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Sample records for borderline ovarian tumor

  1. Borderline ovarian tumors: a review of treatment.

    PubMed Central

    Chambers, J. T.

    1989-01-01

    Borderline ovarian tumors have an excellent prognosis. In stage I disease, no therapy in addition to surgery is needed, and conservation of ovarian tissue for future childbearing may be appropriate. In advanced stages, the use of adjuvant therapy has not consistently led to cures, and complications have been reported. A randomized study of no adjuvant therapy versus adjuvant treatment with long-term follow-up will be necessary to determine the efficacy of additional treatment. PMID:2556863

  2. Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman

    PubMed Central

    Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep

    2015-01-01

    Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682

  3. Mucinous borderline ovarian tumor: a case report with diagnostic insights on ultrasound findings

    PubMed Central

    Śniadecki, Marcin; Bianek-Bodzak, Agnieszka; Liro, Marcin; Szurowska, Edyta

    2016-01-01

    Borderline ovarian tumors represent about 10% of all epithelial ovarian cancers, but in contrast to epithelial ovarian cancers, they constitute a group of tumors with a much better prognosis. An assessment of clinical presentation, physical examination, radiological and biochemical findings is necessary to tailor management strategies for patients with ovarian tumors. The article, which is based on a case report, describes different approaches for preoperative diagnosis as well as discusses approaches that might bring some insights on tumor histology. Furthermore, it raises a question about which imaging techniques should be proposed for a reliable diagnosis of borderline ovarian tumors to ensure safe surgery planning. PMID:28138412

  4. The molecular pathology of ovarian serous borderline tumors.

    PubMed

    Malpica, A; Wong, K-K

    2016-04-01

    Molecular studies in ovarian serous borderline tumors (OSBTs) have been used to understand different aspects of this neoplasm. (i) Pathogenesis, Kras and Braf mutations represent very early events in the tumorigenesis of OSBT as both are detected in serous cystadenomas associated with OSBTs. In contrast, serous cystadenomas without OSBTs do not show Kras or Braf mutations. In OSBTs, Kras mutations range from 17% to 39.5%, while Braf mutations range from 23% to 48%. The former is comparable with the range of Kras mutations in ovarian low-grade serous carcinomas (OLGSCa), 19%-54.5%. In contrast, Braf mutations in OLGSCa range from 0% to 33%. Serous cystadenomas appear to progress to OSBT due to a Braf mutation, but this mutation is rarely involved in the progression to OLGSCa. OSBTs with Braf mutation are associated with cellular senescence and up-regulation of tumor suppressor genes. In contrast, OSBTs without a Braf mutation may progress to OLGSCa due to Kras mutation or some other genetic alterations. (ii) The relationship between OSBTs and the extraovarian disease, a monoclonal versus mutifocal origin? This is still matter of debate as studies using different techniques have failed to settle this controversy. (iii) Biological behavior, Braf mutations appear to have a protective role against the progression of OSBT to OLGSCa, while Kras mutations are commonly seen in cases of OSBT that recurred as LGSCa. Nevertheless, LGSCa as a recurrence of an OSBT can originate from OSBTs with or without detectable Kras mutations. Also, it appears to be an association between Kras G12v mutation and a more aggressive phenotype of OSBT that recurred as LGSCa. (iv) Actionable targets, currently there are limited data. It has been reported that cancer cell lines with Kras G12v mutation are more sensitive to selumetinib than cell lines with wild-type Kras.

  5. Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

    PubMed

    Halperin, R; Zehavi, S; Dar, P; Habler, L; Hadas, E; Bukovsky, I; Schneider, D

    2001-01-01

    The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.

  6. Ovarian serous borderline tumors with noninvasive and invasive peritoneal implants: A case report each.

    PubMed

    Srinivasamurthy, Banushree C; Kulandai Velu, Ambedkar Raj; Krishnan, Nagarajan; Patil, Anand Shankar Rao

    2015-01-01

    Serous borderline tumors (SBT) are defined by the World Health Organization (WHO) as serous neoplasms that show epithelial proliferation greater than that seen in serous cystadenomas, as evidenced by cellular stratification, cytologic atypicality, and epithelial tufting, but which exhibit no evidence of "destructive stromal" invasion and can show extra-ovarian implants. Characterization of invasive peritoneal implants from patients with noninvasive serous ovarian tumors has important prognostic and treatment implications. Peritoneal implants have been classified as either noninvasive or invasive based on their histopathologic appearance. Three criteria were applied for the diagnosis of "invasive" implants: Invasion of underlying normal tissue, micropapillary architecture, and solid epithelial nests surrounded by clefts. We encountered two cases of unilateral ovarian serous borderline tumors with non-invasive peritoneal implants in a 43-year-old female, and invasive peritoneal implants in 76-year-old female.

  7. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  8. Borderline ovarian tumors: a study of 100 cases from a Tertiary Care Hospital

    PubMed Central

    Mun, Semih; Uysal, Fatma; Öztekin, Murat; Büyüktosun, Cem; Şehirali1, Salim; Başoğul, Ömer; Taner, Cüneyt E.

    2013-01-01

    Aim of the study The purpose of the study was to evaluate patients with borderline ovarian tumors. Material and methods Clinical features, treatment and survival status of 100 patients with borderline ovarian tumors were retrospectively evaluated between 1998 and 2007. Results Patients’ mean age was 37.75 years (range: 15–72); 22 of them were postmenopausal. Histopathological diagnoses were serous, mucinous, endometrioid and clear cell in 54%, 41%, 2% and 3% of the patients, respectively; 70 patients had stage IA disease, 8 were at stage IB, 16 at stage IC, 2 at stage IIIA, 3 at stage IIIB and 1 at stage IIIC. Restaging laparotomies were performed on 19 patients; fertility-sparing surgery was performed on 52 patients; 2 patients received chemotherapy because of advanced-stage disease. All patients are currently alive. The 5-year disease-free survival rate for 71 cases was 100%. Conclusions Borderline ovarian tumors have excellent prognoses, and fertility-conserving surgery can be performed in young patients with early-stage disease. PMID:24596520

  9. Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature

    PubMed Central

    Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard

    2016-01-01

    Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651

  10. Mucinous borderline ovarian tumors: Analysis of 75 patients from a single center

    PubMed Central

    Cömert, Duygu Kavak; Üreyen, Işın; Karalok, Alper; Taşçı, Tolga; Türkmen, Osman; Öcalan, Reyhan; Turan, Taner; Tulunay, Gökhan

    2016-01-01

    Objective To analyze the clinicopathologic features, recurrence and survival rates, reproductive history, and treatment of patients with mucinous borderline ovarian tumors (mBOTs). Material and Methods Patients with a diagnosis of mBOT were evaluated retrospectively. Patients with borderline ovarian tumors other than mucinous type and concomitant invasive cancer were excluded. Results A total of 75 patients were identified. Median age was 38 years. The most common symptom was pain (42.7%). Median CA-125 level was 23.5 IU/mL (range, 1–809 IU/mL). Median tumor size was 200 mm (range, 40–400 mm), and 6.7% of mBOTs were bilateral. Thirty-six (48%) patients underwent staging surgery. Two patients (5.9%) had nodal involvement. One patient received platinum-based adjuvant chemotherapy. One (1.3%) patient had recurrence. None of the patients died because of the ovarian tumor. A total of 43 patients had conservative surgery. Conclusion Prognosis of mBOTs is excellent, and fertility-sparing surgery should be considered in the reproductive age group. Furthermore, the necessity of staging surgery is controversial. PMID:27403076

  11. Decision making in borderline ovarian tumors: report of a rare case of mesosigma psammocarcinoma.

    PubMed

    Grimaldi, Luciano; Danzi, Michele; Reggio, Stefano; Pannullo, Mario; Danzi, Roberta; Lauria, Rossella

    2013-09-03

    Psammocarcinoma is a rare variant of serous carcinoma arising either from ovary or peritoneum, characterized by massive psammoma body formation, low-grade of cytologic differentiation and invasiveness. Its clinical behavior is similar to the serous borderline tumors, whose prognosis is significantly better compared to invasive forms, with a 5-year survival in stage I greater than 95%. A typical feature of borderline ovary tumors is the presence, in more than 30% of cases, of borderline peritoneal implants similar to primary ovarian cancer or of invasive forms. We report a case of a 44-years-old woman who referred to our clinic for mesosigmoid mass , accidentally discovered by ultrasonography. Sigmoidectomy with fertility sparing surgery was performed in september 2010. The mass was hystologically characterized by many psammoma bodies and low grade cytological features with diagnosis of psammocarcinoma of mesosigma. One year after the primary surgery, the patient showed with left adnexial mass; optimal debulking surgery was performed including omentectomy, total abdominal hysterectomy, bilateral adnexectomy and appendicectomy. The patient did not receive any adjuvant chemotherapy and to date she is alive and with no evidence of disease. The conclusion is that psammocarcinoma is a very rare tumor that behaves less aggressively than typical serous carcinoma, the mainstay of treatment is surgical debulking , with fertility sparing surgery as possible option in young patients with ovaries macroscopically free of disease.

  12. Ovarian high-grade serous carcinoma with a noninvasive growth pattern simulating a serous borderline tumor.

    PubMed

    Imamura, Hiroko; Ohishi, Yoshihiro; Aman, Murasaki; Shida, Kaai; Shinozaki, Tomoko; Yasutake, Nobuko; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

    2015-10-01

    Ovarian serous borderline tumors (SBTs) being a precursor of low-grade serous carcinomas are morphologically characterized by noninvasive growth and low-grade cytology. On the other hand, many pathologists regard cytologically high-grade, noninvasive (HG-noninv) ovarian serous tumors resembling SBTs in low magnification as conventional high-grade serous carcinomas (HGSCs) by personal experiences. Nonetheless, there are no established molecular characteristic of such tumors. In this study, therefore, we attempted to provide the molecular evidence. We selected 37 ovarian serous tumors that exhibited a cytologically HG-noninv growth pattern, including 36 tumors that coexisted with conventional invasive HGSC components (HG-inv) and a single tumor exclusively composed of pure HG-noninv. Histologically, all HG-noninv showed many mitotic figures, and serous tubal intraepithelial carcinomas were identified in 3 tumors with HG-noninv. Immunohistochemically, most HG-noninv showed aberrant p53 expression, frequent IMP3 positivity, p16 overexpression, a high MIB-1 labeling index, and infrequent PAX2. By molecular analysis, the pure HG-noninv and 13 HGSCs with HG-noninv showed TP53 mutations, but KRAS/BRAF mutations were not detected in any of them. In 1 tumor, we detected an identical TP53 mutation in both HG-noninv and HG-inv components by using laser capture microdissection. These immunohistochemical and molecular features of HG-noninv were similar to those of conventional invasive HGSCs but different from those of SBTs. In conclusion, our results showed that a cytologically HG-noninv growth pattern simulating an SBT is a morphological spectrum of HGSC, but not a true SBT.

  13. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

    PubMed Central

    el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.

    2015-01-01

    BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284

  14. HER-2 and cancer antigen 125 evaluation in ovarian borderline tumors by immunohistochemistry and fluorescence in situ hybridization.

    PubMed

    Heinrich, J K R; Böttcher-Luiz, F; Andrade, L L A; Davidson, S; Bonds, L; Stephens, J; Varella-Garcia, M

    2004-01-01

    The study determined the expression of cancer antigen (CA) 125 and HER-2 in 45 borderline ovarian tumors (BOTs) and investigated the correlation of these biologic markers with histologic type, clinical stage, and outcome. The level of CA 125 protein was assessed using DAKO's M-11 clone antibody in immunohistochemistry (IHC) assays (Carpinteria, CA). The HER-2 protein expression was assessed in IHC assays using the HercepTest (DAKO), and the HER-2 gene copy number per cell was investigated through fluorescence in situ hybridization (FISH) assays using VYSIS' PathVysion DNA Probe (Downers Grove, IL). Expression of the CA 125 protein was detected in 49% of the samples (22 out of 45 tumors) and significantly associated with the serous histologic type. However, CA 125 expression did not associate with clinical stage or outcome. Protein overexpression or gene amplification of HER-2 was not found. However, abnormal FISH results were detected in 16% (seven out of 45 patients) of specimens comprising extranumerary copies of HER-2 and/or chromosome 17 per cell. Abnormal FISH results were found to be independent of CA 125 expression and histologic type whereas they positively associate with advanced clinical stage. Our data show that HER-2 is not altered in BOTs, and the presence of aneusomy for chromosome 17 and HER-2 may predict tumor progression.

  15. An unusual case of a borderline Brenner tumor associated with bilateral serous cystadenoma and endometrial carcinoma.

    PubMed

    Cruz-Galarza, Daniel; Pérez-Rodríguez, Omar; Laboy-Torres, Joaquín; Gutiérrez-Rivera, Silvia

    2014-01-01

    Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.

  16. Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor

    2016-06-01

    Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.

  17. Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

    PubMed

    Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

    2017-02-06

    Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT.

  18. Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.

    PubMed

    Horn, Lars-Christian; Höhn, Anne K; Einenkel, Jens; Siebolts, Udo

    2014-11-01

    Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.

  19. Diagnosis problems in a case of ovarian tumor - case presentation.

    PubMed

    Albu, Dinu Florin; Albu, Cristina CrenguŢa; Văduva, Constantin Cristian; Niculescu, Mihaela; Edu, Antoine

    2016-01-01

    Ovarian epithelial tumors are the most common ovarian neoplasms, standing for more than half of all ovarian tumors. Borderline ovarian tumors represent a distinct group recognized by the World Health Organization (WHO), histologically distinct low ovarian carcinomas. They are tumors with low grade of malignancy with good progress and prognosis. The authors present a case of an ovarian tumor with diagnosis problems. It was the case of a 38-year-old patient with no genital pathological history, presenting hypogastric pain, dysmenorrhea, abdominal distension. The imaging performed examinations suggested an ovarian tumor with potential malignancy. The symptoms were nonspecific and the treatment was surgical. The piece was processed by paraffin inclusion and microscopically examined. Although the imaging examinations may be suggestive for potentially malignant lesions, the histopathological relation with the immunohistochemical one is the one that establishes the diagnosis. Following these examinations, there was established an ovarian borderline tumor. This is included in the lesions with low malignancy, the further evolution of the patient being a good one. The purpose of this presentation was the warning of the importance of histopathological examination linked with the immunohistochemical one, although the imaging may present lesions with malignancy criteria. Also, it was performed a literature review of borderline tumors in young women in terms of diagnosis and therapeutic conduct.

  20. Principles of Treatment for Borderline, Micropapillary Serous, and Low-Grade Ovarian Cancer.

    PubMed

    Hacker, Kari E; Uppal, Shitanshu; Johnston, Carolyn

    2016-09-01

    Borderline ovarian tumors (BOTs) are less common than epithelial ovarian cancers (EOCs). Low-grade EOCs (LG-EOCs) occur even less frequently than BOTs. After primary therapy, recurrence rates of BOTs and LG-EOCs are significantly lower and the stage-adjusted survival is higher than for high-grade EOCs. Thus, determining the best management in terms of traditional ovarian cancer staging and debulking procedures is more challenging and has been recently brought to question. This article reviews the particulars of BOTs and LG-EOCs, their similarities and differences, and how they are best managed and treated, and emphasizes the major role of surgery and the controversial role of chemotherapy. Because these tumors disproportionately affect younger women, this review addresses ovarian preservation in circumstances when fertility or hormonal preservation is desired.

  1. Interventions for the treatment of borderline ovarian tumours

    PubMed Central

    Faluyi, Olusola; Mackean, Melanie; Gourley, Charlie; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown. Objectives To evaluate the benefits and harm of different treatment modalities offered for borderline ovarian tumours. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and EMBASE to 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) that compared different interventions in adult women diagnosed with borderline ovarian tumours of any histological variant. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed. Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intraperitoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias. One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral

  2. [Ovarian fibrothecal tumor: case report].

    PubMed

    González Gleason, Alejandro; De la Cruz, Sebastián Iris; Torres Salas, María Esther; Guzmán Patraca, Carlos; Chavarría Olarte, María Eugenia; Reyes Fuentes, Alejandro

    2002-05-01

    Tumors with stromal or sex-cords origin are scarce, and comprise only 5% or less of all ovarian tumors. Nevertheless functional tumor types are the most striking ones, only few of them produce hormonal symptoms. Fibrothecal tumors belong to the stromal cells tumor class, with differentiation towards both fibroblastic-type cells of thecal cell. We present a case report of a 68 years old woman with an ovarian tumor sized 14 x 9 x 7 cm. The treatment was the extirpation of the tumor. Microscopic evaluation of the surgical piece reported an ovarian fibrothecal tumor.

  3. Epithelial membrane protein 1 expression in ovarian serous tumors.

    PubMed

    Demirag, Guzin Gonullu; Kefeli, Mehmet; Kemal, Yasemin; Yucel, Idris

    2016-03-01

    The present study aimed to analyze the clinical significance of epithelial membrane protein 1 (EMP1) expression in ovarian serous tumors. A total of 84 cases of ovarian serous tumor (50 patients with malignant ovarian serous tumors and 34 patients with borderline and benign serous tumors) were retrospectively analyzed. Differences in the expression levels of EMP1 between the malignant and non-malignant tumor groups were evaluated by immunohistochemical staining. In addition, the association between EMP1 expression and prognostic factors in malignant ovarian serous tumors was investigated. The expression levels of EMP1 were significantly reduced in all the 50 malignant ovarian serous tumors, compared with the 34 non-malignant ovarian serous tumors (P<0.000). Reduced expression of EMP1 was correlated with high grade (P=0.009) and stage (P<0.000) of malignant tumors. EMP1 expression was not observed to be correlated with any other investigated parameters, including surgery, type of operation and chemotherapy response (P>0.005). These results indicated that EMP1 may have a significant role as a negative regulator in ovarian serous tumors, and reduced EMP1 expression in serous tumors may be associated with increased disease severity.

  4. Selection of suitable reference genes for gene expression studies in normal human ovarian tissues, borderline ovarian tumours and ovarian cancer.

    PubMed

    Ofinran, Olumide; Bose, Ujjal; Hay, Daniel; Abdul, Summi; Tufatelli, Cristina; Khan, Raheela

    2016-12-01

    The use of reference genes is the most common method of controlling the variation in mRNA expression during quantitative polymerase chain reaction, although the use of traditional reference genes, such as β‑actin, glyceraldehyde‑3‑phosphate dehydrogenase or 18S ribosomal RNA, without validation occasionally leads to unreliable results. Therefore, the present study aimed to evaluate a set of five commonly used reference genes to determine the most suitable for gene expression studies in normal ovarian tissues, borderline ovarian and ovarian cancer tissues. The expression stabilities of these genes were ranked using two gene stability algorithms, geNorm and NormFinder. Using geNorm, the two best reference genes in ovarian cancer were β‑glucuronidase and β‑actin. Hypoxanthine phosphoribosyltransferase‑1 and β‑glucuronidase were the most stable in ovarian borderline tumours, and hypoxanthine phosphoribosyltransferase‑1 and glyceraldehyde‑3‑phosphate dehydrogenase were the most stable in normal ovarian tissues. NormFinder ranked β‑actin the most stable in ovarian cancer, and the best combination of two genes was β‑glucuronidase and β‑actin. In borderline tumours, hypoxanthine phosphoribosyltransferase‑1 was identified as the most stable, and the best combination was hypoxanthine phosphoribosyltransferase‑1 and β‑glucuronidase. In normal ovarian tissues, β‑glucuronidase was recommended as the optimum reference gene, and the most optimum pair of reference genes was hypoxanthine phosphoribosyltransferase‑1 and β‑actin. To the best of our knowledge, this is the first study to investigate the selection of a set of reference genes for normalisation in quantitative polymerase chain reactions in different ovarian tissues, and therefore it is recommended that β‑glucuronidase, β‑actin and hypoxanthine phosphoribosyltransferase‑1 are the most suitable reference genes for such analyses.

  5. Endometrioid Paraovarian Borderline Cystic Tumor in an Infant with Proteus Syndrome

    PubMed Central

    Vasquez, Liliana; Tello, Mariela; Maza, Ivan; Oscanoa, Monica; Dueñas, Milagros; Castro, Haydee; Latorre, Alan

    2015-01-01

    Ovarian and paraovarian neoplasms are uncommon in children, mainly originating from germ cell tumors and, least frequently, epithelial tumors. There is an association between genital tract tumors and Proteus syndrome, a rare, sporadic, and progressive entity, characterized by a postnatal overgrowth in several tissues caused by a mosaic mutation in the AKT1 gene. We describe a 20-month-old asymptomatic infant with Proteus syndrome who developed an endometrioid paraovarian borderline cystic tumor. This is the youngest patient so far reported in the literature with this rare syndrome and an adnexal tumor of borderline malignancy. A total of nine patients have been described with female tract tumors and associated Proteus syndrome, which includes bilateral ovarian cystadenomas and other benign masses. A paraovarian neoplasm is extremely rare in children and could be considered a criterion for Proteus syndrome. Standardized staging and treatment of these tumors are not well established; however, most authors conclude that these neoplasms must be treated as their ovarian counterparts. PMID:26558123

  6. Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination

    PubMed Central

    Miyoshi, Ai; Miyatake, Takashi; Hara, Takeya; Tanaka, Asuka; Komura, Naoko; Komiya, Shinnosuke; Kanao, Serika; Takeda, Masumi; Mimura, Mayuko; Nagamatsu, Masaaki; Yokoi, Takeshi

    2015-01-01

    Borderline ovarian tumors are benign but relatively large tumors that are often initially mistaken as ovarian cancers. We report three cases of stage I borderline ovarian tumors having massive ascites that we (preoperatively) suspected of being advanced ovarian cancer. The three patients (35, 47, and 73 years old) reported feeling fullness of the abdomen before consulting their gynecologist. By CT scan, they were diagnosed with a pelvic tumor accompanied by massive ascites, the diameters of which were 11, 20, and 11 cm, respectively. Postsurgical pathology showed all were stage I borderline ovarian tumors without dissemination; two were mucinous and one was serous. The amount of ascites was 6,300, 2,600, and 3,600 mL, respectively, and was serous in all. Cytodiagnosis of the ascites found that one was positive for tumor cells and two were negative. After resection of the mass, the ascites disappeared in all three cases. No pleural effusion was present at any time. The literature is reviewed concerning ascites and pleural effusions linked to ovarian tumors, and a supposition is forwarded of why pleural effusion presents sporadically in these cases. PMID:26858849

  7. The accuracy of frozen section by tumor weight for ovarian epithelial neoplasms.

    PubMed

    Puls, L; Heidtman, E; Hunter, J E; Crane, M; Stafford, J

    1997-10-01

    This study evaluated the effect ovarian weight has on the accuracy of frozen sections in serous and mucinous ovarian tumors. The study group included 294 patients who had an initial frozen section (189 serous and 105 mucinous tumors) at surgery. The pathology reports were separated into subgroups (benign, borderline, or malignant). Tumors were broken down into three weight categories: < or = 450 g, > 450 to < or = 1360 g, and > 1360 g. In each weight category, accuracy, sensitivity, specificity, and positive and negative predicative values were calculated on frozen sections. The mean weight of the ovarian tumors was 1042 g. As the weight increased in serous tumors, the sensitivity fell from 96.2 to 93.8 to 75%, respectively, in each weight category. The same trend was noted with mucinous tumors as sensitivity fell from 91.7 to 87.5 to 66.7%, respectively. With an increase in the size of ovarian tumors, a decrease in the sensitivity of frozen section was observed. With tumors greater than 1360 g, sensitivity was only 69%. Twenty-three percent of ovarian tumors revealing borderline diagnosis at frozen section were malignant on the final pathology report, with the greatest misclassification in > 1360-g mucinous tumors (50%). For patients with large ovarian tumors, consideration should be given to performing staging at the time of the initial laparotomy.

  8. Paired box gene 2 is associated with estrogen receptor α in ovarian serous tumors: Potential theory basis for targeted therapy.

    PubMed

    Wang, Min; Ma, Haifen

    2016-08-01

    It has been suggested that Paired box gene (PAX)2 is activated by estradiol via estrogen receptor (ER)α in breast and endometrial cancer. The expression of PAX2 was restricted to ovarian serous tumors and only one case was positive in borderline mucinous tumor in our previous study. In the present study, immunohistochemistry was performed to assess the expression of ERα in 58 cases of ovarian serous tumors, including 30 serous cystadenomas, 16 borderline serous cystadenomas, 12 serous carcinomas and 67 cases of ovarian mucinous tumors, including 29 mucinous cystadenoma, 23 borderline mucinous cystadenoma and 15 mucinous carcinoma, which were the same specimens with detection of PAX2 expression. The results demonstrated that ERα was expressed in 10% (3/30) of serous cystadenomas, 62.5% (10/16) borderline serous cystadenomas and 66.7% (8/12) serous carcinomas. The expression of ERα in borderline serous cystadenomas and serous carcinomas were significantly higher compared with that in serous cystadenomas (P<0.01). ERα was detected in 3.4% (1/29) mucinous cystadenoma, 26.1% (6/23) borderline mucinous cystadenoma and only 6.7% (1/15) mucinous carcinoma. Furthermore, a scatter plot of the expression of PAX2 and ERα revealed a linear correlation between them in ovarian serous tumors (P<0.0001). With few positive results, no correlation was determined in ovarian mucinous tumors. It was demonstrated that PAX2 is associated with ERα in ovarian serous tumors, and this may become a potential theory basis for targeted therapy for ovarian serous tumors. Further research is required to determine how PAX2 and ERα work together, and the role of targeted therapy in ovarian serous tumors.

  9. Diagnostic potential of tumor DNA from ovarian cyst fluid

    PubMed Central

    Wang, Yuxuan; Sundfeldt, Karin; Mateoiu, Constantina; Shih, Ie-Ming; Kurman, Robert J; Schaefer, Joy; Silliman, Natalie; Kinde, Isaac; Springer, Simeon; Foote, Michael; Kristjansdottir, Björg; James, Nathan; Kinzler, Kenneth W; Papadopoulos, Nickolas; Diaz, Luis A; Vogelstein, Bert

    2016-01-01

    We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts. Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions. DOI: http://dx.doi.org/10.7554/eLife.15175.001 PMID:27421040

  10. Extremely rare borderline phyllodes tumor in the male breast: a case report.

    PubMed

    Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun

    2015-01-01

    Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation.

  11. Pattern of HER-2 Gene Amplification and Protein Expression in Benign, Borderline, and Malignant Ovarian Serous and Mucinous Neoplasms.

    PubMed

    Mohammed, Rabab A A; Makboul, Rania; Elsers, Dalia A H; Elsaba, Tarek M A M; Thalab, Abeer M A B; Shaaban, Omar M

    2016-06-15

    Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur more frequently.

  12. Incidentally Discovered Extensive Squamous Metaplasia within Borderline Phyllodes Tumor: Presentation of a Rare Tumor.

    PubMed

    Uğraş, Nesrin; Tolunay, Şahsine; Öz Atalay, Fatma; Gökgöz, Şehsuvar

    2016-01-01

    Phyllodes tumors are uncommon biphasic fibroepithelial neoplasms of breast, comprising less than 1% of all breast neoplasms. We therefore aimed to present the case with its microscopic findings. In this article, we report a 59-year-old female admitted to the general surgery department with a rapidly, enlarging, palpable mass in right breast. After histopathological examination, it was diagnosed as borderline phyllodes tumor with extensive squamous metaplasia. Metaplastic changes are infrequent in the stromal and epithelial component of these tumors. Extensive squamous metaplasia within phyllodes tumor is rare and may occur in benign, borderline and malign subtypes.

  13. Requirement for expert histopathological assessment of ovarian cancer and borderline tumours

    PubMed Central

    Sengupta, P S; Shanks, J H; Buckley, C H; Ryder, W D J; Davies, J; Reynolds, K; Slade, R J; Kitchener, H C; Jayson, G C

    2000-01-01

    The distinction between borderline ovarian tumours (BOT) and ovarian carcinoma is made by histopathological assessment. Of 64 patients managed according to institutional BOT protocols, 27 (42%) had been referred with a diagnosis of ovarian carcinoma that was subsequently changed to BOT following histopathological review. The 70% 6-year event-free survival of the patients with a revised diagnosis was not significantly different from those who were referred with a diagnosis of BOT. This change in diagnosis is important as it avoids the need for chemotherapy for most patients and results in patients receiving appropriate information concerning prognosis. Interestingly, 24 patients (38.1%) reported a family history of epithelial cancer, a finding that has not been reported previously.© 2000 Cancer Research Campaign PMID:10732741

  14. Novel Treatment Shrinks Ovarian Tumors in Mice

    Cancer.gov

    Researchers have developed a new approach for treating tumors that express mutant versions of the p53 protein, which are present in more than half of all cancers, including an aggressive and common subtype of ovarian cancer.

  15. Twenty-five-year-old Woman with Bilateral Borderline Ovarian Tumour Desiring to Preserve Fertility – Case Report and Literature Review on the Current State of Fertility Preservation in Women with Borderline Ovarian Tumours

    PubMed Central

    Findeklee, S.; Lotz, L.; Heusinger, K.; Hoffmann, I.; Dittrich, R.; Beckmann, M. W.

    2016-01-01

    Borderline ovarian tumours are semimalignant tumours occurring unilaterally or bilaterally with a peak incidence among women of reproductive age. Since the affected women often wish to preserve fertility, particular precautions must be taken when counselling the patient and obtaining consent prior to planning an individual treatment. Options for preserving fertility include an organ-sparing surgical procedure and cryopreservation of oocytes and/or ovarian tissue. In this article, we report on a 25-year-old patient with a bilateral seromucinous borderline tumour who desired all fertility-preserving options. In order to perform the procedure without delay, we opted to perform luteal phase stimulation prior to oocyte retrieval. We conclude by discussing the current literature on the state of fertility preservation in the treatment of borderline ovarian tumours. PMID:27904170

  16. Twenty-five-year-old Woman with Bilateral Borderline Ovarian Tumour Desiring to Preserve Fertility - Case Report and Literature Review on the Current State of Fertility Preservation in Women with Borderline Ovarian Tumours.

    PubMed

    Findeklee, S; Lotz, L; Heusinger, K; Hoffmann, I; Dittrich, R; Beckmann, M W

    2016-11-01

    Borderline ovarian tumours are semimalignant tumours occurring unilaterally or bilaterally with a peak incidence among women of reproductive age. Since the affected women often wish to preserve fertility, particular precautions must be taken when counselling the patient and obtaining consent prior to planning an individual treatment. Options for preserving fertility include an organ-sparing surgical procedure and cryopreservation of oocytes and/or ovarian tissue. In this article, we report on a 25-year-old patient with a bilateral seromucinous borderline tumour who desired all fertility-preserving options. In order to perform the procedure without delay, we opted to perform luteal phase stimulation prior to oocyte retrieval. We conclude by discussing the current literature on the state of fertility preservation in the treatment of borderline ovarian tumours.

  17. Dub3 expression correlates with tumor progression and poor prognosis in human epithelial ovarian cancer.

    PubMed

    Zhou, Bo; Shu, Bin; Xi, Tao; Su, Ning; Liu, Jing

    2015-03-01

    Dub3 is a deubiquitinating enzyme. It is highly expressed in tumor-derived cell lines and has an established role in tumor proliferation. However, the role of Dub3 in human ovarian cancer remains unclear. Expression of Dub3 was evaluated in ovarian cancer tissues and cell lines by immunohistochemistry and Western blot analysis. The relationship between Dub3 expression and clinicopathological characteristics was analyzed. Using RNA interference, the effects of Dub3 on cell proliferation and apoptosis were investigated in ovarian cancer cell line. All normal ovary tissues exhibited very little or no Dub3 immunoreactivity. High levels of Dub3 expression were examined by immunohistochemical analysis in 13.3% of cystadenomas, in 30.0% of borderline tumors, and in 58.9% of ovarian carcinomas, respectively. Dub3 expression was significantly associated with lymph node metastasis and clinical staging (P<0.05). Multivariate survival analysis indicated that Dub3 expression was an independent prognostic indicator of the survival of patients with ovarian cancer. Furthermore, the expression of Cdc25A was closely correlated with that of Dub3 in cancer cells and tissues. Knockdown of Dub3 could inhibit the proliferation of ovarian cancer cells and increase cell apoptosis. These data indicate that the Dub3 might be a valuable biomarker for the prediction of ovarian cancer prognosis and Dub3 inhibition might be a potential strategy for ovarian cancer treatment.

  18. Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas

    PubMed Central

    Zang, Xingxing; Sullivan, Peggy S; Soslow, Robert A; Waitz, Rebecca; Reuter, Victor E; Wilton, Andrew; Thaler, Howard T; Arul, Manonmani; Slovin, Susan F; Wei, Joyce; Spriggs, David R; Dupont, Jakob; Allison, James P

    2010-01-01

    B7-H3 and B7x are members of the B7 family of immune regulatory ligands that are thought to attenuate peripheral immune responses through co-inhibition. Previous studies have correlated their overexpression with poor prognosis and decreased tumor-infiltrating lymphocytes in various carcinomas including uterine endometrioid carcinomas, and mounting evidence supports an immuno-inhibitory role in ovarian cancer prognosis. We sought to examine the expression of B7-H3 and B7x in 103 ovarian borderline tumors and carcinomas and study associations with clinical outcome. Using immunohistochemical tissue microarray analysis on tumor specimens, we found that 93 and 100% of these ovarian tumors express B7-H3 and B7x, respectively, with expression found predominantly on cell membranes and in cytoplasm. In contrast, only scattered B7-H3- and B7x-positive cells were detected in non-neoplastic ovarian tissues. B7-H3 was also expressed in the endothelium of tumor-associated vasculature in 44% of patients, including 78% of patients with high-stage tumors (FIGO stages III and IV), nearly all of which were high-grade serous carcinomas, and 26% of patients with low-stage tumors (FIGO stages I and II; P<0.001), including borderline tumors. Analysis of cumulative survival time and recurrence incidence revealed that carcinomas with B7-H3-positive tumor vasculature were associated with a significantly shorter survival time (P=0.02) and a higher incidence of recurrence (P=0.03). The association between B7-H3-positive tumor vasculature and poor clinical outcome remained significant even when the analysis was limited to the high-stage subgroup. These results show that ovarian borderline tumors and carcinomas aberrantly express B7-H3 and B7x, and that B7-H3-positive tumor vasculature is associated with high-grade serous histological subtype, increased recurrence and reduced survival. B7-H3 expression in tumor vasculature may be a reflection of tumor aggressiveness and has diagnostic and

  19. Epigenetic Regulation of Ovarian Tumor Immunity

    DTIC Science & Technology

    2009-11-01

    of tumor challenge. Results: In the past year, we have established that: 1. The administration of HDACi (Trichostatin A) to ovarian tumor...10 0 0 20 40 60 80 Days post treatment % C D 4+ C D 25 +F ox p3 + ce lls  PBS  1-MT  TSA Figure 1: HDACi

  20. Tumor infiltrating lymphocytes in ovarian cancer.

    PubMed

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

    The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.

  1. Ovarian tumor-derived ectopic hyperprolactinemia.

    PubMed

    Elms, Autumn F; Carlan, S J; Rich, Amy E; Cerezo, Lizardo

    2012-12-01

    To describe extreme hyperprolactinemia originating from a pituitary adenoma in the wall of an ovarian dermoid. This is a description of an unusual case and a review of ectopic prolactin production. Ectopic production of prolactin is a rare condition that has been reported in isolated organ system pathology including ovaries. An ovarian dermoid is a benign neoplasm that has the potential for active unregulated endocrine function. Hyperprolactinemia can result from functioning lactotrophs found in ovarian dermoids and can lead to clinical sequelae. Definitive treatment of the condition requires surgical removal of the functioning endocrine tissue. Extreme hyperprolactinemia caused by a pituitary tumor located within a dermoid has not been reported before. We present a case of profound hyperprolactinemia originating from a pituitary adenoma found in the wall of an ovarian dermoid and give a broad overview of the condition and literature. Ectopic prolactin production should always be considered in symptomatic patients found to have elevated serum levels and no findings on brain imaging.

  2. Ovarian tumor characterization using 3D ultrasound.

    PubMed

    Acharya, U Rajendra; Sree, S Vinitha; Krishnan, M Muthu Rama; Saba, Luca; Molinari, Filippo; Guerriero, Stefano; Suri, Jasjit S

    2012-12-01

    Among gynecological malignancies, ovarian cancer is the most frequent cause of death. Preoperative determination of whether a tumor is benign or malignant has often been found to be difficult. Because of such inconclusive findings from ultrasound images and other tests, many patients with benign conditions have been offered unnecessary surgeries thereby increasing patient anxiety and healthcare cost. The key objective of our work is to develop an adjunct Computer Aided Diagnostic (CAD) technique that uses ultrasound images of the ovary and image mining algorithms to accurately classify benign and malignant ovarian tumor images. In this algorithm, we extract texture features based on Local Binary Patterns (LBP) and Laws Texture Energy (LTE) and use them to build and train a Support Vector Machine (SVM) classifier. Our technique was validated using 1000 benign and 1000 malignant images, and we obtained a high accuracy of 99.9% using a SVM classifier with a Radial Basis Function (RBF) kernel. The high accuracy can be attributed to the determination of the novel combination of the 16 texture based features that quantify the subtle changes in the images belonging to both classes. The proposed algorithm has the following characteristics: cost-effectiveness, complete automation, easy deployment, and good end-user comprehensibility. We have also developed a novel integrated index, Ovarian Cancer Index (OCI), which is a combination of the texture features, to present the physicians with a more transparent adjunct technique for ovarian tumor classification.

  3. Comparison of loss of heterozygosity patterns between ovarian tumors of low malignant potential and malignant ovarian tumors

    SciTech Connect

    Crawford, E.C.; Miller, D.M.; Finley, W.H.

    1994-09-01

    Ovarian tumors of low malignant potential (LMP) represent a pathologic subtype of ovarian tumor that possess many features common to malignant tumors including epithelial stratification, increased mitotic activity and atypical cellularity. These tumors, however, do not invade the ovarian stroma and have a much improved patient prognosis. Utilizing dinucleotide repeats, loss of heterozygosity (LOH) studies were performed on a total of 12 ovarian tumors of LMP in 5 regions found to have significant levels of LOH in malignant ovarian tumors. The regions chosen for study were 3p, 6q, 11p, 17p and 17q. LOH could be demonstrated in malignant ovarian tumors in loci from 3p, 11p and both chromosomal arms of 17 when compared to normal tissue from the same patient. Loss in malignant tumors was more common in loci mapped to 3p21 and to 11p15. OH was not noted in any samples for a repeat in the TP53 gene even though flanking markers on 17p were lost in 1 patient with a malignant tumor. Loss was not demonstrated in any of the loci examined from 6q in malignant ovarian tumors. LOH was not demonstrated in any of the 39 loci examined from any of the five chromosomal regions in the ovarian tumors of LMP. Cytogenetic analyses of these LMP tumors were consistent with lack of involvement in these chromosomal regions. These data suggest the mechanism of tumorigenesis is different in tumors of LMP from that in malignant ovarian tumors.

  4. Classification of serous ovarian tumors based on microarray data using multicategory support vector machines.

    PubMed

    Park, Jee Soo; Choi, Soo Beom; Chung, Jai Won; Kim, Sung Woo; Kim, Deok Won

    2014-01-01

    Ovarian cancer, the most fatal of reproductive cancers, is the fifth leading cause of death in women in the United States. Serous borderline ovarian tumors (SBOTs) are considered to be earlier or less malignant forms of serous ovarian carcinomas (SOCs). SBOTs are asymptomatic and progression to advanced stages is common. Using DNA microarray technology, we designed multicategory classification models to discriminate ovarian cancer subclasses. To develop multicategory classification models with optimal parameters and features, we systematically evaluated three machine learning algorithms and three feature selection methods using five-fold cross validation and a grid search. The study included 22 subjects with normal ovarian surface epithelial cells, 12 with SBOTs, and 79 with SOCs according to microarray data with 54,675 probe sets obtained from the National Center for Biotechnology Information gene expression omnibus repository. Application of the optimal model of support vector machines one-versus-rest with signal-to-noise as a feature selection method gave an accuracy of 97.3%, relative classifier information of 0.916, and a kappa index of 0.941. In addition, 5 features, including the expression of putative biomarkers SNTN and AOX1, were selected to differentiate between normal, SBOT, and SOC groups. An accurate diagnosis of ovarian tumor subclasses by application of multicategory machine learning would be cost-effective and simple to perform, and would ensure more effective subclass-targeted therapy.

  5. Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

    PubMed Central

    Virant-Klun, Irma; Stimpfel, Martin

    2016-01-01

    Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

  6. Collecting Tumor Samples From Patients With Gynecological Tumors

    ClinicalTrials.gov

    2016-10-26

    Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell

  7. ATR-FTIR spectroscopy coupled with chemometric analysis discriminates normal, borderline and malignant ovarian tissue: classifying subtypes of human cancer.

    PubMed

    Theophilou, Georgios; Lima, Kássio M G; Martin-Hirsch, Pierre L; Stringfellow, Helen F; Martin, Francis L

    2016-01-21

    Surgical management of ovarian tumours largely depends on their histo-pathological diagnosis. Currently, screening for ovarian malignancy with tumour markers in conjunction with radiological investigations has a low specificity for discriminating benign from malignant tumours. Also, pre-operative biopsy of ovarian masses increases the risk of intra-peritoneal dissemination of malignancy. Intra-operative frozen section, although sufficiently accurate in differentiating tumours according to their histological type, increases operation times. This results in increased surgery-related risks to the patient and additional burden to resource allocation. We set out to determine whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, combined with chemometric analysis can be applied to discriminate between normal, borderline and malignant ovarian tumours and classify ovarian carcinoma subtypes according to the unique spectral signatures of their molecular composition. Formalin-fixed, paraffin-embedded ovarian tissue blocks were de-waxed, mounted on Low-E slides and desiccated before being analysed using ATR-FTIR spectroscopy. Chemometric analysis in the form of principal component analysis (PCA), successive projection algorithm (SPA) and genetic algorithm (GA), followed by linear discriminant analysis (LDA) of the obtained spectra revealed clear segregation between benign versus borderline versus malignant tumours as well as segregation between different histological tumour subtypes, when these approaches are used in combination. ATR-FTIR spectroscopy coupled with chemometric analysis has the potential to provide a novel diagnostic approach in the accurate diagnosis of ovarian tumours assisting surgical decision making to avoid under-treatment or over-treatment, with minimal impact to the patient.

  8. Ovarian Hormones and Borderline Personality Disorder Features: Preliminary Evidence for Interactive Effects of Estradiol and Progesterone

    PubMed Central

    Eisenlohr-Moul, Tory A.; DeWall, C. Nathan; Girdler, Susan S.; Segerstrom, Suzanne C.

    2015-01-01

    Cyclical fluctuations in the ovarian hormones 17β-estradiol (E2; estrogen) and progesterone (P4) predict emotions, cognitive processes, and behaviors relevant to Borderline Personality Disorder (BPD); however, there are individual differences in sensitivity to normal hormone shifts. This study examined associations of naturally occurring hormonal changes with concurrent BPD feature expression. Forty women sampled for a flat distribution of the PAI-BOR (n=10 where T<50, n=10 where 5070) provided 4 weekly saliva samples and psychological assessments. Across most outcomes (e.g., BPD features, felt rejection, anger rumination, negative urgency) P4 deviation (from one’s person mean) moderated the effect of current E2 deviation (from one’s person mean) among women high (+1 SD) in trait BPD features such that E2 deviation was negatively associated with symptoms only when P4 was higher-than-usual. Cyclical hormone changes (e.g., higher P4 in the luteal phase; E2 fluctuations at ovulation and in the luteal phase) may impact BPD feature expression among at-risk women. PMID:25837710

  9. The status of epidermal growth factor receptor in borderline ovarian tumours

    PubMed Central

    Showeil, Rania; Romano, Claudia; Valganon, Mikel; Lambros, Maryou; Trivedi, Pritesh; Van Noorden, Susan; Sriraksa, Ruethairat; El-Kaffash, Dalal; El-Etreby, Nour; Natrajan, Rachael; Foroni, Letizia; Osborne, Richard; El-Bahrawy, Mona

    2016-01-01

    The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear

  10. Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression.

    PubMed

    Kurosaki, Akira; Hasegawa, Kosei; Kato, Tomomi; Abe, Kenji; Hanaoka, Tatsuya; Miyara, Akiko; O'Shannessy, Daniel J; Somers, Elizabeth B; Yasuda, Masanori; Sekino, Tetsuo; Fujiwara, Keiichi

    2016-04-15

    Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy.

  11. Endometriosis-associated serous borderline tumor and endometrial stromal sarcoma of the ovary: a report of a rare lesion in an infant.

    PubMed

    Ho, Ronnie S L; Chan, Godfrey C F; Ha, Shau Yin; Ip, Philip P C

    2012-01-01

    Endometriosis in infancy is most unusual, and associated tumors in this age group are exceptionally rare. We report a case of a serous borderline tumor and endometrial stromal sarcoma arising in an ovarian endometriotic cyst. The patient was an infant of 18 months of age who presented with an incidental abdominal mass. The serum sex hormones were at prepubertal levels. There was no evidence of precocious puberty or any obvious genital anomaly. Intraoperative findings included a solitary solid and multicystic right ovarian mass without evidence of any extraovarian disease. On microscopic examination, the tumor was composed of an intimate mixture of florid papillary and stromal cell proliferation in the wall of an endometriotic cyst. The papillae showed hierarchical branching and had hyalinized and edematous cores with scattered psammoma bodies. The epithelial cells were mildly atypical and mitotically inactive. The underlying endometrial stromal cells were arranged in irregular tongues that permeated the thickened fibrous cyst wall. They were mitotically active and immunoreactive for CD10. There was no evidence of any primitive germ cell tumor. The patient received no adjuvant treatment and had an uneventful postoperative follow-up period of 30 months. To the best of our knowledge, endometriosis associated with this most unusual combination of ovarian tumors has never been reported in an infant.

  12. Mitochondrial DNA Mutations in Epithelial Ovarian Tumor Progression

    DTIC Science & Technology

    2007-12-01

    histological subtype of ovarian cancer and is the most lethal gynecologic malignancy. The relationship between stage at presentation and survival in serous ...among and within stages of epithelial ovarian cancer , focusing on serous , mucinous and endometrioid subtypes (1-18 Months). a. Collections and...not serous or mucinous epithelial ovarian tumors. Cancer Res 58: 2095-2097, 1998. 7. Aikhionbare FO et al:.: Is cumulative frequency of mitochondrial

  13. A rare ovarian tumor, leydig stromal cell tumor, presenting with virilization: a case report

    PubMed Central

    Aminimoghaddam, Soheila; Hashemi, Forough

    2012-01-01

    Leydig stromal cell tumor is a rare ovarian tumor that belongs to the group of sex-cord stromal tumors. They produce testosterone leading to hyperandrogenism. We present a 41yr old woman with symptoms of virilization and a mass of right adenex via ultra Sonography, and a rise of total and free serum testosterone. An ovarian source of androgen was suspected and a surgery performed. A diagnosis of leydig-stromal cell tumor was confirmed. Our report is a reminder that although idiopathic hirsutism and other benign androgen excess disorder like Polycystic Ovarian Syndrome (PCOs) are common, ovarian mass should be considered in differential diagnosis. PMID:23482693

  14. Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype

    DTIC Science & Technology

    2012-06-01

    blocks apoptosis induced by the mammalian lectin, galectin - 3 , which our studies show is expressed in human ovarian tumor tissues and in ascitic fluid...omental cultures. • Optimized immunoblotting protocol for galectin - 3 in ascites • Determination that sialylation of Fas and TNFR1 blocks apoptotic...REPORT DATE 2. REPORT TYPE Annual report 3 . DATES COVERED 4. TITLE AND SUBTITLE Role of receptor sialylation in the ovarian tumor cell

  15. Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-04-05

    Borderline Ovarian Mucinous Tumor; Ovarian Mucinous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer

  16. Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

    ClinicalTrials.gov

    2016-03-16

    Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

  17. CT and MR findings of Krukenberg tumors: Comparison with primary ovarian tumors

    SciTech Connect

    Kim, Seung Hyup; Kim, Won Hong; Park, Kyung Joo

    1996-05-01

    The purposes of this study were to evaluate the CT and MR findings of Krukenberg tumors and to compare them with those of primary ovarian tumors. This study included 20 patients with Krukenberg tumors and 65 patients with various primary ovarian tumors. CT/MR/both imaging studies were available in 15/1/4 patients with Krukenberg tumor and 31/10/24 patients with primary ovarian tumors, respectively. Imaging findings of the tumors were categorized into three subgroups: a solid mass with intratumoral cysts, a solid mass without intratumoral cysts, and a predominantly cystic mass. Among 32 Krukenberg tumors (bilateral in 12 patients), 22 were solid masses with intratumoral cysts, in 14 of which the wall of the intratumoral cysts showed apparently strong contrast enhancement on CT and/or MRI. Six Krukenberg tumors were solid masses without intratumoral cysts, and four were predominantly cystic masses. Imaging findings of 88 primary ovarian tumors (bilateral in 23 patients) were 5 solid masses with intratumoral cysts, 27 solid masses without intratumoral cysts, and 56 predominantly cystic masses. None of the five primary ovarian tumors with solid mass with intratumoral cysts demonstrated apparently strong contrast enhancement of the cyst wall. Krukenberg tumor should be suspected when one sees solid ovarian tumors containing well demarcated intratumoral cystic lesions, especially if the walls of those cysts demonstrate apparently strong contrast enhancement. 11 refs., 4 figs., 1 tab.

  18. The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

    PubMed Central

    Vitiazeva, Varvara; Kattla, Jayesh J.; Flowers, Sarah A.; Lindén, Sara K.; Premaratne, Pushpa; Weijdegård, Birgitta; Sundfeldt, Karin; Karlsson, Niclas G.

    2015-01-01

    Background Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer. Methods In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes. Results The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC). Conclusion Mucinous benign and LMPs along with mucinous low-grade carcinomas

  19. Cadherin-11 mRNA and protein expression in ovarian tumors of different malignancy: No evidence of oncogenic or tumor-suppressive function

    PubMed Central

    VON BÜLOW, CHARLOTTE; OLIVEIRA-FERRER, LETICIA; LÖNING, THOMAS; TRILLSCH, FABIAN; MAHNER, SVEN; MILDE-LANGOSCH, KARIN

    2015-01-01

    Cadherin-11 (CDH11, OB-cadherin) is a mesenchymal cadherin found to be upregulated in various types of tumors and implicated in tumor progression and metastasis. In order to determine the role of CDH11 expression in ovarian tumors, we performed a combined reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemical study on a large cohort of benign, borderline and invasive ovarian tumors. The RT-qPCR and western blot analysis demonstrated that the CDH11 expression was high in benign cystadenomas and decreased with increasing malignancy. This may be explained by the different tumor-stroma ratios, since immunohistochemistry revealed strong staining of stromal cells, particularly vascular smooth muscle cells and endothelial cells, but only weak cytoplasmic or nuclear immunoreactivity of cancer cells. Within the group of invasive carcinomas, high CDH11 protein expression, as detected by western blot analysis, was found to be significantly correlated with advanced stage and nodal involvement. However, the recurrence-free and overall survival analyses did not reveal any prognostic or predictive significance. In conclusion, in contrast to other tumor types, CDH11 does not play an important role in ovarian cancer progression. PMID:26623052

  20. Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype

    DTIC Science & Technology

    2014-08-01

    transit through the peritoneal cavity. Additionally, ST6Gal-I appears to contribute to metastatic targeting of omentum and resistance to cisplatin ...protection of tumor cells against cisplatin - mediated cell death (Task 3). Progress: We have by far made the most progress on Aim 3 and research...ovarian cancer resistance to cisplatin -mediated cell death, as well as death receptor signaling by ovarian cancer cells within the peritoneal cavity

  1. Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism

    PubMed Central

    Penet, Marie-France; Krishnamachary, Balaji; Wildes, Flonne; Mironchik, Yelena; Mezzanzanica, Delia; Podo, Franca; de Reggi, Max; Gharib, Bouchra; Bhujwalla, Zaver M.

    2016-01-01

    Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. Therefore, we used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were ~100 mm3 and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution 1H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action. PMID:27900284

  2. Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism

    PubMed Central

    YUAN, LEI; LIU, XISHI

    2015-01-01

    Platelets are known to facilitate tumor metastasis and thrombocytosis has been associated with an adverse prognosis in ovarian cancer. However, the role of platelets in primary tumour growth remains to be elucidated. The present study demonstrated that the expression levels of various markers in platelets, endothelial adherence and angiogenesis, including, platelet glycoprotein IIb (CD41), platelet endothelial cell adhesion molecule 1 (CD31), vascular endothelial growth factor (VEGF), lysyl oxidase, focal adhesion kinase and breast cancer anti-estrogen resistance 1, were expressed at higher levels in patients with malignant carcinoma, compared with those with borderline cystadenoma and cystadenoma. In addition, the endothelial markers CD31 and VEGF were found to colocalize with the platelet marker CD41 in the malignant samples. Since mice transplanted with human ovarian cancer cells (SKOV3) demonstrated elevated tumor size and decreased survival rate when treated with thrombin or thrombopoietin (TPO), the platelets appeared to promote primary tumor growth. Depleting platelets using antibodies or by pretreating the cancer cells with hirudin significantly attenuated the transplanted tumor growth. The platelets contributed to late, but not early stages of tumor proliferation, as mice treated with platelet-depleting antibody 1 day prior to and 11 days after tumor transplantation had the same tumor volumes. By contrast, tumor size in the early TPO-injected group was increased significantly compared with the late TPO-injected group. These findings suggested that the interplay between platelets and angiogenesis may contribute to ovarian cancer growth. Therefore, platelets and their associated signaling and adhesive molecules may represent potential therapeutic targets for ovarian cancer. PMID:25502723

  3. Ovarian Tumor Cells Studied Aboard the International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    2001-01-01

    In August 2001, principal investigator Jeanne Becker sent human ovarian tumor cells to the International Space Station (ISS) aboard the STS-105 mission. The tumor cells were cultured in microgravity for a 14 day growth period and were analyzed for changes in the rate of cell growth and synthesis of associated proteins. In addition, they were evaluated for the expression of several proteins that are the products of oncogenes, which cause the transformation of normal cells into cancer cells. This photo, which was taken by astronaut Frank Culbertson who conducted the experiment for Dr. Becker, shows two cell culture bags containing LN1 ovarian carcinoma cell cultures.

  4. Using Artificial Neural Networks to Predict Malignancy of Ovarian Tumors

    DTIC Science & Technology

    2007-11-02

    This paper discusses the application of artificial neural networks (ANNs) to preoperative discrimination between benign and malignant ovarian tumors...With the input variables selected by logistic regression analysis, two types of feed-forward neural networks were built: multi-layer perceptrons

  5. Comparison of c-met Expression in Ovarian Epithelial Tumors and Normal Epithelia of the Female Reproductive Tract by Quantitative Laser Scan Microscopy

    PubMed Central

    Huntsman, David; Resau, James H.; Klineberg, Eric; Auersperg, Nelly

    1999-01-01

    The transmembrane tyrosine kinase receptor c-met with its ligand, hepatocyte growth factor/scatter factor (HGF/SF), acts as a mitogen, motogen, and morphogen in many normal epithelia. HGF/SF-met signaling has also been implicated in neoplastic progression and metastasis. In this study, immunofluorescence staining and quantitative laser scanning confocal microscopy were used to measure c-met expression in ovarian surface epithelial tumors from 17 oophorectomy specimens. These specimens were from patients aged 25 to 81 (mean age, 52) and included 10 malignant tumors, 4 borderline tumors, and five benign tumors including a Brenner tumor. For comparison, c-met expression was measured in normal tissues from the same patients, including 4 ovarian surface epithelia, 4 fallopian tube epithelia, 2 endometria, and 3 endocervical epithelia, as well as 3 cases of endometriosis. Relative pixel intensity values of c-met expression ranged from 0.4 in a normal ovarian surface epithelium to 22.3 in a borderline serous tumor. Malignant tumors (mean, 9.6) and borderline tumors (mean, 12.9) had higher average c-met expression levels than normal tissues (mean, 3.6) and endometriosis (mean, 1.8). The expression levels of benign tumors were intermediate (mean, 7.9). Among the normal tissues, c-met expression in fallopian tubes (mean, 8.2; range, 3.4–12.9) was higher than that of the other normal epithelia (mean, 1.6; range, 0.4–4.3). In eight cases where both normal and malignant tissues were sampled, c-met expression was significantly greater in malignant than in normal epithelia (P = 0.01). These findings indicate that c-met plays a role in the biology of the normal tissues examined. They confirm that its expression increases in the malignant progression of ovarian surface epithelial tumors, and suggest that increases comparable to those in frankly malignant carcinomas have already been reached in borderline lesions, ie, early in the neoplastic process. PMID:10433927

  6. Bilateral Sclerosing Stromal Ovarian Tumor in an Adolescent

    PubMed Central

    Naidu, Anjani; Chung, Betty; Simon, Mitchell; Marshall, Ian

    2015-01-01

    Sclerosing stromal tumor of the ovary is a rare, benign, sex cord stromal tumor occurring predominantly in younger women in the 2nd and 3rd decades of life. It typically presents unilaterally with only 2 previously reported cases of bilateral presentation. Common clinical presentations include pelvic or abdominal pain, a mass, or menstrual changes. Although occasionally presenting with hormonal manifestations, virilization as a result of androgen production by the tumor is rare. Here we present an extremely rare case of a sclerosing stromal ovarian tumor in a 14-year-old patient with bilateral presentation and with clinical and biochemical evidence of hyperandrogenemia. PMID:26064755

  7. Estrogen receptor beta, a possible tumor suppressor involved in ovarian carcinogenesis

    PubMed Central

    Lazennec, Gwendal

    2006-01-01

    Ovarian cancer is one of the leading cause of death from gynecological tumors in women. Several lines of evidence suggest that estrogens may play an important role in ovarian carcinogenesis, through their receptors, ERα and ERβ. Interestingly, malignant ovarian tumors originating from epithelial surface constitute about 90% of ovarian cancers and expressed low levels of ERβ, compared to normal tissues. In addition, restoration of ERβ in ovarian cancer cells, leads to strong inhibition of their proliferation and invasion, while apoptosis is enhanced. In this manuscript, recent data suggesting a possible tumor-suppressor role for ERβ in ovarian carcinogenesis are discussed. PMID:16399219

  8. Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study

    PubMed Central

    Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

    2015-01-01

    Background: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). Results: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Conclusion: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed. PMID:25562434

  9. Epigenetic Regulation of Ovarian Tumor Immunity

    DTIC Science & Technology

    2010-11-01

    immunity PRINCIPAL INVESTIGATOR: Protul A. Shrikant, Ph.D. CONTRACTING ORGANIZATION : Health Research Inc., Roswell Park Cancer...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Roswell Park Cancer...intraperitoneal injection on day 10 post-tumor challenge. 2. The cells harvested from the tumor draining LN’s, spleen and the tumor site starting on day 2

  10. Expression of MAGE-C1/CT7 and selected cancer/testis antigens in ovarian borderline tumours and primary and recurrent ovarian carcinomas.

    PubMed

    Zimmermann, Anne-Katrin; Imig, Jochen; Klar, Agnes; Renner, Christoph; Korol, Dimitri; Fink, Daniel; Stadlmann, Sylvia; Singer, Gad; Knuth, Alexander; Moch, Holger; Caduff, Rosmarie

    2013-05-01

    MAGE-C1/CT7, NY-ESO-1, GAGE and MAGE-A4 are members of the cancer/testis (CT) antigen family, which have been proposed as potential targets for cancer immunotherapy. To determine the prevalence and biologic relevance of the novel CT antigen MAGE-C1/CT7 and other antigens, 36 ovarian borderline tumours (BTs), 230 primary ovarian carcinomas (OCs) and 80 recurrent OCs were immunohistochemically analysed using the monoclonal antibodies CT7-33 (MAGE-C1/CT7), E978 (NY-ESO-1), clone 26 (GAGE) and 57B (MAGE-A4). Positivity of at least one CT antigen was present in 39.5 % (81/205) of primary OC and in 50 % (26/52) of all recurrences. Expression of the novel CT antigen MAGE-C1/CT7 was most commonly seen with positivity in 24.5 % of primary and 35.1 % of recurrent OC. MAGE-A4, GAGE and NY-ESO-1 expressions were seen in 22.7, 13.9 and 7.1 % of primary and 22.6, 17.5 and 8.9 % of recurrent OC, respectively. Analysis of histological subtypes (serous, endometrioid, clear cell, mucinous and transitional) exhibited variable expression with negativity in all mucinous OC. High-grade serous OC revealed CT antigen expression in 5.6 to 28 % with MAGE-C1/CT7 being the most frequent, but without correlation with stage or overall survival. MAGE-C1/CT7 expression and coexpression of CT antigens were significantly correlated with grade of endometrioid OC. None of the BT showed CT antigen expression. No significant correlation was seen with stage, overall survival or response to chemotherapy. In summary, CT antigens are expressed in a certain subset of OC with no expression in BT or OC of mucinous histology. These findings may have implications for the design of polyvalent vaccination strategies for ovarian carcinomas.

  11. Evidence for ovarian tumor necrosis factor

    SciTech Connect

    Roby, K.F.

