1.New era of immunotherapy for colorectal cancer
Ziwen ZHANG ; Tingting ZHANG ; Yuxian BAI
Clinical Medicine of China 2017;33(9):861-864
Colorectal cancer is one of the common malignant tumors and the overall prognosis is poor. The search for a more effective treatment for colorectal cancer has never stopped. The current interaction between the modulated immune system and the tumor microenvironment is a hot topic in the treatment of colorectal cancer. The achievements involve immune checkpoint inhibition, cytokine therapy, toll?like receptors and autologous cell therapy. It has been proved that these methods have mild effect on tumor loading reduction. However, significant breakthrough has been achieved with the use of checkpoint inhibitors targeting cytotoxic T lymphocyte associated antigen?4 (CTLA?4),programmed death?1 (PD?1) and programmed death receptor ligand 1 (PD?L1). Immunotherapy is promising in the treatment of patients with refractory tumors. The success of this current immunotherapy approach is largely limited to tumors with high mutation amplification, such as melanoma,renal cell carcinoma ( RCC) and non?small cell lung cancer. However,this discovery has led the development of checkpoint inhibitors in the treatment of colorectal cancer with highly mutated amplification of mismatch repair gene to a new era.
2.Expression of multi-drug resistance genes in cervical cancer before and after neoadjuvant chemotherapy and its relationship with the effect of chemotherapy
Rong SHEN ; Xiaoling WU ; Ziwen XIAO ; Qizhu ZHANG ; Shu XU
The Journal of Practical Medicine 2015;(20):3327-3330
Objective To explore the impact of preoperative neoadjuvant chemotherapy on the expressions of multi-drug resistance genes in patients with cervical cancer and its relationship with the effect of chemotherapy. Methods Ninety-eight cervical cancer patients with TP regimen selected to perform preoperative chemotherapy were enrolled in the Affiliated Hospital of Guiyang Medical College between January 2010 and June 2014. Immunohistochemisty (En vision method) was used to determine the expressions of P-gP, GST-π and TopoII of the same patients before and after neoadjuvant chemotherapy and explore the relationship with the effect of chemotherapy. Results The positive expression rates of P-gp and GST-π were 71.43% and 64.29% before chemotherapy and 80.61%and 74.49%after chemotherapy, respectively. The former two had significant differences (P<0.01). The positive expression rates of TopoII was 48.98%before chemotherapy and 28.57%after chemotherapy , respectively, showing significant differences (P < 0.01). The expressions of P-gp, GST-π and TopoⅡ gene were not affected by the clinical and pathological features of cervical cancer (P > 0.05). Before neoadjuvant chemotherapy, the positive expression of GST-π in the ineffective group was statistically higher than that in the effective group (P<0.05). The positive expressions of P-gp and Topo II showed no statistical significance between the effective group and the ineffective group (P > 0.05). There was significant correlation in the expressions of P-gp, GST-π and TopoⅡ(P < 0.05) before and after neoadjuvant chemotherapy. Conclusions The expression of P-gp, GST-πand TopoⅡgene may not be affected by the clinical and pathological features of cervical cancer, but may change expressions of multi-drug resistance genes in cervical cancer by neoadjuvant chemotherapy. Monitoring their expression has a guiding significance for drug selection, prognostic judgment, and the following treatment regimen decision. The GST-π, expression level can be used as a biological parameter to predict the effect of TP regimen neoadjuvant chemotherapy.
