LncRNA IDH1-AS1 sponges miR-518c-5p to suppress proliferation of epithelial ovarian cancer cell by targeting RMB47

Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.

Adenocarcinoma of sigmoid colon with metastasis to an ovarian mature teratoma: A case report

BACKGROUND Colorectal cancer ranks third in global cancer-related mortality,often due to metastases to liver and lungs.Ovarian metastases are less common,accounting for 3.6%to 7.4%of cases.In contrast,mature ovarian teratomas are frequently benign.Tumor-to-tumor metastasis is a rare phenomenon,with a limited number of documented cases.Three cases of mature ovarian teratomas metastasizing from different cancers have been reported.This report focuses on a case of tumor-totumor metastasis from sigmoid colon adenocarcinoma to a mature ovarian teratoma.CASE SUMMARY A 41-year-old Taiwan residents woman with no known systemic diseases presented with lower back pain,which led to imaging revealing malignant lesions in the spine,pelvis,liver,and multiple lung metastases.She was diagnosed with sigmoid colon adenocarcinoma with metastases to the liver,lung,bone,and a left ovarian teratoma.Treatment involved radiotherapy and chemotherapy,resulting in regression of the primary tumor and stable lung and liver lesions.Due to abdominal symptoms,she underwent exploratory surgery,unveiling a mature teratoma in the left ovary with signs of metastatic adenocarcinoma.CONCLUSION Consider resecting mature ovarian teratomas with concurrent colorectal adenocarcinoma to prevent tumor-to-tumor metastasis.

Chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 correlate with lymph node metastasis in epithelial ovarian carcinoma

Recent evidence suggests that the chemokine axis of CXC chemokine ligand-12 and its receptor CXC chemokine receptor-4(CXCL12/CXCR4) is highly expressed in gynecological tumors and the axis of CXC chemokine ligand-16 and CXC chemokine receptor-6(CXCL16/CXCR6) is overexpressed in inflammation-associated tumors.This study aimed to determine the relationship between CXCL12/CXCR4,CXCL16/CXCR6 and ovarian carcinoma's clinicopathologic features and prognosis.Accordingly,the expression of these proteins in ovarian tissues was detected by tissue microarray and immunohistochemistry.The expressions of CXCL12/CXCR4 and CXCL16/CXCR6 were significantly higher in epithelial ovarian carcinomas than in normal epithelial ovarian tissues or benign epithelial ovarian tumors.The expression of chemokines CXCL12 and CXCL16 were positively correlated with their receptors CXCR4 and CXCR6 in ovarian carcinoma,respectively(r = 0.300,P < 0.05;r = 0.395,P < 0.05).Moreover,the expression of CXCL12 was related to the occurrence of ascites(χ2 = 4.76,P < 0.05),the expression of CXCR4 was significantly related to lymph node metastasis(χ2 = 4.37,P < 0.05),the expression of CXCR6 was significantly related to lymph node metastasis(χ2 = 7.43,P < 0.05) and histological type(χ2 = 33.48,P < 0.05).In univariate analysis,the expression of CXCR4 and CXCL16 significantly correlated with reduced median survival(χ2 = 4.67,P < 0.05;χ2 = 4.48,P < 0.05).Therefore,we conclude that the chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 may play important roles in the growth,proliferation,invasion,and metastasis of epithelial ovarian carcinoma.

Study on Tumor Angiogenesis in Epithelial Ovarian Carcinoma

To investigate tumor angiogenesis in benign, borderline and malignant epithelial ovarian tumors and its relation with the pathogenesis of ovarian carcinoma, polycolonal antibody directed against human von Willebrand factor (factor Ⅷ ) was used to measure the microvessel density (MVD) in 66 cases (11 benign, 10 borderline, and 45 malignant) of epithelial ovarian tumors by using immunohistochemistry. The results showed that the mean MVD in epithelial ovarian cancer (31. 7 ± 11. 2, 400 × ) was higher than in benign and borderline tumors (16. 7± 6. 3, 20. 7± 8. 8 respectively, P<0. 05). There was no difference in MVDs among those in different tumor grades (P>0. 05). But there was significant difference in MVDs among those in different tumor stages (P< 0. 05). MVD in stage Ⅲ - Ⅳ cancer was higher than that in stage Ⅰ - Ⅱ (P<0. 05). It is concluded that the tumor angiogenesis is an early event in ovarian tumorgenesis. The increased tumor micovessel might be responsible for tumor development.