    1989-01-01

    Ovarian folliculogenesis and luteal formation occur concomitantly with the development of new blood vessels that function in nutritional support of the developing follicles. As follicles undergo atresia and the corpus luteum regresses, blood vessels supplying these tissues degenerate. The first study determined if the ovary contained factors that might regulate ovarian angiogenesis. The bovine ovary was subjected to ammonium sulfate (AS) precipitation and the precipitates (ppt.) were assayed in vitro for effects on endothelial cell (CPAE) and fibroblast (3T3 and L929) incorporation of {sup 3}H-thymidine. Heparin sepharose (HS) chromatography of the 80% AS ppt. revealed the inhibitory activity on CPAE and L929 cells did not bind to HS but was found in the HS column breakthrough (80% BT). Sizing chromatography of the 80% BT indicated thymidine incorporation inhibitory activity exhibited a molecular weight of 30,000-50,000 Daltons. TNF was immunohistochemically localized in the human, bovine and rat ovary. Frozen sections were incubated with polyclonal antibody to human recombinant TNF. Antigen-antibody binding was visualized using a Biotin-StreptAvidin peroxidase technique. Immunoreactive TNF (I-TNF) was localized in corpora lutea and the more antral layers of granulosa cells in antral follicles. Incubation of sections with anti-TNF in the presence of excess TNF resulted in lose of immunostaining. Cell blotting and ELISA further indicated I-TNF was present in granulosa cells. In order to determine whether TNF had an effect on follicular steroidogenesis, preovulatory follicles from cyclic proestrus rats were incubated in vitro for up to 24 hours with various doses of human recombinant TNF. Stepwise increases in progesterone (P) accumulation in the incubation media were observed with 30-300 pM TNF.

  12. Virilizing ovarian tumor of cell tumor type not otherwise specified: a case report.

    PubMed

    Faraj, G; Di Gregorio, S; Misiunas, A; Faure, E N; Villabrile, P; Stringa, I; Petroff, N; Bur, G

    1998-10-01

    Whereas ovarian tumors with overt endocrine manifestations account for less than 5% of all ovarian neoplasms, the incidence of virilizing type tumors in postmenopausal women is even lower since the average age of occurrence is 43 years. Steroid cell tumors not otherwise specified (NOS) are even more rare. We report the case of a 56-year-old woman (age of onset of menopause 43 years) who consulted our service due to a hyperandrogenic syndrome: deepening of the voice, temporal balding, hirsutism and cliteromegaly. Laboratory findings indicated hyperandrogenism in male range. The dexamethasone suppression test did not modify basal values, indicating that adrenal origin was unlikely. Transvaginal ultrasound disclosed multiple microcysts in the left ovary. Abdominal tomography was normal. Suspecting an ovarian tumor, bilateral oophorectomy was performed and a pediculate, 3 cm in diameter, was encountered in the left ovary. Histopathological studies determined it to be a virilizing ovarian tumor NOS. Postoperative recovery was fast; normal hormonal values were reached together with visible clinical improvement. This case is reported because this type of tumor is very infrequent in postmenopausal women, and because in this case it was the functional hormonal test that allowed tumor localization.

  13. Analysis of DNA Copy Number Alterations in Ovarian Serous Tumors Identifies New Molecular Genetic Changes in Low-grade and High-grade Carcinomas

    PubMed Central

    Kuo, Kuan-Ting; Guan, Bin; Feng, Yuanjian; Mao, Tsui-Lien; Chen, Xu; Jinawath, Natini; Wang, Yue; Kurman, Robert J.; Shih, Ie-Ming; Wang, Tian-Li

    2009-01-01

    Ovarian serous carcinoma, the most common and lethal type of ovarian cancer, was thought to develop from two distinct molecular pathways. High-grade (HG) serous carcinomas contain frequent TP53 mutations while low-grade (LG) carcinomas arise from serous borderline tumors (SBT) and harbor mutations in KRAS/BRAF/ERBB2 pathway. However, the molecular alterations involved in the progression from SBT to LG carcinoma remain largely unknown. As well, the extent of deletion of tumor suppressors in ovarian serous carcinomas has not been well-studied. To further address these two issues, we assessed DNA copy number changes among affinity-purified tumor cells from 37 ovarian serous neoplasms including SBT, LG and HG tumors using high density 250K SNP arrays. Chromosomal instability index as measured by changes in DNA copy number was significantly higher in HG than in LG serous carcinomas. Hemizygous ch1p36 deletion was common in LG serous carcinomas but was rarely seen in SBT. This region contains several candidate tumor suppressors including miR-34a. In contrast, in HG serous carcinomas, significant numbers of amplifications and deletions including homozygous deletions were identified. Among homozygous deletions, loci containing Rb1, CDKN2A/B, CSMD1, and DOCK4 were most common, being present in 10.6%, 6.4%, 6.4% and 4.3%, respectively, in independent 47 affinity-purified HG serous carcinomas. Except the CDKN2A/B region, these homozygous deletions were not present in either SBT or LG tumors. Our study provides a genome-wide homozygous deletion profiles in HG serous carcinomas, serving as a molecular foundation to study tumor suppressors in ovarian cancer. PMID:19383911

  14. Medial hypertrophy of the ovarian vein: a novel type of vascular pathology associated with a primary ovarian carcinoid tumor.

    PubMed

    Dessauvagie, Benjamin F; Lai, Patrick H; Oost, Ebo; Thomas, Anitha; Stewart, Colin J R

    2015-01-01

    Primary carcinoid tumors of the ovary are rare accounting for only 1% of neoplasms that are associated with the carcinoid syndrome. However, the carcinoid syndrome can occur in the absence of hepatic metastases due to the release of vasoactive peptides directly into the systemic circulation via the ovarian vein. We present a 69-yr-old woman presenting with carcinoid valvular disease and congestive cardiac failure who was found to have a primary left ovarian carcinoid tumor. At operation it was noted that the left ovarian vein had an unusually firm and thickened appearance, and histologic examination revealed marked fibromuscular medial hypertrophy with luminal compression. There was no associated vascular elastosis. This ovarian venous alteration appears to represent a novel addition to the spectrum of cardiovascular injuries associated with carcinoid tumors.

  15. A Case of a Giant Borderline Phyllodes Tumor Early in Pregnancy Treated with Mastectomy and Immediate Breast Reconstruction.

    PubMed

    Gentile, Lori F; Gaillard, William Foster; Wallace, Jodi-Ann; Spiguel, Lisa R P; Alizadeh, Layla; Lentz, Ashley; Shaw, Christiana

    2016-11-01

    Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester.

  16. Ovarian tumor-initiating cells display a flexible metabolism

    PubMed Central

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-01-01

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-LFFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. PMID:25172556

  17. Ovarian tumor-initiating cells display a flexible metabolism

    SciTech Connect

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  18. Ovarian tumors with elevated CA-125 levels and severe juvenile hypothyroidism: a need for increased awareness.

    PubMed

    Krishnamurthy, Sriram; Seth, Anju; Puri, Archana; Anand, Rama; Aneja, Satinder

    2010-06-01

    A 15-yr-old girl presented with bilateral gross ovarian tumors, clinical features of long-standing unrecognized hypothyroidism and markedly elevated CA-125 levels. Ovarian resection was avoided, as the presentation was consistent with the Van Wyk and Grumbach syndrome; and the patient was treated with replacement of thyroid hormone. Regression of the ovarian tumors occurred 6 months after initiation of the treatment. The authors emphasise the need for increased awareness and screening for hypothyroidism in patients with ovarian tumors, in order to prevent inadvertent operative interventions.

  19. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

    PubMed Central

    Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar

    2016-01-01

    Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484

  20. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer

    PubMed Central

    Chuong, Michael D.; Frakes, Jessica M.; Figura, Nicholas; Hoffe, Sarah E.; Shridhar, Ravi; Mellon, Eric A.; Hodul, Pamela J.; Malafa, Mokenge P.; Springett, Gregory M.

    2016-01-01

    Background While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. Methods This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. Results We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. Conclusions These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients. PMID:27034789

  1. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    SciTech Connect

    Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas; Townsend, Reid; Davies, Sherri; Li, Shunqiang; Ellis, Matthew; Boja, Emily; Rivers, Robert; Rodriguez, Henry; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-01-02

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

  2. A case of carcinoid tumor of the terminal ileum and simultaneous ovarian dermoid cyst.

    PubMed

    Hamada, Hosam

    2011-04-01

    Carcinoid tumors are slow-growing malignant neoplasms associated with an indolent clinical course. About 60% of such tumors are located within the gastrointestinal tract. Here, we describe the first case, to our knowledge, of a carcinoid tumor of the terminal ileum and a simultaneous ovarian dermoid cyst. A 57-year-old woman was presented with abdominal pain, vomiting, and clinical signs of mechanical bowel obstruction. Radiograph and computed tomography scan of the abdomen showed hydroaeric levels. Laparotomy revealed a mass in the terminal ileum and a right ovarian cystic mass. Right hemicolectomy and right oopherectomy were performed. The histopathological workup showed a carcinoid tumor of the terminal ileum and ovarian dermoid cyst. Small intestinal carcinoid tumor, an uncommon disease, has been reported earlier to coincide with various neoplasms. No association between small intestinal carcinoid tumor and ovarian dermoid cyst has been reported earlier in the English literature.

  3. Tumor Stroma Engraftment of Gene-Modified Mesenchymal Stem Cells as Anti-Tumor Therapy against Ovarian Cancer

    PubMed Central

    Dembinski, Jennifer L.; Wilson, Shanna M.; Spaeth, Erika L.; Studeny, Matus; Zompetta, Claudia; Samudio, Ismael; Roby, Katherine; Andreeff, Michael; Marini, Frank C.

    2013-01-01

    Many ovarian cancers originate from ovarian surface epithelium, where they develop from cysts intermixed with stroma. The stromal layer is critical to the progression and survival of the neoplasm and consequently is recruited into the tumor microenvironment. Using both syngenic mouse tumors (ID8-R), and human xenograft (OVCAR3, SKOV3) tumor models, we first confirmed intraperitoneally-circulating MSC could target, preferentially engraft and differentiate into α-SMA+ myofibroblasts, suggesting their role as “reactive stroma” in ovarian carcinoma development and confirming their potential as a targeted delivery vehicle for the intratumoral production of interferon-beta (IFNβ). Then, mice with ovarian carcinomas received weekly IP injections of IFNβ expressing MSC, resulting in complete eradication of tumors in 70% of treated OVCAR3 mice (P = 0.004) and an increased survival of treated SKOV3 mice compared with controls (P = 0.01). Similar tumor growth control was observed using murine IFNβ delivered by murine MSC in ID8-R ovarian carcinoma. As a potential mechanism of tumor killing, MSC produced IFNβ induced caspase-dependent tumor cell apoptosis. Our results demonstrate that ovarian carcinoma engraft MSC to participate in myofibrovascular networks and that IFNβ produced by MSC intratumorally modulates tumor kinetics, resulting in prolonged survival. PMID:23260083

  4. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer

    PubMed Central

    Yin, Mingzhu; Li, Xia; Tan, Shu; Zhou, Huanjiao Jenny; Ji, Weidong; Bellone, Stefania; Xu, Xiaocao; Zhang, Haifeng; Santin, Alessandro D.; Lou, Ge

    2016-01-01

    Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage–like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM. Moreover, EGF secreted by TAMs activated EGFR on tumor cells, which in turn upregulated VEGF/VEGFR signaling in surrounding tumor cells to support tumor cell proliferation and migration. Pharmacological blockade of EGFR or antibody neutralization of ICAM-1 in TAMs blunted spheroid formation and ovarian cancer progression in mouse models. These findings suggest that EGF secreted from TAMs plays a critical role in promoting early transcoelomic metastasis of ovarian cancer. As transcoelomic metastasis is also associated with many other cancers, such as pancreatic and colon cancers, our findings uncover a mechanism for TAM-mediated spheroid formation and provide a potential target for the treatment of ovarian cancer and other transcoelomic metastatic cancers. PMID:27721235

  5. Incidence of serous tubal intraepithelial carcinoma (STIC) by algorithm classification in serous ovarian tumor associated with PAX8 expression in tubal epithelia: a study of single institution in Japan.

    PubMed

    Munakata, Satoru; Yamamoto, Toshiya

    2015-01-01

    Serous ovarian carcinoma is now hypothesized to originate from fallopian tube epithelium (FTE). We investigated the FTE abnormalities in the patients with epithelial ovarian tumors. Our study included 55 cases of serous tumors (24 carcinomas, 8 borderline tumors, and 23 adenomas), 14 mucinous carcinomas, 22 endometrioid carcinomas, 5 clear cell carcinomas, and 2 malignant Brenner tumors. FTE was diagnosed by the diagnostic algorithm, which combines the data of morphology, and p53, Ki-67 immunostaining, as serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive. Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive were observed in 5, 3, 0, and 16 cases in serous carcinoma; 0, 3, 0, and 5 cases in serous borderline tumor; 0, 1, 1, and 21 cases in serous adenoma; 0, 0, 1, and 13 cases in mucinous carcinoma; 0, 0, 3, and 19 cases in endometrioid carcinoma; 0, 0, 0, and 5 cases in clear cell carcinoma; and 0, 1, 0, and 1 case in malignant Brenner tumor. Among tumors of serous histology and between carcinomas, FTE abnormalities differed significantly (P<0.05). Serous tubal intraepithelial carcinomas were only found in serous carcinoma. The incidence of secretory cell proliferation (SCP) was examined by PAX8 expression. The rate of SCP was extremely high in serous carcinoma (96%). Among tumors of serous histology and between carcinomas, an incidence of SCP differed significantly (P<0.05). Patients with SCP were significantly older (P<0.0001). Our observations were concordant with the hypothesis of serous ovarian carcinogenesis. The SCP has a meaningful association with serous ovarian cancer.

  6. Ovarian steroid cell tumor, not otherwise specified: A case report and literature review

    PubMed Central

    Qian, Lili; Shen, Zhen; Zhang, Xuefen; Wu, Dabao; Zhou, Ying

    2016-01-01

    Steroid cell tumors (SCT), not otherwise specified (NOS) are particularly rare ovarian sex cord-stromal tumors, which comprise <0.1% of all ovarian tumors. These tumors are uncommon in patients' prior to puberty without any typical syndromes involving hirsutism, virilization and hypertension. We here in present the case of a 5-year-old female patient who presented with sudden abdominal pain, repeated vomiting and a pelvic mass. Our patient underwent urgent exploratory laparotomy and right salpingo-oophorectomy and the histopathological examination revealed an ovarian SCT-NOS. The patient has been followed up for 5 years since the surgery, without evidence of disease recurrence. The purpose of this study was to discuss the available information on the presentation, diagnosis and recommended treatment of ovarian SCT-NOS; and describes the immunohistochemical characteristics of these tumors. PMID:28105366

  7. Immunologic aspect of ovarian cancer and p53 as tumor antigen

    PubMed Central

    Nijman, HW; Lambeck, A; van der Burg, SH; van der Zee, AGJ; Daemen, T

    2005-01-01

    Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit significant immune responses against their tumor. In this review the knowledge obtained thus far on the interaction of ovarian cancer tumor cells and the immune system is discussed. Furthermore the role of p53 as tumor antigen and its potential role as target antigen in ovarian cancer is summarized. Based on the increased knowledge on the role of the immune system in ovarian cancer major improvements are to be expected of immunotherapy based treatment of this disease. PMID:16164749

  8. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    ClinicalTrials.gov

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  9. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    NASA Astrophysics Data System (ADS)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  10. Correlation between tumor histology, steroid receptor status, and adenosine deaminase complexing protein immunoreactivity in ovarian cancer.

    PubMed

    Rao, B R; Slotman, B J; Geldof, A A; Dinjens, W N

    1990-01-01

    Adenosine deaminase complexing protein (ADCP) immunoreactivity was investigated in 40 ovarian tumors and correlated with clinicopathologic parameters, including tumor steroid receptor content. Ten (29%) of 34 common epithelial ovarian carcinomas showed ADCP reactivity. Reactivity for ADCP was seen more frequently in mucinous (100%; p less than 0.001), well-differentiated (73%; p less than 0.001) and Stage I (56%; p less than 0.05) ovarian carcinomas. Furthermore, tumors that contained high levels of androgen receptors and tumors that did not contain estrogen receptors were more frequently ADCP positive (p less than 0.05). However, after stratifying for histologic grade, no correlation between ADCP reactivity and receptor status was found. Determination of ADCP reactivity appears to be of limited value in ovarian cancer.

  11. Unusual liver locations of growing teratoma syndrome in ovarian malignant germ cell tumors.

    PubMed

    Lorusso, Domenica; Malaguti, Paola; Trivellizzi, Ilaria Nausica; Scambia, Giovanni

    2011-01-01

    ► Growing teratoma syndrome (GTS) with unusual liver locations are described after fertility preserving surgery and chemotherapy treatment for mixed malignant ovarian germ cell tumors (MGCT). ► It's a rare syndrome of mixed malignant ovarian germ cell tumors and in both cases enlarged and growing liver masses appeared during cisplatin-etoposide-bleomicin (BEP) chemotherapy. ► Radiological exams (CT scan and MRI) were suggestive for secondary metastasis and serum markers became negative during chemotherapy.

  12. Primary ovarian carcinoid tumor showing unusual histology and nuclear accumulation of β-catenin.

    PubMed

    Kim, Hyun-Soo; Yoon, Gun; Jang, Hye-In; Song, Sang Yong; Kim, Byoung-Gie

    2015-01-01

    Carcinoid tumor of the ovary is uncommon. We herein report a very rare case of primary ovarian carcinoid tumor with aggressive histology and an unusual immunophenotype. A 21-year-old woman presented with a palpable abdominal mass. Computed tomographic scan revealed a large, extensively necrotic solid mass in the left ovary. The patient underwent a left salpingo-oophorectomy. Grossly, the left adnexa showed a large, vaguely lobulated ovarian tumor measuring 22×15×13 cm. Histologically, the tumor had a readily identifiable neuroendocrine growth pattern, but some areas showed solid growth pattern associated with mild nuclear pleomorphism and multiple foci of punctate necrosis. Furthermore, mitotic figures were recognized in 8 per 10 high-power fields, and a few foci of large coagulative tumor necrosis were also noted. In addition, the tumor tissue exhibited uniform, strong nuclear β-catenin immunoreactivity, indicating the nuclear accumulation of β-catenin in the individual tumor cells. In summary, we described the first case of primary ovarian carcinoid tumor with loss of neuroendocrine growth pattern, increased mitotic activity and large areas of coagulative tumor necrosis. According to the WHO classification of pulmonary carcinoid tumor, this case may be classified as "atypical" carcinoid. However, currently, no primary ovarian atypical carcinoid exists in the classification system. Due to its rarity, there are no established diagnostic criteria and clinical data on patient outcomes for ovarian carcinoid tumors with aggressive histology. Additional reports are clearly necessary. We also showed for the first time the nuclear accumulation of β-catenin in carcinoid tumor cells, suggestive of a role for β-catenin in the tumorigenesis of ovarian atypical carcinoid tumor or its aggressive histology.

  13. FGF18 as a potential biomarker in serous and mucinous ovarian tumors.

    PubMed

    El-Gendi, Saba; Abdelzaher, Eman; Mostafa, Mohamed Farouk; Sheasha, Ghada Abu

    2016-03-01

    Fibroblast growth factor 18 (FGF18) has been suggested to play important roles in promoting progression of ovarian high-grade serous carcinoma. Our aim was to investigate FGF18 expression in the whole spectrum of serous and mucinous ovarian tumors, highlighting differences in expression within the adenoma-carcinoma sequence and differences between type I and type II tumors. We also aimed to test the prognostic significance of this expression and its relation to microvessel density (MVD). We evaluated the immunohistochemical expression of FGF18 and CD31 in 103 ovarian tumors and statistically analyzed their association with clinicopathological variables and patients' outcome. FGF18 score increased significantly within the adenoma-carcinoma sequence for serous and mucinous tumors. MVD increased significantly only among serous tumors. FGF18 and MVD correlated significantly (overall and among serous tumors only) and were significantly higher in type II than type I tumors. Cox regression models were built. Independent predictors could not be determined due to multicollinearity between the predictors. However, the combination of International Federation of Gynecology and Obstetrics (FIGO) stage, ovarian carcinoma type, and/or FGF18 score achieved the highest predictability of poor prognosis. FGF18 could play a role within the adenoma-carcinoma sequence in type I tumors and might modulate angiogenesis among serous tumors. Our findings further augment the differences between type I and type II tumors. The combination of FIGO stage, ovarian carcinoma type, and/or FGF18 score could predict poor prognosis among ovarian carcinoma patients. Our work identifies FGF18 in ovarian neoplasia as a promising field of research, although evaluation of the performance of the developed models is still needed.

  14. Polyglutamate Paclitaxel and Carboplatin in Treating Patients With Ovarian Epithelial, Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-05-07

    Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  15. Ovarian interstitial cell tumor in a South American sea lion (Otaria flavescens).

    PubMed

    Biancani, Barbara; Lacave, Geraldine; Magi, Gian Enrico; Rossi, Giacomo

    2010-07-01

    A case of an ovarian tumor is reported in an 8-yr-old South American sea lion (Otaria flavescens) kept in a marine park in Malta (35.57 degrees N, 14.25 degrees E). The neoplasm was a solid mass of dense sheets and nests of round to polyhedral, irregularly shaped cells with abundant, finely vacuolated cytoplasm. The nuclei were uniformly small and round to oval. The supporting stroma contained thecal cells. The tumor cells were positive for positive inhibin and vimentin and focally positive for cytokeratin by immunohistochemistry. The neoplasm was diagnosed as an ovarian sex cord-stromal tumor, specifically an interstitial cell tumor.

  16. Tumor promoting properties of the ETS protein MEF in ovarian cancer.

    PubMed

    Yao, J J; Liu, Y; Lacorazza, H D; Soslow, R A; Scandura, J M; Nimer, S D; Hedvat, C V

    2007-06-07

    We have previously shown that MEF (myeloid ELF1-like factor, also known as ELF4) functions as a transcriptional activator of the interleukin (IL)-8, perforin, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-3 genes in hematopoietic cells. MEF is also expressed in non-hematopoietic tissues including certain ovarian cancer cells. To define the function of MEF in these cells, we examined primary human ovarian epithelial tumors and found that MEF is expressed in a significant proportion of ovarian carcinomas, and in the CAOV3 and SKOV3 ovarian cancer cell lines, but not in normal ovarian surface epithelium. Manipulating MEF levels in these cell lines altered their behavior; reducing MEF levels, using short hairpin RNA expressing vectors, significantly inhibited the proliferation of SKOV3 and CAOV3 cells in culture, and impaired the anchorage-independent growth of CAOV3 cells. Overexpression of MEF in SKOV3 cells (via retroviral transduction) significantly increased their growth rate, enhanced colony formation in soft agar and promoted tumor formation in nude mice. The oncogenic activity of MEF was further shown by the ability of MEF to transform NIH3T3 cells, and induce their tumor formation in nude mice. MEF is an important regulator of the tumorigenic properties of ovarian cancer cells and could be used a therapeutic target in ovarian cancer.

  17. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    PubMed

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

  18. Five-Year Disease-Free Follow-Up of a Borderline Breast Phyllodes Tumor in a 15-year-old Patient

    PubMed Central

    Güler, Sertaç Ata; Uğurlu, M. Ümit; Güllüoğlu, Bahadır M.

    2015-01-01

    Phyllodes tumors are large breast tumors representing only 1% of breast neoplasms and are rarely seen in young women. Histologically, phyllodes tumors are classified as benign, borderline, or malignant based on the characteristics of the stroma. Although wide local excision is recommended for the treatment modality, the reoccurrence rate after surgical excision varies between 36% and 65%, with recurrence more likely in those with the tumor at the margins of excision. Our aim was to report -a case in a 15-year-old girl with a 115-mm borderline phyllodes tumor in her left breast mimicking a juvenile fibroadenoma. We presented a 5-year disease-free follow-up after wide local excision with negative margins.

  19. A Survey of DICER1 Hotspot Mutations in Ovarian and Testicular Sex Cord-Stromal Tumors

    PubMed Central

    Conlon, Niamh; Schultheis, Anne M; Piscuoglio, Salvatore; Silva, Annacarolina; Guerra, Esther; Tornos, Carmen; Reuter, Victor E; Soslow, Robert A; Young, Robert H; Oliva, Esther; Weigelt, Britta

    2015-01-01

    Sertoli-Leydig cell tumors are characterized by the presence of somatic DICER1 hotspot mutations. In this study, we sought to define the association between DICER1 hotspot mutations and different morphologic subtypes of ovarian Sertoli-Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord-stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous differentiation. We subjected a series of ovarian Sertoli-Leydig cell tumors (n=32), Sertoli cell tumors (n=5) and gynandroblastomas (n=5), testicular sex cord-stromal tumors (n=15) and a diverse group of female genital tract tumors with rhabdomyosarcomatous morphology (n=10) to DICER1 hotspot mutation analysis using Sanger sequencing. We also tested 2 gynandroblastomas for the presence of FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli-Leydig cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K mutation. No association was found between DICER1 mutation status and the presence of heterologous or retiform differentiation in Sertoli-Leydig cell tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma (2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; p>0.1), and all mutated tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous component of a uterine carcinosarcoma. No DICER1 mutations were detected in testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli-Leydig cell tumors, and are unrelated to tumor differentiation. We also widened the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation, in which DICER1 mutations are known to occur

  20. A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors.

    PubMed

    Conlon, Niamh; Schultheis, Anne M; Piscuoglio, Salvatore; Silva, Annacarolina; Guerra, Esther; Tornos, Carmen; Reuter, Victor E; Soslow, Robert A; Young, Robert H; Oliva, Esther; Weigelt, Britta

    2015-12-01

    Sertoli-Leydig cell tumors are characterized by the presence of somatic DICER1 hotspot mutations. In this study, we sought to define the association between DICER1 hotspot mutations and different morphologic subtypes of ovarian Sertoli-Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord-stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous differentiation. We subjected a series of ovarian Sertoli-Leydig cell tumors (n=32), Sertoli cell tumors (n=5) and gynandroblastomas (n=5), testicular sex cord-stromal tumors (n=15) and a diverse group of female genital tract tumors with rhabdomyosarcomatous morphology (n=10) to DICER1 hotspot mutation analysis using Sanger sequencing. We also tested two gynandroblastomas for the presence of FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli-Leydig cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K mutation. No association was found between DICER1 mutation status and the presence of heterologous or retiform differentiation in Sertoli-Leydig cell tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma (2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; P>0.1), and all mutated tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous component of a uterine carcinosarcoma. No DICER1 mutations were detected in testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli-Leydig cell tumors, and are unrelated to tumor differentiation. We also widened the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation, in which DICER1 mutations are known to

  1. NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas

    PubMed Central

    Yu, Yinhua; Xu, Fengji; Peng, Hongqi; Fang, Xianjun; Zhao, Shulei; Li, Yang; Cuevas, Bruce; Kuo, Wen-Lin; Gray, Joe W.; Siciliano, Michael; Mills, Gordon B.; Bast, Robert C.

    1999-01-01

    Using differential display PCR, we have identified a gene [NOEY2, ARHI (designation by the Human Gene Nomenclature Committee)] with high homology to ras and rap that is expressed consistently in normal ovarian and breast epithelial cells but not in ovarian and breast cancers. Reexpression of NOEY2 through transfection suppresses clonogenic growth of breast and ovarian cancer cells. Growth suppression was associated with down-regulation of the cyclin D1 promoter activity and induction of p21WAF1/CIP1. In an effort to identify mechanisms leading to NOEY2 silencing in cancer, we found that the gene is expressed monoallelically and is imprinted maternally. Loss of heterozygosity of the gene was detected in 41% of ovarian and breast cancers. In most of cancer samples with loss of heterozygosity, the nonimprinted functional allele was deleted. Thus, NOEY2 appears to be a putative imprinted tumor suppressor gene whose function is abrogated in ovarian and breast cancers. PMID:9874798

  2. Rare Skin Adnexal and Melanocytic Tumors Arising in Ovarian Mature Cystic Teratomas: A Report of 3 Cases and Review of the Literature.

    PubMed

    Moulla, Alexandra A; Magdy, Nesreen; Francis, Nicholas; Taube, Janis; Ronnett, Brigitte M; El-Bahrawy, Mona

    2016-09-01

    Mature teratoma of the ovary is the most common primary ovarian tumor accounting for 15% (10%-20%) of all ovarian neoplasms. Skin and skin adnexal structures are the most common elements identified in mature teratomas. Benign and malignant skin tumors can arise in ovarian teratomas, the most common being epithelial tumors. Melanocytic and adnexal tumors developing in a teratoma are rare and can be easily overlooked. We report 3 cases and review melanocytic and skin adnexal tumors encountered in ovarian teratomas.

  3. Identification of Tumor Suppressors and Oncogenes from Genomic and Epigenetic Features in Ovarian Cancer

    PubMed Central

    Wrzeszczynski, Kazimierz O.; Varadan, Vinay; Byrnes, James; Lum, Elena; Kamalakaran, Sitharthan; Levine, Douglas A.; Dimitrova, Nevenka; Zhang, Michael Q.; Lucito, Robert

    2011-01-01

    The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatic analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We separately examined CNV and DNA methylation for 42 primary serous ovarian cancer samples using MOMA-ROMA assays and 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with altered copy number and correlated changes in expression. Among these genes CCNE1, POP4, UQCRB, PHF20L1 and C19orf2 were identified within both data sets. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We therefore identify changes in DNA methylation and expression for all amplified and deleted genes. We statistically define tumor suppressor and oncogenic features for these modalities and perform a correlation analysis with expression. We predicted 611 potential oncogenes and tumor suppressors candidates by integrating these data types. Genes with a strong correlation for methylation dependent expression changes exhibited at varying copy number aberrations include CDCA8, ATAD2, CDKN2A, RAB25, AURKA, BOP1 and EIF2C3. We provide copy number variation and DNA methylation analysis for over 11,500 individual genes covering the genetic landscape of ovarian cancer tumors. We show the extent of genomic and epigenetic alterations for known tumor suppressors and oncogenes and also use these defined features to identify potential ovarian cancer gene candidates. PMID

  4. ShRNA-mediated silencing of the RFC3 gene suppress ovarian tumor cells proliferation

    PubMed Central

    Shen, Huimin; Xu, Juan; Zhao, Shanshan; Shi, Haijuan; Yao, Shuzhong; Jiang, Nan

    2015-01-01

    Ovarian carcinoma is one of the most common and lethal malignancies in the world. Replication factor C (RFC) plays an important role in DNA replication, DNA damage repair, and checkpoint control during cell cycle progression in all eukaryotes. Our previous study found that one unit of RFC complex, RFC3, is over-expressed in ovarian tumor tissues. However, its role in the development of ovarian carcinoma remains unclear. Western blot and real-time RT-PCR analysis were used to measure the expression of RFC3 in ovarian cancer cells. Lentivirus-mediated RFC3-specific shRNA was used to knock down RFC3 expression in ovarian cancer cells. Furthermore, the effect of RFC3 on tumor cellular proliferation and growth were examined, respectively. The expression level of RFC3 was remarkably up-regulated in ovarian cancer OVCAR-3 cells. With MTS and cell growth assays, the viability and proliferation of RFC3 knocking-down OVCAR-3 cell line were shown to be effectively restrained. Down-regulation of RFC3 expression arrested the cell cycle of OVCAR-3 cell in the S-phase and induced apoptosis. This study suggests that RFC3 may play an important role in the the process of ovarian carcinoma, and that it may be a potential biological treatment target in the future. PMID:26464638

  5. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    PubMed Central

    2010-01-01

    Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL), which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in metastasizing within the peritoneal

  6. Mechanism of Ovarian Epithelial Tumor Predisposition in Individuals Carrying Germline BRCA1 Mutations

    DTIC Science & Technology

    2006-01-01

    gene knockout developed ovarian/ tubal tumors morphologically very similar to human ovarian serous cystadenomas in strong support of our hypothesis. We...proliferation activity in the uterus of 5 wild type and 5 mutant mice at the diestrus ad estrus phases of the estrus cycle. Histological cross- sections were...zygous knockout restricted to granulosa cells. One ovary was removed from each of 30 Brca1 flox/flox; Fshr-Cre mice at 2 months of age. Histological

  7. Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch

    DTIC Science & Technology

    2015-07-01

    cell behavior and ovarian tumor growth. 15. SUBJECT TERMS Ovarian cancer αSMA Integrin α10β1 Stromal Fibroblast Angiogenesis Cisplatin ...Fibroblast 5). Angiogenesis 6). Cisplatin 7). Chemosensitivity 8). Cell adhesion 9). Cell migration 10). Cell proliferation 11). Cytokines 3...from 3 experiments. * Pɘ.05 as compared to controls.   5     Effects of antagonists of α10β1 alone and in combination with Cisplatin on

  8. Identification of novel candidate plasma metabolite biomarkers for distinguishing serous ovarian carcinoma and benign serous ovarian tumors

    PubMed Central

    Buas, Matthew F.; Gu, Haiwei; Djukovic, Danijel; Zhu, Jiangjiang; Drescher, Charles W.; Urban, Nicole; Raftery, Daniel; Li, Christopher I.

    2017-01-01

    OBJECTIVE Serous ovarian carcinoma (OC) represents a leading cause of cancer-related death among U.S. women. Non-invasive tools have recently emerged for discriminating benign from malignant ovarian masses, but evaluation remains ongoing, without widespread implementation. In the last decade, metabolomics has matured into a new avenue for cancer biomarker development. Here, we sought to identify novel plasma metabolite biomarkers to distinguish serous ovarian carcinoma and benign ovarian tumor. METHODS Using liquid chromatography-mass spectrometry, we conducted global and targeted metabolite profiling of plasma isolated at the time of surgery from 50 serous OC cases and 50 serous benign controls. RESULTS Global lipidomics analysis identified 34 metabolites (of 372 assessed) differing significantly (P<0.05) between cases and controls in both training and testing sets, with 17 candidates satisfying FDR q<0.05, and two reaching Bonferroni significance. Targeted profiling of ~150 aqueous metabolites identified a single amino acid, alanine, as differentially abundant (P<0.05). A multivariate classification model built using the top four lipid metabolites achieved an estimated AUC of 0.85 (SD=0.07) based on Monte Carlo cross validation. Evaluation of a hybrid model incorporating both CA125 and lipid metabolites was suggestive of increased classification accuracy (AUC=0.91, SD=0.05) relative to CA125 alone (AUC=0.87, SD=0.07), particularly at high fixed levels of sensitivity, without reaching significance. CONCLUSIONS Our results provide insight into metabolic changes potentially correlated with the presence of serous OC versus benign ovarian tumor and suggest that plasma metabolites may help differentiate these two conditions. PMID:26521694

  9. Effect of histone deacetylase inhibitors on cell apoptosis and expression of the tumor suppressor genes RUNX3 and ARHI in ovarian tumors.

    PubMed

    Zhang, Lan; Liu, Peishu; Li, Hua; Xue, Fuying

    2013-05-01

    The aim of this study was to investigate the expression of Runt box 3 (RUNX3) and aplasia Ras homolog member I (ARHI) in ovarian tumors, and the effects of histone deacetylase inhibitors (HDACIs) on the expression of these genes and the growth of ovarian cancer cells. The mRNA expression of the RUNX3 and ARHI genes in normal ovaries and ovarian tumors was determined using reverse transcription polymerase chain reaction (RT-PCR). The effects of HDACIs on RUNX3 and ARHI expression in four ovarian cancer cell lines (SKOV3, A2780, COC1 and OC3) were determined using RT-PCR and the MTT assay. The expression of RUNX3 and ARHI in normal ovarian cells was 86 and 100%, respectively. Although the two genes were downregulated in ovarian tumors, the extent of downregulation differed. The expression of RUNX3 and ARHI was correlated with the degree of tumor malignancy (P<0.05). ARHI was expressed in all four ovarian cancer cell lines, whereas RUNX3 was expressed only in the OC3 cell line. Treatment with HDACIs upregulated the expression of ARHI and RUNX3 in the SKOV3 cell line only. In A2780 cells, HDACIs upregulated ARHI expression only in the presence of trichostatin A (TSA) plus cisplatin. HDACIs induced significant apoptosis in ovarian cancer cells, which was inversely correlated with the concentration and duration of treatment (P<0.05). In conclusion, RUNX3 and ARHI were shown to be expressed in normal ovarian cells; however, their expression was downregulated or lost in ovarian tumor cells. The combined detection of ARHI and RUNX3 expression may offer improved prediction and monitoring of ovarian malignancies. HDACIs were revealed to inhibit the growth of ovarian tumor cells and may constitute a novel therapeutic option for ovarian tumors.

  10. Ovarian stromal tumor with minor sex cord elements with coexistent endometrial carcinoma.

    PubMed

    Kumar, Sunesh; Mathur, Sandeep; Subbaiah, Murali; Singh, Lavleen

    2013-01-01

    Ovarian stromal tumor with minor sex cord elements is a rare tumor. It is composed of predominantly fibrothecomatous tumor with scattered minor sex cord elements in less than 10% of the tumor area. These tumors may be hormonally active and predispose to carcinoma endometrium. A case of ovarian fibroma-thecoma with minor sex cord elements in which coexistent endometrial carcinoma was also discovered is being reported. Though thecoma may be a predisposing factor for endometrial cancer, meticulous histopathological examination of the ovary may reveal additional sources of estrogen like granulosa cell aggregates as in our patient. Such patients would require long-term follow-up to detect any recurrence of granulosa cell tumor.

  11. Early Detection of Ovarian Cancer by Tumor Epithelium-Targeted Molecular Ultrasound

    DTIC Science & Technology

    2013-10-01

    were examined. 3. Archived ultrasound images were examined off-line, ovarian tumor associated changes in gray scale intensity and Doppler indices...tumor was selected and the average image intensity (in pixel values) was determined using 7 Figure 1: Enhancement of ultrasound signal intensity ...16 targeted imaging agents increased ultrasound signal intensity remarkably in post-targeted imaging. The tumor showed septa of tissue mass during

  12. Nuclear Factor-Kappa B Activity in the Host-Tumor Microenvironment of Ovarian Cancer

    DTIC Science & Technology

    2014-10-01

    of NF-κB such as thymoquinone (TQ) potentiate the effects of cytotoxic agents, including cisplatin , in ovarian cancer cells. Equally relevant are the...Combined TQ and cisplatin treatment lead to synergistic anti-tumor effects in vitro, reduced tumor burden and apoptotic marks in tumors to a greater...extent than treatment with cisplatin alone, reduced M2 and induced M1 macrophage markers, and decreased levels of known pro-tumorigenic cytokines in

  13. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors.

    PubMed

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  14. "Borderline" Children.

    ERIC Educational Resources Information Center

    Gualtieri, C. Thomas C.; And Others

    1983-01-01

    The use of the diagnosis "borderline" was evaluated with 16 children (6 to 13 years old) who were referred for comprehensive evaluation. None met DSM III criteria for borderline personality disorder. The borderline label had a negative impact on some children and was not helpful for treatment planning or disposition. (Author/SEW)

  15. Uterine tumor resembling ovarian sex cord tumor. Case report and review of literature.

    PubMed

    Stefanovic, A; Jeremic, K; Kadija, S; Mitrovic, M; Filimonovic, D; Jankovic-Raznatovic, S; Tavcar, J

    2013-01-01

    A uterine tumor resembling an ovarian sex cord tumor (UTROSCT) shows a poly phenotypic immunophenotype with coexpression of epithelial, myoid, and sex cord markers, as well as hormone receptors. The authors present a case of a 59-year-old multiparous woman admitted to the Institute of Gynecology and Obstetrics Clinical Centre of Serbia in January 2010 due to prolonged vaginal bleeding and abdominal discomfort. The vaginal ultrasound showed an enlarged uterus size of 100 x 74 x 81 mm, with extended cavity with an unhomogenic content and myomas sized 54 x 69 mm located in fundus with secondary changes. She underwent abdominal hysterectomy with adnexectomy. Microscopic examination revealed submucosal uterine tumor with variabile histological organization that had anastomotic trabeculae with solid cellular grupations. Rare mitotic figures (2/10 HPF) were found. Additional imunohistochemistry showed immunophenotype: the sex cord areas were positive for vimentin(++), aSMA(++), AE1/AE3(+), PR(+), and ER(+). The poly phenotypic immunophenotype can be useful in differential diagnosis from other neoplasms but also suggests an origin of UTROSCT from uncommitted stem cell enabling for multidirectional differentiation.

  16. Expression of Leukocyte Inhibitory Immunoglobulin-like Transcript 3 Receptors by Ovarian Tumors in Laying Hen Model of Spontaneous Ovarian Cancer.

    PubMed

    Khan, Mohammad Faisal; Bahr, Janice M; Yellapa, Aparna; Bitterman, Pincas; Abramowicz, Jacques S; Edassery, Seby L; Basu, Sanjib; Rotmensch, Jacob; Barua, Animesh

    2012-04-01

    Attempts to enhance a patient's immune response and ameliorate the poor prognosis of ovarian cancer (OVCA) have largely been unsuccessful owing to the suppressive tumor microenvironment. Leukocyte immunoglobulin-like transcript 3 (ILT3) inhibitory receptors have been implicated in immunosuppression in several malignancies. The expression and role of ILT3 in the progression of ovarian tumors are unknown. This study examined the expression and association of ILT3 in ovarian tumors in laying hens, a spontaneous preclinical model of human OVCA. White Leghorn laying hens were selected by transvaginal ultrasound scanning. Serum and normal ovaries or ovarian tumors were collected. The presence of tumors and the expression of ILT3 were examined by routine histology, immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction. In addition to stromal immune cell-like cells, the epithelium of the ovarian tumors also expressed ILT3 with significantly high intensity than normal ovaries. Among different subtypes of ovarian carcinomas, serous OVCA showed the highest ILT3 staining intensity, whereas endometrioid OVCA had the lowest intensity. Similar to humans, an immunoreactive protein band of approximately 55 kDa for ILT3 was detected in the ovarian tumors in hens. The patterns of ILT3 protein and messenger RNA expression by ovarian tumors in different subtypes and stages were similar to those of immunohistochemical staining. The results of this study suggest that laying hens may be useful to generate information on ILT3-associated immunosuppression in OVCA. This animal model also offers the opportunity to develop and test anti-ILT3 immunotherapy to enhance antitumor immunity against OVCA in humans.

  17. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    SciTech Connect

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  18. PKC iota promotes ovarian tumor progression through deregulation of cyclin E

    PubMed Central

    Nanos-Webb, Angela; Bui, Tuyen; Karakas, Cansu; Zhang, Dong; Carey, Jason P.W.; Mills, Gordon B.; Hunt, Kelly K.; Keyomarsi, Khandan

    2016-01-01

    The high frequency of relapse of epithelial ovarian tumors treated with standard chemotherapy has highlighted the necessity to identify targeted therapies that can improve patient outcomes. The dynamic relationship between Cyclin E and PKCiota frequent overexpression in high-grade ovarian tumors poses a novel pathway for therapeutic investigation. We hypothesized that a PI3K dependent signaling pathway activating PKCiota perpetuates cyclin E deregulation during ovarian tumorigenesis. We observed a positive correlation between PKCiota and cyclin E in a panel of 19 ovarian cancer cell lines. Modulation of cyclin E had no effect on PKCiota knockdown/overexpression however PKCiota differentially regulated cyclin E expression. In the serous ovarian cancer cells (IGROV, OVCAR-3), shPKCiota decreased proliferation, caused a G1 arrest, and significantly prolonged overall survival in xenograft mouse models. In vitro shPKCiota decreased the ability of IGROV cells to grow under anchorage independent conditions and form aberrant acini, which was dependent upon Ad-cyclin E or Ad-LMW-E expression. RPPA analysis of PKCiota wild-type, catalytic active, dominant negative protein isoforms strengthened the association between phospho-PKCiota levels and PI3K pathway activation. Inhibitors of PI3K coordinately decreased phospho-PKCiota and Cyclin E protein levels. In conclusion, we have identified a PI3K/PKCiota/Cyclin E signaling pathway as a therapeutic target during ovarian tumorigenesis. PMID:26279297

  19. [Metastatic tumors in the ovary, difficulties of histologic diagnosis].

    PubMed

    Tamás, Judit; Vereczkey, Ildikó; Tóth, Erika

    2015-09-01

    The ovary is a common site of metastases. Secondary tumors account for 3-40% of all ovarian malignancies. Most ovarian metastases arise from the colon, although tumors of the breast, stomach and endometrium are also common places of origin. Clinical and histological features of metastatic tumors frequently mimic primary ovarian malignancies, causing serious diagnostic problems for the surgical pathologist. However, differentiation between primary ovarian cancer and ovarian metastasis is important in order to prevent inappropriate management and suboptimal treatment. The distinction between primary and secondary ovarian malignancies is especially difficult in cases when the metastasis is diagnosed before the primary tumor. Frozen section is widely used in the intra-operative assessment of patients with ovarian tumors but it can be very difficult to distinguish certain types of primary ovarian tumors and metastases from other sites. We examined 152 cases of secondary ovarian neoplasm diagnosed at the National Institute of Oncology, Hungary from 2000 to 2014. Colorectal cancer was the most common primary tumor (58 cases), followed by breast (33 cases), endometrium (30 cases) and stomach cancer (13 cases). The differential diagnosis proved the most difficult in cases when endometrioid and mucinous tumors were present in the ovaries. Metastases of colorectal and gastric adenocarcinomas may simulate benign or borderline cystadenomas too. In these cases the knowledge of the patient's history and immunohistochemical stains were helpful. In our study we discuss the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasms and the limits of the intraoperative frozen sections.

  20. Adoptive Immunotherapy for Epithelial Ovarian Cancer Using T Cells Simultaneously Targeted to Tumor and Tumor-Associated Macrophages

    DTIC Science & Technology

    2011-07-01

    will be delivered to separate T-cell populations using the SFG retroviral vector and retronectin - coated tissue culture dishes: (i) HOX – targets MUC1 and...cancer. Patient derived T-cells were activated with CSD3+CD28- coated beads and transduced with retroviral expression vectors. A representative example for...cells from ascites and tumor tissue stained from a patient with ovarian cancer. Tumor cells were separated using magnetic beads coated with antibodies

  1. A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors.

    PubMed

    Zou, Yang; Deng, Wei; Wang, Feng; Yu, Xiao-Hong; Liu, Fa-Ying; Yang, Bi-Cheng; Huang, Mei-Zhen; Guo, Jiu-Bai; Xie, Qiu-Hua; He, Ming; Huang, Ou-Ping

    2016-02-01

    A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co‑occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC‑115, the MAPK1‑mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit α (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase ε (POLE1), ribonuclease type III (DICER1), CCCTC‑binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3α (DNMT3A), transformation/transcription domain‑associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease.

  2. Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma

    PubMed Central

    Hua, Yuanyuan; Choi, Pui-Wah; Trachtenberg, Alexander J.; Ng, Allen C.; Kuo, Winston P.; Ng, Shu-Kay; Dinulescu, Daniela M.; Matzuk, Martin M.; Berkowitz, Ross S.; Ng, Shu-Wing

    2016-01-01

    Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with conditional Dicer-Pten double knockout (Dicer-Pten DKO) developed primary tumors, intriguingly, from the fallopian tube stroma. We examined the growth and epithelial phenotypes of the Dicer-Pten DKO mouse tumor cells contributable by each gene knockout. Unlike human ovarian epithelial cancer cells that expressed full-length E-cadherin, the Dicer-Pten DKO stromal tumor cells expressed cleaved E-cadherin fragments and metalloproteinase 2, a mixture of epithelial and mesenchymal markers. Although the Dicer-Pten DKO tumor cells lost the expression of mature microRNAs as expected, they showed high levels of tRNA fragment expression and enhanced AKT activation due to the loss of PTEN function. Introduction of a Dicer1-expressing construct into the DKO mouse tumor cells significantly reduced DNA synthesis and the cell growth rate, with concurrent diminished adhesion and ZO1 epithelial staining. Hence, it is likely that the loss of Dicer promoted mesenchymal-epithelial transition in fallopian tube stromal cells, and in conjunction with Pten loss, further promoted cell proliferation and epithelial-like tumorigenesis. PMID:27602775

  3. Solid pseudopapillary tumor: an invasive case report of primary ovarian origin and review of the literature

    PubMed Central

    He, Shuqian; Yang, Xiaoqing; Zhou, Ping; Cheng, Yuxia; Sun, Qing

    2015-01-01

    Solid pseudopapillary neoplasm occurring as a primary tumor outside the pancreas is a rare event. We report a case of an ovarian primary occurring with an ill-defined cystic mass in a 39-year-old woman. The morphologic and immunohistochemical features of the ovarian neoplasm described in this report are compatible with those of solid pseudopapillary neoplasm of the pancreas. Histologically, the tumor cells of the case we report infiltrate into the ovarian parenchyma. Because of the diagnosis is not clear before surgery, the patient had a reoccurrence two months after the operation in which laparoscopic simple ovarian cystectomy and part ovarian tissue removal, followed by the right salpingo-oophorectomy. The case herein confirms that solid pseudopapillary neoplasm of the ovary belongs to the class of low-grade malignant tumor with certain invasiveness. The diagnosis should be taken into serious consideration in order to avoid missed diagnosis and delay treatment. Through this case we have a better understanding of the biological behavior of solid pseudopapillary neoplasm of the ovary. PMID:26339451

  4. Management of bilateral malignant ovarian germ cell tumors: Experience of a single institute

    PubMed Central

    Zhao, Ting; Liu, Yan; Jiang, Hongyuan; Zhang, Hao; Lu, Yuan

    2016-01-01

    Bilateral malignant ovarian germ cell tumors (MOGCTs) are rare. Determination of the optimal treatment modalities is crucial, as these malignancies mainly affect girls and young women who may wish to preserve their fertility. In order to review the prevalence, clinical characteristics, treatment and outcome of bilateral MOGCTs, we performed a retrospective review of patients who were diagnosed with bilateral MOGCTs and underwent primary surgery at the Obstetrics and Gynecology Hospital of Fudan University (Shanghai, China) between January, 2001 and December, 2014. Of the 130 patients investigated, 8 were diagnosed with bilateral disease, most of whom were International Federation of Gynecology and Obstetrics stage I. There was no significant difference in overall and disease-free survival between patients with unilateral and those with bilateral disease. Cases with dysgerminoma, dysgerminoma coexisting with gonadoblastoma, yolk sac tumor and ovarian primary choriocarcinoma were included in this study. Fertility was spared in 2 patients (1 with dysgerminoma and 1 with ovarian primary choriocarcinoma). The patient with ovarian choriocarcinoma experienced relapse and was finally salvaged by radical surgery and adjuvant chemotherapy. According to our results and the published data, patients affected by bilateral MOGCTs have a satisfactory prognosis. The treatment modalities largely depend on the histological type of the tumor. Fertility-sparing surgery may be safe for patients affected by dysgerminoma, but should be considered with caution in patients with ovarian primary choriocarcinoma. PMID:27446585

  5. MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian Cancer

    ClinicalTrials.gov

    2017-03-14

    Malignant Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  6. Recognition of serous ovarian tumors in human samples by multimodal nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Adur, Javier; Pelegati, Vitor B.; Costa, Leverson F. L.; Pietro, Luciana; de Thomaz, Andre A.; Almeida, Diogo B.; Bottcher-Luiz, Fatima; Andrade, Liliana A. L. A.; Cesar, Carlos L.

    2011-09-01

    We used a multimodal nonlinear optics microscopy, specifically two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG/THG) microscopies, to observe pathological conditions of ovarian tissues obtained from human samples. We show that strong TPEF + SHG + THG signals can be obtained in fixed samples stained with hematoxylin and eosin (H&E) stored for a very long time, and that H&E staining enhanced the THG signal. We then used the multimodal TPEF-SHG-THG microscopies in a stored file of H&E stained samples of human ovarian cancer to obtain complementary information about the epithelium/stromal interface, such as the transformation of epithelium surface (THG) and the overall fibrillary tissue architecture (SHG). This multicontrast nonlinear optics microscopy is able to not only differentiate between cancerous and healthy tissue, but can also distinguish between normal, benign, borderline, and malignant specimens according to their collagen disposition and compression levels within the extracellular matrix. The dimensions of the layers of epithelia can also be measured precisely and automatically. Our data demonstrate that optical techniques can detect pathological changes associated with ovarian cancer.

  7. The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

    PubMed Central

    Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M.; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M.; Gehrig, Paola A.; Zhou, Chunxiao; Bae-Jump, Victoria L.

    2016-01-01

    Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women. PMID:27074576

  8. Targeted endostatin-cytosine deaminase fusion gene therapy plus 5-fluorocytosine suppresses ovarian tumor growth.

    PubMed

    Sher, Y-P; Chang, C-M; Juo, C-G; Chen, C-T; Hsu, J L; Lin, C-Y; Han, Z; Shiah, S-G; Hung, M-C

    2013-02-28

    There are currently no effective therapies for cancer patients with advanced ovarian cancer, therefore developing an efficient and safe strategy is urgent. To ensure cancer-specific targeting, efficient delivery, and efficacy, we developed an ovarian cancer-specific construct (Survivin-VISA-hEndoyCD) composed of the cancer specific promoter survivin in a transgene amplification vector (VISA; VP16-GAL4-WPRE integrated systemic amplifier) to express a secreted human endostatin-yeast cytosine deaminase fusion protein (hEndoyCD) for advanced ovarian cancer treatment. hEndoyCD contains an endostatin domain that has tumor-targeting ability for anti-angiogenesis and a cytosine deaminase domain that converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic drug, 5-fluorouracil. Survivin-VISA-hEndoyCD was found to be highly specific, selectively express secreted hEndoyCD from ovarian cancer cells, and induce cancer-cell killing in vitro and in vivo in the presence of 5-FC without affecting normal cells. In addition, Survivin-VISA-hEndoyCD plus 5-FC showed strong synergistic effects in combination with cisplatin in ovarian cancer cell lines. Intraperitoneal (i.p.) treatment with Survivin-VISA-hEndoyCD coupled with liposome attenuated tumor growth and prolonged survival in mice bearing advanced ovarian tumors. Importantly, there was virtually no severe toxicity when hEndoyCD is expressed by Survivin-VISA plus 5-FC compared with CMV plus 5-FC. Thus, the current study demonstrates an effective cancer-targeted gene therapy that is worthy of development in clinical trials for treating advanced ovarian cancer.

  9. [A case of coexisting borderline phyllodes tumor and non-invasive ductal carcinoma].

    PubMed

    Toyoda, Yasuhiro; Hojo, Shigeyuki; Yoshioka, Setsuko; Kojima, Fumiyoshi; Matsunaga, Hiroki; Fujie, Yujiro; Fukunaga, Hiroki; Ota, Hirofumi; Endo, Wakio; Maeura, Yoshiichi

    2013-11-01

    A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.

  10. Bioprosthetic tricuspid valve replacement in carcinoid heart disease from primary ovarian carcinoid tumor.

    PubMed

    Tsugu, Toshimitsu; Iwanaga, Shiro; Murata, Mitsushige; Fukuda, Keiichi

    2015-07-01

    Carcinoid heart disease (CHD) commonly occurs in association with primary gastrointestinal tract carcinoid tumors with hepatic metastases. Unlike primary gastrointestinal tract carcinoid tumors, primary ovarian carcinoid tumors may cause CHD without hepatic metastases, accounting for only 0.3 % of all carcinoid tumors. Only 37 cases of CHD from primary ovarian carcinoid tumors have been reported. We present a case of CHD in which tricuspid valve thickening and shortening led to reduced valve mobility with the resulting severe tricuspid regurgitation. Considering these characteristics of an abnormal tricuspid valve, we suspected CHD, but prosthetic valve replacement was performed without sufficient systemic examination before surgery. Two years after valve replacement, the patient underwent excision of a mass in the lower abdomen, which was diagnosed as an ovarian carcinoid tumor by histopathological examination. The patient has been observed for more than 3 years after tricuspid valve replacement. She has not experienced bioprosthetic valve leaflet degeneration or dysfunction, although it has been reported that bioprosthetic valves may degenerate in patients with carcinoid tumors. Sufficient systemic examinations should be performed to explore the cause of disease.

  11. Stromal p16 expression is significantly increased in malignant ovarian neoplasms

    PubMed Central

    Yoon, Nara; Yoon, Gun; Park, Cheol Keun; Kim, Hyun-Soo

    2016-01-01

    Alterations in p16 protein expression have been reported to be associated with tumor development and progression. However, p16 expression status in the peritumoral stroma has been rarely investigated. We investigated the stromal p16 expression in ovarian neoplasms using immunohistochemistry, and differences in the expression status depending on the degree of malignancy and histological type were analyzed. This study included 24, 21, and 46 cases of benign, borderline, and malignant ovarian lesions, respectively, of which 29, 25, and 32 cases were serous, mucinous, and endometriosis-associated lesions. Most benign lesions showed negative or weak expression, whereas borderline lesions showed focal, moderate expression. Malignant lesions showed markedly elevated stromal p16 expression compared with benign or borderline lesions. There were significant differences in stromal p16 expression between benign and borderline lesions (P < 0.001) and between borderline and malignant lesions (P < 0.001). These significances remained when analysis was performed based on lesion classification as serous, mucinous, and endometriosis-associated. In contrast, differences in stromal p16 expression among the histological types were not significant. Stromal p16 expression in ovarian neoplasms was absent or weak in benign and focal, moderate in borderline lesions, whereas malignant lesions exhibited diffuse, moderate-to-strong p16 immunoreactivity. Our observations suggest that stromal p16 expression is involved in the development of ovarian carcinoma. Further studies are necessary to confirm our preliminary results. PMID:27572321

  12. Stromal p16 expression is significantly increased in malignant ovarian neoplasms.

    PubMed

    Yoon, Nara; Yoon, Gun; Park, Cheol Keun; Kim, Hyun-Soo

    2016-10-04

    Alterations in p16 protein expression have been reported to be associated with tumor development and progression. However, p16 expression status in the peritumoral stroma has been rarely investigated. We investigated the stromal p16 expression in ovarian neoplasms using immunohistochemistry, and differences in the expression status depending on the degree of malignancy and histological type were analyzed. This study included 24, 21, and 46 cases of benign, borderline, and malignant ovarian lesions, respectively, of which 29, 25, and 32 cases were serous, mucinous, and endometriosis-associated lesions. Most benign lesions showed negative or weak expression, whereas borderline lesions showed focal, moderate expression. Malignant lesions showed markedly elevated stromal p16 expression compared with benign or borderline lesions. There were significant differences in stromal p16 expression between benign and borderline lesions (P < 0.001) and between borderline and malignant lesions (P < 0.001). These significances remained when analysis was performed based on lesion classification as serous, mucinous, and endometriosis-associated. In contrast, differences in stromal p16 expression among the histological types were not significant. Stromal p16 expression in ovarian neoplasms was absent or weak in benign and focal, moderate in borderline lesions, whereas malignant lesions exhibited diffuse, moderate-to-strong p16 immunoreactivity. Our observations suggest that stromal p16 expression is involved in the development of ovarian carcinoma. Further studies are necessary to confirm our preliminary results.

  13. Combined Adrenal and Ovarian Venous Sampling to Localize an Androgen Producing Tumor

    SciTech Connect

    Agarwal, Monica D.; Trerotola, Scott O.

    2010-12-15

    A postmenopausal woman presented with hirsutism and elevated serum testosterone levels. A 1-cm adrenal adenoma was noted on computed tomography. Combined adrenal and ovarian venous sampling was performed to localize an androgen producing tumor to the left ovary. The patient underwent a bilateral salpingo-oophrectomy and was spared an unnecessary adrenalectomy.

  14. Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor

    PubMed Central

    Boussios, Stergios; Moschetta, Michele; McLachlan, Jennifer; Banerjee, Susana

    2015-01-01

    Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis. PMID:26798532

  15. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

    PubMed

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-03-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (P<0.05) than those in benign ovarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

  16. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells

    PubMed Central

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-01-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1-ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (P<0.05) than those in benign ovarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma. PMID

  17. A Case of Giant Borderline Phyllodes Tumor of the Breast Associated with Hypoglycemia.

    PubMed

    Saito, Yuki; Suzuki, Yasuhiro; Inomoto, Chie; Kumaki, Nobue; Yokoyama, Kozue; Ogiya, Rin; Oshitanai, Risa; Terao, Mayako; Tsuda, Banri; Morioka, Tooru; Niikura, Naoki; Okamura, Takuho; Masuda, Shinobu; Tokuda, Yutaka

    2016-09-20

    We report a patient with a giant phyllodes tumor of the right breast associated with a hypoglycemic attack. A 48-year-old woman experienced a loss of consciousness and was transferred via ambulance to our hospital emergency department. Upon arrival, her blood glucose level was 26 mg/dl, and a giant tumor (>20 cm in diameter) with skin ulceration was observed on the right breast. Core needle biopsy led to a histological diagnosis of a phyllodes tumor of the breast. Ultrasonography and computed tomography detected neither distant metastasis nor a pancreatic endocrine tumor. Her preoperative serum insulin-like growth factor (IGF)-II and insulin levels were 1,330 ng/ml (normal range, 519-1067 ng/ml) and <1.0 µU/ml, respectively. Following a simple mastectomy, the 24-h postoperative serum IGF-II and insulin levels were 496 ng/ml and 10.0 µU/ml, respectively. The IGF-II levels detected in the phyllodes tumor and normal breast tissue were 10,600 ng/Wg (wet weight in grams) and 855 ng/Wg. We conclude from these findings that the hypoglycemic attack was related to the elevated IGF-II level in the giant phyllodes tumor of the breast.

  18. Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-01-31

    Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  19. The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

    PubMed Central

    de Lacerda Almeida, Bernardo Gomes; Bacchi, Carlos E; Carvalho, Jesus P; Ferreira, Cristiane R; Carvalho, Filomena M

    2014-01-01

    OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. PMID:25518016

  20. In vitro ovarian tumor growth and treatment response dynamics visualized with time-lapse OCT imaging

    PubMed Central

    Evans, Conor L.; Rizvi, Imran; Hasan, Tayyaba; de Boer, Johannes F.