3.Effect of rhTRAIL on survivin expression of human lung adeno-carcinoma A549 xenografted tumor in nude mice
Meichun ZHANG ; Jun ZENG ; Ziwen ZHAO ; Zhaohui LIU
Chinese Journal of Primary Medicine and Pharmacy 2015;22(2):203-207
Objective To observe the effect of rhTRAIL on survivin gene expression of human lung adeno-carcinoma A549 xenografted tumor in nude mice,and investigate the possible inhibitory mechanism of rhTRAIL on the implanted-tumor growth.Methods The solid tumor model was formed in nude mice with human lung adeno-carcinoma cell line.A549.24 mice were randomly divided into the four groups,rhTRAIL single treated group (1 μg/mL),rhTRAIL combined with cisplatin (DDP) treated group,cisplatin treated (1.5mg/kg) and 0.9% sodium chloride injection(NS) control group.The rhTRAIL and DDP were injected once every other day by intraperitoneal injection to mice in the treated groups,lasting eight times,the same volume of saline solution was injected to the control group.After these,mice were killed and dissected completely.The expression level of survivin mRNA and protein in the tumor tissues was detected by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry,respectively.And the expression of survivin gene in serum of each group was tested by ELISA.Results The expression levels of survivin mRNA in implanted-tumor tissues in rhTRAIL,rhTRAIL combined with DDP,DDP and NS group were (48.7 ± 2.5) %,(53.1 ± 4.6) %,(99.1 ± 5.3) % and (95.6 ± 3.7) %,respectively.While the protein expressions of survivin gene in those groups were (0.319 ± 0.025),(0.483 ± 0.058),(0.635 ± 0.041) and (0.619 ± 0.017),respectively.Moreover,the serum levels of survivin were (71.9 ± 7.05),(80.26 ± 10.80),(112.75 ± 15.41) and (105.03 ± 20.37),respectively.The data showed that the expression levels of rhTRAIL and rhTRAIL combined with DDP group were lower than that of DDP-treated group or the NS control group (P < 0.0 5).Compared with the rhTRAIL combined with DDP group,the survivin gene expression level of rhTRAIL-single treated group decreased a little lower,but the difference was not significant (P > 0.05).Conversely,the survivin gene level was increased to some degree compared with the NS control group,and uniformly there was no significant difference (P > 0.05).Conclusion rhTRAIL can downregulate the expression level of survivin gene of human lung adeno-carcinoma A549 xenografted tumor in nude mice.It may be one of the possible inhibitory mechanisms of rhTRAIL on the implanted-tumor growth that rhTRAIL can downregulate survivin gene expression and promote tumor cell apoptosis.
4.Retroperitoneal laparoscopic nephron-sparing surgery for renal tumor (a report of 6 cases)
Xianjun ZHANG ; Ziwen LU ; Hongyuan YU ; Tianji WANG ; Chongbiao DING
Chinese Journal of Postgraduates of Medicine 2008;31(29):23-25
Objective To evaluate the methods and efficacy of retroperitoneal laparoscopic nephron-sparing surgery for the treatment of renal tumor. Methods A total of 6 patients with renal tumors underwent retroperitoueal laparoscopie nephron-sparing surgery during warm ischacmia. Among the 6 eases, 2 had malignant tumor with the diameter of 2.5 cm and 2.2 cm,and 4 had renal angiomyolipoma with the diameter from 2.5 cm to 3.5 cm.The renal yes,Is were secured by a self-made equipment. Tumors were excised with a cold Endo-shear. Parenehymal edges were approximated using a absorbable hemostatic gauze. Results All procedures were successfully completed without open conversion. Mean surgical time was 150 minutes (range 120-210 minutes). Mean ischaemia time was 22 minutes (range 18-33 minutes) and the mean blood loss was 170 ml (range 150-200 ml). Surgical margins were negative in all patients.During a follow-up for 6-12 months, no patient had local or port site recurrence. Conclusions Betroperitoneal laparoscopic nephron-sparing surgery for renal tumor by using serf-made equipment is safe and effective. This procedure has the advantages of minimal invasion, less blood loss, good vision, and rapid convalescence and so on.
5.Serum expression of DKK1 protein in patients with non-small cell lung cancer and its relationship with osseous metastasis
Meichun ZHANG ; Jing WU ; Weinong ZHONG ; Zhaohui LIU ; Ziwen ZHAO
Cancer Research and Clinic 2017;29(7):466-469
Objective To explore the serum expression of DKK1 protein, a Wnt signaling pathway inhibitor in patients with non-small cell lung cancer (NSCLC) and its relationship with osseous metastasis. Methods Serum DKK1 protein levels were assayed by enzyme-linked immunosorbent assay (ELISA) in NSCLC patients, including 33 NSCLC patients with osseous metastasis and 41 NSCLC patients without respectively, and 32 healthy volunteers were served as the control group. Furthermore, the differential expression of the serum DKK1 protein level between the patients and the volunteers was compared by using the variance analysis and the independent sample t test. The correlation between DKK1 expression and bone metastasis was detected by Pearson correlation analysis. Results Serum DKK1 protein level of NSCLC patients was (79.6±8.3) ng/ml, which was significantly higher than that in healthy volunteers [(21.5±6.4) ng/ml, t=13.17, P=0.001]. The serum DKK1 level in osseous metastasis group was (110.3±11.4) ng/ml, which was significantly higher than that in non-skeletal metastasis group [(60.7±10.5) ng/ml, t=14.128, P=0.003]. The positive association was observed between the DKK1 level in the peripheral blood and osseous metastasis in NSCLC patients (r=0.855, P<0.001). Conclusion The serum expression level of DKK1 protein in NSCLC patients is closely related to the osseous metastasis, which may be a predicting biomarker for the osseous metastasis.
