Ovarian cancer(OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that d...Ovarian cancer(OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination,pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy,pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology,primary prevention, early detection, and possibly even therapeutic strategies.展开更多
Background Ginsenoside Rg3, the main component isolated from ginseng, inhibits some kinds of tumour growth and angiogenesis. The combination of low dose chemotherapy and antiangiogenesis inhibitors suppresses growth o...Background Ginsenoside Rg3, the main component isolated from ginseng, inhibits some kinds of tumour growth and angiogenesis. The combination of low dose chemotherapy and antiangiogenesis inhibitors suppresses growth of experimental tumours more effectively than conventional therapy. The effect of this combination on ovarian cancer remains to be evaluated. Therefore, we investigated the synergism of ginsenoside Rg3 and cyclophosphamide (CTX) on growth and angiogenesis of human ovarian cancer. Methods Twenty-eight female athymic mice were divided randomly into 4 groups of 7: ginsenoside Rg3, CTX, ginsenoside Rg3 and CTX combination and control, after being transplanted with ovarian cancer cells (SKOV-3). The mice were given intraperitoneal injection of ginsenoside Rg3 and CTX for the 10 days following inoculation of SKOV-3 cells. The life quality and number of living days of mice were recorded. The size of tumour, tumour inhibitive rate, life elongation rate, proliferating cell nuclear antigen labelling index (PCNALI), expression of vascular endothelial cell growth factor (VEGF) and microvessel density (MVD) of the tumour tissues were estimated. Results Life quality of mice in ginsenoside Rg3 and combined treatment groups were better and number of living days longer than control. Average tumour weights of each treated group were less than control and there was no significant difference among the treated groups. PCNALI of treated groups was lower than control. The MVD value and VEGF expression in treated groups were significantly lower than control and the MVD values of ginsenoside Rg3 and combined treatment groups were lower than that of CTX group. Conclusions Ginsenoside Rg3 significantly inhibited growth and angiogenesis of ovarian cancer when used alone or combined with CTX. Ginsenoside Rg3 and CTX combination reinforced the antitumour effect each other and improved the living quality and survival time of mice with tumour.展开更多
Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis(PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of...Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis(PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery(CRS) + hyperthermic intraperitoneal chemotherapy(HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases Ⅰ, Ⅱ and Ⅲ clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.展开更多
Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can acti...Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.展开更多
This article is to offer a concise review on the use of cytoreductive surgery (CRS) plus intraperitoneal hyperthermic chemotherapy (IPHC) for the treatment of peritoneal carcinomatosis (PC). Traditionally, PC wa...This article is to offer a concise review on the use of cytoreductive surgery (CRS) plus intraperitoneal hyperthermic chemotherapy (IPHC) for the treatment of peritoneal carcinomatosis (PC). Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 too. With the establishment of several phase Ⅱ studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase Ⅲ studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future.展开更多
Premature ovarian failure(POF) is a kind of gynecological disease that causes amenorrhea, infertility, menopause and urogenital symptoms. Currently hormone replacement therapy(HRT) is the most popular choice for w...Premature ovarian failure(POF) is a kind of gynecological disease that causes amenorrhea, infertility, menopause and urogenital symptoms. Currently hormone replacement therapy(HRT) is the most popular choice for women with POF to get rid of menopausal syndrome. However, as the popularization of Chinese herbs made Chinese medicine(CM) shine new lights, physicians are able to treat POF with both meno-herbs and integrated therapy. HRT has its own indications and contraindications. For example, unexplained vaginal bleeding, acute liver damage, liver dysfunction, vascular embolization, and breast cancer are all contraindications of HRT, and CM is taken by more physicians as an adjuvant therapy. This review, including a range of common Chinese herbs and formulations according to the existing literature, provides a general description of CM treating POF from the aspects of mechanisms and clinical application. It also highlights acupuncture as a unique physiotherapy for POF. Although the validity of CM has been supported by the evidence of many preclinical trials, clinical trials and meta-analysis, the adverse events with CM therapy still exist and no guarantee has been made for its safety. This review concludes the updated information for CM treating POF contributing to further studies.e展开更多
AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function classification.METHODS:Surgically resected spec...AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function classification.METHODS:Surgically resected specimens of 361 gastric carcinomas(GC) were investigated with enzyme-, mucin-, and tumor-related marker immunohistochemistry. According to the direction of cell-function differentiation, stomach carcinomas were divided into five functionally differentiated types. RESULTS: (1) Absorptive function differentiation type (AFDT): there were 82 (22.7%) patients including 76 (92.7%) aged 45 years. Sixty-nine (84.1%) cases belonged to the intestinal type. Thirty-eight (46.3%) expressed CD44v6 and 9 (13.6%) of 66 male patients developed liver metastasis.The 5-year survival rate of patients in this group (58.5%) was higher than those with the other types (P【0.01). (2) Mucin secreting function differentiation type (MSFDT): 54 (15%) cases. Fifty-three (98.1%) tumors had penetrated the serosa, 12 (22.2%) expressed ER and 22 (40.7%) expressed CD44v6. The postoperative 5-year survival rate was 28.6%. (3) Absorptive and mucin-producing function differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%) aged younger than 45 years. The tumor was more common in women (62, 34.4%,) and expressed more frequently estrogen receptors (ER) (129, 81.7%) than other types (P【0.01). Ovary metastasis was found in 12 (19.4%) out of 62 female subjects. The patients with this type GC had the lowest 5-year survival rate (24.7%) among all types. (4) Specific function differentiation type (SFDT): 13 (3.6%) cases. Nine (69.2%) tumors of this type derived from APUD system, the other 4 (30.7%) were of different histological differentiation. Sixty per cent of the patients survived at least five years. (5) Non-function differentiation type (NFDT): 32 (8.9%) cases. Nineteen (59.4%) cases had lymph node metastases but no one with liver or ovary metastasis. The 5-year survival rate was 28.1%. CONCLUSION: This new cell-f展开更多
Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The p...Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism. Methods The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells. Results In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3. Conclusions Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced an qioqenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.展开更多
Objective. To understanding the molecular mechanisms in invasion andmetastasis of the ovarian carcinoma, we investigate a novel candidate metastasis―associated gene (MTA1) and nm23Hl mRNA expression and mutation in o...Objective. To understanding the molecular mechanisms in invasion andmetastasis of the ovarian carcinoma, we investigate a novel candidate metastasis―associated gene (MTA1) and nm23Hl mRNA expression and mutation in ovarian carcinoma. Methods. Twenty primary ovariancarcinoma specimens, 20 corresponding lymph nodes and 8 normal ovarian was examined for mRNAexpression and mutation of MTA1 and nm23Hl genes by reverse-transcription ploymerase chain reaction(RT―PCR) and RT―PCR―SSCP analysis. The level of the expression was determined by the relativeoptic desity (ROD) of the PCR products. Results. The frequency of MAT1 overexpression was 100% (7/7)in primary ovarian carcinoma with metastasis but only 38.5% (5/13) in those without metastasis(P=0.0103). Overexpression of MAT1 was observed in 87.5% (6/7) of lymph nodes with metastasis butonly 23% (3/13). of lymph nodes without metastasis (P=0.0118). In contrast with MAT1, low expressionof nm23H1 mRNA was seen in 7 of 7 o-varian carcinoma with metastasis but only in 4 of 13(30%) ofthose without metastassis (P=0.0043). Low nm23H1 expression was also seen in 7 of 7 lymph nodes withmetastasis but only in 5 of 13 (38.5%) nonmetastatic lymph nodes (P=0.0102). The ROD ratio of MAT1to nm23Hl increased with the development of metastasis. No mutation of MAT1 and nm23H1 genes wasfound by SSCP analysis. Conclusion. The mRNA expression of MTA1 and nm23H1 is positively andnegatively correlated with lymph node metastasis, respectively. Expression abnormalities but notmutation of the two genes are frequent events related to lymph node metastasis of ovarian cancer.展开更多
Background Vitrification is a prospective technology in ovarian tissue cryopreservation, but it is still in an initial stage. This study was conducted to investigate a modified vitrification protocol for human ovarian...Background Vitrification is a prospective technology in ovarian tissue cryopreservation, but it is still in an initial stage. This study was conducted to investigate a modified vitrification protocol for human ovarian tissue, which can be used as an alternative to preserve fertility for young women with cancer who have to undergo cytotoxic therapy and sterilization. Methods Ovarian tissue samples were collected from 15 patients and randomly allocated to groups of fresh, vitrification, and conventional slow freezing. A modified carrierless vitrification method was applied. The proportion of morphologically intact follicles in fresh ovarian tissues was compared with that in warmed/thawed tissues. The initial growth of the follicles and the concentrations of estradiol and progesterone were detected to determine the viability and endocrine function of the cryopreserved tissues. Results The proportion of morphologically intact primordial follicles in the fresh group (97.6%) was significantly higher than that in the other two groups (vitrification group 80.3% and slow-freezing group 72.6%, P〈0.001). In both the vitrification and slow-freezing groups, estradiol and progesterone were secreted continuously during 2-week culture in vitro, the proportion of primary follicles were both significantly increased compared to the fresh group. No statistically significant differences existed between the two groups after cryopreservation in the proportion of both primordial and primary follicles, and the concentrations of estradiol and progesterone (P〉0.05).Conclusion The modified vitrification method for cryopreservation of human ovarian tissues is effective, simple, and inexpensive.展开更多