    2010-01-01

    In vitro three-dimensional models for metastatic ovarian cancer have been useful for recapitulating the human disease. These spheroidal tumor cultures, however, can grow in excess of 1 mm in diameter, which are difficult to visualize without suitable imaging technology. Optical coherence tomography (OCT) is an ideal live imaging method for non-perturbatively visualizing these complex systems. OCT enabled detailed observations of the model at both nodular and cellular levels, revealing growth dynamics not previously observed. The development of a time-lapse OCT system, capable of automated, multidimensional acquisition, further provided insights into the growth and chemotherapeutic response of ovarian cancer. PMID:19466138

  1. Recurrent ovarian Sertoli–Leydig cell tumor in a child with Peutz–Jeghers syndrome

    PubMed Central

    Bellfield, Edward J.; Alemzadeh, Ramin

    2016-01-01

    We present a female child with Peutz–Jeghers syndrome (PJS) with a recurrent ovarian Sertoli–Leydig cell tumor (SLCT). SLCTs are relatively rare sex cord neoplasms that can occur in PJS. The patient was an African-American female who first presented at the age of 3 years with precocious puberty, and then at the age of 17 years with abdominal pain and irregular menses. In each case, she had resection of the mass, which included oophorectomy. To our knowledge, this is the first reported case in a child with PJS to have a recurrent ovarian SLCT. PMID:28101370

  2. A6 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-02-27

    Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Recurrent Ovarian Carcinoma; Undifferentiated Ovarian Carcinoma

  3. Contrast-enhanced ultrasound in ovarian tumors – diagnostic parameters: method presentation and initial experience

    PubMed Central

    MAXIM, ANITA-ROXANA; BADEA, RADU; TAMAS, ATILLA; TRAILA, ALEXANDRU

    2013-01-01

    The aim of this paper is to discuss and illustrate the use of contrast-enhanced ultrasound in evaluating ovarian tumors compared to conventional ultrasound, Doppler ultrasound and the histopathological analysis and suggest how this technique may best be used to distinguish benign from malignant ovarian masses. We present the method and initial experience of our center by analyzing the parameters used in contrast-enhanced ultrasound in 6 patients with ovarian tumors of uncertain etiology. For examination we used a Siemens ultrasound machine with dedicated contrast software and the contrast agent SonoVue, Bracco. The patients underwent conventional ultrasound, Doppler ultrasound and i.v. administration of the contrast agent. The parameters studied were: inflow of contrast (rise time), time to peak enhancement, mean transit time. The series of patients is part of an extensive prospective PhD study aimed at elaborating a differential diagnosis protocol for benign versus malignant ovarian tumors, by validating specific parameters for contrast-enhanced ultrasound. Although the method is currently used with great success in gastroenterology, urology and senology, its validation in gynecology is still in the early phases. Taking into consideration that the method is minimally invasive and much less costly that CT/MRI imaging, demonstrating its utility in oncologic gynecology would be a big step in preoperative evaluation of these cases. PMID:26527912

  4. Inhibition of EGFR-AKT Axis Results in the Suppression of Ovarian Tumors In Vitro and in Preclinical Mouse Model

    PubMed Central

    Gupta, Parul; Srivastava, Sanjay K.

    2012-01-01

    Ovarian cancer is the leading cause of cancer related deaths in women. Genetic alterations including overexpression of EGFR play a crucial role in ovarian carcinogenesis. Here we evaluated the effect of phenethyl isothiocyanate (PEITC) in ovarian tumor cells in vitro and in vivo. Oral administration of 12 µmol PEITC resulted in drastically suppressing ovarian tumor growth in a preclinical mouse model. Our in vitro studies demonstrated that PEITC suppress the growth of SKOV-3, OVCAR-3 and TOV-21G human ovarian cancer cells by inducing apoptosis in a concentration-dependent manner. Growth inhibitory effects of PEITC were mediated by inhibition of EGFR and AKT, which are known to be overexpressed in ovarian tumors. PEITC treatment caused significant down regulation of constitutive protein levels as well as phosphorylation of EGFR at Tyr1068 in various ovarian cancer cells. In addition, PEITC treatment drastically reduced the phosphorylation of AKT which is downstream to EGFR and disrupted mTOR signaling. PEITC treatment also inhibited the kinase activity of AKT as observed by the down regulation of p-GSK in OVCAR-3 and TOV-21G cells. AKT overexpression or TGF treatment blocked PEITC induced apoptosis in ovarian cancer cells. These results suggest that PEITC targets EGFR/AKT pathway in our model. In conclusion, our study suggests that PEITC could be used alone or in combination with other therapeutic agents to treat ovarian cancer. PMID:22952709

  5. Differential vimentin expression in ovarian and uterine corpus endometrioid adenocarcinomas: diagnostic utility in distinguishing double primaries from metastatic tumors.

    PubMed

    Desouki, Mohamed M; Kallas, Sarah J; Khabele, Dineo; Crispens, Marta A; Hameed, Omar; Fadare, Oluwole

    2014-05-01

    This study aimed to assess the diagnostic value of vimentin expression in differentiating endometrioid adenocarcinoma of primary uterine corpus and ovarian origin. Immunohistochemical analyses for the expression of vimentin in tumoral epithelial cells were performed on 149 endometrioid adenocarcinomas wherein the primary sites were not in question, including whole tissue sections of 27 carcinomas of uterine corpus origin (and no synchronous ovarian tumor), 7 carcinomas of ovarian origin (and no synchronous uterine corpus tumor) and a tissue microarray (TMA) containing 91 primary uterine corpus and 24 primary ovarian carcinomas. We also assessed 15 cases that synchronously involved the uterine corpus and ovary, 15 cases of metastasis to organs/tissues other than uterine corpus or ovary as well as 7 lymph node metastases. Vimentin was negative in 97% (30/31) of primary ovarian carcinomas. In contrast, 82% (97/118) of primary uterine corpus carcinomas were vimentin-positive. Vimentin expression was discordant in 53% of synchronous tumors. The sensitivity and specificity of negative vimentin staining in predicting an ovarian primary were 97% and 82%, respectively, whereas parallel values for positive vimentin staining in predicting a primary uterine tumor were 82% and 97%, respectively. The pattern of vimentin expression in all cases was maintained in their respective regional lymph nodes and distant metastases. In conclusion, ovarian and uterine corpus endometrioid adenocarcinomas have different patterns of vimentin expression. If validated in larger and/or different data sets, these findings may have diagnostic value in distinguishing metastatic lesions from double primary tumors involving both sites.

  6. A Tete – a – tete of benign, borderline and malignant fibrohistiocytic tumor

    PubMed Central

    M.V, Rashmi.; P, Pavithra; G.M, Shivakumarappa

    2016-01-01

    Dermatofibrosarcoma protruberans is a relatively uncommon slow growing, locally aggressive fibrous tumor of the skin. It has a prospensity of progressing to fibrosarcomatous change in 5% of the cases. We present a case of a 56 yr old male with presented to the outpatient department of surgery, Sri Siddhartha Medical College, Tumkur with a chest swelling in 2013. FNAC was inconclusive and the mass was excised. On histopathology, areas of benign fibrohistiocytic tumor, dermatofibrosarcoma protruberans and fibrosarcomatous dermatofibrosarcoma were identified in the same tumor. Immunohistochemistry confirmed the diagnosis of DFSP with fibrosarcomatous change. Although, transformed DFSP is more aggressive, the prognosis is influenced by the extent of excision and with wide excision, there may be little increased risk for recurrence and metastasis over that of conventional DFSP. PMID:27799980

  7. Stromal Overgrowth in a Brenner Tumor or Ovarian Fibroma With Minor Sex Cord Elements?

    PubMed

    Ross, Julia A; Saglam, Ozlen

    2015-07-01

    Computed tomography obtained as part of a urinary tract assessment in a 68-year-old woman incidentally detected a solid adnexal mass. Bilateral salpingo-oophorectomy revealed a unilateral, 4-cm, white to tan-yellow colored, focally calcified, left ovarian mass. Microscopically, the tumor was composed of bland fibroblasts, abundant collagen, and areas of calcification with a minor component composed of nests of epithelial cells with nuclear clefts focally evident, some of which contained central lumens with eosinophilic secretions. The major considerations were fibromatous overgrowth in a Brenner tumor or ovarian fibroma with minor sex cord elements. Immunostains for cytokeratin 7 showed diffuse positivity in the epithelial nests, whereas cytokeratin 20 and inhibin were negative, further supporting the diagnosis of a Brenner tumor.

  8. Symptomatic Ovarian Steroid Cell Tumor not Otherwise Specified in a Post-Menopausal Woman

    PubMed Central

    Sood, Neha; Desai, Kaniksha; Chindris, Ana-Maria; Lewis, Jason; Dinh, Tri A.

    2016-01-01

    Steroid cell tumor not otherwise specified (NOS) is a rare subtype of sex cord stromal tumor of the ovary and contributes less than 0.1% of all ovarian neoplasms. The majority of tumors occur in pre-menopausal women (mean age: 43 years), in which 56-77% of patients present with virilization due to excess testosterone. An 80-year-old woman with worsening alopecia and excessive growth of coarse hair on abdomen and genital area was found to have elevated serum testosterone level (462 ng/mL). Radiologic studies were consistent with bilateral adrenal adenomas. Bilateral adrenal venous sampling ruled out the adrenal gland as origin of hormone secretion. A diagnostic and therapeutic bilateral salpingo-oophorectomy confirmed steroid cell tumor NOS of the left ovary. Post-operatively, the patient had complete resolution of her symptoms and normalization of testosterone level. Our case emphasizes the importance of a clinical suspicion for an occult testosterone secreting ovarian tumor in a symptomatic patient without obvious ovarian mass on imaging. PMID:27441075

  9. Erlotinib Plus Carboplatin and Paclitaxel in Ovarian Carcinoma

    ClinicalTrials.gov

    2015-10-29

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  10. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  11. Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer target ID4

    PubMed Central

    Ren, Yin; Cheung, Hiu Wing; von Maltzhan, Geoffrey; Agrawal, Amit; Cowley, Glenn S.; Weir, Barbara A.; Boehm, Jesse S.; Tamayo, Pablo; Karst, Alison M.; Liu, Joyce F.; Hirsch, Michelle S.; Mesirov, Jill P.; Drapkin, Ronny; Root, David E.; Lo, Justin; Fogal, Valentina; Ruoslahti, Erkki; Hahn, William C.; Bhatia, Sangeeta N.

    2013-01-01

    The comprehensive characterization of a large number of cancer genomes will eventually lead to a compendium of genetic alterations in specific cancers. Unfortunately, the number and complexity of identified alterations complicate endeavors to identify biologically relevant mutations critical for tumor maintenance, because many of these targets are not amenable to manipulation by small molecules or antibodies. RNAi provides a direct way to study putative cancer targets; however, specific delivery of therapeutics to the tumor parenchyma remains an intractable problem. We describe a platform for the discovery and initial validation of cancer targets, composed of a systematic effort to identify amplified and essential genes in human cancer cell lines and tumors partnered with a novel modular delivery technology. We developed a tumor-penetrating nanocomplex (TPN) comprised of siRNA complexed with a tandem tumor-penetrating and membrane-translocating peptide, which enabled the specific delivery of siRNA deep into the tumor parenchyma. We employed TPN in vivo to evaluate inhibitor of DNA binding 4 (ID4) as a novel oncogene. Treatment of ovarian tumor-bearing mice with ID4-specific TPN suppressed growth of established tumors and significantly improved survival. These observations not only credential ID4 as an oncogene in 32% of high-grade ovarian cancers, but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets. PMID:22896676

  12. Biologic Effects of Dopamine on Tumor Vasculature in Ovarian Carcinoma12

    PubMed Central

    Moreno-Smith, Myrthala; Lee, Sun Joo; Lu, Chunhua; Nagaraja, Archana S; He, Guangan; Rupaimoole, Rajesha; Han, Hee Dong; Jennings, Nicholas B; Roh, Ju-Won; Nishimura, Masato; Kang, Yu; Allen, Julie K; Armaiz, Guillermo N; Matsuo, Koji; Shahzad, Mian M K; Bottsford-Miller, Justin; Langley, Robert R; Cole, Steve W; Lutgendorf, Susan K; Siddik, Zahid H; Sood, Anil K

    2013-01-01

    Chronic sympathetic nervous system activation results in increased angiogenesis and tumor growth in orthotopic mouse models of ovarian carcinoma. However, the mechanistic effects of such activation on the tumor vasculature are not well understood. Dopamine (DA), an inhibitory catecholamine, regulates the functions of normal and abnormal blood vessels. Here, we examined whether DA, an inhibitory catecholamine, could block the effects of chronic stress on tumor vasculature and tumor growth. Exogenous administration of DA not only decreased tumor microvessel density but also increased pericyte coverage of tumor vessels following daily restraint stress in mice. Daily restraint stress resulted in significantly increased tumor growth in the SKOV3ip1 and HeyA8 ovarian cancer models. DA treatment blocked stress-mediated increases in tumor growth and increased pericyte coverage of tumor endothelial cells. Whereas the antiangiogenic effect of DA is mediated by dopamine receptor 2 (DR2), our data indicate that DA, through DR1, stimulates vessel stabilization by increasing pericyte recruitment to tumor endothelial cells. DA significantly stimulated migration of mouse 10T1/2 pericyte-like cells in vitro and increased cyclic adenosine mono-phosphate (cAMP) levels in these cells. Moreover, DA or the DR1 agonist SKF 82958 increased platinum concentration in SKOV3ip1 tumor xenografts following cisplatin administration. In conclusion, DA stabilizes tumor blood vessels through activation of pericyte cAMP-protein kinase A signaling pathway by DR1. These findings could have implications for blocking the stimulatory effects of chronic stress on tumor growth. PMID:23633922

  13. Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer

    PubMed Central

    Wen, Wei; Liang, Wei; Wu, Jun; Kowolik, Claudia M.; Buettner, Ralf; Scuto, Anna; Hsieh, Meng-Yin; Hong, Hao; Brown, Christine E.; Forman, Stephen J.; Horne, David; Morgan, Robert; Wakabayashi, Mark; Dellinger, Thanh H.; Han, Ernest S.; Yim, John H.; Jove, Richard

    2015-01-01

    JAK/STAT3 is one of the major signaling pathways that is aberrantly activated in ovarian cancer and associated with tumor progression and poor prognosis in ovarian cancer patients. In this study, we evaluated the therapeutic potential of targeting JAK/STAT3 signaling in ovarian cancer using a peritoneal dissemination mouse model. We developed this mouse model by injecting a metastatic human ovarian cancer cell line, SKOV3-M-Luc, into the peritoneal cavity of immunodeficient mice. This model displayed a phenotype similar to late stage ovarian cancer, including extensive peritoneal metastasis and ascites production. The constitutive activation of STAT3 in human ovarian cancer cells appeared to be mediated by an autocrine-cytokine loop involving the IL-6 family of cytokines and JAK1 kinase. shRNA-mediated knockdown of JAK1 or STAT3 in ovarian cancer cells led to reduced tumor growth, decreased peritoneal dissemination and diminished ascites production, suggesting a critical role of STAT3 in ovarian cancer progression. Similar results were obtained when a small-molecule inhibitor (JAKi) of the JAK1 kinase was used to treat ovarian cancer in this model. In addition, we found that the expression level of IL-6 was correlated with activation of STAT3 in ovarian cancer cells both in vitro and in vivo, suggesting a potential application of IL-6 as a biomarker. Altogether, our results demonstrate that targeting JAK1/STAT3, using shRNA knockdown or a small molecule inhibitor, effectively suppressed ovarian tumor progression and, therefore, could be a potential novel therapeutic approach for treating advanced ovarian cancer. PMID:25319391

  14. Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer.

    PubMed

    Wen, Wei; Liang, Wei; Wu, Jun; Kowolik, Claudia M; Buettner, Ralf; Scuto, Anna; Hsieh, Meng-Yin; Hong, Hao; Brown, Christine E; Forman, Stephen J; Horne, David; Morgan, Robert; Wakabayashi, Mark; Dellinger, Thanh H; Han, Ernest S; Yim, John H; Jove, Richard

    2014-12-01

    JAK/STAT3 is one of the major signaling pathways that is aberrantly activated in ovarian cancer and associated with tumor progression and poor prognosis in patients with ovarian cancer. In this study, we evaluated the therapeutic potential of targeting JAK/STAT3 signaling in ovarian cancer using a peritoneal dissemination mouse model. We developed this mouse model by injecting a metastatic human ovarian cancer cell line, SKOV3-M-Luc, into the peritoneal cavity of immunodeficient mice. This model displayed a phenotype similar to late-stage ovarian cancer, including extensive peritoneal metastasis and ascites production. The constitutive activation of STAT3 in human ovarian cancer cells appeared to be mediated by an autocrine cytokine loop involving the IL6 family of cytokines and JAK1 kinase. shRNA-mediated knockdown of JAK1 or STAT3 in ovarian cancer cells led to reduced tumor growth, decreased peritoneal dissemination, and diminished ascites production, suggesting a critical role of STAT3 in ovarian cancer progression. Similar results were obtained when a small-molecule inhibitor (JAKi) of the JAK1 kinase was used to treat ovarian cancer in this model. In addition, we found that the expression level of IL6 was correlated with activation of STAT3 in ovarian cancer cells both in vitro and in vivo, suggesting a potential application of IL6 as a biomarker. Altogether, our results demonstrate that targeting JAK1/STAT3, using shRNA knockdown or a small-molecule inhibitor, effectively suppressed ovarian tumor progression and, therefore, could be a potential novel therapeutic approach for treating advanced ovarian cancer.

  15. In vivo bioengineered ovarian tumors based on collagen, matrigel, alginate and agarose hydrogels: a comparative study.

    PubMed

    Zheng, Li; Hu, Xuefeng; Huang, Yuanjie; Xu, Guojie; Yang, Jinsong; Li, Li

    2015-01-29

    Scaffold-based tumor engineering is rapidly evolving the study of cancer progression. However, the effects of scaffolds and environment on tumor formation have seldom been investigated. In this study, four types of injectable hydrogels, namely, collagen type I, Matrigel, alginate and agarose gels, were loaded with human ovarian cancer SKOV3 cells and then injected into nude mice subcutaneously. The growth of the tumors in vitro was also investigated. After four weeks, the specimens were harvested and analyzed. We found that tumor formation by SKOV3 cells was best supported by collagen, followed by Matrigel, alginate, control (without scaffold) and agarose in vivo. The collagen I group exhibited a larger tumor volume with increased neovascularization and increased necrosis compared with the other materials. Further, increased MMP activity, upregulated expression of laminin and fibronectin and higher levels of HIF-1α and VEGF-A in the collagen group revealed that the engineered tumor is closer to human ovarian carcinoma. In order, collagen, Matrigel, alginate, control (without scaffold) and agarose exhibited decreases in tumor formation. All evidence indicated that the in vivo engineered tumor is scaffold-dependent. Bioactive hydrogels are superior to inert hydrogels at promoting tumor regeneration. In particular, biomimetic hydrogels are advantageous because they provide a microenvironment that mimics the ECM of natural tumors. On the other hand, typical features of cancer cells and the expression of genes related to cancer malignancy were far less similar to the natural tumor in vitro, which indicated the importance of culture environment in vivo. Superior to the in vitro culture, nude mice can be considered satisfactory in vivo 'bioreactors' for the screening of favorable cell vehicles for tumor engineering in vitro.

  16. Ovarian malignant mixed mesodermal tumor with neuroectodermal differentiation: a multifaceted evaluation.

    PubMed

    Mott, Ryan T; Murphy, Bettina A; Geisinger, Kim R

    2010-05-01

    Malignant mixed mesodermal tumors (MMMTs) of the ovary are rare, highly aggressive neoplasms that arise most commonly in postmenopausal women. Histologically, they consist of a mixed population of malignant epithelial and mesenchymal elements. Neuroectodermal differentiation in ovarian MMMTs is exceedingly uncommon, with only a few case reports in the literature. We present a case of an ovarian MMMT with neuroectodermal differentiation in a 78-year-old female patient. Histologically, the tumor was composed of epithelial, mesenchymal, and neuroectodermal elements. The neuroectodermal component was predominantly that of a medulloepithelioma, with scattered areas displaying features of an anaplastic astrocytoma, including rare ganglion cell differentiation. The neuroectodermal component showed immunoreactivity for glial fibrillary acidic protein, synaptophysin, and S100 protein. Ultrastructurally, the neuroectodermal component was populated by cells with irregular nuclei, finely dispersed chromatin, rudimentary cell junctions, and a delicate basement membrane, all of which have been described in medulloepitheliomas. DNA ploidy analysis was also performed on the various components of the tumor and compared with 3 additional cases of MMMT without neuroectodermal differentiation and 2 ovarian immature teratomas. Our findings suggest that the neuroectodermal component may arise from a separate clone or at least evolves at an earlier stage of tumor development.

  17. Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells

    PubMed Central

    Ahmed, Nuzhat; Greening, David; Samardzija, Chantel; Escalona, Ruth M.; Chen, Maoshan; Findlay, Jock K.; Kannourakis, George

    2016-01-01

    Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within <5 years due to episodes of recurrences resulting from the growth of residual chemoresistant cells. In an effort to identify mechanisms associated with chemoresistance and recurrence, we compared the expression of proteins in ascites-derived tumor cells isolated from advanced-stage ovarian cancer patients obtained at diagnosis (chemonaive, CN) and after chemotherapy treatments (chemoresistant/at recurrence, CR) by using in-depth, high-resolution label-free quantitative proteomic profiling. A total of 2,999 proteins were identified. Using a stringent selection criterion to define only significantly differentially expressed proteins, we report identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients. PMID:27470985

  18. Contrast-Enhanced Ultrasonography in Differential Diagnosis of Benign and Malignant Ovarian Tumors

    PubMed Central

    Qiao, Jing-Jing; Yu, Jing; Yu, Zhe; Li, Na; Song, Chen; Li, Man

    2015-01-01

    Objective To evaluate the accuracy of contrast-enhanced ultrasonography (CEUS) in differential diagnosis of benign and malignant ovarian tumors. Methods The scientific literature databases PubMed, Cochrane Library and CNKI were comprehensively searched for studies relevant to the use of CEUS technique for differential diagnosis of benign and malignant ovarian cancer. Pooled summary statistics for specificity (Spe), sensitivity (Sen), positive and negative likelihood ratios (LR+/LR−), and diagnostic odds ratio (DOR) and their 95%CIs were calculated. Software for statistical analysis included STATA version 12.0 (Stata Corp, College Station, TX, USA) and Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain). Results Following a stringent selection process, seven high quality clinical trials were found suitable for inclusion in the present meta-analysis. The 7 studies contained a combined total of 375 ovarian cancer patients (198 malignant and 177 benign). Statistical analysis revealed that CEUS was associated with the following performance measures in differential diagnosis of ovarian tumors: pooled Sen was 0.96 (95%CI = 0.92∼0.98); the summary Spe was 0.91 (95%CI = 0.86∼0.94); the pooled LR+ was 10.63 (95%CI = 6.59∼17.17); the pooled LR− was 0.04 (95%CI = 0.02∼0.09); and the pooled DOR was 241.04 (95% CI = 92.61∼627.37). The area under the SROC curve was 0.98 (95% CI = 0.20∼1.00). Lastly, publication bias was not detected (t = −0.52, P = 0.626) in the meta-analysis. Conclusions Our results revealed the high clinical value of CEUS in differential diagnosis of benign and malignant ovarian tumors. Further, CEUS may also prove to be useful in differential diagnosis at early stages of this disease. PMID:25764442

  19. Eudaimonic Well-Being and Tumor Norepinephrine in Epithelial Ovarian Cancer Patients

    PubMed Central

    Davis, Lauren Z.; Slavich, George M.; Thaker, Premal H.; Goodheart, Michael J.; Bender, David; Dahmoush, Laila; Farley, Donna; Markon, Kristian; Penedo, Frank J.; Lubaroff, David M.; Cole, Steve W.; Sood, Anil K.; Lutgendorf, Susan K.

    2015-01-01

    Background The impact of psychological well-being on physiologic processes involved in cancer progression remains unclear. Prior research has implicated adrenergic signaling in tumor growth and metastasis. Given that adrenergic signaling is influenced by both positive and negative factors, we examined how two different aspects of well-being (eudaimonic and positive affect) and psychological distress were associated with tumor norepinephrine (NE) in ovarian cancer patients. Methods Women with suspected ovarian cancer (N=365) completed psychosocial assessments pre-surgery and clinical information was obtained from medical records. Study inclusion was confirmed following histological diagnosis. Tumor NE was measured in frozen tissue samples using HPLC with electrochemical detection. We employed confirmatory factor analysis to model eudaimonic well-being, positive affect, and psychological distress, and structural equation modeling (SEM) to examine associations between these factors and tumor NE. Results Eudaimonic well-being, positive affect, and psychological distress, modeled as distinct but correlated constructs, best fit the data (i.e., compared to unitary or 2-factor models) (RMSEA=.048, CFI=.982, SRMR=.035). SEM analyses that included physical well-being, stage, histology, psychological treatment history, beta-blocker use, and caffeine use as covariates had good model fit (RMSEA=.052, CFI=.955, SRMR=.036) and showed that eudaimonic well-being was related to lower tumor NE (β=−.24, p=.045). In contrast, we found no effects for positive affect or psychological distress. Conclusion Eudaimonic well-being is associated with lower tumor NE, independent of positive affect and psychological distress. Because adrenergic signaling is implicated in tumor progression, increasing eudaimonic well-being may improve both psychological and physiologic resilience in ovarian cancer patients. PMID:26096769

  20. Ovarian tumor in a 12-year old female with severe hypothyroidism: A case of Van Wyk and Grumbach syndrome.

    PubMed

    Hunold, Andrea; Alzen, Gerhard; Wudy, Stefan A; Bluetters-Sawatzki, Renate; Landmann, Eva; Reiter, Alfred; Wagner, Hans-Joachim

    2009-05-01

    We report a 12-year-old female presenting with an abdominal tumor. Diagnostic workup revealed giant bilateral ovarian cysts, severe hypothyroidism as well as an elevation of CA 125. We refrained from ovariectomy, which would be necessary for a malignant tumor, in view of an evident Van Wyk and Grumbach syndrome. The patient promptly responded to L-thyroxine with complete regression of all symptoms. Hypothyroidism should be considered in the evaluation of ovarian cysts. Although the Van Wyk and Grumbach syndrome is rare, it is crucial to rule it out in order to avoid unnecessary ovarian surgery when thyroid replacement is completely sufficient.

  1. Bilateral Ovarian Krukenberg Tumor in a Full-Term Pregnancy

    PubMed Central

    Dueñas-García, Omar Felipe; Diaz-Sotomayor, Maricela; Chanana, Charu

    2011-01-01

    Objective. Krukenberg tumors in pregnancy are very rare and their management can present a dilemma for the obstetrician gynecologist. Case Report. We present the case of a G3P2002 who presented to us and the 38 weeks gestation with bilateral massive Krukenberg tumors. Despite at surgery and chemotherapy she died 3 months postpartum. Conclusion. Early detection followed by surgery and chemotherapy could possibly result in a favorable outcome with such patients. PMID:21637363

  2. Fine-needle aspiration cytology of ovarian steroid cell tumor: A rare case report

    PubMed Central

    Agrawal, Nidhi; Vardhan, Harsh; Khokhar, Singh; Rai, Naresh; Saxena, Rajeev; Riyaz, Shahida

    2015-01-01

    Steroid cell tumors (SCTs) of the ovary are a rare subgroup of sex cord tumors that account for less than 0.1% of all ovarian tumors. These tumors can produce steroids, especially testosterone, which produces symptoms such as hirsutism, amenorrhea/oligomenorrhea, and male patterned voice. For evaluation of the androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S) are the first laboratory tests to be measured. Abdominal ultrasound and magnetic resonance imaging (MRI) are useful radiologic imaging techniques. Although SCTs are generally benign, the risk of malignant transformation is always present. Surgical excision of tumor is the most important and hallmark treatment. The present case signifies the early preoperative diagnosis of a virilizing SCT, based on cytological features and its careful correlation with clinicopathological and radiological findings. PMID:26811582

  3. Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes: the EPIC cohort

    PubMed Central

    Ose, Jennifer; Schock, Helena; Tjonneland, Anne; Hansen, Louise; Overvad, Kim; Dossus, Laure; Clavel-Chapelon, Francoise; Baglietto, Laura; Boeing, Heiner; Trichopolou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Masala, Giovanna; Tagliabue, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; de Mesquita, H.Bas Bueno; Peeters, Petra H M; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Gram, Inger T; Sánchez, Soledad; Obon-Santacana, Mireia; Sànchez-Pérez, Maria-José; Larrañaga, Nerea; Castaño, José María Huerta; Ardanaz, Eva; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Travis, Ruth C; Khaw, Kay-Tee; Rinaldi, Sabina; Romieu, Isabelle; Merrit, Melissa A; Gunter, Marc J; Riboli, Elio; Kaaks, Rudolf; Fortner, Renée T

    2015-01-01

    Background Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. Methods We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), interleukin-6 (IL-6), and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n=1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. Results CRP and IL-6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 vs. CRP ≤1 mg/L was associated with higher overall EOC risk (OR=1.67 [1.03 - 2.70]). We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference: (e.g., IL-6: waist ≤80: ORlog2=0.97 [0.81 - 1.16]; waist >88: ORlog2=1.78 [1.28 - 2.48], pheterogeneity ≤0.01). Conclusions Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL-6 and CRP may be associated with EOC risk among women with higher adiposity. Impact Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. PMID:25855626

  4. High-resolution analysis of copy number alterations and associated expression changes in ovarian tumors

    PubMed Central

    Haverty, Peter M; Hon, Lawrence S; Kaminker, Joshua S; Chant, John; Zhang, Zemin

    2009-01-01

    Background DNA copy number alterations are frequently observed in ovarian cancer, but it remains a challenge to identify the most relevant alterations and the specific causal genes in those regions. Methods We obtained high-resolution 500K SNP array data for 52 ovarian tumors and identified the most statistically significant minimal genomic regions with the most prevalent and highest-level copy number alterations (recurrent CNAs). Within a region of recurrent CNA, comparison of expression levels in tumors with a given CNA to tumors lacking that CNA and to whole normal ovary samples was used to select genes with CNA-specific expression patterns. A public expression array data set of laser capture micro-dissected (LCM) non-malignant fallopian tube epithelia and LCM ovarian serous adenocarcinoma was used to evaluate the effect of cell-type mixture biases. Results Fourteen recurrent deletions were detected on chromosomes 4, 6, 9, 12, 13, 15, 16, 17, 18, 22 and most prevalently on X and 8. Copy number and expression data suggest several apoptosis mediators as candidate drivers of the 8p deletions. Sixteen recurrent gains were identified on chromosomes 1, 2, 3, 5, 8, 10, 12, 15, 17, 19, and 20, with the most prevalent gains localized to 8q and 3q. Within the 8q amplicon, PVT1, but not MYC, was strongly over-expressed relative to tumors lacking this CNA and showed over-expression relative to normal ovary. Likewise, the cell polarity regulators PRKCI and ECT2 were identified as putative drivers of two distinct amplicons on 3q. Co-occurrence analyses suggested potential synergistic or antagonistic relationships between recurrent CNAs. Genes within regions of recurrent CNA showed an enrichment of Cancer Census genes, particularly when filtered for CNA-specific expression. Conclusion These analyses provide detailed views of ovarian cancer genomic changes and highlight the benefits of using multiple reference sample types for the evaluation of CNA-specific expression changes

  5. Overexpression of clusterin promotes angiogenesis via the vascular endothelial growth factor in primary ovarian cancer.

    PubMed

    Fu, Yanxia; Lai, Yingrong; Wang, Qiongjuan; Liu, Xingyang; He, Weipeng; Zhang, Haihong; Fan, Chunyang; Yang, Guofen

    2013-06-01

    Clusterin (CLU), a multifunctional glycoprotein, is ubiquitously produced in mammalian tissues. CLU has been shown to play significant roles in many of the biological behaviours of human tumors, such as cell proliferation, apoptosis, chemoresistance and angiogenesis. However, the relationship of CLU expression with angiogenesis in ovarian cancer has not been studied. A total of 275 epithelial ovarian tumors were obtained from archives of paraffin‑embedded tissues. Immunohistochemical (IHC) staining for CLU and vascular endothelial growth factor (VEGF) was performed on a tissue microarray (TMA) including 181 primary ovarian epithelial cancer, 40 borderline ovarian tumors and 54 ovarian cancer mesenteric metastasis samples. Of the 174 cases, overexpression of CLU and VEGF were detected in 107 (61.5%) and 109 (62.9%) cases of primary ovarian carcinoma, respectively. Of the 107 cases of primary ovarian carcinoma with overexpression of CLU, expression of VEGF was increased in 82 (75.2%) cases. However, in another 67 cases without CLU overexpression, overexpression of VEGF was observed in only 27 (24.8%) cases (P<0.05). Overexpression of CLU in epithelial ovarian cancer appears to be correlated with increased tumor angiogenesis, consistent with the established role of CLU as an oncogene in the biology of ovarian cancer. In the treatment of ovarian cancer, these two markers may be used in the selection of patients for targeted therapy.

  6. Role of diffusion-weighted magnetic resonance imaging in differentiating malignancies from benign ovarian tumors

    PubMed Central

    Fan, Xinhua; Zhang, Hongbin; Meng, Shuang; Zhang, Jing; Zhang, Chuge

    2015-01-01

    Objective: We conducted a case-control study to evaluate the diagnostic values of computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in differentiating malignancies from benign ovarian tumors and a meta-analysis to further confirm our results on DW-MRI. Methods: Totally 64 patients pathologically confirmed as ovarian cancer were included in this study. CT scan and DWI-MRI were performed and analyzed to get compared with pathological results, thereby assessing their accuracy, sensitivity and specificity. Meta-analysis was conducted by database searching and strict eligibility criteria, using STATA 12.0 (Stata Corp, College Station, TX, USA) software. Results: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ovarian cancer in CT were 81.82%, 84.48%, 76.67%, 87.50% and 71.88%, respectively; those in DW-MRI were 89.77%, 93.10%, 83.33%, 91.53% and 86.21%, respectively. The Kappa coefficient of DW-MRI (K = 0.771) compared with pathological results was higher than CT (K = 0.602). The average apparent diffusion coefficient values of DW-MRI in diagnosis of benign and malignant ovarian tumors suggested statistically significant difference (1.325 ± 0.269×10-3 mm2/s vs. 0.878 ± 0.246×10-3 mm2/s, P < 0.001). Meta-analysis results showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of DW-MRI in discriminating benign versus malignant ovarian tumors were 0.93, 0.88, 7.70, 0.08 and 101.24, respectively. The area under the summary receiver operating characteristic curve was 0.95. Conclusions: Both CT and DW-MRI were of great diagnostic value in differentiating malignancies from benign ovarian tumors, while DW-MRI was superior to CT with higher accuracy, sensitivity and specificity. PMID:26884905

  7. c-Met inhibitors attenuate tumor growth of small cell hypercalcemic ovarian carcinoma (SCCOHT) populations.

    PubMed

    Otte, Anna; Rauprich, Finn; von der Ohe, Juliane; Yang, Yuanyuan; Kommoss, Friedrich; Feuerhake, Friedrich; Hillemanns, Peter; Hass, Ralf

    2015-10-13

    A cellular model (SCCOHT-1) of the aggressive small cell hypercalcemic ovarian carcinoma demonstrated constitutive chemokine and growth factor production including HGF. A simultaneous presence of c-Met in 41% SCCOHT-1 cells suggested an autocrine growth mechanism. Expression of c-Met was also observed at low levels in the corresponding BIN-67 cell line (6.5%) and at high levels in ovarian adenocarcinoma cells (NIH:OVCAR-3 (84.4%) and SK-OV-3 (99.3%)). Immunohistochemistry of c-Met expression in SCCOHT tumors revealed a heterogeneous distribution between undetectable levels and 80%. Further characterization of SCCOHT-1 and BIN-67 cells by cell surface markers including CD90 and EpCAM demonstrated similar patterns with differences to the ovarian adenocarcinoma cells. HGF stimulation of SCCOHT-1 cells was associated with c-Met phosphorylation at Tyr1349 and downstream Thr202/Tyr204 phosphorylation of p44/42 MAP kinase. This HGF-induced signaling cascade was abolished by the c-Met inhibitor foretinib. Cell cycle analysis after foretinib treatment demonstrated enhanced G2 accumulation and increasing apoptosis within 72 h. Moreover, the IC50 of foretinib revealed 12.4 nM in SCCOHT-1 cells compared to 411 nM and 481 nM in NIH:OVCAR-3 and SK-OV-3 cells, respectively, suggesting potential therapeutic effects. Indeed, SCCOHT-1 and BIN-67 tumor xenografts in NODscid mice exhibited an approximately 10-fold and 5-fold reduced tumor size following systemic application of foretinib, respectively. Furthermore, foretinib-treated tumors revealed a significantly reduced vascularization and little if any c-Met-mediated signal transduction. Similar findings of reduced proliferative capacity and declined tumor size were observed after siRNA-mediated c-Met knock-down in SCCOHT-1 cells demonstrating that in vivo inhibition of these pathways contributed to an attenuation of SCCOHT tumor growth.

  8. Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread

    PubMed Central

    Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T.; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar

    2016-01-01

    High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors. 23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed. Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer. PMID:27172797

  9. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    ClinicalTrials.gov

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  10. Elesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-12-23

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  11. TLR8 Agonist VTX-2337 and Pegylated Liposomal Doxorubicin Hydrochloride or Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-23

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  12. Resolution of right-sided heart failure symptoms after resection of a primary ovarian carcinoid tumor.

    PubMed

    Goldman, Todd; Adamson, Kathi; Yang, Eugene

    2014-10-01

    Carcinoid tumors are rare neuroendocrine malignancies that typically originate from the gastrointestinal tract. Patients who are diagnosed with carcinoid heart disease generally have poor prognoses because of advanced metastases during staging and few therapeutic options. We present the case of a 61-year-old woman with right-sided heart failure, secondary to carcinoid heart disease caused by a primary ovarian carcinoid tumor. After undergoing surgical resection of the left ovary and fallopian tube, the patient experienced complete resolution of her heart failure symptoms. In addition to the patient's case, we discuss the diagnosis, nature, and treatment of this rare condition.

  13. Ovarian cancer survival by tumor dominance, a surrogate for site of origin

    PubMed Central

    Ivanova, Anna; Loo, Anneli; Tworoger, Shelley; Crum, Christopher P.; Fan, Isabel; McLaughlin, John R.; Rosen, Barry; Risch, Harvey; Narod, Steven A.; Kotsopoulos, Joanne

    2015-01-01

    Objectives Recent studies suggest that a proportion of ovarian tumors may actually originate in the distal fallopian tube. The objective of this study was to examine the relationship between dominance (a surrogate for site of origin) and survival following a diagnosis of epithelial ovarian cancer. Methods We classified 1,386 tumors as dominant (putatively originating in the ovary and non-dominant (putatively originating in the fallopian tube), using parameters obtained from pathology reports. Dominant tumors were restricted to one ovary or one involved ovary that exceeded the other in dimension by at least two-fold, while non-dominant tumors were identified as having a greater likelihood of a tubal origin if the disease was equally distributed across the ovaries. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with dominance. Results Non-dominant tumors were more likely to be serous, stage III/IV, and be associated with a BRCA1/2 mutation, increasing parity and use of estrogen hormone replacement therapy (P ≤ 0.01). In contrast, 46% and 26% of the dominant tumors were serous and endometrioid, respectively, with a more even distribution of stage (P < 0.0001). Women with a non-dominant tumor had an increased risk of death compared to women with a dominant tumor (multivariate HR = 1.28; 95%CI 1.02–1.60). Findings were similar in our analysis restricted to serous only subtypes (HR = 1.28; 95%CI 1.01–1.63). Conclusion These preliminary findings suggest significantly worse survival among women diagnosed with a tumor putatively arising from fallopian tube. PMID:25771796

  14. Differential diagnosis of ovarian tumors based primarily on their patterns and cell types.

    PubMed

    Young, R H; Scully, R E

    2001-08-01

    The differential diagnosis of ovarian tumors is reviewed based on their patterns and cell types. This approach, which differs from the standard textbook discussion of each neoplasm as an entity, has practical value as differential diagnosis depends largely on the pattern or patterns and cell type or types of tumors. Awareness of the broad range of lesions that may exhibit particular patterns or contain one or more cell types is crucial in formulating a differential diagnosis. The following patterns are considered: moderate-to-large-glandular and hollow-tubular; solid tubular and pseudotubular; cords and ribbons; insular; trabecular; slit-like and reticular spaces; microglandular and microfollicular; macrofollicular and pseudomacrofollicular; papillary; diffuse; fibromatous-thecomatous; and biphasic and pseudobiphasic. The following cell types are considered: small round cells; spindle cells; mucinous cells, comprising columnar, goblet cell and signet ring cell subtypes; clear cells; hobnail cells; oxyphil cells; and transitional cells. The morphologic diversity of ovarian tumors poses many challenges; knowledge of the occurrence and frequency of these patterns and cell types in various tumors and tumor-like lesions is of paramount diagnostic importance. A specific diagnosis can usually be made by evaluating routinely stained slides, but much less often, special staining, immunohistochemical staining or, very rarely, ultrastructural examination is also required. Finally, clinical data, operative findings, and gross features of the lesions may provide important, and at times decisive diagnostic clues.

  15. Ovarian malignant mixed mullerian tumor with primitive neuroectodermal differentiation: case report with review of the literature.

    PubMed

    Nasser, Haitham; Morris, Robert T; Fathallah, Lamia

    2011-03-15

    Ovarian malignant mixed mullarian tumor (OMMMT) is a rare and aggressive tumor of the female genital tract, occurring mainly in elderly women. Stage of disease is the most important predictor for survival with no prognostic effect, yet, of heterologous elements. Rare case reports described the peculiar presence of primitive neuroectodermal tissue among other heterologous elements in these tumors. Attractive designations, such as teratoid carcinosarcoma, were set by some authors to describe this subset of lesions, where it was considered a primary neuroectodermal tumor capable of multilineage differentiation. We here report a case of OMMMT in an elderly woman with focal primitive neuroectodermal differentiation as the sole heterologous element, and review the controversy on this topic in the literature.

  16. Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy.

    PubMed

    McAuliffe, Shannon M; Morgan, Stefanie L; Wyant, Gregory A; Tran, Lieu T; Muto, Katherine W; Chen, Yu Sarah; Chin, Kenneth T; Partridge, Justin C; Poole, Barish B; Cheng, Kuang-Hung; Daggett, John; Cullen, Kristen; Kantoff, Emily; Hasselbatt, Kathleen; Berkowitz, Julia; Muto, Michael G; Berkowitz, Ross S; Aster, Jon C; Matulonis, Ursula A; Dinulescu, Daniela M

    2012-10-23

    Chemoresistance to platinum therapy is a major obstacle that needs to be overcome in the treatment of ovarian cancer patients. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). This study demonstrates that the Notch signaling pathway and Notch3 in particular are critical for the regulation of CSCs and tumor resistance to platinum. We show that Notch3 overexpression in tumor cells results in expansion of CSCs and increased platinum chemoresistance. In contrast, γ-secretase inhibitor (GSI), a Notch pathway inhibitor, depletes CSCs and increases tumor sensitivity to platinum. Similarly, a Notch3 siRNA knockdown increases the response to platinum therapy, further demonstrating that modulation of tumor chemosensitivity by GSI is Notch specific. Most importantly, the cisplatin/GSI combination is the only treatment that effectively eliminates both CSCs and the bulk of tumor cells, indicating that a dual combination targeting both populations is needed for tumor eradication. In addition, we found that the cisplatin/GSI combination therapy has a synergistic cytotoxic effect in Notch-dependent tumor cells by enhancing the DNA-damage response, G(2)/M cell-cycle arrest, and apoptosis. Based on these results, we conclude that targeting the Notch pathway could significantly increase tumor sensitivity to platinum therapy. Our study suggests important clinical applications for targeting Notch as part of novel treatment strategies upon diagnosis of ovarian cancer and at recurrence. Both platinum-resistant and platinum-sensitive relapses may benefit from such an approach as clinical data suggest that all relapses after platinum therapy are increasingly platinum resistant.

  17. Application of X-Ray Fluorescence Analysis to Determine the Elemental Composition of Tissues from Different Ovarian Neoplasms

    NASA Astrophysics Data System (ADS)

    Motevich, I. G.; Strekal, N. D.; Papko, N. M.; Glebovich, M. I.; Shulha, A. V.; Maskevich, S. A.

    2015-03-01

    We present the results of x-ray fluorescence analysis of tissues from healthy ovaries and from ovaries with different pathologies: benign and borderline tumors, mucinous and endometrioid cancers, serous carcinomas. We determine the average copper, zinc, calcium, selenium, cadmium, lead, and mercury levels. We observed that in the benign ovarian tumors, we see a significant decrease in the cadmium, mercury, and lead levels compared with healthy tissues. In the borderline neoplasms, the copper level is reduced relative to zinc (Cu/Zn), cadmium, mercury, and lead, and also the zinc concentration is increased. In the ovarian carcinomas, we observed changes in the ratio of the chemical elements in the tumor tissues, depending on the histologic type. The results obtained can be used for differentiation, diagnosis, and adjustment of treatment for different ovarian neoplasms.

  18. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  19. The diagnosis and pathological value of combined detection of HE4 and CA125 for patients with ovarian cancer

    PubMed Central

    Qu, Jun-ying; He, Fei

    2016-01-01

    Abstract Objective To evaluate the value of individual and combined measurement of human epididymis protein 4 (HE4) and cancer antigen 125 (CA-125) in the diagnosis of ovarian cancer. Methods A clinical case-control study was performed in which the levels of serum HE4 and CA-125 of subjects with malignant, borderline, benign ovarian tumors and healthy women were measured before surgery. An immunohistochemistry method was used to measure the expression of HE4 in different tissues. Statistical analysis was performed to determine the relationship between the level of HE4 and the pathologic type as well as the stage of the ovarian tumors. Results The level of HE4 in the serum was significantly elevated in the malignant ovarian cancer group compared with other groups. Women with benign ovarian tumors and non-neoplastic lesions, and healthy women were designated as references. When the level of HE4 in the serum was 58.66 pmol/L, the sensitivity and specificity of HE4 in diagnosing malignant ovarian tumors was 82.35% and 96.03%, respectively. The level of HE4 was negatively correlated with the differentiation extent of the tumors whereas positively correlated to the clinical staging. In the groups of malignant and borderline tumors, the levels of HE4 were higher than the other groups. The expression of HE4 was significant higher in the serous types of ovarian tumors than that of the mucous types (P<0.05). The level of HE4 in the serum and tissues were positively correlated with each other. Conclusion HE4 can be used as a novel clinical biomarker for predicting malignant ovarian tumors and its expression was closely related with the clinical pathological features of malignant ovarian tumors. PMID:28352780

  20. A High-Throughput Screening Model of the Tumor Microenvironment for Ovarian Cancer Cell Growth.

    PubMed

    Lal-Nag, Madhu; McGee, Lauren; Guha, Rajarshi; Lengyel, Ernst; Kenny, Hilary A; Ferrer, Marc

    2017-01-01

    The tumor microenvironment plays an important role in the processes of tumor growth, metastasis, and drug resistance. We have used a multilayered 3D primary cell culture model that reproduces the human ovarian cancer metastatic microenvironment to study the effect of the microenvironment on the pharmacological responses of different classes of drugs on cancer cell proliferation. A collection of oncology drugs was screened to identify compounds that inhibited the proliferation of ovarian cancer cells growing as monolayers or forming spheroids, on plastic and on a 3D microenvironment culture model of the omentum metastatic site, and also cells already in preformed spheroids. Target-based analysis of the pharmacological responses revealed that several classes of targets were more efficacious in cancer cells growing in the absence of the metastatic microenvironment, and other target classes were less efficacious in cancer cells in preformed spheres compared to forming spheroid cultures. These findings show that both the cellular context of the tumor microenvironment and cell adhesion mode have an essential role in cancer cell drug resistance. Therefore, it is important to perform screens for new drugs using model systems that more faithfully recapitulate the tissue composition at the site of tumor growth and metastasis.

  1. Rare case of an ovarian vein tumor thrombosis identified on fluorodeoxyglucose positron emission tomography/computed tomography

    PubMed Central

    Chandra, Piyush; Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Rangarajan, Venkatesh

    2016-01-01

    Fludeoxyglucose positron emission tomography/computed tomography is valuable in the identification of tumor thrombus and differentiating it from bland thrombus which has implications in initiating anticoagulation. We present a rare case of tumor thrombosis in ovarian vein, in a recurrent case of uterine carcinosarcoma. PMID:27833321

  2. Large moderately-differentiated ovarian Sertoli-Leydig cell tumor in a 13-year-old female: A case report

    PubMed Central

    ZHANG, HUI; HAO, JING; LI, CHUN-YAN; LI, TAO; MU, YU-LAN

    2016-01-01

    Sertoli-Leydig cell tumor of the ovary, also known as androblastoma, is a rare neoplasm from the group of sex cord-stromal tumors of the ovary. The tumor accounts for <0.5% of all primary ovarian neoplasms. The clinical signs and symptoms of Sertoli-Leydig cell tumors can be associated with either hormonal production or the presence of a mass-occupying lesion. In the current study, a 13-year-old female was diagnosed with a stage Ic ovarian Sertoli-Leydig cell tumor following abdominal pain and distension. One month after a right oophorectomy, the follow-up magnetic resonance imaging scan was negative for residual or recurrent tumor. The overall 5-year survival rate for moderately-differentiated (grade 2) and poorly-differentiated (grade 3) Sertoli-Leydig cell tumors is 80%, and long-term follow-up is therefore highly advised in this patient. PMID:26893701

  3. [Case of ischemic heart disease resulting from persistent diuresis after giant ovarian tumor resection].

    PubMed

    Sata, Naho; Satoh, Masaaki; Seo, Norimasa

    2010-02-01

    A patient with a giant ovarian tumor weighing about 7 kg was successfully removed by operation. However, her ECG demonstrated ischemic changes after the operation. We report a case of ischemic heart disease due to persistent diuresis after giant ovarian tumor resection. A 75-year-old, 56.5 kg, 143.5 cm woman was admitted to our hospital for ovarian tumor resection. The preoperative ECG showed normal sinus rhythm and no ischemic changes. Both general anesthesia and epidural anesthesia were planed. An epidural catheter was inserted at T12-L1. Anesthesia was induced with propofol 100 mg, fentanyl 100 microg and vecuronium 8 mg under 100% oxygen inhalation. General anesthesia was maintained with sevoflurane while epidural anesthesia was achieved using 0.375% ropivacaine 6 ml. During the operation, blood pressure was 90-110/70-80 mmHg, with SaO2, 100% and heart rate, 70-80 beats x min(-1). The content of tumor was suctioned for 30 minutes. Surgery was successfully finished without any other incidence. After extubation, her ECG changed to atrial fibrillation from normal sinus rhythm and showed ST-T depression. And then her systolic blood pressure became 80 mmHg or below, but we found continued diuresis at about 10 ml x kg(-1) x hr(-1) for over 2 hr. The total of 7 unit vasopressin was intermittently given for vasoconstriction and antidiuresis. Her hemodynamic was immediately restored, and ECG turned to normal ST-T. The patient had uneventful postoperative recovery.

  4. Reduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian cancer

    PubMed Central

    2014-01-01

    AMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remains obscure. Here, we provide evidence to show that reduced expression of the AMPK-β1 subunit during tumor progression is associated with the increased oncogenic capacity of advanced ovarian cancer cells. Immunohistochemical analysis revealed that AMPK-β1 levels were reduced in advanced-stage (P = 0.008), high-grade (P = 0.013) and metastatic ovarian cancers (P = 0.008). Intriguingly, down-regulation of AMPK-β1 was progressively reduced from tumor stages 1 to 3 of ovarian cancer. Functionally, enforced expression of AMPK-β1 inhibited ovarian-cancer-cell proliferation, anchorage-independent cell growth, cell migration and invasion. Conversely, depletion of AMPK-β1 by siRNA enhanced the oncogenic capacities of ovarian cancer cells, suggesting that the loss of AMPK-β1 favors the aggressiveness of ovarian cancer. Mechanistically, enforced expression of AMPK-β1 increased AMPK activity, which, in turn, induced cell-cycle arrest via inhibition of AKT/ERK signaling activity as well as impaired cell migration/invasion through the suppression of JNK signaling in ovarian cancer cells. Taken together, these findings suggest that the reduced expression of AMPK-β1 confers lower AMPK activity, which enhances the oncogenic capacity of advanced-stage ovarian cancer. PMID:24602453

  5. In vivo tumor growth of high-grade serous ovarian cancer cell lines

    PubMed Central

    Mitra, Anirban; Davis, David A.; Tomar, Sunil; Roy, Lynn; Gurler, Hilal; Xie, Jia; Lantvit, Daniel D.; Cardenas, Horacio; Fang, Fang; Liu, Yueying; Loughran, Elizabeth; Yang, Jing; Stack, M. Sharon; Emerson, Robert E; Cowden Dahl, Karen D.; Barbolina, Maria; Nephew, Kenneth P.; Matei, Daniela; Burdette, Joanna E.

    2015-01-01

    Objective Genomic studies of ovarian cancer (OC) cell lines frequently used in research revealed that these cells do not fully represent high-grade serous ovarian cancer (HGSOC), the most common OC histologic type. However, OC lines that appear to genomically resemble HGSOC have not been extensively used and their growth characteristics in murine xenografts are essentially unknown. Methods To better understand growth patterns and characteristics of HGSOC cell lines in vivo, CAOV3, COV362, KURAMOCHI, NIH-OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVSAHO, OVKATE, SNU119, UWB1.289 cells were assessed for tumor formation in nude mice. Cells were injected intraperitoneally (i.p.) or subcutaneously (s.c.) in female athymic nude mice and allowed to grow (maximum of 90 days) and tumor formation was analyzed. All tumors were sectioned and assessed using H&E staining and immunohistochemistry for p53, PAX8 and WT1 expression. Results Six lines (OVCAR3, OVCAR4, OVCAR5, OVCAR8, CAOV3, and OVSAHO) formed i.p xenografts with HGSOC histology. OVKATE and COV362 formed s.c. tumors only. Rapid tumor formation was observed for OVCAR3, OVCAR5 and OVCAR8, but only OVCAR8 reliably formed ascites. Tumors derived from OVCAR3, OVCAR4, and OVKATE displayed papillary features. Of the 11 lines examined, three (Kuramochi, SNU119 and UWB1.289) were non-tumorigenic. Conclusions Our findings help further define which HGSOC cell models reliably generate tumors and/or ascites, critical information for preclinical drug development, validating in vitro findings, imaging and prevention studies by the OC research community. PMID:26050922

  6. DMU-212 inhibits tumor growth in xenograft model of human ovarian cancer.

    PubMed

    Piotrowska, Hanna; Myszkowski, Krzysztof; Abraszek, Joanna; Kwiatkowska-Borowczyk, Eliza; Amarowicz, Ryszard; Murias, Marek; Wierzchowski, Marcin; Jodynis-Liebert, Jadwiga

    2014-05-01

    DMU-212 has been shown to evoke a mitochondrial apoptotic pathway in transformed fibroblasts and breast cancer. However, recently published data indicated the ability of DMU-212 to evoke apoptosis in both mitochondria- and receptor-mediated manner in two ovarian cancer cell lines, namely A-2780 and SKOV-3, which showed varied sensitivity to the compound tested. The pronounced cytotoxic effects of DMU-212 observed in A-2780 cells were related to the execution of extracellular apoptosis pathway and cell cycle arrest in G2/M phase. In view of the great anticancer potential of DMU-212 against A-2780 cell line, the aim of the current study was to assess antiproliferative activity of DMU-212 in xenograft model of ovarian cancer. To evaluate in vitro metabolic properties of cells that were to be injected into SCID mice, uptake and decline of DMU-212 in A-2780 ovarian cancer cell line was investigated. It was found that the concentration of the test compound in A-2780 cells was growing within first eight hours, and then the gradual decline was observed. A-2780 cells stably transfected with pcDNA3.1/Zeo(-)-Luc vector were subcutaneously inoculated into the right flanks of SCID mice. After seven days of the treatment with DMU-212 (50mg/kg b.w), tumor growth appeared to be suppressed in the animals treated with the compound tested. At day 14 of the experiment, tumor burden in mice treated with DMU-212 was significantly lower, as compared to untreated controls. Our findings suggest that DMU-212 might be considered as a potential anticancer agent used in ovarian cancer therapy.

  7. Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    PubMed

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-01-01

    Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P < 0.05) and late stages (P < 0.001). Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  8. Induction of ovarian granulosa cell tumors in SWXJ-9 mice with dehydroepiandrosterone.

    PubMed

    Beamer, W G; Shultz, K L; Tennent, B J

    1988-05-15

    Spontaneous ovarian granulosa cell (GC) tumors develop in SWXJ-9 inbred mice at approximately the time of puberty. The effect of dehydroepiandrosterone (DHEA), a steroid secreted by the adrenals and reported to have antitumor actions, was examined in this ovarian tumor model. In contrast with expectations, administration of diet supplemented with 0.4% DHEA or Silastic capsules containing 10 mg DHEA resulted in a significant multifold increase in GC tumor incidence. Similar studies with metabolites of DHEA, i.e., testosterone (TESTO), dihydrotestosterone (DHT), and 17 beta-estradiol (E2), revealed that TESTO was as effective as DHEA in increasing GC tumor incidence. DHT was without effect, and E2 suppressed GC tumor incidence. Serum steroid levels and steroid target tissue responses were assessed to determine if a correlation between a change in level or response to specific steroids and GC tumorigenesis existed. In both tumor-free and GC tumor host mice, dietary or capsular treatment with DHEA, TESTO, or DHT resulted in substantial alteration in one or more of serum steroids, DHEA, androstenedione, TESTO, and DHT, in addition to the administered steroid. No consistent correlation was observed between changes in a single steroid or pattern of steroids and GC tumorigenesis. Although significant increases in serum estrogens could be detected in GC tumor hosts treated with DHEA but not TESTO, estrogens did not induce these tumors. Treatment with E2 increased only serum E2 levels. In tumor-free mice, DHEA and E2 treatments were associated with vaginal cytological evidence of estrogen action, whereas the androgens induced a leukocytic pattern. Eighty-eight % of GC tumor host mice, regardless of steroid treatment, showed a vaginal cytology pattern that included cornified cells. The evidence presented in this report leads us to hypothesize that (a) spontaneous and steroid-induced GC tumorigenesis in these mice have the same mechanism, and (b) subtle increases in DHEA or a

  9. Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression

    PubMed Central

    Duckworth, C; Zhang, L; Carroll, S L; Ethier, S P; Cheung, H W

    2016-01-01

    We previously found that the scaffold adapter GRB2-associated binding protein 2 (GAB2) is amplified and overexpressed in a subset of primary high-grade serous ovarian cancers and cell lines. Ovarian cancer cells overexpressing GAB2 are dependent on GAB2 for activation of the phosphatidylinositol 3-kinase (PI3K) pathway and are sensitive to PI3K inhibition. In this study, we show an important role of GAB2 overexpression in promoting tumor angiogenesis by upregulating expression of multiple chemokines. Specifically, we found that suppression of GAB2 by inducible small hairpin RNA in ovarian cancer cells inhibited tumor cell proliferation, angiogenesis and peritoneal tumor growth in immunodeficient mice. Overexpression of GAB2 upregulated the secretion of several chemokines from ovarian cancer cells, including CXCL1, CXCL2 and CXCL8. The secreted chemokines not only signal through endothelial CXCR2 receptor in a paracrine manner to promote endothelial tube formation, but also act as autocrine growth factors for GAB2-induced transformation of fallopian tube secretory epithelial cells and clonogenic growth of ovarian cancer cells overexpressing GAB2. Pharmacological inhibition of inhibitor of nuclear factor kappa-B kinase subunit β (IKKβ), but not PI3K, mechanistic target of rapamycin (mTOR) or mitogen-activated protein kinase (MEK), could effectively suppress GAB2-induced chemokine expression. Inhibition of IKKβ augmented the efficacy of PI3K/mTOR inhibition in suppressing clonogenic growth of ovarian cancer cells with GAB2 overexpression. Taken together, these findings suggest that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. PMID:26657155

  10. Virilizing Ovarian Stromal Tumor in a Young Woman With Carney Complex

    PubMed Central

    Carney, J. Aidan; Stratakis, Constantine A.