6.Clinical study on prevention of no-reflow by early administration of intracoronary diltiazem through coronary artery during direct PCI
Dong SHI ; Li HAN ; Feng ZHANG ; Ziwen REN
The Journal of Practical Medicine 2014;(23):3832-3834
Objective To evaluate the effects of the administration of intracoronary diltiazem before the occurrence of no-reflow during direct PCI. Mtthods One hundred and thirty four AMI patients hospitalized from June 2001 to November 2003 were selected as research objects. 60 patients with AMI received intracoronary diltiazem before the occurrence of no-reflow during direct PCI. 74 AMI patients did not receive intracoronary diltiazem and were enrolled as control subjects. Patients with refractory low blood pressure and complete atrioventricular block before PCI were excluded. Thrombolysis in Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count (CTFC) were assessed during angiography, before and after PCI. Results The two groups had similar baseline. There were significant difference in post-PCI no reflow assessment (P = 0.04) and CTFC (P = 0.00). Conclusion Early administration of intracoronary diltiazem during direct PCI reduces the no reflow occurrence.
7.Diagnosis and treatment of diffuse alveolar hemorrhage
Yushan ZHANG ; Ziwen ZHAO ; Zhike LIANG ; Yujun LI ; Weinong ZHONG
The Journal of Practical Medicine 2016;32(19):3200-3204
Objective To investigate the clinical characteristics of diffuse alveolar hemorrhage. Methods 12 patients with diffuse alveolar hemorrhage hospitalized in Guangzhou NO.1 Hospital were included in the research, whose clinical characteristics were analyzed. Results 7 cases of the 12 diffuse alveolar hemorrhage cases were male and 5 cases were female. 8 cases were caused by ANCA associated vasculitis , 1 cases by connective tissue disease, 1 cases by poisoning, and 2 cases of unknown etiology (medication could be considered). The clinical manifestations were fever (91.67%), hemoptysis (100%), anemia (100%), and dyspnea (3.33%). Conclusion Diffuse alveolar hemorrhage is a life-threatening clinical syndrome. It can be caused by many causes. It should be considered if there is the presence of hemoptysis, dyspnea, anemia, etc. Timely examination and early intervention can effectively improve the prognosis of the disease.
8.Clinical significance of the level change of serum WAVE1 and vascular endothelial growth factor C before and after chemotherapy in patients with advanced non-small lung cancer
Meichun ZHANG ; Jun ZENG ; Weinong ZHONG ; Weiguo HE ; Ziwen ZHAO ; Zhaohui LIU
Cancer Research and Clinic 2015;27(3):153-156,160
Objective To evaluate the level changes of serum WASP-family verprolin homologous protein-1 (WAVE1) and vascular endothelial growth factor-C (VEGF-C) and their clinical significance in patients with advanced non-small lung cancer (NSCLC) before and after chemotherapy.Methods Serum WAVE1 and VEGF-C were measured in 43 patients with advanced NSCLC by ELISA,and the results were compared with 43 healthy volunteers.Results The levels of serum WAVE1 and VEGF-C before chemotherapy in patients group were (0.573±0.082) ng/ml and (947.3±125.4) pg/ml respectively,while in healthy volunteers group,they were (0.256±0.064) ng/ml and (425.5±110.1) pg/ml respectively,which suggested that before chemotherapy the levels of serum WAVE1 and VEGF-C in NSCLC group were significantly higher than those of in the control (P < 0.05).The serum levels of WAVE1 and VEGF-C in advanced NSCLC patients were closely related to lymph node metastasis status and distant metastasis status (P < 0.05),but not to the gender,age,tumor length,histology type,differentiation grade and C-TNM stage (P > 0.05).The serum WAVE1 and VEGF-C levels of the effective treatment group was (0.290±0.037) ng/ml and (596.1±127.5) pg/ml after chemotherapy respectively,which decreased obviously compared with the group before chemotherapy which levels were (0.517±0.051) ng/ml and (964.6±100.3) pg/ml (both P < 0.05).But the serum WAVE1 and VEGF-C levels of the ineffective treatment group were (0.547±0.065) ng/ml and (957.0±111.2) pg/ml after treatment,which had no difference compared with the group before chemotherapy which levels were (0.517±0.051) ng/ml and (964.6±100.3) pg/ml (both P > 0.05).Furthermore,statistically significant relationship was found between the serum WAVE1 and the VEGF-C levels (r =0.331,r =0.540,both P < 0.05).Conclusion Serum WAVE1 and VEGF-C may be used as indicators for prediction of the efficacy of chemotherapy in patients with advanced NSCLC.