Oncological and Reproductive Outcomes of Fertility-sparing Surgery in Women with Early-stage Epithelial Ovarian Carcinoma:A Multicenter Retrospective Study

Summary:With delayed childbearing in women,preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma(EOC).Fertility-sparing surgery(FSS)can be considered in patients with early-stage disease in order to preserve fertility and improve quality of life.In order to evaluate oncological safety,attitudes toward childbearing and reproductive outcomes in women with EOC who underwent FSS,this multicenter retrospective study was conducted.Between January 2005 and December 2014,total of 87 young women with FIGO stage I EOC were included,with their clinicopathologic parameters in relation to disease-free survival(DFS)and overall survival(OS)assessed.Attitudes toward childbearing,ovarian function and fertility were studied in women undergoing FSS(n=36).As a result,in contrast to radical sur ery,FSS did not affect prognosis by Kaplan-Meier curves(log-rank test;DFS:P=0.484;OS:P=0.125).However,two of the three recurrence cases and both death cases were in FSS group stage IC.All women undergoing FSS resumed regular menstrual periods after chemotherapy.Only 16(44.44%)had tried to conceive,and 17 pregnancies occurred in 15(93.75%)women.Among 20 women who did not attempt conception,the most common reason was not being married(70%),followed by already having children(15%).In summary,FSS is considered safe in young women with stage IA EOC.Regular menstruation and good obstetric outcomes can be achieved.This study also provides some insight into the attitudes and social factors regarding fertility in EOC patients.

P16 GENE EXPRESSION IN OVARIAN EPITHELIAL CYSTADENOCARCINOMA

P16 gene expression was measured by immnohistochemical method in poor differentiated serous cystadenocarcinoma cell line, xenograft of highly metastasizing human ovarian carcinoma in nude mice and paramn embedded tissues from 69 patients with ovarian carcinoma. The result showed that P16 gene was positive expression in HO-8910 cell of mother line,HO8910PM cell line and xenograft of highly mcatstasizing human ovarian carcinoma in nude mice. However, P16gene in the metastatic cell had a weaker expression. P16gene positive expression were also found in sl cases of 69cases (73.9%) in the ovarian epithelial carcinoma paramn embedded tissues. Comparative studies showed that the positive rate of P16 gene expression markedly reduced with the increase of pathologic grade and clinical stage,metastasis in the lymph node and decrease of 5-year survival (P<0.05, p<0.01).P16 gene is not only a controller of cytokerastic cycle, but also a key member of tumorigenic suppresser:its absence and expression degree are also correlated with the ovarian carcinoma genesis and development,especially with the metastasis of the ovarian cancer.

Surgery in platinum-resistant recurrent epithelial ovarian carcinoma

BACKGROUND Ovarian cancer is one of the three most common malignant tumors of the female reproductive tract and ranks first in terms of mortality among gynecological tumors.Epithelial ovarian carcinoma(EOC)is the most common ovarian malignancy,accounting for 90%of all primary ovarian tumors.The clinical value of cytoreductive surgery in patients with platinum-resistant recurrent EOC remains largely unclear.AIM To evaluate the feasibility of secondary cytoreductive surgery for treating platinum-resistant recurrent EOC.METHODS This was a retrospective study of the clinical data of patients with platinumresistant EOC admitted to the Cancer Hospital of the University of Chinese Academy of Sciences between September 2012 and June 2018.Patient baseline data were obtained from clinical records.Routine follow-up of disease progression was performed as follows.CA125 assessment and physical examination were performed every 3 wk during treatment,including gynecological examination.Imaging assessment was carried out every 12 wk by B-mode ultrasound,computed tomography,or magnetic resonance imaging.The primary outcome was progression-free survival(PFS).Secondary outcomes included overall survival(OS),chemotherapy-free interval(CFI),and complications.Follow-up ended on April 15,2019.RESULTS A total of 38 patients were included.R0 resection was achieved in 25(65.8%) patients and R1/2 in 13 (34.2%). Twenty-five (65.8%) patients required organ resection. Nine(23.7%) patients had operative complications, 36 (94.7%) received chemotherapy, and five (13.2%)had targeted therapy. Median PFS and OS were 10 (95%CI: 8.27-11.73) months and 28 (95%CI:12.75-43.25) months, respectively;median CFI was 9 (95%CI: 8.06-9.94) months. R0 resection andpostoperative chemotherapy significantly prolonged PFS and OS (all P < 0.05), and R0 resectionalso significantly prolonged CFI (P < 0.05). Grade ≥ 3 complications were observed, includingrectovaginal fistula (n = 1), intestinal and urinary fistulas (n = 1), and renal failure-associated death(n = 1). Except for the patient who died after surgery, all other patients with complications weresuccessfully managed. Two patients developed intestinal obstruction and showed improvementafter conservative treatment.CONCLUSIONSecondary cytoreductive surgery is feasible for treating platinum-resistant recurrent EOC. Thesefindings provide important references for the selection of clinical therapeutic regimens.