Objective: To identify differentially expressed long non-coding RNAs (lncRNAs) involved in the metastasis of epithelial ovarian cancer. Methods: An in vitro invasion assay was performed to validate the invasive ca...Objective: To identify differentially expressed long non-coding RNAs (lncRNAs) involved in the metastasis of epithelial ovarian cancer. Methods: An in vitro invasion assay was performed to validate the invasive capability of SKOV3 and SKOV3.ip1 cell lines. Total R.NA was then extracted, and microarray analysis was performed. Moreover, nine lncRNAs were selected for validation using RT-qPCR. Results: Compared with the SKOV3 cells, the SKOV3.ip1 cells significantly improved in the in vitro invasive activity. Of the 4,956 lncRNAs detected in the microarra~ 583 and 578 lncRNAs were upregulated and downregulated, respectivel~ in SKOV3.ip1 cells, compared with the parental SKOV3 cells. Seven of the analyzed lncRNAs (MALAT1, H19, UCA1, CCAT1, LOC645249, LOC100128881, and LOC100292680) confirmed the deregulation found by microarray analysis. Conclusion: LncRNAs clusters were differentially expressed in ovarian cancer cells with varying metastatic potentials. This result indicates that some lncRNAs might exert a partial or key role in epithelial ovarian cancer metastasis. Further studies should be conducted to determine the roles of these lncRNAs in ovarian cancer metastasis.展开更多
BACKGROUND Premature ovarian insufficiency(POI)and premature ovarian failure(POF)have become one of the major problems threatening women of childbearing age.Studies have shown that stem cells transplanted from bone ma...BACKGROUND Premature ovarian insufficiency(POI)and premature ovarian failure(POF)have become one of the major problems threatening women of childbearing age.Studies have shown that stem cells transplanted from bone marrow,umbilical cord,peripheral blood and amniotic fluid can migrate and proliferate to the ovary,promote ovarian function repair,increase the number of follicles and granulosa cells at all levels of ovary,improve endocrine function,and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.AIM To study the ability of human umbilical cord mesenchymal stem cells(hUCMSCs)to repair ovarian injury after chemotherapy.METHODS A total of 110 female BALB/c mice(aged 7-8 wk old)with body masses of 16.0-20.0 g were selected.The mice were fed until 12 wk of age,and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice.Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight:model group,positive control group and hUCMSC group,and each group had 25 mice.Another 25 mice were used as negative controls.The mice in the hUCMSC group were injected with hUCMSCs in the tail vein,and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein.On the 1^st,15^th,30^th,45^th,and 60^th days after intravenous administration,vaginal smears were made to monitor the estrous cycles of the mice.The ovaries were weighed,and pathological sections were made to observe the morphology of the follicles;blood samples were collected to monitor the concentration of sex hormones(oestradiol and follicle-stimulating hormone).RESULTS The estrous cycles of the model group mice were disrupted throughout the experiment.Mice in the hUCMSC group and the positive control group resumed normal estrous cycles.The ovarian weight of the model group mice continued to decline.The ovarian wei展开更多
Objective: Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition ofextracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review...Objective: Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition ofextracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis. Data Sources: We searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix rnetalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-[31), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-T), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms. Study Selection: Articles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases. Results: Many cytokines, such as MMPs, TIMPs, TGF-β1, CTGF, PPAR-γ, VEGK and ET- 1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide. Conclusions: Patients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.展开更多
Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on ou...Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields.展开更多
Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three pr...Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three presumable mechanisms involved in the development of POI,namely apoptosis acceleration,follicular maturation blocking and premature follicle activation,through the following studied causes:(i) chromosomal abnormalities or gene mutations:mostly involve X chromosome,such as FMR1 premutation;more and more potentially causal genes have been screened recently;(ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency;(iii) autoimmune mediated ovarian damage:observed alone or with some certain autoimmune disorders and syndromes;but the specificity and sensitivity of antibodies towards ovary are still questionable;(iv) iatrogenic:radiotherapy or chemotherapy used in cancer treatment,as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function;(v) virus infection such as HIV and mumps;(vi) toxins and other environmental/lifestyle factors:cigarette smoking,toxins(e.g.,4-vinylcyclohexene diepoxide),and other environmental factors are associated with the development of POI.The etiology of a majority of POI cases is not identified,and is believed to be multifactorial.Strategies to POI include hormone replacement and infertility treatment.Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women.Embryo cryopreservation,ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments.展开更多
The present study aimed to investigate the clinical value of serum anti-mullerian hormone(AMH) and inhibin B(INHB) in predicting the ovarian response of patients with polycystic ovary syndrome(PCOS). A total of ...The present study aimed to investigate the clinical value of serum anti-mullerian hormone(AMH) and inhibin B(INHB) in predicting the ovarian response of patients with polycystic ovary syndrome(PCOS). A total of 120 PCOS patients were enrolled and divided into three groups in terms of the ovarian response: a low-response group(n=36), a normal-response group(n=44), and a high-response group(n=40). The serum AMH and INHB levels were measured by enzyme-linked immunosorbent assay(ELISA). The follicle stimulating hormone(FSH), luteinizing hormone(LH), and estradiol(E2) levels were determined by chemiluminescence microparticle immunoassay. The correlation of the serum AMH and INHB levels with other indicators was analyzed. A receiver operating characteristic(ROC) curve was established to analyze the prediction of ovarian response by AMH and INHB. The results showed that there were significant differences in age, body mass index(BMI), FSH, total gonadotropin-releasing hormone(Gn RH), LH, E2, and antral follicle counts(AFCs) between the groups(P〈0.05). The serum AMH and INHB levels were increased significantly with the ovarian response of PCOS patients increasing(P〈0.05). The serum AMH and INHB levels were negatively correlated with the age, BMI, FSH level, Gn, and E2 levels(P〈0.05). They were positively correlated with the LH levels and AFCs(P〈0.05). ROC curve analysis of serum AMH and INHB in prediction of a low ovarian response showed that the area under the ROC curve(AUC) value of the serum AMH level was 0.817, with a cut-off value of 1.29 ng/m L. The sensitivity and specificity were 71.2% and 79.6%, respectively. The AUC value of serum INHB was 0.674, with a cut-off value of 38.65 ng/m L, and the sensitivity and specificity were 50.7% and 74.5%, respectively. ROC curve analysis showed when the serum AMH and INHB levels were used to predict a high ovarian response, the AUC value of the serum AMH level was 0.742, with a cut-off value 展开更多
Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a successful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of no...Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a successful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of non-coding RNAs,microRNAs(miRNAs) in cancer development,with several conjectures regarding their possible involvement in the evolution of drug resistance.This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer.The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line(OV2008) and its resistant variant(C13*) was identified by real-time PCR.An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry,were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells.Real-time PCR,Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b.As compared with OV2008 cells,the expression levels of miR-125b in C13* cells were increased.It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13* cells.Moreover,Bak1 was a direct target of miR-125b,and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin.Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13* cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression.This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.展开更多
Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in n...Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary(n = 5), ovarian cyst (n =5), ovarian borderline tumor (n = 9), epithelial ovarian cancer(n = 60), and ovarian cancer cell line (n = 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clini-copathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5(7.1%)cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst(P < 0.05). The level of PTEN gene mRNA expression was negatively correlated with clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05=. Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.展开更多
文摘Ovarian cancer(OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination,pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy,pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology,primary prevention, early detection, and possibly even therapeutic strategies.
