1.Preoperative blood neutrophil to lymphocyte ratio as an independent prognostic predictor for epithelial ovarian cancer
Chinese Journal of Clinical Oncology 2014;(10):634-638
Objective:This study aims to evaluate the effect of an elevated preoperative neutrophil to lymphocyte ratio (NLR) on outcome after comprehensive staging laparotomy or optimal tumor debulking surgery for epithelial ovarian cancer (EOC) and determine the value of the NLR as an independent prognostic prediction marker. Methods:A total of 80 women with primary EOC and with complete clinical and pathological information documented at the time of surgery were selected for this study. The optimum cut-off value of the preoperative NLR was identified through receiver operator characteristic (ROC) curve, and the patients were then classified into two groups: low and high NLR group. Univariate and multivariate analyses were performed to assess the prognostic effect of the preoperative NLR patients who underwent comprehensive staging laparotomy or optimal tumor debulking surgery. The levels of expression of CD68 were measured through immunohistochemistry. Results:The optimal cut-off value of the NLR was 3.8. The preoperative NLR differed significantly in the FIGO stage between the low NLR group (NLR ≤3.8) and the high NLR group (NLR>3.8), but no discrimination was observed in other parameters. The mean follow-up time was 45 months, and the post-operative 1-and 3-year survival rates were 93.7%and 60.0%, respectively. The preoperative NLR>3.8 and stageⅢ/Ⅳwere all risk factors for poor overall and disease-free survival. Multivariate analysis revealed the patients with high NLR (P<0.05) and stage Ⅲ/Ⅳ (P<0.05) had prognostic significance for poor overall survival. The number of CD68-positive tumor-associated macrophages was significantly higher in the high NLR group than in the low NLR group (54.65 ± 8.78 and 41.78 ± 9.10, respectively; P<0.001). Conclusion: An elevated blood preoperative NLR indicates poor prognosis in patients with EOC. Preoperative NLR may function as an important independent prognostic factor for patients with EOC.
2.Correlation of lymphatic vessel density with a high mobility group Box-1 protein and tumor-associated macrophages in cervical carci-noma
Chinese Journal of Clinical Oncology 2014;46(4):222-226
Objective: To detect the correlation of lymphatic vessel density (LVD) with a high mobility group box-1 Protein (HMGB1) and tumor-associated macrophages (TAMs) in cervical carcinoma and the effect on prognosis. Methods:Immunohistochem-istry was applied to detect HMGB1, CD68, and D2-40 expressions in cervical squamous cell carcinoma in 93 cases. t test,χ2 test, Spear-man rank correlation analysis, Kaplan-Meier method, and Cox regression were performed to analyze the expression levels, correlation, and prognosis. Results: HMGB1 protein, CD68, and D2-40 were highly expressed in CSCC. As HMGB1 and TAM expressions in-creased, lymphatic vessel density increased. As HMGB1 and TAM expressions decreased, lymphatic vessel density decreased. Positive correlations were also found between the HMGB1 protein, TAM content, and LVD. In the group with low HMGB1 and TAM expres-sions, the survival time of the group with a high LVD expression was significantly lower than that of the group with a low LVD expres-sion. A multivariate Cox regression model showed that HMGB1 and lymph node metastasis were independent prognostic factors. TAMs and LVD were not independent prognostic factors. Conclusion:HMGB1 proteins and TAMs were highly expressed in CSCC. Patients who exhibit increased HMGB1 expression or increased TAM count consequently show enhanced LVD expressions, increased lymph node metastasis, and poor prognosis.
3.Research progress in molecular targeted therapy for gynecological cancer
Chinese Journal of Clinical Oncology 2013;(21):1341-1343
Molecular targeted therapy (MTT) refers to a new therapy designed to interfere with a specific molecular target or signaling pathway that may have a significant influence in tumor growth or progression. MTT can inhibit cell proliferation and induce apoptosis by specific interventions in the signaling pathways of tumor cells. MTT exhibits potential as an effective treatment against cancer. This approach can improve the ability to kill cancer cells and reduce damage to normal tissues. MTT has gradually been used clinically in treating cancer and shown advantages over traditional methods. This paper reviews research progress in this targeted therapy to treat gynecological cancer.