9.Investigation of microRNA-373 function and mechanism in HepG2 cell growth suppression induced by 5-fluorouracil
Ziwen LIU ; Yongxing DU ; Lei YOU ; Hong SHU ; Taiping ZHANG ; Yupei ZHAO
Chinese Journal of Hepatobiliary Surgery 2014;20(9):675-678
Objective To investigate the inhibitory effect of 5-fluorouracil (5-FU) on hepatocellular carcinoma (HCC) cell growth and to elucidate its potential molecular mechanism.Methods Real-time PCR analysis was conducted to determine the expression of miR-373 in HCC tissue specimens and HCC cell lines.The expression of miR-373 was also evaluated in HepG2 cells after 5-FU treatment.Western blot analysis was performed to detect the protein levels of PPP6C,a verified target of miR-373,with transfection of miR-373 mimics or 5-FU treatment.A rescue assay was conducted to investigate the cell growth in HepG2 cells by using CCK-8.Results miR-373 expression was up-regulated in both HCC tissues and cell lines.miR-373 expression depicted about 2.94-fold augment in HepG2 cells as compared to normal liver cells control (P <0.01).5-FU treatment led to a significant decrease of miR-373 levels (approximately 50%,P <0.01,48 h) and resulted in a marked increase of PPP6C protein (approximately 2.1-fold,48 h) in HepG2 cells.The overexpression of miR-373 could prevent the impact of 5-FU treatment on cell growth in HepG2 cells and CCK-8 assay showed that HepG2 cell growth was rescued approximately 81% and 84% at 24 h (P < 0.05) and 48 h (P < 0.01),respectively.Conclusion 5-FU can repress endogenous miR-373 level,which activates the expression of downstream targeted gene PPP6C,thereby exerting an inhibitory effect on HepG2 cells.
10.Detection of ESBL-producing clinical isolates of gram negative bacilli and their antibiotic resistance in Shantou
Bin HUANG ; Shengbin ZHANG ; Linhuan HUANG ; Hongjun ZHU ; Zhaohui LIU ; Ziwen ZHAO ; Canmao XIE
Chinese Journal of Primary Medicine and Pharmacy 2011;18(12):1585-1586
Objective To investigate the extended-spectrum beta-lactamases ( ESBLs) producing clinical isolates of gram negative bacilli and their antibiotic resistance in Shantou and to provide suggestions on empirical treatment against the bacteria.Methods A total of 1 445 strains of gram negative bacilli (895 strains of Escherichia coli and 550 strains of Klebsiella pneumonia) were collected and examined for the production of ESBLs and antibacterial susceptibility test by Vitek-2.Results There were 69.4% of escherichia coli and 33.6% of klebsiella pneumonia producing ESBLs.The resistance rate of the ESBLs-producing strains to penicillins,cephalosporins and monocyclic beta-lactam antibiotics were very high.The ESBLs-producing strains were multidrug resistant and the resistance rates were higher than that of the non-ESBLs-producing strains.Both ESBLs-producing and non-ESBLs-producing strains were susceptible to Imipenem.Conclusion The incidence of ESBLs-producing strains was high in gram negative bacilli in Shantou.The resistance rates of the ESBLs-producing strains were higher than that of the non-ESBLs-producing strains and they expressed multiple drug resistance phenotypes.Imipenem was the best drug in the treatment of infections caused by ESBLs-producing strains.