1.Clinical Observation of Oxaliplatin Combined with Thymosin in the Treatment of Lung Cancer with Malig-nant Pleural Effusion
China Pharmacy 2016;27(27):3767-3770
OBJECTIVE:To observe the efficacy and safety of oxaliplatin combined with thymosin in the treatment of lung can-cer with malignant pleural effusion. METHODS:120 lung cancer patients with malignant pleural effusion were randomly divided in-to control group(60 cases)and observation group(60 cases). All patients received chest microtubules drainage,then thoracic cavi-ty drug infusion after clean effusion drainage verified by B ultrasound,10 mg Loratadine tablet was orally given before going to bed 1 d before drug infusion,for 1 week;25 mg Promethazine hydrochloride injection was intramuscularly injected 30 min before drug infusion for allergy prevention,20 mg metoclopramide for gastrointestinal reaction prevention,10 mg dexamethasone and 10 ml 2% lidocaine,adding into 10 ml 0.9%Sodium chloride solution,injected to thoracic cavity by drainage tube to prevent and re-lief chest pain,fever,and other pleural reaction symptoms. Based on it,control group was injected 100 mg/m2 Oxaliplatin for injec-tion to thoracic cavity by drainage tube. Observation group was additionally given 300 mg Thymosin injection,to thoracic cavity by drainage tube. Pleural effusion was drained after 2 d. Once every week in 2 groups,4-week was regarded as 1 coure,and it lasted 2 courses. Clinical efficacy,clinical benefit rate,and serum T lymphocyte subsets(CD3+,CD4+,CD8+),inflammatory cytokines lev-els [interleukin(IL)-6,tumor necrosis factor(TNF)-α)] before and after treatment in 2 groups were observed,survival status and the incidence of toxicity reactions were followed-up. RESULTS:The objective response rate,disease control rate,clinical benefit rate,survival rate in observation group were significantly higher than control group,the incidence of toxicity reactions was signifi-cantly lower than control group,the differences were statistically significant(P<0.05). After treatment,CD3+,CD4+,CD8+ levels in observation group were significantly lower than before,and observation group was lower than control group,the differences were statistically significant(P<0.05),there were no significant differences in CD3+,CD4+,CD8+ levels before and after treatment in 2 groups(P>0.05). CONCLUSIONS:Oxaliplatin combined with thymosin can improve efficacy in the treatment of lung cancer with malignant pleural effusion,prolong survival period,improve survival quality and reduce the incidence of toxicity reactions.
2.Effect of formoononetin on endostatin, VEGF, MMP-2 and bFGF in hydrothorax and serum and tumor biomarkers of elderly patients with advanced lung cancer
Lei ZHANG ; Zhonghai REN ; Yongfei XUE
Chinese Journal of Biochemical Pharmaceutics 2015;(8):154-157
Objective To investigate the effect of formoononetin on endostatin ( ES ) , vascular endothelial growth factor ( VEGF ) , matrix metalloproteinases 2(MMP-2), basic fibroblast growth factor (bFGF) in hydrothorax and serum, and tumor biomarkers of patients with elderly advanced lung cancer.Methods 67 cases elder with advanced lung cancer were selected and randomly divided into two groups.33 cases in control group were treated with conventional therapy of NP chemotherapy regimen, 34 cases in experiment group were combined with formononetin.The changes of ES, VEGF, MMP-2, bFGF, tumor marker levels in hydrothorax and serum and life quality evaluation were compared.ResuIts Compared with control group, the contents of ES, VEGF, MMP-2, bFGF in hydrothorax and serum of experiment group significantly decreased (P<0.05); the carcino embryonie antigen (CEA), neuron specific enolase (NSE), cytokeratin-19-fragments (CYFRA21-1), and carbohydrate antigen 125 (CA125) in serum of experiment group significantly decreased ( P<0.05 ); the life quality evaluation improved better of experiment group (χ2 =4.96, P<0.05 ). ConcIusion Formononetin has better clinical effect in treatment of elderly patients with advanced lung cancer patients.It could effectively improve the quality of life, reduce ES, VEGF, MMP-2, bFGF and other indicators in hydrothorax and serum, which has the vital significance to the clinical therapy.