    2011-01-01

    A woman with Carney complex presented at age 22 years with abdominal pain and hirsutism. As a baby, she had excision of a right eyelid lesion and at age 14 years removal of a left lower eyelid nodule that subsequently recurred. Investigation revealed an elevated level of serum testosterone and a 2-cm left ovarian tumor. A left salpingo-oophorectomy was performed. Postoperatively, the abdominal pain was relieved, the serum level of testosterone was normalized, and the hirsutism was ameliorated. The tumor featured sheets of eosinophilic cells with lipochrome pigment, myeloid metaplasia, stromal metaplasia, and markedly abnormal blood vessels. Immunocytochemically, the tumor cells were positive for vimentin, synaptophysin, inhibin A and calrenin. Because of the clinical setting in which the neoplasm occurred, it is unlikely that the occurrence was unrelated to Carney complex.. PMID:21934476

  11. Ovarian low and high grade serous carcinomas: hidden divergent features in the tumor microenvironment

    PubMed Central

    Buttarelli, Marianna; Martinelli, Enrica; Mascilini, Floriana; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Gallo, Daniela

    2016-01-01

    Only recently low-grade serous carcinoma (LGSOC) of the ovary has been recognized as a disease entity distinct from the more common high-grade serous carcinoma (HGSOC), with significant differences in pathogenesis and clinical and pathologic features. The present study aimed at evaluating whether the different natural histories and patterns of response to therapy demonstrated for LGSOC and HGSOC, along with a diverse genomic landscape, may also reside in the supporting tumor stroma, specifically in the state of differentiation and activation of tumor associated macrophages (TAMs). TAMs play complex roles in tumorigenesis since they are believed to possess both tumor rejecting (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we showed that, when compared to HGSOC (n = 55), LGSOC patients (n = 25) exhibited lower density of tumor-infiltrating CD68+ macrophage, along with an attenuated M2-skewed (CD163+) phenotype. Accordingly, assessment of intratumoral vascularization and of matrix metalloproteinase 9 expression (a key protein involved in tumor invasion and metastasis) revealed lower expression in LGSOC compared to HGSOC patients, in line with emerging evidence supporting a role for TAMs in all aspects of tumor initiation, growth, and development. In conclusion, results from the present study demonstrate that microenvironmental factors contribute greatly to determine clinical and pathological features that differentiate low and high grade serous ovarian carcinomas. This understanding may increase possibilities and opportunities to improve disease control and design new therapeutic strategies. PMID:27462782

  12. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer.

    PubMed

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-09-20

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.

  13. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    PubMed Central

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff; Pedersen, Magnus; Hansen, Morten; Svane, Inge Marie

    2015-01-01

    Personalized cancer immunotherapy based on infusion of T cells holds the promise to specifically target a patient’s individual tumor. Accumulating evidence indicates that the T cells mediating these tumor regressions after cancer immunotherapies may primarily target patient-specific mutations expressed by the patients’ tumors and that the presence of these “neo-antigen” specific T-cells may be related to a high number of mutations in the tumor. In melanoma, treatment with autologous tumor-infiltrating lymphocytes (TILs) can mediate durable complete responses. Previous trials investigating TIL therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe the major advances in the characterization and application of TIL therapy for patients with RCC and OC. PMID:26308285

  14. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer

    PubMed Central

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G.; Meier, Samuel M.; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-01-01

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors. PMID:27665539

  15. Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17

    PubMed Central

    Gaarenstroom, Katja N.; de Kroon, Cor D.; van Poelgeest, Mariette I.E.; Vuyk, Jaap; Bosse, Tjalling; Smit, Vincent T.H.B.M; van de Velde, Cornelis J.H.; Cohen, Adam F.; Low, Philip S.; Burggraaf, Jacobus; Vahrmeijer, Alexander L.

    2016-01-01

    Introduction Intraoperative fluorescence imaging of the folate-receptor alpha (FRα) could support completeness of resection in cancer surgery. Feasibility of EC17, a FRα-targeting agent that fluoresces at 500nm, was demonstrated in a limited series of ovarian cancer patients. Our objective was to evaluate EC17 in a larger group of ovarian cancer patients. In addition, we assessed the feasibility of EC17 in patients with breast cancer. Methods Two-to-three hours before surgery 0.1mg/kg EC17 was intravenously administered to 12 patients undergoing surgery for ovarian cancer and to 3 patients undergoing surgery for biopsy-proven FRα-positive breast cancer. The number of lesions/positive margins detected with fluorescence and concordance between fluorescence and tumor- and FRα-status was assessed in addition to safety and pharmacokinetics. Results Fluorescence imaging in ovarian cancer patients allowed detection of 57 lesions of which 44 (77%) appeared malignant on histopathology. Seven out of these 44 (16%) were not detected with inspection/palpation. Histopathology demonstrated concordance between fluorescence and FRα- and tumor status. Fluorescence imaging in breast cancer patients, allowed detection of tumor-specific fluorescence signal. At the 500nm wavelength, autofluorescence of normal breast tissue was present to such extent that it interfered with tumor identification. Conclusions FRα is a favorable target for fluorescence-guided surgery as EC17 produced a clear fluorescent signal in ovarian and breast cancer tissue. This resulted in resection of ovarian cancer lesions that were otherwise not detected. Notwithstanding, autofluorescence caused false-positive lesions in ovarian cancer and difficulty in discriminating breast cancer-specific fluorescence from background signal. Optimization of the 500nm fluorophore, will minimize autofluorescence and further improve intraoperative tumor detection. PMID:27014973

  16. Neutrophil Granulocytes in Ovarian Cancer - Induction of Epithelial-To-Mesenchymal-Transition and Tumor Cell Migration

    PubMed Central

    Mayer, Christine; Darb-Esfahani, Silvia; Meyer, Anne-Sophie; Hübner, Katrin; Rom, Joachim; Sohn, Christof; Braicu, Ioana; Sehouli, Jalid; Hänsch, G. Maria; Gaida, Matthias M.

    2016-01-01

    Background: Ovarian cancer (OvCa) is a highly aggressive malignoma with a tumor-promoting microenvironment. Infiltration of polymorphonuclear neutrophils (PMN) is frequently seen, raising the question of their impact on tumor development. In that context, effects of PMN on human ovarian cancer cells were assessed. Methods: Human epithelial ovarian cancer cells were incubated with human PMN, lysate of PMN, or neutrophil elastase. Morphological alterations were observed by time-lapse video-microscopy, and the underlying molecular mechanism was analyzed by flow cytometry and Western blotting. Functional alternations were assessed by an in vitro wound healing assay. In parallel, a large cohort of n=334 primary OvCa tissue samples of various histological subtypes was histologically evaluated. Results: Co-cultivation of cancer cells with either PMN or PMN lysate causes a change of the polygonal epithelial phenotype of the cells towards a spindle shaped morphology, causing a cribriform cell growth. The PMN-induced alteration could be attributed to elastase, a major protease of PMN. Elastase-induced shape change was most likely due to the degradation of membranous E-cadherin, which results in loss of cell contacts and polarity. Moreover, in response to elastase, epithelial cytokeratins were downmodulated, in parallel with a nuclear translocation of β-catenin. These PMN-elastase induced alterations of cells are compatible with an epithelial-to-mesenchymal transition (EMT) of the cancer cells. Following EMT, the cells displayed a more migratory phenotype. In human biopsies, neutrophil infiltration was seen in 72% of the cases. PMN infiltrates were detected preferentially in areas with low E-cadherin expression. Conclusion: PMN in the microenvironment of OvCa can alter tumor cells towards a mesenchymal and migratory phenotype. PMID:27053953

  17. VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    PubMed

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-07-01

    Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics.

  18. Anti-ovarian tumor response of donor peripheral blood mononuclear cells is due to infiltrating cytotoxic NK cells

    PubMed Central

    Pandey, Veethika; Oyer, Jeremiah L.; Igarashi, Robert Y.; Gitto, Sarah B.; Copik, Alicja J.; Altomare, Deborah A.

    2016-01-01

    Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for tumor remission, although logistical concerns impede widespread implementation. In this study, healthy PBMCs were used to examine the immune response in a mouse model with human ovarian cancer, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion in mice treated intraperitoneally with PBMC+Interleukin-2 (IL-2), as compared to no expansion in non-tumor-bearing mice given the same treatment. PBMC+IL-2 treated mice exhibiting NK cell expansion had complete tumor remission. To validate NK cell mediated anti-tumor response, the intratumoral presence of NK cells and their cytotoxicity was confirmed by immunohistochemistry and granzyme activity of NK cells recovered from the tumor. Collectively, this study highlights the significance of NK cell-cytotoxic response to tumor, which may be attributed to interacting immune cell types in the PBMC population, as opposed to clinically used isolated NK cells showing lack of anti-tumor efficacy in ovarian cancer patients. PMID:26802025

  19. Anti-ovarian tumor response of donor peripheral blood mononuclear cells is due to infiltrating cytotoxic NK cells.

    PubMed

    Pandey, Veethika; Oyer, Jeremiah L; Igarashi, Robert Y; Gitto, Sarah B; Copik, Alicja J; Altomare, Deborah A

    2016-02-09

    Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for tumor remission, although logistical concerns impede widespread implementation. In this study, healthy PBMCs were used to examine the immune response in a mouse model with human ovarian cancer, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion in mice treated intraperitoneally with PBMC+Interleukin-2 (IL-2), as compared to no expansion in non-tumor-bearing mice given the same treatment. PBMC+IL-2 treated mice exhibiting NK cell expansion had complete tumor remission. To validate NK cell mediated anti-tumor response, the intratumoral presence of NK cells and their cytotoxicity was confirmed by immunohistochemistry and granzyme activity of NK cells recovered from the tumor. Collectively, this study highlights the significance of NK cell-cytotoxic response to tumor, which may be attributed to interacting immune cell types in the PBMC population, as opposed to clinically used isolated NK cells showing lack of anti-tumor efficacy in ovarian cancer patients.

  20. Human endometrial mesenchymal stem cells exhibit intrinsic anti-tumor properties on human epithelial ovarian cancer cells

    PubMed Central

    Bu, Shixia; Wang, Qian; Zhang, Qiuwan; Sun, Junyan; He, Biwei; Xiang, Charlie; Liu, Zhiwei; Lai, Dongmei

    2016-01-01

    Epithelial ovarian cancer (EOC) is the most lethal tumor of all gynecologic tumors. There is no curative therapy for EOC thus far. The tumor-homing ability of adult mesenchymal stem cells (MSCs) provide the promising potential to use them as vehicles to transport therapeutic agents to the site of tumor. Meanwhile, studies have showed the intrinsic anti-tumor properties of MSCs against various kinds of cancer, including epithelial ovarian cancer. Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood are a novel source for adult MSCs and exert restorative function in some diseases. Whether EnSCs endow innate anti-tumor properties on EOC cells has never been reported. By using tumor-bearing animal model and ex vivo experiments, we found that EnSCs attenuated tumor growth by inducing cell cycle arrest, promoting apoptosis, disturbing mitochondria membrane potential and decreasing pro-angiogenic ability in EOC cells in vitro and/or in vivo. Furthermore, EnSCs decreased AKT phosphorylation and promoted nuclear translocation of Forkhead box O-3a (FoxO3a) in EOC cells. Collectively, our findings elucidated the potential intrinsic anti-tumor properties of EnSCs on EOC cells in vivo and in vitro. This research provides a potential strategy for EnSC-based anti-cancer therapy against epithelial ovarian cancer. PMID:27845405

  1. EphB3 protein is associated with histological grade and FIGO stage in ovarian serous carcinomas.

    PubMed

    Gao, Weiwei; Zhang, Qin; Wang, Yan; Wang, Jiandong; Zhang, Shu

    2017-02-01

    Eph (Erythropoietin-producing human hepatocellular carcinoma cell) is the largest subfamily of receptor tyrosine kinases. Eph receptors and their ephrin ligands are involved in embryonic development and physiological processes. Aberrant expression of Eph/ephrin may contribute to a variety of diseases including cancer. EphB3 is a member of Eph receptors and has been found to play roles in carcinogenesis of some types of human cancer. But, its expression and clinical significance in ovarian serous carcinoma have not been well investigated and are unknown. In this study, a set of ovarian tissues including normal fallopian tube, serous borderline tumor, and serous carcinoma were subjected to immunohistochemistry using a specific polyclonal antibody for EphB3. The relationship between EphB3 expression and clinicopathological parameters was statistically analyzed. EphB3 was strongly expressed in all fallopian tube specimens (19/19, 100%). EphB3 was negatively or weekly expressed in 1 of 17 (5.8%) in borderline tumors and 26 of 50 (52.0%) in serous carcinomas, moderately expressed in 7 of 17 (41.2%) in borderline tumors and 14 of 50 (28%) in serous carcinomas, and strongly expressed in 9 17 (52.9%) in borderline tumors and 10 of 50 (20%) in serous carcinomas. EphB3 expression is significantly reduced in serous carcinomas compared with normal fallopian tubes and borderline tumors (p < 0.001). EphB3 expression is negatively associated with histological grade (p < 0.001, rs = -0.613) and FIGO stage (p = 0.001, rs = -0.464) of serous carcinomas. Our results show EphB3 protein lost in ovarian serous carcinoma and is associated with tumor grade and FIGO stage, which indicate EphB3 protein may play a role in carcinogenesis of ovarian serous carcinoma and may be used as a molecular marker for prognosis.

  2. Ovarian tumor characterization and classification: a class of GyneScan™ systems.

    PubMed

    Acharya, U Rajendra; Sree, Vinitha S; Saba, Luca; Molinari, Filippo; Guerriero, Stefano; Suri, Jasjit S

    2012-01-01

    In this work, we have developed an adjunct Computer Aided Diagnostic (CAD) technique that uses 3D acquired ultrasound images of the ovary and data mining algorithms to accurately characterize and classify benign and malignant ovarian tumors. In this technique, we extracted image-texture based and Higher Order Spectra (HOS) based features from the images. The significant features were then selected and used to train and test the Decision Tree (DT) classifier. The proposed technique was validated using 1000 benign and 1000 malignant images, obtained from 10 patients with benign and 10 with malignant disease, respectively. On evaluating the classifier with 10-fold stratified cross validation, we observed that the DT classifier presented a high accuracy of 95.1%, sensitivity of 92.5% and specificity of 97.7%. Thus, the four significant features could adequately quantify the subtle changes and nonlinearities in the pixel intensities. The preliminary results presented in this paper indicate that the proposed technique can be reliably used as an adjunct tool for ovarian tumor classification since the system is accurate, completely automated, cost-effective, and can be easily written as a software application for use in any computer.

  3. Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2014-12-29

    Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

  4. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    PubMed Central

    Chen, Ying; Zhang, Lei; Liu, Wenxin; Liu, Xiangyu

    2015-01-01

    Tumor-stroma ratio (TSR) has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC) and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P < 0.001). The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%), LN metastasis (51.93% versus 27.25%), and recurrence (34.27% versus 6.82%). Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months) and overall survival (50 versus 58 months), respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC. PMID:26609529

  5. High expression of S100P is associated with unfavorable prognosis and tumor progression in patients with epithelial ovarian cancer

    PubMed Central

    Wang, Xiangyu; Tian, Tian; Li, Xukun; Zhao, Meng; Lou, Yanhui; Qian, Jingfeng; Liu, Zhihua; Chen, Hongyan; Cui, Zhumei

    2015-01-01

    Accumulating evidence has demonstrated that S100P is involved in the tumorigenesis and progression of multiple cancers. In the current study, we evaluated the expression of S100P in epithelial ovarian cancer and assessed its relevance to clinicopathological characteristics. Moreover, we investigated the biological effects of S100P using A2780 and SKOV3 cells. S100P expression was significantly increased in epithelial ovarian cancer specimens compared with fallopian tube tissues and normal ovary tissues. And high expression of S100P in epithelial ovarian cancer samples was significantly associated with tumor stage (P<0.001), serum CA125 level (P=0.026), residual tumor (P<0.001), ascites (P<0.001) and lymph nodes metastasis (P<0.001). Multivariate Cox analysis showed that S100P expression was an independent prognostic factor of overall survival (OS) and progression free survival (PFS) (P=0.017 and 0.031, respectively). Functional assays showed that overexpression of S100P promoted cell proliferation and cell cycle progression but did not affect cell migration and invasion in A2780 and SKOV3 cells. These data suggest that S100P may contribute to tumor development in epithelial ovarian cancer and could be a useful marker for the prognosis of epithelial ovarian cancer patients. PMID:26396916

  6. Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

    ClinicalTrials.gov

    2013-01-23

    Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  7. TLR4 activates NF-{kappa}B in human ovarian granulosa tumor cells

    SciTech Connect

    Woods, Dori C.; Johnson, A.L.

    2011-06-17

    Highlights: {yields} TLR4 is expressed in human ovarian granulosa tumor cells. {yields} Acting through TLR4, LPS and HSP60 induce a NF{kappa}B signaling cascade in human ovarian granulosa tumor cells. {yields} NF{kappa}B activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-{kappa}B) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to I{kappa}B degradation and activation of NF-{kappa}B. NF-{kappa}B activation was confirmed by nuclear localization of NF-{kappa}B p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-{kappa}B signaling attenuated LPS-induced TNF{alpha} plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-{kappa}B signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-{kappa}B does not sensitize GCTs to TRAIL or cisplatin.

  8. Regression of subcutaneous lymphoma following removal of an ovarian granulosatheca cell tumor in a horse.

    PubMed

    Henson, K L; Alleman, A R; Cutler, T J; Ginn, P E; Kelley, L C

    1998-05-01

    A 9-year-old Arabian mare was admitted for evaluation of multiple subcutaneous nodules and infertility. Fine-needle aspiration of one of the subcutaneous nodules resulted in a cytologic diagnosis of histiolymphocytic lymphoma. Palpation per rectum and transrectal ultrasonography revealed a mass associated with the left ovary. Excision of the ovarian tumor was performed, and a histopathologic diagnosis of granulosa-theca cell tumor was made. After removal of the granulosa-theca cell tumor, subcutaneous nodules regressed. The referring veterinarian reported that the nodules had also disappeared and then recurred after administration of a synthetic progestin. To further characterize the lymphoma and investigate this possible hormonal relationship, immunophenotyping and estrogen and progesterone receptor assays were performed. The subcutaneous lymphoma was classified as a T-cell rich B-cell lymphoma, results of estrogen receptor assays were negative, and results of progesterone receptor assays were positive. Clinical observations of subcutaneous lymphoma in horses indicate that the waxing and waning nature of these tumors may be associated with the estrous cycle, pregnancy, foaling, and lactation. Clinical observations and identification of progesterone receptors suggest that a relationship between serum steroid hormone concentrations, such as estrogen and progesterone, and subcutaneous lymphoma may exists.

  9. HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

    EPA Science Inventory

    Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.

    Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker

    Abstract
    The studies review...

  10. Expression of wilms' tumor gene and protein localization during ovarian formation and follicular development in sheep.

    PubMed

    Logan, Kathleen A; McNatty, Kenneth P; Juengel, Jennifer L

    2003-02-01

    Wilms' tumor protein (WT1) is a transcriptional repressor essential for the development of mammalian kidneys and gonads. To gain insight into possible roles of WT1 in ovarian formation and follicular function, we studied patterns of mRNA and protein localization throughout fetal gonadal development and in ovaries of 4-wk-old and adult sheep. At Day 24 after conception, strong expression of WT1 mRNA and protein was observed in the coelomic epithelial region of the mesonephros where the gonad was forming. By Day 30, expression was observed in the surface epithelium and in many mesenchymal and endothelial cells of the gonad. Epithelial cells continued to express WT1 throughout gonadal development, as did pregranulosa cells during the process of follicular formation. However, WT1 expression was not observed in germ cells. During follicular growth, granulosa cells expressed WT1 from the type 1 (primordial) to the type 4 stages, but thereafter expression was reduced in type 5 (antral) follicles, consistent with the differentiation of granulosa cells into steroid-producing cells. The possible progenitor cells for the theca interna (i.e., the cell streams in the ovarian interstitium) expressed WT1 heterogeneously. However, differentiated theca cells in antral follicles did not express WT1. Strong expression of WT1 was observed during gonadal development, which is consistent with a role for WT1 in ovarian and follicular formation in the ewe. WT1 was identified in many cells of the neonatal and adult ovaries, including granulosa cells, suggesting that this factor is important for preantral follicular growth. However, the decline in WT1 expression in antral follicles suggests that WT1 may prevent premature differentiation of somatic cells of the follicle during early follicular growth.

  11. Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-Analysis

    PubMed Central

    Yuan, Xiangliang; Xie, Guohua; Ma, Yanhui; Shen, Lisong

    2015-01-01

    Background The prognostic value of circulating tumor cells (CTCs) in ovarian cancer has been investigated in previous studies, but the results are controversial. Therefore we performed a meta-analysis to systematically review these data and evaluate the value of CTCs in ovarian cancer. Materials and Methods A literary search for relevant studies was performed on Embase, Medline and Web of Science databases. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, sensitivity analyses, meta-regression analyses and publication bias were conducted. Results This meta-analysis is based on 11 publications and comprises a total of 1129 patients. The prognostic value of the CTC status was significant in overall survival (OS) (HR, 1.61;95% CI,1.22–2.13) and progression-free survival (PFS)/disease-free survival (DFS) (HR, 1.44; 95%CI, 1.18–1.75). Furthermore, subgroup analysis revealed that the value of CTC status in OS was significant in "RT-PCR" subgroup (HR, 2.02; 95% CI, 1.34–3.03), whereas it was not significant in "CellSearch" subgroup (HR, 1.15; 95% CI 0.45–2.92) and "other ICC" subgroup (HR, 1.09; 95% CI 0.62–1.90). The presence of CTC was also associated with an increased CA-125 (OR, 4.07; 95%CI, 1.87–8.85). Conclusion Our study demonstrates that CTC status is associated with OS and PFS/DFS in ovarian cancer. PMID:26098665

  12. Differential distribution of tumor-associated macrophages and Treg/Th17 cells in the progression of malignant and benign epithelial ovarian tumors

    PubMed Central

    Zhu, Qinyi; Wu, Xiaoli; Wang, Xipeng

    2017-01-01

    Epithelial ovarian cancer (EOC) is one of the predominant causes of cancer-associated mortality in women with gynecological oncology. Tumor-associated macrophages (TAMs), regulatory T cells (Treg cells) and T helper cell 17 (Th17) cells have been hypothesized to be involved in the progression of EOC. However, the association between TAMs and T cells remains to be elucidated. The aim of the present study was to investigate the differential distribution of TAMs, Treg cells and Th17 cells in benign ovarian tumor tissues and in tissues from patients with EOC, and to examine their association with the clinical pathology of EOC. A total of 126 tissue samples from patients with EOC and 26 tissue samples from patients with benign ovarian tumors were analyzed, and it was identified that the distribution of TAMs, Treg cells, Th17 cells and the ratio of Treg/Th17 cells were higher in the patients with EOC using triple color immunofluorescence confocal microscopy. The high frequency of TAMs and ratio of Treg/Th17 cells in late tumor grades suggested that they may be significant in tumor progression. The frequency of TAMs was different between the histological types of EOC. Immunohistochemistry was used to investigate the microvessel density (MVD) in the EOC and benign ovarian tumor tissues. A higher MVD was observed in the EOC patient tissues, particularly, in the late tumor grade tissues. The present study provided clinical data demonstrating the high distribution of TAMs and T-cells in EOC, which may contribute to tumor progression through angiogenesis. The mechanisms by which TAMs are associated with Treg cells and Th17 cells requires further investigation as prognostic factors and therapeutic targets for EOC. PMID:28123537

  13. Tracking NF-κB activity in tumor cells during ovarian cancer progression in a syngeneic mouse model

    PubMed Central

    2013-01-01

    Background Nuclear factor-kappa B (NF-kappaB) signaling is an important link between inflammation and peritoneal carcinomatosis in human ovarian cancer. Our objective was to track NF-kappaB signaling during ovarian cancer progression in a syngeneic mouse model using tumor cells stably expressing an NF-kappaB reporter. Methods ID8 mouse ovarian cancer cells stably expressing an NF-kappaB-dependent GFP/luciferase (NGL) fusion reporter transgene (ID8-NGL) were generated, and injected intra-peritoneally into C57BL/6 mice. NGL reporter activity in tumors was non-invasively monitored by bioluminescence imaging and measured in luciferase assays in harvested tumors. Ascites fluid or peritoneal lavages were analyzed for inflammatory cell and macrophage content, and for mRNA expression of M1 and M2 macrophage markers by quantitative real-time RT-PCR. 2-tailed Mann-Whitney tests were used for measuring differences between groups in in vivo experiments. Results In ID8-NGL cells, responsiveness of the reporter to NF-kappaB activators and inhibitors was confirmed in vitro and in vivo. ID8-NGL tumors in C57BL/6 mice bore histopathological resemblance to human high-grade serous ovarian cancer and exhibited similar peritoneal disease spread. Tumor NF-kappaB activity, measured by the NGL reporter and by western blot of nuclear p65 expression, was markedly elevated at late stages of ovarian cancer progression. In ascites fluid, macrophages were the predominant inflammatory cell population. There were elevated levels of the M2-like pro-tumor macrophage marker, mannose-receptor, during tumor progression, and reduced levels following NF-kappaB inhibition with thymoquinone. Conclusions Our ID8-NGL reporter syngeneic model is suitable for investigating changes in tumor NF-kappaB activity during ovarian cancer progression, how NF-kappaB activity influences immune cells in the tumor microenvironment, and effects of NF-kappaB-targeted treatments in future studies. PMID:24020521

  14. Monoclonal antibodies to an epithelial ovarian adenocarcinoma: distinctive reactivity with xenografts of the original tumor and a cultured cell line.

    PubMed

    Baumal, R; Law, J; Buick, R N; Kahn, H; Yeger, H; Sheldon, K; Colgan, T; Marks, A

    1986-08-01

    Four monoclonal antibodies (mAb) (8C, 10B, M2A, and M2D) were produced against the human epithelial ovarian adenocarcinoma cell line, HEY. The affinity constants of binding of the mAb to cultured HEY cells were 8 X 10(8) M-1 (M2D) and 10(9) M-1 (8C and 10B). mAb 8C reacted with a major glycoprotein of Mr 90,000 on the surface of HEY cells. The four mAb differed from previously reported mAb to epithelial ovarian adenocarcinomas on the basis of their reactivity with cultured ovarian adenocarcinoma cell lines using a cell-binding radioimmunoassay, and their staining of cryostat sections of various human normal and tumor tissues using an immunoperoxidase reaction. All four mAb reacted with s.c. tumors derived by injecting cultured HEY cells into thymectomized CBA/CJ mice. However, only two of the four mAb (8C and 10B) also reacted with s.c. tumors of the original HEY xenograft from which the cultured cell line was derived. In addition, mAb 8C and 10B reacted by immunoperoxidase staining with 2 and 4 different cases, respectively, of 11 epithelial ovarian adenocarcinomas examined. Cultured HEY cells were adapted to grow i.p. in BALB/c-nu/nu mice and the i.p. tumors retained their reactivity with the monoclonal antibodies. These tumor-bearing mice offer a useful model system for studying the potential of mAb, especially 8C and 10B, for the diagnosis and treatment of patients with peritoneal extension of epithelial ovarian adenocarcinomas.

  15. Functional EpoR Pathway Utilization Is Not Detected in Primary Tumor Cells Isolated from Human Breast, Non-Small Cell Lung, Colorectal, and Ovarian Tumor Tissues

    PubMed Central

    Patterson, Scott D.; Rossi, John M.; Paweletz, Katherine L.; Fitzpatrick, V. Dan; Begley, C. Glenn; Busse, Leigh; Elliott, Steve; McCaffery, Ian

    2015-01-01

    Several clinical trials in oncology have reported increased mortality or disease progression associated with erythropoiesis-stimulating agents. One hypothesis proposes that erythropoiesis-stimulating agents directly stimulate tumor proliferation and/or survival through cell-surface receptors. To test this hypothesis and examine if human tumors utilize the erythropoietin receptor pathway, the response of tumor cells to human recombinant erythropoietin was investigated in disaggregated tumor cells obtained from 186 patients with colorectal, breast, lung, ovarian, head and neck, and other tumors. A cocktail of well characterized tumor growth factors (EGF, HGF, and IGF-1) were analyzed in parallel as a positive control to determine whether freshly-isolated tumor cells were able to respond to growth factor activation ex vivo. Exposing tumor cells to the growth factor cocktail resulted in stimulation of survival and proliferation pathways as measured by an increase in phosphorylation of the downstream signaling proteins AKT and ERK. In contrast, no activation by human recombinant erythropoietin was observed in isolated tumor cells. Though tumor samples exhibited a broad range of cell-surface expression of EGFR, c-Met, and IGF-1R, no cell-surface erythropoietin receptor was detected in tumor cells from the 186 tumors examined (by flow cytometry or Western blot). Erythropoiesis-stimulating agents did not act directly upon isolated tumor cells to stimulate pathways known to promote proliferation or survival of human tumor cells isolated from primary and metastatic tumor tissues. PMID:25807104

  16. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells

    PubMed Central

    Coffelt, Seth B.; Marini, Frank C.; Watson, Keri; Zwezdaryk, Kevin J.; Dembinski, Jennifer L.; LaMarca, Heather L.; Tomchuck, Suzanne L.; zu Bentrup, Kerstin Honer; Danka, Elizabeth S.; Henkle, Sarah L.; Scandurro, Aline B.

    2009-01-01

    Bone marrow-derived mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have been shown to engraft into the stroma of several tumor types, where they contribute to tumor progression and metastasis. However, the chemotactic signals mediating MSC migration to tumors remain poorly understood. Previous studies have shown that LL-37 (leucine, leucine-37), the C-terminal peptide of human cationic antimicrobial protein 18, stimulates the migration of various cell types and is overexpressed in ovarian, breast, and lung cancers. Although there is evidence to support a pro-tumorigenic role for LL-37, the function of the peptide in tumors remains unclear. Here, we demonstrate that neutralization of LL-37 in vivo significantly reduces the engraftment of MSCs into ovarian tumor xenografts, resulting in inhibition of tumor growth as well as disruption of the fibrovascular network. Migration and invasion experiments conducted in vitro indicated that the LL-37-mediated migration of MSCs to tumors likely occurs through formyl peptide receptor like-1. To assess the response of MSCs to the LL-37-rich tumor microenvironment, conditioned medium from LL-37-treated MSCs was assessed and found to contain increased levels of several cytokines and pro-angiogenic factors compared with controls, including IL-1 receptor antagonist, IL-6, IL-10, CCL5, VEGF, and matrix metalloproteinase-2. Similarly, Matrigel mixed with LL-37, MSCs, or the combination of the two resulted in a significant number of vascular channels in nude mice. These data indicate that LL-37 facilitates ovarian tumor progression through recruitment of progenitor cell populations to serve as pro-angiogenic factor-expressing tumor stromal cells. PMID:19234121

  17. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells.

    PubMed

    Coffelt, Seth B; Marini, Frank C; Watson, Keri; Zwezdaryk, Kevin J; Dembinski, Jennifer L; LaMarca, Heather L; Tomchuck, Suzanne L; Honer zu Bentrup, Kerstin; Danka, Elizabeth S; Henkle, Sarah L; Scandurro, Aline B

    2009-03-10

    Bone marrow-derived mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have been shown to engraft into the stroma of several tumor types, where they contribute to tumor progression and metastasis. However, the chemotactic signals mediating MSC migration to tumors remain poorly understood. Previous studies have shown that LL-37 (leucine, leucine-37), the C-terminal peptide of human cationic antimicrobial protein 18, stimulates the migration of various cell types and is overexpressed in ovarian, breast, and lung cancers. Although there is evidence to support a pro-tumorigenic role for LL-37, the function of the peptide in tumors remains unclear. Here, we demonstrate that neutralization of LL-37 in vivo significantly reduces the engraftment of MSCs into ovarian tumor xenografts, resulting in inhibition of tumor growth as well as disruption of the fibrovascular network. Migration and invasion experiments conducted in vitro indicated that the LL-37-mediated migration of MSCs to tumors likely occurs through formyl peptide receptor like-1. To assess the response of MSCs to the LL-37-rich tumor microenvironment, conditioned medium from LL-37-treated MSCs was assessed and found to contain increased levels of several cytokines and pro-angiogenic factors compared with controls, including IL-1 receptor antagonist, IL-6, IL-10, CCL5, VEGF, and matrix metalloproteinase-2. Similarly, Matrigel mixed with LL-37, MSCs, or the combination of the two resulted in a significant number of vascular channels in nude mice. These data indicate that LL-37 facilitates ovarian tumor progression through recruitment of progenitor cell populations to serve as pro-angiogenic factor-expressing tumor stromal cells.

  18. Primitive neuroectodermal tumor in an ovarian cystic teratoma: natural killer and neuroblastoma cell analysis.

    PubMed

    Tabellini, Giovanna; Benassi, Marzia; Marcenaro, Emanuela; Coltrini, Daniela; Patrizi, Ornella; Ricotta, Doris; Rampinelli, Fabio; Moretta, Alessandro; Parolini, Silvia

    2014-01-01

    In the present study, we report an extremely rare case of a 31-year-old woman with neuroblastoma arising in an ovarian cystic teratoma. We analyzed the expression of activating receptors on natural killer (NK) cells derived from the patient's peripheral blood and peritoneal fluid. In addition, we investigated the presence of specific ligands recognized by different NK cell receptors on tumor cells. We show that NK cells isolated from peritoneal fluid expressed certain triggering receptors including DNAM-1 (CD226) and CD16 with lower intensity as compared to peripheral blood NK cells. Remarkably, at variance with most cases of childhood neuroblastoma, the tumor cells from this patient expressed substantial amounts of HLA class-I molecules. These molecules are known to be protective against NK cell-mediated lysis. In addition, neuroblastoma cells expressed B7-H3 (CD276), another surface molecule that inhibits NK cell function. Finally, this tumor did not express the PVR (CD155) and nectin-2 (CD112) ligands for the DNAM-1 activating NK receptor, which plays a crucial role in NK/neuroblastoma interactions. Altogether, these findings indicate that the neuroblastoma cells of this patient express an NK-resistant surface phenotype, which is at least in part similar to that previously described in a fraction of childhood neuroblastoma.

  19. Differences in risk for type 1 and type 2 ovarian cancer in a large cancer screening trial

    PubMed Central

    2016-01-01

    Objective To investigate the role of previous gynecologic surgery, hormone use, and use of non-steroidal anti-inflammatory drugs on the risk of type 1 and type 2 ovarian cancer. Methods We utilized data collected for the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. All diagnosed ovarian cancers were divided into three groups: type 1, endometrioid, clear cell, mucinous, low grade serous, and low grade adenocarcinoma/not otherwise specified (NOS); type 2, high grade serous, undifferentiated, carcinosarcoma, and high grade adenocarcinoma/NOS; and other: adenocarcinoma with grade or histology not specified, borderline tumors, granulosa cell tumors. The odds ratios for type 1, type 2, and other ovarian cancers were assessed with regard to historical information for specific risk factors. Results Ibuprofen use was associated with a decrease in risk for type 1 ovarian cancer. Tubal ligation and oral contraceptive use were associated with a decrease in risk for type 2 ovarian cancer. A history of ectopic pregnancy was associated with a decreased risk for all ovarian cancers by almost 70%. Conclusion These findings support the hypothesis that carcinogenic pathways for type 1 and type 2 ovarian cancer are different and distinct. The marked reduction in all ovarian cancer risk noted with a history of ectopic pregnancy and salpingectomy implies that the fallopian tube plays a key role in carcinogenesis for both type 1 and type 2 ovarian cancer. PMID:27029746

  20. Tumor suppressor KAI1 affects integrin {alpha}v{beta}3-mediated ovarian cancer cell adhesion, motility, and proliferation

    SciTech Connect

    Ruseva, Zlatna; Geiger, Pamina Xenia Charlotte; Hutzler, Peter; Kotzsch, Matthias; Luber, Birgit; Schmitt, Manfred; Gross, Eva; Reuning, Ute

    2009-06-10

    The tetraspanin KAI1 had been described as a metastasis suppressor in many different cancer types, a function for which associations of KAI1 with adhesion and signaling receptors of the integrin superfamily likely play a role. In ovarian cancer, integrin {alpha}v{beta}3 correlates with tumor progression and its elevation in vitro provoked enhanced cell adhesion accompanied by significant increases in cell motility and proliferation in the presence of its major ligand vitronectin. In the present study, we characterized integrin {alpha}v{beta}3-mediated tumor biological effects as a function of cellular KAI1 restoration and proved for the first time that KAI1, besides its already known physical crosstalk with {beta}1-integrins, also colocalizes with integrin {alpha}v{beta}3. Functionally, elevated KAI1 levels drastically increased integrin {alpha}v{beta}3/vitronectin-dependent ovarian cancer cell adhesion. Since an intermediate level of cell adhesive strength is required for optimal cell migration, we next studied ovarian cancer cell motility as a function of KAI1 restoration. By time lapse video microscopy, we found impaired integrin {alpha}v{beta}3/vitronectin-mediated cell migration most probably due to strongly enhanced cellular immobilization onto the adhesion-supporting matrix. Moreover, KAI1 reexpression significantly diminished cell proliferation. These data strongly indicate that KAI1 may suppress ovarian cancer progression by inhibiting integrin {alpha}v{beta}3/vitronectin-provoked tumor cell motility and proliferation as important hallmarks of the oncogenic process.

  1. F14512, a polyamine-vectorized inhibitor of topoisomerase II, exhibits a marked anti-tumor activity in ovarian cancer.

    PubMed

    Thibault, Benoît; Clement, Emily; Zorza, Grégoire; Meignan, Samuel; Delord, Jean-Pierre; Couderc, Bettina; Bailly, Christian; Narducci, Fabrice; Vandenberghe, Isabelle; Kruczynski, Anna; Guilbaud, Nicolas; Ferré, Pierre; Annereau, Jean-Philippe

    2016-01-01

    Epithelial ovarian cancer is the fourth cause of death among cancer-bearing women and frequently associated with carboplatin resistance, underlining the need for more efficient and targeted therapies. F14512 is an epipodophylotoxin-core linked to a spermine chain which enters cells via the polyamine transport system (PTS). Here, we investigate this novel concept of vectorization in ovarian cancer. We compared the effects of etoposide and F14512 on a panel of five carboplatin-sensitive or resistant ovarian cancer models. We assessed the incorporation of F17073, a spermine-linked fluorescent probe, in these cells and in 18 clinical samples. We then showed that F14512 exhibits a high anti-proliferative and pro-apoptotic activity, particularly in cells with high levels of F17073 incorporation. Consistently, F14512 significantly inhibited tumor growth compared to etoposide, in a cisplatin-resistant A2780R subcutaneous model, at a dose of 1.25 mg/kg. In addition, ex vivo analysis indicated that 15 out of 18 patients presented a higher F17073 incorporation into tumor cells compared to normal cells. Overall, our data suggest that F14512, a targeted drug with a potent anti-tumor efficacy, constitutes a potential new therapy for highly PTS-positive and platinum-resistant ovarian cancer-bearing patients.

  2. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-10-26

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  3. Evaluation of a novel ELISA for the tumor-associated antigen CA 72–4 in patients with ovarian cancer

    PubMed Central

    Buderath, Paul; Kasimir-Bauer, Sabine; Aktas, Bahriye; Rasch, Jens; Kimmig, Rainer; Zeller, Thomas; Heubner, Martin

    2016-01-01

    Aim: Cancer antigen 72–4 (CA 72–4) is an established tumor marker in ovarian cancer. We evaluated a new solid-phase ELISA (DRG TM-CA 72–4 ELISA). Materials & methods: Repeated measures of test samples and controls were performed to evaluate reliability and reproducibility. Afterward, we performed analyses on the sera of 150 patients with primarily diagnosed ovarian cancer. Results were compared with those of the Cobas CA 72–4 kit. Results were correlated with clinical patient data. Results: Results of the DRG TM-CA 72–4 ELISA were reproducible with acceptable deviations within measures, and the measured CA 72–4 serum concentrations were well in accordance with the references. High concentrations were significantly associated with grading, tumor stage and tumor residuals after surgery. PMID:28116127

  4. A sandwiched biological fluorescent probe for the diagnosis of human ovarian tumor based on TiO2 nanoparticles.

    PubMed

    Zhu, Peisi; Huang, Shasheng; Li, Mengyao; Ding, Na; Peng, Bing; Kong, Lingmi; Bo, Yang

    2011-01-01

    In this paper, we report a novel biological fluorescent probe for the diagnosis of human ovarian tumor based on sandwiched TiO(2) nanoparticles. The fluorescence nanoparticles consist of a fluorescent molecule, tetramethyl rhodamine isothiocyanate (TRITC), sandwiched between titanium dioxide (TiO(2)) nanoparticles and nano-gold via reacting with each other. The antibodies HER2, labeled on the surface of the biofluorescence nanoparticles, have granted nanoparticles the privilege of aiming at peculiar tumor antigen. The specificity of antibody-nanoparticles interacting with cells was characterized by Laser Scanning Confocal Microscope. The results showed that these sandwiched nanoparticles were innocuous and stable, and the method offered potential advantages of sensitivity and simplicity due to high combing efficiency between nanoparticles and cells and provided an alternative method for the diagnosis of human ovarian tumor (HOT).

  5. A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs.

    PubMed

    Roomi, Mohd Waheed; Kalinovsky, Tatiana; Rath, Matthias; Niedzwiecki, Aleksandra

    2017-03-18

    Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a specific nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract, and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice (n = 12) were all inoculated intraperitoneally (IP) with 2 × 10⁶ cells in 0.1 mL of phosphate buffered saline (PBS) and randomly divided into two groups. Upon injection, the Control group (n = 6) was fed a regular diet and the EPQ group (n = 6) a regular diet supplemented with 0.5% EPQ. Four weeks later, the mice were sacrificed and tumors that developed in the ovary were excised, weighed, and processed for histology. Lungs were inspected for metastasis. In vitro, A-2780 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and antibiotics. At near confluence, cells were treated with EPQ in triplicate at concentrations between 0 and 1000 μg/mL. Cell proliferation was measured via MTT assay, MMP-9 secretion via gelatinase zymography, invasion through Matrigel and morphology via hematoxylin and eosin (H & E) staining. All Control mice developed large ovarian tumors, whereas 5 out of 6 mice in the EPQ group developed no tumors, and one, a small tumor. Control mice also showed lung metastasis in 6 out of 6 mice, while no lung metastasis was evident in EPQ mice. Zymography demonstrated only MMP-9 expression, which EPQ inhibited in a dose-dependent fashion, with virtual total block at 250 μg/mL concentration. EPQ significantly inhibited invasion through Matrigel with total block at 250 μg/mL concentration. MTT showed dose-dependent inhibition of cell proliferation

  6. A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs

    PubMed Central

    Roomi, Mohd Waheed; Kalinovsky, Tatiana; Rath, Matthias; Niedzwiecki, Aleksandra

    2017-01-01

    Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a specific nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract, and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice (n = 12) were all inoculated intraperitoneally (IP) with 2 × 106 cells in 0.1 mL of phosphate buffered saline (PBS) and randomly divided into two groups. Upon injection, the Control group (n = 6) was fed a regular diet and the EPQ group (n = 6) a regular diet supplemented with 0.5% EPQ. Four weeks later, the mice were sacrificed and tumors that developed in the ovary were excised, weighed, and processed for histology. Lungs were inspected for metastasis. In vitro, A-2780 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and antibiotics. At near confluence, cells were treated with EPQ in triplicate at concentrations between 0 and 1000 μg/mL. Cell proliferation was measured via MTT assay, MMP-9 secretion via gelatinase zymography, invasion through Matrigel and morphology via hematoxylin and eosin (H & E) staining. All Control mice developed large ovarian tumors, whereas 5 out of 6 mice in the EPQ group developed no tumors, and one, a small tumor. Control mice also showed lung metastasis in 6 out of 6 mice, while no lung metastasis was evident in EPQ mice. Zymography demonstrated only MMP-9 expression, which EPQ inhibited in a dose-dependent fashion, with virtual total block at 250 μg/mL concentration. EPQ significantly inhibited invasion through Matrigel with total block at 250 μg/mL concentration. MTT showed dose-dependent inhibition of cell proliferation

  7. Surgical technique for single-port laparoscopy in huge ovarian tumors: SW Kim's technique and comparison to laparotomy

    PubMed Central

    Kim, Jeong Sook; Lee, In Ok; Eoh, Kyung Jin; Chung, Young Shin; Lee, Inha; Lee, Jung-Yun; Nam, Eun Ji; Kim, Sunghoon; Kim, Young Tae

    2017-01-01

    Objective This study aimed to introduce a method to remove huge ovarian tumors (≥15 cm) intact with single-port laparoscopic surgery (SPLS) using SW Kim's technique and to compare the surgical outcomes with those of laparotomy. Methods Medical records were retrospectively reviewed for patients who underwent either SPLS (n=21) with SW Kim's technique using a specially designed 30×30-cm2-sized 3XL LapBag or laparotomy (n=22) for a huge ovarian tumor from December 2008 to May 2016. Perioperative surgical outcomes were compared. Results In 19/21 (90.5%) patients, SPLS was successfully performed without any tumor spillage or conversion to multi-port laparoscopy or laparotomy. There was no significant difference in patient characteristics, including tumor diameter and total operation time, between both groups. The postoperative hospital stay was significantly shorter for the SPLS group than for the laparotomy group (median, 2 [1 to 5] vs. 4 [3 to 17] days; P<0.001). The number of postoperative general diet build-up days was also significantly shorter for the SPLS group (median, 1 [1 to 4] vs. 3 [2 to 16] days; P<0.001). Immediate post-operative pain score was lower in the SPLS group (median, 2.0 [0 to 8] vs. 4.0 [0 to 8]; P=0.045). Patient-controlled anesthesia was used less in the SPLS group (61.9% vs. 100%). Conclusion SPLS was successful in removing most large ovarian tumors without rupture and showed quicker recovery and less immediate post-operative pain in comparison to laparotomy. SPLS using SW Kim's technique could be a feasible solution to removing huge ovarian tumors. PMID:28344959

  8. Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary

    ClinicalTrials.gov

    2017-02-03

    Malignant Ovarian Epithelial Tumor; Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

  9. Promoter hypermethylation of FBXO32, a novel TGF-beta/SMAD4 target gene and tumor suppressor, is associated with poor prognosis in human ovarian cancer.

    PubMed

    Chou, Jian-Liang; Su, Her-Young; Chen, Lin-Yu; Liao, Yu-Ping; Hartman-Frey, Corinna; Lai, Yi-Hui; Yang, Hui-Wen; Deatherage, Daniel E; Kuo, Chieh-Ti; Huang, Yi-Wen; Yan, Pearlly S; Hsiao, Shu-Huei; Tai, Chien-Kuo; Lin, Huey-Jen L; Davuluri, Ramana V; Chao, Tai-Kuang; Nephew, Kenneth P; Huang, Tim H-M; Lai, Hung-Cheng; Chan, Michael W-Y

    2010-03-01

    Resistance to TGF-beta is frequently observed in ovarian cancer, and disrupted TGF-beta/SMAD4 signaling results in the aberrant expression of downstream target genes in the disease. Our previous study showed that ADAM19, a SMAD4 target gene, is downregulated through epigenetic mechanisms in ovarian cancer with aberrant TGF-beta/SMAD4 signaling. In this study, we investigated the mechanism of downregulation of FBXO32, another SMAD4 target gene, and the clinical significance of the loss of FBXO32 expression in ovarian cancer. Expression of FBXO32 was observed in the normal ovarian surface epithelium, but not in ovarian cancer cell lines. FBXO32 methylation was observed in ovarian cancer cell lines displaying constitutive TGF-beta/SMAD4 signaling, and epigenetic drug treatment restored FBXO32 expression in ovarian cancer cell lines regardless of FBXO32 methylation status, suggesting that epigenetic regulation of this gene in ovarian cancer may be a common event. In advanced-stage ovarian tumors, a significant (29.3%; P<0.05) methylation frequency of FBXO32 was observed and the association between FBXO32 methylation and shorter progression-free survival was significant, as determined by both Kaplan-Meier analysis (P<0.05) and multivariate Cox regression analysis (hazard ratio: 1.003, P<0.05). Reexpression of FBXO32 markedly reduced proliferation of a platinum-resistant ovarian cancer cell line both in vitro and in vivo, due to increased apoptosis of the cells, and resensitized ovarian cancer cells to cisplatin. In conclusion, the novel tumor suppressor FBXO32 is epigenetically silenced in ovarian cancer cell lines with disrupted TGF-beta/SMAD4 signaling, and FBXO32 methylation status predicts survival in patients with ovarian cancer.

  10. Ovarian Sertoli-Leydig cell tumor with heterologous elements of gastrointestinal type associated with elevated serum alpha-fetoprotein level: an unusual case and literature review

    PubMed Central

    Horta, Mariana; Cunha, Teresa Margarida; Marques, Rita Canas; Félix, Ana

    2014-01-01

    Here we describe the case of a 19-year-old woman with a poorly differentiated ovarian Sertoli-Leydig cell tumor and an elevated serum alpha-fetoprotein level. The patient presented with diffuse abdominal pain and bloating. Physical examination, ultrasound, and magnetic resonance imaging revealed a right ovarian tumor that was histopathologically diagnosed as a poorly differentiated Sertoli-Leydig cell tumor with heterologous elements. Her alpha-fetoprotein serum level was undetectable after tumor resection. Sertoli-Leydig cell tumors are rare sex cord-stromal tumors that account for 0.5% of all ovarian neoplasms. Sertoli-Leydig cell tumors tend to be unilateral and occur in women under 30 years of age. Although they are the most common virilizing tumor of the ovary, about 60% are endocrine-inactive tumors. Elevated serum levels of alpha-fetoprotein are rarely associated with Sertoli-Leydig cell tumors, with only approximately 30 such cases previously reported in the literature. The differential diagnosis should include common alpha-fetoprotein-producing ovarian entities such as germ cell tumors, as well as other non-germ cell tumors that have been rarely reported to produce this tumor marker. PMID:25926909

  11. Intraepithelial T Cells and Tumor Proliferation: Impact on the Benefit from Surgical Cytoreduction in Advanced Serous Ovarian Cancer

    PubMed Central

    Adams, Sarah F.; Levine, Douglas A.; Cadungog, Mark G.; Hammond, Rachel; Facciabene, Andrea; Olvera, Narciso; Rubin, Stephen C.; Boyd, Jeff; Gimotty, Phyllis A.; Coukos, George

    2009-01-01

    Background We sought to determine whether tumor-infiltrating lymphocytes and/or tumor mitotic activity could identify subgroups of patients with advanced serous epithelial ovarian cancer who would maximally benefit from aggressive surgical cytoreduction. Methods Snap-frozen specimens from 134 consecutive patients with stage III or IV serous or poorly differentiated ovarian adenocarcinoma undergoing primary debulking surgery from a single US institution were characterized based on CD3+, CD8+, FoxP3+ tumor infiltrating lymphocytes, and Ki67 expression. Kaplan-Meier survival curves were estimated and compared using a log-rank statistic. A multivariate Cox model was used to estimate adjusted hazard ratios (HR). Interactions were modeled using recursive partitioning based on maximal prognostic differentiation. Results Brisk intraepithelial CD8+ cells (p=0.035) and low Ki67 expression (p=0.042) portended prolonged survival. T cell infiltration was more likely to occur in tumors with high proliferation index. Patients whose tumors exhibited low Ki67 expression and high intraepithelial CD8+ frequency had a 5-year survival rate of 73.3%. Patients with aggressive tumor behavior, i.e. whose tumors exhibited low frequency of intraepithelial CD8+ T cells or high Ki67 expression were more likely to draw benefit from aggressive surgical cytoreduction. Survival was similar for patients with brisk CD8+ T cells who had optimal or suboptimal debulking. Likewise, survival was similar for patients with low Ki67 expression who had optimal or suboptimal debulking. Conclusions These novel interactions of T cells, tumor proliferation index and surgical treatment reveal for the first time that biological prognosticators may be useful for surgical decision making in ovarian cancer. PMID:19472394

  12. CA125-related tumor cell kinetics variables after chemotherapy in advanced ovarian cancer: a systematic review.

    PubMed

    Colloca, G; Venturino, A; Governato, I

    2016-08-01

    Various kinetic parameters, based on a minimum of two time points, have been built with CA125 determinations. The aim of this study is to review studies about the clinical application of CA125-related tumor cell kinetics variables in patients with advanced ovarian cancer (AOC) receiving chemotherapy. A literature search for studies about CA125-related variables in patients with AOC was undertaken on three databases, by predefined search criteria, and a selection of studies was performed. Sixty-two studies were selected. CA125-related variables were summarized in three groups: response-related, time-to-event, and other CA125-related tumor cell kinetics variables. Even though CA125 changes and half-life after chemotherapy were the most studied, other variables and two models have been well defined, and often showed an interesting power to predict survival. These kinetics variables are related to the CA125 regression curve, pre- and post-chemotherapy kinetics, or are variables inferred from a population model of CA125 kinetics.

  13. Establishment of an orthotopic transplantation tumor model in nude mice using a drug-resistant human ovarian cancer cell line with a high expression of c-Kit.

    PubMed

    Yi, Cunjian; Zhang, Lei; Li, Li; Liu, Xiangqiong; Ling, Shengrong; Zhang, Fayun; Liang, Wei

    2014-12-01

    The resistance of ovarian cancer to platinum-based chemotherapy is a critical issue in the clinical setting. The present study aimed to establish animal models to replicate this clinical condition, as well as to investigate the resistance mechanisms of ovarian cancer. A cisplatin (DDP)-resistant human ovarian cancer cell line, SKOV3/DDP, was screened, validated and injected subcutaneously into the neck of female nude mice. Following tumor establishment, the tumor was collected and cut into small sections, which were subsequently implanted into the ovaries of other nude mice. The growth of the orthotopic tumors was observed and the tumor-bearing mice were sacrificed and dissected. The orthotopic and metastatic tumor tissues were collected, sectioned, stained with hematoxylin and eosin and analyzed. In the present study, 16 nude mice underwent orthotopic transplantation surgery and a tumor model was successfully established in 14/16 of the mice, with an in situ tumor formation rate of 87.5%. Following euthanasia, a laparotomy demonstrated the tumor formation at the site of transplantation, as well as varying degrees of metastasis to additional organs and tissues. Therefore, the present study successfully established an orthotopic tumor transplantation model in nude mice using a c-Kit-positive DDP-resistant human ovarian cancer cell line. This model may represent a useful tool for investigating the resistance mechanism of ovarian cancer, as well as evaluating the efficacy of therapeutic strategies.

  14. Ovarian tumor characterization and classification using ultrasound-a new online paradigm.

    PubMed

    Acharya, U Rajendra; Sree, S Vinitha; Saba, Luca; Molinari, Filippo; Guerriero, Stefano; Suri, Jasjit S

    2013-06-01

    Among gynecological malignancies, ovarian cancer is the most frequent cause of death. Image mining algorithms have been predominantly used to give the physicians a more objective, fast, and accurate second opinion on the initial diagnosis made from medical images. The objective of this work is to develop an adjunct computer-aided diagnostic technique that uses 3D ultrasound images of the ovary to accurately characterize and classify benign and malignant ovarian tumors. In this algorithm, we first extract features based on the textural changes and higher-order spectra information. The significant features are then selected and used to train and evaluate the decision tree (DT) classifier. The proposed technique was validated using 1,000 benign and 1,000 malignant images, obtained from ten patients with benign and ten with malignant disease, respectively. On evaluating the classifier with tenfold stratified cross validation, the DT classifier presented a high accuracy of 97 %, sensitivity of 94.3 %, and specificity of 99.7 %. This high accuracy was achieved because of the use of the novel combination of the four features which adequately quantify the subtle changes and the nonlinearities in the pixel intensity variations. The rules output by the DT classifier are comprehensible to the end-user and, hence, allow the physicians to more confidently accept the results. The preliminary results show that the features are discriminative enough to yield good accuracy. Moreover, the proposed technique is completely automated, accurate, and can be easily written as a software application for use in any computer.

  15. Unexpected ovarian malignancy found after laparoscopic surgery in patients with adnexal masses--a single institutional experience.

    PubMed

    Saito, Shigeko; Kajiyama, Hiroaki; Miwa, Yoko; Mizuno, Mika; Kikkawa, Fumitaka; Tanaka, Shiho; Okamoto, Tomomitsu

    2014-02-01

    Laparoscopy has become the standard surgery for the treatment of benign ovarian tumors. The aim of this study was to evaluate the appropriateness of laparoscopy for ovarian tumors, including those with malignant potential. A total of 487 patients with adnexal masses underwent laparoscopic surgery in Social Insurance Chukyo Hospital from January 2000 to December 2012. We reviewed 471 cases that fulfilled the criteria set for this study, and examined 10 cases with unexpected ovarian malignancy to analyze their preoperative diagnosis, second surgery, postoperative chemotherapy, and prognosis. The ages of the 471 patients ranged from 13 to 50 years, with a median of 31. Nulliparous patients numbered 321(68.1%). Of all, 436 patients mostly consisted of those with endometrioma, benign ovarian neoplasm or functional cyst. In all, we histologically identified 10 women with malignancy: 6 with borderline ovarian tumors (BOT), 2 with ovarian cancer, and 2 with histologically rare tumors (immature teratoma and granulosa cell tumor). All patients with BOT were diagnosed with a mucinous histology. Two patients underwent both second radical surgery (hysterectomy and contra- or bilateral salpingo-oophorectomy) and chemotherapies that consisted of CBDCA and PTX or DTX. Thus, 2 patients underwent staging procedures, but the remaining 8 cases did not. None of them had evidence of recurrences. With accurate staging and careful postoperative follow-up, laparoscopic surgery could be a feasible initial operation for patients with adnexal masses including early-stage ovarian malignancy.

  16. Feto-maternal outcomes of pregnancy complicated by ovarian malignant germ cell tumor: a systematic review of literature.

    PubMed

    Kodama, Michiko; Grubbs, Brendan H; Blake, Erin A; Cahoon, Sigita S; Murakami, Ryusuke; Kimura, Tadashi; Matsuo, Koji

    2014-10-01

    Malignant germ cell tumors (MGCT) are a rare type of ovarian cancer with poorly understood behavior during pregnancy. This systematic review evaluated feto-maternal outcomes and management patterns of 102 ovarian MGCT-complicated pregnancies identified in PubMed/MEDLINE. Mean age was 25.8. The most common histology type was dysgerminoma (38.2%) followed by yolk sac tumor (30.4%). Abdomino-pelvic pain (35.3%) was the most common symptom. The majority were stage I disease (76.4%) with a mean tumor size of 17.9cm. Most cases had live births (77.5%) at term (56.6%). Tumor surgery without fetal conservation took place in 22 (21.6%) cases (Group 1). This group was characterized by the first trimester tumor detection and intervention, non-viable pregnancy, and frequent concurrent hysterectomy. There were 59 (57.8%) cases which underwent expectant management of pregnancy: mean delay 16.4 weeks for 46 (45.1%) cases with tumor surgery and fetal conservation (Group 2); and 7.8 weeks for 13 (12.7%) cases with tumor surgery after delivery (Group 3). The live birth rate in Groups 2 and 3 was 98.3%. There were 21 (20.6%) cases in which the tumor was incidentally found intra/postpartum (Group 4). Group 2 showed the highest 5-year overall survival rate (92.8%) followed by Group 4 (79.5%), Group 3 (71.4%), and Group 1 (56.2%, p=0.028). Group 1 had more advanced-stage disease when compared to Group 2 (proportion of stages II-IV disease, 36.4% versus 11.4%, p=0.023). In multivariate analysis, age ≤20 (p=0.032) and stages II-IV (p=0.02) remained independent prognosticators for decreased overall survival in all cases. Expectant management of pregnancy was not associated with poor survival outcome in multivariate analysis (p=0.43). In conclusion, our analysis demonstrated that timing of tumor intervention and delivery significantly impacted feto-maternal outcome of ovarian MGCT-complicated pregnancies. It is suggested that early detection and tumor intervention with expectant

  17. Conundrums in the management of malignant ovarian germ cell tumors: Toward lessening acute morbidity and late effects of treatment.

    PubMed

    Gershenson, David M; Frazier, A Lindsay

    2016-11-01

    One of the most extraordinary stories in the chronicles of gynecologic cancers has been that of malignant ovarian germ cell tumors. Prior to the mid-1960s, most patients died of disease. Fifty years later, most survive. Precisely because high cure rates are achievable, the concentration over the past decade has been on minimizing toxicity and late effects. The present review focuses on five areas of interest related to the management of malignant ovarian germ cell tumors that highlight the different therapeutic strategies practiced by pediatric and gynecologic oncologists: 1) primary surgery, 2) surgery alone (surveillance) for patients with FIGO stage IA disease, 3) postoperative management of FIGO stage IC-III disease, 4) postoperative management of pure immature teratoma, and 5) postoperative management of metastatic pure dysgerminoma. All of these topics share a common overarching theme: Lessening acute morbidity and late effects of treatment.

  18. Trisomy 14pter --> q21: a case with associated ovarian germ cell tumor and review of the literature.

    PubMed

    Lee-Jones, Lisa; Williams, Tom; Little, Elizabeth; Sampson, Julian

    2004-07-01

    We report a patient with trisomy X and a supernumerary marker chromosome. The marker chromosome was characterized by comparative genomic hybridization and shown to be derived from chromosome 14, resulting in trisomy for 14pter --> q21. The karyotype was thus redefined as 48,XXX,+mar.rev ish enh(14pterq21). The patient presented with facial dysmorphism and a high-pitched cry, exhibited severe developmental delay, and developed an aggressive ovarian immature teratoma. In this paper, we also review reports of 11 other patients with constitutional trisomy of the same chromosomal region. Previous studies have identified somatic gains of chromosome 14 in ovarian germ cell tumors. We propose that the constitutional gain of chromosomal 14 material may have predisposed to the development of this tumor.

  19. Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis

    PubMed Central

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E.; Alagaratnam, Sharmini; Skotheim, Rolf I.; Abeler, Vera M.