4.The clinical feature analysis of acute ischemic bowl disease
Wei QUAN ; Dening FANG ; Hao JIA ; Zhe QUAN
Chinese Journal of Primary Medicine and Pharmacy 2013;20(2):227-229,后插4
Objective To explore the clinical features of acute ischemic bowl disease in order to guide clinical treatment and avoid the severe complications.Methods 25 cases diagnosed as ischemic bowl disease were enrolled retrospectivly analysed the clinical features of symptoms,signs,laboratory test results,abbominal enhanced CT and CTA,enteroscopes of these patients.Results Among the 25 cases accorrding to first presentation of first contacts,the cardinal symptoms were spectively abdomial pain 20 (80%),abdomial distension 16 (64%),diarrhea 18 (72%),vomiting 13 (52%),hemafecia 6 (24%),bloody purulent stool 8 (32%),watery stool 7 (28%),fever 11 (44%) and physical signs were spectively local tenderness 12(48%),peritonitis sign 9(36%),active bowl sound 7 (28%),weak or disappeared bowl sound 5 (20%).22 of 25 cases were positive with ocult blood test of stool and 23 of 25 cases showed elevated D-dimer concentration(more than 500μg/L) within 24 hours after first contacts.All the 25 cases were dignosed with CTA and 1 case was performed with enteroscopy which showed that local mucosa of sigmoid colon was congestive,edema,submucosal extravasated blood and some part was bleeding.Conclusion The patient with high risk factors who suffered from the tetralogy of severe abdominal pain,intense evacuation symptoms,highly elevated D-dimer concentration and positive ocult blood test,is stongly suggested to be a ischemic bowl disease and should be performed the abdomial CTA or DSA examination in time to avoid missing the golden opportunity to cure.
5.Construction of CDK7 siRNA expression vector and its effect on cisplatin sensitivity of endometrial carcinoma cells
Wenxin LIU ; Ying CHEN ; Quan HAO
Chinese Journal of Clinical Oncology 2013;(15):893-897
Objective:This study was aimed to investigate the influence of CDK7 siRNA on the sensitivity of endometrial carci-noma cell line HEC-1-A to cisplatin (DDP)-based chemotherapy. Methods:Different CDK7 siRNA fragments were synthesized based on the designs of the CDK gene sequence and were transfected into HEC-1-A. Real time reverse transcription polymerase chain reac-tion (RT-PCR) and Western blot analysis were employed to demonstrate the effects of transfection. The best CDK7 siRNA was chosen to specifically silence CDK7 expression in HEC-1-A.The sensitivity of the cells to DDP therapy before and after transfection was deter-mined by methyl thiazol tetrazolium (MTT) cytotoxicity assay, flow cytometry, and Hoechst/PI double-staining fluorescence microsco-py. Results:A total of four different CDK7 siRNA segments were designed and successfully transfected into HEC-1-A cells. The inter-ference effect in each group was confirmed by real time RT-PCR and Western blot assays. CDK7-423 was determined as the best per-forming CDK7 siRNA (over 70%) to transfect into HEC-1-A cells. MTT cytotoxicity test showed that IC50 of DDP decreased to a range from 45.122 μg/mL and 3.200 μg/mL after inhibition of CDK7 expression. DDP toxicity to the endometrial carcinoma cells sig-nificantly increased (P<0.05). Flow cytometry revealed that the average cell apoptosis rate significantly increased after the inhibition of CDK7 expression (11.66%to 37.57%, P<0.05). Similar results were observed using Hoechst/PI double-staining fluorescence microsco-py, and the number of apoptotic corpuscle demonstrated an apparent increase in the low CDK7-expressing group compared with the pa-rental cells. Conclusion:After the downregulation of CDK7 expression by CDK7 siRNA transfection, DDP chemotherapy sensitivity and apoptosis of endometrial carcinoma cells significantly increased. Further research is anticipated on the use of CDK7 as a new treat-ment target for endometrial carcinoma.