3.Biomechanics characteristics of four anterior cervical reconstructive techniques in the surgical management of multilevel cervical spondylotic myelopathy:a finite element model study
Zhonghai LI ; Bin LIN ; Jiaguang TANG ; Dongfeng REN ; Li LI ; Wenwen WU ; Shuxun HOU
Chinese Journal of Tissue Engineering Research 2016;20(44):6612-6619
BACKGROUND:Surgical treatment is commonly used for decompressing the spinal cord in multilevel cervical spondylotic myelopathy, but the optimum anterior cervical reconstructive method has not been determined. OBJECTIVE:To compare and analyze the biomechanical characteristics of four anterior cervical reconstructive techniques in the surgical management of multilevel cervical spondylotic myelopathy utilizing the three-dimensional finite element model. METHODS:A three-dimensional finite element model of an intact C2–7 segment was developed and validated based on healthy adult male CT images. Four additional models were developed from the fusion model, including anterior cervical discectomy and fusion, anterior cervical corpectomy and fusion, anterior cervical hybrid decompression and fusion and anterior cervical discectomy and fusion with Cage alone. Von Mises stresses on the plate and the disc of adjacent levels (C2/3, C6/7) were comparatively analyzed. RESULTS AND CONCLUSION:(1) The C2/3 disc stress in flexion, extension, lateral bending and rotation condition was significantly higher than the C6/7 disc in 4 anterior cervical reconstructive techniques, and the adjacent disc stress (C2/3, C6/7) was lowest in the anterior cervical discectomy and fusion with Cage alone, and highest in the anterior cervical corpectomy and fusion. (2) The stress at the plate-screw interface was highest in the anterior cervical corpectomy and fusion, and lowest in the anterior cervical discectomy and fusion. (3) In conclusion, among the four anterior cervical reconstructive techniques for multilevel cervical spondylotic myelopathy, the anterior cervical discectomy and fusion with Cage alone makes little effect on the adjacent disc stress, which might reduce the incidence of adjacent segment disease after fusion. However, the accompanying risk of the increased incidence of cage subsidence should never be neglected.
4.Effect of circ-SFMBT2 on the biological behavior of non-small cell lung cancer cells by targeting the miR-7-5p/ADAM10 axis.
Changsheng LI ; Guanping ZHANG ; Zhonghai REN
Chinese Journal of Medical Genetics 2022;39(2):162-170
OBJECTIVE:
To explore the effect of circ-SFMBT2 on the biological behavior of non-small cell lung cancer (NSCLC) cells and its regulatory role on the miR-7-5p/ADAM10 axis.
METHODS:
qRT-PCR and Western blotting were used to determine the expression of circ-SFMBT2, miR-7-5p, and ADAM10 in NSCLC tissues and adjacent tissues. Pearson analysis was used to analyze the correlation between circ-SFMBT2 and miR-7-5p, and between miR-7-5p and ADAM10. In vitro cultured human bronchial epithelial-like cells (HBE) and lung cancer cell lines H1650, H460, A549, H1299. CCK-8 and EdU methods were used to assess the ability of cell proliferation. Plate experiment was used to detect the clone formation ability. Flow cytometry was used to detect the apoptosis rate. Transwell experiment was used to detect cell invasion ability. Dual luciferase reporter experiment detects the targeting relationship between circ-SFMBT2 and miR-7-5p, and between miR-7-5p and ADAM10. Transplanted tumor experiment in nude mice assessed the effect of knocking down circ-SFMBT2 on the growth of transplanted tumor. Immunohistochemical experiments were performed to detect the positive rates of ADAM10 and Ki67 proteins in transplanted tumor tissues.