文摘Background Ginsenoside Rg3, the main component isolated from ginseng, inhibits some kinds of tumour growth and angiogenesis. The combination of low dose chemotherapy and antiangiogenesis inhibitors suppresses growth of experimental tumours more effectively than conventional therapy. The effect of this combination on ovarian cancer remains to be evaluated. Therefore, we investigated the synergism of ginsenoside Rg3 and cyclophosphamide (CTX) on growth and angiogenesis of human ovarian cancer. Methods Twenty-eight female athymic mice were divided randomly into 4 groups of 7: ginsenoside Rg3, CTX, ginsenoside Rg3 and CTX combination and control, after being transplanted with ovarian cancer cells (SKOV-3). The mice were given intraperitoneal injection of ginsenoside Rg3 and CTX for the 10 days following inoculation of SKOV-3 cells. The life quality and number of living days of mice were recorded. The size of tumour, tumour inhibitive rate, life elongation rate, proliferating cell nuclear antigen labelling index (PCNALI), expression of vascular endothelial cell growth factor (VEGF) and microvessel density (MVD) of the tumour tissues were estimated. Results Life quality of mice in ginsenoside Rg3 and combined treatment groups were better and number of living days longer than control. Average tumour weights of each treated group were less than control and there was no significant difference among the treated groups. PCNALI of treated groups was lower than control. The MVD value and VEGF expression in treated groups were significantly lower than control and the MVD values of ginsenoside Rg3 and combined treatment groups were lower than that of CTX group. Conclusions Ginsenoside Rg3 significantly inhibited growth and angiogenesis of ovarian cancer when used alone or combined with CTX. Ginsenoside Rg3 and CTX combination reinforced the antitumour effect each other and improved the living quality and survival time of mice with tumour.
基金Supported by Key Project of the National Natural Science Foundation of China,No.81230031
文摘Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis(PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery(CRS) + hyperthermic intraperitoneal chemotherapy(HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases Ⅰ, Ⅱ and Ⅲ clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.
基金supported by Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030501 to Haixiang Sun)National Natural Science Foundation of China (31571189, 81571391, 30900847 to Lijun Ding)+1 种基金Jiangsu Provincial Medical Youth Talent (QNRC2016006)Nanjing Medical Science Development Project (JQX14004, ZKX16042)
文摘Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.
基金New-Century Excellent Talents Supporting Program of the Ministry of Education of China NCET-04-0669Foundation for the Author of National Excellent Doctoral Dissertation of China+2 种基金 FANEDD-200464Young Talents Supporting Program of Hubei Province 301161202National Natural Science Foundation of China No. 20675058
文摘This article is to offer a concise review on the use of cytoreductive surgery (CRS) plus intraperitoneal hyperthermic chemotherapy (IPHC) for the treatment of peritoneal carcinomatosis (PC). Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 too. With the establishment of several phase Ⅱ studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase Ⅲ studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future.
