1.Expression of Jagged1 mRNA in human epithelial ovarian carcinoma tissues and effect of RNA interference of Jagged1 on growth of xenograft in nude mice
Guoyan LIU ; Zhihui GAO ; Li LI ; Tingting SONG ; Xiugui SHENG
Chinese Journal of Obstetrics and Gynecology 2016;51(6):448-453
Objective To investigate the expression of Jagged1 in human epithelial ovarian carcinoma tissues and the effect of Jagged1 on growth of xenograft in nude mice. Methods (1) Forty-eight cases of ovarian cancer and 30 cases of patients with benign epithelial ovarian tumor in the Henan Province Xinxiang Central Hospital during Feb. 2011 to Mar. 2014 were enrolled in this study. The mRNA expression of Jagged1, Notch1 and the downstream target genes Hes1, Hey1 were analyzed by using realtime PCR method. (2) The ovarian cancer xenograft models in nude mice were constructed by injecting SKOV3 cells in axillary subcutaneouswere. The nude mice were randomly divided into Jagged1 interference group, blank plasmid group and control group. Each group had 10 mice. They were transfected with pcDNA3.1(+)-siRNA-Jagged1, blank plasmid pDC3.1 and phosphate buffer, respectively. The tumor volumes and tumor masses were measured 14 days after transfection and the inhibition rate was calculated. The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues after transfection in each group was detected by using realtime PCR technique and the relative protein expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues was detected by utilizing western blot method. Results (1) The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in ovarian cancer tissues were higher than benign ovarian tumor tissues, the differences were statistically significant (P<0.01). (2) The tumor volume was (491 ± 68) mm3 and tumor mass was (2.6±0.4) g in Jagged1 interference group, which were significantly lower than that in the blank plasmid group [(842 ± 88) mm3 and (4.4 ± 0.8) g, respectively] and that in the control group [(851 ± 90) mm3 and (4.5 ± 0.9) g, respectively;P<0.05], the tumor inhibition rate was 42.2% in Jagged1 interference group, which was significantly higher than that in the blank plasmid group and that in the control group (2.2%and 0, respectively), the differences were statistically significant (P<0.05). The relative mRNA and protein expression of Jagged1, Hes1 and Hey1 in xenograft tissues of nude micein Jagged1 interference group were lower than that in the other two groups, the differences were statistically significant (P<0.05). There were no differences of relative mRNA and protein expression of Notch1 in xenograft tissues of nude mice among the three groups (P>0.05). Conclusions Jagged1 is highly expressed in epithelial ovarian carcinoma. Jagged1 gene interference in xenograft tumor can inhibit ovarian cancer cell growth and improve tumor suppressor rate, which probably play roles by inhibiting Notch1 signaling pathway.
2.The related factors of endometrial cancer induced by obesity
Journal of International Oncology 2015;(10):789-792
Large amounts of clinical studies and epidemiological data have confirmed that obesity is closely related to the development and progression of endometrial cancer.The mechanism of the endometrial cancer may be involved estrogen,insulin,insulin-like growth factor,leptin,adiponectin,resistin fat factor, inflammatory factors and so on.
3.Incidence and influencing factors of distal external iliac lymph node metastasis in early cervical cancer.
Yueju YIN ; Xiugui SHENG ; Xinglan LI ; Dapeng LI ; Xiaoyun HAN ; Xiaoling ZHANG ; Tingting ZHANG
Chinese Journal of Oncology 2014;36(6):457-460
OBJECTIVEThe distal external iliac lymph nodes are located along the external iliac artery between the deep circumflex iliac vein and the inguinal canal. Our study aimed to investigate the incidence of metastasis in distal external iliac lymph nodes and its association with clinicopathological factors in patients with early stage cervical cancer, and to determine the role of distal external iliac lymph nodes dissection in the surgery.
METHODSFive hundred and twenty-four patients with early stage cervical cancer underwent radical hysterectomy and bilateral pelvic lymphadenectomy in the Shandong Province Cancer Hospital between June 1995 and December 2011, and their clinicopathological features were analyzed retrospectively.
RESULTSOf the 524 patients, 124 (23.7%) had pelvic lymph node metastasis. The metastasis rates were 16.2% (85 of 524 patients) in the obturator lymph nodes, 12.2% (64 of 524 patients) in the internal and external iliac lymph nodes, 2.9% (15 of 524 patients) in the common iliac lymph nodes, 2.1% (11 of 524 patients) in the distal external iliac lymph nodes, and 1.7% (9 of 524 patients) in the para-aortic nodes. The incidence of isolated positive distal external iliac lymph nodes was 0.2%. Univariate analysis showed that lymphovascular space invasion, pelvic lymph node metastases (excluding distal external iliac lymph nodes) were significantly associated with distal external iliac lymph node metastasis (P < 0.05). Logistic regression analysis showed that pelvic lymph node metastasis (excluding distal external iliac lymph nodes) was the independent risk factor for metastasis to distal external iliac lymph nodes.
