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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 (P0.05). 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.
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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.
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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%) (P0.05). 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.
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<p><b>OBJECTIVE</b>The 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.</p><p><b>METHODS</b>Five 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.</p><p><b>RESULTS</b>Of 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.</p><p><b>CONCLUSIONS</b>In 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.</p>
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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 , EpidemiologyABSTRACT
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.
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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 P0.05). 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.
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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.
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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.
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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.
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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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Objective To explore the clinicopathological characteristics of hereditary ovarian cancer syndrome(HOCS). Methods From Jan. 2000 to Jan. 2007, among 580 cases of primary ovarian cancer, 42 cases(herediatary group),who had a positive family history of ovarian cancer and met the diagnostic criteria of HOCS, were analyzed retrospectively. One hundred cases without a family history of ovarian cancer were enrolled randomizely as control group (sporadic group). Results The incidence of HOCS was 7.2% (42/580). Forty-two cases associated tumors affected at least 2 successive generations in 31 families and affected 1 generation in 8 families. Eighty-seven percent (27/31)was from maternal lineage, while 13% (4/31)from paternal lineage. Earlier age of onset was significantly difference between two groups[(49±10) years vs. (55±10) years, P<0.05]. There were 90% belong to serous adenocarcinoma in the herediatary group, while 84% in the sporadic group. There was statistical difference in the proportion of mucinous adenocarcinoma (0 vs. 11%, P<0.05). The most common clinical manifestations were abdominal distention and anorexia (64% vs. 70%, P>0.05), International Federational of Gynecology Obstetrics(FIGO)stage Ⅲ (62% vs. 63%, P>0.05) between two groups. Fourteen cases (33%,14/42) were previously untreated in the herediatary group, while 40 cases (40%, 40/100) in the sporadic group. There were 15 cases (36%, 15/42) underwent secondary surgery and 15 cases (36%, 15/42) underwent third surgery or more in berediatary group, while 50 cases (50%, 50/100) and 27 cases(27%, 27/100) in the sporadic group. The mean number of ehemotberapy cycles received in two groups was 13.3 and 11.8 (P>0.05). The 3-year and 5-year survival rate in herediatary group were 73.6% and 54.9% respectively, compared with 47.4% and 21.2% (P<0.05) in sporadic group. Conclusion Hereditary ovarian cancer mostly from maternal lineage are featuring in early age of onset, serous adenocarcinoma, advanced stage (stage Ⅲ), and better prognosis after the comprehensive treated by cytoreductive surgery plus with chemotherapy.
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Objective To study the clinical value of operation in advanced endometrial carcinoma.Methods A retrospective study was carried out in 78 patients with advanced endometrial carcinoma received operation in our hospital from Jan.1,1997 to Dec.31,2007.The basic operation procedures were included total hysterectomy,adnexectomy,omentectomy,appendectomy and resection of metastatic lesions located in abdomino-pelvic cavity.The criteria of satisfied operation Was considered that the sizes of residual leision was smaller than or equal to 2 cm,which Was used to evaluate the effect of operation.The prognostic factors were also analyzed.Results Among the 78 cases,the rate of ideal cytoreductive surgery was 83%(65/78),included 23 cases of no residual leisions,42 cases of residual leisions size smaller than or equal to 2 cm,while 13 cases of residual leisions size larger than 2 cm.The Survival rate of 1-year,3-year and 5-year were 91%(61/67),55%(28/51)and 28%(10/36),respectively.The results by single factor analysis shown that the survival rate were correlated with prognostic factors included extent of disease,ascites,size of residual lesions,circles of chemotherapy.Conclusion It is important value for advanced endometrial carcinoma to ideal cytoredutive surgery followed by combined chemotherapy,while radiotherapy no further therapeutic effects.
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Objective To establish nude mice xenograft tumor models of human endometrial carcinoma for basic and clinical study. Methods Fourteen samples of human endometrial carcinoma were subcutaneously heterotransplanted to nude mice (BALB/C, nu/nu),3～4 mice were transplanted for every sample. Results The initial take rate was 42.8%,then it increased to 100.0% after the 5th passage. Five of 14 samples were transplanted for 48～63 passages.The characteristics of histology,ultrastructure and chromosome were identical to those of human donour tumors. The DNA ploidy was consistent for SL-1,SL-2 and SL-3,but changed for SL-4 and SL-5 by cytometric analysis. The expression of estrogen receptor and progesterone receptor for 5 models was all negative. The expression of p53 was positive for SL-1,SL-2 and SL-4,but negative for SL-3 and SL-5.The expression of c-erbB-2 was positive for SL-1,SL-2 and SL-4,negative for SL-3 and SL-5.The expression of p16 was positive for SL-2 and SL-3,negative for SL-1,SL-4 and SL-5. Conclusions Five nude mice xenograft tumor models of human endometrial carcinoma were established successfully. It will be helpful for the basic and clinical study of human endometrial carcinoma.