Primary Ovarian Small Cell Carcinoma of Pulmonary Type: Analysis of 6 Cases and Review of 31 Cases in the Literatures

Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence.The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical,imaging,laboratorical and pathological characteristics of 37 SCCOPT cases,in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases(n=37)was 56.00(range,22-80)years.Almost 80%of them had a stageⅢorⅣtumor.All patients underwent an operation and postoperative chemotherapy.Nevertheless,all cases had a poor prognosis,with a median overall survival time of 12 months.Immunohistochemical y,the SCCOPT of all patients showed positive expressions of epithelial markers,such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2(SOX-2),and negative expressions of estrogen receptor,progesterone receptor,vimentin,Leu-7,and somatostatin receptor 2.The tumor of above 80%cases expressed synaptophysin.Only a few cases expressed neuron-specific enolase,chromogranin A,and thyroid transcription factor-1.Conclusions SCCOPT had a poor prognosis.SOX-2 could be a biomarker to be used to diagnose SCCOPT.

Epithelial Ovarian Cancer Patients and Clinicopathological Features and Survival: A Comparison of Outcomes of Two Age Cohorts in Bangladesh

Objective: This study compared the clinicopathologic characteristics and overall survival of epithelial ovarian carcinoma in women younger versus older than 45 years in Bangladesh. Methods: A retrospective analysis identified 129 epithelial ovarian carcinoma patients who were admitted to the National Institute of Cancer Research and Hospital, in Dhaka, Bangladesh from 2016 through 2017 for surgery. These patients were grouped into two categories: the younger group (≤45 years) and the older group (>45 years). Clinicopathological features of epithelial ovarian carcinoma were analyzed in each age group. Cox proportional hazards model identified factors affecting survival and Kaplan-Meier survival curves with log rank test compared outcomes for each age group. Results: The median age of the 129 women was 46 years (IQR: 38, 56) and median time of follow-up was 9 months (inter-quartile range: 4, 26.5). We found a significant difference in the CA-125 level (p < 0.044), age of menopause (p < 0.001), follow-up duration (p < 0.016), disease outcome (p < 0.005) and histopathological type (p < 0.021) between the two groups. No significant differences were found in breakdown of Federation of Gynecology and Obstetrics (FIGO) stage of the disease. There was a significant difference in overall survival between the patients of two groups (p = 0.021) where there was a higher probability of death among the older cohort. The 5-year overall survival rates for the younger age versus older group were 34.0%, and 11.7% respectively. Independent prognostic factors by univariate analysis for the overall survival were age, FIGO stage, preoperative CA-125 and CEA level. However, when controlling for stage, survival was similar between age cohorts. Conclusions: Our data suggests that women in Bangladesh with epithelial ovarian cancer who are under the age of 45 years have a different clinical profile and better overall survival than women in the older age cohort.