CONCLUSIONSIn early stage cervical cancer, distal external iliac lymph node metastasis is rare, especially in cases with stage IA or without pelvic lymph node metastasis. Less extensive pelvic lymphadenectomy may be considered in these patients in order to reduce operative complications and improve patients' quality of life. The deep circumflex iliac vein may be an appropriate landmark for the caudal limit of external iliac lymphadenectomy. However, if pelvic lymph node metastasis (excluding distal external iliac lymph nodes) is found by intraoperative rapid pathological diagnosis, systematic pelvic lymphadenectomy including removal of the distal external iliac lymph nodes should be performed in order to reduce the risk of distant metastasis.
Female ; Humans ; Hysterectomy ; Iliac Artery ; Iliac Vein ; Incidence ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; diagnosis ; Neoplasm Staging ; Neoplasms, Second Primary ; Pelvis ; Quality of Life ; Retrospective Studies ; Uterine Cervical Neoplasms ; epidemiology
4.No postoperative survival benefit in concurrent chemoradiation treated patients with low-risk early-stage cervical squamous cell carcinoma
Hao YU ; Linlin ZHANG ; Xuelian DU ; Xiugui SHENG
Chinese Journal of Clinical Oncology 2014;46(4):242-245
Objective:The benefits of postoperative adjuvant therapy method for low-risk early-stage cervical squamous cell carcinoma were investigated. Methods:A total of 133 patients with low-risk early-stage cervical squamous cell carcinoma were treated at Shandong Cancer Hospital&Institute from February 2008 to March 2012. All patients received adjuvant therapy:42 were treated with pelvic ra-diotherapy (RT), 47 were treated with adjuvant chemotherapy (CT)+intracavitary radiotherapy (ICRT), and 44 were treated with concurrent chemoradiation (CCRT). Disease-free survival (DFS) and complications of the therapy were evaluated. Results:No significant differences in DFS were observed in the patients treated with RT, CT+ICRT, and CCRT (P>0.05), and the three-year DFS rates were 94.0%, 93.4%, and 97.6%, respectively. The frequencies of grade III to IV acute toxicities were significantly higher in patients treated with CCRT (34.1%) than in those treated with RT (9.5%) or CT+ICRT (16.7%) (P<0.05). No statistically significant difference was observed between the RT group and the CT+ICRT group (P>0.05). Grade I to II late toxicity was significantly more frequent in the CCRT (25%) and RT (19.0%) groups compared with the CT+ICRT group (4.3%) (P>0.05), but no statistically significant differences were observed between the CCRT and the RT groups (P>0.05). Conclusion:CT+ICRT or RT has a three-year DFS rate equivalent to CCRT but with fewer therapy com-plications for low-risk early-stage cervical squamous cell carcinoma.
5.Clinical observation of conformal radiotherapy with topotecan che-motherapy on patients with platinum-resistant recurrent ovarian cancer
Ping WEI ; Xiugui SHENG ; Changping SHAN ; Xiaoyun HAN
Chinese Journal of Clinical Oncology 2013;(13):779-783
Objective: This study aims to observe the efficacy and toxicity of three-dimensional conformal radiotherapy (3DCRT) combined with weekly topotecan hydrochloride (Top-Hyd) chemotherapy on patients with platinum-resistant recurrent ovarian cancer. Methods: Medical data of 42 patients with platinum-resistant recurrent ovarian cancer between June 2008 and June 2011 were retrospectively reviewed. OAOf these 42 patients, 22 underwent 3DCRT combined with weekly Top–Hyd chemotherapy, whereas the remaining 20 underwent simple chemotherapy (SCT). Doses from 45 Gy to 65 Gy were planned to deliver fractions ranging from 1.8 Gy to 2 Gy to patient abdomen and pelvis. Top–Hyd (4 mg/m2) was aintravenously administered 1, 8, and 15 days from radiotherapy, with a cycle of 28 days. Results: By December 31, 2011, the median follow-up time for the 3DRT group was 18.5 months, whereas that for the SCT group was 10.8 months . The total response rate and the clinical beneficial rate were significantly higher in the 3DCRT group than in the SCT group (total response rate, 42.1% vs. 11.1%; clinical beneficial rate, 68.4% vs 22.2% at P< 0.05). The median of progression-free survival time was 9.8 months for the 3DCRT group and 6.6 months for the SCT group. The median total survival time was 19.7 months in the 3DCRT group, and 12.5 months in the SCT group. Significant differences between the 2 groups were indicated (P<0.001). No significant difference in overall toxicity was indicated between the two groups (P>0.05). Conclusion: The combined 3DCRT treatment and Top-Hyd chemotherapy results in enhanced response and tolerable toxicity compared with SCT in patients with recurrent ovarian cancer infiltrating the pelvic and retroperitoneal lymph node metastasis. So, it may be the salvage regimen for recurrent ovarian cancer and provide a new therapeutic option for the consolidation treatment of advanced ovarian carcinoma.