RESULTS:
The expression levels of circ-SFMBT2 and ADAM10 were increased in NSCLC tissues and cell lines, while decreased the expression of miR-7-5p. circ-SFMBT2 was negatively correlated with miR-7-5p, while miR-7-5p was negatively correlated with ADAM10. Silencing the overexpression of circ-SFMBT2 and miR-7-5p could inhibit cell proliferation, clone formation and invasion, and also promote apoptosis. circ-SFMBT2 could target miR-7-5p, and ADAM10 was the target gene of miR-7-5p. The combined effect of silencing circ-SFMBT2 and inhibition of miR-7-5p, as well as miR-7-5p overexpression and ADAM10 overexpression could promote cell proliferation, clone formation and invasion, and also suppress cell apoptosis. Silencing circ-SFMBT2 could inhibit the growth of transplanted tumors.
CONCLUSION
Silencing circ-SFMBT2 can suppress the proliferation, clone formation, invasion ability and induce apoptosis of NSCLC cells by regulating the miR-7-5p/ADAM10 axis.
ADAM10 Protein/genetics*
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Amyloid Precursor Protein Secretases/genetics*
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Animals
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Carcinoma, Non-Small-Cell Lung/genetics*
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Cell Proliferation
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Lung Neoplasms/genetics*
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Membrane Proteins/genetics*
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Mice
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Mice, Nude
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MicroRNAs/genetics*
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RNA, Circular
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Repressor Proteins
5.Effect of miR-449a on radiosensitivity of pancreatic cancer cells
Jingwei ZHANG ; Dongmei DUAN ; Junzhong SUN ; zhonghai REN
Chinese Journal of Radiation Oncology 2017;26(11):1332-1335
Objective The purpose of this study is to investigate the effect of miR-449a on pancreatic cancer cells and the molecular mechanism. Methods The expression levels of miR-449a in pancreatic cancer cells treated or untreated with radiation was detected by qRT-PCR.High expression of miR-449a was achieved by transfecting miR-449a mimics into SW1990 cells. The cell growth,apoptosis and colony formation ability was assessed by MTT assay,flow cytometry and colony formation assay,respectively. The relationship of miR-449a and Cyclin D1 was determined by the TargetScan and dual luciferase reporter. Immunohistochemistry was used to examine protein levels of Cyclin D1 in pancreatic cancer and normal pancreas tissues. Si-Cyclin D1 was used to detecte the effect of Cyclin D1 on radiosensitivity of pancreatic cancer cells. Results The expression levels of miR-449a in pancreatic cancer cells with radiation treatment were decreased significantly. Mir-449a mimics increased the cell proliferation rates and apoptosis rates obviously,and decreased the colony formation ability in SW1990 cells treated with radiation. Results from the TargetScan and dual luciferase reporter showed that Cyclin D1 was the target of miR-449a. The positive staining rates of Cyclin D1 in pancreatic cancer tissue(85.7%,30/35)was higher than those in normal pancreas tissue(20%,2/10).Knockdown of Cyclin D1 enhanced the radiosensitivity of pancreatic cancer cells.Conclusion MiR-449a enhances the radiosensitivity of pancreatic cancer cells by targeting Cyclin D1.
6.circ-PRKDC affects the proliferation, apoptosis and radiosensitivity of lung cancer cells by regulating miR-505-3p
Xiaosun YUAN ; Lei ZHANG ; Shilei RAO ; Kai ZHANG ; Huili MA ; Changsheng LI ; Jingwei ZHANG ; Zhonghai REN
Chinese Journal of Radiation Oncology 2021;30(12):1309-1315