6.The clone and identification of cDNA fragments of relevant gene of human bladder cancer
Chinese Journal of Urology 2001;0(10):-
Objective To isolate and identificate a specific new gene highly related to human bladder cancer and to investigate the carcinogenesis mechanism and genetic susceptibility. Methods Normal bladder epithelia and cancer tissue collected from 8 cases of primary bladder transitional cell carcinoma were studied using the high performance?sensitive technique of mRNA differential display.The differential fragments were found by comparing with genetic expression. 6 of them were reamplificated?cloned?sequenced,and performed the autoploidy index in the public database of genbank. Results (1)37 differential fragments have been isolated.36 of which are expressed or highly expressed in cancer tissues,but not so or lowly expressed in normal tissues;while it has been expressed in 1 normal tissue but not in the cancer tissue.(2)Results of indexing:1 is homologous to TBX3 (T box gene),autoploidy 99%.1 is homologous to cl.Ca4 gene (member 4 of Calcium activated chloride channel gene family), autoploidy 99%.1 is homologous to Cu,Zn SOD gene (Cu,Zn superoxide dismutase),99%.The remaining fragments are not homologous to unknown sequences in the public database of genbank,assigned as YHHQ1,XHL,LHX. Conclusions (1)It is verified at genetic level the relation between the conment's increasing of Cu,Zn SOD in bladder cancer derived tissue and the occurrence,advance of bladder cancer.(2)The relation between TBX3,cl.Ca4 gene and human carcinoma has been observed.(3)YHHQ1 may be the new candidate of anti oncogene related to bladder cancer.XHL and LHX may be the new candidates of oncogene related to bladder cancer.
7.High-mobility group protein B1 (HMGB1) and its potential in diagnosis and treatment of ovarian cancer
Yingchun LI ; Jing TIAN ; Hairong YAO ; Wenqi ZHANG ; Quan HAO
Chinese Journal of Clinical Oncology 2014;(7):425-429
Objective:The objective of this research is to study the serum level of the high-mobility group protein B1 (HMGB1) in human ovarian tumor (OvCa) and in a healthy control. This study also aims to identify different HMGB1 levels before and after sur-gery and to explore the inhibitory effect of HMGB1 gene silencing in the proliferation and invasion ability of OvCa. Methods: En-zyme-linked immunosorbent assay was used to measure the serum level of HMGB1 in OvCa patients and healthy subjects. Lentivirus vector with HMGB1 shRNA was constructed and used to infect OvCa cells. The expressions of HMGB1 mRNA and protein were test-ed by real-time PCR and Western blot. Cell proliferation was detected using the Cell Counting Kit-8 assay, whereas cell invasion and migration were detected by Transwell assay. Results:The serum level of HMGB1 was more elevated in patients with malignant diseas-es compared with individuals with benign diseases and the control groups. In the malignant group, the serum level of HMGB1 de-creased noticeably after therapy. Down-regulation of HMGB1 expression resulted in the inhibition of the biological behavior and metas-tasis of ovarian cancer cells. Conclusion: HMGB1 is closely associated with clinicopathologic features of OvCa. Knockdown of HMGB1 expression can significantly inhibit cell proliferation, cell migration, and cell invasion of OvCa. These findings indicate that HMGB1 can function as a therapeutic target for ovarian neoplasm in the future.