6.Clinical study of sentinel lymph node detection guided radical abdominal trachelectomy
Xuelian DU ; Xiugui SHENG ; Yan ZHONG ; Dapeng LI ; Naifu LIU
Chinese Journal of Obstetrics and Gynecology 2013;(5):348-351
Objective To evaluate the clinical value of sentinel lymph nodes (SLN) in predicting pelvic lymph node status for early cervical squamous cell carcinoma,and approach the clinical significance of SLN detection for guiding radical abdominal trachelectomy (RAT).Outcomes of follow up and fertility were also observed.Methods A total of 31 patients with stage Ⅰ a2-Ⅰ bl squamous cell carcinoma planned to be given RAT and pelvic lymphadenectomy were enrolled.99mTe-labeled phytate was injected before surgery.Intraoperatively,SLN were identified,excised,and submitted to fast frozen section.Systematic bilateral pelvic lymphadenectomy was performed,and then RAT was performed in patients with negative SLN.All nodes were sent for routine pathological examination and immunostained with anti-cytokeratin antibody to detect micrometastases.Results SLN were detected in all patients (100%,31/31).A total of 109 SLN were identified with a mean number of 3.5 per patient.Of these,SLN of 2 patients were positive on frozen sections and proved to be metastasis by final pathologic examination and quitted the RAT.No missed micrometastasis was found using immunohistochemical staining in SLN and other lymph nodes using histologically node-negative cases.No false negative cases was found and the negative value was 100% (31/31).The sensitivity,accuracy,and false negative rates were 100%,100%,and 0,respectively.Perioperative complications occured in 5 patients including 2 cases of bladder injury and 3 cases of uterine artery injury.No relapses occurred during follow-up.Five of 19 patients with procreative desire conceived pregnancies (4 spontaneous abortion and 1 premature birth) after surgery.Conclusions The identification of SLN using 99mTc-labeled phytate could predict the pelvic lymph node status in early stage cervical cancer.Under the guidance of SLN detection,RAT is a feasible operative modality with well prognosis and low complications for young patients who desire to preserve reproductive function.
7.Angiogenesis related gene expression profiles of human endometrial endothelial cells isolated from tissue of endometrial cancer
Xuelian DU ; Xiugui SHENG ; Chunxiao YAN ; Ting LIU ; Cong WANG ; Quqing SONG ; Qingshui LI
Chinese Journal of Obstetrics and Gynecology 2012;47(10):756-763
Objective To identify and verify the different genes expression pattern between human endometrial endothelial cells (HEEC) isolated from endometrial cancer and normal endometrium.Methods Endothelial cells were isolated from 5 patients with endometrial cancer (endometrial cancer group 1) and 5 patients with normal endometria tissue (control group 1) admitted from June to November 2007 in Shandong Cancer Hospital.Global expression patterns of endothelial cells were examined using oligonucleotide microarrays.Tissues from 36 patients with endometrial cancer(endometrial cancer group 2) and 10 normal endometrial tissues (control group 2) admitted from January 2007 to April 2008 were selected to verify the expression of different genes,in which up-regulated genes including ESM1,MMP-10,SPP1 and HMGB1 were tested by quantitative real-time PCR and immunohistochemistry.Results Microarray analyses revealed 317 genes that exhibited > 2-fold or < 0.5 differences were identified (including 191 genes up-regulated and 126 down-regulated).Pathway analysis showed that these genes involved cell cycle,cell adhesion molecules,and extracellular matrix-receptor interaction were obviously predominant.Of them,97 up-regulated genes and 44 down-regulated genes were related to angiogenesis.The mRNA expression of ESM1,MMP-10,SPP1 and HMGB1 in endometrial cancer group 2 were 0.898、3.890、1.433 and 1.881,respectively.Positive expression of SPP1,MMP-10,ESM1 and HMGB1 was observed in endometrial cancer group 2.However,the SPP1,ESM1 and HMGB1 was negative expressed in control group 2.Conclusion It shows that there are the different angiogenesis related genes between endometrial cancer and normal endothelium,which will provide insights into the anti-angiogenesis therapy for endometrial cancers.