Objective:To investigate the effect of circ-PRKDC on lung cancer cell proliferation, apoptosis and radiosensitivity and its molecular mechanism.Methods:Normal lung epithelial cells BEAS-2B and lung cancer cell lines NCI-H1299, NCI-H2170, NCI-H1975 were cultured. NCI-H1299 cells were divided into the si-NC, si-PRKDC, pcDNA-NC, pcDNA-PRKDC, miR-NC, miR-505-3p, anti-miR-NC, anti-miR-505-3p, si-PRKDC+ anti-miR-NC and si-PRKDC+ anti-miR-505-3p groups. RT-qPCR was used to detect the expression levels of circ-PRKDC and miR-505-3p. Western blot was employed to measure the protein expression. MTT was used to detect cell proliferation. Flow cytometry was utilized to detect cell apoptosis. Plate clone formation assay was conducted to detect the cell radiosensitivity. Dual luciferase reporter assay was performed to analyze the targeting relationship between circ-PRKDC and miR-505-3p.Results:Compared with normal lung epithelial cells BEAS-2B, the expression levels of circ-PRKDC in the lung cancer cell lines NCI-H1299, NCI-H2170 and NCI-H1975 were significantly up-regulated (3.65, 3.10, 2.67 vs. 1.00, all P<0.05), whereas those of miR-505-3p were significantly down-regulated (0.42, 0.50, 0.54 vs. 1.02, all P<0.05). After low expression of circ-PRKDC, the expression level of CyclinD1 was significantly down-regulated (0.42 vs. 0.81, P<0.05), whereas those of Cleaved-caspase-3(0.71 vs. 0.33, P<0.05) and γ-H 2AX (0.89 vs. 0.46, P<0.05) were significantly up-regulated, the cell A value was significantly decreased (0.413 vs. 0.839, P<0.05), cell apoptosis rate was significantly increased (20.35 vs. 6.21, P<0.05), cell survival fraction was significantly decreased ( P<0.05), and β-catenin expression was significantly down-regulated (0.35 vs. 0.73, P<0.05). After high expression of miR-505-3p, the expression level of CyclinD1 was significantly down-regulated (0.34 vs. 0.83, P<0.05), those of Cleaved-caspase-3(0.65 vs. 0.32, P<0.05) and γ-H 2AX (0.96 vs. 0.45, P<0.05) were significantly up-regulated, the cell A value was significantly decreased (0.386 vs. 0.851, P<0.05), the apoptosis rate was significantly increased (16.38 vs. 6.20, P<0.05), and the cell survival fraction was significantly decreased ( P<0.05). Compared with miR-NC, the luciferase activity of miR-505-3p group transfected with circ-PRKDC wild-type reporter plasmid was significantly decreased (0.44 vs. 1.00, P<0.05). Down-regulation of miR-505-3p could reverse the effect of low expression of circ-PRKDC on the proliferation, apoptosis, radiosensitivity and β-catenin expression of NCI-H1299 cells. Conclusion:Low expression of circ-PRKDC may inhibit lung cancer cell proliferation, promote cell apoptosis and enhance cell radiosensitivity by up-regulating miR-505-3p, which is probably associated with the Wnt/β-catenin signaling pathway.
7.Effect of circLPAR3 on radiosensitivity of esophageal cancer cells by targeting miR-1238
Xiaosun YUAN ; Lei ZHANG ; Shilei RAO ; Kai ZHANG ; Huili MA ; Changsheng LI ; Jingwei ZHANG ; Zhonghai REN
Chinese Journal of Radiation Oncology 2022;31(1):71-78
Objective:To evaluate the effect of circLPAR3 on the radiosensitivity of esophageal cancer cells and investigate its mechanism.Methods:The cancer tissues and and adjacent tissues of 37 patients with esophageal cancer were collected, and esophageal cancer cell lines Eca-109, EC9706 and KYSE30 and esophageal epithelial cells HET-1A were cultured in vitro. The expression levels of circLPAR3 and miR-1238 in the tissues and cells were measured by RT-qPCR. Eca-109 cells were transfected with circLPAR3 siRNA and miR-1238 mimics or co-transfected with circLPAR3 siRNA and miR-1238 inhibitor. Cell cloning experiment was conducted to evaluate the effects of silencing circLPAR3, overexpressing miR-1238, or silencing both circLPAR3 and miR-1238 on the radiosensitivity of Eca-109 cells. After Eca-109 cells that silenced circLPAR3, overexpressed miR-1238 or silenced both circLPAR3 and miR-1238 were exposed to 4 Gy irradiation, CCK-8 assay (A value), flow cytometry and Western blot were employed to assess the effects of silencing circLPAR3, overexpressing miR-1238, or silencing both circLPAR3 and miR-1238 combined with 4 Gy irradiation on the proliferation and apoptosis of Eca-109 cells and the expression levels of CyclinD1, p21, Bcl-2 and Bax proteins. Dual luciferase reporter gene experiment and RNA