基金Supported by the National Natural Science Foundation of China(No.31571196,No.30801502,No.81401171)the Municipal Science and Technology Commission of Shanghai,China(Medical Guidance Technology Project,No.15401932200)+2 种基金a FY2008 JSPS Postdoctoral Fellowship for Foreign Researchers(No.P08471)the Shanghai Pujiang Program(No.11PJ1401900)the Development Project of Shanghai Peak Disciplines-Integrated Chinese and Western Medicine(No.20150407)
文摘Premature ovarian failure(POF) is a kind of gynecological disease that causes amenorrhea, infertility, menopause and urogenital symptoms. Currently hormone replacement therapy(HRT) is the most popular choice for women with POF to get rid of menopausal syndrome. However, as the popularization of Chinese herbs made Chinese medicine(CM) shine new lights, physicians are able to treat POF with both meno-herbs and integrated therapy. HRT has its own indications and contraindications. For example, unexplained vaginal bleeding, acute liver damage, liver dysfunction, vascular embolization, and breast cancer are all contraindications of HRT, and CM is taken by more physicians as an adjuvant therapy. This review, including a range of common Chinese herbs and formulations according to the existing literature, provides a general description of CM treating POF from the aspects of mechanisms and clinical application. It also highlights acupuncture as a unique physiotherapy for POF. Although the validity of CM has been supported by the evidence of many preclinical trials, clinical trials and meta-analysis, the adverse events with CM therapy still exist and no guarantee has been made for its safety. This review concludes the updated information for CM treating POF contributing to further studies.e
基金Project supported by the National Natural Science Foundation of China, No. 39270300. No. 39370772Training Program for Trans-Century Talents by the State Education Commission of China
文摘AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function classification.METHODS:Surgically resected specimens of 361 gastric carcinomas(GC) were investigated with enzyme-, mucin-, and tumor-related marker immunohistochemistry. According to the direction of cell-function differentiation, stomach carcinomas were divided into five functionally differentiated types. RESULTS: (1) Absorptive function differentiation type (AFDT): there were 82 (22.7%) patients including 76 (92.7%) aged 45 years. Sixty-nine (84.1%) cases belonged to the intestinal type. Thirty-eight (46.3%) expressed CD44v6 and 9 (13.6%) of 66 male patients developed liver metastasis.The 5-year survival rate of patients in this group (58.5%) was higher than those with the other types (P【0.01). (2) Mucin secreting function differentiation type (MSFDT): 54 (15%) cases. Fifty-three (98.1%) tumors had penetrated the serosa, 12 (22.2%) expressed ER and 22 (40.7%) expressed CD44v6. The postoperative 5-year survival rate was 28.6%. (3) Absorptive and mucin-producing function differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%) aged younger than 45 years. The tumor was more common in women (62, 34.4%,) and expressed more frequently estrogen receptors (ER) (129, 81.7%) than other types (P【0.01). Ovary metastasis was found in 12 (19.4%) out of 62 female subjects. The patients with this type GC had the lowest 5-year survival rate (24.7%) among all types. (4) Specific function differentiation type (SFDT): 13 (3.6%) cases. Nine (69.2%) tumors of this type derived from APUD system, the other 4 (30.7%) were of different histological differentiation. Sixty per cent of the patients survived at least five years. (5) Non-function differentiation type (NFDT): 32 (8.9%) cases. Nineteen (59.4%) cases had lymph node metastases but no one with liver or ovary metastasis. The 5-year survival rate was 28.1%. CONCLUSION: This new cell-f
文摘Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism. Methods The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells. Results In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3. Conclusions Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced an qioqenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.
文摘Objective. To understanding the molecular mechanisms in invasion andmetastasis of the ovarian carcinoma, we investigate a novel candidate metastasis―associated gene (MTA1) and nm23Hl mRNA expression and mutation in ovarian carcinoma. Methods. Twenty primary ovariancarcinoma specimens, 20 corresponding lymph nodes and 8 normal ovarian was examined for mRNAexpression and mutation of MTA1 and nm23Hl genes by reverse-transcription ploymerase chain reaction(RT―PCR) and RT―PCR―SSCP analysis. The level of the expression was determined by the relativeoptic desity (ROD) of the PCR products. Results. The frequency of MAT1 overexpression was 100% (7/7)in primary ovarian carcinoma with metastasis but only 38.5% (5/13) in those without metastasis(P=0.0103). Overexpression of MAT1 was observed in 87.5% (6/7) of lymph nodes with metastasis butonly 23% (3/13). of lymph nodes without metastasis (P=0.0118). In contrast with MAT1, low expressionof nm23H1 mRNA was seen in 7 of 7 o-varian carcinoma with metastasis but only in 4 of 13(30%) ofthose without metastassis (P=0.0043). Low nm23H1 expression was also seen in 7 of 7 lymph nodes withmetastasis but only in 5 of 13 (38.5%) nonmetastatic lymph nodes (P=0.0102). The ROD ratio of MAT1to nm23Hl increased with the development of metastasis. No mutation of MAT1 and nm23H1 genes wasfound by SSCP analysis. Conclusion. The mRNA expression of MTA1 and nm23H1 is positively andnegatively correlated with lymph node metastasis, respectively. Expression abnormalities but notmutation of the two genes are frequent events related to lymph node metastasis of ovarian cancer.