SEVEN CASES OF EPITHELIAL OVARIAN CARCINOMA WITH BRAIN METASTASIS

Objective To summarize the clinical characteristics,treatment,and prognosis of brain metastasis in patients with epithelial ovarian carcinoma.Methods Retrospective analysis was conducted in 7 cases of brain metastases of epithelial ovarian carcinoma from January 1986 to March 2007 in Peking Union Medical College Hospital for summarizing therapy results and prognosis-affecting factors.Results Incidence of brain metastases of epithelial ovarian carcinoma was about 0.66%(7/1055).Serous adenocarcinoma was the predominant pathological type in 4 cases and the subsequent was adenocarcinoma in 3 cases.All the patients were diagnosed at late stage,6 cases with the International Federation of Gynecology and Obstetrics(FIGO)stage IIIc and 1 with FIGO stage IV.The mean duration from diagnosis of ovarian carcinoma to brain metastasis was 32.7±20.0 months(range,23-73 months).Single metastasis focus occurred in 43% of cases and multiple metastases in 57% of cases.Fifty-seven percent of patients presented extracranial metastasis.Serum CA125 played a role in monitoring reoccurrence and brain metastases.The average survival time was about 12 months.Better treatment with prolonged survival could be achieved by combination of operation and chemotherapy or combination of radiotherapy with chemotherapy.Conclusions As a rare condition,brain metastasis of epithelial ovarian carcinoma is rising in incidence with improved treatment of ovarian carcinoma and prolonged survival.However,brain metastasis indicates bad prognosis which can be improved by combined therapy.

Primary ovarian cancer combined with primary fallopian tube cancer:A case report

BACKGROUND Low grade serous carcinoma of the ovary(LGSOC)is a rare type of epithelial ovarian cancer with a low incidence rate.The origin of ovarian cancer has always been a hot topic in gynecological oncology research,and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes.Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system.There are only a few reports in the literature,but the mortality rate is very high.But in clinical practice,fallopian tube cancer is very common,but in most cases,it is classified as ovarian cancer.CASE SUMMARY We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment.The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube.No special treatment was performed after the surgery,and the patient was instructed to undergo regular follow-up without any signs of disease progression.CONCLUSION The prognosis of LGSOC is relatively good,over 80%of patients still experience disease recurrence.

New Progress of CA125 Surveillance in Diagnosis and Treatment of Ovarian Cancer

The fatality rate of ovarian cancer (OC) is the highest, and the 5-year survival rate is only 50.8%. For more than 40 years, CA125 has been the most concerned and widely used biomarker of OC in clinical practice. In recent years, many researchers have proposed a reliable strategy of multiple markers combined with CA125 to screen OC to make up for the lack of accuracy of CA125, redefine the biochemical recurrence threshold of CA125, and use mathematical model scores to provide help for the feasibility of treatment and survival prognosis. To fully understand the role of CA125 in OC screening, initial treatment, and recurrence prediction, and summarize the limitations of CA125, this review has summarized the new progress of CA125 in the diagnosis and treatment of OC in recent years which can also provide a reference for clinicians.

Epithelial ovarian carcinoma in women aged below 30 years

Objective:To study the manifestation,pathohistologic type,stage of disease,treatment andoutcome of epithelial ovarian carcinoma in women under the age of 30 years.Methods:The 21 cases of epithelial ovarian carcinoma in women aged below 30 years betweenJan,1986 and Mar,2002 were analyzed retrospectively.Results:The median age at the time of diagnosis was 24 years(range,16-29 years).All car-cinomas occurred after menarche.The most common symptoms were abdominal pain(50%),fol-lowed by tympanites(25%)and menstrual disorders(19%).The initial diagnosis was usuallymade by physical examination,ultrasonography and serum CA125.The mean maximal tumor di-ameter was 17.6 cm.Ten patients had Stage Ⅰ disease(5 Ⅰa,5 Ⅰc),five had Stage Ⅲ disease,andthe other six were unknown during staging operation.There were nine mucinous tumors,six se-rous tumors.Most tumors were well-differentiated and classified as Grade1 in 11 cases,Grade2 in2 cases,Grade3 in 2 cases,unknown in 6 cases.Optimal and suboptimal cytoreduction wasachieved in 14 patients in primary treatment and 5 in recurrent treatment.8 patients were treatedwith conservative surgery.18 patients were treated with chemotherapy and 7 patients had experi-enced six or more than six courses of chemotherapy.The median follow-up was 50 months(range,2-192 months).There were 6 deaths,2 alive with tumor,11 alive without the disease,2losing follow-up.The 3-year survival rate was 89%,and 5-year survival rate was 76%.Conclusion:Young patients with epithelial ovarian carcinoma appeared to have a less aggres-sive form of the disease and a more favorable prognosis.