pull down experiment were performed to verify the regulatory relationship between circLPAR3 and miR-1238. Results:Compared with adjacent tissues, the expression level of circLPAR3 was up-regulated in the esophageal cancer tissues ( P<0.05), while that of miR-1238 was down-regulated ( P<0.05). Compared with HET-1A cells, the expression levels of circLPAR3 were up-regulated in the esophageal cancer cell lines Eca-109, EC9706 and KYSE30(all P<0.05), whereas those of miR-1238 were down-regulated (all P<0.05). Silencing circLPAR3 or overexpressing miR-1238 reduced the survival fraction of Eca-109 cells (all P<0.05), and the sensitization ratio was 1.21 and 1.75, respectively. Silencing circLPAR3 or overexpressing miR-1238 decreased the A value of Eca-109 cells and the expression levels of CyclinD1 and Bcl-2 proteins (all P<0.05), while increased the apoptosis rate of Eca-109 cells and the expression levels of p21 and Bax proteins (all P<0.05). After silencing circLPAR3 or overexpressing miR-1238 combined with 4 Gy irradiation, the A value of Eca-109 cells and the expression levels of CyclinD1 and Bcl-2 proteins were decreased (all P<0.05), while Eca-109 cell apoptosis rate and the expression levels of p21 and Bax proteins were increased (all P<0.05). circLPAR3 targeted and negatively regulated the expression level of miR-1238 in Eca-109 cells. After silencing miR-1238 and circLPAR3 simultaneously, the survival fraction of Eca-109 cells was higher than that when only silencing circLPAR3, and the sensitization ratio was 0.59. Silencing miR-1238 reversed the effects of silencing circLPAR3 combined with 4 Gy irradiation on the proliferation and apoptosis of Eca-109 cells. Conclusion:circLPAR3 is highly expressed in esophageal cancer tissues and cell lines, and silencing the expression of circLPAR3 can inhibit the proliferation of esophageal cancer Eca-109 cells, promote their apoptosis, and enhance cell radiosensitivity by up-regulating miR-1238.
8.Effects of status of lymph vascular invasion on the survival of patients with squamous cell carcinoma of the penis
Minglin LI ; Zhonghai REN ; Huili MA ; Xinyue MEI ; Yueshi HU ; Lixin YANG
Journal of Modern Urology 2023;28(7):597-602
【Objective】 To explore the effects of status of lymph vascular invasion (LVI) on the survival of patients with squamous cell carcinoma of the penis (SCCP). 【Methods】 Data of patients diagnosed as SCCP during Jan.1, 2010 and Dec.31, 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method was used to draw the survival curve of patients with different LVI statuses, and log-rank test was conducted in parallel. Univariate and multivariate Cox regression analyses were used to assess the effects of LVI status on the overall survival. Patients were divided into different subgroups based on stage (localized, regional, and distant metastasis) and grade (well, moderately and poorly differentiated) of tumor, and the effects of LVI status on the overall survival of patients in different subgroups were assessed. 【Results】 A total of 1 435 patients were involved, including 1 102 (76.8%) without LVI and 333 (23.2%) with LVI. Median survival time of patients without LVI and with LVI were 27.5 months and 17.0 months, respectively (χ2=55.028, P<0.001). Cox regression analyses showed LVI was a significant prognostic factor in SCCP patients (HR=1.280, 95%CI:1.044-1.569, P=0.018). In the subgroup analysis, LVI was an independent risk factor affecting the overall survival of patients with localized tumor (HR=1.446, 95%CI:1.009-2.110, P=0.046) and regional tumor (HR=1.323, 95%CI:1.018-1.720, P=0.036);it was also an independent risk factor affecting the overall survival of SCCP patients with well differentiated tumor (HR=2.797, 95%CI:1.573-4.971, P=0.046) and moderately differentiated tumor (HR=1.431, 95%CI:1.071-1.914, P=0.015). 【Conclusion】 LVI status is a significant factor affecting the prognosis of SCCP patients. LVI is an independent risk factor for the overall survival of SCCP patients with localized and regional tumor, moderately differentiated and well differentiated tumor.