RC28-E1 group were significantly lower than those in VEGF+FGF2+conbercept group and VEGF + FGF2 + FGF trap group (both at P < 0.05),but comparable to those in OIR+RC28-E2 group (P =0.39).Western blot result showed that,the protein expression of VEGF and FGF2 in the OIR mouse retinas were significantly upregulated compared to those in the normal ones (both at P<0.001).The upregulation of both genes were normalized by both RC28-E1 and RC28-E2.In addition,the stimulation of VEGF and FGF2 induced an enhanced activity in MEK-Erk pathway in RF/6A cells,whereas RC28-E1 inhibited the overactivation.Conclusions RC28-E1 and RC28-E2 both can inhibit angiogenesis in the retinal explants isolated from neonatal mice;they also reduce vessel obliteration and mitigate neovascularization in the OIR mouse model.Therefore,the pharmacology batch and pilot test batch of RC28-E have similar efficacies and reliable stability,and are superior in the anti-angiogenic and anti-neovascular efficacy to the currently clinically available drugs conbercept and FGF trap.RC28-E1 may suppress pathological neovascularization through inhibiting the overactivation of MEK-Erk pathway in retinal vascular endothelial cells.