Expressions of HLA class Ⅰ and CD80 in human epithelial ovarian carcinomas

Objective:To determine expressions of HLA class I and CD80 in humanepithelial ovarian carcinomas(EOC) and the clinical significance.Methods:Expression of HLA class I was detected by immunohistochemical technique. Expression of CD80 mRNA was examined by reverse transcriptions-polymerase chain reaction(RT-PCR).Results:The positive rate of HLA classⅠ was 59.09%.CD80 mRNA was expressed on 9.09% of all 44 EOC tissues.HLA classⅠ expression rate in stage Ⅲ-Ⅳ was lower than that in stage Ⅰ-Ⅱ;in tumors of node-positive patients was lower than that of node-negative patients(P<0.05).In patiens with tumors expressing HLA class Ⅰ antigens,recurrence rate was lower than that in patients with tumors deficient in HLA class Ⅰ(P<0.01).In four patients with tumors expressing CD80 mRNA,recurrence did not occur,in contrast to patients with tumors lacking CD80 mRNA,in whom tumor relapse rate was 57.5%(P<0.05).Relapse ratein tumors deficient both HLA class Ⅰ and CD80 was significantly higher than that of tumors coexpression the two molecules.Conclusions:EOC cells may escapefrom the immune surveillance of the host through downregulating expressions ofHLA class Ⅰ and CD80.Evaluation of expressions of these surface immunoregulatory molecules may be helpful for judging prognoses of EOC patients and guiding immunotherapy.

Study of consolidation chemotherapy in advanced epithelial ovarian carcinoma

Objective:A prospective randomized study was designed to evaluate the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.Methods:50 patients with advanced epithelial ovarian carcinoma treated in our hospital during the period from March 2000 to October 2005 were enrolled in this study.All patients had achieved clinical complete remission by means of standard treatments,and were randomly divided into consolidation chemotherapy group and control group.Relapse rate,and disease-free survival(DFS)time were analyzed in both groups.Results:24 patients were assigned in consolidation chemotherapy group,and 26 patients in control group.Tumor relapse interval in consolidation group was(26.5±7.4)months,vs.(16.8±7.0)months in control group respectively,P=0.001.Time to relapse(TTR)in consolidation group was(19.2±6.8)months,vs.(10.0±6.9)months in control group,P=0.002.Analysis of DFS time and overall survival time,Log Rank test:P=0.042 and P=0.062,respectively.Conclusions:Consolidation chemotherapy could be the relevant factor that postpones tumor relapse interval and prolongs DFS time in advanced epithelial ovarian carcinoma patients who had achived chlinical complete remission.But so far the statistic result of our clinical study is beyond the conclusion that consolidation chemotherapy can decrease relapse rate or increase survival rate.Multicenter randomized clinical trial should be performed to confirm the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.

Overexpression and Immunosuppressive Functions of Transforming Growth Factor 1,Vascular Endothelial Growth Factor and Interleukin-10 in Epithelial Ovarian Cancer

Objective： Transforming growth factor-1 （TGF-βI）, vascular endothelial growth factor （VEGF）, and interleukin-lO （IL-10） may be critical cytokines in the microenvironment of a tumor, playing roles in immune suppression. This study was conducted to elucidate the roles and immunosuppressive functions of these cytokines in epithelial ovarian cancer （EOC）. Methods： The expression levels of TGF-β1, VEGF and IL-10 in malignant tissue were evaluated by immune- histochemistry and compared with corresponding borderline, benign, and tumor-free tissues. Moreover, relationships among the levels of these cytokines and correlations between expression and the prognosis of EOC were analyzed by Pearson rank correlations and multi-factor Logistic regression. The roles of TGF-βI, VEGF, and IL-lO in the immunosuppressive microenvironment of ovarian cancer were studied through dendritic cell （DC） maturation and CD4＋CD25＋FoxP3＋ Treg generation in vitro experiments. Results： TGF-β1, VEGF, and IL-IO were expressed TGF-β1 was an independent prognostic factor for EOC n 100%, 74.69%, and 54.96% of EOC patients, respectively. L-IO was significantly co-expressed with VEGF. In vitro, VEGF and TGF-β31 strongly interfered with DC maturation and consequently led to immature DCs, which secreted high levels of IL-IO that accumulated around the tumor site. TGF-β1 and IL-10 induced Treg generation without antigen presentation in DCs. Conclusions： TGF-βI, VEGF and IL-IO play important roles in EOC and can lead to frequent immune evasion events.