基金grants from the Major Clinical Project Foundation of Ministry of Health,China(No.[2004]468)the Fund of Guangdong Provincial Scientific Pivotal(No.2003 A3020305)the Fund of Guangzhou Scientific Research(No.2004Z1-E0101)
文摘Background Vitrification is a prospective technology in ovarian tissue cryopreservation, but it is still in an initial stage. This study was conducted to investigate a modified vitrification protocol for human ovarian tissue, which can be used as an alternative to preserve fertility for young women with cancer who have to undergo cytotoxic therapy and sterilization. Methods Ovarian tissue samples were collected from 15 patients and randomly allocated to groups of fresh, vitrification, and conventional slow freezing. A modified carrierless vitrification method was applied. The proportion of morphologically intact follicles in fresh ovarian tissues was compared with that in warmed/thawed tissues. The initial growth of the follicles and the concentrations of estradiol and progesterone were detected to determine the viability and endocrine function of the cryopreserved tissues. Results The proportion of morphologically intact primordial follicles in the fresh group (97.6%) was significantly higher than that in the other two groups (vitrification group 80.3% and slow-freezing group 72.6%, P〈0.001). In both the vitrification and slow-freezing groups, estradiol and progesterone were secreted continuously during 2-week culture in vitro, the proportion of primary follicles were both significantly increased compared to the fresh group. No statistically significant differences existed between the two groups after cryopreservation in the proportion of both primordial and primary follicles, and the concentrations of estradiol and progesterone (P〉0.05).Conclusion The modified vitrification method for cryopreservation of human ovarian tissues is effective, simple, and inexpensive.
文摘Objective: To identify differentially expressed long non-coding RNAs (lncRNAs) involved in the metastasis of epithelial ovarian cancer. Methods: An in vitro invasion assay was performed to validate the invasive capability of SKOV3 and SKOV3.ip1 cell lines. Total R.NA was then extracted, and microarray analysis was performed. Moreover, nine lncRNAs were selected for validation using RT-qPCR. Results: Compared with the SKOV3 cells, the SKOV3.ip1 cells significantly improved in the in vitro invasive activity. Of the 4,956 lncRNAs detected in the microarra~ 583 and 578 lncRNAs were upregulated and downregulated, respectivel~ in SKOV3.ip1 cells, compared with the parental SKOV3 cells. Seven of the analyzed lncRNAs (MALAT1, H19, UCA1, CCAT1, LOC645249, LOC100128881, and LOC100292680) confirmed the deregulation found by microarray analysis. Conclusion: LncRNAs clusters were differentially expressed in ovarian cancer cells with varying metastatic potentials. This result indicates that some lncRNAs might exert a partial or key role in epithelial ovarian cancer metastasis. Further studies should be conducted to determine the roles of these lncRNAs in ovarian cancer metastasis.
文摘BACKGROUND Premature ovarian insufficiency(POI)and premature ovarian failure(POF)have become one of the major problems threatening women of childbearing age.Studies have shown that stem cells transplanted from bone marrow,umbilical cord,peripheral blood and amniotic fluid can migrate and proliferate to the ovary,promote ovarian function repair,increase the number of follicles and granulosa cells at all levels of ovary,improve endocrine function,and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.AIM To study the ability of human umbilical cord mesenchymal stem cells(hUCMSCs)to repair ovarian injury after chemotherapy.METHODS A total of 110 female BALB/c mice(aged 7-8 wk old)with body masses of 16.0-20.0 g were selected.The mice were fed until 12 wk of age,and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice.Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight:model group,positive control group and hUCMSC group,and each group had 25 mice.Another 25 mice were used as negative controls.The mice in the hUCMSC group were injected with hUCMSCs in the tail vein,and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein.On the 1^st,15^th,30^th,45^th,and 60^th days after intravenous administration,vaginal smears were made to monitor the estrous cycles of the mice.The ovaries were weighed,and pathological sections were made to observe the morphology of the follicles;blood samples were collected to monitor the concentration of sex hormones(oestradiol and follicle-stimulating hormone).RESULTS The estrous cycles of the model group mice were disrupted throughout the experiment.Mice in the hUCMSC group and the positive control group resumed normal estrous cycles.The ovarian weight of the model group mice continued to decline.The ovarian wei
基金The work presented in this manuscript was supported by grants from the Natural Science Foundation of Zhejiang Province (No. LY 15H040004) and the Medical and Health Program in Zhejiang Province (No. 2015KYA 142).