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. PMID:23575763

  20. Sam68 is Overexpressed in Epithelial Ovarian Cancer and Promotes Tumor Cell Proliferation

    PubMed Central

    Dong, Lijuan; Che, Hailuo; Li, Mingmei; Li, Xuepeng

    2016-01-01

    Background Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy, and evidence is accumulating on how molecular markers may be associated with the origin and process of EOC. Sam68 (Src-associated in mitosis, of 68 kD), is a K homology domain RNA-binding protein that has been investigated as a risk factor in multiple types of tumors. The aim of the present study was to investigate the contribution of the Sam68 gene in the pathogenesis of EOC. Material/Methods Western blot assay and real-time quantitative PCR methods were performed to examine Sam68 expression in EOC tissue specimens. The association of Sam68 expression with clinic-pathologic variables of EOC was evaluated. Then gain-of-function and loss-of-function strategies were adopted to examine the regulation of Sam68 on the proliferation of EOC OVCAR-3 cells using CCK-8 and colony forming assays. Results Sam68 was overexpressed in both mRNA and protein levels in EOC tumor tissue (n=152) in an association with malignant factors of EOC such as International Federation of Gynecology and Obstetrics (FIGO) stage, residual tumor size (cm), histological grade, and lymph node metastasis. In vitro results demonstrated that Sam68 overexpression was upregulated while Sam68 knockdown downregulated the proliferation of EOC OVCAR-3 cells via regulation of cell growth and colony formation. Conclusions Sam68 was overexpressed in EOC tissue in association with such cancer malignant factors of FIGO stage, histological grade, and lymph node metastasis, and also positively regulated the proliferation of EOC cells. Our research suggests that Sam68 might accelerate cell cycle progression, and present as a prognostic marker for EOC. PMID:27623016

  1. New insights in the pathophysiology of ovarian cancer and implications for screening and prevention.

    PubMed

    Nezhat, Farr R; Apostol, Radu; Nezhat, Camran; Pejovic, Tanja

    2015-09-01

    Despite advances in medicine, ovarian cancer remains the deadliest of the gynecological malignancies. Herein we present the latest information on the pathophysiology of ovarian cancer and its significance for ovarian cancer screening and prevention. A new paradigm for ovarian cancer pathogenesis presupposes 2 distinct types of ovarian epithelial carcinoma with distinct molecular profiles: type I and type II carcinomas. Type I tumors include endometrioid, clear-cell carcinoma, and low-grade serous carcinoma and mostly arise via defined sequence either from endometriosis or from borderline serous tumors, mostly presenting in an early stage. More frequent type II carcinomas are usually high-grade serous tumors, and recent evidence suggests that the majority arise from the fimbriated end of the fallopian tube. Subsequently, high-grade serous carcinomas usually present at advanced stages, likely as a consequence of the rapid peritoneal seeding from the open ends of the fallopian tubes. On the other hand, careful clinical evaluation should be performed along with risk stratification and targeted treatment of women with premalignant conditions leading to type I cancers, most notably endometriosis and endometriomas. Although the chance of malignant transformation is low, an understanding of this link offers a possibility of prevention and early intervention. This new evidence explains difficulties in ovarian cancer screening and helps in forming new recommendations for ovarian cancer risk evaluation and prophylactic treatments.

  2. Multiple direct and indirect mechanisms drive estrogen-induced tumor growth in high grade serous ovarian cancers.

    PubMed

    Ciucci, Alessandra; Zannoni, Gian Franco; Buttarelli, Marianna; Lisi, Lucia; Travaglia, Daniele; Martinelli, Enrica; Scambia, Giovanni; Gallo, Daniela

    2016-02-16

    The notion that menopausal estrogen replacement therapy increases ovarian cancer risk, but only for the two more common types (i.e. serous and endometrioid), while possibly decreasing risk for clear cell tumors, is strongly suggestive of causality. However, whether estradiol (E2) is tumorigenic or promotes development of occult preexisting disease is unknown. The present study investigated molecular and cellular mechanisms by which E2 modulates the growth of high grade serous ovarian cancer (HGSOC). Results showed that ERα expression was necessary and sufficient to induce the growth of HGSOC cells in in vitro models. Conversely, in vivo experimental studies demonstrated that increasing the levels of circulating estrogens resulted in a significant growth acceleration of ERα-negative HGSOC xenografts, as well. Tumors from E2-treated mice had significantly higher proliferation rate, angiogenesis, and density of tumor-associated macrophage (TAM) compared to ovariectomized females. Accordingly, immunohistochemical analysis of ERα-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women. This study describes novel insights into the impact of E2 on tumor microenvironment, independently of its direct effect on tumor cell growth, thus supporting the idea that multiple direct and indirect mechanisms drive estrogen-induced tumor growth in HGSOC.

  3. Analysis of the Mitogen-activated protein kinase kinase 4 (MAP2K4) tumor suppressor gene in ovarian cancer

    PubMed Central

    2011-01-01

    Background MAP2K4 is a putative tumor and metastasis suppressor gene frequently found to be deleted in various cancer types. We aimed to conduct a comprehensive analysis of this gene to assess its involvement in ovarian cancer. Methods We screened for mutations in MAP2K4 using High Resolution Melt analysis of 149 primary ovarian tumors and methylation at the promoter using Methylation-Specific Single-Stranded Conformation Polymorphism analysis of 39 tumors. We also considered the clinical impact of changes in MAP2K4 using publicly available expression and copy number array data. Finally, we used siRNA to measure the effect of reducing MAP2K4 expression in cell lines. Results In addition to 4 previously detected homozygous deletions, we identified a homozygous 16 bp truncating deletion and a heterozygous 4 bp deletion, each in one ovarian tumor. No promoter methylation was detected. The frequency of MAP2K4 homozygous inactivation was 5.6% overall, and 9.8% in high-grade serous cases. Hemizygous deletion of MAP2K4 was observed in 38% of samples. There were significant correlations of copy number and expression in three microarray data sets. There was a significant correlation between MAP2K4 expression and overall survival in one expression array data set, but this was not confirmed in an independent set. Treatment of JAM and HOSE6.3 cell lines with MAP2K4 siRNA showed some reduction in proliferation. Conclusions MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort. PMID:21575258

  4. Belinostat and Carboplatin in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Carboplatin or Cisplatin

    ClinicalTrials.gov

    2014-06-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer

  5. Inverse expression of cystein-rich 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2) in borderline tumors and carcinomas of the ovary.

    PubMed

    Bartel, Frank; Balschun, Katharina; Gradhand, Elise; Strauss, Hans G; Dittmer, Jürgen; Hauptmann, Steffen

    2012-09-01

    Members of the CCN [cystein-rich 61 (Cyr61)/connective tissue growth factor (CTGF)/nephroblastoma (NOV)] protein family are involved in the regulation of cellular proliferation, apoptosis, and migration and are also assumed to play a role in carcinogenesis. Therefore, we performed a retrospective study to investigate the immunohistochemical expression of both Cyr61 and CTGF in 92 borderline tumors (BOTs) and 107 invasive carcinomas of the ovary (IOCs). To determine their diagnostic and prognostic value, we correlated protein expression with clinicopathologic factors including overall and disease-free survival. Cyr61 and CTGF were found to be inversely expressed in both BOTs and IOCs, with a stronger expression of Cyr61 in IOCs. Moreover, Cyr61 was found to be preferentially expressed in high-grade serous carcinomas, whereas CTGF was found more frequently in low-grade serous carcinomas. Weak Cyr61 levels correlated with both low estrogen receptor and p53 expression (P=0.038, P=0.04, respectively). However, no association was observed between CTGF, estrogen receptor, and p53 expression levels in IOCs. Regarding prognosis, Cyr61 was found to be of no value, but the loss of CTGF was found to be associated with a poor prognosis in multivariate analysis of overall (relative risk 2.8; P=0.050) and disease-free (relative risk 2.3; P=0.031) survival. Cyr61 and CTGF are inversely expressed in BOTs and IOCs, and loss of CTGF independently indicates poor prognosis in IOCs.

  6. CD24 and Nanog identify stem cells signature of ovarian epithelium and cysts that may develop to ovarian cancer.

    PubMed

    Schreiber, Letizia; Raanan, Calanit; Amsterdam, Abraham

    2014-03-01

    Ovarian cancer is the most lethal gynecological cancer. There is a general debate whether ovarian cancer is an intrinsic or an imported disease. We investigated whether in normal morphological appearance and in early stages of ovarian tumorgenesis typical cancer cell markers such as CD24 and Nanog are expressed. In 25% of normal appearing ovaries of post-menopausal women there was co-localization of CD24 and Nanog in the walls of the ovarian cysts, leaving the epithelial cells on the surface of these ovaries free of Nanog or CD24 expression. In benign ovarian tumors 37% of specimens were positive to CD24 and Nanog labeling while 26% of them were localized in the cyst walls. In contrast, in serous borderline tumors 79% specimens were labeled with CD24, 42% of them were localized in cysts and in 32% of them showed co-localization with CD24 and Nanog was evident: the rest were labeled in the ovarian epithelial cells. In serous ovarian carcinomas 81% specimens were labeled with CD24 antibodies. In 45% of them co-localization with Nanog was evident in the bulk of the cancerous tissue. In mucinous carcinomas no labeling with CD24 or Nanog was evident. In view of the synergistic effect of CD24 and Nanog expressed in malignant cancer development in other systems, it is suggested that such an analysis can be valuable for early detection of ovarian cancer. Moreover, the abundance of these markers in cysts in the development of ovarian cancer may suggest that they present an intrinsic source of the development of the highly malignant disease. Finally, since CD24 is exposed on the surface of the cancer cells, it may be highly beneficial to target these cells with antibodies to CD24 conjugated to cytotoxic drugs for more efficient treatment of this malignant disease.

  7. Metformin Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2017-01-24

    Ovarian Papillary Serous Carcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer

  8. Desmocollin 3 mediates follicle stimulating hormone-induced ovarian epithelial cancer cell proliferation by activating the EGFR/Akt signaling pathway.

    PubMed

    Yang, Xiao; Wang, Jing; Li, Wen-Ping; Jin, Zhi-Jun; Liu, Xiao-Jun

    2015-01-01

    Follicle-stimulating hormone (FSH) is associated with the pathogenesis of ovarian cancer. We sought to explore whether desmocollin 3 (Dsc3) mediates FSH-induced ovarian epithelial cancer cell proliferation and whether the EGFR/Akt signaling pathway may be involved in this process. Dsc3 positivity in ovarian tissue specimens from 72 patients was assessed by immunohistochemistry. The positive expression rates of Dsc3 were similar in ovarian cancer tissues (24/31:77.4%) and borderline ovarian tumor tissues (18/22:81.8%) (P>0.05), but were significantly higher in these cancerous tissues than in benign ovarian cyst tissues (3/19:15.8%) (P<0.05). Consistently, the expression of Dsc3 in four out of five ovarian cancer cells (HO8910, Skov3ip, Skov and Hey cells, but not ES-2 and in borderline ovarian MCV152 tumor cells was higher than in the immortalized ovarian epithelial cell line, Moody. FSH up-regulated the expression of Dsc3 and EGFR in a dose- and time-dependent manner. Furthermore, a converse relationship between the expression of Dsc3, EFGR and PI3K/Akt signaling was elucidated using RNA interference and PI3K/Akt inhibitor in the absence and presence of FSH. A role for these proteins in FSH-induced cell proliferation was verified, highlighting their interdependence in mediating ovarian cancer cell function. These results suggest that Dsc3 can mediate FSH-induced ovarian cancer cell proliferation by activating the EGFR/Akt signaling pathway.

  9. Nerve growth factor modulates the tumor cells migration in ovarian cancer through the WNT/β-catenin pathway

    PubMed Central

    Li, Bo; Cai, Shaoxi; Zhao, Yi; He, Qiyi; Yu, Xiaodong; Cheng, Longcong; Zhang, Yingfeng; Hu, Xiancheng; Ke, Ming; Chen, Sijia; Zou, Misha

    2016-01-01

    Nerve growth factor (NGF)/nerve growth factor receptors (NGFRs) axis and canonical WNT/β-catenin pathway have shown to play crucial roles in tumor initiation, progression and prognosis. But little did we know the relationship between them in modulation of tumor progress. In this report, we found that NGF/NGFRs and β-catenin were coexpression in ovarian cancer cell lines, and NGF can decrease the expression level of β-catenin and affect its activities, which may be related to the NGF-induced down-regulation of B-cell CLL/lymphoma 9-like (BCL9L, BCL9-2). Furthermore, NGF can also increase or decrease the downstream target gene expression levels of WNT/β-catenin depending on the cell types. Especially, we created a novel in vitro cell growth model based on a microfluidic device to intuitively observe the effects of NGF/NGFRs on the motility behaviors of ovarian cancer cells. The results showed that the migration area and maximum distance into three dimensional (3D) matrigel were decreased in CAOV3 and OVCAR3 cells, but increased in SKOV3 cells following the stimulation with NGF. In addition, we found that the cell colony area was down-regulated in CAOV3 cells, however, it was augmented in OVCAR3 cells after treatment with NGF. The inhibitors of NGF/NGFRs, such as Ro 08-2750, K252a and LM11A-31,can all block NGF-stimulated changes of gene expression or migratory behavior on ovarian cancer cells. The different results among ovarian cancer cells illustrated the heterogeneity and complexity of ovarian cancer. Collectively, our results suggested for the first time that NGF is functionally linked to β-catenin in the migration of human ovarian cancer cells, which may be a novel therapeutic perspective to prevent the spread of ovarian carcinomas by studying the interaction between NGF/NGFRs and canonical WNT/β-catenin signaling. PMID:27835587

  10. NSAIDs induce apoptosis in nonproliferating ovarian cancer cells and inhibit tumor growth in vivo.

    PubMed

    Duncan, Kristal; Uwimpuhwe, Henriette; Czibere, Akos; Sarkar, Devanand; Libermann, Towia A; Fisher, Paul B; Zerbini, Luiz F

    2012-07-01

    Ovarian cancer (OC) is one of the most lethal gynaecological cancers, which usually has a poor prognosis due to late diagnosis. A large percentage of the OC cell population is in a nonproliferating and quiescent stage, which poses a barrier to success when using most chemotherapeutic agents. Recent studies have shown that several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of OC. Furthermore, we have previously described the molecular mechanisms of NSAIDs' induction of cancer apoptosis. In this report, we evaluated various structurally distinct NSAIDs for their efficacies in inducing apoptosis in nonproliferating OC cells. Although several NSAIDs-induced apoptosis, Flufenamic Acid, Flurbiprofen, Finasteride, Celocoxib, and Ibuprofen were the most potent NSAIDs inducing apoptosis. A combination of these agents resulted in an enhanced effect. Furthermore, we demonstrate that the combination of Flurbiprofen, which targets nonproliferative cells, and Sulindac Sulfide, that affects proliferative cells, strongly reduced tumor growth when compared with a single agent treatment. Our data strongly support the hypothesis that drug treatment regimens that target nonproliferating and proliferating cells may have significant efficacy against OC. These results also provide a rationale for employing compounds or even chemically modified NSAIDs, which selectively and efficiently induce apoptosis in cells during different stages of the cell cycle, to design more potent anticancer drugs.

  11. Targeting FXYD2 by cardiac glycosides potently blocks tumor growth in ovarian clear cell carcinoma

    PubMed Central

    Hsu, I-Ling; Chou, Cheng-Yang; Wu, Yi-Ying; Wu, Jia-En; Liang, Chen-Hsien; Tsai, Yao-Tsung; Ke, Jhen-Yu; Chen, Yuh-Ling; Hsu, Keng-Fu; Hong, Tse-Ming

    2016-01-01

    Ovarian clear cell carcinoma (OCCC) is an aggressive neoplasm with a high recurrence rate that frequently develops resistance to platinum-based chemotherapy. There are few prognostic biomarkers or targeted therapies exist for patients with OCCC. Here, we identified that FXYD2, the modulating subunit of Na+/K+-ATPases, was highly and specifically expressed in clinical OCCC tissues. The expression levels of FXYD2 were significantly higher in advanced-stage of OCCC and positively correlated with patients' prognoses. Silencing of FXYD2 expression in OCCC cells inhibited Na+/K+-ATPase enzyme activity and suppressed tumor growth via induction of autophagy-mediated cell death. We found that high FXYD2 expression in OCCC was transcriptionally regulated by the transcriptional factor HNF1B. Furthermore, up-regulation of FXYD2 expression significantly increased the sensitivity of OCCC cells to cardiac glycosides, the Na+/K+-ATPase inhibitors. Two cardiac glycosides, digoxin and digitoxin, had a great therapeutic efficacy in OCCC cells in vitro and in vivo. Taken together, our results demonstrate that FXYD2 is functionally upregulated in OCCC and may serve as a promising prognostic biomarker and therapeutic target of cardiac glycosides in OCCC. PMID:26910837

  12. Drosophila OVO regulates ovarian tumor transcription by binding unusually near the transcription start site.

    PubMed

    Lü, J; Oliver, B

    2001-05-01

    Evolutionarily conserved ovo loci encode developmentally regulated, sequence-specific, DNA-binding, C(2)H(2)-zinc-finger proteins required in the germline and epidermal cells of flies and mice. The direct targets of OVO activity are not known. Genetic experiments suggest that ovo acts in the same regulatory network as ovarian tumor (otu), but the relative position of these genes in the pathway is controversial. Three OVO-binding sites exist in a compact regulatory region that controls germline expression of the otu gene. Interestingly, the strongest OVO-binding site is very near the otu transcription start, where basal transcriptional complexes must function. Loss-of-function, gain-of-function and promoter swapping constructs demonstrate that OVO binding near the transcription start site is required for OVO-dependent otu transcription in vivo. These data unambiguously identify otu as a direct OVO target gene and raise the tantalizing possibility that an OVO site, at the location normally occupied by basal components, functions as part of a specialized core promoter.

  13. Prognostic analysis of invasive circulating tumor cells (iCTCs) in epithelial ovarian cancer

    PubMed Central

    Pearl, Michael L.; Zhao, Qiang; Yang, Jie; Dong, Huan; Tulley, Shaun; Zhang, Qiao1; Golightly, Marc; Zucker, Stanley; Chen, Wen-Tien

    2014-01-01

    Goals: Circulating tumor cells (CTCs) have been introduced as a biomarker in detecting advanced Epithelial Ovarian Cancer (EOC). The goals are to examine the prevalence of the invasive subpopulation of CTCs (iCTCs) in patients at high risk of EOC and to compare this biomarker to serum CA125. Methods: We used a unique Cell Adhesion Matrix (CAM)-based, functional cell enrichment and identification platform to isolate iCTCs from 129 preoperative patients. We confirmed the identity of iCTCs using positive epithelial (Epi+) markers and negative hematopoietic lineage (HL-) markers. Sensitivity and specificity of the assays were examined and iCTCs / CA125 were correlated with overall survival (OS), progression-free survival (PFS) and clinical parameters. Results: We found a 41.2% sensitivity, 95.1% specificity and 77.8% positive predictive value (PPV) of the iCTC assay in detecting patients with stage I and II EOC malignancy, and a 83% sensitivity and 97.3% PPV in detecting all stages of EOC malignancy. However, a positive CA125 test provided weak evidence to detect stage I and II malignancy (61.6% PPV) and all EOC (92.1% PPV), because of its 76.2% specificity. A significantly stronger concordance in OS and PFS of clinical factors (tumor stage, debulking and platinum sensitivity) was noted for elevated iCTCs than for serum CA125. Conclusion: The CAM-initiated CTC enrichment / identification method enabled the detection of early stage EOC. iCTCs were better correlated with worse OS and PFS, more specific and better PPV than CA125 in detecting EOC malignancy in patients at high risk of EOC. PMID:24972191

  14. PD-1 Blockade and OX40 Triggering Synergistically Protects against Tumor Growth in a Murine Model of Ovarian Cancer

    PubMed Central

    Guo, Zhiqiang; Wang, Xin; Cheng, Dali; Xia, Zhijun; Luan, Meng; Zhang, Shulan

    2014-01-01

    The co-inhibitory receptor Programmed Death-1 (PD-1) curtails immune responses and prevent autoimmunity, however, tumors exploit this pathway to escape from immune destruction. The co-stimulatory receptor OX40 is upregulated on T cells following activation and increases their clonal expansion, survival and cytokine production when engaged. Although antagonistic anti-PD-1 or agonistic anti-OX40 antibodies can promote the rejection of several murine tumors, some poorly immunogenic tumors were refractory to this treatment. In the present study, we evaluated the antitumor effects and mechanisms of combinatorial PD-1 blockade and OX40 triggering in a murine ID8 ovarian cancer model. Although individual anti-PD-1 or OX40 mAb treatment was ineffective in tumor protection against 10-day established ID8 tumor, combined anti-PD-1/OX40 mAb treatment markedly inhibited tumor outgrowth with 60% of mice tumor free 90 days after tumor inoculation. Tumor protection was associated with a systemic immune response with memory and antigen specificity and required CD4+ cells and CD8+ T cells. The anti-PD-1/OX40 mAb treatment increased CD4+ and CD8+ cells and decreased immunosuppressive CD4+FoxP3+ regulatory T (Treg) cells and CD11b+Gr-1+ myeloid suppressor cells (MDSC), giving rise to significantly higher ratios of both effector CD4+ and CD8+ cells to Treg and MDSC in peritoneal cavity; Quantitative RT-PCR data further demonstrated the induction of a local immunostimulatory milieu by anti-PD-1/OX40 mAb treatment. The splenic CD8+ T cells from combined mAb treated mice produced high levels of IFN-γ upon tumor antigen stimulation and exhibited antigen-specific cytolytic activity. To our knowledge, this is the first study testing the antitumor effects of combined anti-PD-1/OX40 mAb in a murine ovarian cancer model, and our results provide a rationale for clinical trials evaluating ovarian cancer immunotherapy using this combination of mAb. PMID:24586709

  15. PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer.

    PubMed

    Guo, Zhiqiang; Wang, Xin; Cheng, Dali; Xia, Zhijun; Luan, Meng; Zhang, Shulan

    2014-01-01

    The co-inhibitory receptor Programmed Death-1 (PD-1) curtails immune responses and prevent autoimmunity, however, tumors exploit this pathway to escape from immune destruction. The co-stimulatory receptor OX40 is upregulated on T cells following activation and increases their clonal expansion, survival and cytokine production when engaged. Although antagonistic anti-PD-1 or agonistic anti-OX40 antibodies can promote the rejection of several murine tumors, some poorly immunogenic tumors were refractory to this treatment. In the present study, we evaluated the antitumor effects and mechanisms of combinatorial PD-1 blockade and OX40 triggering in a murine ID8 ovarian cancer model. Although individual anti-PD-1 or OX40 mAb treatment was ineffective in tumor protection against 10-day established ID8 tumor, combined anti-PD-1/OX40 mAb treatment markedly inhibited tumor outgrowth with 60% of mice tumor free 90 days after tumor inoculation. Tumor protection was associated with a systemic immune response with memory and antigen specificity and required CD4(+) cells and CD8(+) T cells. The anti-PD-1/OX40 mAb treatment increased CD4(+) and CD8(+) cells and decreased immunosuppressive CD4(+)FoxP3(+) regulatory T (Treg) cells and CD11b(+)Gr-1(+) myeloid suppressor cells (MDSC), giving rise to significantly higher ratios of both effector CD4(+) and CD8(+) cells to Treg and MDSC in peritoneal cavity; Quantitative RT-PCR data further demonstrated the induction of a local immunostimulatory milieu by anti-PD-1/OX40 mAb treatment. The splenic CD8(+) T cells from combined mAb treated mice produced high levels of IFN-γ upon tumor antigen stimulation and exhibited antigen-specific cytolytic activity. To our knowledge, this is the first study testing the antitumor effects of combined anti-PD-1/OX40 mAb in a murine ovarian cancer model, and our results provide a rationale for clinical trials evaluating ovarian cancer immunotherapy using this combination of mAb.

  16. Ovarian cancer stem-like cells differentiate into endothelial cells and participate in tumor angiogenesis through autocrine CCL5 signaling.

    PubMed

    Tang, Shu; Xiang, Tong; Huang, Shuo; Zhou, Jie; Wang, Zhongyu; Xie, Rongkai; Long, Haixia; Zhu, Bo

    2016-06-28

    Cancer stem cells (CSCs) are well known for their self-regeneration and tumorigenesis potential. In addition, the multi-differentiation potential of CSCs has become a popular issue and continues to attract increased research attention. Recent studies demonstrated that CSCs are able to differentiate into functional endothelial cells and participate in tumor angiogenesis. In this study, we found that ovarian cancer stem-like cells (CSLCs) activate the NF-κB and STAT3 signal pathways through autocrine CCL5 signaling and mediate their own differentiation into endothelial cells (ECs). Our data demonstrate that CSLCs differentiate into ECs morphologically and functionally. Anti-CCL5 antibodies and CCL5-shRNA lead to markedly inhibit EC differentiation and the tube formation of CSLCs, both in vitro and in vivo. Recombinant human-CCL5 significantly promotes ovarian CSLCs that differentiate into ECs and form microtube network. The CCL5-mediated EC differentiation of CSLCs depends on binding to receptors, such as CCR1, CCR3, and CCR5. The results demonstrated that CCL5-CCR1/CCR3/CCR5 activates the NF-κB and STAT3 signal pathways, subsequently mediating the differentiation of CSLCs into ECs. Therefore, this study was conducted based on the theory that CSCs improve tumor angiogenesis and provides a novel strategy for anti-angiogenesis in ovarian cancer.

  17. Elevated TAK1 augments tumor growth and metastatic capacities of ovarian cancer cells through activation of NF-κB signaling

    PubMed Central

    Cai, Patty C.H.; Shi, Lei; Liu, Vincent W.S.; Tang, Hermit W.M.; Liu, Iris J.; Leung, Thomas H.Y.; Chan, Karen K.L.; Yam, Judy W.P.; Yao, Kwok-Ming; Ngan, Hextan Y.S.; Chan, David W.

    2014-01-01

    Transforming growth factor (TGF)-β-activating kinase 1 (TAK1) is a serine/threonine kinase which is frequently associated with human cancer progression. However, its functional role in tumorigenesis is still controversial. Here, we report that TAK1 enhances the oncogenic capacity of ovarian cancer cells through the activation of NF-κB signaling. We found that TAK1 is frequently upregulated and significantly associated with high-grade and metastatic ovarian cancers. Mechanistic studies showed that Ser412 phosphorylation is required for TAK1 in activating NF-κB signaling and promotes aggressiveness of ovarian cancer cells. Conversely, suppression of TAK1 activity by point mutation at Ser412, RNAi mediated gene knockdown or TAK1 specific inhibitor ((5Z) -7-Oxozeaenol) remarkably impairs tumor growth and metastasis in ovarian cancer in vitro and in vivo. Our study underscores the importance of targeting TAK1 as a promising therapeutic approach to counteract the ovarian cancer progression. PMID:25277189

  18. Cushing's syndrome secondary to ectopic ACTH secretion from carcinoid tumor within an ovarian mature teratoma: a case report and review of the literature.

    PubMed

    Huang, Baoyou; Wu, Xueqing; Zhou, Qing; Hu, Yan; Zhao, Hongqin; Zhu, Hua; Zhang, Qian; Zheng, Feiyun

    2014-03-01

    A 46-year-old woman with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion caused by primary ovarian mature teratoma with carcinoid components was presented in our case. The patient manifested sustained hypercortisolemia without circadian rhythm and a lack of suppression of either low-dose dexamethasone suppression test (LDDST) or high-dose dexamethasone suppression test (HDDST). There was no evidence of a pituitary mass or secretion of other hormones. After careful clinical evaluation, no other tumor masses were found. Resection of the ovarian tumors led to sharp reduction of serum ACTH and cortisol concentrations. Immunohistochemistry showed positivity in CgA, Syn, CK, NSE. To the best of our knowledge, there are rare reports of an ACTH-secreting carcinoid components located in an ovarian mature teratoma, and bilateral ovarian mature teratoma makes it rarer.

  19. Gene for ovarian granulosa cell tumor susceptibility, Gct, in SWXJ recombinant inbred strains of mice revealed by dehydroepiandrosterone.

    PubMed

    Beamer, W G; Tennent, B J; Shultz, K L; Nadeau, J H; Shultz, L D; Skow, L C

    1988-09-15

    Spontaneous, malignant ovarian granulosa cell (GC) tumors occur in pubertal SWR and specific SWXJ recombinant inbred strains of mice. Treatment of these mice with dehydroepiandrosterone (DHEA), an adrenal secretory steroid with anticancer actions against spontaneous and carcinogen-induced tumors of different tissues, gave unexpected results. Diet supplemented with 0.4% DHEA (a) induced significantly more GC tumors in spontaneous tumor-susceptible strains (SWR and SWXJ-1, -4, and -9), (b) induced the first GC tumors observed in five previously tumor-free strains (SWXJ-6, -7, -8, -10, and -12), and (c) failed to induce GC tumors in SJL and in the remaining six SWXJ strains (SWXJ-2, -3, -5, -11, -13, and -14). The strain distribution pattern of DHEA-induced GC tumor susceptibility versus resistance was compared with strain distribution patterns for 35 different loci known to distinguish SWR and SJL progenitor strains. A complete match of DHEA-induced GC tumors with pancreas-2 (Pan-2) on mouse chromosome 4 was found. We have named this new locus GC tumor susceptibility (Gct), with the Gcts (susceptible) allele found in SWR and the Gctr (resistant) allele found in SJL mice. The Gct locus is closely linked to pancreas-2, Pan-2, but the order of genes is not yet confirmed. In addition, data from F1 progeny of matings between SWR and selected inbred strains provide suggestive evidence for a second gene controlling GC tumor incidence that we hypothesize involves steroid metabolism. Differences in GC tumor incidence data from reciprocal F1 progeny of matings between SWR and SJL mice reveal a strong maternal effect that may represent yet a third gene. These data support a heritable basis for GC tumorigenesis in the SWR model involving a small number of genes.

  20. MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer

    ClinicalTrials.gov

    2016-06-24

    Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Serous Tumor; Ovarian Seromucinous Carcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  1. [The value of urine cystein proteinase and serum CA125 measurement in monitoring the treatment of malignant ovarian tumor].

    PubMed

    Gao, G; Peng, Z; He, B

    1996-09-01

    Urine cystein proteinase (UCP) and serum CA125 were measured in 40 patients with malignant ovarian tumor (malignant group), 40 patients with benign ovarian tumor (benign group), and 40 normal control (normal group). 28 patients in the malignant group underwent UCP and CA125 measurement pre-operation, post-operation, and during three courses of chemotherapy. The enzyme activity of UCP in the malignant group was significantly higher than that in the benign and normal groups (P < 0.05 or 0.01). The values of UCP in patients with malignant tumor of stages II-IV were significantly higher compared with those of stages I-II (P < 0.01, 0.05). The activity of UCP was elevated pre-operation, post-operation, and was much higher on the seventh day postoperation. After the seventh day, UCP activity decreased gradually. Serum CA125 was also detected pre-operation, at 7.30 and 60 days post-operation. The levels of UCP and CA125 pre-operation and 30, 60 days post-operation in the patients whose residual carcinoma lesions were > 2 cm in diameter were apparantly higher than those with no residual lesions (P < 0.05). UCP and CA125 values were measured in six patients before relaparotomy. The sensitivity, specificity, accuaracy, positive predictive value and negative predictive value for UCP assay are 980%, 100%, 83%, 100% and 50% and those for CA125 assay are 40%, 100%, 80%, 100%, and 25%, respectively.

  2. Metformin limits the adipocyte tumor-promoting effect on ovarian cancer.

    PubMed

    Tebbe, Calvin; Chhina, Jasdeep; Dar, Sajad A; Sarigiannis, Kalli; Giri, Shailendra; Munkarah, Adnan R; Rattan, Ramandeep

    2014-07-15

    Omental adipocytes promote ovarian cancer by secretion of adipokines, cytokines and growth factors, and acting as fuel depots. We investigated if metformin modulates the ovarian cancer promoting effects of adipocytes. Effect of conditioned media obtained from differentiated mouse 3T3L1 preadipoctes on the proliferation and migration of a mouse ovarian surface epithelium cancer cell line (ID8) was estimated. Conditioned media from differentiated adipocytes increased the proliferation and migration of ID8 cells, which was attenuated by metformin. Metformin inhibited adipogenesis by inhibition of key adipogenesis regulating transcription factors (CEBPα, CEBPß, and SREBP1), and induced AMPK. A targeted Cancer Pathway Finder RT-PCR (real-time polymerase chain reaction) based gene array revealed 20 up-regulated and 2 down-regulated genes in ID8 cells exposed to adipocyte conditioned media, which were altered by metformin. Adipocyte conditioned media also induced bio-energetic changes in the ID8 cells by pushing them into a highly metabolically active state; these effects were reversed by metformin. Collectively, metformin treatment inhibited the adipocyte mediated ovarian cancer cell proliferation, migration, expression of cancer associated genes and bio-energetic changes. Suggesting, that metformin could be a therapeutic option for ovarian cancer at an early stage, as it not only targets ovarian cancer, but also modulates the environmental milieu.

  3. Focused screening of mitochondrial metabolism reveals a crucial role for a tumor suppressor Hbp1 in ovarian reserve

    PubMed Central

    Dong, Z; Huang, M; Liu, Z; Xie, P; Dong, Y; Wu, X; Qu, Z; Shen, B; Huang, X; Zhang, T; Li, J; Liu, J; Yanase, T; Zhou, C; Xu, Y

    2016-01-01

    Granulosa cells (GCs) are tightly associated with fertility and the fate of ovarian follicles. Mitochondria are the central executers of apoptosis. However, the genetic basis underlying mitochondrial modulation in GCs during the ovarian development is poorly understood. Here, CRISPR/Cas9-mediated genetic screening was used to identify genes conferring mitochondrial metabolism in human GCs. The results uncovered roles for several tumor suppressors, including HBP1, in the augmentation of mitochondrial function. Focused analysis revealed that high-mobility group (HMG)-box transcription factor 1 (Hbp1) levels regulate mitochondrial biogenesis, which is associated with global changes in transcription including Tfam. The systemic or granulosa-specific but not oocyte-specific ablation of Hbp1 promoted follicle growth and oocyte production, and is associated with the reduced apoptotic signals in mouse GCs. Consistent with increased mitochondrial function and attenuated GC apoptosis, the regulation of Hbp1 conferred substantial protection of ovarian reserve. Thus, the results of the present study provide a critical target to understand the control of the reproductive lifespan. PMID:27206316

  4. PAX2, PAX8 and CDX2 Expression in Metastatic Mucinous, Primary Ovarian Mucinous and Seromucinous Tumors and Review of the Literature.

    PubMed

    Ates Ozdemir, D; Usubutun, A

    2016-07-01

    Ovarian cancer is the most common cause of gynecologic cancer death. Both morphologically and immunohistochemically, metastatic mucinous tumors are the best mimickers of mucinous ovarian tumors; its pathogenesis still remains a mystery. PAX2 and PAX8 immunohisyochemistries are useful for differentiating numerous primary tumour types from metastatic ones. There are few studies in literature about PAX expressions in mucinous and seromucinous tumors. None of these are takes into account the histologic type (whether it is seromucinous or mucinous) or the metastatic origin. With this purpose hematoxylin and eosine slides of ovarian mucinous and seromucinous tumors were re-evaluated and one block was chosen for each case. The study included 76 ovarian mucinous and seromucinous tumors of the ovary reported in Hacettepe University department of pathology between 2000 and 2013. Tissue microarray (TMA) was designed from the chosen blocks, PAX2, PAX8, CDX2 immunostains was preformed to the TMA slides. As a result, most of the metastatic cases were negative for PAX2 (91.2 %) and PAX8 (86.3 %), many were diffusely and strongly positive for CDX2 (68.2 %). Seromucinous tumors were devoid of CDX2 expression; but all cases (except one) displayed strong and diffuse positivity with PAX8. In other words differing from mucinous tumors, seromucinous tumors show strong PAX8 positivity-similar to serous tumors. This study shows that PAX8 and CDX2 could be useful in differentiating primary mucinous from metastatic tumor. Furthermore unlike the homogeneity in seromucinous tumors for PAX8 and CDX2 mucinous tumors shows heterogeneity with different expression patterns.

  5. What Are the Key Statistics about Ovarian Cancer?

    MedlinePlus

    ... Cancer About Ovarian Cancer What Are the Key Statistics About Ovarian Cancer? The American Cancer Society estimates ... ovarian cancer is about 1 in 100. (These statistics don’t count low malignant potential ovarian tumors.) ...

  6. A novel clinicopathological analysis of early stage ovarian Sertoli-Leydig cell tumors at a single institution

    PubMed Central

    Nam, Seon Mi; Kim, Jee Whan; Eoh, Kyung Jin; Kim, Hye Min; Lee, Jung Yun; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun

    2017-01-01

    Objective To evaluate the clinical and pathologic characteristics of patients who were diagnosed with ovarian Sertoli-Leydig cell tumors (SLCTs) in a single institution. Methods The medical records of 11 patients who were pathologically diagnosed with SLCTs beginning in 1995 in a single institute was reviewed. Results The median patient age was 31 years (range, 16 to 70 years). Patient International Federation of Gynecology and Obstetrics stages were IA, IC, and IIB in 3 (27.3%), 6 (54.5%), and 2 (18.2%) patients, respectively. Six patients (54.5%) had grade 3 tumors, 3 patients (27.3%) had grade 2 tumors, and 1 patient (9.1%) had a grade 1 tumor. Four patients without children underwent fertility-sparing surgery, and 7 patients had full staging surgery, including a hysterectomy and bilateral salpingo-oophorectomy, with a laparoscopic approach used in 3. Eight patients underwent pelvic lymph node dissection, and 8 patients were administered adjuvant chemotherapy consisting of bleomycin, etoposide, and cisplatin in 6 cases, a modified bleomycin, etoposide, and cisplatin regimen in 1 case, and a combined paclitaxel and cisplatin regimen in 1 case. Two patients died of disease and were re-diagnosed with Sertoli form endometrioid carcinoma. The other patients remain alive without recurrence at the time of reporting. Conclusion Our findings suggest that regardless of tumor stage or grade, ovarian SLCT patients have a good prognosis. Close observation and unilateral salpingo-oophorectomy would be beneficial for women who still wish to have children, while hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy would be the optimal treatment in other cases. Furthermore, meticulous pathologic diagnosis is needed to develop a precise treatment strategy. PMID:28217670

  7. Absence of PD-L1 on tumor cells is associated with reduced MHC I expression and PD-L1 expression increases in recurrent serous ovarian cancer

    PubMed Central

    Aust, Stefanie; Felix, Sophie; Auer, Katharina; Bachmayr-Heyda, Anna; Kenner, Lukas; Dekan, Sabine; Meier, Samuel M.; Gerner, Christopher; Grimm, Christoph; Pils, Dietmar

    2017-01-01

    Immune-evasion and immune checkpoints are promising new therapeutic targets for several cancer entities. In ovarian cancer, the clinical role of programmed cell death receptor ligand 1 (PD-L1) expression as mechanism to escape immune recognition has not been clarified yet. We analyzed PD-L1 expression of primary ovarian and peritoneal tumor tissues together with several other parameters (whole transcriptomes of isolated tumor cells, local and systemic immune cells, systemic cytokines and metabolites) and compared PD-L1 expression between primary tumor and tumor recurrences. All expressed major histocompatibility complex (MHC) I genes were negatively correlated to PD-L1 abundances on tumor tissues, indicating two mutually exclusive immune-evasion mechanisms in ovarian cancer: either down-regulation of T-cell mediated immunity by PD-L1 expression or silencing of self-antigen presentation by down-regulation of the MHC I complex. In our cohort and in most of published evidences in ovarian cancer, low PD-L1 expression is associated with unfavorable outcome. Differences in immune cell populations, cytokines, and metabolites strengthen this picture and suggest the existence of concurrent pathways for progression of this disease. Furthermore, recurrences showed significantly increased PD-L1 expression compared to the primary tumors, supporting trials of checkpoint inhibition in the recurrent setting. PMID:28266500

  8. Local morphologic scale: application to segmenting tumor infiltrating lymphocytes in ovarian cancer TMAs

    NASA Astrophysics Data System (ADS)

    Janowczyk, Andrew; Chandran, Sharat; Feldman, Michael; Madabhushi, Anant

    2011-03-01

    classes based on local structural properties. In this paper, we apply LMS to the specific problem of classifying regions of interest in Ovarian Cancer (OCa) histology images as either tumor or stroma. This approach is used to classify lymphocytes as either tumor infiltrating lymphocytes (TILs) or non-TILs; the presence of TILs having been identified as an important prognostic indicator for disease outcome in patients with OCa. We present preliminary results on the tumor/stroma classification of 11,000 randomly selected locations of interest, across 11 images obtained from 6 patient studies. Using a Probabilistic Boosting Tree (PBT), our supervised classifier yielded an area under the receiver operation characteristic curve (AUC) of 0.8341 +/-0.0059 over 5 runs of randomized cross validation. The average LMS computation time at every spatial location for an image patch comprising 2000 pixels with 24 particles at every location was only 18s.

  9. HtrA3 Is Downregulated in Cancer Cell Lines and Significantly Reduced in Primary Serous and Granulosa Cell Ovarian Tumors.

    PubMed

    Singh, Harmeet; Li, Ying; Fuller, Peter J; Harrison, Craig; Rao, Jyothsna; Stephens, Andrew N; Nie, Guiying

    2013-01-01

    Objective. The high temperature requirement factor A3 (HtrA3) is a serine protease homologous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of cancers, suggesting a widespread loss of these proteases in cancer. This study examined how extensively the HtrA (HtrA1-3) proteins are downregulated in commonly used cancer cell lines and primary ovarian tumors.Methods. RT-PCR was applied to various cancer cell lines (n=17) derived from the ovary, endometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian tumors [granulosa cell tumors (n=19), mucinous cystadenocarcinomas (n=6), serous cystadenocarcinomas (n=8)] and normal ovary (n = 9). HtrA3 protein was localized by immunohistochemistry.Results. HtrA3 was extensively downregulated in the cancer cell lines examined including the granulosa cell tumor-derived cell lines. In primary ovarian tumors, the HtrA3 was significantly lower in serous cystadenocarcinoma and granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and tumors. In normal postmenopausal ovary, HtrA3 protein was localized to lutenizing stromal cells and corpus albicans. In serous cystadenocarcinoma, HtrA3 protein was absent in the papillae but detected in the mesenchymal cyst wall.Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian serous cystadenocarcinoma and granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian malignancy.

  10. Cisplatin and Paclitaxel in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-29

    Chemotherapeutic Agent Toxicity; Endometrial Adenocarcinoma; Fallopian Tube Carcinoma; Gastrointestinal Complication; Malignant Ovarian Mixed Epithelial Tumor; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage II Ovarian Cancer; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  11. Human C1q Induces Apoptosis in an Ovarian Cancer Cell Line via Tumor Necrosis Factor Pathway

    PubMed Central

    Kaur, Anuvinder; Sultan, Sami H. A.; Murugaiah, Valarmathy; Pathan, Ansar A.; Alhamlan, Fatimah S.; Karteris, Emmanouil; Kishore, Uday

    2016-01-01

    Complement protein C1q is the first recognition subcomponent of the complement classical pathway that plays a vital role in the clearance of immune complexes, pathogens, and apoptotic cells. C1q also has a homeostatic role involving immune and non-immune cells; these functions not necessarily involve complement activation. Recently, C1q has been shown to be expressed locally in the microenvironment of a range of human malignant tumors, where it can promote cancer cell adhesion, migration, and proliferation, without involving complement activation. C1q has been shown to be present in the ascitic fluid formed during ovarian cancers. In this study, we have examined the effects of human C1q and its globular domain on an ovarian cancer cell line, SKOV3. We show that C1q and the recombinant globular head modules induce apoptosis in SKOV3 cells in a time-dependent manner. C1q expression was not detectable in the SKOV3 cells. Exogenous treatment with C1q and globular head modules at the concentration of 10 µg/ml induced apoptosis in approximately 55% cells, as revealed by immunofluorescence microscopy and FACS. The qPCR and caspase analysis suggested that C1q and globular head modules activated tumor necrosis factor (TNF)-α and upregulated Fas. The genes of mammalian target of rapamycin (mTOR), RICTOR, and RAPTOR survival pathways, which are often overexpressed in majority of the cancers, were significantly downregulated within few hours of the treatment of SKOV3 cells with C1q and globular head modules. In conclusion, C1q, via its globular domain, induced apoptosis in an ovarian cancer cell line SKOV3 via TNF-α induced apoptosis pathway involving upregulation of Bax and Fas. This study highlights a potentially protective role of C1q in certain cancers. PMID:28066412

  12. A novel splicing mutation in the SLC9A3R1 gene in tumors from ovarian cancer patients.

    PubMed

    Kreimann, Erica Lorena; Ratajska, Magdalena; Kuzniacka, Alina; Demacopulo, Brenda; Stukan, Maciej; Limon, Janusz

    2015-12-01

    The aim of the present study was to investigate novel molecular markers that could improve the diagnosis of ovarian cancer patients or be of predictive value. The sequence of the sodium-hydrogen antiporter 3 regulator 1 (SLC9A3R1) gene that codes for the PDZ2 motif of the Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) protein was analyzed. Changes in migration and cell transformation, and alterations of growth factor signaling pathways have been described in cells lacking endogenous NHERF1 or expressing an isoform lacking the function of the PDZ2 domain. Exons 2 and 3, together with flanking intronic sequences of the SLC9A3R1 gene, were amplified and bi-directionally sequenced in 31 primary tumor samples from epithelial ovarian cancer patients. In total, 3 different previously undescribed mutations were detected in 8 out of 31 serous adenocarcinoma tumor samples (25.8%). Bioinformatics analysis predicted a significant effect in the splicing process as a result of the mutations that could disrupt the NHERF1 PDZ2 domain. Point mutations in consensus splicing recognition are a major cause of the splicing defects that are found in several diseases, including cancer. It has previously been shown that a lack of exon 2 and disruption of the PDZ2 domain contribute to cell transformation and leads to modifications in the physiological regulation of the conformational state of NHERF1. Further studies in bigger groups of ovarian cancer patients will determine the importance of this mutation in disease progression and patient survival.

  13. Assessment of Ovarian Cancer Tumors Treated with Intraperitoneal Cisplatin Therapy by Nanoscopic X-ray Fluorescence Imaging

    PubMed Central

    Laforce, Brecht; Carlier, Charlotte; Vekemans, Bart; Villanova, Julie; Tucoulou, Rémi; Ceelen, Wim; Vincze, Laszlo

    2016-01-01

    Ovarian cancer is amongst the most common types of cancer in women, with a relatively low overall cure rate of approximately 30%. This is therefore an important incentive to urge for further research in order to maximize the chances of survival for these patients. Intraperitoneal chemotherapy with Cisplatin is an effective treatement for ovarian cancer; however, many questions still remain concerning the ideal treatment protocol and tumor resistance towards the drug, which should be resolved for optimal application of this therapy. For the first time in-vivo grown tumors treated with both hyper- and normothermic intraperitoneal chemotherapy have been studied using nano-XRF spectroscopy to examine the platinum (Pt) distribution within the analyzed tissues. These measurements prove Pt resides predominantly outsides the cancer cells in the stroma of the tissue. These findings indicate the resistance mechanism of the cancer cells prevents Cisplatin from diffusing through their cell membranes. This is an important addition to the existing knowledge on the resistance mechanism providing insights which might help to overcome this effect. In our aim to find the optimal treatment protocol, no significant differences were found between the two examined procedures. A more extensive data set will be needed to draw definite conclusions. PMID:27444797

  14. Assessment of Ovarian Cancer Tumors Treated with Intraperitoneal Cisplatin Therapy by Nanoscopic X-ray Fluorescence Imaging

    NASA Astrophysics Data System (ADS)

    Laforce, Brecht; Carlier, Charlotte; Vekemans, Bart; Villanova, Julie; Tucoulou, Rémi; Ceelen, Wim; Vincze, Laszlo

    2016-07-01

    Ovarian cancer is amongst the most common types of cancer in women, with a relatively low overall cure rate of approximately 30%. This is therefore an important incentive to urge for further research in order to maximize the chances of survival for these patients. Intraperitoneal chemotherapy with Cisplatin is an effective treatement for ovarian cancer; however, many questions still remain concerning the ideal treatment protocol and tumor resistance towards the drug, which should be resolved for optimal application of this therapy. For the first time in-vivo grown tumors treated with both hyper- and normothermic intraperitoneal chemotherapy have been studied using nano-XRF spectroscopy to examine the platinum (Pt) distribution within the analyzed tissues. These measurements prove Pt resides predominantly outsides the cancer cells in the stroma of the tissue. These findings indicate the resistance mechanism of the cancer cells prevents Cisplatin from diffusing through their cell membranes. This is an important addition to the existing knowledge on the resistance mechanism providing insights which might help to overcome this effect. In our aim to find the optimal treatment protocol, no significant differences were found between the two examined procedures. A more extensive data set will be needed to draw definite conclusions.

  15. Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin.

    PubMed

    Zhao, Sufen; Ye, Gang; Fu, Guodong; Cheng, Jian-Xin; Yang, Burton B; Peng, Chun

    2011-05-01

    Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported. In this study, we determined whether Ganoderma lucidum regulates EOC cell activity. Using several cell lines derived from EOC, we found that Ganoderma lucidum strongly decreased cell numbers in a dose-dependent manner. Ganoderma lucidum also inhibited colony formation, cell migration and spheroid formation. In particular, Ganoderma lucidum was effective in inhibiting cell growth in both chemosensitive and chemoresistant cells and the treatment with Ganoderma lucidum significantly enhanced the effect of cisplatin on EOC cells. Furthermore, Ganoderma lucidum induced cell cycle arrest at the G2/M phase and also induced apoptosis by activating caspase 3. Finally, Ganoderma lucidum increased p53 but inhibited Akt expression. Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin.

  16. Microsatellite instability is rare in sporadic ovarian cancer

    SciTech Connect

    Chen, S.S.; Han, H.; Schwartz, P.E.

    1994-09-01

    Microsatellite instability was first demonstrated to be a common underlying mechanism in hereditary nonpolyposis colorectal cancer (HNPCC) and has recently been implicated in the development of several other human cancers. Although numerous genetic changes have been documented in ovarian cancer, their molecular bases are poorly understood. In investigating the molecular genetics of ovarian cancer, we analyzed twelve short tandem repeats that were amplified by PCR from DNA of 48 tumors and their corresponding lymphocyte samples. All of the 48 cases studied have no noticeable family history and, of them, 42 are epithelial (benign/borderline, 5; grade I, 4; GII, 4; GIII, 29) and 6 are nonepithelial. A microsatellite instability has been shown to be inversely correlated with the occurrence of allelic losses, half of those cases chosen have a fractional allele loss of {le}15 (median = .18 of 50 tumors tested for 86 loci from every chromosomal arm). The loci examined included eight dinucleotide repeats (D2S123, D9S104, D10S197, D11S904, D16S408, D16S421, D17S250, and D17S579), two trinucleotide repeats (DM and AR) and two tetranucleotide repeats (DXS981 and VWF). Despite the fact that HNPCC phenotype includes ovarian cancer and that microsatellite instability has been shown in one ovarian cancer from an HNPCC family, the allele sizes of 12 loci were found to be identical in all paired tumor and normal samples we studied except for one tumor at a single locus. The band shift displayed on polyacrylamide gel representing an additional allele of VWF was only observed in one grade III tumor. Our results are thus a strong indication that the alteration of microsatellite repeats may not play a major role in the development of sporadic ovarian cancer.

  17. Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy.

    PubMed

    Lo, Charlotte S; Sanii, Sanaz; Kroeger, David R; Milne, Katy; Talhouk, Aline; Chiu, Derek S; Rahimi, Kurosh; Shaw, Patricia A; Clarke, Blaise A; Nelson, Brad H

    2017-02-15

    Purpose: Some forms of chemotherapy can enhance antitumor immunity through immunogenic cell death, resulting in increased T-cell activation and tumor infiltration. Such effects could potentially sensitize tumors to immunotherapies, including checkpoint blockade. We investigated whether platinum- and taxane-based chemotherapy for ovarian cancer induces immunologic changes consistent with this possibility.Experimental Design: Matched pre- and post-neoadjuvant chemotherapy tumor samples from 26 high-grade serous carcinoma (HGSC) patients were analyzed by immunohistochemistry (IHC) for a large panel of immune cells and associated factors. The prognostic significance of post-chemotherapy TIL patterns was assessed in an expanded cohort (n = 90).Results: Neoadjuvant chemotherapy was associated with increased densities of CD3(+), CD8(+), CD8(+) TIA-1(+), PD-1(+) and CD20(+) TIL. Other immune subsets and factors were unchanged, including CD79a(+) CD138(+) plasma cells, CD68(+) macrophages, and MHC class I on tumor cells. Immunosuppressive cell types were also unchanged, including FoxP3(+) PD-1(+) cells (putative regulatory T cells), IDO-1(+) cells, and PD-L1(+) cells (both macrophages and tumor cells). Hierarchical clustering revealed three response patterns: (i) TIL(high) tumors showed increases in multiple immune markers after chemotherapy; (ii) TIL(low) tumors underwent similar increases, achieving patterns indistinguishable from the first group; and (iii) TIL(negative) cases generally remained negative. Despite the dramatic increases seen in the first two patterns, post-chemotherapy TIL showed limited prognostic significance.Conclusions: Chemotherapy augments pre-existing TIL responses but fails to relieve major immune-suppressive mechanisms or confer significant prognostic benefit. Our findings provide rationale for multipronged approaches to immunotherapy tailored to the baseline features of the tumor microenvironment. Clin Cancer Res; 23(4); 925-34. ©2016 AACR.

  18. Efficacy of tumor-targeting Salmonella typhimurium A1-R on nude mouse models of metastatic and disseminated human ovarian cancer.

    PubMed

    Matsumoto, Yasunori; Miwa, Shinji; Zhang, Yong; Hiroshima, Yukihiko; Yano, Shuya; Uehara, Fuminari; Yamamoto, Mako; Toneri, Makoto; Bouvet, Michael; Matsubara, Hisahiro; Hoffman, Robert M; Zhao, Ming

    2014-11-01

    We report here the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on mouse models of disseminated and metastatic ovarian cancer. The proliferation-inhibitory efficacy of A1-R on human ovarian cancer cell lines (SKOV-3-GFP, OVCAR-3-RFP) was initially demonstrated in vitro. Orthotopic and dissemination mouse models of ovarian cancer were made with the human ovarian cancer cell line SKOV-3-GFP. After tumor implantation, the mice were treated with A1-R (5 × 10(7)  colony-forming units [CFU], i.v.), and there were no severe adverse events observed. In the orthotopic model, tumor volume after treatment was 276 ± 60.8 mm(3), compared to 930 ± 342 mm(3) in the untreated control group (P = 0.022). There was also a significant difference in survival between treated mice and untreated mice in a peritoneal dissemination model (P = 0.005). The results of this report demonstrate that A1-R is effective for highly aggressive human ovarian cancer in metastatic and dissemination mouse models and suggest its clinical potential for this highly treatment-resistant disease.

  19. Nano-siRNA Particles and Combination Therapies for Ovarian Tumor Targeting

    DTIC Science & Technology

    2015-08-01

    ability to load LbL nanoparticles with different cargos, ranging from cisplatin to paclitaxel, with sufficient control for effective thereapies (Aim...using siRNA sensitizes COV362, Caov3, and SKOV3 ovarian cancer cells to cisplatin . a) Caov3 cells were transfected with EZH2 siRNA (siEZH2) or control...of three biological replicates. c) The fold change in cisplatin IC50 due to EZH2 depletion was determined for COV362, Caov3, and SKOV3 ovarian cancer

  20. A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer.

    PubMed

    Vollan, Hans Kristian Moen; Rueda, Oscar M; Chin, Suet-Feung; Curtis, Christina; Turashvili, Gulisa; Shah, Sohrab; Lingjærde, Ole Christian; Yuan, Yinyin; Ng, Charlotte K; Dunning, Mark J; Dicks, Ed; Provenzano, Elena; Sammut, Stephen; McKinney, Steven; Ellis, Ian O; Pinder, Sarah; Purushotham, Arnie; Murphy, Leigh C; Kristensen, Vessela N; Brenton, James D; Pharoah, Paul D P; Børresen-Dale, Anne-Lise; Aparicio, Samuel; Caldas, Carlos

    2015-01-01

    Complex focal chromosomal rearrangements in cancer genomes, also called "firestorms", can be scored from DNA copy number data. The complex arm-wise aberration index (CAAI) is a score that captures DNA copy number alterations that appear as focal complex events in tumors, and has potential prognostic value in breast cancer. This study aimed to validate this DNA-based prognostic index in breast cancer and test for the first time its potential prognostic value in ovarian cancer. Copy number alteration (CNA) data from 1950 breast carcinomas (METABRIC cohort) and 508 high-grade serous ovarian carcinomas (TCGA dataset) were analyzed. Cases were classified as CAAI positive if at least one complex focal event was scored. Complex alterations were frequently localized on chromosome 8p (n = 159), 17q (n = 176) and 11q (n = 251). CAAI events on 11q were most frequent in estrogen receptor positive (ER+) cases and on 17q in estrogen receptor negative (ER-) cases. We found only a modest correlation between CAAI and the overall rate of genomic instability (GII) and number of breakpoints (r = 0.27 and r = 0.42, p < 0.001). Breast cancer specific survival (BCSS), overall survival (OS) and ovarian cancer progression free survival (PFS) were used as clinical end points in Cox proportional hazard model survival analyses. CAAI positive breast cancers (43%) had higher mortality: hazard ratio (HR) of 1.94 (95%CI, 1.62-2.32) for BCSS, and of 1.49 (95%CI, 1.30-1.71) for OS. Representations of the 70-gene and the 21-gene predictors were compared with CAAI in multivariable models and CAAI was independently significant with a Cox adjusted HR of 1.56 (95%CI, 1.23-1.99) for ER+ and 1.55 (95%CI, 1.11-2.18) for ER- disease. None of the expression-based predictors were prognostic in the ER- subset. We found that a model including CAAI and the two expression-based prognostic signatures outperformed a model including the 21-gene and 70-gene signatures but excluding CAAI. Inclusion of CAAI in the

  1. Activating mutation of the stimulatory G protein (gsp) as a putative cause of ovarian and testicular human stromal Leydig cell tumors.

    PubMed

    Fragoso, M C; Latronico, A C; Carvalho, F M; Zerbini, M C; Marcondes, J A; Araujo, L M; Lando, V S; Frazzatto, E T; Mendonca, B B; Villares, S M

    1998-06-01

    Activating mutations of the G protein genes have been associated with the development of several endocrine neoplasms. Such activating mutations, gip2, affecting the alpha-subunit of the G alpha i2 protein were previously described by a single group in 30% of ovarian sex cord stromal tumors. Other activating mutations of the alpha-subunit of the Gs (gsp) have been identified in GH-secreting and nonfunctioning pituitary tumors, autonomous thyroid adenomas, and all affected McCune-Albright tissues, but not in sex cord stromal tumors. In the present study, we investigated the presence of gip2 and gsp mutations in 14 human sex cord stromal tumors. Six Leydig cell tumors (4 ovaries and 2 testes), 2 thecomas, 2 granulosa cell tumors, 3 androblastomas, and 1 gonadoblastoma (sex cord and germ cell) were included in this study. Genomic DNA was obtained from either fresh-frozen tumor tissues or paraffin-embedded sections and in some cases from blood samples. Using PCR, denaturing gradient gel electrophoresis, and direct sequencing, we detected 4 tumors (66.6%) with the gsp mutation (R201C) in our series of ovarian and testicular Leydig cell tumors. In contrast, no gip2 mutations were found in any of the sex cord stromal tumors studied. In conclusion, our findings suggest that the putative oncogene gsp may play a significant role in the molecular mechanism of these tumors.

  2. Mechanism of Ovarian Epithelial Tumor Predispostion in Individuals Carrying Germline BRCA1 Mutations

    DTIC Science & Technology

    2005-01-01

    are predisposed to ovarian cancer is that the ensuing decrease in BRCA1 gene dosage results in a disruption of normal cellular interactions between...Bioactivation of Mullerian inhibiting substance during gonadal development by a kex2/ subtilisin -like endoprotease. Proc. Natl. Acad. Sci. 93, 7711

  3. A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development

    DTIC Science & Technology

    2016-05-01

    2014) The steroid hormone environment during primordial follicle formation in perinatal mouse ovaries. Biology of Reproduction 91. Eppig JJ & O’Brien...FF & Quirk SM (2012) Overactivation of hedgehog signaling alters development of the ovarian vasculature in mice. Biology of reproduction 86, 174

  4. Borderline Space for Voice

    ERIC Educational Resources Information Center

    Batchelor, Denise

    2012-01-01

    Being on the borderline as a student in higher education is not always negative, to do with marginalisation, exclusion and having a voice that is vulnerable. Paradoxically, being on the edge also has positive connections with integration, inclusion and having a voice that is strong. Alternative understandings of the concept of borderline space can…

  5. Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages.

    PubMed

    Ying, Xiang; Wu, Quanfeng; Wu, Xiaoli; Zhu, Qinyi; Wang, Xinjing; Jiang, Lu; Chen, Xin; Wang, Xipeng

    2016-07-12

    Cancer secreted exosomal miRNAs are emerging as mediators between tumor-stoma crosstalk. Here, we show epithelial ovarian cancer (EOC)-derived exosomes activated macrophages to a tumor-associated macrophage (TAM)-like phenotype with SOCS3/STAT3 pathway involvement, which could facilitate the progression of cancer. MiR-222-3p was enrichment in exosomes released from EOC cells and it could be transferred to macrophages. Overexpression of miR-222-3p in macrophages induced polarization of the M2 phenotype. Luciferase assay verified miR-222-3p targeted SOCS3 genes and expression of SOCS3 was decreased after transfection with a miR-222-3p mimic. Down-regulation of SOCS3 correlated with an increased expression of STAT3 activation. MiR-222-3p could be detected in the exosomes from serum and its levels were related to EOC. These observations propose tumor-derived exosomal miR-222-3p is an effective regulator in the polarization of tumor-promoting M2 macrophages and may be a biomarker of EOC.