8.Progress of the angiogenesis correlation factors for endometrial carcinoma
Journal of International Oncology 2012;39(3):230-233
Angiogenesis is closely related to the occurrence,development,invasion and metastasis of endometrial carcinoma.In recent years,a large number of researches on the angiogenesis correlation factors for endometrial carcinoma have been carried out It is shown that endometrial carcinoma angiogenesis is a complex process with many factors involved in.
9.Gemcitabine based combination chemotherapy, a new salvage regimen for recurrent platinum resistant epithelial ovarian cancer
Ping CHU ; Chunhua LU ; Xiugui SHENG ; Caixia ZHOU ; Dapeng LI ; Xuelian DU ; Naifu LIU
Chinese Journal of Obstetrics and Gynecology 2010;45(11):808-812
Objective To evaluate the efficacy and toxicities of gemcitabine combined with ifosfamide and anthracycline chemotherapy for recurrent platinum resistant ovarian epithelial cancer.Methods Gemcitabine 800 mg/m2 ( day 1, 8 ), ifosfamide 1.5 g/m2 ( day 1 - 3 ), adriamycin 40 mg/m2 or epirubicin 60 mg/m2 (day 1 ) or mitoxantrone 10 mg/m2 (day 1, 8 ) were used in recurrent platinum resistant/refractory ovarian cancer patients, the cycle was repeated at interval of 21 to 28 days.Results A total of 60 patients received 172 cycles combined chemotherapy.There were no one cases complete response, while partial response 22 (37%, 22/60), stable 23 (38%, 23/60) and progression 15 (25%,15/60) were observed, with clinical benefit rate 75% (45/60).The median time of progression-free survival was 7 months, and the median overall survival time was 20 months.The main side effect was hematologic toxicity with leukopenia rate of 82% (49/60), among which Ⅲ - Ⅳ accounted for 31%(15/49).Digestive reaction was all in Ⅰ - Ⅱ , accounted for 42% (25/60).Conclusion The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer.
10.Observation of hyperfractional integrated intracavitary brachytherapy on efficacy and complications in patients with middle and advanced squamous cell carcinoma of the cervix
Chunxia PAN ; Xiugui SHENG ; Xiaoling ZHANG ; Xuelian DU ; Qingshui LI ; Zhifang MA ; Huaqin MIAO ; Yuebing MA ; Naifu LIU
Chinese Journal of Radiological Medicine and Protection 2010;30(3):324-326
Objective To observe and cpmpare the efficacy and complications of hyperfractional integrated intraeavitary brachtherapy in middle-advanced squamous-cell carcinoma with the traditionsl brachytherapy.Methods In the observed group,328 patients with cervical cancer received hypeffractional integrated intracavitary after loading therapy between Jan 2004 and Jan 2005 were selected.The dose of point A was 2.5 Gy-3.0 Gy/fraction,2 fractions per week,and the total dose of reference point A was 49.8 Gy in stage Ⅱ b,52.6 Gy in stage in Ⅲb.In the control group,331 cases treated with traditional aflerloading brachytherapy between Jan 2002 and Dec 2003 were selected.The dose of point A was 5.0~7.0 Gy/fraction,1 fraction per week,and the total dose of point A was 50.1 Gy in stage Ⅱb,53.5 Gy in stage Ⅲb.In vitro irradiation began at the same time with the intracavitary brachytherapy.The whole pelvic was irradiated with 15 MV X-rays.Results In the observed group,the recent control rate of stage Ⅱb was 97.2%(104/107),94.1%(208/221)for stage Ⅲb.The 3-year survival rate was 80.5%(264/328).and the 5-year survival rate was 68.6%(225/328).The complication rate was 5.2%(17/328)for cystitis, 14.6%(48/328) for proctitis.Out of 331 cases in control group,the recent control rate of stage Ⅱb was 95.4%(103/108),92.8%(207/223)for stage Ⅲb.The 3-year survival rate was 75.2%(249/331),the 5-vear survival rate was 62.5%(207/331).The complication rate was 13.3%(44/331)for cystitis,and 32.3%(107/331)for proctitis.Conclusions Compared with combination of traditional brachytherapy and external radiotherapy,combination of hyperfraetional integrated brachtherapy therapy and external radiotherapy has no significant improvement for recent control rate and long-term survival rate,but could reduce the complication rates of cystitis and proctitis.

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