文摘Objective: Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition ofextracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis. Data Sources: We searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix rnetalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-[31), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-T), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms. Study Selection: Articles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases. Results: Many cytokines, such as MMPs, TIMPs, TGF-β1, CTGF, PPAR-γ, VEGK and ET- 1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide. Conclusions: Patients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.
文摘Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields.
文摘Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three presumable mechanisms involved in the development of POI,namely apoptosis acceleration,follicular maturation blocking and premature follicle activation,through the following studied causes:(i) chromosomal abnormalities or gene mutations:mostly involve X chromosome,such as FMR1 premutation;more and more potentially causal genes have been screened recently;(ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency;(iii) autoimmune mediated ovarian damage:observed alone or with some certain autoimmune disorders and syndromes;but the specificity and sensitivity of antibodies towards ovary are still questionable;(iv) iatrogenic:radiotherapy or chemotherapy used in cancer treatment,as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function;(v) virus infection such as HIV and mumps;(vi) toxins and other environmental/lifestyle factors:cigarette smoking,toxins(e.g.,4-vinylcyclohexene diepoxide),and other environmental factors are associated with the development of POI.The etiology of a majority of POI cases is not identified,and is believed to be multifactorial.Strategies to POI include hormone replacement and infertility treatment.Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women.Embryo cryopreservation,ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments.
文摘The present study aimed to investigate the clinical value of serum anti-mullerian hormone(AMH) and inhibin B(INHB) in predicting the ovarian response of patients with polycystic ovary syndrome(PCOS). A total of 120 PCOS patients were enrolled and divided into three groups in terms of the ovarian response: a low-response group(n=36), a normal-response group(n=44), and a high-response group(n=40). The serum AMH and INHB levels were measured by enzyme-linked immunosorbent assay(ELISA). The follicle stimulating hormone(FSH), luteinizing hormone(LH), and estradiol(E2) levels were determined by chemiluminescence microparticle immunoassay. The correlation of the serum AMH and INHB levels with other indicators was analyzed. A receiver operating characteristic(ROC) curve was established to analyze the prediction of ovarian response by AMH and INHB. The results showed that there were significant differences in age, body mass index(BMI), FSH, total gonadotropin-releasing hormone(Gn RH), LH, E2, and antral follicle counts(AFCs) between the groups(P〈0.05). The serum AMH and INHB levels were increased significantly with the ovarian response of PCOS patients increasing(P〈0.05). The serum AMH and INHB levels were negatively correlated with the age, BMI, FSH level, Gn, and E2 levels(P〈0.05). They were positively correlated with the LH levels and AFCs(P〈0.05). ROC curve analysis of serum AMH and INHB in prediction of a low ovarian response showed that the area under the ROC curve(AUC) value of the serum AMH level was 0.817, with a cut-off value of 1.29 ng/m L. The sensitivity and specificity were 71.2% and 79.6%, respectively. The AUC value of serum INHB was 0.674, with a cut-off value of 38.65 ng/m L, and the sensitivity and specificity were 50.7% and 74.5%, respectively. ROC curve analysis showed when the serum AMH and INHB levels were used to predict a high ovarian response, the AUC value of the serum AMH level was 0.742, with a cut-off value
基金supported by grants from the National Natural Sciences Foundation of China (No.81001153)the "973" Program of China (No. 2009CB521808)
文摘Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a successful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of non-coding RNAs,microRNAs(miRNAs) in cancer development,with several conjectures regarding their possible involvement in the evolution of drug resistance.This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer.The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line(OV2008) and its resistant variant(C13*) was identified by real-time PCR.An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry,were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells.Real-time PCR,Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b.As compared with OV2008 cells,the expression levels of miR-125b in C13* cells were increased.It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13* cells.Moreover,Bak1 was a direct target of miR-125b,and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin.Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13* cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression.This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.
文摘Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary(n = 5), ovarian cyst (n =5), ovarian borderline tumor (n = 9), epithelial ovarian cancer(n = 60), and ovarian cancer cell line (n = 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clini-copathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5(7.1%)cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst(P < 0.05). The level of PTEN gene mRNA expression was negatively correlated with clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05=. Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.