  6. Transitional cell carcinoma of the endometrium associated with benign ovarian brenner tumor: a case report with immunohistochemistry molecular analysis and a review of the literature.

    PubMed

    Giordano, Giovanna; D'Adda, Tiziana; Gnetti, Letizia; Merisio, Carla; Raboni, Stefano

    2007-07-01

    Transitional cell carcinoma of the endometrium (TCCE) is a subtype of endometrial carcinoma, characterized by a prominent papillary pattern, resembling the papillary carcinoma of the urothelium. This neoplasm is very rare, with only 13 cases reported in the international literature. In this paper, a new case of TCCE associated with benign ovarian Brenner tumor is described. This association is extremely rare, with only 1 other case reported. A review of the literature is performed to delineate the clinico pathologic features of this malignancy. Moreover, immunohistochemical and molecular studies are carried out in the effort to establish the phenotype and etiology of this rare neoplasm. The molecular study, by polymerase chain reaction (PCR) failing to reveal the presence of HPV DNA, demonstrates that neither the TCCE nor the ovarian Brenner tumor is caused by an HPV infection. The association of TCCE with benign ovarian Brenner tumor could be a coincidental event. Conversely, this finding could be the manifestation of a multicentric metaplastic process (neometaplasia), involving both the coelomic epithelium of the ovary and the Mullerian epithelium of the uterus, or the evidence of "field effect" that manifests differently at different anatomical sites. In our view, other cases of TCCE associated with ovarian Brenner tumor should be reported to confirm the last 2 hypotheses.

  7. p16/MTS1 inactivation in ovarian carcinomas: high frequency of reduced protein expression associated with hyper-methylation or mutation in endometrioid and mucinous tumors.

    PubMed

    Milde-Langosch, K; Ocon, E; Becker, G; Löning, T

    1998-02-20

    Inactivation of the tumor-suppressor gene p16 (MTS1/ CDKN2/INK4a) has been described in various human malignancies. Although p16 deletion has been found in various ovarian tumor cell lines, p16 inactivation by homozygous deletion or mutation has been reported only sporadically in primary ovarian carcinomas. In a comprehensive study, we analyzed p16 protein expression by immuno-histochemistry (IHC) on paraffin sections of 94 primary ovarian carcinomas of different histological subtype. Loss of expression was detected in 19 primary tumors (20%), mainly mucinous and endometrioid carcinomas. To reveal the cause of suppressed expression, we performed (i) analysis of homozygous deletions by comparative PCR after micro-dissection, (ii) mutation analysis by single-strand conformation polymorphism analysis and subsequent direct sequencing and (iii) methylation-specific PCR to determine the methylation status of 5'-CpG islands. Loss of or weak p16 expression was caused by hyper-methylation (12/19 IHC-negative cases), somatic mutation (10 tumors) or homozygous deletion (1 case). Aberrant p 16 results by one of these methods were detected in 71-79% of endometrioid and mucinous, but in only 10% of serous-papillary, carcinomas. Our data suggest that p16 inactivation is a typical feature of certain subtypes of ovarian carcinoma.

  8. CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling.

    PubMed

    Baldwin, Lauren A; Hoff, John T; Lefringhouse, Jason; Zhang, Michael; Jia, Changhe; Liu, Zeyi; Erfani, Sonia; Jin, Hongyan; Xu, Mei; She, Qing-Bai; van Nagell, John R; Wang, Chi; Chen, Li; Plattner, Rina; Kaetzel, David M; Luo, Jia; Lu, Michael; West, Dava; Liu, Chunming; Ueland, Fred R; Drapkin, Ronny; Zhou, Binhua P; Yang, Xiuwei H

    2014-12-15

    Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by impaired cell-cell contacts and aberrant expression of E-cadherin, Mucin 5AC and fibronectin, largely reminiscent of an epithelial to mesenchymal transition (EMT)-like change. Importantly, Slug, a master regulator of EMT, is markedly elevated. Knocking down Slug partially restores CD151-α3β1 integrin complex-dependent suppression of cell proliferation. Moreover, disruption of these adhesion protein complexes is accompanied by a concomitant activation of canonical Wnt signaling, including elevated levels of β-catenin and Axin-2 as well as resistance to the inhibition in β-catenin-dependent transcriptional complexes. Together, our study demonstrates that CD151-α3β1 integrin complexes regulate ovarian tumor growth by repressing Slug-mediated EMT and Wnt signaling.

  9. Expression of preoperative KISS1 gene in tumor tissue with epithelial ovarian cancer and its prognostic value.

    PubMed

    Cao, Fang; Chen, Liping; Liu, Manhua; Lin, Weiwei; Ji, Jinlong; You, Jun; Qiao, Fenghai; Liu, Hongbin

    2016-11-01

    Our study aimed to elucidate the role of Kisspeptin (KISS1) in tumor tissues of patients with epithelial ovarian cancer (EOC) and investigate the prognostic value of this biomarker.Forty EOC patients and 20 uterine fibroids female patients with healthy ovaries undergoing cytoreductive surgery between January 2010 and January 2014 in our hospital were enrolled in this study. KISS1 expression in tumor and normal tissues was detected. Correlations between clinic-pathologic variables and KISS1 expression in EOC tissues and the prognostic value of KISS1 for overall survival were evaluated.During the follow-up of 11.2 to 62.1 months, the overall survival rate and mean survival time were 28.9% (11/38) and 38.35 ± 2.84 months. Preoperative KISS1 mRNA was higher in tumor tissue than in normal tissue (P <0.001), and it was associated with histologic grade of tumor, surgical FIGO stage, metastasis, and residual tumor size (all P <0.05). Multivariate survival analysis indicated significant influence of residual tumor size (HR = 2.357, P = 0.039) and preoperative KISS1 mRNA (HR = 0.0001, P <0.001) on mean survival time. Patients with low KISS1 mRNA expression had shorter survival time than those with high expression (P = 0.001).Preoperative KISS1 mRNA was a potential prognostic biomarker for EOC, and high preoperative KISS1 expression indicated a favorable prognosis.

  10. Expression of preoperative KISS1 gene in tumor tissue with epithelial ovarian cancer and its prognostic value

    PubMed Central

    Cao, Fang; Chen, Liping; Liu, Manhua; Lin, Weiwei; Ji, Jinlong; You, Jun; Qiao, Fenghai; Liu, Hongbin

    2016-01-01

    Abstract Our study aimed to elucidate the role of Kisspeptin (KISS1) in tumor tissues of patients with epithelial ovarian cancer (EOC) and investigate the prognostic value of this biomarker. Forty EOC patients and 20 uterine fibroids female patients with healthy ovaries undergoing cytoreductive surgery between January 2010 and January 2014 in our hospital were enrolled in this study. KISS1 expression in tumor and normal tissues was detected. Correlations between clinic-pathologic variables and KISS1 expression in EOC tissues and the prognostic value of KISS1 for overall survival were evaluated. During the follow-up of 11.2 to 62.1 months, the overall survival rate and mean survival time were 28.9% (11/38) and 38.35 ± 2.84 months. Preoperative KISS1 mRNA was higher in tumor tissue than in normal tissue (P <0.001), and it was associated with histologic grade of tumor, surgical FIGO stage, metastasis, and residual tumor size (all P <0.05). Multivariate survival analysis indicated significant influence of residual tumor size (HR = 2.357, P = 0.039) and preoperative KISS1 mRNA (HR = 0.0001, P <0.001) on mean survival time. Patients with low KISS1 mRNA expression had shorter survival time than those with high expression (P = 0.001). Preoperative KISS1 mRNA was a potential prognostic biomarker for EOC, and high preoperative KISS1 expression indicated a favorable prognosis. PMID:27861355

  11. RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

    PubMed

    Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

    2017-02-10

    The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

  12. Extracellular vesicles in ovarian cancer: applications to tumor biology, immunotherapy and biomarker discovery.

    PubMed

    Nawaz, Muhammad; Fatima, Farah; Nazarenko, Irina; Ekström, Karin; Murtaza, Iram; Anees, Mariam; Sultan, Aneesa; Neder, Luciano; Camussi, Giovanni; Valadi, Hadi; Squire, Jeremy A; Kislinger, Thomas

    2016-01-01

    In recent years there has been tremendous interest in both the basic biology and applications of extracellular vesicles (EVs) in translational cancer research. This includes a better understanding of their biogenesis and mechanisms of selective cargo packaging, their precise roles in horizontal communication, and their application as non-invasive biomarkers. The rapid advances in next-generation omics technologies are the driving forces for these discoveries. In this review, the authors focus on recent results of EV research in ovarian cancer. A deeper understanding of ovarian cancer-derived EVs, the types of cargo molecules and their biological roles in cancer growth, metastases and drug resistance, could have significant impact on the discovery of novel biomarkers and innovative therapeutics. Insights into the role of EVs in immune regulation could lead to novel approaches built on EV-based immunotherapy.

  13. [Ovarian tumor in a koi carp (Cyprinus carpio): Diagnosis, surgery, postoperative care and tumour classification].

    PubMed

    Lewisch, E; Reifinger, M; Schmidt, P; El-Matbouli, M

    2014-01-01

    Although ovarian tumour in the koi (Cyprinus carpio) does not appear to be an uncommon condition, its occurrence and therapy has rarely been reported. In the present case, the decision for surgery was based on clinical and sonographic findings of an intracoelomic mass. We used tricaine methansulfonate for the anaesthesia. Laparotomy was performed by ventral access and an ovarian tumour of 12-cm diameter was removed. The wound was sutured in two layers using Vicryl®. In addition to the application of an analgesic, an antibiotic and vitamins, the postoperative conditions the patient was kept under were adapted to support wound healing. The fish recovered uneventfully and was clinically healthy during the 16-month observation period. Based on the histological findings, the tumour was diagnosed as a thecoma. Investigations using antibodies against vimentin, cytokeratin, S 100 and glial fibrillary acidic protein (GFAP) failed to provide reliable results.

  14. Dairy foods and nutrients in relation to risk of ovarian cancer and major histological subtypes.

    PubMed

    Merritt, Melissa A; Cramer, Daniel W; Vitonis, Allison F; Titus, Linda J; Terry, Kathryn L

    2013-03-01

    Inconsistent results for the role of dairy food intake in relation to ovarian cancer risk may reflect the potential adverse effects of lactose, which has been hypothesized to increase gonadotropin levels, and the beneficial antiproliferative effects of calcium and vitamin D. Using data from the New England case-control study (1,909 cases and 1,989 controls), we examined dairy foods and nutrients in relation to risk of ovarian cancer overall, histological subtypes and rapidly fatal versus less aggressive disease. We used logistic regression and polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). In models that were simultaneously adjusted for total (dietary plus supplements) calcium, total vitamin D and lactose, we observed a decreased overall risk of ovarian cancer with high intake of total calcium [Quartile 4 (Q4, >1,319 mg/day) vs. Quartile 1 (Q1, <655 mg/day), OR = 0.62, 95% CI = 0.49-0.79]; the inverse association was strongest for serous borderline and mucinous tumors. High intake of total vitamin D was not associated overall with ovarian cancer risk, but was inversely associated with risk of serous borderline (Q4, >559 IU/day vs. Q1, <164 IU/day, OR = 0.51, 95% CI = 0.34-0.76) and endometrioid tumors (Q4 vs. Q1, OR = 0.55, 95% CI = 0.39-0.80). We found no evidence that lactose intake influenced ovarian cancer risk or that risk varied by tumor aggressiveness in the analyses of intake of dairy foods and nutrients. The overall inverse association with high intake of calcium and the inverse associations of calcium and vitamin D with specific histological subtypes warrant further investigation.

  15. Anti-Tumor Effects of Atractylenolide-I on Human Ovarian Cancer Cells

    PubMed Central

    Long, Fangyi; Wang, Ting; Jia, Ping; Wang, Huafei; Qing, Yi; Xiong, Tingting; He, Mengjie; Wang, Xiaoli

    2017-01-01

    Background The aim of this study was to investigate the effects of Atractylenolide-I (AT-I), a naturally occurring sesquiterpene lactone isolated from Atractylodes macrocephala Koidz, on human ovarian cancer cells. Material/Methods The viability and anchorage-independent growth of ovarian cancer cells were evaluated using MTT and colony formation assay, respectively. Cell cycle and apoptosis were detected with flow cytometry analysis. The level of cyclin B1 and CDK1 was measured using qPCR and ELISA analysis. The expression of Bax, cleaved caspase-9, cleaved caspase-3, cytochrome c, AIF, and Bcl-2, and phosphorylation level of PI3K, AKT, and mTOR were determined with Western blot analysis. Results AT-I decreased the cell viability and suppressed anchorage-independent growth of A2780 cells. Cell cycle was arrested in G2/M phase transition by AT-I treatment, which was related to decreased expression of cyclin B1 and CDK1 in a dose-dependent manner. In addition, the treatment induced apoptosis, as shown by up-regulation of Bax, cleaved caspase-9, cleaved caspase-3, and cytosolic release of cytochrome c and AIF, and down-regulation of Bcl-2, in a dose-dependent manner. Then, the effects of AT-I on PI3K/Akt/mTOR pathways were examined to further investigate the underlying anti-cancer mechanism of AT-I, and the results showed that treatment with AT-I significantly decreased the phosphorylation level of PI3K, Akt, and mTOR. Conclusions This study demonstrated that AT-I induced cell cycle arrest and apoptosis through inhibition of PI3K/Akt/mTOR pathway in ovarian cancer cells. These results suggest that AT-I might be a potential therapeutic agent in the treatment of ovarian cancer. PMID:28141785

  16. Ovarian Tumor-Stroma Interactions in an In Vivo Orthotopic Model

    DTIC Science & Technology

    2011-08-01

    cancer cells to the novel environment. We have devised an Intravital Video Microscopy approach to this problem in which MOVCAR cells labeled with green...Ovarian cancer, gene expression, metastasis, intravital video microscopy 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER...placed in a dorsal skin-fold chamber for Intravital Video Microscopy (IVM). The minced pseudo-organ tissue revascularizes and recapitulates some of the

  17. Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

    ClinicalTrials.gov

    2016-05-06

    Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

  18. Ovarian Tumor (OTU)-domain Containing Viral Proteases Evade Ubiquitin- and ISG15-dependent Innate Immune Responses

    PubMed Central

    Frias-Staheli, Natalia; Giannakopoulos, Nadia V.; Kikkert, Marjolein; Taylor, Shannon L.; Bridgen, Anne; Paragas, Jason J.; Richt, Juergen A.; Rowland, Raymond R.; Schmaljohn, Connie S.; Lenschow, Deborah J.; Snijder, Eric J.; García-Sastre, Adolfo; Virgin, Herbert Whiting

    2007-01-01

    Summary Ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) reversibly conjugate to proteins via a conserved LRLRGG C-terminal motif, mediating important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial and viral proteins, some of which have Ub-deconjugating activity. We show that the OTU domain-containing proteases of nairoviruses and arteriviruses hydrolyze Ub and ISG15 from cellular target proteins. This broad activity contrasts with the target specificity of known mammalian OTU domain-containing proteins. The biological significance of this activity of viral OTU domain-containing proteases was evidenced by their capacity to inhibit NF-κB dependent signaling and to antagonize the antiviral effects of ISG15 during Sindbis virus infection in vivo. The deconjugating activity of viral OTU proteases represents a novel viral immune evasion mechanism that inhibits Ub-and ISG15-dependent antiviral pathways. PMID:18078692

  19. PD-1 blunts the function of ovarian tumor-infiltrating dendritic cells by inactivating NF-κB

    PubMed Central

    Karyampudi, Lavakumar; Lamichhane, Purushottam; Krempski, James; Kalli, Kimberly R.; Behrens, Marshall D.; Vargas, Doris M.; Hartmann, Lynn C; Janco, Jo Marie T; Dong, Haidong; Hedin, Karen E; Dietz, Allan B.; Goode, Ellen L.; Knutson, Keith L.

    2015-01-01

    The PD-1:PD-L1 immune signaling axis mediates suppression of T cell-dependent tumor immunity. PD-1 expression was recently found to be upregulated on tumor-infiltrating murine (CD11c+CD11b+CD8−CD209a+) and human (CD1c+CD19−) myeloid dendritic cells (TIDC), an innate immune cell type also implicated in immune escape. However, there is little knowledge concerning how PD-1 regulates innate immune cells. In the present study, we examined the role of PD-1 in TIDC derived from mice bearing ovarian tumors. Similar to lymphocytes, TIDC expression of pd-1 was associated with expression of the adapter protein SHP-2, which signals to NF-κB, however, in contrast to its role in lymphocytes, we found that expression of PD-1 in TIDC tonically paralyzed NF-kB activation. Further mechanistic investigations showed that PD-1 blocked NF-kB-dependent cytokine release in a SHP-2-dependent manner. Conversely, inhibition of NF-kB-mediated antigen presentation by PD-1 occurred independently of SHP-2. Collectively, our findings revealed that PD-1 acts in a distinct manner in innate immune cells compared to adaptive immune cells, prompting further investigations of the signaling pathways controlled by this central mediator of immune escape in cancer. PMID:26567141

  20. Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors.

    PubMed

    Labidi-Galy, S I; Clauss, A; Ng, V; Duraisamy, S; Elias, K M; Piao, H-Y; Bilal, E; Davidowitz, R A; Lu, Y; Badalian-Very, G; Györffy, B; Kang, U-B; Ficarro, S; Ganesan, S; Mills, G B; Marto, J A; Drapkin, R

    2015-01-15

    High-grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirm that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients. Elafin confers a proliferative advantage to tumor cells through the activation of the MAP kinase pathway. This mitogenic effect can be neutralized by RNA interference, specific antibodies and a MEK inhibitor. Elafin expression in patient-derived samples was also associated with chemoresistance and strongly correlates with bcl-xL expression. We extended these findings into the examination of 1100 primary breast tumors and six breast cancer cell lines. We observed that Elafin is overexpressed and secreted specifically by BLBC tumors and cell lines, leading to a similar mitogenic effect through activation of the MAP kinase pathway. Here too, Elafin overexpression is associated with poor overall survival, suggesting that it may serve as a biomarker and therapeutic target in this setting.

  1. A Pyloric Gland-Phenotype Ovarian Mucinous Tumor Resembling Lobular Endocervical Glandular Hyperplasia in a Patient with Peutz-Jeghers Syndrome.

    PubMed

    Kim, Eun Na; Kim, Gu-Hwan; Kim, Jiyoon; Park, In Ah; Shin, Jin Ho; Chai, Yun; Kim, Kyu-Rae

    2017-03-01

    We describe an ovarian mucinous neoplasm that histologically resembles lobular endocervical glandular hyperplasia (LEGH) containing pyloric gland type mucin in a patient with Peutz-Jeghers syndrome (PJS). Although ovarian mucinous tumors rarely occur in PJS patients, their pyloric gland phenotype has not been clearly determined. The histopathologic features of the ovarian mucinous tumor were reminiscent of LEGH. The cytoplasmic mucin was stained with periodic acid-Schiff reaction after diastase treatment but was negative for Alcian blue pH 2.5, suggesting the presence of neutral mucin. Immunohistochemically, the epithelium expressed various gastric markers, including MUC6, HIK1083, and carbonic anhydrase-IX. Multiple ligation-dependent probe amplification detected a germline heterozygous deletion mutation at exons 1-7 of the STK11 gene (c.1-?_920+?del) in peripheral blood leukocytes and mosaic loss of heterozygosity in ovarian tumor tissue. Considering that LEGH and/or gastric-type cervical adenocarcinoma can be found in patients with PJS carrying germline and/or somatic STK11 mutations, our case indicates that STK11 mutations have an important role in the proliferation of pyloric-phenotype mucinous epithelium at various anatomical locations.

  2. A Pyloric Gland-Phenotype Ovarian Mucinous Tumor Resembling Lobular Endocervical Glandular Hyperplasia in a Patient with Peutz-Jeghers Syndrome

    PubMed Central

    Kim, Eun Na; Kim, Gu-Hwan; Kim, Jiyoon; Park, In Ah; Shin, Jin Ho; Chai, Yun; Kim, Kyu-Rae

    2017-01-01

    We describe an ovarian mucinous neoplasm that histologically resembles lobular endocervical glandular hyperplasia (LEGH) containing pyloric gland type mucin in a patient with Peutz-Jeghers syndrome (PJS). Although ovarian mucinous tumors rarely occur in PJS patients, their pyloric gland phenotype has not been clearly determined. The histopathologic features of the ovarian mucinous tumor were reminiscent of LEGH. The cytoplasmic mucin was stained with periodic acid-Schiff reaction after diastase treatment but was negative for Alcian blue pH 2.5, suggesting the presence of neutral mucin. Immunohistochemically, the epithelium expressed various gastric markers, including MUC6, HIK1083, and carbonic anhydrase-IX. Multiple ligation-dependent probe amplification detected a germline heterozygous deletion mutation at exons 1–7 of the STK11 gene (c.1-?_920+?del) in peripheral blood leukocytes and mosaic loss of heterozygosity in ovarian tumor tissue. Considering that LEGH and/or gastric-type cervical adenocarcinoma can be found in patients with PJS carrying germline and/or somatic STK11 mutations, our case indicates that STK11 mutations have an important role in the proliferation of pyloric-phenotype mucinous epithelium at various anatomical locations. PMID:27550049

  3. Extracellular Vesicles Present in Human Ovarian Tumor Microenvironments Induce a Phosphatidylserine-Dependent Arrest in the T-cell Signaling Cascade.

    PubMed

    Kelleher, Raymond J; Balu-Iyer, Sathy; Loyall, Jenni; Sacca, Anthony J; Shenoy, Gautam N; Peng, Peng; Iyer, Vandana; Fathallah, Anas M; Berenson, Charles S; Wallace, Paul K; Tario, Joseph; Odunsi, Kunle; Bankert, Richard B

    2015-11-01

    The identification of immunosuppressive factors within human tumor microenvironments, and the ability to block these factors, would be expected to enhance patients' antitumor immune responses. We previously established that an unidentified factor, or factors, present in ovarian tumor ascites fluids reversibly inhibited the activation of T cells by arresting the T-cell signaling cascade. Ultracentrifugation of the tumor ascites fluid has now revealed a pellet that contains small extracellular vesicles (EV) with an average diameter of 80 nm. The T-cell arrest was determined to be causally linked to phosphatidylserine (PS) that is present on the outer leaflet of the vesicle bilayer, as a depletion of PS-expressing EV or a blockade of PS with anti-PS antibody significantly inhibits the vesicle-induced signaling arrest. The inhibitory EV were also isolated from solid tumor tissues. The presence of immunosuppressive vesicles in the microenvironments of ovarian tumors and our ability to block their inhibition of T-cell function represent a potential therapeutic target for patients with ovarian cancer.

  4. Hyaline globules and papillary fragments in cytologic smears from two intra-abdominal tumors (ovarian and hepatic) in female patients: A diagnostic pitfall with histologic correlation.

    PubMed

    Machado, Isidro; López-Soto, María Victoria; Pérez-López, Albadio Samir; Domínguez-Álvarez, Carlos; Llombart-Bosch, Antonio

    2016-11-01

    Hyaline globules and papillary fragments in cytologic samples from two intra-abdominal tumors in young females are presented including the cytological features and the correlation with the histopathologic and immunohistochemical findings. In the first case a cytologic study from an ovarian mass showed papillary structures and isolated tumor cells with epithelioid morphology, irregular reniform-like nuclear contour, pale or vacuolated cytoplasm, abundant hyaline globules and occasional glomeruloid structures resembling Schiller-Duval bodies. Yolk sac tumor (YST) was the diagnosis on the histological slides. Tumor cells showed positivity for cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), alpha-fetoprotein (AFP) and Sal-like protein 4 (SALL4). In case number two the cytologic study from a liver metastasis displayed papillary and rosette-like clusters composed of uniform and bland cells showing occasional long cytoplasmic tails, hyaline globules and nuclear grooves. A diagnosis of hepatic metastasis from solid pseudopapillary neoplasm of the pancreas (SPNP) was rendered from the histology. Tumor cells revealed immunoreactivity for cytokeratin (AE1/AE3), Vimentin, Galectin-1 (GAL-1), Neuron specific-enolase, CD10, progesterone and β-catenin (nuclear stain). Regarding differential diagnosis, in the patient with the ovarian mass an ovarian clear cell carcinoma was considered, as well as other germ cell tumors or metastatic carcinoma, while in the patient with a liver metastasis a neuroendocrine carcinoma was taken into account. YST and SPNP share some cytological findings, including hyaline globules, papillary structures, clear cells and intercellular eosinophilic basement membrane deposits. Thus, a detailed study and careful interpretation of the cytological, histological and immunohistochemical findings may be worthwhile to avoid a potential misdiagnosis, particularly in the cytologic specimens of the ovarian and/or intra-abdominal mass, when involving young

  5. Ovarian Brenner tumors and Walthard nests: a histologic and immunohistochemical study.

    PubMed

    Roma, Andres A; Masand, Ramya P

    2014-12-01

    Brenner tumors are composed of urothelial/transitional-type epithelium and, hence, are morphologically similar to Walthard nests and tubal/mesothelial transitional metaplasia. In this study, we analyzed immunohistochemical markers on Brenner tumors to explore Müllerian as well as Wolffian and germ cell derivation. We also attempted to explore their possible association with tubal/paratubal Walthard nests/transitional metaplasia, using the same immunostains. Thirty-two consecutive cases of Brenner tumors were identified. Thirteen (43%) of the patients had Walthard nests in the tubal/periovarian soft tissue. All Brenner tumors were diffusely positive for GATA3 (strongly positive in 30/32 and weakly positive in the remaining 2) and negative for PAX8, PAX2, and SALL4. Similarly, all Walthard nests were positive for GATA3, whereas only 3 (23%) of 13 showed occasional PAX8 expression; all were negative for PAX2 and SALL4. In our study, more than 40% of Brenner tumors had associated Walthard nests. The similar morphology and immunoprofile of Brenner tumors and Walthard nests suggest a probable link between Brenner tumors and Walthard nests. Two additional cases presented highlight small transitional lesions involving the ovary: a possible precursor lesion or the initial steps of Brenner tumor formation. Brenner tumors and most Walthard nests lacked staining for Müllerian (PAX8 and PAX2) and germ cell tumor markers (SALL4).

  6. Carboplatin and Paclitaxel With or Without Bevacizumab Compared to Docetaxel, Carboplatin, and Paclitaxel in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Carcinoma (Cancer)

    ClinicalTrials.gov

    2013-03-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  7. Borderline personality disorder

    MedlinePlus

    American Psychiatric Association. Borderline personality disorder. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013:663-666. Blais MA, Smallwood P, Groves ...

  8. Treatment of Borderline Adolescents.

    ERIC Educational Resources Information Center

    Green, Maurice R.

    1983-01-01

    Describes characteristics of borderline adolescents and reviews diagnostic issues. Uses two case studies to illustrate general treatment strategies that could be useful to clinicians in mental health programs and family courts. (JAC)

  9. Adaptive Upregulation of EGFR Limits Attenuation of Tumor Growth by Neutralizing IL6 Antibodies, with Implications for Combined Therapy in Ovarian Cancer.

    PubMed

    Milagre, Carla S; Gopinathan, Ganga; Everitt, Gemma; Thompson, Richard G; Kulbe, Hagen; Zhong, Haihong; Hollingsworth, Robert E; Grose, Richard; Bowtell, David D L; Hochhauser, Daniel; Balkwill, Frances R

    2015-04-01

    Excess production of the proinflammatory IL6 has both local and systemic tumor-promoting activity in many cancers, including ovarian cancer. However, treatment of advanced ovarian cancer patients with a neutralizing IL6 antibody yielded little efficacy in a previous phase II clinical trial. Here, we report results that may explain this outcome, based on the finding that neutralizing antibodies to IL6 and STAT3 inhibition are sufficient to upregulate the EGFR pathway in high-grade serous and other ovarian cancer cells. Cell treatment with the EGFR inhibitor gefitinib abolished upregulation of the EGFR pathway. Combining neutralizing IL6 antibodies and gefitinib inhibited malignant cell growth in 2D and 3D culture. We found that ErbB-1 was localized predominantly in the nucleus of ovarian cancer cells examined, contrasting with plasma membrane localization in lung cancer cells. Treatment with anti-IL6, gefitinib, or their combination all led to partial restoration of ErbB-1 on the plasma membrane. In vivo experiments confirmed the effects of IL6 inhibition on the EGFR pathway and the enhanced activity of a combination of anti-IL6 antibodies and gefitinib on malignant cell growth. Taken together, our results offer a preclinical rationale to combine anti-IL6 and gefitinib to treat patients with advanced stage ovarian cancer.

  10. Rare recurrence of a rare ovarian stromal tumor with luteinized cells: a case report

    PubMed Central

    2011-01-01

    Introduction Sex cord-stromal tumors of the ovary are uncommon. They behave unpredictably and often have a late recurrence, making counseling, management, and prediction of prognosis challenging. Case presentation A 52-year-old Moroccan woman with an sex cord-stromal tumors underwent a bilateral oophorectomy. The histology was unusual but was likely to be a luteinized thecoma with suspicious features for invasion. Seven years later, after a gastrointestinal bleed, a metastasis within the small bowel mucosa was detected. This represents probable isolated hematogenous or lymphatic spread, which is highly unusual, especially in the absence of concurrent peritoneal disease. Conclusions To the best of our knowledge, this is the second reported case of an sex cord-stromal tumors recurring in small bowel mucosa and mimicking a primary colorectal tumor. This highlights the diverse nature and behavior of these tumors. PMID:21816048

  11. Intraperitoneal Bortezomib and Carboplatin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2017-01-31

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Transitional Cell Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  12. Adoptive Immunotherapy for Epithelial Ovarian Cancer Using T-cells Simultaneously Targeted to Tumor and Tumor-Associated Macrophages

    DTIC Science & Technology

    2013-12-01

    Figure   10   that   demonstrate   ring   enhancement   around   the   viable   circumference   of   the   tumor.   When...in head and neck cancer. Taken together, it is logical to build on this experience by developing the use of TiN-4+ T-cell immunotherapy for the

  13. Aberrant TGFβ/SMAD4 signaling contributes to epigenetic silencing of a putative tumor suppressor, RunX1T1 in ovarian cancer.

    PubMed

    Yeh, Kun-Tu; Chen, Tze-Ho; Yang, Hui-Wen; Chou, Jian-Liang; Chen, Lin-Yu; Yeh, Chia-Ming; Chen, Yu-Hsin; Lin, Ru-Inn; Su, Her-Young; Chen, Gary C W; Deatherage, Daniel E; Huang, Yi-Wen; Yan, Pearlly S; Lin, Huey-Jen; Nephew, Kenneth P; Huang, Tim H-M; Lai, Hung-Cheng; Chan, Michael W Y

    2011-06-01

    Aberrant TGFβ signaling pathway may alter the expression of down-stream targets and promotes ovarian carcinogenesis. However, the mechanism of this impairment is not fully understood. Our previous study has identified RunX1T1 as a putative SMAD4 target in an immortalized ovarian surface epithelial cell line, IOSE. In this study, we report that transcription of RunX1T1 was confirmed to be positively regulated by SMAD4 in IOSE cells and epigenetically silenced in a panel of ovarian cancer cell lines by promoter hypermethylation and histone methylation at H3 lysine 9. SMAD4 depletion increased repressive histone modifications of RunX1T1 promoter without affecting promoter methylation in IOSE cells. Epigenetic treatment can restore RunX1T1 expression by reversing its epigenetic status in MCP3 ovarian cancer cells. When transiently treated with a demethylating agent, the expression of RunX1T1 was partially restored in MCP3 cells, but gradual re-silencing through promoter re-methylation was observed after the treatment. Interestingly, SMAD4 knockdown accelerated this re-silencing process, suggesting that normal TGF-beta signaling is essential for the maintenance of RunX1T1 expression. In vivo analysis confirmed that hypermethylation of RunX1T1 was detected in 35.7% (34/95) of ovarian tumors with high clinical stages (P=0.035) and in 83% (5/6) of primary ovarian cancer-initiating cells. Additionally, concurrent methylation of RunX1T1 and another SMAD4 target, FBXO32 which was previously found to be hypermethylated in ovarian cancer was observed in this same sample cohort (P< 0.05). Restoration of RunX1T1 inhibited cancer cell growth. Taken together, dysregulated TGFβ/SMAD4 signaling may lead to epigenetic silencing of a putative tumor suppressor, RunX1T1, during ovarian carcinogenesis.

  14. DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings

    ClinicalTrials.gov

    2016-10-05

    Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Embryonal Carcinoma; Testicular Seminoma; Testicular Teratoma; Testicular Yolk Sac Tumor

  15. Comparison of total plasma lysophosphatidic acid and serum CA-125 as a tumor marker in the diagnosis and follow-up of patients with epithelial ovarian cancer

    PubMed Central

    Barbaros, Merve; Baykara, Elif; Guralp, Onur; Cengiz, Salih; Demirkiran, Fuat; Sanioglu, Cevdet; Arvas, Macit

    2010-01-01

    Objective To evaluate the role of lysophosphatidic acid (LPA) as a tumor marker in diagnosis and follow-up of patients with epithelial ovarian cancer. Methods Eighty-seven epithelial ovarian cancer patients, 74 benign ovarian tumor patients, and 50 healthy women were enrolled in the study. Twenty-nine of 87 epithelial ovarian cancer patients were followed up for 6 cycles of paclitaxel-carboplatin chemotherapy. CA-125 and total plasma LPA levels were measured preoperatively and before each chemotherapy cycle. Results Preoperative total plasma LPA and serum CA-125 levels were significantly higher in patients with epithelial ovarian cancer compared to patients with benign ovarian tumors and healthy women. Cut-off value for LPA was determined as 1.3 µmol/L and sensitivity, specificity, positive predictive value and negative predictive value were 95%, 92%, 95% and 92%, respectively. Mean total plasma LPA level of 29 patients who received chemotherapy was 7.21±6.63 µmol/L preoperatively and 6.84±6.34 µmol/L, 6.34±5.92 µmol/L, 6.14±5.79 µmol/L, 5.86±5.68 µmol/L, 5.23±5.11 µmol/L and 5.21±5.32 µmol/L in measurements held just before the 1st, 2nd, 3rd, 4th, 5th and 6th chemotherapy cycles, respectively (ANOVA, p=0.832). Total plasma LPA levels decreased slightly with chemotherapy administration and there was a weak negative correlation (Spearman, rs=-0.151, p=0.034), compared to a significant negative correlation in CA-125 (Spearman, rs=-0.596, p<0.001). Conclusion LPA is a better biomarker for diagnosis of epithelial ovarian cancer compared to CA-125. However, measurement of total plasma LPA levels during chemotherapy administration have no superiority to the serum CA-125 levels. PMID:21278887

  16. The anti-tumor effect of cross-reacting material 197, an inhibitor of heparin-binding EGF-like growth factor, in human resistant ovarian cancer

    SciTech Connect

    Tang, Xiao-han; Deng, Suo; Li, Meng; Lu, Mei-song

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer HB-EGF over-expression in A2780/Taxol, A2780/CDDP cells and the matched xenografts. Black-Right-Pointing-Pointer CRM197 induces enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. Black-Right-Pointing-Pointer CRM197 arrests A2780/Taxol and A2780/CDDP cells at G0/G1 phase. Black-Right-Pointing-Pointer CRM197 suppressed the A2780/Taxol and A2780/CDDP growth of xenografts. -- Abstract: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. Cross-reacting material 197 (CRM197), a specific HB-EGF inhibitor, has been proven to represent possible chemotherapeutic agent for ovarian cancer. However, the effect of CRM197 on the resistant ovarian carcinoma cells has not been sufficiently elucidated. Here, we found that HB-EGF was over-expressed in a paclitaxel-resistant human ovarian carcinoma cell line (A2780/Taxol) and a cisplatin-resistant cell line (A2780/CDDP), as well as the xenograft mouse tissue samples with these cells. To investigate the possible significance of the HB-EGF over-expression in A2780/Taxol and A2780/CDDP cells, we inhibited HB-EGF expression by CRM197 to investigate the effect of CRM197 treatment on these cells. We observed that CRM197 significantly induced anti-proliferative activity in a dose-dependent manner with the cell-cycle arrest at the G0/G1 phase and enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. The sensitive ovarian carcinoma parental cell line (A2780), A2780/Taxol and A2780/CDDP cells formed tumors in nude mice, and enhanced tumorigenicity was observed in drug-resistant tumors. Furthermore, we observed that CRM197 significantly suppressed the growth of drug-resistant ovarian cancer xenografts in vivo (p < 0.001). These results suggest that CRM197 as an HB-EGF-targeted agent has potent anti-tumor activity in paclitaxel- and cisplatin-resistant ovarian cancer which over-express HB-EGF.

  17. Functional and molecular mapping of uncoupling between vascular permeability and loss of vascular maturation in ovarian carcinoma xenografts: the role of stroma cells in tumor angiogenesis.

    PubMed

    Gilad, Assaf A; Israely, Tomer; Dafni, Hagit; Meir, Gila; Cohen, Batya; Neeman, Michal

    2005-11-01

    Maintaining homogeneous perfusion in tissues undergoing remodeling and vascular expansion requires tight orchestration of the signals leading to endothelial sprouting and subsequent recruitment of perivascular contractile cells and vascular maturation. This regulation, however, is frequently disrupted in tumors. We previously demonstrated the role of tumor-associated myofibroblasts in vascularization and exit from dormancy of human ovarian carcinoma xenografts in nude mice. The aim of this work was to determine the contribution of stroma- and tumor cell-derived angiogenic growth factors to the heterogeneity of vascular permeability and maturation in MLS human ovarian carcinoma tumors. We show by RT-PCR and by in situ hybridization that VEGF was expressed by the tumor cells, while angiopoietin-1 and -2 were expressed only by the infiltrating host stroma cells. Vascular maturation was detected in vivo by vasoreactivity to hypercapnia, measured by BOLD contrast MRI and validated by immunostaining of histologic sections to alpha-smooth muscle actin. Vascular permeability was measured in vivo by dynamic contrast-enhanced MRI using albumin-based contrast material and validated in histologic sections by fluorescent staining of the biotinylated contrast material. MRI as well as histologic correlation maps between vascular maturation and vascular permeability revealed a wide range of vascular phenotypes, in which the distribution of vascular maturation and vasoreactivity did not overlap spatially with reduced permeability. The large heterogeneity in the degree of vascular maturation and permeability is consistent with the differential expression pattern of VEGF and angiopoietins during tumor angiogenesis.

  18. Expression of betaglycan, an inhibin coreceptor, in normal human ovaries and ovarian sex cord-stromal tumors and its regulation in cultured human granulosa-luteal cells.

    PubMed

    Liu, Jianqi; Kuulasmaa, Tiina; Kosma, Veli-Matti; Bützow, Ralf; Vänttinen, Teemu; Hydén-Granskog, Christel; Voutilainen, Raimo

    2003-10-01

    Activins and inhibins are often antagonistic in the regulation of ovarian function. TGFbeta type III receptor, betaglycan, has been identified as a coreceptor to enhance the binding of inhibins to activin type II receptor and thus to prevent the binding of activins to their receptor. In this study we characterized the expression and regulation pattern of betaglycan gene in normal ovaries and sex cord-stromal tumors and in cultured human granulosa-luteal cells from women undergoing in vitro fertilization. Expression of betaglycan mRNA was detected by RT-PCR or Northern blotting in normal ovarian granulosa, thecal, and stroma cells as well as in granulosa-luteal cells. Immunohistochemical analysis revealed positive staining for betaglycan in antral and preovulatory follicular granulosa and thecal cells and in corpora lutea of normal ovaries. Furthermore, betaglycan expression was detected in the vast majority of granulosa cell tumors, thecomas, and fibromas, with weaker staining in granulosa cell tumors compared with fibrothecomas. In cultured granulosa-luteal cells, FSH and LH treatment increased dose-dependently the accumulation of betaglycan mRNA, as did the protein kinase A activator dibutyryl cAMP and the protein kinase C inhibitor staurosporine. In contrast, the protein kinase C activator 12-O-tetradecanoyl phorbol 13-acetate had no significant effect on betaglycan mRNA levels. Treatment with prostaglandin E(2) and with its receptor EP2 subtype agonist butaprost increased betaglycan mRNA accumulation and progesterone secretion dose- and time-dependently. In summary, betaglycan gene is expressed in normal human ovarian steroidogenic cells and sex cord-stromal ovarian tumors. The accumulation of its mRNA in cultured granulosa-luteal cells is up-regulated by gonadotropins and prostaglandin E(2), probably via the protein kinase A pathway. The specific expression and regulation pattern of betaglycan gene may be related to the functional antagonism of inhibins to

  19. Early Detection of Ovarian Cancer by Molecular Targeted Ultrasound Imaging Together with Serum Markers of Tumor-Associated Nuclear Change and Angiogenesis

    DTIC Science & Technology

    2014-03-01

    of ovarian tumors at early stage using imaging indices established in Specific Aim 1. Hens were maintained under standard poultry husbandry practices...Illinois at Urbana-Champaign Poultry Research Farm, for maintenance of the hens. We also thank Heather Lopez, research Assistant, Department of...hens (Gallus domesticus, 74 approximately 4-years old) were reared under standard poultry care and management and 75 provided with feed and water ad

  20. Gene expression profiling of human ovarian tumours

    PubMed Central

    Biade, S; Marinucci, M; Schick, J; Roberts, D; Workman, G; Sage, E H; O'Dwyer, P J; LiVolsi, V A; Johnson, S W

    2006-01-01

    There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT–PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers. PMID:16969345

  1. Gene expression profiling of human ovarian tumours.

    PubMed

    Biade, S; Marinucci, M; Schick, J; Roberts, D; Workman, G; Sage, E H; O'Dwyer, P J; Livolsi, V A; Johnson, S W

    2006-10-23

    There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT-PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers.

  2. The Association Between Talc Use and Ovarian Cancer

    PubMed Central

    Vitonis, Allison F.; Terry, Kathryn L.; Welch, William R.; Titus, Linda J.

    2016-01-01

    Background: Multiple studies of ovarian cancer and genital talc use have led only to consensus about possible carcinogenicity. Seeking greater clarity, we examined this association in 2,041 cases with epithelial ovarian cancer and 2,100 age- and-residence-matched controls. Methods: We defined genital talc use as regular application to the genital/rectal area directly, on sanitary napkins, tampons, or underwear. To estimate “talc-years,” we multiplied applications per year by years used. Unconditional logistic regression, Wald statistics, likelihood-ratio tests, and polytomous logistic regression were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI), trends, effect-modification, and heterogeneity by ovarian cancer histologic subtype. Results: Overall, genital talc use was associated with an OR (95% CI) of 1.33 (1.16, 1.52), with a trend for increasing risk by talc-years. Women who used talc were more likely to be older, heavier, asthma sufferers, and regular analgesic users—none of which was a confounder. Dose–responses were more apparent for premenopausal women, especially nonsmokers and those heavier or postmenopausal users of menopausal hormones (hormone therapy [HT]). Subtypes of ovarian cancer more likely to be associated with talc included invasive serous and endometrioid tumors and borderline serous and mucinous tumors. Premenopausal women and postmenopausal HT users with these subtypes who had accumulated >24 talc-years had ORs (95% CI) of 2.33 (1.32, 4.12) and 2.57 (1.51, 4.36), respectively. Conclusion: Risks for epithelial ovarian cancer from genital talc use vary by histologic subtype, menopausal status at diagnosis, HT use, weight, and smoking. These observations suggest that estrogen and/or prolactin may play a role via macrophage activity and inflammatory response to talc. PMID:26689397

  3. The plasma concentration of VEGF, HE4 and CA125 as a new biomarkers panel in different stages and sub-types of epithelial ovarian tumors

    PubMed Central

    2013-01-01

    Background VEGF may play a role in the pathogenesis of cancer disease, for example in cell growth, proliferation and angiogenesis. In this study, we investigated plasma levels of this cytokine in comparison to plasma levels of a new biomarker - HE4 and the established tumor marker CA125 in ovarian cancer patients (100) as compared to control groups: patients with a benign ovarian tumor (80) and healthy subjects (50). Methods Plasma levels of VEGF were determined by ELISA, HE4 and CA125 by CMIA method. Results The results showed that levels of VEGF, CA125 and HE4 were significantly higher in ovarian cancer (OC) patients as compared to the both control groups. VEGF has demonstrated as high as comparative markers values of the diagnostic sensitivity (SE), specificity (SP), the predictive values of positive and negative test results (PV-PR, PV-NR), and the area under the ROC curve (AUC) in early stages of cancer tested groups. The combined use of parameters studied resulted in the increase in the diagnostic criteria values and the AUC. Conclusions These findings suggest the usefulness of VEGF in the early diagnostics of ovarian cancer, especially in combination with CA125 and HE4, as a new biomarkers panel. Additionally, VEGF is the most useful tool in the diagnostics of locally advanced ovarian cancer without metastases. Investigated cytokine presented similar to HE4 usefulness in differentiation of OC according to its histopathlogical sub-type, and could be used especially in the diagnostics of endometrioid epithelial OC. PMID:23819707

  4. Ovarian granulosa cell tumors: a retrospective study of 27 cases and a review of the literature

    PubMed Central

    2013-01-01

    Background Granulosa tumors were described for the first time in 1855 by Rokitansky. These tumors are malignancies with a relatively favorable prognosis. They are characterized by a prolonged natural history and a tendency to late recurrences. The aim of this study is to investigate the epidemiological and pathological characteristics of granulosa cell tumors and to investigate the prognosis factor for recurrences. Methods The clinical data of patients who were treated in the period from January 2003 to December 2010 at the National Institute of Oncology in Rabat, Morocco for adult granulosa cell tumors of the ovary were investigated retrospectively. Data for age, clinical manifestation, imaging, diagnosis and treatment of the patients were reviewed and analyzed. Post-operative histology was obtained for all patients. Results Twenty-seven cases were retrieved. The median patient age was 53 years. The most common clinical manifestations at diagnosis were abdominal pain and vaginal bleeding. Mean tumor size was 14 cm. The majority of patients had stage I (63%, n = 17), while (18,5%, n = 5) had stage III, (7.4%, n = 2) had stage IV, and (11%, n = 3) of patients had an unknown stage. In the follow-up period (median = 63.44 months), five (18.51%) patients relapsed. The median time to relapse was 41.8 months, (range: 18 to 62 months). Conclusions Granulosa cell tumor of the ovary is an uncommon neoplasm. The adult form progresses slowly and often is diagnosed in an early stage of disease. Surgery is indicated. A prolonged post-therapeutic follow-up is necessary because of the risk of recurrences, late and exceptional for the adult form. PMID:23777285

  5. Plexin-B1 silencing inhibits ovarian cancer cell migration and invasion

    PubMed Central

    2010-01-01

    Background Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro. Methods Plexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKTSer473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining. Results Expression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell

  6. [Cystic struma ovarii, a rare form of ovarian tumor--case report, and review of the literature].

    PubMed

    Ostör, Gabriella; Tóth, Ildikó; Hrubyné Tóth, Zsuzsanna; Bazsa, Sándor

    2007-12-02

    Struma ovarii represents less than 3% of ovarian teratomas. It can be associated with thyroid biology abnormalities, and in exceptionally rare cases it can be malignant. The authors report a case of a 31-year-old woman who underwent resection of a left ovarian cyst, presenting with the clinical features of an ovarian cancer (large pelvic mass, ascites and elevated CA-125 serum levels). The pathologic diagnosis was benign struma ovarii. The postoperative thyroid function remained normal.

  7. MiR-143 targets CTGF and exerts tumor-suppressing functions in epithelial ovarian cancer

    PubMed Central

    Wang, Lufei; He, Jin; Xu, Hongmei; Xu, Longjie; Li, Na

    2016-01-01

    A series of recent studies suggested that miR-143 might involve in the tumorigenesis and metastasis of various cancer types. However, the biological function and underlying mechanisms of miR-143 in human epithelial ovarian carcinoma (EOC) remain unknown. Therefore, this study aimed to investigate the miR-143 expression and its clinical diagnosis significance in patients suffering EOC and to analyze its role and underlying molecular mechanism in EOC. Our result showed that the expression levels of miR-143 were downregulated in EOC tissues and cell lines, was associated with International Federation of Gynaecology and Obstetrics (FIGO) stage, pathological grade and lymph node metastasis (all P < 0.01) . Overexpression of miR-143 significantly inhibited EOC cell proliferation, migration, and invasion. Furthermore, computational algorithm combined with luciferase reporter assays identified connective tissue growth factor (CTGF) as the direct target of miR-143 in EOC cells. The expression level of CTGF was significantly increased in EOC tissues, was inversely correlated with miR-143 expression in clinical EOC tissues. Knockdown of CTGF mimicked the suppression effect induced by miR-143 overexpression. Restoration of CTGF expression partially reversed the suppression effect induced by miR-143 overexpression. These results suggested that miR-143 inhibited EOC cell proliferation, migration, and invasion, at least in part, via suppressing CTGF expression. PMID:27398154

  8. Hyperandrogenism produced by ovarian tumors in women at different life stages.

    PubMed

    Fux-Otta, Carolina; Szafryk de Mereshian, Paula; López de Corominas, Mónica; Fuster, Margarita; López, Carlos R

    2014-01-01

    Objetivo: evaluar las diferentes manifestaciones del hiperandrogenismo tumoral de origen ovárico en distintos grupos etarios. Diseño: reporte de casos.Lugar de trabajo: centros académicos.Pacientes: son reportadas tres pacientes con exceso de andrógenos. Resultados: describimos una paciente de 10 años con hiperandrogenemia y signos de masculinización secundarios a un tumor de células de Leydig; otra paciente, en edad fértil, con un tumor carcinoide de ovario asociado a hiperplasia estromal que se manifestó con signos de masa abdominal y de virilización. El tercer caso una mujer, en etapa postmenopáusica con alopecia severa, tenía un tumor de células esteroideas, raro en este grupo etario. onclusión: la evaluación de una mujer con signos y síntomas de virilización debe incluir una detallada historia clínica, examen físico y apropiados dosajes hormonales, especialmente si existe dificultad en establecer su origen cuando los estudios imagenológicos son normales.

  9. Anti-proliferative and pro-apoptotic actions of a novel human and mouse ovarian tumor-associated gene OTAG-12: downregulation, alternative splicing and drug sensitization.

    PubMed

    Chen, X; Zhang, H; Aravindakshan, J P; Gotlieb, W H; Sairam, M R

    2011-06-23

    In studying the age dependence and chronology of ovarian tumors in follicle stimulating hormone receptor knockout mice, we identified a novel ovarian tumor associated gene-12 (OTAG-12), which is progressively downregulated and maps to Chr. 8B3.3. OTAG-12 protein overexpression in mouse ovarian and mammary tumor cells suggested powerful anti-proliferative effects. In human epithelial ovarian cancers (OCs) and OC cell lines, OTAG-12 mRNA expression is downregulated in comparison with normal ovaries. Cloning and identification revealed that human OTAG-12 mapping to gene-rich Chr. 19p13.12 is expressed in three spliced forms: hOTAG-12a, hOTAG-12b and hOTAG-12c, of which b is predominant in the normal ovary. Functionally active hOTAG-12b is a simple protein with no disulfide bonds and a nuclear localization signal is present in all variants. Transfection of OTAG-12 variants in OC and tumorigenic HEK293 cells confirmed nuclear localization. hOTAG-12b overexpression in OC and HEK293 cells effectively suppressed cell growth, anchorage-dependent and independent colony formation followed by apoptosis, whereas hOTAG-12a and hOTAG-12c had no such effects. Deletion mutants identified the critical importance of carboxyl terminus for hOTAG-12b function. Doxycycline-inducible growth inhibition of HEK293 cells by hOTAG-12a was associated with effects on G2 cell cycle arrest and apoptosis induction. hOTAG-12b expression rendered tumorigenic cells more sensitive to four apoptotic stimuli including etoposide-a topoisomerase-II inhibitor. Doxycycline-induced hOTAG-12b expression blocked xenograft tumor growth in nude mice, whereas hOTAG-12a was ineffective. Although p53-pathway-dependent apoptotic agents could upregulate endogenous hOTAG-12b and p53 in UCI-101/107 OC cells, hOTAG-12b could also induce apoptosis in p53-null and platinum-resistant SKOV3 OC cells and Doxycycline-induced hOTAG-12b did not alter p53. Further study showed that hOTAG-12b increases mRNAs of pro-apoptotic genes

  10. [An exceptional mimicker of ovarian tumors: cancer in a pelvic horseshoe kidney].

    PubMed

    Ortiz-Mendoza, Carlos Manuel

    2013-01-01

    Introducción: aunque el riñón en herradura es una anomalía congénita frecuente, hasta el momento no se había informado que produjera un tumor maligno que pareciera una neoplasia de ovario. Caso clínico: mujer de 53 años de edad con un tumor pélvico, que tenía el antecedente de una histerectomía simple debida a miomatosis. Mediante la exploración abdominal se detectó una masa en hipogastrio, edondeada, de 20 cm, firme y fija. En el tacto vaginal, la lesión era palpable a través del fondo de saco. Con el diagnóstico de una probable neoplasia por síndrome de ovario residual, la paciente fue remitida al servicio de ginecología para su estudio y atención. Una tomografía computarizada demostró que la masa se originaba del lado derecho de un riñón pélvico malformado. Por lo anterior, la paciente fue enviada al servicio de oncología quirúrgica, donde se corroboró el hallazgo. Al analizar los estudios de imagen se emitió el diagnóstico de una probable neoplasia de un riñón pélvico en herradura. La paciente fue sometida a una laparotomía exploradora, en la que se extirpó un tumor de 19 cm del riñón malformado, cuyo polo inferior ocupaba la pelvis verdadera. Mediante el examen histopalógico se determinó que se trataba de un carcinoma de células cromófobas. Conclusiones: en las mujeres, los tumores del riñón pélvico en herradura pueden simular un tumor de ovario.

  11. Preclinical evaluation on the tumor suppression efficiency and combination drug effects of fermented wheat germ extract in human ovarian carcinoma cells.

    PubMed

    Wang, Chia-Woei; Wang, Chien-Kai; Chang, Yu-Jia; Choong, Chen-Yen; Lin, Chi-Shian; Tai, Cheng-Jeng; Tai, Chen-Jei

    2015-01-01

    Fermented wheat germ extract (FWGE) is a nutrient supplement and a potential antitumor ingredient for developing an integrated chemotherapy with standard chemotherapeutic drugs for treating ovarian cancer patients. In this study, we evaluated the tumor suppression efficiency of FWGE in human ovarian carcinoma cells, SKOV-3 and ES-2, and found the half-maximal inhibitory concentrations (IC50s) to be 643.76 μg/mL and 246.11 μg/mL after 48 h of FWGE treatment. FWGE treatment also induced programmed cell death by activating the caspase-7 cleavage in both SKOV-3 and ES-2 cells, but only caspase-3 and poly(adenosine diphosphate-ribose) polymerase cleavages were activated in SKOV-3 cells. Moreover, FWGE exhibited combination drug effects with cisplatin and docetaxel in SKOV-3 and ES-2 cells by enhancing the cytotoxicity of both drugs. In conclusion, we found that FWGE not only suppressed cell growth but also induced caspase-3-related and caspase-7-related cell death in human ovarian carcinoma cells. FWGE treatment further enhanced the cytotoxicity of cisplatin and docetaxel, suggesting that FWGE is a potential ingredient in the development of adjuvant chemotherapy with cisplatin or docetaxel for treating ovarian cancer patients.

  12. Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase.

    PubMed

    Yan, Qin; Wang, Fangyuan; Miao, Yi; Wu, Xiaomei; Bai, Mingzhu; Xi, Xiaowei; Feng, Youji

    2016-09-01

    Ovarian cancer is one of the most common cancers which cause female mortality. The knowledge of ovarian cancer initiation and progression is critical to develop new therapeutic strategies to treat and prevent it. Recently, SOX3 has been reported to play a pivotal role in tumor progression. However, the clinical significance of SOX3 in human ovarian cancer remains elusive, and the identity of SOX3 in ovarian cancer initiation, progression, and the related underlying mechanism is unknown. In this study, we showed that SOX3 expression increased from benign and borderline to malignant ovarian tumors. Subsequently, we found that overexpression of SOX3 in EOC cells promoted proliferation, migration, and invasion, while restrained apoptosis and adhesion of ovarian cancer cells. In contrast, silencing of SOX3 gained the opposite results. Finally, we discovered SOX3 targeted Src kinase in EOC cells. These data imply that SOX3, acting as an oncogene in EOC, is not only a crucial factor in the carcinogenesis but also a promising therapeutic target for EOC.

  13. Overcoming platinum resistance in preclinical models of ovarian cancer using the neddylation inhibitor MLN4924.

    PubMed

    Jazaeri, Amir A; Shibata, Etsuko; Park, Jonghoon; Bryant, Jennifer L; Conaway, Mark R; Modesitt, Susan C; Smith, Peter G; Milhollen, Michael A; Berger, Allison J; Dutta, Anindya

    2013-10-01

    The nearly ubiquitous development of chemoresistant disease remains a major obstacle against improving outcomes for patients with ovarian cancer. In this investigation, we evaluated the preclinical activity of MLN4924, an investigational inhibitor of the NEDD8-activating enzyme, in ovarian cancer cells. Efficacy of MLN4924 both alone and in combination with platinum was assessed. Overall, single-agent MLN4924 exhibited moderate activity in ovarian cancer cell lines. However, the combination of MLN4924 with cisplatin or carboplatin produced synergistic effects in SKOV3 and ES2 cells, as well as in primary ovarian cancer cell lines established from high-grade serous, clear cell, and serous borderline ovarian tumors. The efficacy of cisplatin plus MLN4924 was also evident in several in vitro models of platinum-resistant ovarian cancer. Mechanistically, the combination of cisplatin and MLN4924 was not associated with DNA re-replication, altered platinum-DNA adduct formation, abrogation of FANCD2 monoubiquitination, or CHK1 phosphorylation. An siRNA screen was used to investigate the contribution of each member of the cullin RING ligase (CRL) family of E3 ubiquitin ligases, the best-characterized downstream mediators of MLN4924's biologic effects. Cisplatin-induced cytotoxicity was augmented by depletion of CUL3, and antagonized by siCUL1 in both ES2 and SKOV3 ovarian cancer cells. This investigation identifies inhibition of neddylation as a novel mechanism for overcoming platinum resistance in vitro, and provides a strong rationale for clinical investigations of platinum and MLN4924 combinations in ovarian cancer.

  14. Low Grade Serous Ovarian Carcinoma: from the molecular characterization to the best therapeutic strategy.

    PubMed

    Della Pepa, Chiara; Tonini, Giuseppe; Santini, Daniele; Losito, Simona; Pisano, Carmela; Di Napoli, Marilena; Cecere, Sabrina Chiara; Gargiulo, Piera; Pignata, Sandro

    2015-02-01

    Low Grade Serous Ovarian Carcinoma, LGSOC, is certainly a rare disease, accounting for only a small proportion of all ovarian carcinomas, nevertheless in the last decade we have acquired many data about its molecular and clinical features and it has been largely accepted that it has distinct pathogenesis, genetic aberrations and clinical behavior compared to High Grade Serous Ovarian Carcinoma, HGSOC, which is the most common ovarian cancer histotype. A large number of series pointed out the high rate of KRAS and BRAF mutations in LGSOCs and Serous Borderline Tumors, SBLTs, in contrast with their rarity in HGSOC. Such finding, together with the recurrent observation of focus of LGSOC associated with areas of SBLT in the same lesion, led to abandon the traditional histology classification, defining three types of serous carcinomas, in favor of a new dualistic grading system which recognizes only LG and HG carcinomas corresponding to distinct tumorigenesis pathways, the former based on KRAS/BRAF mutations and alteration of the MAP/ERK signaling, the latter characterized by early genetic instability and wild type status of KRAS and BRAF. LGSOC shows favorable overall survival, compared to general ovarian cancer population, but worrying resistance to conventional treatments. MEK inhibitors are emerging as active agents and may well represent an effective therapeutic strategy in the near future.

  15. Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

    ClinicalTrials.gov

    2013-01-15

    Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

  16. Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2014-06-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  17. Sargramostim and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Previous Chemotherapy

    ClinicalTrials.gov

    2014-01-15

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  18. Nuclear Factor-Kappa B Activity in the Host-Tumor Microenvironment of Ovarian Cancer

    DTIC Science & Technology

    2012-08-01

    Thymoquinone, macrophages 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC...from ascites fluid or peritoneal lavages. Quantification of raw NF-B reporter activity indicated that there was a time-dependent increase (Fig 5D...relative proportion of M2 to M1 macrophages changes in response to tumor cells. We would anticipate such an increase, but are currently limited by

  19. Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2017-04-13

    Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Endometrial Undifferentiated Carcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Tumor; Ovarian Seromucinous Carcinoma; Ovarian Serous Tumor; Ovarian Transitional Cell Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  20. Association between individual ovarian dimensions with ovarian reserve indices

    PubMed Central

    Naeini, Elham Hashemian; Neyestanak, Mohammad Zare; Berjis, Katayon; Shokoohi, Mostafa

    2013-01-01

    Introduction: In some young female candidates of assisted reproductive technology (ART), ovarian response to simulative treatments is less than what is expected. More precise assessment of oocyte quality and quantity through studying ovarian dimensions can be useful for determining the dose of ovarian stimulant drugs and for preventing ART cycles cancellation. The aim of the present study is to determine the association between ovarian dimensions and ovarian reserve (OR) indices and whether ovarian dimensions can predict ovarian reserve. Methods: In this cross-sectional study, 85 infertile women were studied. In early follicular phase, ovarian diameters (including length and width of the ovaries) were measured using transvaginal ultrasonography. Mean ovarian diameters (MOD) were calculated according to average length and width of the ovaries. A serum sample was taken from all patients to measure the level of Follicular Stimulating Hormone (FSH) and oestradiol as OR indices. Results: The results of univariate analysis showed that FSH and oestradiol had a negative significant association with width, length and MOD (P < 0.01). The results of multivariate regression analysis showed that FSH and oestradiol had a negative significant association with width (βFSH = -0.59, P = 0.001 and βOestradiol = -0.019, P = 0.029) and MOD (βFSH = -0.52, P = 0.003 and βOestradiol = -0.021, P = 0.017) and had a borderline negative significant correlation with ovarian length (βFSH = -0.49, P=0.077 and βOestradiol = 0.022, P = 0.08) Conclusions: The results of this study revealed that despite a moderate correlation, ovarian diameters could be an applicable index for predicting OR. Using this method along with other methods may be useful in treatment with ovarian stimulants. PMID:26966426

  1. [Borderline personality disorder].