Epithelial membrane protein 1 negatively regulates cell growth and metastasis in colorectal carcinoma

AIM:To determine the expression and function of epithelial membrane protein 1(EMP1)in colorectal carcinoma.METHODS:Colorectal samples were taken from cancer lesions and adjacent normal tissue in colorectal cancer patients immediately after endoscopic biopsy.A portion of the sample was either fixed in 4%paraformaldehyde and embedded in paraffin for immunohistochemistry or stored in liquid nitrogen for Western blot.In order to determine protein expression of EMP1in colorectal cancer(n=63)and normal tissue(n=31),semi-quantitative immunohistochemistry and Western blot were utilized.For in vitro studies,the human colorectal cancer cell line SW-480 was maintained in RPMI-1640 medium supplemented with 10%fetal bovine serum.Recombinant lentivirus mediated overexpression of EMP1 in SW-480 cells was quantified by real-time reverse transcription-polymerase chain reaction and Western blot.Control SW-480 cells were transfected with an empty vector.To further study the effect of EMP1 overexpression in SW-480 cells,cell proliferation,apoptosis,migration and invasion assays were conducted.RESULTS:Expression of EMP1 was significantly lower in colorectal cancer tissue than in normal tissue using both immunohistochemistry(39.7%vs 90.3%of tissues,P<0.05)and Western blot(0.126±0.022 vs0.632±0.053,P<0.05).The level of EMP1 protein expression was not correlated with gender,age,or tumor location.Decreased expression of EMP1 was significantly correlated with T stage,lymph node metastasis,clinic stage,and histological grade in patients with colorectal cancer(P<0.05).According to Kaplan-Meier analysis,low EMP1 expression correlated significantly with poor overall five-year survival(34.2%vs 64.0%survival,P<0.05).SW-480 cells transfected with EMP1 had a lower survival fraction,higher cell apoptosis(12.1%±1.3%vs 3.1%±0.6%,P<0.05),a significant decrease in migration and invasion(124.0±17.0 and 87.0±12.0,respectively vs 213.0±29.0 and 178.0±21.0,respectively,P<0.05),higher caspase-9(0.635±0.063 vs0.315±0.032,P<0.05),and lower VEGFC protein expression(0.229±0.021 vs 0.519±0.055,P<0.05)relative to cells not transfected with EMP1.CONCLUSION:Low EMP1 expression in colorectal cancer is associated with increased disease severity,suggesting that EMP1 may be a negative regulator of colorectal cancer.

Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action

Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.

Usefulness of human epididymis protein 4 in predicting cytoreductive surgical outcomes for advanced ovarian tubal and peritoneal carcinoma

Objective： Human epididymis protein 4（HE4） is a promising biomarker of epithelial ovarian cancer（EOC）. But its role in assessing the primary optimal debulking（OD） of EOC remains unknown. The purpose of this study is to elucidate the ability of preoperative HE4 in predicting the primary cytoreductive outcomes in advanced EOC, tubal or peritoneal carcinoma.Methods： We reviewed the records of 90 patients with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at the Department of Obstetrics and Gynecology of Peking University People＇s Hospital between November 2005 and October 2010. Preoperative serum HE4 and CA125 levels were detected with EIA kit. A receiver operating characteristic（ROC） curve was used to determine the most useful HE4 cut-off value. Logistic regression analysis was performed to identify significant preoperative clinical characteristics to predict optimal primary cytoreduction.Results： OD was achieved in 47.7%（43/48） of patients. The median preoperative HE4 level for patients with OD vs. suboptimal debulking was 423 and 820 pmol/L, respectively（P〈0.001）. The areas under the ROC curve for HE4 and CA125 were 0.716 and 0.599, respectively（P=0.080）. The most useful HE4 cut-off value was 473 pmol/L. Suboptimal cytoreduction was obtained in 66.7%（38/57） of cases with HE4 ≥473 pmol/L compared with only 27.3%（9/33） of cases with HE4 〈473 pmol/L. At this threshold, the sensitivity, specificity, positive predictive value（PPV） and negative predictive value（NPV） for diagnosing suboptimal debulking were 81%, 56%, 67%, and 73%, respectively. Logistic regression analysis showed that the patients with HE4 ≥473 pmol/L were less likely to achieve OD（odds ratio =5.044, P=0.002）.Conclusions： Preoperative serum HE4 may be helpful to predict whether optimal cytoreductive surgery could be obtained or whether extended cytoreduction would be needed by an interdisciplinary team.