8.Immuno-suppression and mechanism of CD4+CD25+T cells in ascites of ovarian cancer patients
Hairong YAO ; Jing TIAN ; Yingchun LI ; Wenqi ZHANG ; Quan HAO
Chinese Journal of Clinical Oncology 2014;(9):560-565
Objective: This research explores the relationship between the immuno-suppression function of regulatory T cells (Treg) in the ascites of ovarian cancer (OC) patients, the clinico-pathologic features of these patients, and the correlation of the function of Treg with initial treatment and relapse status of the patients to further investigate the specific mechanism of immuno-regulatory func-tion of CD4+ CD25+ Treg in the ascites of OC. Methods: Immuno-magnetic activated cell sorting (MACS) was conducted to sort CD4+CD25+Treg and autologous CD4+CD25-Treg from the ascites of 28 OC patients. Carboxyfluorescein-diacetate succinimidyl ester (CFSE) was used to label the autologous CD4+CD25-Treg. These labeled cells were then used as controls and co-cultured with autologous CD4+CD25+Treg at the ratio of 1∶1 or 1∶2. The mean inhibition ratio of Treg in specimens to the proliferation of autolo-gous CD4+ CD25-Treg was calculated after the flow cytometry of the CFSE expression and Modfit software analysis of the CD4+CD25-Treg proliferation index (PI) were performed. Anti-IL-10 and/or anti-TGF-β1 antibodies were neutralized to investigate whether the CD4+CD25+Treg-mediated immuno-suppression escaped through the ascites can produce a marked effect by the inhibitory cyto-kine IL-10 or TGF-β1. Results: The mean inhibition ratio of CD4+ CD25- Treg in the ascites of stage Ⅲ to Ⅳ OC patients was (75.72±17.04)%, which is significantly higher than that of stageⅠtoⅡOC patients (59.61±16.97)%;P<0.05. In addition, Treg in the as-cites of OC patients with recurrent disease showed a significantly higher inhibition ratio than that of patients with primary disease;P<0.001. Moreover, Treg in groups added into neutralizing anti-IL-10 and/or anti-TGF-β1 antibodies displayed significantly lower depres-sant effect than the control group;P<0.05. Conclusion:The immuno-suppression of CD4+CD25+Treg in the ascites of OC patients is correlated with the tumor staging and status of the primary or recurrent diseases. Moreover, Treg may indicate a suppressor function by secreting cytokine IL-10 and TGF-β1.
9.Exploration on necessity of establishing global health undergraduate program in China
Hao XIANG ; Qiqiang HE ; Yongyi BI ; Zongfu MAO ; Quan WANG
Chinese Journal of Medical Education Research 2013;(7):649-651
With the rapid development and increased integration of Chinese economy with global economy, China assumes more responsibilities and obligations for global health, resulting in great poten-tial needs for professionals in global health. From the angle of global health talent need , this article deeply illuminated that the global health talent training was helpful to take advantage of international resources to solve the problem of health, serve China's peaceful development strategy, comply with development trend of public health, and remedy limitations of traditional medicine undergraduate. Training undergraduates in global health who are China-specific and global competent is the only way to meet the talent demand of China's future. Multi-level global health education will become an important part of medical education in future in China.
10.Effects of low protein diet with α-keto acid supplement on kidney sclerosis and renin-angiotensin system in renal ablation rats
Quan LONG ; Jing CHEN ; Chuauming HAO ; Shantan LIN ; Yong GU
Chinese Journal of Nephrology 2011;27(6):428-434
Objective To observe the influence of low protein diet with α-keto acid on kidney sclerosis and renin-angiotensin system in renal ablation rats. Methods Chronic renal failure rat model was established by renal ablation in 30 male SD rats,then the animals were randomly assigned to the following diet groups:normal protein group (NPD:18%casein protein),low protein group (LPD:6%casein protein) and supplemented low protein group (LK:5%casein protein+1%α-keto acids).Ten male SD sham-operated rats received 18%casein protein as control.All the rats were killed at the end of the 12th week.Pathologic changes were assessed by PAS staining.Ang II in homogenate and plasma were measured by radioimmunoassay and ELISA respectively.Immunohistochemistry and Western blotting were used to detect the protein expression of TGF-β1,renin and AT1R.Real-time PCR was used to detect the gene expression of renin and ATla,the main subtype of AT1 receptor. Results Body weight,total protein and serum albumin had not significant difference among the four groups(all P>0.05).Serum creatinine and proteinuria of nephrectomized rats were significantly higher compared to the control group (all P<0.05).Proteinuria of the LK group was lower than that of NPD and LPD groups (all P<0.05).Pathological results indicated fibrosis indices were significantly improved after LPD and LK intervention.Expressions of renin,Ang II and AT1R in LK group were significantly lower than those in NPD group (all P<0.05). Conclusions Low protein diet with α-keto acids supplement therapy exhibits renal protective effects of reducing urine protein excretion and improving renal fibrosis,which might be related to the attenuation of local renin-angiotensin system in activity nephrectomized rats.