    PubMed

    Sipos, V; Schweiger, U

    2006-02-23

    Characteristics of a borderline personality disorder include emotional instability and a self-threatening lack of impulsive control. As a result, interpersonal relationships are rendered difficult. The central elements of treatment are psychoeducation, self-management, improved stress tolerance and awareness, emotion managment and training in social competence.

  2. Plasma anti-Müllerian hormone as a biomarker for bovine granulosa-theca cell tumors: comparison with immunoreactive inhibin and ovarian steroid concentrations.

    PubMed

    El-Sheikh Ali, Hossam; Kitahara, Go; Nibe, Kazumi; Yamaguchi, Ryoji; Horii, Yoichiro; Zaabel, Samy; Osawa, Takeshi

    2013-11-01

    Granulosa-theca cell tumors (GTCTs) are the most frequently reported ovarian tumors in cattle. Clinically, GTCTs could be confused with other ovarian abnormalities; therefore, the only definitive diagnosis for such tumors is histopathology of a biopsy from the affected ovary. However, this is an invasive technique and unsuitable for farm conditions. As a result, the key aim of this study was to evaluate the diagnostic value of anti-Müllerian hormone (AMH), a glycoprotein hormone that is synthesized exclusively by ovarian granulosa cells, as a sensitive noninvasive biomarker for diagnosing GTCTs in cattle. To achieve this aim, we conducted two experiments. In experiment 1, four clinically healthy Japanese Black cows had blood samples taken daily over one estrous cycle to characterize their AMH profiles throughout the estrous cycle. Additionally, single blood samples were collected from 21 cyclic cows to clarify the physiological range of AMH. In experiment 2, cows with histologically confirmed GTCT (GTCT group, n = 9) and cows affected with cystic ovarian disease (COD group, n = 8) had one blood sample taken before extraction of the tumorous ovary or therapeutic treatment for the COD. Blood samples (n = 105) from cyclic cows (n = 25) in experiment 1 were assigned as a physiologically cyclic group (PC group). Plasma AMH, immunoreactive inhibin (ir-INH), estradiol-17β (E2), testosterone (T), and progesterone (P4) concentrations were assayed in all samples. In experiment 1, the mean plasma AMH concentration was 0.09 ± 0.003 ng/mL and did not show substantial fluctuation throughout the estrous cycle. In experiment 2, plasma AMH, ir-INH, and E2 concentrations were significantly elevated in the GTCT group in comparison with the PC group; among these parameters, only the AMH concentrations were significantly higher in the GTCT group than in the COD group. The area under the receiver operating characteristic curve of AMH for diagnosis of GTCT was 0.99 and was

  3. Metformin Hydrochloride and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-11-28

    Brenner Tumor; Malignant Ascites; Malignant Pleural Effusion; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

  4. HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy

    PubMed Central

    2009-01-01

    Background The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer. Methods HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy. Results Amplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy. Conclusion HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression. PMID:20003286

  5. Phenotypic and functional analysis of tumor-infiltrating lymphocytes compared with tumor-associated lymphocytes from ascitic fluid and peripheral blood lymphocytes in patients with advanced ovarian cancer.

    PubMed

    Santin, A D; Hermonat, P L; Ravaggi, A; Bellone, S; Roman, J J; Smith, C V; Pecorelli, S; Radominska-Pandya, A; Cannon, M J; Parham, G P

    2001-01-01

    To investigate and compare the phenotype and function of lymphocytes collected from patients harboring advanced ovarian cancer, leukocytes from peripheral blood (n = 18), ascitic fluid (n = 13) and tumor tissues (n = 13) were evaluated for the relative proportions of lymphocyte subsets, including CD3+, CD4+, CD8+, CD19+, CD56 and the early (CD25) and late (HLA-DR) activation markers on CD3+ T cells. The ability to synthesize type 1 cytokines (IFN-gamma and IL-2) and a type 2 cytokine (IL-4) was assessed by flow cytometry. In all patients, T cells (CD3+) were the major leukocyte population detected in each tissue, with CD4+ T cells being dominant in peripheral blood lymphocytes (PBL) and tumor-associated lymphocytes (TAL) but not in tumor-infiltrating lymphocytes (TIL) (CD4:CD8 ratios: 3.0 vs. 2.0 vs. 1.0, respectively). CD19+ lymphocytes (B cells) and CD56+ lymphocytes (NK cells) were significantly higher in PBL compared to TAL and TIL (p < 0.05). TAL and TIL had a higher proportion of T cells expressing the late activation marker HLA-DR compared to PBL. In contrast, no significant differences were detected in PBL, TAL and TIL in the expression of the early activation marker CD25. Type 1 cytokines were the dominant type produced by in vitro stimulated T cells for each population, with a greater proportion of IFN-gamma+ T cells in TAL and TIL compared to PBL (p < 0.01), and a higher proportion of IL-2+ T cells in PBL compared with TAL and TIL (p < 0.05). Low percentages of IL-4+ T cells (i.e. Th2) were detected in each tissue. Taken together, these data demonstrate the recruitment and accumulation of high concentrations of antigen-experienced T lymphocytes in TAL and TIL compared to PBL. However, low surface expression of IL-2 receptor (i.e. CD25), as well as depressed intracellular IL-2 production in chronically stimulated TAL and TIL suggests that the impaired antitumor function commonly detected in these lymphocyte populations may be secondary to an acquired

  6. Ovarian Tumor-Stroma Interactions in an In Vivo Orthotopic Model

    DTIC Science & Technology

    2012-08-01

    Tanaka, Y ., et al. 2008. Secreted CXCL1 is a potential mediator and marker of the tumor invasion of bladder cancer. Clin Cancer Res 14:2579-2587.(PMID...pathway, as demonstrated by the low and indirect connectivit t a T be in y in this diagram. These CM1 cells have gone quite far in avoiding apoptosis...GO:0006260 DNA replication 8x10-6 GO:0007076 mitotic chromosome condensation 4x10-7 GO:0006281 DNA repair 0.0002 GO:0030261 chromosome

  7. Leucine-rich alpha-2-glycoprotein-1 is upregulated in sera and tumors of ovarian cancer patients

    PubMed Central

    2010-01-01

    Background New biomarkers that replace or are used in conjunction with the current ovarian cancer diagnostic antigen, CA125, are needed for detection of ovarian cancer in the presurgical setting, as well as for detection of disease recurrence. We previously demonstrated the upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) in the sera of ovarian cancer patients compared to healthy women using quantitative mass spectrometry. Methods LRG1 was quantified by ELISA in serum from two relatively large cohorts of women with ovarian cancer and benign gynecological disease. The expression of LRG1 in ovarian cancer tissues and cell lines was examined by gene microarray, reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, immunocytochemistry and mass spectrometry. Results Mean serum LRG1 was higher in 58 ovarian cancer patients than in 56 healthy women (89.33 ± 77.90 vs. 42.99 ± 9.88 ug/ml; p = 0.0008) and was highest among stage III/IV patients. In a separate set of 193 pre-surgical samples, LRG1 was higher in patients with serous or clear cell ovarian cancer (145.82 ± 65.99 ug/ml) compared to patients with benign gynecological diseases (82.53 ± 76.67 ug/ml, p < 0.0001). CA125 and LRG1 levels were moderately correlated (r = 0.47, p < 0.0001). LRG1 mRNA levels were higher in ovarian cancer tissues and cell lines compared to their normal counterparts when analyzed by gene microarray and RT-PCR. LRG1 protein was detected in ovarian cancer tissue samples and cell lines by immunocytochemistry and Western blotting. Multiple iosforms of LRG1 were observed by Western blot and were shown to represent different glycosylation states by digestion with glycosidase. LRG1 protein was also detected in the conditioned media of ovarian cancer cell culture by ELISA, Western blotting, and mass spectrometry. Conclusions Serum LRG1 was significantly elevated in women with ovarian cancer compared to healthy women and women with benign gynecological disease, and was

  8. Anti-Müllerian hormone inhibits growth of AMH type II receptor-positive human ovarian granulosa cell tumor cells by activating apoptosis.

    PubMed

    Anttonen, Mikko; Färkkilä, Anniina; Tauriala, Hanna; Kauppinen, Marjut; Maclaughlin, David T; Unkila-Kallio, Leila; Bützow, Ralf; Heikinheimo, Markku

    2011-11-01

    Ovarian granulosa cell tumors (GCTs) are sex cord stromal tumors that constitute 3-5% of all ovarian cancers. GCTs usually present with an indolent course but there is a high risk of recurrence, which associates with increased mortality, and targeted treatments would be desirable. Anti-Müllerian hormone (AMH), a key factor regulating sexual differentiation of the reproductive organs, has been implicated as a growth inhibitor in ovarian cancer. GCTs and normal granulosa cells produce AMH, but its expression in large GCTs is usually downregulated. Further, as the lack of specific AMH-signaling pathway components leads to GCT development in mice, we hypothesized that AMH inhibits growth of GCTs. Utilizing a large panel of human GCT tissue samples, we found that AMH type I receptors (ALK2, ALK3 and ALK6) and type II receptor (AMHRII), as well as their downstream effectors Smad1/5, are expressed and active in GCTs. AMHRII expression was detected in the vast majority (96%) of GCTs and correlated with AMH mRNA and protein expression. AMH mRNA level was low in large GCTs, confirming previous findings on low-AMH protein expression in large human as well as mouse GCTs. To study the functional role of AMH in this peculiar ovarian cancer, we utilized a human GCT cell line (KGN) and 10 primary GCT cell cultures. We found that the AMH-Smad1/5-signaling pathway was active in these cells, and that exogenous AMH further activated Smad1/5 in KGN cells. Furthermore, AMH treatment reduced the number of KGN cells and primary GCT cells, with increasing amounts of AMH leading to augmented activation of caspase-3 and subsequent apoptosis. All in all, these data support the premise that AMH is a growth inhibitor of GCTs.

  9. Implications of Proprotein Convertases in Ovarian Cancer Cell Proliferation and Tumor Progression: Insights for PACE4 as a Therapeutic Target1

    PubMed Central

    Longuespée, Rémi; Couture, Frédéric; Levesque, Christine; Kwiatkowska, Anna; Desjardins, Roxane; Gagnon, Sandra; Vergara, Daniele; Maffia, Michelle; Fournier, Isabelle; Salzet, Michel; Day, Robert

    2014-01-01

    Proprotein convertases are a family of kexin-like serine proteases that process proteins at single and multiple basic residues. Among the predicted and identified PC substrates, an increasing number of proteins having functions in cancer progression indicate that PCs may be potential targets for antineoplastic drugs. In support of this notion, we identified PACE4 as a vital PC involved in prostate cancer proliferation and progression, contrasting with the other co-expressed PCs. The aim of the present study was to test the importance of PCs in ovarian cancer cell proliferation and tumor progression. Based on tissue-expression profiles, furin, PACE4, PC5/6 and PC7 all displayed increased expression in primary tumor, ascites cells and metastases. These PCs were also expressed in variable levels in three model ovarian cell lines tested, namely SKOV3, CAOV3 and OVCAR3 cells. Since SKOV3 cells closely represented the PC expression profile of ovarian cancer cells, we chose them to test the effects of PC silencing using stable gene-silencing shRNA strategy to generate knockdown SKOV3 cells for each expressed PC. In vitro and in vivo assays confirmed the role of PACE4 in the sustainment of SKOV3 cell proliferation, which was not observed with the other three PCs. We also tested PACE4 peptide inhibitors on all three cell lines and observed consequent reduced cell proliferation which was correlated with PACE4 expression. Overall, these data support a role of PACE4 in promoting cell proliferation in ovarian cancer and provides further evidence for PACE4 as a potential therapeutic target. PMID:24818756

  10. Are there any more ovarian tumor suppressor genes? A new perspective using ultra high-resolution copy number and loss of heterozygosity analysis.

    PubMed

    Gorringe, Kylie L; Ramakrishna, Manasa; Williams, Louise H; Sridhar, Anita; Boyle, Samantha E; Bearfoot, Jennifer L; Li, Jason; Anglesio, Michael S; Campbell, Ian G

    2009-10-01

    Ovarian cancer is characterized by complex genetic alterations, including copy number loss and copy number-neutral loss of heterozygosity (LOH). These alterations are assumed to represent the "second hit" of the underlying tumor suppressor gene (TSG), however, relative to the number of LOH hotspots reported, few ovarian TSGs have been identified. We conducted a high-resolution LOH analysis using SNP arrays (500K and SNP6.0) of 106 primary ovarian tumors of various histological subtypes together with matching normal DNA. LOH was detected in at least 35% of samples on chromosomes 17, 19p, 22q, Xp, 13q, 8p, 6q, 4q, 5q, 1p, 16q, and 9q with a median minimal region of overlap of only 300 kb. Subtype-specific differences in LOH frequency were noted, particularly for mucinous cases. We also identified 192 somatic homozygous deletions (HDs). Recurrent HDs targeted known TSGs such as CDKN2A (eight samples), RB1 (five samples), and PTEN (three samples). Additional recurrent HDs targeted 16 candidate TSGs near minimal regions of LOH on chromosomes 17, 13, 8p, 5q, and X. Given the importance of HDs in inactivating known genes, these candidates are highly likely to be ovarian TSGs. Our data suggest that the poor success of previous LOH studies was due to the inability of previous technology to resolve complex genomic alterations and distinguish true LOH from allelic imbalance. This study shows that recurrent regions of LOH and HD frequently align with known TSGs suggesting that LOH analysis remains a valid approach to discovering new candidates.

  11. Do We Know What Causes Ovarian Cancer?

    MedlinePlus

    ... stromal tumors of the ovaries. There are many theories about the causes of ovarian cancer. Some of ... hysterectomy lower the risk of ovarian cancer. One theory to explain this is that some cancer-causing ...

  12. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    ClinicalTrials.gov

    2017-02-07

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  13. Clinical Significance of Programmed Death Ligand‑1 and Intra-Tumoral CD8+ T Lymphocytes in Ovarian Carcinosarcoma

    PubMed Central

    Zhu, Jun; Wen, Hao; Ju, Xingzhu; Bi, Rui; Zuo, Wenjia; Wu, Xiaohua

    2017-01-01

    Ovarian carcinosarcoma (OCS) accounts for high mortality and lacks effective therapeutic methods. So far, we lack reliable biomarkers capable of predicting the risk of aggressive course of the disease. Programmed death ligand-1 (PD-L1) is expressed in various tumors, and antibodies targeting its receptor programmed cell death 1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and intratumoral CD8+ T lymphocytes by immunohistochemistry from 19 OCS patients who underwent primary surgery at Fudan University Shanghai Cancer Center. The correlations between PD-L1 expression and CD8+ T lymphocytes as well as the patients’ clinicopathologic characteristics were integrated and statistically analyzed. PD-L1-positive expression was observed in 52.6% of intraepithelial tissues and 47.4% of mesenchymal tissues (p = 0.370). Meanwhile, intraepithelial and mesenchymal CD8+ T lymphocytes were positive in 36.8% and 84.2% of OCS, respectively (p = 0.628). A significantly negative correlation was found between mesenchymal CD8+ T lymphocytes and PD-L1 expression (r = -0.630, p = 0.011). Intraepithelial PD-L1-positive expression was associated only with positive ascitic fluid (p = 0.008). Mesenchymal PD-L1-positive patients had a poorer survival than those with negative expression (p = 0.036). Meanwhile, intraepithelial PD-L1-positive patients had a better survival trend than PD-L1-negative patients, though no statistical significance was found (p = 0.061). There was a better postoperative survival noted in mesenchymal CD8-positive patients (p = 0.024), and allthough a better trend of OS was observed in intraepithelial CD8-positive patients, no statistical significance was found (p = 0.382). Positive tumoral CD8+ T lymphocytes and mesenchymal PD-L1-negative expression seem to be associated with better survival in OCS. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCS. PMID:28125702

  14. Pelvic pain, free fluid in pelvis, and human chorionic gonadotropin serum elevation: recurrence of malignant ovarian germ-cell tumor or early pregnancy?

    PubMed

    Barczyński, B; Rogala, E; Nowicka, A; Nurzyńska-Flak, J; Kotarski, J

    2013-01-01

    Conservative treatment of metastatic germ-cell tumor of the ovary does not exclude the possibility of pregnancy in the future. Serum beta-human chorionic gonadotropin (beta-hCG) serves as pregnancy test, and has also been proven to be a useful marker for ovarian germ-cell tumors. This paper is a case report of a 19-year-old patient who was admitted to a district hospital in emergency due to pelvic pain, amenorrhoea, and free fluid in the pelvis. Laboratory tests demonstrated slight increase in beta-hCG serum concentration and transvaginal ultrasound (TVUS) showed no evidence of gestational sac in the uterus. At the age of 14, the patient was diagnosed with malignant germ-cell tumor of the left ovary in FIGO Stage IV and was treated with four courses of chemotherapy according to TGM-95 protocol with etoposide, ifosfamide, and cisplatin, followed by conservative surgery and adjuvant two courses of cytostatics. The initial diagnosis was recurrence of ovarian malignancy and the patient was referred to an oncology center. Wait-and-see approach and repeated ultrasound examination confirmed a normal intrauterine pregnancy which concluded with the delivery of a healthy newborn through cesarean section.

  15. Ubiquitous induction of resistance to platinum drugs in human ovarian, cervical, germ-cell and lung carcinoma tumor cells overexpressing isoforms 1 and 2 of dihydrodiol dehydrogenase.

    PubMed

    Deng, Hong Bing; Adikari, Mahesha; Parekh, Hemant K; Simpkins, Henry

    2004-10-01

    We have recently demonstrated that overexpression of dihydrodiol dehydrogenase (DDH) in human ovarian carcinoma cells (2008/C13*) is associated with cisplatin and carboplatin resistance. Furthermore, we have also elucidated that transfection of parental human ovarian carcinoma cells with a full-length DDH1 cDNA leads to induction of resistance to the platinum drugs. The development of cisplatin resistance in the transfected cells is associated with an increase in DDH enzyme activity. Previous studies have identified several different mechanisms for development of cisplatin resistance, including altered DNA repair capacity, increased GSH-based detoxification, and increased metallothionein content. However, none of these mechanisms has been found to be universally associated with the development of cisplatin resistance in tumor cells from different tissue sources. The present study was undertaken to assess whether overexpression of DDH1 or DDH2 (in human ovarian, cervical, lung and germ-cell tumor cell lines) could specifically induce resistance to the platinum drugs in these cell lines. We demonstrated a ubiquitous association of increased expression of DDH1 or DDH2 (as judged by increased enzyme activity in transfected clones) with development of resistance to cisplatin and carboplatin. Moreover, we also found a lack of cross-resistance to anticancer drugs that have a different mode of action including paclitaxel, vincristine, doxorubicin hydrochloride, and melphalan. Although at present it is not clear how DDH is involved in platinum drug resistance, the identification of this gene as a causal factor in a series of cell lines derived from different tumors with different intracellular compositions indicates the importance of deciphering this hitherto undefined pathway which can produce resistance to platinum drugs.

  16. Repeatability of quantitative FDG-PET/CT and contrast enhanced CT in recurrent ovarian carcinoma: test retest measurements for tumor FDG uptake, diameter and volume

    PubMed Central

    Rockall, Andrea G.; Avril, Norbert; Lam, Raymond; Iannone, Robert; Mozley, P. David; Parkinson, Christine; Bergstrom, Donald; Sala, Evis; Sarker, Shah-Jalal; McNeish, Iain A.; Brenton, James D.

    2014-01-01

    Purpose Repeatability of baseline FDG-PET/CT measurements has not been tested in ovarian cancer. This dual-center, prospective study assessed variation in tumor FDG uptake, tumor diameter (TD) and tumor volume (TV) from sequential FDG-PET/CT and contrast-enhanced CT (CECT) in patients with recurrent platinum-sensitive ovarian cancer. Methods Patients underwent two pre-treatment baseline FDG-PET/CT (n=21) and CECT (n=20) at 2 clinical sites with different PET/CT instruments. Patients were included if they had at least one target lesion (TL) in the abdomen with an SUV maximum (SUVmax) of ≥2.5 and a long axis diameter of ≥15mm. Two independent reading methods were used to evaluate repeatability of TD and SUV uptake: on site and at an imaging clinical research organization (CRO). TV reads were only performed by CRO. In each reading set, TLs were independently measured on sequential imaging. Results Median time between FDG-PET/CT was 2 days (range 1-7). For site reads, concordance correlation coefficient (CCC) for SUVmean, SUVmax and TD were 0.95, 0.94 and 0.99 respectively. Repeatability coefficients were 16.3%, 17.3% and 8.8% for SUVmean, SUVmax and TD respectively. Similar results were observed for CRO reads. TV CCC was 0.99 with a repeatability coefficient of 28.1%. Conclusions There was excellent test/retest repeatability for FDG-PET/CT quantitative measurements across two sites and two independent reading methods. Cut-off values for determining change in SUVmean, SUVmax and TV establish limits to determine metabolic and/or volumetric response to treatment in platinum-sensitive relapsed ovarian cancer. PMID:24573555

  17. Dietary influences on survival after ovarian cancer.

    PubMed

    Nagle, Christina M; Purdie, David M; Webb, Penelope M; Green, Adèle; Harvey, Philip W; Bain, Christopher J

    2003-08-20

    We evaluated the effects of various food groups and micronutrients in the diet on survival among women who originally participated in a population-based case-control study of ovarian cancer conducted across 3 Australian states between 1990 and 1993. This analysis included 609 women with invasive epithelial ovarian cancer, primarily because there was negligible mortality in women with borderline tumors. The women's usual diet was assessed using a validated food frequency questionnaire. Deaths in the cohort were identified using state-based cancer registries and the Australian National Death Index (NDI). Crude 5-year survival probabilities were estimated using the Kaplan-Meier technique, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression models. After adjusting for important confounding factors, a survival advantage was observed for those who reported higher intake of vegetables in general (HR = 0.75, 95% CI = 0.57-0.99, p-value trend 0.01 for the highest third, compared to the lowest third), and cruciferous vegetables in particular (HR = 0.75, 95% CI = 0.57-0.98, p-value trend 0.03), and among women in the upper third of intake of vitamin E (HR = 0.76, 95% CI = 0.58-1.01, p-value trend 0.04). Inverse associations were also seen with protein (p-value trend 0.09), red meat (p-value trend 0.06) and white meat (p-value trend 0.07), and modest positive trends (maximum 30% excess) with lactose (p-value trend 0.04), calcium and dairy products. Although much remains to be learned about the influence of nutritional factors after a diagnosis of ovarian cancer, our study suggests the possibility that a diet high in vegetable intake may help improve survival.

  18. Complement component 7 (C7), a potential tumor suppressor, is correlated with tumor progression and prognosis

    PubMed Central

    Pan, Xiaodan; Chen, Kaiyan; Zhang, Nan; Jin, Jiaoyue; Wu, Junzhou; Feng, Jianguo; Yu, Herbert; Jin, Hongchuan; Su, Dan

    2016-01-01

    Our previous study found copy number variation of chromosome fragment 5p13.1-13.3 might involve in the progression of ovarian cancer. In the current study, the alteration was validated and complement component 7 (C7), located on 5p13.1, was identified. To further explore the clinical value of C7 in tumors, 156 malignant, 22 borderline, 33 benign and 24 normal ovarian tissues, as well as 173 non-small cell lung cancer (NSCLC) tissues along with corresponding adjacent and normal tissues from the tissue bank of Zhejiang Cancer Hospital were collected. The expression of C7 was analyzed using reverse transcriptase quantitative polymerase chain reaction. As a result, the C7 expression displayed a gradual downward trend in normal, benign, borderline and malignant ovarian tissues, and the decreased expression of C7 was correlative to poor differentiation in patients with ovarian cancer. Interestingly, a similar change of expression of C7 was found in normal, adjacent and malignant tissues in patients with NSCLC, and low expression of C7 was associated with worse grade and advanced clinical stage. Both results from this cohort and the public database indicated that NSCLC patients with low expression of C7 had a worse outcome. Furthermore, multivariate cox regression analysis showed NSCLC patients with low C7 had a 3.09 or 5.65-fold higher risk for relapse or death than those with high C7 respectively, suggesting C7 was an independent prognostic predictor for prognoses of patients with NSCLC. Additionally, overexpression of C7 inhibited colony formation of NSCLC cells, which hints C7 might be a potential tumor suppressor. PMID:27852032

  19. Identification and Functional Characterization of Somatic Mutations in Human MicroRNAs and their Responsive Elements in Target Genes in Ovarian Tumor Tissues

    DTIC Science & Technology

    2009-05-01

    sequenced 50 microRNAs in 75 OC tumor tissues . So far, seven novel somatic mutations were observed in seven primary or precursor miRNA genes. WE...f miRNA m ay be a hallmark of h uman cancers . M iRNA m isexpression m ight be due t o genetic mutations i n miRNA ge nes an d t heir responsive...15. SUBJECT TERMS microRNA ovarian cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF

  20. Synergistic suppression effect on tumor growth of ovarian cancer by combining cisplatin with a manganese superoxide dismutase-armed oncolytic adenovirus

    PubMed Central

    Wang, Shibing; Shu, Jing; Chen, Li; Chen, Xiaopan; Zhao, Jianhong; Li, Shuangshuang; Mou, Xiaozhou; Tong, Xiangmin

    2016-01-01

    Gene therapy on the basis of oncolytic adenovirus is a novel approach for human cancer therapeutics. We aim to investigate whether it will synergistically reinforce their antiovarian cancer activities when the combined use of ZD55-manganese superoxide dismutase (MnSOD) and cisplatin was performed. The experiments in vitro showed that ZD55-MnSOD enhances cisplatin-induced apoptosis and causes remarkable ovarian cancer cell death. Apoptosis induction by treatment with ZD55-MnSOD and/or cisplatin was detected in SKOV-3 by apoptotic cell staining, flow cytometry, and western blot analysis. In addition, the cytotoxicity caused by ZD55-MnSOD to normal cells was examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and western blot analysis. Animal experiment further confirmed that combination of ZD55-MnSOD and cisplatin achieved significant inhibition of SKOV-3 ovarian tumor xenografted growth. In summary, we have demonstrated that ZD55-MnSOD can sensitize human ovarian cancer cells to cisplatin-induced cell death and apoptosis in vitro and in vivo. These findings indicate that the combined treatment with ZD55-MnSOD and cisplatin could represent a rational approach for antiovarian cancer therapy. PMID:27799786

  1. Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-12-21

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  2. Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma

    PubMed Central

    Arakawa, Noriaki; Kobayashi, Hiroshi; Yonemoto, Naohiro; Masuishi, Yusuke; Ino, Yoko; Shigetomi, Hiroshi; Furukawa, Naoto; Ohtake, Norihisa; Miyagi, Yohei; Hirahara, Fumiki; Hirano, Hisashi; Miyagi, Etsuko

    2016-01-01

    Background There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. Methods Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. Results The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. Conclusions TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC. PMID:27798689

  3. Ovarian Cancer

    MedlinePlus

    ... deaths than other female reproductive cancers. The sooner ovarian cancer is found and treated, the better your chance for recovery. But ovarian cancer is hard to detect early. Women with ovarian ...

  4. Origin and molecular pathogenesis of ovarian high-grade serous carcinoma.

    PubMed

    Kurman, R J

    2013-12-01

    A new paradigm for the pathogenesis of ovarian cancer has recently been proposed which helps to explain persistent problems in describing the development and diverse morphology of these neoplasms. The paradigm incorporates recent advances in our understanding of the molecular pathogenesis of epithelial 'ovarian' cancer with new insights into the origin of these tumors. Correlated clinicopathologic and molecular genetic studies led to the development of a dualistic model that divides all the various histologic types of epithelial ovarian carcinomas into two broad categories designated 'type I' and 'type II'. The prototypic type I tumor is low-grade serous carcinoma and the prototypic type II tumor is high-grade serous carcinomas (HGSCs). As the serous tumors comprise ∼70% of all epithelial ovarian tumors and account for the majority of deaths, the serous tumors will be the subject of this review. There are marked differences between the low-grade and high-grade serous tumors. Briefly, the former are indolent, present in stage I (tumor confined to the ovary) and develop from well-established precursors, so-called 'atypical proliferative (borderline) tumors,' which are characterized by specific mutations, including KRAS, BRAF and ERBB2; they are relatively genetically stable. In contrast, HGSCs are aggressive, present in the advanced stage, and develop from intraepithelial carcinomas in the fallopian tube. They harbor TP53 mutations in over 95% of cases, but rarely harbor the mutations detected in the low-grade serous tumors. At the time of diagnosis they demonstrate marked chromosomal aberrations but over the course of the disease these changes remain relatively stable. Along with the recent advances in understanding the molecular pathogenesis of these tumors, studies have demonstrated that the long sought for precursor of ovarian HGSC appears to develop from an occult intraepithelial carcinoma in the fimbrial region of the fallopian tube designated 'serous tubal

  5. Chromosome X loci and spontaneous granulosa cell tumor development in SWR mice: epigenetics and epistasis at work for an ovarian phenotype.

    PubMed

    Dorward, Ann M; Yaskowiak, Edward S; Smith, Kerri N; Stanford, Kaitlyn R; Shultz, Kathryn L; Beamer, Wesley G

    2013-02-01

    Females of the SWR/Bm (SWR) inbred mouse strain possess a unique susceptibility to juvenile-onset tumors originating from the granulosa cells (GC) of the ovarian follicles. Tumor susceptibility is an inherited, polygenic trait in SWR females, minimally involving an oncogenic Granulosa cell tumor susceptibility (Gct) locus on chromosome (Chr) 4 (Gct1), and two GC tumor susceptibility modifier genes mapped to distinct regions of Chr X (Gct4 and Gct6). Shifts in the frequency of GC tumor initiation in the SWR female population from low penetrance to moderate penetrance, or phenotype switching between GC tumor-susceptible and GC tumor-resistant, is strongly influenced by the allelic contributions at Gct4 and Gct6. In addition to the allele-specific effects, GC tumor susceptibility is controlled by the mode of X-linked transmission with a dominant, paternal parent-of-origin effect. We took advantage of the robust paternal effect with a recombinant male progeny testing strategy to resolve the Gct4 locus interval to 1.345 million base (Mb) pairs. Based on the mapping resolution and the phenotype sensitivity to endogenous and exogenous androgen exposure, a promising candidate for Gct4 identity is the androgen receptor (Ar) gene. We explored the mechanism of allelic variation for Ar between SWR (low penetrance allele) and SJL/Bm (SJL) (moderate penetrance allele) using an SWR.SJL-X congenic strain resource and a quantitative gene expression method. We report the low GC tumor penetrance allele of the SWR strain correlates with significantly reduced Ar transcript levels in the female ovary at the pubertal transition.

  6. [Whose borderline is it? Hypothesized etiologies of borderline personality].

    PubMed

    Gil, Tsvi E

    2008-11-01

    Borderline personality is a well known concept in psychiatric literature, however, not fully understood as to its very nature. This article presents a short review of hypothesized etiologies of the borderline personality, starting with so called traditional theories, namely, borderline personality as a consolidated personality organization, in which the patient pathologically deals with his or her inner aggression, or with an enduring developmental failure. More modern hypotheses focus on possible childhood sexual abuse as the origin of the borderline, viewing the adult personality as a chronic, unresolved, post-traumatic disorder. Additionally, a neuro-epigenetic view hypothesized that a unique congenital neurological structure interacts with consequential events in early childhood to create the borderline personality.

  7. Pathogenesis and the role of ARID1A mutation in endometriosis-related ovarian neoplasms

    PubMed Central

    Maeda, Daichi; Shih, Ie-Ming

    2012-01-01

    Endometriosis-related ovarian neoplasms (ERONs) are a unique group of tumors as they are associated with endometriosis, especially endometriosis presenting as an ovarian endometriotic cyst (endometrioma). ERONs include clear cell carcinoma, endometrioid carcinoma, and seromucinous borderline tumor. A growing body of evidence from both clinicopathological and molecular studies suggests that most, if not all, ERONs develop from endometriotic cyst epithelium through different stages of tumor progression. The endometriotic cyst contains abundant iron-induced reactive oxygen species which are thought to be mutagenic, and chronic exposure of cystic epithelium to this microenvironment facilitates the accumulation of somatic mutations that ultimately result in tumor development. Molecular analyses of ERONs, including genome-wide screens, have identified several molecular genetic alterations that lead to aberrant activation or inactivation of pathways involving ARID1A, PI3K, Wnt, and PP2A. Among all molecular genetic changes identified to date, inactivating mutations of the ARID1A tumor suppressor gene are the most common in ERON. Understanding the molecular changes and pathogenesis involved in the development of ERON is fundamental for future translational studies aimed at designing new diagnostic tests for early detection and identifying critical molecular features for targeted therapeutics. PMID:23232571

  8. The four and a half LIM domains 2 (FHL2) regulates ovarian granulosa cell tumor progression via controlling AKT1 transcription

    PubMed Central

    Hua, G; He, C; Lv, X; Fan, L; Wang, C; Remmenga, S W; Rodabaugh, K J; Yang, L; Lele, S M; Yang, P; Karpf, A R; Davis, J S; Wang, C

    2016-01-01

    The four and a half LIM domains 2 (FHL2) has been shown to play important roles in the regulation of cell proliferation, survival, adhesion, motility and signal transduction in a cell type and tissue-dependent manner. However, the function of FHL2 in ovarian physiology and pathology is unclear. The aim of this study was to determine the role and functional mechanism of FHL2 in the progression of ovarian granulosa cell tumors (GCTs). Immunohistochemical analysis indicated that FHL2 was overexpressed in GCT tissues. Cellular localization of FHL2 in GCT cells was cell cycle dependent. Knockdown of FHL2 suppressed GCT cell growth, reduced cell viability and inhibited cell migration. Consistently, ectopic expression of FHL2 in GCT cells with very low endogenous FHL2 promoted cell growth, improved cell viability and enhance cell migration. Importantly, overexpression of FHL2 promoted GCT progression in vivo. Mechanistic studies indicated that FHL2 regulates AKT1 gene expression in vitro and in vivo. Knockdown of FHL2 or AKT1 in GCT cell lines induced very similar phenotypes. Ectopic expression of constitutively active AKT1 rescued FHL2 knockdown-induced arrest of GCT cell growth and reduction of GCT cell viability, suggesting that FHL2 regulates GCT cell growth and viability through controlling AKT1 expression. Finally, co-immunoprecipitation and chromatin immunoprecipitation analyses indicated that FHL2 functions as a co-activator of NFκB and AP-1 to regulate AKT1 gene transcription. In conclusion, results from the present study indicate that FHL2 exerts its oncogenic action in GCT cells via controlling AKT1 gene expression. FHL2 is a promising target for the development of novel drugs against ovarian granulosa cell tumor. PMID:27415427

  9. Novel BRCA1 and BRCA2 Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas

    PubMed Central

    Weren, Robbert D.A.; Mensenkamp, Arjen R.; Simons, Michiel; Eijkelenboom, Astrid; Sie, Aisha S.; Ouchene, Hicham; van Asseldonk, Monique; Gomez‐Garcia, Encarna B.; Blok, Marinus J.; de Hullu, Joanne A.; Nelen, Marcel R.; Hoischen, Alexander; Bulten, Johan; Tops, Bastiaan B.J.; Hoogerbrugge, Nicoline

    2016-01-01

    ABSTRACT With the recent introduction of Poly(ADP‐ribose) polymerase inhibitors, a promising novel therapy has become available for ovarian carcinoma (OC) patients with inactivating BRCA1 or BRCA2 mutations in their tumor. To select patients who may benefit from these treatments, assessment of the mutation status of BRCA1 and BRCA2 in the tumor is required. For reliable evaluation of germline and somatic mutations in these genes in DNA derived from formalin‐fixed, paraffin‐embedded (FFPE) tissue, we have developed a single‐molecule molecular inversion probe (smMIP)‐based targeted next‐generation sequencing (NGS) approach. Our smMIP‐based NGS approach provides analysis of both strands of the open reading frame of BRCA1 and BRCA2, enabling the discrimination between real variants and formalin‐induced artefacts. The single molecule tag enables compilation of unique reads leading to a high analytical sensitivity and enabling assessment of the reliability of mutation‐negative results. Multiplex ligation‐dependent probe amplification (MLPA) and Methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) were used to detect exon deletions of BRCA1 and methylation of the BRCA1 promoter, respectively. Here, we show that this combined approach allows the rapid and reliable detection of both germline and somatic aberrations affecting BRCA1 and BRCA2 in DNA derived from FFPE OCs, enabling improved hereditary cancer risk assessment and clinical treatment of ovarian cancer patients. PMID:27767231

  10. Combined nonlinear laser imaging (two-photon excitation fluorescence, second and third-harmonic generation, and fluorescence lifetime imaging microscopies) in ovarian tumors

    NASA Astrophysics Data System (ADS)

    Adur, J.; Pelegati, V. B.; de Thomaz, A. A.; Bottcher-Luiz, F.; Andrade, L. A. L. A.; Almeida, D. B.; Carvalho, H. F.; Cesar, C. L.

    2012-03-01

    We applied Two-photon Excited Fluorescence (TPEF), Second/Third Harmonic Generation (SHG and THG) and Fluorescence Lifetime Imaging (FLIM) Non Linear Optics (NLO) Laser-Scanning Microscopy within the same imaging platform to evaluate their use as a diagnostic tool in ovarian tumors. We assess of applicability of this multimodal approach to perform a pathological evaluation of serous and mucinous tumors in human samples. The combination of TPEF-SHG-THG imaging provided complementary information about the interface epithelium/stromal, such as the transformation of epithelium surface (THG) and the overall fibrillar tissue architecture (SHG). The fact that H&E staining is the standard method used in clinical pathology and that the stored samples are usually fixed makes it important a re-evaluation of these samples with NLO microscopy to compare new results with a library of already existing samples. FLIM, however, depends on the chemical environment around the fluorophors that was completely changed after fixation; therefore it only makes sense in unstained samples. Our FLIM results in unstained samples demonstrate that it is possible to discriminate healthy epithelia from serous or mucinous epithelia. Qualitative and quantitative analysis of the different imaging modalities used showed that multimodal nonlinear microscopy has the potential to differentiate between cancerous and healthy ovarian tissue.

  11. YKL-40 in Serum Samples From Patients With Newly Diagnosed Stage III-IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer Receiving Chemotherapy

    ClinicalTrials.gov

    2016-02-19

    Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Mixed Epithelial Tumor; Malignant Ovarian Mucinous Tumor; Malignant Ovarian Neoplasm; Malignant Ovarian Serous Tumor; Malignant Ovarian Transitional Cell Tumor; Ovarian Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  12. Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-04-13

    Clear Cell Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Mucinous Adenocarcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  13. K-ras activation occurs frequently in mucinous adenocarcinomas and rarely in other common epithelial tumors of the human ovary.

    PubMed Central

    Enomoto, T.; Weghorst, C. M.; Inoue, M.; Tanizawa, O.; Rice, J. M.

    1991-01-01

    To explore the role of mutational activation of members of the ras family of cellular protooncogenes in the development of human ovarian neoplasms, a series of 37 ovarian tumors from Japanese patients was studied. These included 30 common epithelial tumors (1 mucinous tumor of borderline malignancy, 7 mucinous adenocarcinomas, and 22 nonmucinous carcinomas: 10 serous, 3 clear cell, 8 endometrioid, and 1 undifferentiated), 5 tumors of germ cell origin, and 2 sex cord/stromal cell tumors. Polymerase chain reaction was performed from selected areas of deparaffinized sections of formalin-fixed paraffin-embedded tissue, and the presence of activating point mutations in codons 12, 13, and 61 of the H-, N-, and K-ras genes was probed by dot-blot hybridization analysis with mutation specific oligonucleotides. Mutations in K-ras were also looked for by direct genomic sequencing. The overall frequency of ras gene mutations was 10/37 (27%). Mutations were detected only in K-ras, and were found in most of the mucinous tumors, including the one such tumor of borderline malignancy (6/8; 75%). In one mucinous adenocarcinoma, two mutations were detected in paraffin-embedded material that had not previously been found in high molecular weight DNA isolated from frozen tissue from the same case. K-ras mutations occurred significantly more frequently in mucinous tumors (6/8, 75%) than in serous carcinomas (2/10, 20%; P = 0.031) or in all nonmucinous types of epithelial ovarian tumors combined (3/22, 14%; P = 0.0031). Images Figure 1 Figure 2 PMID:1656759

  14. Study of ovarian cancer management.

    PubMed

    Gaughan, E; Javaid, T; Cooley, S; Byrne, P; Gaughan, G

    2006-10-01

    Ovarian cancer is the most lethal gynecological malignancy. Many patients present at an advanced stage as the symptoms of early stage disease can be vague. AIM We evaluated the demographics, treatment regimens and survival rates of ovarian cancer patients attending Beaumont Hospital Dublin over a nine year period. A retrospective chart review of ovarian cancer patients attending Beaumont Hospital between 11/10/94 and 30/6/3 was performed. Patients were selected from pathology records. Patients with borderline histology and those who died of unrelated causes were excluded. 31% of individuals presented with distension as their only clinical sign. 20% presented with a mass as their only clinical sign. The most common cell type was papillary serous adenocarcinoma in two thirds of cases. 54% presented with advanced disease [stage IIl-IV]. Treatment involved surgical clearance or debulking +/- chemotherapy. 5 year survival for Stage I was 95% versus 19% for Stage IlI. This highlights the importance of early diagnosis.

  15. Ovarian Carcinoma: Quantitative Biexponential MR Imaging Relaxometry Reveals the Dynamic Recruitment of Ferritin-expressing Fibroblasts to the Angiogenic Rim of Tumors

    PubMed Central

    Vandsburger, Moriel H.; Radoul, Marina; Addadi, Yoseph; Mpofu, Senzeni; Cohen, Batya; Eilam, Raya

    2013-01-01

    Purpose: To quantitatively monitor the dynamic perivascular recruitment of ferritin heavy chain (FHC)–overexpressing fibroblasts to ovarian carcinoma xenografts by using R2 mapping and biexponential magnetic resonance (MR) relaxometry. Materials and Methods: In vivo studies of female mice were approved by the institutional animal care and use committee. In vitro analysis included MR-based R2 relaxation measurements of monkey kidney cell line (CV1) fibroblasts that overexpress FHC, followed by inductively coupled plasma mass spectrometry to assess cellular iron content. For in vivo analysis, CV1-FHC fibroblasts were either mixed with fluorescent human ovarian carcinoma cells before subcutaneous implantation (coinjection) or injected intraperitoneally 4 days after the cancer cells were injected (remote recruitment). Dynamic changes in tumor R2 were used to derive CV1-FHC cell fraction in both models. In coinjection tumors, dynamic contrast material–enhanced MR imaging was used to measure tumor fractional blood volume. Whole-body fluorescence imaging and immunohistochemical staining were performed to validate MR results. One-way repeated measures analysis of variance was used to assess MR and fluorescence imaging results and tumor volume, and one-way analysis of variance was used to assess spectrometric results, fractional blood volume, and immunohistochemical evaluation. Results: CV1-FHC fibroblasts (vs CV1 fibroblasts) showed enhanced iron uptake (1.8 mmol ± 0.5 × 10−8 vs 0.9 mmol ± 0.5 × 10−8; P < .05), retention (1.6 mmol ± 0.5 × 10−8 vs 0.5 mmol ± 0.5 × 10−8, P < .05), and cell density–dependent R2 contrast. R2 mapping in vivo revealed preferential recruitment of CV1-FHC cells to the tumor rim in both models. Measurement of fractional blood volume was similar in all tumors (2.6 AU ± 0.5 × 10−3 for CV1, 2.3 AU ± 0.3 × 10−3 for CV1-FHC, 2.9 ± 0.3 × 10−3 for CV1-FHC-ferric citrate). Dynamic changes in CV1-FHC cell fraction

  16. Ovarian teratoma and endometritis in a mare

    PubMed Central

    2005-01-01

    Abstract An 8-year-old Arabian mare was admitted for a large ovarian anovulatory follicle. A clinical diagnosis of ovarian tumor and endometritis was established. Histological examinations revealed an ovarian teratoma and a grade II endometritis. Three months after unilateral ovariectomy, the mare was confirmed pregnant and eventually gave birth uneventfully. PMID:16363331

  17. Development of Mouse Models of Ovarian Cancer for Studying Tumor Biology and Testing Novel Molecularly Targeted Therapeutic Strategies

    DTIC Science & Technology

    2011-09-01

    canonical Wnt (i.e., Wnt/b-catenin/Tcf) and PI3K/Akt/mTOR signaling pathways often occur together in human ovarian endome - trioid adenocarcinoma (OEA...results as a single agent for patients with recurrent endome - trioid adenocarcinomas of the endometrium (38), which like OEAs, have frequent mutations that

  18. Development of Mouse Models of Ovarian Cancer for Studying Tumor Biology and Testing Novel Molecularly Targeted Therapeutic Strategies

    DTIC Science & Technology

    2011-09-01

    pathways often occur together in human ovarian endome - 74 trioid adenocarcinoma (OEA; refs. 7, 8). Given substantial 75 overlap in the molecular...756 mTOR inhibitor, everolimus, has shown encouraging 757 results as a single agent for patients with recurrent endome - 758 trioid adenocarcinomas of

  19. Modulators of Response to Tumor Necrosis-Factor-Related Apoptosis Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

    DTIC Science & Technology

    2010-04-01

    antibody, MORAb-003. Methods: FRα expression was examined in ovarian cell lines (SKOV3ip1, IGROV, HeyA8, A2780-par, and HIO -180) with fluorescence...IGROVand SKOV3ip1 cell lines both expressed high levels of FRα compared with the non-transformed ( HIO -180) cells. HeyA8 and A2780-par cell lines lacked

  20. Regulation of Leukocyte Infiltration into Ovarian Cancer by Tumor-Stroma Interactions, a Microarray View of Cancer Microenvironment

    DTIC Science & Technology

    2007-03-01

    Mesenchymal Transition of the cancer cells (shRNA-mediated E-Cadherin knock down) attenuates the co- culture reaction, suggesting a mechanism for cancer cell ... transition , while boosting migratory features in the epithelial cells , also turns these cells into stealth cells , in terms of the co- culture reaction... cells from ovarian cancer tissue, in response to epithelial -fibroblast co- culture medium:

  1. Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer.

    PubMed

    Matsuzaki, Junko; Gnjatic, Sacha; Mhawech-Fauceglia, Paulette; Beck, Amy; Miller, Austin; Tsuji, Takemasa; Eppolito, Cheryl; Qian, Feng; Lele, Shashikant; Shrikant, Protul; Old, Lloyd J; Odunsi, Kunle

    2010-04-27

    NY-ESO-1 is a "cancer-testis" antigen frequently expressed in epithelial ovarian cancer (EOC) and is among the most immunogenic tumor antigens defined to date. In an effort to understand in vivo tolerance mechanisms, we assessed the phenotype and function of NY-ESO-1-specific CD8(+) T cells derived from peripheral blood lymphocytes (PBLs), tumor-infiltrating lymphocytes (TILs), and tumor-associated lymphocytes (TALs) of EOC patients with NY-ESO-1-expressing tumors, with or without humoral immunity to NY-ESO-1. Whereas NY-ESO-1-specific CD8(+) T cells were readily detectable ex vivo with tetramers in TILs and TALs of seropositive patients, they were only detectable in PBLs following in vitro stimulation. Compared with PBLs, tumor-derived NY-ESO-1-specific CD8(+) T cells demonstrated impaired effector function, preferential usage of dominant T-cell receptor, and enriched coexpression of inhibitory molecules LAG-3 and PD-1. Expression of LAG-3 and PD-1 on CD8(+) T cells was up-regulated by IL-10, IL-6 (cytokines found in tumor ascites), and tumor-derived antigen-presenting cells. Functionally, CD8(+)LAG-3(+)PD-1(+) T cells were more impaired in IFN-gamma/TNF-alpha production compared with LAG-3(+)PD-1(-) or LAG-3(-)PD-1(-) subsets. Dual blockade of LAG-3 and PD-1 during T-cell priming efficiently augmented proliferation and cytokine production by NY-ESO-1-specific CD8(+) T cells, indicating that antitumor function of NY-ESO-1-specific CD8(+) T cells could potentially be improved by therapeutic targeting of these inhibitory receptors.

  2. Carboplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor VX-970 in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-01-31

    High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  3. Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer

    PubMed Central

    Mir, Rashid; Gandhi, Gauri; Ray, Prakash Chandra

    2016-01-01

    MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan—Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC. PMID:27092777

  4. Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer.

    PubMed

    Zuberi, Mariyam; Khan, Imran; Mir, Rashid; Gandhi, Gauri; Ray, Prakash Chandra; Saxena, Alpana

    2016-01-01

    MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan-Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

  5. Prescribing and borderline personality disorder

    PubMed Central

    Chanen, Andrew M; Thompson, Katherine N

    2016-01-01

    Summary Accurate diagnosis is fundamental to effective management of borderline personality disorder, but many patients remain undetected. The first-line management for borderline personality disorder is psychosocial treatment, not drugs. There are major prescribing hazards including polypharmacy, overdose and misuse. Drug treatment might be warranted for patients who have a co-occurring mental disorder such as major depression. If a drug is prescribed for borderline personality disorder, it should only be as an adjunct to psychosocial treatment. There should be clear and collaborative goals that are regularly reviewed with the patient. Use single drugs prescribed in limited quantities for a limited time. Stop drugs that are ineffective. PMID:27340322

  6. Olaparib and Cediranib Maleate in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-01-31

    BRCA1 Gene Mutation; BRCA2 Gene Mutation; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

  7. Invasion patterns in stage I endometrioid and mucinous ovarian carcinomas: a clinicopathologic analysis emphasizing favorable outcomes in carcinomas without destructive stromal invasion and the occasional malignant course of carcinomas with limited destructive stromal invasion.

    PubMed

    Chen, Shirley; Leitao, Mario M; Tornos, Carmen; Soslow, Robert A

    2005-07-01

    Stage I, low-grade endometrioid and mucinous ovarian carcinomas have an excellent prognosis. Published data have suggested that destructive stromal invasion, a relatively uncommon finding in these tumors, is a poor prognostic factor. We investigated this by studying all FIGO stage I, grades 1 and 2 (of 3) endometrioid and mucinous ovarian carcinomas that were surgically staged at the Memorial Sloan-Kettering Cancer Center from 1980 to 2000. We undertook a careful review of all available slides using current diagnostic criteria and correlated histopathologic indices with clinical outcome data. Cases studied included 13 endometrioid ovarian carcinomas (stage IA, eight; stage IC, five) and six intestinal mucinous ovarian carcinomas (stage IA, three; stage IC, three). All of the tumors contained areas of expansile invasion, greater than that acceptable for microinvasion, and were thus diagnosed as carcinomas instead of borderline tumors. Nevertheless, nearly all demonstrated borderline tumor (noninvasive) components. Six tumors contained at least one focus of destructive stromal invasion (two endometrioid and four mucinous ovarian carcinomas). Four additional cases showed a focus suspicious for but not diagnostic of destructive invasion ('indeterminate for destructive invasion') (two endometrioid and two mucinous ovarian carcinomas). Follow-up data were available for 17 patients. The median follow-up was 81 months (range, 9-161 months). In all, 14 patients were alive with no evidence of disease (expansile invasion alone, eight; destructive stromal invasion, four; and indeterminate for destructive invasion, two). Three patients died of their disease (destructive stromal invasion, two; and indeterminate for destructive invasion, one). The size, number, and nuclear grade of destructive stromal invasion foci did not appear to have an impact on survival in this relatively limited number of patients. Outcome data in patients with stage I, low-grade endometrioid and mucinous

  8. The basics of CAR T design and challenges in immunotherapy of solid tumors - ovarian cancer as a model.

    PubMed

    Xu, Xuequn; Qiu, Jin; Sun, Yi

    2017-03-08

    Chimeric antigen receptor T cells are T cells genetically engineered with CAR constructs which mainly contain scFV and TCR zeta chain. With promising development in blood cancers, CAR T trials are also applied in solid cancers. However, the treatment effect in solid cancers is lower than expected. This review summarizes difference of CAR T applications in solid and blood cancers. Future challenges of CAR T cell treatment in solid cancer are also discussed using ovarian cancer as an example.

  9. Suppression of Chromosome Instability (CIN) to Enhance Chemosensitivity of Ovarian Tumor Cells by Modulating the Aurora B Pathway at Kinetochores

    DTIC Science & Technology

    2013-02-01

    Cancer Research Philadelphia, PA 19111 REPORT DATE: (Enter month and year, i.e., January 2001) TYPE OF REPORT: Revised Annual (Enter type of report...UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT Institute for Cancer Research 333 Cottman Avenue...TELEPHONE NUMBER Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 USAMRMC UU UUU Aneuploidy is a hallmark of virtually all ovarian cancer cells

  10. ABT-751 in Treating Young Patients With Refractory Solid Tumors

    ClinicalTrials.gov

    2012-03-14

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  11. Gamma secretase inhibitor impairs epithelial-to-mesenchymal transition induced by TGF-β in ovarian tumor cell lines.

    PubMed

    Pazos, M C; Abramovich, D; Bechis, A; Accialini, P; Parborell, F; Tesone, M; Irusta, G

    2017-01-15

    Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β. DAPT impaired the translocation of phospho-β-catenin to the inner cell compartment observed in TGF-β-treated cells, but was not able to block the induction at protein level induced by TGF-β. Moreover, the inhibitor blocked the increased cell migration and invasiveness ability of both cell lines induced by TGF-β. Notch target genes (Hes1 and Hey1) were induced by TGF-β, decreased by DAPT treatment and remained low in the presence of both stimuli. However, DAPT alone caused no effects on most of the parameters analyzed. These results demonstrate that the γ-secretase inhibitor used in this study exerted a blockade on TGF-β-induced EMT in ovarian cancer cells.

  12. MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer

    PubMed Central

    Chen, Li-Lan; Wang, Luo-Qiao; Nephew, Kenneth P.; Wu, Ying-Li; Zhang, Shu

    2014-01-01

    Metastasis is major cause of mortality in patients with ovarian cancer. MiR-373 has been shown to play pivotal roles in tumorigenesis and metastasis; however, a role for miR-373 in ovarian cancer has not been investigated. In this study, we show that the miR-373 expression is down-regulated in human epithelial ovarian cancer (EOC) and inversely correlated with clinical stage and histological grade. Ectopic overexpression of miR-373 in human EOC cells suppressed cell invasion in vitro and metastasis in vivo, and the epithelial–mesenchymal transition process. Silencing the expression of miR-373 resulted in an increased migration and invasion of EOC cells. Using integrated bioinformatics analysis, gene expression arrays, and luciferase assay, we identified Rab22a as a direct and functional target of miR-373 in EOC cells. Expression levels of miR-373 were inversely correlated with Rab22a protein levels in human EOC tissues. Rab22a knockdown inhibited invasion and migration of EOC cells, increased E-cadherin expression, and suppressed the expression of N-cadherin. Moreover, overexpression of Rab22a abrogated miR-373-induced invasion and migration of EOC cells. Taken together, these results demonstrate that miR-373 suppresses EOC invasion and metastasis by directly targeting Rab22a gene, a new potential therapeutic target in EOC. PMID:25460499

  13. A variant c-KIT mutation, D816H, fundamental to the sequential development of an ovarian mixed germ cell tumor and systemic mastocytosis with chronic myelomonocytic leukemia.

    PubMed

    Mitchell, Sarah G; Bunting, Silvia T; Saxe, Debra; Olson, Thomas; Keller, Frank G

    2017-04-01

    An activating point mutation of the c-KIT tyrosine kinase receptor gene, D816H, has been described in germ cell tumors (GCTs). We report an adolescent diagnosed with an ovarian mixed GCT and systemic mastocytosis with chronic myelomonocytic leukemia (SM-CMML). The teratoma and dysgerminoma differed by copy number aberrations via single nucleotide polymorphism (SNP) microarray, but were inclusive of the same c-KIT D816H point mutation (c.2446G>C) also identified in blood and bone marrow mast cells. These findings indicate not only a clonal origin of the GCT and hematologic malignancy, but also suggest a rare KIT mutation may be playing a fundamental role in malignancy development.

  14. Oncolytic virotherapy for ovarian cancer.

    PubMed

    Li, Shoudong; Tong, Jessica; Rahman, Masmudur M; Shepherd, Trevor G; McFadden, Grant

    2012-08-01

    In the past two decades, more than 20 viruses with selective tropism for tumor cells have been developed as oncolytic viruses (OVs) for treatments of a variety of malignancies. Of these viruses, eleven have been tested in human ovarian cancer models in preclinical studies. So far, nine phase I or II clinical trials have been conducted or initiated using four different types of OVs in patients with recurrent ovarian cancers. In this article, we summarize the different OVs that are being assessed as therapeutics for ovarian cancer. We also present an overview of recent advances in identification of key genetic or immune-response pathways involved in tumorigenesis of ovarian cancer, which provides a better understanding of the tumor specificities and oncolytic properties of OVs. In addition, we discuss how next-generation OVs could be genetically modified or integrated into multimodality regimens to improve clinical outcomes based on recent advances in ovarian cancer biology.

  15. Oncolytic virotherapy for ovarian cancer

    PubMed Central

    Li, Shoudong; Tong, Jessica; Rahman, Masmudur M; Shepherd, Trevor G; McFadden, Grant

    2012-01-01

    In the past two decades, more than 20 viruses with selective tropism for tumor cells have been developed as oncolytic viruses (OVs) for treatments of a variety of malignancies. Of these viruses, eleven have been tested in human ovarian cancer models in preclinical studies. So far, nine phase I or II clinical trials have been conducted or initiated using four different types of OVs in patients with recurrent ovarian cancers. In this article, we summarize the different OVs that are being assessed as therapeutics for ovarian cancer. We also present an overview of recent advances in identification of key genetic or immune-response pathways involved in tumorigenesis of ovarian cancer, which provides a better understanding of the tumor specificities and oncolytic properties of OVs. In addition, we discuss how next-generation OVs could be genetically modified or integrated into multimodality regimens to improve clinical outcomes based on recent advances in ovarian cancer biology. PMID:25977900

  16. Systemic co-delivery of doxorubicin and siRNA using nanoparticles conjugated with EGFR-specific targeting peptide to enhance chemotherapy in ovarian tumor bearing mice

    NASA Astrophysics Data System (ADS)

    Liu, C. W.; Lin, W. J.

    2013-10-01

    This aim of this study was to develop peptide-conjugated nanoparticles (NPs) for systemic co-delivery of siRNA and doxorubicin to enhance chemotherapy in epidermal growth factor receptor (EGFR) high-expressed ovarian tumor bearing mice. The active targeting NPs were prepared using heptapeptide-conjugated poly( d, l-lactic-co-glycolic acid)-poly(ethylene glycol). The particle sizes of peptide-free and peptide-conjugated NPs were 159.3 ± 32.5 and 184.0 ± 52.9 nm, respectively, with zeta potential -21.3 ± 3.8 and -15.3 ± 2.8 mV. The peptide-conjugated NPs uptake were more efficient in EGFR high-expressed SKOV3 cells than in EGFR low-expressed HepG2 cells due to heptapeptide specificity. The NPs were used to deliver small molecule anticancer drug (e.g., doxorubicin) and large molecule genetic agent (e.g., siRNA). The IC50 of doxorubicin-loaded peptide-conjugated NPs (0.09 ± 0.06 μM) was significantly lower than peptide-free NPs (5.72 ± 2.64 μM). The similar result was observed in siRNA-loaded NPs. The peptide-conjugated NPs not only served as a nanocarrier to efficiently deliver doxorubicin and siRNA to EGFR high-expressed ovarian cancer cells but also increased the intracellular accumulation of the therapeutic agents to induce assured anti-tumor growth effect in vivo.

  17. In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous recombination deficient and proficient ovarian carcinoma☆,☆☆

    PubMed Central

    AlHilli, Mariam M.; Becker, Marc A.; Weroha, S. John; Flatten, Karen S.; Hurley, Rachel M.; Harrell, Maria I.; Oberg, Ann L.; Maurer, Matt J.; Hawthorne, Kieran M.; Hou, Xiaonan; Harrington, Sean C.; McKinstry, Sarah; Meng, X. Wei; Wilcoxen, Keith M.; Kalli, Kimberly R.; Swisher, Elizabeth M.; Kaufmann, Scott H.; Haluska, Paul

    2017-01-01

    Objective Poly(ADP-ribose) polymerase (PARP) inhibitors have yielded encouraging responses in high-grade serous ovarian carcinomas (HGSOCs), but the optimal treatment setting remains unknown. We assessed the effect of niraparib on HGSOC patient-derived xenograft (PDX) models as well as the relationship between certain markers of homologous recombination (HR) status, including BRCA1/2 mutations and formation of RAD51 foci after DNA damage, and response of these PDXs to niraparib in vivo. Methods Massively parallel sequencing was performed on HGSOCs to identify mutations contributing to HR deficiency. HR pathway integrity was assessed using fluorescence microscopy-based RAD51 focus formation assays. Effects of niraparib (MK-4827) on treatment-naïve PDX tumor growth as monotherapy, in combination with carboplatin/paclitaxel, and as maintenance therapy were assessed by transabdominal ultrasound. Niraparib responses were correlated with changes in levels of poly(ADP-ribose), PARP1, and repair proteins by western blotting. Results Five PDX models were evaluated in vivo. Tumor regressions were induced by single-agent niraparib in one of two PDX models with deleterious BRCA2 mutations and in a PDX with RAD51C promoter methylation. Diminished formation of RAD51 foci failed to predict response, but Artemis loss was associated with resistance. Niraparib generally failed to enhance responses to carboplatin/paclitaxel chemotherapy, but maintenance niraparib therapy delayed progression in a BRCA2-deficient PDX. Conclusions Mutations in HR genes are neither necessary nor sufficient to predict response to niraparib. Assessment of repair status through multiple complementary assays is needed to guide PARP inhibitor therapy, design future clinical trials and identify ovarian cancer patients most likely to benefit from PARP inhibition. PMID:27614696

  18. Targeting tissue factor as a novel therapeutic oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer

    PubMed Central

    Hu, Zhiwei; Xu, Jie; Cheng, Jijun; McMichael, Elizabeth; Yu, Lianbo; Carson, William E.

    2017-01-01

    Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients. TF-targeted agents, i.e., a factor VII (fVII)-conjugated photosensitizer (fVII-PS for targeted photodynamic therapy) and fVII-IgG1Fc (Immunoconjugate or ICON for immunotherapy), can eradicate CSC via the induction of apoptosis and necrosis and via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, respectively. In conclusion, these results demonstrate that TF is a novel surface therapeutic oncotarget for CSC, in addition to cancer cell TF and tumor angiogenic vascular endothelial TF. Moreover, this research highlights that TF-targeting therapeutics can effectively eradicate CSCs, without drug resistance, isolated from breast, lung and ovarian cancer with potential to translate into other most commonly diagnosed solid cancer, in which TF is also highly expressed. PMID:27903969

  19. Borderline Personality Disorder

    PubMed Central

    Brüne, Martin

    2016-01-01

    The term ‘Borderline Personality Disorder’ (BPD) refers to a psychiatric syndrome that is characterized by emotion dysregulation, impulsivity, risk-taking behavior, irritability, feelings of emptiness, self-injury and fear of abandonment, as well as unstable interpersonal relationships. BPD is not only common in psychiatric populations but also more prevalent in the general community than previously thought, and thus represents an important public health issue. In contrast to most psychiatric disorders, some symptoms associated with BPD may improve over time, even without therapy, though impaired social functioning and interpersonal disturbances in close relationships often persist. Another counterintuitive and insufficiently resolved question is why depressive symptoms and risk-taking behaviors can occur simultaneously in the same individual. Moreover, there is an ongoing debate about the nosological position of BPD, which impacts on research regarding sex differences in clinical presentation and patterns of comorbidity. In this review, it is argued that many features of BPD may be conceptualized within an evolutionary framework, namely behavioral ecology. According to Life History Theory, BPD reflects a pathological extreme or distortion of a behavioral ‘strategy’ which unconsciously aims at immediate exploitation of resources, both interpersonal and material, based on predictions shaped by early developmental experiences. Such a view is consistent with standard medical conceptualizations of BPD, but goes beyond classic ‘deficit’-oriented models, which may have profound implications for therapeutic approaches. PMID:26929090

  20. Modulators of Response to Tumor Necrosis-Related Apoptosis-Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

    DTIC Science & Technology

    2009-04-01

    was minimally expressed in the nontrans- formed HIO -180 ovarian epithelial cells, but was detected at high levels in the HeyA8, HeyA8-MDR, SKOV3ip1...lines (SKOV3ip1, IGROV, HeyA8, A2780-par, and HIO -180) with fluorescence-activated cell sorting analysis. In vitro (cell viability, migration...with the non-transformed ( HIO -180) cells. HeyA8 and A2780-par cell lines lacked FRα expression. In vivo, MORAb-003 led to 44 and 84% decreases in

  1. Ovarian Cyst

    MedlinePlus

    ... accurate way to tell if a woman has ovarian cancer. For example, some women who do have ovarian cancer have a normal CA-125 level. Also, this ... for women who show signs or symptoms of ovarian cancer or who have genetic mutations that increase the ...

  2. Anti-CCR4 monoclonal antibody enhances antitumor immunity by modulating tumor-infiltrating Tregs in an ovarian cancer xenograft humanized mouse model

    PubMed Central

    Chang, De-Kuan; Peterson, Eric; Sun, Jiusong; Goudie, Calum; Drapkin, Ronny I.; Liu, Joyce F.; Matulonis, Ursula; Zhu, Quan; Marasco, Wayne A.

    2016-01-01

    ABSTRACT Recent studies have demonstrated that regulatory T cells (Tregs) are recruited to tumor sites where they can suppress antitumor immunity. The chemokine receptor CCR4 is expressed at high levels on functional CD4+CD25+FoxP3+ Tregs and production of the CCR4 ligand CCL22 by tumor cells and tumor-associated macrophages is associated with Treg recruitment to the tumor site. Here, we tested IgG1 and IgG4 isotypes of human anti-CCR4 mAb2-3 for their in vitro activity and in vivo capacity in a NSG mouse model bearing CCL22-secreting ovarian cancer (OvCA) xenograft to modulate Tregs and restore antitumor activity. Both mAb2-3 isotypes blocked in vitro chemoattraction of Tregs to CCL22-secreting OvCA cells. However, they differed in their in vivo mode of action with IgG1 causing Treg depletion and IgG4 blocking migration to the tumors. Primary T cells that were primed with OvCA-pulsed dendritic cells (DCs) demonstrated INFγ secretion that could be enhanced through Treg depletion by mAb2-3. Humanized mice reconstructed with allogeneic tumor-primed T cells (TP-T) were used to evaluate the restoration of OvCA immunity by depletion or blockade of Tregs with mAb2-3. We observed that IgG1 was more potent than IgG4 in inhibiting tumor growth. Mechanism studies demonstrated that mAb2-3 treatment lead to inhibition of IL-2 binding to its receptor. Further studies showed that mAb2-3 induced CD25 shedding (sCD25) from Tregs which lead to a decrease in IL-2-dependent survival. Together, the results demonstrate that mAb2-3 is an agonist antibody that can restore anti-OvCA immunity through modulation of Treg activity. PMID:27141347

  3. Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer

    PubMed Central

    Grisham, Rachel N.; Sylvester, Brooke E.; Won, Helen; McDermott, Gregory; DeLair, Deborah; Ramirez, Ricardo; Yao, Zhan; Shen, Ronglai; Dao, Fanny; Bogomolniy, Faina; Makker, Vicky; Sala, Evis; Soumerai, Tara E.; Hyman, David M.; Socci, Nicholas D.; Viale, Agnes; Gershenson, David M.; Farley, John; Levine, Douglas A.; Rosen, Neal; Berger, Michael F.; Spriggs, David R.; Aghajanian, Carol A.; Solit, David B.; Iyer, Gopa

    2015-01-01

    Purpose No effective systemic therapy exists for patients with metastatic low-grade serous (LGS) ovarian cancers. BRAF and KRAS mutations are common in serous borderline (SB) and LGS ovarian cancers, and MEK inhibition has been shown to induce tumor regression in a minority of patients; however, no correlation has been observed between mutation status and clinical response. With the goal of identifying biomarkers of sensitivity to MEK inhibitor treatment, we performed an outlier analysis of a patient who experienced a complete, durable, and ongoing (> 5 years) response to selumetinib, a non-ATP competitive MEK inhibitor. Patients and Methods Next-generation sequencing was used to analyze this patient's tumor as well as an additional 28 SB/LGS tumors. Functional characterization of an identified novel alteration of interest was performed. Results Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors identified mutations predicted to induce extracellular signal-regulated kinase pathway activation in 82% (23 of 28), including two patients with BRAF fusions, one of whom achieved an ongoing complete response to MEK inhibitor–based combination therapy. Conclusion Alterations affecting the mitogen-activated protein kinase pathway are present in the majority of patients with LGS ovarian cancer. Next-generation sequencing analysis revealed deletions and fusions that are not detected by older sequencing approaches. These findings, coupled with the observation that a subset of patients with recurrent LGS ovarian cancer experienced dramatic and durable responses to MEK inhibitor therapy, support additional

  4. [Whose borderline is it? Reconsidering diagnosing borderline personality].

    PubMed

    Gil, Tsvi E

    2008-11-01

    The present article critically discusses diagnosing borderline personality, demonstrating ideas raised with a treated case. In contrast to routine diagnoses made by psychiatrists according to common diagnosing systems (such as the American DSM or the WHO's ICD), we wonder whether this diagnosis reflects a medico-social construct, which is associated to the female status in masculine (or even patriarch) society, and probably associated even to the context of a woman diagnosed by a psychiatric system. In the context of critically viewing aetiological hypotheses to borderline personality (presented in our former article as a personality constellated around complex and prolonged trauma) in this article we suggest viewing borderline behaviours and symptoms as manifestations of coping and survival of a woman-victim in abusing surroundings.

  5. Quantitative imaging reveals heterogeneous growth dynamics and treatment-dependent residual tumor distributions in a three-dimensional ovarian cancer model

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan P.; Rizvi, Imran; Evans, Conor L.; Abu-Yousif, Adnan O.; Hasan, Tayyaba

    2010-09-01

    Three-dimensional tumor models have emerged as valuable in vitro research tools, though the power of such systems as quantitative reporters of tumor growth and treatment response has not been adequately explored. We introduce an approach combining a 3-D model of disseminated ovarian cancer with high-throughput processing of image data for quantification of growth characteristics and cytotoxic response. We developed custom MATLAB routines to analyze longitudinally acquired dark-field microscopy images containing thousands of 3-D nodules. These data reveal a reproducible bimodal log-normal size distribution. Growth behavior is driven by migration and assembly, causing an exponential decay in spatial density concomitant with increasing mean size. At day 10, cultures are treated with either carboplatin or photodynamic therapy (PDT). We quantify size-dependent cytotoxic response for each treatment on a nodule by nodule basis using automated segmentation combined with ratiometric batch-processing of calcein and ethidium bromide fluorescence intensity data (indicating live and dead cells, respectively). Both treatments reduce viability, though carboplatin leaves micronodules largely structurally intact with a size distribution similar to untreated cultures. In contrast, PDT treatment disrupts micronodular structure, causing punctate regions of toxicity, shifting the distribution toward smaller sizes, and potentially increasing vulnerability to subsequent chemotherapeutic treatment.

  6. Performance of multiplicom's BRCA MASTR Dx kit on the detection of BRCA1 and BRCA2 mutations in fresh frozen ovarian and breast tumor samples

    PubMed Central

    Badoer, Cindy; Garrec, Céline; Goossens, Dirk; Ellison, Gillian; Mills, John; Dzial, Mélina; Housni, Hakim El; Berwouts, Sarah; Concolino, Paola; Guevellou, Virginie Guibert-Le; Delnatte, Capucine; Favero, Jurgen Del

    2016-01-01

    Next-generation sequencing (NGS) has enabled new approaches for detection of mutations in the BRCA1 and BRCA2 genes responsible for hereditary breast and ovarian cancer (HBOC). The search for germline mutations in the BRCA1 and BRCA2 genes is of importance with respect to oncogenetic and surgical (bilateral mastectomy, ovariectomy) counselling. Testing tumor material for BRCA mutations is of increasing importance for therapeutic decision making as the poly ADP ribose polymerase (PARP) inhibitor, olaparib, is now available to treat patients with specific forms of ovarian cancer and BRCA mutations. Molecular genetics laboratories should develop reliable and sensitive techniques for the complete analysis of the BRCA1 and BRCA2 genes. This is a challenge due to the size of the coding sequence of the BRCA1/2 genes, the absence of hot spot mutations, and particularly by the lower DNA quality obtained from Formalin-Fixed Paraffin-Embedded (FFPE) tissue. As a result, a number of analyses are uninterpretable and do not always provide a result to the clinician, limiting the optimal therapeutic management of patients. The availability of Fresh Frozen Tissue (FFT) for some laboratories and the excellent quality of the DNA extracted from it offers an alternative. For this reason, we evaluated Multiplicom's BRCA MASTR Dx assay on a set of 97 FFT derived DNA samples, in combination with the MID for Illumina MiSeq for BRCA1 and BRCA2 mutation detection. We obtained interpretable NGS results for all tested samples and showed > 99,7% sensitivity, specificity and accuracy. PMID:27793035

  7. A case of ovarian enterobiasis.

    PubMed

    Hong, Sung-Tae; Choi, Min-Ho; Chai, Jong-Yil; Kim, Young Tak; Kim, Mi Kyung; Kim, Kyu Rae

    2002-09-01

    A 36-year old Korean woman consulted a clinic for a regular gynecological examination, and a mass was noticed in her pelvis. She was referred to the Asan Medical Center, Seoul where transvaginal ultrasonography confirmed a pelvic mass exceeding 10 cm in diameter. She received total abdominal hysterectomy and bilateral salpingoophorectomy, and a borderline serous neoplasm with micropapillary features involving the left ovary and right ovarian serosa was histopathologically confirmed. In addition, a section of a nematode with numerous eggs was found in the parenchyma of the left ovary. The worm had degenerated but the eggs were well-preserved and were identified as those of Enterobius vermicularis. She is an incidentally recognized case of ovarian enterobiasis.

  8. Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2017-01-31

    Fallopian Tube Carcinosarcoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Tumor; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  9. Spectroscopic imaging system for high-throughput viability assessment of ovarian spheroids or microdissected tumor tissues (MDTs) in a microfluidic chip

    NASA Astrophysics Data System (ADS)

    St-Georges-Robillard, A.; Masse, M.; Kendall-Dupont, J.; Strupler, M.; Patra, B.; Jermyn, M.; Mes-Masson, A.-M.; Leblond, F.; Gervais, T.

    2016-02-01

    There is a growing effort in the biomicrosystems community to develop a personalized treatment response assay for cancer patients using primary cells, patient-derived spheroids, or live tissues on-chip. Recently, our group has developed a technique to cut tumors in 350 μm diameter microtissues and keep them alive on-chip, enabling multiplexed in vitro drug assays on primary tumor tissue. Two-photon microscopy, confocal microscopy and flow cytometry are the current standard to assay tissue chemosensitivity on-chip. While these techniques provide microscopic and molecular information, they are not adapted for high-throughput analysis of microtissues. We present a spectroscopic imaging system that allows rapid quantitative measurements of multiple fluorescent viability markers simultaneously by using a liquid crystal tunable filter to record fluorescence and transmittance spectra. As a proof of concept, 24 spheroids composed of ovarian cancer cell line OV90 were formed in a microfluidic chip, stained with two live cell markers (CellTrackerTM Green and Orange), and imaged. Fluorescence images acquired were normalized to the acquisition time and gain of the camera, dark noise was removed, spectral calibration was applied, and spatial uniformity was corrected. Spectral un-mixing was applied to separate each fluorophore's contribution. We have demonstrated that rapid and simultaneous viability measurements on multiple spheroids can be achieved, which will have a significant impact on the prediction of a tumor's response to multiple treatment options. This technique may be applied as well in drug discovery to assess the potential of a drug candidate directly on human primary tissue.

  10. [Case report of re-expansion pulmonary edema in a patient with anorexia nervosa after removal of a huge ovarian tumor].

    PubMed

    Hari, Junko; Arai, Masayasu; Kosaka, Yasuharu; Toda, Masaya; Kuroiwa, Masayuki; Okamoto, Hirotsugu

    2014-04-01

    We described a case of 19-year-old female who developed re-expansion pulmonary edema (RPE) after removal of a huge ovarian tumor. Altered lung volume after the surgery was observed by chest X-ray. Preoperatively, the lung was highly compressed by the tumor. Patient was intubated under general anesthesia and was ventilated by pressure controlled mode with only 5 cmH2O of positive end-expiratory pressure (PEEP). P/F ratio was changed from 163 to 444 after removal of the tumor. At the end of the surgery, P/F ratio decreased to 263 with yellow frothy sputum in the endotracheal tube and we diagnosed re-expansion pulmonary edema based on appearing yellow frothy sputum and chest X-ray. No recruitment procedure was carried out through the course except positive pressure ventilation with 5 cmH2O of PEEP in the intensive care unit after surgery. Twelve hours after the surgery, we could not confirm the recovery of lung volume on chest X-ray; however the patient was extubated because of P/F ratio increasing to 507. After 8 days of the surgery, the chest X-ray showed recovery of the lung volume to almost normal size. In this case, the compressed lung needed almost 1 week to recover the lung volume. This change in chest X-ray might indicate inadequate recovery of lung volume by recruitment maneuver and this should be avoided in order not to allow development of unfavorable clinical course of RPE.

  11. Nuclear β-arrestin1 is a critical cofactor of hypoxia-inducible factor-1α signaling in endothelin-1-induced ovarian tumor progression

    PubMed Central

    Rosanò, Laura; Caprara, Valentina; Sestito, Rosanna; Di Castro, Valeriana; Bagnato, Anna

    2016-01-01

    Hypoxia-inducible factor-1α (HIF-1α) mediates the response to hypoxia or other stimuli, such as growth factors, including endothelin-1 (ET-1), to promote malignant progression in numerous tumors. The importance of cofactors that regulate HIF-1α signalling within tumor is not well understood. Here we elucidate that ET-1/ETA receptor (ETAR)-induced pathway physically and functionally couples the scaffold protein β-arrestin1 (β-arr1) to HIF-1α signalling. In epithelial ovarian cancer (EOC) cells, ET-1/ETAR axis induced vascular-endothelial growth factor (VEGF) expression through HIF-1α nuclear accumulation. In these cells, activation of ETAR by ET-1, by mimicking hypoxia, promoted the nuclear interaction between β-arr1 and HIF-1α and the recruitment of p300 acetyltransferase to hypoxia response elements on the target gene promoters, resulting in enhanced histone acetylation, and HIF-1α target gene transcription. Indeed, β-arr1-HIF-1α interaction regulated the enhanced expression and release of downstream targets, such as ET-1 and VEGF, required for tumor cell invasion and pro-angiogenic effects in endothelial cells. These effects were abrogated by β-arr1 or HIF-1α silencing or by pharmacological treatment with the dual ET-1 receptor antagonist macitentan. Interestingly, ETAR/β-arr1 promoted the self-amplifying HIF-1α-mediated transcription of ET-1 that sustained a regulatory circuit involved in invasive and angiogenic behaviors. In a murine orthotopic model of metastatic human EOC, treatment with macitentan, or silencing of β-arr1, inhibits intravasation and metastasis formation. Collectively, these findings reveal the interplay of β-arr1 with HIF-1α in the complexity of ET-1/ETAR signalling, mediating epigenetic modifications directly involved in the metastatic process, and suggest that targeting ET-1-dependent β-arr1/HIF-1α pathway by using macitentan may impair EOC progression. PMID:26909598

  12. Class III β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel.

    PubMed

    Roque, Dana M; Buza, Natalia; Glasgow, Michelle; Bellone, Stefania; Bortolomai, Ileana; Gasparrini, Sara; Cocco, Emiliano; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Rutherford, Thomas J; Schwartz, Peter E; Santin, Alessandro D

    2014-01-01

    Critics have suggested that neoadjuvant chemotherapy (NACT) followed by interval debulking may select for resistant clones or cancer stem cells when compared to primary cytoreduction. β-tubulins are chemotherapeutic targets of taxanes and epothilones. Class III β-tubulin overexpression has been linked to chemoresistance and hypoxia. Herein, we describe changes in class III β-tubulin in patients with advanced ovarian carcinoma in response to NACT, in relationship to clinical outcome, and between patients who underwent NACT versus primary debulking; we characterize in vitro chemosensitivity to paclitaxel/patupilone of cell lines established from this patient population, and class III β-tubulin expression following repeated exposure to paclitaxel. Using immunohistochemistry, we observed among 22 paired specimens obtained before/after NACT decreased expression of class III β-tubulin following therapy within stroma (p=0.07), but not tumor (p=0.63). Poor median overall survival was predicted by high levels of class III β-tubulin in both tumor (HR 3.66 [1.11,12.05], p=0.03) and stroma (HR 4.53 [1.28,16.1], p=0.02). Class III β-tubulin expression by quantitative-real-time-polymerase-chain-reaction was higher among patients who received NACT (n=12) compared to primary cytoreduction (n=14) (mean±SD fold-change: 491.2±115.9 vs. 224.1±55.66, p=0.037). In vitro subculture with paclitaxel resulted in class III β-tubulin upregulation, however, cell lines that overexpressed class III β-tubulin remained sensitive to patupilone. Overexpression of class III β-tubulin in patients dispositioned to NACT may thus identify an intrinsically aggressive phenotype, and predict poor overall survival and paclitaxel resistance. Decreases in stromal expression may represent normalization of the tumor microenvironment following therapy. Epothilones warrant study for patients who have received neoadjuvant carboplatin and paclitaxel.

  13. A new tumor suppressor lncRNA RP11-190D6.2 inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells

    PubMed Central

    Tong, Wenxian; Yang, Liu; Yu, Qiang; Yao, Jie; He, Anbing

    2017-01-01

    At present, a large number of long noncoding RNAs (lncRNAs) from the human genome have been discovered. Meanwhile, emerging evidence has indicated that lncRNAs could play a critical role in the regulation of cellular processes such as cancer progression and metastasis. However, the functions of some new lncRNAs in the complex transcriptional process are mostly unknown at present. Existing studies suggest that loss of WW domain-containing oxidoreductase (WWOX) expression is linked with poor prognosis in numerous cancers, including epithelial ovarian cancer (EOC). However, the functional role of its antisense transcript RP11-190D6.2 is not clear to date. In this study, WWOX antisense transcript RP11-190D6.2 was analyzed specifically in EOC cells using real-time polymerase chain reaction and gain-/loss-of-function studies. We found that RP11-190D6.2 expression was positively correlated with WWOX expression. The RP11-190D6.2 expression was markedly downregulated in tumor tissues compared with normal tissues, but the RP11-190D6.2 expression was significantly downregu-lated in four EOC cell lines compared with human ovarian surface epithelial cell line. RP11-190D6.2 overexpression resulted in the increase of WWOX expression, whereas its knockdown led to the decrease of WWOX expression. We also found that RP11-190D6.2 was restored by 5-aza-2′-deoxycytidine treatment in EOC. In addition, the RP11-190D6.2 overexpression and knockdown experiments revealed that RP11-190D6.2 overexpression inhibited proliferation, migration, and invasion abilities in HO8910-PM cells, whereas RP11-190D6.2 knockdown in HEY-A8 cells had the opposite effect. The analyses in EOC implicate that RP11-190D6.2 may play a pivotal role in the regulation of tumor metastasis, suggesting that RP11-190D6.2 may serve as a potential biomarker and therapeutic target for EOC. PMID:28280357

  14. The heterogeneity of ovarian cancer.

    PubMed

    Meinhold-Heerlein, I; Hauptmann, S

    2014-02-01

    Ovarian cancer carries the worst prognosis of all gynecological malignancies. This is mainly due to its resistance against commonly used cytostatic drugs as well as the lack of a screening method for its detection at an early stage. Both basic and translational research have shown over the past decades that ovarian cancer as a medical term includes several types of tumors with different phenotypes, molecular biology, etiology, tumor progression, and even different prognosis. In this issue of Archives of Gynecology and Obstetrics, J. Dietel presents a review article about novel findings of the etiopathogenesis of ovarian cancer and the role that fallopian tubes may play. He also outlines the implied clinical consequences. Here, we give a brief overview of the heterogeneity of ovarian cancer to introduce the topic.

  15. Risk of Ovarian Cancer and the NF-κB Pathway: Genetic association with IL1A and TNFSF10

    PubMed Central

    Charbonneau, Bridget; Block, Matthew S.; Bamlet, William R.; Vierkant, Robert A.; Kalli, Kimberly R.; Fogarty, Zachary; Rider, David N.; Sellers, Thomas A.; Tworoger, Shelley S.; Poole, Elizabeth; Risch, Harvey A.; Salvesen, Helga B.; Kiemeney, Lambertus A.; Baglietto, Laura; Giles, Graham G.; Severi, Gianluca; Trabert, Britton; Wentzensen, Nicolas; Chenevix-Trench, Georgia; Whittemore, Alice S.; Sieh, Weiva; Chang-Claude, Jenny; Bandera, Elisa V.; Orlow, Irene; Terry, Kathryn; Goodman, Marc T.; Thompson, Pamela J; Cook, Linda S.; Rossing, Mary Anne; Ness, Roberta B.; Narod, Steven A.; Kupryjanczyk, Jolanta; Lu, Karen; Butzow, Ralf; Dörk, Thilo; Pejovic, Tanja; Campbell, Ian; Le, Nhu D.; Bunker, Clareann H.; Bogdanova, Natalia; Runnebaum, Ingo B.; Eccles, Diana; Paul, James; Wu, Anna H.; Gayther, Simon A.; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B.; Karlan, Beth Y.; Culver, Hoda Anton; Gronwald, Jacek; Hogdall, Claus K.; Lambrechts, Diether; Fasching, Peter A.; Menon, Usha; Schildkraut, Joellen; Pearce, Celeste Leigh; Levine, Douglas A.; Kjaer, Susanne Kruger; Cramer, Daniel; Flanagan, James M.; Phelan, Catherine M.; Brown, Robert; Massuger, Leon F.A.G.; Song, Honglin; Doherty, Jennifer A.; Krakstad, Camilla; Liang, Dong; Odunsi, Kunle; Berchuck, Andrew; Jensen, Allan; Lubiński, Jan; Nevanlinna, Heli; Bean, Yukie T.; Lurie, Galina; Ziogas, Argyrios; Walsh, Christine; Despierre, Evelyn; Brinton, Louise; Hein, Alexander; Rudolph, Anja; Dansonka-Mieszkowska, Agnieszka; Olson, Sara H.; Harter, Philipp; Tyrer, Jonathan; Vitonis, Allison F.; Brooks-Wilson, Angela; Aben, Katja K.; Pike, Malcolm C.; Ramus, Susan J.; Wik, Elisabeth; Cybulski, Cezary; Lin, Jie; Sucheston, Lara; Edwards, Robert; McGuire, Valerie; Lester, Jenny; du Bois, Andreas; Lundvall, Lene; Wang-Gohrke, Shan; Szafron, Lukasz M; Lambrechts, Sandrina; Yang, Hannah; Beckmann, Matthias W.; Pelttari, Liisa M.; Van Altena, Anne M.; van den Berg, David; Halle, Mari K; Gentry-Maharaj, Aleksandra; Schwaab, Ira; Chandran, Urmila; Menkiszak, Janusz; Ekici, Arif B.; Wilkens, Lynne R; Leminen, Arto; Modugno, Francesmary; Friel, Grace; Rothstein, Joseph H.; Vergote, Ignace; Garcia-Closas, Montserrat; Hildebrandt, Michelle A.T.; Sobiczewski, Piotr; Kelemen, Linda E.; Pharoah, Paul D.P.; Moysich, Kirsten; Knutson, Keith L.; Cunningham, Julie M.; Fridley, Brooke L.; Goode, Ellen L.

    2014-01-01

    A missense single nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). While the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. IL-1α is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many pro-inflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in over 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell and 1,016 low grade serous (LGS), including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium (OCAC). In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer (OR=0.84, 95% CI: 0.76–0.93; p=0.00075), which remained intact even after excluding participants in the prior study (OR=0.85, 95% CI: 0.75–0.95; p=0.006). Considering a multiple-testing-corrected significance threshold of p< 2.5×10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential (LMP) tumors OR=0.85, 95% CI: 0.79–0.91; p=0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation related risk factors is warranted. PMID:24272484

  16. c-Yes enhances tumor migration and invasion via PI3K/AKT pathway in epithelial ovarian cancer.

    PubMed

    Jin, Yunfeng; Huang, Menghui; Wang, Yingying; Yi, Changying; Deng, Yan; Chen, Yannan; Jiang, Lifei; Wang, Juan; Shen, Qin; Liu, Rong; QinghuaXi

    2016-08-01

    Overexpression of c-Yes has been noted to correlation with several human cancers. However, the effects of c-Yes on epithelial ovarian cancer (EOC) development remain unclear. The aim of this study is going to prove the effects of c-Yes and related mechanisms in proliferation, metastasis and invasion of EOC. Immunohistochemical analysis was performed in 119 human EOC samples, and the data was correlated with clinic pathologic features. Furthermore, western blot analysis is performed for c-Yes in EOC samples and cell lines to evaluate their protein levels and molecular interaction. Kaplan-Meier survival analysis shows that the strong expression of c-Yes exhibited a significant correlation with poor prognosis in human EOC (P<0.01(⁎)). Meanwhile, we found that knockdown of c-Yes by shRNA inhibited the ability of migration and invasion in EOC cells via the PI3K/AKT pathway. In a word, these results suggested that c-Yes plays an important role in migration and invasion of EOC.

  17. Coordinate patterns of estrogen receptor, progesterone receptor, and Wilms tumor 1 expression in the histopathologic distinction of ovarian from endometrial serous adenocarcinomas.

    PubMed

    Fadare, Oluwole; James, Samuel; Desouki, Mohamed M; Khabele, Dineo

    2013-10-01

    The purpose of this study is to assess whether composite or coordinate immunoexpression patterns of estrogen receptor (ER), progesterone receptor (PR), and Wilms tumor 1 (WT1) gene can significantly distinguish between endometrial serous carcinoma (ESC) and ovarian serous carcinoma (OSC). Immunohistochemical analyses were performed on whole tissue sections from 22 uterus-confined ESCs and on a tissue microarray of 140 high-grade, pan-stage OSCs, using antibodies to ER, PR, and WT-1. Estrogen receptor, PR, and WT1 expressions were present in 37%, 49%, and 81% of OSC, respectively, but these markers were also present in 18%, 27%, and 36% of ESC. The ER+/PR+/WT1+ coordinate profile was identified in 33.6% of OSC but in none of ESC (P = .0006), resulting in a calculated sensitivity and specificity of this profile for OSC of 33.6% and 100%, respectively. By contrast, the ER-/PR-/WT1- coordinate profile was identified in 41% of ESC but in only 6.4% of OSC (P = .0001), resulting in a calculated sensitivity and specificity of this profile for ESC of 50% and 94%. In summary, in the differential diagnosis between OSC and ESC, positivity for all 3 markers favors an extrauterine origin, whereas negativity for all 3 markers is supportive of an endometrial origin. The use of single markers for this purpose is not recommended, as each lacks optimal discriminatory power. Coordinate profiles, in general, have a high specificity but low sensitivity in this differential diagnosis.

  18. Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft

    PubMed Central

    Chu, Kevin S.; Hasan, Warefta; Rawal, Sumit; Walsh, Mark D.; Enlow, Elizabeth M.; Luft, J. Christopher; Bridges, Arlene S.; Kuijer, Jennifer L.; Napier, Mary E.; Zamboni, William C.; DeSimone, Joseph M.

    2013-01-01

    The particle fabrication technique PRINT® was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80nm; height=320nm (PRINT-Doc-80×320) and d=200nm; h=200nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~18-fold (PRINT-Doc-80×320) and ~33-fold (PRINT-Doc-200×200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently lead to increased tumor exposure of Docetaxel from 0-168 hours (~53% higher for PRINT-Doc-80×320 and ~76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system. PMID:23219874

  19. Structural Analysis of a Viral Ovarian Tumor Domain Protease from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded Ubiquitin

    SciTech Connect

    Capodagli, Glenn C.; McKercher, Marissa A.; Baker, Erica A.; Masters, Emily M.; Brunzelle, Joseph S.; Pegan, Scott D.

    2014-10-02

    Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(-)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage of posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 {angstrom}, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.

  20. Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

    ClinicalTrials.gov

    2015-04-28

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  1. Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

    ClinicalTrials.gov

    2016-03-16

    Malignant Ovarian Mixed Epithelial Tumor; Nausea and Vomiting; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  2. Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-12-21

    Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  3. Ovarian Cancer Proteomic, Phosphoproteomic, and Glycoproteomic Data Released - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) scientists have just released a comprehensive dataset of the proteomic analysis of high grade serous ovarian tumor samples,

  4. Ovarian Cancer: Opportunity for Targeted Therapy

    PubMed Central

    Tagawa, Tomoko; Morgan, Robert; Yen, Yun; Mortimer, Joanne

    2012-01-01

    Ovarian cancer is a common cause of cancer mortality in women with limited treatment effectiveness in advanced stages. The limitation to treatment is largely the result of high rates of cancer recurrence despite chemotherapy and eventual resistance to existing chemotherapeutic agents. The objective of this paper is to review current concepts of ovarian carcinogenesis. We will review existing hypotheses of tumor origin from ovarian epithelial cells, Fallopian tube, and endometrium. We will also review the molecular pathogenesis of ovarian cancer which results in two specific pathways of carcinogenesis: (1) type I low-grade tumor and (2) type II high-grade tumor. Improved understanding of the molecular basis of ovarian carcinogenesis has opened new opportunities for targeted therapy. This paper will also review these potential therapeutic targets and will explore new agents that are currently being investigated. PMID:22235203

  5. OVARIAN CANCER: INVOLVEMENT OF THE MATRIX METALLOPROTEINASES

    PubMed Central

    Al-Alem, Linah; Curry, Thomas E.

    2016-01-01

    Ovarian cancer is the leading cause of death from gynecologic malignancies. Reasons for the high mortality rate associated with ovarian cancer include a late diagnosis at which time the cancer has metastasized throughout the peritoneal cavity. Cancer metastasis is facilitated by the remodeling of the extracellular tumor matrix by a family of proteolytic enzymes known as the matrix metalloproteinases (MMPs). There are 23 members in the MMP family, many of which have been reported to be associated with ovarian cancer. In the current paradigm, ovarian tumor cells and the surrounding stromal cells stimulate the synthesis and/or activation of various MMPs to aid in tumor growth, invasion, and eventual metastasis. This review sheds light on the different MMPs in the various types of ovarian cancer and their impact on the progression of this gynecologic malignancy. PMID:25918438

  6. Ovarian cancer: involvement of the matrix metalloproteinases.

    PubMed

    Al-Alem, Linah; Curry, Thomas E

    2015-08-01

    Ovarian cancer is the leading cause of death from gynecologic malignancies. One of the reasons for the high mortality rate associated with ovarian cancer is its late diagnosis, which often occurs after the cancer has metastasized throughout the peritoneal cavity. Cancer metastasis is facilitated by the remodeling of the extracellular tumor matrix by a family of proteolytic enzymes known as the matrix metalloproteinases (MMPs). There are 23 members of the MMP family, many of which have been reported to be associated with ovarian cancer. In the current paradigm, ovarian tumor cells and the surrounding stromal cells stimulate the synthesis and/or activation of various MMPs to aid in tumor growth, invasion, and eventual metastasis. The present review sheds light on the different MMPs in the various types of ovarian cancer and on their impact on the progression of this gynecologic malignancy.

  7. Ovarian Cancer

    MedlinePlus

    ... factors may increase a woman’s risk for ovarian cancer: • Being middle-aged or older. • Having close family members (such as ... than 40, with the greatest number of ovarian cancers occurring in women aged 60 years or older. Each year, approximately 21, ...

  8. OVARIAN LOW-GRADE AND HIGH-GRADE SEROUS CARCINOMA: Pathogenesis, Clinicopathologic and Molecular Biologic Features, and Diagnostic Problems

    PubMed Central

    Vang, Russell; Shih, Ie-Ming; Kurman, Robert J.

    2009-01-01

    Ovarian serous carcinomas have been graded using various systems. Recently, a 2-tier system in which tumors are subdivided into low-grade and high-grade has been proposed. This approach is simplistic, reproducible, and based on biologic evidence indicating that both tumors develop via different pathways. Low-grade serous carcinomas exhibit low-grade nuclei with infrequent mitotic figures. They evolve from adenofibromas or borderline tumors, have frequent mutations of the KRAS, BRAF, or ERBB2 genes, and lack TP53 mutations (Type I pathway). The progression to invasive carcinoma is a slow step-wise process. Low-grade tumors are indolent and have better outcome than high-grade tumors. In contrast, high-grade serous carcinomas have high-grade nuclei and numerous mitotic figures. Identification of a precursor lesion in the ovary has been elusive and therefore the origin of ovarian carcinoma has been described as de novo. More recently, studies have suggested that a proportion appear to originate from intraepithelial carcinoma in the fallopian tube. The development of these tumors is rapid (Type II pathway). The vast majority are characterized by TP53 mutations and lack mutations of KRAS, BRAF, or ERBB2. Although both types of serous carcinomas evolve along different pathways, rare high-grade serous carcinomas seem to arise through the Type I pathway. Immunohistochemical stains for p53, p16, and Ki-67 for distinction of low- from high-grade tumors are of limited value but can be helpful in selected instances. This review provides an update on the pathogenesis and clinicopathologic features of these two types of serous carcinomas and addresses some of the diagnostic problems that are encountered in routine practice. PMID:19700937

  9. Comprehensive Cross-Population Analysis of High-Grade Serous Ovarian Cancer Supports No More Than Three Subtypes

    PubMed Central

    Way, Gregory P.; Rudd, James; Wang, Chen; Hamidi, Habib; Fridley, Brooke L.; Konecny, Gottfried E.; Goode, Ellen L.; Greene, Casey S.; Doherty, Jennifer A.

    2016-01-01

    Four gene expression subtypes of high-grade serous ovarian cancer (HGSC) have been previously described. In these early studies, a fraction of samples that did not fit well into the four subtype classifications were excluded. Therefore, we sought to systematically determine the concordance of transcriptomic HGSC subtypes across populations without removing any samples. We created a bioinformatics pipeline to independently cluster the five largest mRNA expression datasets using k-means and nonnegative matrix factorization (NMF). We summarized differential expression patterns to compare clusters across studies. While previous studies reported four subtypes, our cross-population comparison does not support four. Because these results contrast with previous reports, we attempted to reproduce analyses performed in those studies. Our results suggest that early results favoring four subtypes may have been driven by the inclusion of serous borderline tumors. In summary, our analysis suggests that either two or three, but not four, gene expression subtypes are most consistent across datasets. PMID:27729437

  10. Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

    ClinicalTrials.gov

    2015-06-11

    Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  11. Loss of Secreted Frizzled-Related Protein 4 Correlates with an Aggressive Phenotype and Predicts Poor Outcome in Ovarian Cancer Patients

    PubMed Central

    Nixdorf, Sheri; Ford, Caroline E.; Olivier, Jake; Caduff, Rosmarie; Scurry, James P.; Guertler, Rea; Hornung, Daniela; Mueller, Renato; Fink, Daniel A.; Hacker, Neville F.; Heinzelmann-Schwarz, Viola A.

    2012-01-01

    Background Activation of the Wnt signaling pathway is implicated in aberrant cellular proliferation in various cancers. In 40% of endometrioid ovarian cancers, constitutive activation of the pathway is due to oncogenic mutations in β-catenin or other inactivating mutations in key negative regulators. Secreted frizzled-related protein 4 (SFRP4) has been proposed to have inhibitory activity through binding and sequestering Wnt ligands. Methodology/Principal Findings We performed RT-qPCR and Western-blotting in primary cultures and ovarian cell lines for SFRP4 and its key downstream regulators activated β-catenin, β-catenin and GSK3β. SFRP4 was then examined by immunohistochemistry in a cohort of 721 patients and due to its proposed secretory function, in plasma, presenting the first ELISA for SFRP4. SFRP4 was most highly expressed in tubal epithelium and decreased with malignant transformation, both on RNA and on protein level, where it was even more profound in the membrane fraction (p<0.0001). SFRP4 was expressed on the protein level in all histotypes of ovarian cancer but was decreased from borderline tumors to cancers and with loss of cellular differentiation. Loss of membrane expression was an independent predictor of poor survival in ovarian cancer patients (p = 0.02 unadjusted; p = 0.089 adjusted), which increased the risk of a patient to die from this disease by the factor 1.8. Conclusions/Significance Our results support a role for SFRP4 as a tumor suppressor gene in ovarian cancers via inhibition of the Wnt signaling pathway. This has not only predictive implications but could also facilitate a therapeutic role using epigenetic targets. PMID:22363760

  12. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma

    PubMed Central

    Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna

    2016-01-01

    Aims Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. Results PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively). Conclusions Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity. PMID:26625204

  13. Eating disorder symptoms and borderline personality symptomatology.

    PubMed

    Sansone, R A; Chu, J W; Wiederman, M W; Lam, C

    2011-06-01

    According to the empirical literature, there are high rates of borderline personality disorder (BPD) among individuals with formal diagnoses of eating disorders, and high rates of eating disorders among individuals with BPD. In this study, we examined relationships between three eating disorder symptoms (i.e., binge eating, starving oneself, abusing laxatives) and borderline personality symptomatology according to two self-report measures (the borderline personality scale of the Personality Diagnostic Questionnaire-4 and the Self- Harm Inventory) in a sample of psychiatric inpatients (N=126) and in a sample of internal medicine outpatients (N=419). Each individual eating disorder item, as well as a composite score of all three items, demonstrated statistically significant correlations with both measures of borderline personality symptomatology in both samples. In addition, endorsement of all three symptoms was invariably associated with borderline personality symptomatology on both measures. Specific eating disorder symptoms, alone, may predict for borderline personality symptomatology.

  14. Germline mutations of BRCA1 gene exon 11 are not associated with platinum response neither with survival advantage in patients with primary ovarian cancer: understanding the clinical importance of one of the biggest human exons. A study of the Tumor Bank Ovarian Cancer (TOC) Consortium.

    PubMed

    Dimitrova, Desislava; Ruscito, Ilary; Olek, Sven; Richter, Rolf; Hellwag, Alexander; Türbachova, Ivana; Woopen, Hannah; Baron, Udo; Braicu, Elena Ioana; Sehouli, Jalid

    2016-09-01

    Germline mutations in BRCA1 gene have been reported in up to 20 % of epithelial ovarian cancer (EOC) patients. Distinct clinical characteristics have been attributed to this special EOC population. We hypothesized that mutations in different BRCA1 gene exons may differently affect the clinical course of the disease. The aim of this study was to analyze, in a large cohort of primary EOCs, the clinical impact of mutations in BRCA1 gene exon 11, the largest exon of the gene sequence encoding the 60 % of BRCA1 protein. Two hundred sixty-three primary EOC patients, treated between 2000 and 2008 at Charité University Hospital of Berlin, were included. Patients' blood samples were obtained from the Tumor Ovarian Cancer (TOC) Network ( www.toc-network.de ). Direct sequencing of BRCA1 gene exon 11 was performed for each patient to detect mutations. Based on their BRCA1 exon 11 mutational status, patients were compared regarding clinico-pathological variables and survival. Mutations in BRCA1 exon 11 were found in 18 out of 263 patients (6.8 %). Further 10/263 (3.8 %) cases showed variants of uncertain significance (VUS). All exon 11 BRCA1-positive tumors (100 %) were Type 2 ovarian carcinomas (p = 0.05). Age at diagnosis was significantly younger in Type 2 exon 11 mutated patients (p = 0.01). On multivariate analysis, BRCA1 exon 11 mutational status was not found to be an independent predictive factor for optimal cytoreduction, platinum response, or survival. Mutations in BRCA1 gene exon 11 seem to predispose women to exclusively develop a Type 2 ovarian cancer at younger age. Exon 11 BRCA1-mutated EOC patients showed distinct clinico-pathological features but similar clinical outcome with respect to sporadic EOC patients.

  15. Recollections of family experience in borderline patients.

    PubMed

    Frank, H; Paris, J

    1981-09-01

    To test psychodynamic hypotheses about the etiology of the borderline syndrome, female borderline patients were asked whether they remembered their mothers and fathers as having responded with approval, disinterest, or criticism to dependent and independent behaviors. Comparisons were made with a group of normal controls and with a group of neurotics and patients with personality disorders. The main finding was that borderline patients remembered their fathers as neglectful. The recollections did not support an overprotection hypothesis.

  16. [A psychoanalytical approach of the borderline personality].

    PubMed

    Slucki, Daniel; Wikinski, Mariana

    A bibliographic review of the last year's psychoanalytic literature on borderline personality is presented. We expose diagnostic considerations, with special emphasis on those which refer to the boundaries between borderline personality, neurosis and psychosis on one hand, and those which distinguish between borderline personality and narcissistic disorders on the other. Vicissitudes of these patient's object relationships, their bond with other significant persons, their main psychic mechanisms, clinical traits and technical difficulties in the treatment are also described.

  17. Practical considerations in ovarian cancer chemotherapy

    PubMed Central

    Cristea, Mihaela; Han, Ernest; Salmon, Lennie; Morgan, Robert J.

    2010-01-01

    Epithelial ovarian cancer remains the most lethal gynecologic malignancy despite advances in treatment. The standard management generally involves a combination of surgical tumor debulking and chemotherapy. Over the decades, chemotherapy for ovarian cancer has evolved and currently involves a combination of intravenous platinum and taxane chemotherapy. Over the past decade, three randomized phase III trials have been reported, and all have demonstrated a significant survival advantage for intraperitoneal compared with intravenous chemotherapy. However, there are potential barriers and controversies related to the administration of intraperitoneal chemotherapy in ovarian cancer patients. In this review, we discuss the evolution and current management considerations of chemotherapy for the treatment of epithelial ovarian cancer. PMID:21789133

  18. Emotional Hypochondriasis, Hyperbole, and the Borderline Patient

    PubMed Central

    ZANARINI, MARY C.; FRANKENBURG, FRANCES R.

    1994-01-01

    The authors define a new defense mechanism, emotional hypochondriasis, that is hypothesized to be central to borderline psychopathology. The behavioral manifestation of this defense—the hyperbolic stance of the borderline patient—is also defined and related to the complex phenomenology of borderline personality disorder. Borderline patients are seen as making an active attempt to maintain a tolerable, if tenuous, adaptation in the face of tremendous subjective emotional pain that has been shaped in large measure by traumatic childhood events that have never been validated. Twelve treatment implications and three expectable, if overlapping, stages of treatment stemming from the use of this defense and its behavioral sequelae are detailed. PMID:22700171

  19. Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

    ClinicalTrials.gov

    2016-02-15

    Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  20. The Inner Workings of Ovarian Cancer

    SciTech Connect

    Rodland, Karin

    2016-06-29

    New research identifies critical proteins present in the tumors of women with ovarian cancer. Karin Rodland discusses the work led by PNNL and Johns Hopkins researchers, working with collaborators across the nation.

  1. The Inner Workings of Ovarian Cancer

    ScienceCinema

    Rodland, Karin

    2016-11-02

    New research identifies critical proteins present in the tumors of women with ovarian cancer. Karin Rodland discusses the work led by PNNL and Johns Hopkins researchers, working with collaborators across the nation.

  2. Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherin.

    PubMed

    Hayashi, Akiko; Horiuchi, Akiko; Kikuchi, Norihiko; Hayashi, Takuma; Fuseya, Chiho; Suzuki, Akihisa; Konishi, Ikuo; Shiozawa, Tanri

    2010-09-01

    Histone acetylation/deacetylation controls chromatin activity and subsequent gene transcription. Recent studies demonstrated the activation of histone deacetylases (HDACs) in various human malignancies; however, the expression and function of HDACs in ovarian tumors are not fully understood. In this study, we examined the immunohistochemical expression of HDAC1, HDAC2 and HDAC3 using tissues obtained from 115 cases of ovarian tumors and compared it with that of Ki-67 (a growth marker), p21, and E-cadherin and clinicopathological parameters. In addition, we analyzed the effect of specific siRNA for HDAC1, HDAC2 and HDAC3 on the expression of cell cycle-related molecules and E-cadherin to clarify the functional difference among the 3 HDACs. The results indicated that the immunohistochemical expression of nuclear HDAC1, HDAC2 and HDAC3 proteins increased stepwise in benign, borderline and malignant tumors. The expression of HDAC1 and HDAC2 was correlated with Ki-67 expression and that of HDAC3 was inversely correlated with E-cadherin expression. Among the HDACs examined, only HDAC1 was associated with a poor outcome, when overexpressed. Treatment with HDAC inhibitors suppressed the proliferation of ovarian cancer cells in association with apoptosis. A specific siRNA for HDAC1 significantly reduced the proliferation of ovarian carcinoma cells via downregulation of cyclin A expression, but siRNA for HDAC3 reduced the cell migration with elevated E-cadherin expression. Our results suggested that HDAC1 plays an important role in the proliferation of ovarian cancer cells, whereas HDAC3 functions in cell adhesion and migration. Therefore, specific therapeutic approaches should be considered according to the HDAC subtypes.

  3. Ovarian cysts

    MedlinePlus

    ... cysts due to hormone-related conditions such as polycystic ovary syndrome . Symptoms Ovarian cysts often cause no symptoms. An ... You may need other treatments if you have polycystic ovary syndrome or another disorder that can cause cysts. Outlook ( ...

  4. Ovarian Cancer

    MedlinePlus

    ... and getting enough rest can help combat the stress and fatigue of cancer. There's no sure way to prevent ovarian cancer. But certain factors are associated with lower risk: Use of oral contraceptives, especially for more than 10 years Previous ...

  5. Ovarian hypofunction

    MedlinePlus

    ... may be caused by genetic factors such as chromosome abnormalities. It may also occur with certain autoimmune disorders that disrupt the normal function of the ovaries. Chemotherapy and radiation therapy can also cause ovarian hypofunction.

  6. Ovarian Cysts

    MedlinePlus

    ... information Endometriosis fact sheet Ovarian cancer fact sheet Polycystic ovary syndrome fact sheet The javascript used in this widget ... ovaries make many small cysts. This is called polycystic ovary syndrome (PCOS). PCOS can cause problems with the ovaries ...

  7. Vaccine Therapy in Treating Patients With Stage IIIC-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer Following Surgery and Chemotherapy

    ClinicalTrials.gov

    2016-12-28

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Tumor; Fallopian Tube Mucinous Neoplasm; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  8. Oncolytic reovirus against ovarian and colon cancer.

    PubMed

    Hirasawa, Kensuke; Nishikawa, Sandra G; Norman, Kara L; Alain, Tommy; Kossakowska, Anna; Lee, Patrick W K

    2002-03-15

    Reovirus selectively replicates in and destroys cancer cells with an activated Ras signaling pathway. In this study, we evaluated the feasibility of using reovirus (serotype 3, strain Dearing) as an antihuman colon and ovarian cancer agent. In in vitro studies, reovirus infection in human colon and ovarian cell lines was assessed by cytopathic effect as detected by light microscopy, [(35)S]Methionine labeling of infected cells for viral protein synthesis and progeny virus production by plaque assay. We observed that reovirus efficiently infected all five human colon cancer cell lines (Caco-2, DLD-1, HCT-116, HT-29, and SW48) and four human ovarian cancer cell lines (MDAH2774, PA-1, SKOV3, and SW626) which were tested, but not a normal colon cell line (CCD-18Co) or a normal ovarian cell line (NOV-31). We also observed that the Ras activity in the human colon and ovarian cancer cell lines was elevated compared with that in normal colon and ovarian cell lines. In animal models, intraneoplastic as well as i.v. inoculation of reovirus resulted in significant regression of established s.c. human colon and ovarian tumors implanted at the hind flank. Histological studies revealed that reovirus infection in vivo was restricted to tumor cells, whereas the surrounding normal tissue remained uninfected. Additionally, in an i.p. human ovarian cancer xenograft model, inhibition of ascites tumor formation and the survival of animals treated with live reovirus was significantly greater than of control mice treated with UV-inactivated reovirus. Reovirus infection in ex vivo primary human ovarian tumor surgical samples was also confirmed, further demonstrating the potential of reovirus therapy. These results suggest that reovirus holds promise as a novel agent for human colon and ovarian cancer therapy.

  9. Borderline Clients: Practice Implications of Recent Research.

    ERIC Educational Resources Information Center

    Johnson, Harriette C.

    1991-01-01

    Reviews current research on treatment of borderline clients with medication, individual counseling, and family interventions. Notes that recent studies indicate that borderline personality is heterogeneous condition in which different underlying disorders (affective, schizotypal, and neurological) may be present. Reviews effectiveness of various…

  10. The Borderline Personality--An Adlerian Overview.

    ERIC Educational Resources Information Center

    Rattner, Leo

    The person with a borderline personality is considered to be neither neurotic nor psychotic, but to exist somewhere in between these two diagnostic categories. Psychoanalytic theorists who have researched the phenomenon of the borderline personality have shifted their emphasis away from Freud's instinct psychology and toward an ego psychology…

  11. Epithelial ovarian cancer: testing the 'androgens hypothesis'.

    PubMed

    Olsen, Catherine M; Green, Adèle C; Nagle, Christina M; Jordan, Susan J; Whiteman, David C; Bain, Christopher J; Webb, Penelope M

    2008-12-01

    In 1998, Risch proposed a hypothesis for the pathogenesis of ovarian cancer relating to the role of androgens in stimulating epithelial cell proliferation. Although this hypothesis has been widely discussed, direct evidence to support it is scant. To address this issue, we have conducted a detailed analysis of factors possibly associated with high circulating levels of androgens, including polycystic ovary syndrome (PCOS), hirsutism and acne (all clinically associated with hyperandrogenism) using the data collected in an Australia-wide, population-based case-control study. Cases aged 18-79 years with a new diagnosis of invasive epithelial ovarian cancer (n=1276) or borderline malignant tumour (n=315) were identified through a network of clinics and cancer registries throughout Australia. Controls (n=1508) were selected from the National Electoral Roll. Women self-reported a history of PCOS, acne, hirsutism and also use of testosterone supplements or the androgenic medication Danazol. We found no evidence that a history of PCOS, acne or hirsutism was associated with ovarian cancer overall, or with specific subtypes, with the exception of serous borderline tumours that were positively associated with a history of PCOS (OR 2.6; 95% CI 1.0-6.1). Women who had ever used testosterone supplements had an increased risk of ovarian cancer (OR 3.7; 95% CI 1.1-12.0); however, use of the androgenic medication Danazol did not increase risk (OR 1.0; 95% CI 0.4-2.9). Overall, our results do not support the hypothesis that androgen-related disorders increase the risk of ovarian cancer.

  12. Diet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-02-09

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  13. Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer

    ClinicalTrials.gov

    2016-05-02

    HER2-positive Breast Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

  14. Activated FGFR2 as a Viable Therapeutic Target in a Subset of Ovarian Cancers

    DTIC Science & Technology

    2009-07-01

    endom etrioid ovarian 70 carcinomas [3], whereas PTEN, PIK3CA, and CTNNB-1 (β-catenin) mutations are more common 71 in low-grade endom etrioid ovarian...100 high-grade advanced stage serous ovarian tumors [16]. FGF9 has also been implicated as playing 101 a key role in ovarian endom etrioid ade...mutations in FGFR2 in endom etrial cancer, 111 predominantly in the endom etrioid histologic subtype [20, 21]. Interestin gly, ovarian cancer and 112

  15. An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma.

    PubMed

    Baratta, Maria Giuseppina; Schinzel, Anna C; Zwang, Yaara; Bandopadhayay, Pratiti; Bowman-Colin, Christian; Kutt, Jennifer; Curtis, Jennifer; Piao, Huiying; Wong, Laura C; Kung, Andrew L; Beroukhim, Rameen; Bradner, James E; Drapkin, Ronny; Hahn, William C; Liu, Joyce F; Livingston, David M

    2015-01-06

    High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive form of epithelial ovarian cancer, for which few targeted therapies exist. To search for new therapeutic target proteins, we performed an in vivo shRNA screen using an established human HGSOC cell line growing either subcutaneously or intraperitoneally in immunocompromised mice. We identified genes previously implicated in ovarian cancer such as AURKA1, ERBB3, CDK2, and mTOR, as well as several novel candidates including BRD4, VRK1, and GALK2. We confirmed, using both genetic and pharmacologic approaches, that the activity of BRD4, an epigenetic transcription modulator, is necessary for proliferation/survival of both an established human ovarian cancer cell line (OVCAR8) and a subset of primary serous ovarian cancer cell strains (DFs). Among the DFs tested, the strains sensitive to BRD4 inhibition revealed elevated expression of either MYCN or c-MYC, with MYCN expression correlating closely with JQ1 sensitivity. Accordingly, primary human xenografts derived from high-MYCN or c-MYC strains exhibited sensitivity to BRD4 inhibition. These data suggest that BRD4 inhibition represents a new therapeutic approach for MYC-overexpressing HGSOCs.

  16. An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma

    PubMed Central

    Baratta, Maria Giuseppina; Schinzel, Anna C.; Zwang, Yaara; Bandopadhayay, Pratiti; Bowman-Colin, Christian; Kutt, Jennifer; Curtis, Jennifer; Piao, Huiying; Wong, Laura C.; Kung, Andrew L.; Beroukhim, Rameen; Bradner, James E.; Drapkin, Ronny; Hahn, William C.; Liu, Joyce F.; Livingston, David M.

    2015-01-01

    High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive form of epithelial ovarian cancer, for which few targeted therapies exist. To search for new therapeutic target proteins, we performed an in vivo shRNA screen using an established human HGSOC cell line growing either subcutaneously or intraperitoneally in immunocompromised mice. We identified genes previously implicated in ovarian cancer such as AURKA1, ERBB3, CDK2, and mTOR, as well as several novel candidates including BRD4, VRK1, and GALK2. We confirmed, using both genetic and pharmacologic approaches, that the activity of BRD4, an epigenetic transcription modulator, is necessary for proliferation/survival of both an established human ovarian cancer cell line (OVCAR8) and a subset of primary serous ovarian cancer cell strains (DFs). Among the DFs tested, the strains sensitive to BRD4 inhibition revealed elevated expression of either MYCN or c-MYC, with MYCN expression correlating closely with JQ1 sensitivity. Accordingly, primary human xenografts derived from high-MYCN or c-MYC strains exhibited sensitivity to BRD4 inhibition. These data suggest that BRD4 inhibition represents a new therapeutic approach for MYC-overexpressing HGSOCs. PMID:25535366

  17. Efficient siRNA delivery and tumor accumulation mediated by ionically cross-linked folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate nanoparticles: for the potential targeted ovarian cancer gene therapy.

    PubMed

    Li, Tony Shing Chau; Yawata, Toshio; Honke, Koichi

    2014-02-14

    For effective ovarian cancer gene therapy, systemic administrated tumor-targeting siRNA/folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate (FA-PEG-COL) nanoparticles is vital for delivery to cancer site(s). siRNA/FA-PEG-COL nanoparticles were prepared by ionic gelation for effective FA receptor-expressing ovarian cancer cells transfection and in vivo accumulation. The chemical structure of FA-PEG-COL conjugate was characterized by MALDI-TOF-MS, FT-IR and (1)H NMR. The average size of siRNA/FA-PEG-COL nanoparticles was approximately 200 nm, and the surface charge was +8.4 mV compared to +30.5 mV with siRNA/COL nanoparticles. FA-PEG-COL nanoparticles demonstrated superior compatibility with erythrocytes in terms of degree of aggregation and haemolytic activity and also effects on cell viability was lower when compared with COL nanoparticles. FA grafting significantly facilitated the uptake of nanoparticles via receptor mediated endocytosis as demonstrated by flow cytometry. The in vitro transfection and gene knockdown efficiency of HIF-1α were superior to COL nanoparticles (76-62%, respectively) and was comparable to Lipofectamine 2000 (79%) as demonstrated by RT-qPCR and Western blot. Gene knockdown at the molecular level translated into effective inhibition of proliferation in vitro. Accumulation efficiency of FA-PEG-COL nanoparticles was investigated in BALB/c mice bearing OVK18 #2 tumor xenograft using in vivo imaging. The active targeting FA-PEG-COL nanoparticles showed significantly greater accumulation than the passive targeting COL nanoparticles. Based on the results obtained, siRNA/FA-PEG-COL nanoparticles show much potential for effective ovarian cancer treatment via gene therapy.

  18. Epigenomics of Ovarian Cancer and Its Chemoprevention

    PubMed Central

    Chen, Huaping; Hardy, Tabitha M.; Tollefsbol, Trygve O.

    2011-01-01

    Ovarian cancer is a major cause of death among gynecological cancers and its etiology is still unclear. Currently, the two principle obstacles in treating this life threatening disease are lack of effective biomarkers for early detection and drug resistance after initial chemotherapy. Similar to other cancers, the initiation and development of ovarian cancer is characterized by disruption of oncogenes and tumor suppressor genes by both genetic and epigenetic mechanisms. While it is well known that it is challenging to treat ovarian cancer through a genetic strategy due in part to its heterogeneity, the reversibility of epigenetic mechanisms involved in ovarian cancer opens exciting new avenues for treatment. The epigenomics of ovarian cancer has therefore become a rapidly expanding field leading to intense investigation. A review on the current status of the field is thus warranted. In this analysis, we will evaluate the current status of epigenomics of ovarian cancer and will include epigenetic mechanisms involved in ovarian cancer development such as DNA methylation, histone modifications, and non-coding microRNA. Development of biomarkers, the epigenetic basis for drug resistance and improved chemotherapy for ovarian cancer will also be assessed. In addition, the potential use of natural compounds as epigenetic modulators in chemotherapy shows promise in moving to the forefront of ovarian cancer treatment strategies. PMID:22303362

  19. Ultrasonography of ovarian masses using a pattern recognition approach

    PubMed Central